Disclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminated by the Centers for Disease Control and Prevention and should not be 

construed to represent any agency determination or policy. 1

APPENDIX 2: PROSTHETIC JOINT ARTHROPLASTY SURGERY

Draft Guideline for the Prevention of Surgical Site Infections
Disclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminated by the Centers for Disease Control and Prevention and should not be 

construed to represent any agency determination or policy. 2

Table of Contents

SECTION 1: SEARCH STRATEGIES ........................................................................................................................................................................................ 4

SECTION A: ORTHO SEARCH ........................................................................................................................................................................................... 4

SECTION B. TARGETED SEARCH: TRANSFUSION............................................................................................................................................................. 6

SECTION C. TARGETED SEARCH: IMMUNOSUPPRESSIVE THERAPY ............................................................................................................................. 11

SECTION D. TARGETED SEARCH: ANTICOAGULATION.................................................................................................................................................. 17

SECTION E. TARGETED SEARCH: SURGICAL ATTIRE ...................................................................................................................................................... 21

SECTION F. TARGETED SEARCH: ANTIMICROBIAL PROPHYLAXIS WITH A DRAIN ........................................................................................................ 28

SECTION G. TARGETED SEARCH: BIOFILM .................................................................................................................................................................... 32

SECTION 2: EVIDENCE, GRADE AND RISK OF BIAS ASSESSMENT TABLES......................................................................................................................... 37

Q11 BLOOD TRANSFUSION........................................................................................................................................................................................... 37

GRADE TABLE Q11 .................................................................................................................................................................................................... 37

EVIDENCE TABLE Q11................................................................................................................................................................................................ 49

RISK OF BIAS ASSESSMENTS OF STUDIES Q11.......................................................................................................................................................... 85

Q12-16 SYSTEMIC IMMUNOSUPPRESSIVE THERAPY.................................................................................................................................................... 86

GRADE TABLE Q12-16 ............................................................................................................................................................................................... 86

EVIDENCE TABLE Q12-16 .......................................................................................................................................................................................... 95

RISK OF BIAS ASSESSMENTS OF STUDIES Q12-16................................................................................................................................................... 121

Q17 ANTICOAGULATION............................................................................................................................................................................................. 122

GRADE TABLE Q17 .................................................................................................................................................................................................. 122

EVIDENCE TABLE Q17.............................................................................................................................................................................................. 128

RISK OF BIAS ASSESSMENTS OF STUDIES Q17........................................................................................................................................................ 158

Q18 ORTHOPAEDIC SPACE SUIT.................................................................................................................................................................................. 159
Disclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminated by the Centers for Disease Control and Prevention and should not be 

construed to represent any agency determination or policy. 3

GRADE TABLE Q18 .................................................................................................................................................................................................. 159

EVIDENCE TABLE Q18.............................................................................................................................................................................................. 161

RISK OF BIAS ASSESSMENTS OF STUDIES Q18........................................................................................................................................................ 170

Q20 BIOFILM ............................................................................................................................................................................................................... 171

GRADE TABLE Q20 .................................................................................................................................................................................................. 171

EVIDENCE TABLE Q20.............................................................................................................................................................................................. 173

RISK OF BIAS ASSESSMENTS OF STUDIES Q20........................................................................................................................................................ 178

SECTION 3: EVALUATION OF THE RISK OF BIAS OF AN INDIVIDUAL STUDY................................................................................................................... 179

CHECKLIST FOR SYSTEMATIC REVIEWS....................................................................................................................................................................... 179

CHECKLIST FOR RANDOMIZED CONTROLLED TRIALS ................................................................................................................................................. 179

CHECKLIST FOR OTHER CONTROLLED STUDIES .......................................................................................................................................................... 180

SECTION 4: EVIDENCE TABLE EXTRACTION TEMPLATES ................................................................................................................................................ 181

1. SYSTEMATIC REVIEW (SR) EXTRACTION TEMPLATE ............................................................................................................................................... 181

2. RANDOMIZED CONTROLLED TRIAL (RCT) EXTRACTION TEMPLATE ....................................................................................................................... 181

3. OTHER CONTROLLED STUDIES EXTRACTION TEMPLATE ........................................................................................................................................ 182

SECTION 5: STUDY TYPE DETERMINATION ALGORITHM................................................................................................................................................ 183

SECTION 6: REFERENCES................................................................................................................................................................................................. 184
Disclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminated by the Centers for Disease Control and Prevention and should not be 

construed to represent any agency determination or policy. 4

SECTION 1: SEARCH STRATEGIES

SECTION A: ORTHO SEARCH 

MEDLINE

# Search History Results

1 (arthroplast* or replac* or replant* or joint* or implant* or reconstruct* or prosthe*).af. 1,052,637

2 exp Arthroplasty, Replacement/ or exp Arthroplasty/ 29,697

3 exp Orthopedic Procedures/ 176,717

4 exp Joints/su [Surgery] 42,769

5 1 or 2 or 3 or 4 1,135,596

6 exp Wound Infection/ 34,108

7 "surgical site infection*".af. 2,130

8 exp Prosthesis-Related Infections/ 6,283

9 exp Bone Diseases, Infectious/ 29,730

10 exp Soft Tissue Infections/ 1,876

11 exp Skin Diseases, Infectious/ 90,359

12 6 or 7 or 8 or 9 or 10 or 11 158,415

13 5 and 12 24,509

14 exp Surgical Procedures, Operative/ 2,113,349

15 (surgical* or surgery* or operati*).af. 2,629,634

16 14 or 15 3,467,669

17 (arthro* or orthop*).af. 316,829

18 16 and 17 206,698

19 12 and 18 9,513

20 13 or 19 26,888
Disclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminated by the Centers for Disease Control and Prevention and should not be 

construed to represent any agency determination or policy. 5

21 limit 20 to (english language and yr="1998 - Current") 11,604

22 limit 21 to systematic reviews 262

23 limit 21 to meta analysis 50

24 limit 21 to guideline 14

25 limit 21 to practice guideline 22

26 limit 21 to "reviews (maximizes specificity)" 137

27 limit 21 to randomized controlled trial 294

28 22 or 23 or 24 or 25 or 26 or 27 595

EMBASE

# Search History Results

1

'wound infection'/exp or 'surgical infection'/exp or 'prosthesis infection'/exp or 'bone infection'/exp or 'soft tissue infection'/exp or 'skin 

infection'/exp or 'surgical site infection'; limit to English language, EMBASE, and [1998-2012]/py 69,175

2

'arthroplasty'/exp or 'arthroplasty replacement'/exp or 'orthopedic surgery'/exp or ('joint'/exp and surg*) or arthroplast* or replac* or 

replant* or (joint* and' surgery'/exp) or implant* or reconstruct* or prosthe* or('surgery'/exp or surgical* or operativ* and (arthro*

ororthop*)) and [1998-2012]/py 856,609

3 1 and 2 14,117

4 ‘meta-analysis’/exp 57,212

5 3 and 4 121

6 limit 3 to ‘systematic review’/de 234

7 limit 3 to ‘practice guideline ‘/de 383

8 limit 3 to ‘randomized controlled trial’/de 430

9 5 or 6 or 7 or 8 1,059
Disclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminated by the Centers for Disease Control and Prevention and should not be 

construed to represent any agency determination or policy. 6

SECTION B. TARGETED SEARCH: TRANSFUSION

MEDLINE

# Search History Results

1 (exp "prostheses and implants"/ or prosthe*.af. or implant*.af. or orthoped*.af. or orthopaed*.af.) and (exp joints/ or joint*.af.) 101,924

2 exp Joints/su [Surgery] 44,456

3 exp Arthroplasty, Replacement/ or exp Arthroplasty/ 32,010

4 arthroplast*.af. 42,928

5 exp "Orthopedic Procedures"/ and exp "Joints"/ 39,956

6 or/1-5 141,563

7 exp Infection/ or infection*.af. or infecting.af. or infected.af. or exp "Prosthesis-Related Infections"/ 1,533,905

8 exp Blood Transfusion/ or (blood and transfus*).af. 114,443

9 exp Blood Platelets/ or platelet*.af. or "blood product*".af. 195,879

10 8 or 9 292,467

11 exp Random Allocation/ 73,596

12 exp Randomized Controlled Trials as Topic/ or exp Randomized Controlled Trial/ 394,924

13 exp Double-Blind Method/ 113,512

14 exp Single-Blind Method/ 15,853

15 exp Clinical Trial/ 667,767

16 exp Clinical Trials as Topic/ 251,205

17 clinical trial.pt. 467,170

18 clinical trial, phase i.pt. 11,868

19

(clinical trial, phase ii or clinical trial, phase iii or clinical trial, phase iv or controlled clinical trial or randomized controlled trial or multicenter 

study or clinical trial).pt. 665,448

20 or/11-19 895,443

21 (clinical adj trial$).tw. 164,609
Disclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminated by the Centers for Disease Control and Prevention and should not be 

construed to represent any agency determination or policy. 7

22 ((singl$ or doubl$ or treb$ or tripl$) adj (blind$3 or mask$3)).tw. 111,059

23 placebo$.tw. 133,778

24 randomly allocated.tw. 13,342

25 (allocated adj2 random$).tw. 15,627

26 exp Placebos/ 30,626

27 or/20-26 996,307

28 case report.tw. 164,158

29 letter/ 735,581

30 historical article/ 280,723

31 exp Editorial/ 291,753

32 or/28-31 1,454,788

33 27 not 32 956,341

34 exp "Sensitivity and Specificity"/ 350,527

35 (sensitivity or specificity).tw. 590,136

36 ((pre-test or pretest) adj probability).tw. 980

37 post-test probability.tw. 268

38 predictive value$.tw. 54,259

39 likelihood ratio$.tw. 6,512

40 exp "Predictive Value of Tests"/ 117,980

41 or/33-40 1,740,790

42 exp Meta-Analysis as Topic/ 11,873

43 (meta analy$ or metaanaly$).tw. or exp Meta-analysis/ 48,899

44 (systematic adj (review$1 or overview$1)).tw. 29,904

45 exp Review Literature as Topic/ 6,079

46 or/41-45 1,784,999
Disclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminated by the Centers for Disease Control and Prevention and should not be 

construed to represent any agency determination or policy. 8

47 (embase or cochrane or psyclit* or psychlit* or psycinfo or psychinfo).tw. 27,796

48 (cinahl or cinhal).ab. 5,997

49 (science citation index or bids or cancerlit).ab. 2,135

50 or/46-49 1,792,516

51 (reference list$ or bibliograph$ or hand-search$ or relevant journals or manual search$).ab. 18,484

52 (selection criteria or data extraction).ab. 20,349

53 exp Review/ 1,675,847

54 52 and 53 14,038

55 50 or 51 or 54 1,800,552

56 exp Comment/ or exp Editorial/ or exp Letter/ 1,108,385

57 55 not 56 1,770,101

58

exp Epidemiologic studies/ or exp case control studies/ or exp cohort studies/ or Case control.tw. or (cohort adj (study or studies)).tw. or 

cohort analy$.tw. or (Follow up adj (study or studies)).tw. or (observational adj (study or studies)).tw. or Longitudinal.tw. or Retrospective.tw. 

or Cross sectional.tw. or exp Cross-sectional studies/ 1,553,551

59 57 or 58 2,972,690

60 6 and 7 and 10 and 59 150

61 limit 60 to english language 136

62 limit 61 to yr="1998 -Current" 103

EMBASE

# Search History Results

1

‘blood transfusion’/exp or (‘blood’/exp and (transfusion’/exp or transfused)) or ‘thrombocyte’/exp or ‘blood’/exp or platelet* or ‘blood 

product’/exp or ‘blood products’ and [english]/lim and [embse]/lim and [1998-2012]/py 627,207

2 ‘prostheses and orthoses’/exp or prosthe$ or implant$ or orthoped$ or orthopaed$ 399,873

3

‘joint’/exp or joint$ or ‘joint surgery’/exp or ‘arthroplasty’/exp or arthroplasty or arthroplasties or ‘arthroplasty replacement’ or (‘orthopedic 

surgery’/exp and ‘joint’/exp) 603,883

4 2 and 3 69,054
Disclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminated by the Centers for Disease Control and Prevention and should not be 

construed to represent any agency determination or policy. 9

5 ‘infection’/exp 2,328,600

6 infection$ or infecting or infected 2,654,665

7 ‘prosthesis related’ and infections 95

8 ‘prosthesis-related infections’/exp 2,328,600

9 5 or 6 or 7 or 8 2,660,483

10 1 and 4 and 9 353

11 ‘clinical study’/exp or ‘case control study’/exp or ‘family study’/exp or ‘longitudinal study’/exp or ‘retrospective study’/exp 5,942,135

12 ‘prospective study’/exp 189,505

13 ‘randomized controlled trial’/exp 307,692

14 12 not 13 165,671

15

‘cohort analysis’/exp or (cohort and adj and (study or studies)) or (case and control and adj and (study or studies)) or (follow and up and adj 

and (study or studies)) or (observational and adj and (study or studies)) or (epidemiologic$ and adj and (study or studies)) or (cross and 

sectional and adj and (study or studies)) 115,089

16 11 or 12 or 14 or 15 5,986,679

17 ‘meta analysis’/exp or (meta and adj and analy$) or metaanaly$ or (systematic and adj and (review$ or overview$)) 61,427

18 cancerlit or cochrane or ‘embase’/exp or psychlit’/exp or ‘psyclit’/ or ‘science citation index’/exp or bids or scopus 44,494

19 ‘reference lists’ or bibliograph$ or ‘hand search$’ or ‘manual search$’ or ‘relevant journals’ or ‘data extraction’/exp or ‘selection criteria’ 28,035

20 review.pt. 4

21 ‘review’/exp 1,831,423

22 20 or 21 1,831,427

23 19 and 22 15,584

24 letter.pt. or editorial.pt. 3

25 ‘letter’/exp or ‘editorial’/exp 1,179,933

26 24 or 25 1,179,934

27 17 or 18 or 23 98,049

28 27 not 26 93,355
Disclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminated by the Centers for Disease Control and Prevention and should not be 

construed to represent any agency determination or policy. 10

29

‘sensitivity and specificity/exp or sensitivity or specificity or (‘pre test’ or pretest and adj and ‘probability’/exp) or ‘post-test probability’ or 

predictive and value$ or likelihood and ratio$ or ‘predictive value’/exp or ‘diagnostic accuracy ‘/exp and [english]/lim and [embase]/lim and 

[1998-2012]/py 144,775

30

‘clinical trial’/exp or ‘randomized controlled trial’/exp or ‘randomization’/exp or ‘single blind procedure’/exp or ‘double blind procedure’/exp 

or ‘crossover procedure’/exp or ‘placebo’/exp or randomi?ed and controlled and trial$ or rct$ or ‘random allocation’ or ‘randomly allocated’ 

or ‘allocated randomly’ or allocated and adj2 and random$ or single and blind$ or double and blind$ or (treble or triple and adj and blind$) or 

placebo$ or ‘prospective study’/exp 541,923

31

‘case study’/exp or ‘case study’ or ‘case report’/exp or ‘case report’ or ‘abstract report’/exp or ‘abstract report’ or ‘letter’/exp or letter and 

[1998-2012]/py 1,237,206

32 30 not 31 529,538

33 16 or 28 or 29 or 32 6,160,948

34 10 and 33 232

COCHRANE DATABASE OF SYSTEMATIC REVIEWS

# Search History Results

1

(transfus* or platelet* or "blood product*") and (surgery or surgical* or operat*) and (joint* or arthroplast* or prosthe* or implant*) in Title, 

Abstract or Keywords 6
Disclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminated by the Centers for Disease Control and Prevention and should not be 

construed to represent any agency determination or policy. 11

SECTION C. TARGETED SEARCH: IMMUNOSUPPRESSIVE THERAPY

MEDLINE

# Search History Results

1 (exp "prostheses and implants"/ or prosthe*.af. or implant*.af. or orthoped*.af. or orthopaed*.af.) and (exp joints/ or joint*.af.) 102,099

2 exp Joints/su [Surgery] 44,522

3 exp Arthroplasty, Replacement/ or exp Arthroplasty/ 32,116

4 arthroplasty*.af. 43,040

5 exp “Orthopedic Procedures”/and exp “Joints”/ 40,017

6 or/1-5 141,821

7 exp Infection/ or infection*.af. or infecting.af. or infected.af. or exp "Prosthesis-Related Infections"/ 1,540,242

8 exp Random Allocation/ 73,745

9 exp Randomized Controlled Trials as Topic/ or exp Randomized Controlled Trial/ 397,784

10 exp Double-Blind Method/ 113,903

11 exp Single-Blind Method/ 15,934

12 exp Clinical Trial/ 670,938

13 exp Clinical Trials as Topic/ 253,167

14 clinical trial.pt. 467,996

15 clinical trial, phase i.pt. 11,949

16 (clinical trial, phase ii or clinical trial, phase iii or clinical trial, phase iv or controlled clinical trial or randomized controlled trial or multicenter 

study or clinical trial).pt. 668,584

17 or/8-16 900,674

18 (clinical adj trial$).tw. 165,764

19 ((singl$ or doubl$ or treb$ or tripl$) adj (blind$3 or mask$3)).tw. 111,446

20 placebo$.tw. 134,478

21 randomly allocated.tw. 13,417
Disclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminated by the Centers for Disease Control and Prevention and should not be 

construed to represent any agency determination or policy. 12

22 (allocated adj2 random$).tw. 15,704

23 exp Placebos/ 30,699

24 or/17-23 1,002,057

25 case report.tw. 164,536

26 letter/ 742,239

27 historical article/ 281,301

28 exp Editorial/ 295,205

29 or/25-28 1,465,799

30 24 not 29 961,541

31 exp “Sensitivity and Specificity”/ 351,908

32 (sensitivity or specificity).tw. 592,438

33 ((pre-test or pretest) adj probability).tw. 988

34 post-test probability.tw. 272

35 predictive value$.tw. 54,458

36 likelihood ratio$.tw. 6,573

37 exp "Predictive Value of Tests"/ 118,435

38 or/30-37 1,748,938

39 exp Meta-Analysis as Topic/ 12,009

40 (meta analy$ or metaanaly$).tw. or exp Meta-analysis/ 49,740

41 (systematic adj (review$1 or overview$1)).tw. 30,487

42 exp Review Literature as Topic/ 6,208

43 or/38-42 1,793,694

44 (embase or cochrane or psyclit* or psychlit* or psycinfo or psychinfo).tw. 28,506

45 (cinahl or cinhal).ab. 6,190

46 (science citation index or bids or cancerlit).ab. 2,196
Disclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminated by the Centers for Disease Control and Prevention and should not be 

construed to represent any agency determination or policy. 13

47 or/43-46 1,801,291

48 (reference list$ or bibliograph$ or hand-search$ or relevant journals or manual search$).ab. 18,852

49 (selection criteria or data extraction).ab. 20,813

50 exp Review/ 1,682,836

51 49 and 50 14,472

52 47 or 48 or 51 1,809,350

53 exp Comment/ or exp Editorial/ or exp Letter/ 1,119,204

54 52 not 53 1,778,639

55 exp Epidemiologic studies/ or exp case control studies/ or exp cohort studies/ or Case control.tw. or (cohort adj (study or studies)).tw. or 

cohort analy$.tw. or (Follow up adj (study or studies)).tw. or (observational adj (study or studies)).tw. or Longitudinal.tw. or Retrospective.tw. 

or Cross sectional.tw. or exp Cross-sectional studies/

1,560,697

56 54 or 55 2,986,243

57 exp Immunosuppressive Agents/ 229,191

58 exp Immunosuppression/ 46,654

59 "immunosuppressive therapy".af. 10,624

60 immune*.af. 408,428

61 immunolog*.af. 56

62 exp Adrenal Cortex Hormones/ 315,501

63 exp Steroids/ 657,932

64 exp methotrexate/ or exp cyclophosphamide/ 67,761

65 exp Tumor Necrosis Factor-alpha/ 83,932

66 "systemic corticosteroids".af. 2,228

67 steroid*.af. 244,914

68 “tumor necrosis factor*”.af. 116,734

69 (cyclophosphamide or cytoxan or methotrexate).af. 83,530

70 tnf.af. 90,322
Disclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminated by the Centers for Disease Control and Prevention and should not be 

construed to represent any agency determination or policy. 14

71 exp Injections, Intra-articular/ or intra-articular*.af. 11,059

72 or/57-71 1,544,611

73 6 and 7 and 56 and 72 360

74 limit 73 to english language 312

75 limit 74 to yr="1998 -Current" 250

EMBASE

# Search History Results

1 ‘prostheses and orthoses’/exp or prosthe$ or implant$ or orthoped$ or orthopaed$ 399,873

2 ‘joint’/exp or joint$ or ‘joint surgery’/exp or ‘arthroplasty’/exp or arthroplasty or arthroplasties or ‘arthroplasty replacement’ or (‘orthopedic 

surgery’/exp and ‘joint’/exp) 603,893

3 1 and 2 69,054

4 ‘infection’/exp 2,328,600

5 infection$ or infecting or infected 2,654,665

6 ‘prosthesis related’ and infections 95

7 ‘prosthesis-related infections’/exp 2,328,600

8 4 or 5 or 6 or 7 2,660,483

9 ‘clinical study’/exp or ‘case control study’/exp or ‘family study’/exp or ‘longitudinal study’/exp or ‘retrospective study’/exp 5,942,135

10 ‘prospective study’/exp 188,505

11 ‘randomized controlled trial’/exp 307,692

12 10 not 11 165,671

13 ‘cohort analysis’/exp or (cohort and adj and (study or studies)) or (case and control and adj and (study or studies)) or (follow and up and adj 

and (study or studies)) or (observational and adj and (study or studies)) or (epidemiologic$ and adj and (study or studies)) or (cross and 

sectional and adj and (study or studies))

115,089

14 9 or 10 or 12 or 13 5,986,679

15 ‘meta analysis’/exp or (meta and adj and analy$) or metaanaly$ or (systematic and adj and (review$ or overview$)) 61,427

16 cancerlit or cochrane or ‘embase’/exp or psychlit’/exp or ‘psyclit’/ or ‘science citation index’/exp or bids or scopus 44,495
Disclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminated by the Centers for Disease Control and Prevention and should not be 

construed to represent any agency determination or policy. 15

17 ‘reference lists’ or bibliograph$ or ‘hand search$’ or ‘manual search$’ or ‘relevant journals’ or ‘data extraction’/exp or ‘selection criteria’ 28,035

18 review.pt. 4

19 ‘review’/exp 1,831,423

20 18 or 19 1,831,427

21 17 and 20 15,584

22 letter.pt. or editorial.pt. 3

23 ‘letter’/exp or ‘editorial’/exp 1,179,933

24 22 or 23 1,179,934

25 15 or 16 or 21 98,049

26 25 not 24 93,355

27 ‘sensitivity and specificity/exp or sensitivity or specificity or (‘pre test’ or pretest and adj and ‘probability’/exp) or ‘post-test probability’ or 

predictive and value$ or likelihood and ratio$ or ‘predictive value’/exp or ‘diagnostic accuracy ‘/exp and [english]/lim and [embase]/lim and 

[1998-2012]/py

144,775

28 ‘clinical trial’/exp or ‘randomized controlled trial’/exp or ‘randomization’/exp or ‘single blind procedure’/exp or ‘double blind procedure’/exp 

or ‘crossover procedure’/exp or ‘placebo’/exp or randomi?ed and controlled and trial$ or rct$ or ‘random allocation’ or ‘randomly allocated’ 

or ‘allocated randomly’ or allocated and adj2 and random$ or single and blind$ or double and blind$ or (treble or triple and adj and blind$) or 

placebo$ or ‘prospective study’/exp

539,487

29 ‘case study’/exp or ‘case study’ or ‘case report’/exp or ‘case report’ or ‘abstract report’/exp or ‘abstract report’ or ‘letter’/exp or letter and 

[1998-2012]/py 1,237,206

30 28 not 29 529,538

31 14 or 26 or 27 or 30 6,160,948

32 ‘immunosuppressive agent’/exp or ‘immunosuppressive treatment’/exp or ‘immunosuppressive therapy’ or ‘immunosuppressive agents’ or 

immunolog* or methotrexate or cyclophosphamide or ‘adrenal cortex hormones’ or ‘systemic corticosteroids’ or ‘tumor necrosis factor’ or 

cytoxan or tnf or ‘intra articular’ or ‘tumor necrosis factor’/exp or ‘intraarticular drug administration’/exp or ‘steroid’/exp or 

‘corticosteroid’/exp or ‘methotrexate’/exp or ‘cyclophosphamide’/exp and [1998-2012]/py

1,749,571

33 3 and 8 and 32 697

34 31 and 33 398

COCHRANE DATABASE OF SYSTEMATIC REVIEWS
Disclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminated by the Centers for Disease Control and Prevention and should not be 

construed to represent any agency determination or policy. 16

# Search History Results

1 "(immuno* or immunolog* or steroid* or corticosteroid* or "adrenal cortex hormone*" or methotrexate or cyclophosphamide or cytoxan or 

tnf or "tumor necrosis factor*" or (intra-articular" and inject*)) and (surgery or surgical* or operat*) and (joint* or arthroplast* or prosthe* or 

implant*) in Title, Abstract or Keywords

21
Disclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminated by the Centers for Disease Control and Prevention and should not be 

construed to represent any agency determination or policy. 17

SECTION D. TARGETED SEARCH: ANTICOAGULATION

MEDLINE

# Search History Results

1 (exp "prostheses and implants"/ or prosthe*.af. or implant*.af. or orthoped*.af. or orthopaed*.af.) and (exp joints/ or joint*.af.) 101,924

2 exp Joints/su [Surgery] 44,456

3 exp Arthroplasty, Replacement/ or exp Arthroplasty/ 32,010

4 arthroplasty*.af. 42,928

5 exp “Orthopedic Procedures”/and exp “Joints”/ 39,956

6 or/1-5 141,563

7 exp Infection/ or infection*.af. or infecting.af. or infected.af. or exp "Prosthesis-Related Infections"/ 1,533,905

8 exp Random Allocation/ 73,596

9 exp Randomized Controlled Trials as Topic/ or exp Randomized Controlled Trial/ 394,924

10 exp Double-Blind Method/ 113,512

11 exp Single-Blind Method/ 15,853

12 exp Clinical Trial/ 667,767

13 exp Clinical Trials as Topic/ 251,205

14 clinical trial.pt. 467,170

15 clinical trial, phase i.pt. 11,868

16

(clinical trial, phase ii or clinical trial, phase iii or clinical trial, phase iv or controlled clinical trial or randomized controlled trial or multicenter 

study or clinical trial).pt. 665,448

17 or/8-16 895,443

18 (clinical adj trial$).tw. 164,609

19 ((singl$ or doubl$ or treb$ or tripl$) adj (blind$3 or mask$3)).tw. 111,059

20 placebo$.tw. 133,778

21 randomly allocated.tw. 13,342
Disclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminated by the Centers for Disease Control and Prevention and should not be 

construed to represent any agency determination or policy. 18

22 (allocated adj2 random$).tw. 15,627

23 exp Placebos/ 30,626

24 or/17-23 996,307

25 case report.tw. 164,158

26 letter/ 735,581

27 historical article/ 280,723

28 exp Editorial/ 291,753

29 or/25-28 1,454,788

30 24 not 29 956,341

31 exp “Sensitivity and Specificity”/ 350,527

32 (sensitivity or specificity).tw. 590,136

33 ((pre-test or pretest) adj probability).tw. 980

34 post-test probability.tw. 268

35 predictive value$.tw. 54,259

36 likelihood ratio$.tw. 6,512

37 exp "Predictive Value of Tests"/ 117,980

38 or/30-37 1,740,790

39 exp Meta-Analysis as Topic/ 11,873

40 (meta analy$ or metaanaly$).tw. or exp Meta-analysis/ 48,899

41 (systematic adj (review$1 or overview$1)).tw. 29,904

42 exp Review Literature as Topic/ 6,079

43 or/38-42 1,784,999

44 (embase or cochrane or psyclit* or psychlit* or psycinfo or psychinfo).tw. 27,796

45 (cinahl or cinhal).ab. 5,997

46 (science citation index or bids or cancerlit).ab. 2,135
Disclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminated by the Centers for Disease Control and Prevention and should not be 

construed to represent any agency determination or policy. 19

47 or/43-46 1,792,516

48 (reference list$ or bibliograph$ or hand-search$ or relevant journals or manual search$).ab. 18,484

49 (selection criteria or data extraction).ab. 20,349

50 exp Review/ 1,675,847

51 49 and 50 14,038

52 47 or 48 or 51 1,800,552

53 exp Comment/ or exp Editorial/ or exp Letter/ 1,108,385

54 52 not 53 1,770,101

55

exp Epidemiologic studies/ or exp case control studies/ or exp cohort studies/ or Case control.tw. or (cohort adj (study or studies)).tw. or 

cohort analy$.tw. or (Follow up adj (study or studies)).tw. or (observational adj (study or studies)).tw. or Longitudinal.tw. or Retrospective.tw. 

or Cross sectional.tw. or exp Cross-sectional studies/ 1,553,551

56 54 or 55 2,972,690

57 exp Heparin/ 53,476

58 exp warfarin/ 12,695

59 exp aspirin/ 35,444

60 exp Anticoagulants/ or anticoagul*.af. 191,442

61 "low-dose unfractionated".af. 111

62 (clopidogrel or plavix).af. 6,385

63 (warfarin* or aspirin* or heparin*).af. 136,516

64 exp Platelet Aggregation Inhibitors/ 84,124

65 anti-platelet*.af. 2,453

66 or/57-65 299,002

67 6 and 7 and 56 and 66 52

68 limit 67 to english language 45

69 limit 68 to yr-“1998-Current” 28

EMBASE
Disclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminated by the Centers for Disease Control and Prevention and should not be 

construed to represent any agency determination or policy. 20

# Search History Results

1 ‘infection’/exp 2,328,600

2 Infection$ or infecting or infected 2,654,665

3 ‘prosthesis related’ and infections 95

4 ‘prosthesis-related infections’/exp 2,328,600

5 1 or 2 or 3 or 4 2,660,483

6 ‘prostheses and orthoses’/exp or prosthe$ or implant$ or orthoped$ or orthopaed$ 399,873

7

‘joint’/exp or joint$ or ‘joint surgery’/exp or ‘arthroplasty’/exp or arthroplasty or arthroplasties or ‘arthroplasty replacement’ or (‘orthopedic 

surgery’/exp and ‘joint’/exp) 603,883

8 6 and 7 69,054

9

‘heparin’/exp or ‘warfarin’/exp or ‘acetylsalicylic acid’/exp or ‘anticoagulant agent’/exp or ‘antithrombotic agent’/exp or anticoagul* or ‘lowdose unfractionated’ or clopidogrel or plavix or warfarin* or heparin* or aspirin or ‘anti platelet’ 481,497

10 5 and 8 and 9 374

11 ‘meta analysis’/exp or (meta and adj and analy$) or metaanaly$ or (systematic and adj and (review$ or overview$)) 61,427

12 cancerlit or cochrane or ‘embase’/exp or psychlit’/exp or ‘psyclit’/ or ‘science citation index’/exp or bids or scopus 44,495

13 ‘reference lists’ or bibliograph$ or ‘hand search$’ or ‘manual search$’ or ‘relevant journals’ or ‘data extraction’/exp or ‘selection criteria’ 28,035

14 review.pt. 4

15 ‘review’/exp 1,831,423

16 14 or 15 1,831,427

17 13 and 16 15,584

18 letter.pt. or editorial.pt. 3

19 ‘letter’/exp or ‘editorial’/exp 1,179,933

20 18 or 19 1,174,934

21 11 or 12 or 17 98,049

22 21 not 20 93,355

23 ‘clinical trial’/exp or ‘randomized controlled trial’/exp or ‘randomization’/exp or ‘single blind procedure’/exp or ‘double blind procedure’/exp 541,923
Disclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminated by the Centers for Disease Control and Prevention and should not be 

construed to represent any agency determination or policy. 21

or ‘crossover procedure’/exp or ‘placebo’/exp or randomi?ed and controlled and trial$ or rct$ or ‘random allocation’ or ‘randomly allocated’ 

or ‘allocated randomly’ or allocated and adj2 and random$ or single and blind$ or double and blind$ or (treble or triple and adj and blind$) or 

placebo$ or ‘prospective study’/exp

24

‘case study’/exp or ‘case study’ or ‘case report’/exp or ‘case report’ or ‘abstract report’/exp or ‘abstract report’ or ‘letter’/exp or letter and 

[1998-2012]/py 1,237,206

25 23 not 24 529,538

26 ‘clinical study’/exp or ‘case control study’/exp or ‘family study’/exp or ‘longitudinal study’/exp or ‘retrospective study’/exp 5,942,135

27 ‘prospective study’/exp 189,505

28 ‘randomized controlled trial’/exp 307,692

29 27 not 28 165,671

30

‘cohort analysis’/exp or (cohort and adj and (study or studies)) or (case and control and adj and (study or studies)) or (follow and up and adj 

and (study or studies)) or (observational and adj and (study or studies)) or (epidemiologic$ and adj and (study or studies)) or (cross and 

sectional and adj and (study or studies)) 115,089

31 26 or 27 or 29 or 30 5,986,679

32

‘sensitivity and specificity/exp or sensitivity or specificity or (‘pre test’ or pretest and adj and ‘probability’/exp) or ‘post-test probability’ or 

predictive and value$ or likelihood and ratio$ or ‘predictive value’/exp or ‘diagnostic accuracy ‘/exp and english]/lim and [embase]/lim and 

[1998-2012]/py 144,775

33 22 or 25 or 31 or 32 6,160,948

34 10 and 33 and [english]/lim and [embase]/lim and [1998-2012]/py 221

COCHRANE DATABASE OF SYSTEMATIC REVIEWS

# Search History Results

1

("low molecular weight" or "low-molecular-weight" or anticoag* or heparin or warfarin or aspirin or clopidogrel or plavix or "Platelet 

Aggregation Inhibit*" or anti platelet* ) and ( surgery or surgical* or operat* ) and (joint* or arthroplast* or prosthe* or implant* ) in Title, 

Abstract or Keywords 8

SECTION E. TARGETED SEARCH: SURGICAL ATTIRE

MEDLINE

# Search History Results
Disclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminated by the Centers for Disease Control and Prevention and should not be 

construed to represent any agency determination or policy. 22

1 (exp “prostheses and implants”/ or prosthe*.af. or implant*.af. or orthoped*.af. or orthpaed*.af.) and (exp joints/ or joint*.af.) 102,254

2 exp Joints/su [Surgery] 44,595

3 exp Arthroplasty, Replacement/ or exp Arthroplasty/ 32,203

4 arthroplasty*.af. 43,132

5 exp “Orthopedic Procedures”/ and exp “Joints”/ 40,095

6 or/ 1-5 142,045

7 exp Infection/ or infection*.af. or infecting.af. or infected.af. or exp “Prosthesis-Related Infections”/ 1,541,705

8 exp Random Allocation/ 73,817

9 exp Randomized Controlled Trials as Topic/ or exp Randomized Controlled Trial/ 398,286

10 exp Double-Blind Method/ 114,004

11 exp Single-Blind Method/ 15,965

12 exp Clinical Trial/ 671,638

13 exp Clinical Trials as Topic/ 253,375

14 clinical trial.pt. 468,127

15 clinical trial, phase i.pt. 11,960

16

(clinical trial, phase ii or clinical trial, phase iii or clinical trial, phase iv or controlled clinical trial or randomized controlled trial or multicenter 

study or clinical trial).pt. 669,278

17 or /8-16 901,656

18 (clinical adj trial$).tw. 166,027

19 ((singl$ or doubl$ or treb$ or tripl$) adj (blind$3 or mask$3)).tw. 111,543

20 placebo$.tw. 134,617

21 randomly allocated.tw. 13,439

22 (allocated adj2 random$).tw. 15,726

23 exp Placebos/ 30,724

24 or/17-23 1,003,206
Disclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminated by the Centers for Disease Control and Prevention and should not be 

construed to represent any agency determination or policy. 23

25 case report.tw. 164,737

26 letter/ 742,890

27 historical article/ 281,494

28 exp Editorial/ 295,617

29 or/25-28 1,467,233

30 24 not 29 962,656

31 exp “Sensitivity and Specifity”/ 352,539

32 (sensitivity or specifity).tw. 593,131

33 ((pre-test or pretest) adj probability).tw. 988

34 post-test probability.tw. 273

35 predictive value$.tw. 54,533

36 likelihood ratio$.tw. 6,584

37 exp “Predictive Value of Tests”/ 118,653

38 or/30-27 1,751,101

39 exp Meta-Analysis as Topic/ 12,014

40 (meta analy$ or metaanaly$).tw. or exp Meta-analysis/ 49,880

41 (systematic adj (review$1 or overview$1)).tw. 30,599

42 exp Review Literature as Topic/ 6,214

43 or/38-42 1,795,992

44 (embase or Cochrane or psyclit* or psychlit* or psycinfo or psychinfo).tw. 28,587

45 (cinahl or cinhal).ab. 6,206

46 (science citation index or bids or cancerlit).ab. 2,197

47 or/43-46 1,803,599

48 (reference list$ or bibliograph$ or hand-search$ or relevant journals or manual search$).ab. 18,879

49 (selection criteria or data extraction).ab. 20,833
Disclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminated by the Centers for Disease Control and Prevention and should not be 

construed to represent any agency determination or policy. 24

50 exp Review/ 1,684,812

51 49 and 50 14,483

52 47 or 48 or 51 1,811,665

53 exp Comment/ or exp Editorial/ or exp Letter/ 1,120,430

54 52 not 53 1,780,921

55

exp Epidemiologic studies/ or exp case control studies/ or exp cohort studies/ or Case control.tw. or (cohort adj (study or studies)).tw. or 

cohort analy$.tw. or (Follow up adj (study or studies)).tw. or (observational adj (study or studies)).tw. or Longitudinal.tw. or Retrospective.tw. 

or Cross sectional.tw. or exp Cross-sectional studies/ 1,563,211

56 54 or 55 2,990,436

57 exp Protective Clothing/ or exp Space Suits/ 9,233

58 (exhaust* or ‘exhaust suit*”).af. 27,803

59 (“body exhaust suit*” or “body-exhaust suit*” or “space suit*”).af. 254

60 57 or 58 or 59 36,996

61 6 and 7 and 56 and 60 37

62 limit 61 to english language 35

63 limit 62 to yr=”1998-Current” 21

EMBASE

# Search History Results

1 ‘meta analysis’/exp or (meta and adj and analy$) or metaanaly$ or (systematic and adj and (review$ or overview$)) 61,427

2 cancerlit or cochrane or ‘embase’/exp or psychlit’/exp or ‘psyclit’/ or ‘science citation index’/exp or bids or scopus 44,494

3 ‘reference lists’ or bibliograph$ or ‘hand search$’ or ‘manual search$’ or ‘relevant journals’ or ‘data extraction’/exp or ‘selection criteria’ 28,035

4 review.pt. 4

5 ‘review’/exp 1,831,422

6 4 or 5 1,831,427

7 3 and 6 15,584

8 letter.pt. or editorial.pt. 3
Disclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminated by the Centers for Disease Control and Prevention and should not be 

construed to represent any agency determination or policy. 25

9 ‘letter’/exp or ‘editorial’/exp 1,179,933

10 8 or 9 1,179,934

11 1 or 2 or 7 98,049

12 11 not 10 93,355

13

‘clinical trial’/exp or ‘randomized controlled trial’/exp or ‘randomization’/exp or ‘single blind procedure’/exp or ‘double blind procedure’/exp 

or ‘crossover procedure’/exp or ‘placebo’/exp or randomi?ed and controlled and trial$ or rct$ or ‘random allocation’ or ‘randomly allocated’ 

or ‘allocated randomly’ or allocated and adj2 and random$ or single and blind$ or double and blind$ or (treble or triple and adj and blind$) or 

placebo$ or ‘prospective study’/exp 541,923

14

‘case study’/exp or ‘case study’ or ‘case report’/exp or ‘case report’ or ‘abstract report’/exp or ‘abstract report’ or ‘letter’/exp or letter and 

[1998-2012]/py 1,237,206

15 13 not 14 529,538

16 ‘clinical study’/exp or ‘case control study’/exp or ‘family study’/exp or ‘longitudinal study’/exp or ‘retrospective study’/exp 5,942,135

17 ‘prospective study’/exp 189,505

18 ‘randomized controlled trial’/exp 307,692

19 17 not 18 165,671

20

‘cohort analysis’/exp or (cohort and adj and (study or studies)) or (case and control and adj and (study or studies)) or (follow and up and adj 

and (study or studies)) or (observational and adj and (study or studies)) or (epidemiologic$ and adj and (study or studies)) or (cross and 

sectional and adj and (study or studies)) 115,089

21 16 or 19 or 20 5,986,679

22

‘sensitivity and specificity/exp or sensitivity or specificity or (‘pre test’ or pretest and adj and ‘probability’/exp) or ‘post-test probability’ or 

predictive and value$ or likelihood and ratio$ or ‘predictive value’/exp or ‘diagnostic accuracy ‘/exp and english]/lim and [embase]/lim and 

[1998-2012]/py 144,775

23 12 or 15 or 21 or 22 6,160,948

24 ‘infection’/exp 2,328,600

25 Infection$ or infecting or infected 2,654,665

26 ‘prosthesis related’ and infections 95

27 ‘prosthesis-related infections’/exp 2,328,600

28 24 or 25 or 26 or 27 2,660,483
Disclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminated by the Centers for Disease Control and Prevention and should not be 

construed to represent any agency determination or policy. 26

29 ‘prostheses and orthoses’/exp or prosthe$ or implant$ or orthoped$ or orthopaed$ 399,873

30

‘joint’/exp or joint$ or ‘joint surgery’/exp or ‘arthroplasty’/exp or arthroplasty or arthroplasties or ‘arthroplasty replacement’ or (‘orthopedic 

surgery’/exp and ‘joint’/exp) 603,883

31 29 and 30 69,054

32 ‘surgical attire’/exp or ‘surgical attire’ or ‘protective clothing’/exp or ‘space suit’ or ‘exhaust suit’ or ‘body exhaust suit’ or ‘body-exhaust suit’ 12,127

33 23 and 28 and 31 and 32 and [english]/lim and [embase]/lim and [1998-2012]/py 7

COCHRANE DATABASE OF SYSTEMATIC REVIEWS

# Search History Results

1 (suit* or clothing) and (surgery or surgical* or operat*) and (joint* or arthroplast* or prosthe* or implant*) in Title, Abstract or Keywords 8

CINAHL

# Search History Results

1 (MH “Protective Clothing+”) 3,434

2 “exhaust suit*” 4

3 “space suit*” 3

4 1 or 2 or 3 3,438

5 (MH “Arthoplasty+”) or (MH “Arthroplasty, Replacement+”) 10,000

6 (MH “Prostheses and Implants+”) 34,039

7 (MH “Joints/SU”) 111

8 (MH “Surgery, Operative+”) 197,035

9 (MH “Surgery, Operative+”) and orthopedic* or orthopaedic* or joint* 20,595

10 ((prosthe* or implant* or orthopaed* or orthoped*)) and MW joints 196

11 arthroplasty or arthroplasties 10,691

12 5 or 6 or 7 or 10 or 11 62,799

13 11 and 12 22

14 13 and 4 21
Disclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminated by the Centers for Disease Control and Prevention and should not be 

construed to represent any agency determination or policy. 27

15 (MH “Infection+”) 62,911

16 (MH “Prosthesis-Related Infections”) 610

17 infection* or infected or infecting 129,848

18 15 or 16 or 17 129,848

19 14 and 18 14

20 (MH “Operating Rooms”) 4,940

21 “operating room*” 8,369

22 20 or 21 8,369

23 19 and 22 7
Disclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminated by the Centers for Disease Control and Prevention and should not be 

construed to represent any agency determination or policy. 28

SECTION F. TARGETED SEARCH: ANTIMICROBIAL PROPHYLAXIS WITH A DRAIN

MEDLINE

# Search History Results

1 exp Anti-Infective Agents/ 1,155,786

2 exp Antibiotic Prophylaxis/ 7,457

3 (antimicrobial or ("anti-infective" and agents) or “anti-infective agents”).af. 139,832

4 1 or 2 or 3 1,181,549

5 exp Time/ or exp Time Factors/ or timing.af. or time.af. or timed.af. or duration.af. 2,675,015

6 exp Drainage/ 41,403

7 drain*.af. 93,852

8 6 or 7 102,200

9 4 and 5 and 8 1,930

10 (exp "prostheses and implants"/ or prosthe*.af. or implant*.af. or orthoped*.af. or orthopaed*.af.) and (exp joints/ or joint*.af.) 102,254

11 exp Joints/su [Surgery] 44,595

12 exp Arthroplasty, Replacement/ or exp Arthroplasty/ 32,203

13 arthroplasty*.af. 43,132

14 exp “Orthopedic Procedures”/and exp “Joints”/ 40,095

15 or/10-14 142,045

16 exp Infection/ or infection*.af. or infecting.af. or infected.af. or exp "Prosthesis-Related Infections"/ 1,541,705

17 exp Random Allocation/ 73,817

18 exp Randomized Controlled Trials as Topic/ or exp Randomized Controlled Trial/ 398,286

19 exp Double-Blind Method/ 114,001

20 exp Single-Blind Method/ 15,965

21 exp Clinical Trial/ 671,638

22 exp Clinical Trials as Topic/ 253,375
Disclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminated by the Centers for Disease Control and Prevention and should not be 

construed to represent any agency determination or policy. 29

23 clinical trial.pt. 468,127

24 clinical trial, phase i.pt. 11,960

25

(clinical trial, phase ii or clinical trial, phase iii or clinical trial, phase iv or controlled clinical trial or randomized controlled trial or multicenter 

study or clinical trial).pt. 669,278

26 or/17-25 901,656

27 (clinical adj trial$).tw. 166,027

28 ((singl$ or doubl$ or treb$ or tripl$) adj (blind$3 or mask$3)).tw. 111,543

29 placebo$.tw. 134,617

30 randomly allocated.tw. 13,439

31 (allocated adj2 random$).tw. 15,726

32 exp Placebos/ 30,724

33 or/26-32 1,003,206

34 case report.tw. 164,737

35 letter/ 742,890

36 historical article/ 281,494

37 exp Editorial/ 295,617

38 or/34-37 1,467,233

39 33 not 38 962,656

40 exp “Sensitivity and Specificity”/ 352,539

41 (sensitivity or specificity).tw. 593,131

42 ((pre-test or pretest) adj probability).tw. 988

43 post-test probability.tw. 273

44 predictive value$.tw. 54,533

45 likelihood ratio$.tw. 6,584

46 exp "Predictive Value of Tests"/ 118,653
Disclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminated by the Centers for Disease Control and Prevention and should not be 

construed to represent any agency determination or policy. 30

47 or/39-46 1,751,101

48 exp Meta-Analysis as Topic/ 12,014

49 (meta analy$ or metaanaly$).tw. or exp Meta-analysis/ 49,880

50 (systematic adj (review$1 or overview$1)).tw. 30,599

51 exp Review Literature as Topic/ 6,214

52 or/47-51 1,795,992

53 (embase or cochrane or psyclit* or psychlit* or psycinfo or psychinfo).tw. 28,587

54 (cinahl or cinhal).ab. 6,206

55 (science citation index or bids or cancerlit).ab. 2,197

56 or/52-55 1,803,599

57 (reference list$ or bibliograph$ or hand-search$ or relevant journals or manual search$).ab. 18,879

58 (selection criteria or data extraction).ab. 20,833

59 exp Review/ 1,684,812

60 58 and 59 14,483

61 56 or 57 or 60 1,811,665

62 exp Comment/ or exp Editorial/ or exp Letter/ 1,120,430

63 61 not 62 1,780,921

64

exp Epidemiologic studies/ or exp case control studies/ or exp cohort studies/ or Case control.tw. or (cohort adj (study or studies)).tw. or 

cohort analy$.tw. or (Follow up adj (study or studies)).tw. or (observational adj (study or studies)).tw. or Longitudinal.tw. or Retrospective.tw. 

or Cross sectional.tw. or exp Cross-sectional studies/ 1,563,211

65 63 or 64 2,990,436

66 9 and 15 and 16 79

67 65 and 66 46

68 limit 67 to english language 38

69 limit 68 to yr=”1998-Current” 24

EMBASE
Disclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminated by the Centers for Disease Control and Prevention and should not be 

construed to represent any agency determination or policy. 31

# Search History Results

1

‘antiinfective agent’/exp or ‘antibiotic prophylaxis’/exp or ‘antimicrobial’/exp or ‘anti infective’ or ‘anti-infective agents’/exp and [english]/lim 

and [embase]/lim and [1998-2012]/py 909,070

2 ‘meta analysis’/exp or (meta and adj and analy$) or metaanaly$ or (systematic and adj and (review$ or overview$)) 61,427

3 cancerlit or cochrane or ‘embase’/exp or psychlit’/exp or ‘psyclit’/ or ‘science citation index’/exp or bids or scopus 44,494

4 ‘reference lists’ or bibliograph$ or ‘hand search$’ or ‘manual search$’ or ‘relevant journals’ or ‘data extraction’/exp or ‘selection criteria’ 28,035

5 review.pt. 4

6 ‘review’/exp 1,831,423

7 5 or 6 1,831,427

8 4 and 7 15,584

9 letter.pt. or editorial.pt. 3

10 ‘letter’/exp or ‘editorial’/exp 1,179,933

11 9 or 10 1,179,934

12 2 or 3 or 8 98,049

13 12 not 11 93,355

14

‘clinical trial’/exp or ‘randomized controlled trial’/exp or ‘randomization’/exp or ‘single blind procedure’/exp or ‘double blind procedure’/exp 

or ‘crossover procedure’/exp or ‘placebo’/exp or randomi?ed and controlled and trial$ or rct$ or ‘random allocation’ or ‘randomly allocated’ 

or ‘allocated randomly’ or allocated and adj2 and random$ or single and blind$ or double and blind$ or (treble or triple and adj and blind$) or 

placebo$ or ‘prospective study’/exp 541,923

15

‘case study’/exp or ‘case study’ or ‘case report’/exp or ‘case report’ or ‘abstract report’/exp or ‘abstract report’ or ‘letter’/exp or letter and 

[1998-2012]/py 1,237,206

16 14 not 15 529,538

17 ‘clinical study’/exp or ‘case control study’/exp or ‘family study’/exp or ‘longitudinal study’/exp or ‘retrospective study’/exp 5,942,135

18 ‘prospective study’/exp 189,505

19 ‘randomized controlled trial’/exp 307,692

20 18 not 19 165,671

21 ‘cohort analysis’/exp or (cohort and adj and (study or studies)) or (case and control and adj and (study or studies)) or (follow and up and adj 115,089
Disclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminated by the Centers for Disease Control and Prevention and should not be 

construed to represent any agency determination or policy. 32

and (study or studies)) or (observational and adj and (study or studies)) or (epidemiologic$ and adj and (study or studies)) or (cross and 

sectional and adj and (study or studies))

22 17 or 20 or 21 5,987,932

23

‘sensitivity and specificity/exp or sensitivity or specificity or (‘pre test’ or pretest and adj and ‘probability’/exp) or ‘post-test probability’ or 

predictive and value$ or likelihood and ratio$ or ‘predictive value’/exp or ‘diagnostic accuracy ‘/exp and english]/lim and [embase]/lim and 

[1998-2012]/py 144,775

24 13 or 16 or 22 or 23 6,162,421

25 ‘infection’/exp 2,328,600

26 Infection$ or infecting or infected 2,654,665

27 ‘prosthesis related’ and infections 95

28 ‘prosthesis-related infections’/exp 2,328,600

29 25 or 26 or 27 or 28 2,660,841

30 ‘prostheses and orthoses’/exp or prosthe$ or implant$ or orthoped$ or orthopaed$ 399,873

31

‘joint’/exp or joint$ or ‘joint surgery’/exp or ‘arthroplasty’/exp or arthroplasty or arthroplasties or ‘arthroplasty replacement’ or (‘orthopedic 

surgery’/exp and ‘joint’/exp) 603,883

32 30 and 31 69,062

33 1 and 24 and 29 and 32 and [english]/lim and [embase]/lim and [1998-2012]/lim 1,364

34 ‘drain’/exp or drain* 138,118

35 33 and 34 115

COCHRANE DATABASE OF SYSTEMATIC REVIEWS

# Search History Results

1

(antisept* or antibiotic* or antimicrobial* or anti-infect*) and (surgery or surgical* or operat*) and (joint* or arthroplast* or prosthe* or 

implant*) in Title, Abstract or Keywords 12

SECTION G. TARGETED SEARCH: BIOFILM

MEDLINE
Disclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminated by the Centers for Disease Control and Prevention and should not be 

construed to represent any agency determination or policy. 33

# Search History Results

1 (exp "prostheses and implants"/ or prosthe*.af. or implant*.af. or orthoped*.af. or orthopaed*.af.) and (exp joints/ or joint*.af.) 100,195

2 exp Joints/su [Surgery] 43,624

3 exp Arthroplasty, Replacement/ or exp Arthroplasty/ 30,982

4 arthroplast*.af. 41,886

5 exp "Orthopedic Procedures"/ and exp "Joints"/ 39,075

6 or/1-5 139,184

7 exp Infection/ or infection*.af. or infecting.af. or infected.af. or exp "Prosthesis-Related Infections"/ 1,511,311

8 (adhesin* or biofilm*).af. 22,728

9 exp Adhesins, Bacterial/ 5,227

10 "adhesin, staphylococcus aureus".af. 93

11

("bacterial adhesin receptor" or "polysaccharide intercellular adhesin" or "adhesin, Pseudomonas" or "Bap protein, Staphylococcus 

aureus").af. 322

12 exp Biofilms/ 11,763

13 exp Staphylococcus aureus/ 42,676

14 or/8-13 64,215

15 6 and 7 and 14 515

16 limit 15 to english language 472

17 limit 16 to yr="1998 -Current" 382

18 exp Random Allocation/ 72,622

19 exp Randomized Controlled Trials as Topic/ or exp Randomized Controlled Trial/ 386,853

20 exp Double-Blind Method/ 111,942

21 exp Single-Blind Method/ 15,496

22 exp Clinical Trial/ 656,004

23 exp Clinical Trials as Topic/ 247,358
Disclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminated by the Centers for Disease Control and Prevention and should not be 

construed to represent any agency determination or policy. 34

24 clinical trial.pt. 464,810

25 clinical trial, phase i.pt. 11,518

26

(clinical trial, phase ii or clinical trial, phase iii or clinical trial, phase iv or controlled clinical trial or randomized controlled trial or multicenter 

study or clinical trial).pt. 653,827

27 or/18-26 878,988

28 (clinical adj trial$).tw. 160,316

29 ((singl$ or doubl$ or treb$ or tripl$) adj (blind$3 or mask$3)).tw. 109,518

30 placebo$.tw. 131,568

31 randomly allocated.tw. 13,041

32 (allocated adj2 random$).tw. 15,306

33 exp Placebos/ 30,269

34 or/28-33 977,370

35 case report.tw. 161,905

36 letter/ 726,601

37 historical article/ 278,462

38 exp Editorial/ 285,735

39 or/35-38 1,435,636

40 34 not 39 937,867

41 exp "Sensitivity and Specificity"/ 342,804

42 (sensitivity or specificity).tw. 578,788

43 ((pre-test or pretest) adj probability).tw. 953

44 post-test probability.tw. 260

45 predictive value$.tw. 53,070

46 likelihood ratio$.tw. 6,322

47 exp "Predictive Value of Tests"/ 114,791
Disclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminated by the Centers for Disease Control and Prevention and should not be 

construed to represent any agency determination or policy. 35

48 or/41-47 833,451

49 exp Meta-Analysis as Topic/ 11,663

50 (meta analy$ or metaanaly$).tw. or exp Meta-analysis/ 46,882

51 (systematic adj (review$1 or overview$1)).tw. 28,388

52 exp Review Literature as Topic/ 5,925

53 or/49-52 74,728

54 (embase or cochrane or psyclit* or psychlit* or psycinfo or psychinfo).tw. 26,489

55 (cinahl or cinhal).ab. 5,754

56 (science citation index or bids or cancerlit).ab. 2,076

57 or/54-56 28,166

58 (reference list$ or bibliograph$ or hand-search$ or relevant journals or manual search$).ab. 18,009

59 (selection criteria or data extraction).ab. 19,848

60 exp Review/ 1,647,360

61 59 and 60 13,695

62 53 or 57 or 58 or 61 96,348

63 exp Comment/ or exp Editorial/ or exp Letter/ 1,090,861

64 62 not 63 90,596

65

exp Epidemiologic studies/ or exp case control studies/ or exp cohort studies/ or Case control.tw. or (cohort adj (study or studies)).tw. or 

cohort analy$.tw. or (Follow up adj (study or studies)).tw. or (observational adj (study or studies)).tw. or Longitudinal.tw. or Retrospective.tw. 

or Cross sectional.tw. or exp Cross-sectional studies/ 1,518,084

66 17 and 40 14

67 17 and 48 23

68 17 and 64 2

69 17 and 65 88

70 66 or 67 or 68 or 69 107

EMBASE
Disclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminated by the Centers for Disease Control and Prevention and should not be 

construed to represent any agency determination or policy. 36

# Search History Results

1 ‘biofilm’/exp or ‘adhesin’/exp or biofilm* or adhesion* and [english]/lim and [1998-2012]/py 23,287

2 ‘arthroplasty’/exp and [english]/lim and [1998-2012]/py 37,286

3 1 and 2 104

4

3 and (‘case control study’/de or ‘clinical protocol’/de or ‘clinical study’/de or ‘clinical trial’/de or ‘consensus development’/de or ‘controlled 

clinical trial’/de or ‘controlled study’/de or ‘culture technique’/de or ‘human’/de or ‘in vitro study’/de or ‘major clinical study’/de or ‘practice 

guideline’/ de or ‘prospective study’/de) 94

5 ‘infection’/exp and [english]/lim and [1998-2012]/py 1,005,608

6 4 and 5 82

7 4 and [embase]/lim and [1998-2012]/py 83

COCHRANE DATABASE OF SYSTEMATIC REVIEWS

# Search History Results

1 (biofilm* or adhesin*) in Title, Abstract or Keywords 8
Disclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminated by the Centers for Disease Control and Prevention and should not be 

construed to represent any agency determination or policy. 37

SECTION 2: EVIDENCE, GRADE AND RISK OF BIAS ASSESSMENT TABLES

Q11 BLOOD TRANSFUSION

GRADE TABLE Q11

Comparison Outcome

Quantity 

and Type 

of 

Evidence

Findings Starting 

GRADE

Decrease GRADE Increase 

GRADE

GRADE of 

Evidence 

for 

Outcome

Overall 

GRADE of 

Evidence 

Base

Study QualityConsistencyDirectnessPrecisionPublication BiasLarge MagnitudeDose-responseConfounders

Q11. How do perioperative blood transfusions impact the risk of SSI in prosthetic joint arthroplasty patients? 

Transfusion 

vs. 

No 

transfusion

SSI*

2 RCT 1, 2

4 OBS 3, 4, 5, 

6

 Meta-analysis of 6 studies (N=8493) shows 

increased risk with transfusion: OR: 1.56; 95% 

CI: 1.18 – 2.06; p=0.002

 Meta-analysis of 4 OBS(N=7484) shows increased 

risk with transfusion : OR 1.59; 95% CI: 1.15 –

2.18; p=0.004

 Both meta-analyses include a high proportion of 

infections in patients transfused with allogeneic 

blood only.

 Meta-analysis of 2 RCT (N=1009) shows no 

increased risk of infection in patients transfused 

with autologous or both autologous plus 

allogeneic blood transfusion: OR 1.07; 95% CI: 

0.39 – 2.89; p=0.90. 

High 0 0 0 0 0 0 0 0 High High

Q11A. Are specific blood products associated with a risk of SSI? 

Allogeneic Blood Transfusion

Allogeneic 

(any) vs. No 

Transfusion SSI* 4 OBS 3, 4, 5, 

6

 In meta-analysis of 4 OBS (N=5737), combing all 

allogeneic transfusions without regard to buffy 

coat depletion or leukoreduction, transfusion 

associated with increased risk of infection: OR: 

1.96; 95% CI: 1.46 – 2.63; p<0.001

Low 0 0 0 0 0 0 0 0 Low Low
Disclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminated by the Centers for Disease Control and Prevention and should not be 

construed to represent any agency determination or policy. 38

Comparison Outcome

Quantity 

and Type 

of 

Evidence

Findings Starting 

GRADE

Decrease GRADE Increase 

GRADE

GRADE of 

Evidence 

for 

Outcome

Overall 

GRADE of 

Evidence 

Base

Study QualityConsistencyDirectnessPrecisionPublication BiasLarge MagnitudeDose-responseConfounders

Reoperation 

due to 

wound

infection*

1 OBS 7

 In a large retrospective OBS (N=28,087) of 

primary THA, using a propensity score matched 

population (N=4508), reoperations due to 

infection were rarely reported (only 5 or 0.2% in 

each group) and there was no difference 

between groups (OR: 0.57; 95% CI: 0.11 – 2.93) 

Low 0 0 0 -1 0 0 0 0 Very low

Allogeneic 

Not WBC 

depleted vs. 

No 

Transfusion

SSI* 1 OBS 4

 In a large prospective study (N=3945) of primary 

(81%) and revision (19%) hip and knee surgeries, 

subanalysis of 1644 patients found allogeneic 

“not- WBC depleted” transfusion was associated 

with increased risk of wound infection (OR: 2.12; 

95% CI: 1.13 – 4.00; p=0.02)

 Actual WBC content was not reported.

Low 0 0 0 -1 0 +1 0 0 Low Low

Allogeneic 

WBC 

depleted vs. 

No 

Transfusion

SSI* 1 OBS 4

 In a large prospective study (N=3945) of primary 

(81%) and revision (19%) hip and knee surgeries, 

subanalysis of 1817 patients suggested no 

difference in risk of infection with allogeneic 

“WBC depleted” blood: 18/637(3%) vs. 

22/1180(2%); p=0.19 

 Actual WBC content was not reported.

Low 0 0 0 -1 0 0 0 0 Very Low Very Low

Allogeneic 

“Buffy Coat 

Depleted vs. 

No 

Transfusion

PJI* 1 OBS 5

 In a prospective study of 444 elective primary 

total hip replacements, PJIs were very rare (1% 

of total population) and no difference was 

observed between groups (both groups 1%)

Low 0 0 0 -1 0 0 0 0 Very low

Very low

SSI* 

Incisional 1 OBS 5

 Positive wound cultures were identified in 2.3% 

of population, and no difference was observed 

between groups (3.3% vs. 2.0 %); p=0.47

Low 0 0 0 -1 0 0 0 0 Very low
Disclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminated by the Centers for Disease Control and Prevention and should not be 

construed to represent any agency determination or policy. 39

Comparison Outcome

Quantity 

and Type 

of 

Evidence

Findings Starting 

GRADE

Decrease GRADE Increase 

GRADE

GRADE of 

Evidence 

for 

Outcome

Overall 

GRADE of 

Evidence 

Base

Study QualityConsistencyDirectnessPrecisionPublication BiasLarge MagnitudeDose-responseConfounders

Woundhealing 

disturbance

1 OBS 5

 Allogeneic buffy coat depleted blood transfusion 

associated with increased risk of wound healing 

disturbance (31% vs. 18%; p<0.05)

 On univariate OR 2.1 (95% CI, 1.2-3.5); p=0.03 

and multivariate analyses, transfusion was the 

only significant risk factor 

Low 0 0 0 -1 0 +1 0 0 Low

Allogeneic 

WBC 

Filtered vs. 

No 

Transfusion

SSI* 2 OBS 3, 6

 In a meta-analysis of 2 OBS (N=1637), allogeneic 

WBC filtered was associated with increased risk 

(OR: 1.92; 95% CI: 1.12 – 3.29; p=0.02)

 One study3(N=201) in primary unilateral hip or 

knee arthroplasty (N=201) no difference with 

allogeneic WBC filtered transfusion: 3/100 (3%) 

vs. 1/101 (1%); p=0.33

 In a second larger study6, subanalysis (N=1436) in

primary and revision TKA reported increased risk 

with allogeneic WBC filtered: 32/637 (5.0%) vs. 

22/799 (2.8%); p=0.03

Low 0 0 0 0 0 0 0 0 Low Low

Allogeneic 

”lower WBC 

content” vs. 

Allogeneic 

“higher WBC 

content

SSI* 2 OBS 4, 6

 One study4 (N=1101) comparing allogeneic 

“WBC depleted” and “WBC-not depleted” found 

no difference between groups: 18/637 (3%) vs. 

18/464 (4%); OR: 0.72; 95% CI: 0.37 – 1.40; 

p=0.33

 One study 6(N=1243) comparing allogeneic 

“WBC filtered” to “WBC-not filtered” found no 

difference between groups: No difference: 

32/637 (5.0%) vs. 43/606 (7.1%); P=0.30

Low 0 0 0 0 0 0 0 0 Low Low

Autologous Blood Transfusion

Autologous 

(Any) vs. No 

Transfusion

SSI* 2 RCT 2, 1

2 OBS 4, 3

 No difference in a meta-analysis of 2 RCTs 

(N=970) OR: 1.15, 95% CI: 0.43 – 3.13; p=0.78

 In a small RCT 2of hip arthroplasties subanalyis 

High 0 0 0 -1 0 0 0 0 Moderate Moderate
Disclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminated by the Centers for Disease Control and Prevention and should not be 

construed to represent any agency determination or policy. 40

Comparison Outcome

Quantity 

and Type 

of 

Evidence

Findings Starting 

GRADE

Decrease GRADE Increase 

GRADE

GRADE of 

Evidence 

for 

Outcome

Overall 

GRADE of 

Evidence 

Base

Study QualityConsistencyDirectnessPrecisionPublication BiasLarge MagnitudeDose-responseConfounders

(N=58), no infections were observed in either 

group: 0/49 vs. 0/9, but study was designed to 

evaluate transfusion induced 

immunomodulation, not SSI. (7day follow up)

 1 larger RCT 1 in hip arthroplasties, subanalysis 

(N=912); no difference at 90 day follow up: 

9/481(1.7%) vs. 7/431(1.6%);p>0.05 

 In a large prospective (N=3945) OBS study 4of 

primary and revision hip and knee surgeries, 

subanalysis (N=2491) found autologous 

transfusion was associated with a reduction in 

wound infections: 11/1311 (1%) vs. 22/1180 

(2%); OR: 0.45; 95% CI: 0.22 – 0.92; p=0.03

 In an OBS study3 (N=186) of primary hip or knee 

arthroplasty patients: 0/85 vs.1/101- too few 

events to perform additional analysis.

Autologous 

± WBC 

Filtration 

vs. No 

transfusion

SSI* 1 RCT 1

 No difference in a large RCT (N=1089) in THA 

(regardless of WBC filtration status):

 Subanalysis of 657 patients reported no 

difference with autologous “no WBC filtration” 

transfusions: 5/226(2.2%) vs. 7/431(1.6%); 

p=0.59

 Subanalysis of 686 patients reported no 

difference with autologous WBC filtered blood 

transfusions: 3/255(1.2%) vs. 7/431(1.6%); 

p=0.64

High 0 0 0 -1 0 0 0 0 Moderate Moderate
Disclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminated by the Centers for Disease Control and Prevention and should not be 

construed to represent any agency determination or policy. 41

Comparison Outcome

Quantity 

and Type 

of 

Evidence

Findings Starting 

GRADE

Decrease GRADE Increase 

GRADE

GRADE of 

Evidence 

for 

Outcome

Overall 

GRADE of 

Evidence 

Base

Study QualityConsistencyDirectnessPrecisionPublication BiasLarge MagnitudeDose-responseConfounders

Autologous 

Whole 

Blood vs. No 

Transfusion

SSI* 1 RCT 2

 In a small RCT of THA, subanalysis of 34 patients, 

no infections in either group at 7 day follow up. 

Whole blood included autologous donated and 

perioperative salvage blood.

 The study was designed to evaluate transfusion 

induced immunomodulation, not SSI.

High 0 0 0 -2 0 0 0 0 Low Low

Autologous 

“Not WBC 

depleted” 

vs. No 

Transfusion

SSI* 1 OBS 4

 In a large prospective (N=3945) study of primary 

and revision hip and knee surgeries, subanalysis 

(N=2491) found autologous transfusion 

(including autologous blood donated whole 

blood or packed red blood cells, cell saver, acute 

normovolemic hemodilution, and postoperative 

salvage) was associated with a reduction in 

wound infections: OR: 0.45; 95% CI: 0.22 – 0.92; 

p=0.03, follow up period was limited to the 

patient’s stay in the surgical unit. Transfusion 

trigger for autologous blood transfusion is not 

reported

 Autologous donated blood only: 4/610 (0.66%) 

vs. 22/1180 (1.86%); p=0.053

 Autologous postoperative salvage blood only: 

8/191 (4.19%) vs. 22/1180 (1.86%)p<0.05

Low 0 0 0 -1 0 0 0 0 Very low Very Low

Autologous 

Buffy Coat 

Depleted vs. 

No 

Transfusion

SSI* 1 RCT 2

1 OBS 3

 In a small RCT (107942) of hip arthroplasties 

(N=33), no infections were observed in either 

group at 7 day follow up. The study was designed 

to evaluate transfusion induced 

immunomodulation, not SSI. 

 In 1 OBS (108043) (N=186) of primary hip or knee 

arthroplasty patients: 0/85 vs.1/101- too few 

events to perform additional analysis.

High 0 0 0 -2 0 0 0 0 Low Low
Disclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminated by the Centers for Disease Control and Prevention and should not be 

construed to represent any agency determination or policy. 42

Comparison Outcome

Quantity 

and Type 

of 

Evidence

Findings Starting 

GRADE

Decrease GRADE Increase 

GRADE

GRADE of 

Evidence 

for 

Outcome

Overall 

GRADE of 

Evidence 

Base

Study QualityConsistencyDirectnessPrecisionPublication BiasLarge MagnitudeDose-responseConfounders

Autologous 

“lower WBC 

content” vs. 

Autologous 

”higher WBC 

content”

SSI* 2 RCT 2, 1

 In a small RCT 2of hip arthroplasties (N=49), no 

infections were observed in either group at 7 day 

follow up. The study was designed to evaluate 

transfusion induced immunomodulation, not SSI.

 In a large RCT 1of total hip arthroplasties (per 

protocol analysis, n=481), no difference was 

observed between groups: OR: 0.53; 95% CI: 0.12 

– 2.23; p=0.30. Only 1 PJI reported in each group 

(Intention to treat analysis n=951)

High 0 0 0 -1 0 0 0 0 Moderate Moderate

Postoperative 

salvage only 

vs.

Autologous 

Donated 

blood-only

SSI* 1 OBS 4

 In one large OBS study of elective primary and 

revision hip and knee arthroplasties, subanalysis 

in 801 patients showed significantly higher 

infection rates with postoperative salvage 

recovery only autologous blood versus 

autologous donated blood only in both hip: 3/69

(4%) vs. 4/462 (1%); p<0.05 and knee

arthroplasties: 5/122 (4%) vs. 0/148 (0%); 

p<0.05. Hip and knee arthroplasties combined: 

8/191 (4.19%) vs. 4/610 (0.66%) OR: 0.15; 95% 

CI: 0.04 – 0.51; p=0.002

Low 0 0 0 -1 0 +1 0 0 Low Low

Allogeneic vs. Autologous blood transfusion

Allogeneic 

(Any) vs. 

Autologous 

(Any)

SSI* 3 OBS 8, 3, 4

 When combining transfusions without regard to 

buffy coat depletion or leukoreduction, 

transfusion with allogeneic blood was associated 

with increased risk of SSI as compared to 

autologous transfusion (OR: 4.53; 95% CI: 2.37 –

8.65; p<0.0001) 

Low 0 0 0 0 0 +1 0 0 Moderate Moderate
Disclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminated by the Centers for Disease Control and Prevention and should not be 

construed to represent any agency determination or policy. 43

Comparison Outcome

Quantity 

and Type 

of 

Evidence

Findings Starting 

GRADE

Decrease GRADE Increase 

GRADE

GRADE of 

Evidence 

for 

Outcome

Overall 

GRADE of 

Evidence 

Base

Study QualityConsistencyDirectnessPrecisionPublication BiasLarge MagnitudeDose-responseConfounders

Allogeneic ± 

WBC 

depleted vs. 

Autologous 

Not WBC 

depleted

SSI* 2 OBS 4, 8

 Allogeneic NOT WBC Depleted: In a large 

prospective study 4of hip and knee surgeries, 

subanalysis in 1775 patients showed increased 

risk: 18/464 (4%) vs. 11/1311 (1%); (OR: 4.77; 

95% CI: 2.24 – 10.18; p<0.0001)

 WBC Not Depleted: In one prospective study 4

Allogeneic versus autologous blood donation 

only: 18/464 (4%) vs. 4/610 (0.66%); p=0.001

 WBC Not Depleted: One prospective study 4

Allogeneic versus postoperative salvage only: 

18/464 (4%) vs. 8/191 (4.19%); p=0.85

 WBC depleted: One prospective study 4

Subanalysis in 1948 patients showed allogeneic 

“WBC depleted” transfusion was associated with 

increased risk of wound infection: 18/637(3%) vs. 

11/1311(1%); p=0.001

 WBC Depleted: In one small observational study8

in hip arthroplasties, allogeneic “WBC depleted” 

blood transfusion was not associated with 

increased risk of infection as compared to 

perioperative cell saver shed washed blood: 2/48 

(4.17%) vs. 0/49; p=0.28

Low 0 0 0 0 0 +1 0 0 Moderate Moderate

Allogeneic 

WBC 

Filtered vs. 

Autologous 

Buffy coat 

depleted

SSI* 1 OBS 3

 No difference: 3/100 (3%) vs. 0/85; p=0.23. Low 0 0 0 -1 0 0 0 0 Very low Very low 

Both Autologous and Allogeneic Blood Transfusion
Disclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminated by the Centers for Disease Control and Prevention and should not be 

construed to represent any agency determination or policy. 44

Comparison Outcome

Quantity 

and Type 

of 

Evidence

Findings Starting 

GRADE

Decrease GRADE Increase 

GRADE

GRADE of 

Evidence 

for 

Outcome

Overall 

GRADE of 

Evidence 

Base

Study QualityConsistencyDirectnessPrecisionPublication BiasLarge MagnitudeDose-responseConfounders

Both 

Autologous 

and 

Allogeneic

(Any) vs. No 

Transfusion

SSI* 1 RCT 1

2 OBS 4, 3

 No difference in post-hoc subanalysis1(N=470) : 

0 of 39 transfused vs. 1.6% of 431 not transfused

(p=0.82)

 One study4No difference: 8/329 (2%) vs. 

22/1180 (2%) OR: 1.31; 95% CI: 0.58 – 2.97; 

p=0.52

 No difference in subanalysis 3(n=123): 0/22 vs. 

1/101 (1%)

High 0 0 0 -1 0 0 0 0 Moderate Moderate

Both 

Autologous 

and 

Allogeneic 

vs. 

Autologousonly 

SSI* 2 OBS 9, 4

 In a large OBS study 9(N=2884) of primary total 

hip (n=2016) and knee (n=480) arthroplasties 

and hip revisions (n=388), transfusion with both 

allogeneic (buffy coat depleted) and autologous 

(buffy coat depleted and salvaged blood) was 

associated with increased risk of wound infection 

compared with autologous (buffy coat depletedonly) blood alone. Statistical testing was not 

possible (data presented in graph format).

 In 1 study4SSI= 8/329 (2%) vs. 11/1311 (1%); 

p=0.02

Low 0 0 0 0 0 0 0 0 Low Low

Q11B. If the risk of SSI is increased, can this effect be isolated from the risk associated more complex cases?

Revision vs. 

Primary 

Arthroplasty 

(Hip [THA] 

and knee 

[TKA] 

combined)

Transfusion* 2 OBS 4, 6

 Increased risk of transfusion among revisions 

(THA and TKA combined) in a meta-analysis of 2 

OBS studies (N=6385): OR 3.81; 95% CI: 1.61 –

9.03; p=0.002

 In one study 4Increased risk among revisions: 

303/362 (84%) vs. 2112/3118 (68%); p<0.001

 In one observational study6Increased risk 

among revisions: 274/350(78%) vs. 

969/2555(38%); p<0.001

Low 0 0 0 0 0 +1 0 0 Moderate Moderate
Disclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminated by the Centers for Disease Control and Prevention and should not be 

construed to represent any agency determination or policy. 45

Comparison Outcome

Quantity 

and Type 

of 

Evidence

Findings Starting 

GRADE

Decrease GRADE Increase 

GRADE

GRADE of 

Evidence 

for 

Outcome

Overall 

GRADE of 

Evidence 

Base

Study QualityConsistencyDirectnessPrecisionPublication BiasLarge MagnitudeDose-responseConfounders

Revision 

THA 

vs. Revision 

TKA

Transfusion* 1 OBS 4  Higher risk of transfusion among revision THA: 

252/293(86%) vs. 51/69(74%); p=0.02 Low 0 0 0 -1 0 0 0 0 Very Low

Very Low

Calculated 

blood loss 1 OBS 4  No difference in median calculated blood loss: 

2875ml vs. 2528ml; p=0.23 Low 0 0 0 -1 0 0 0 0 Very Low

Revision 

THA 

vs.

Primary THA

Transfusion* 2 OBS 4, 9

 Any blood transfusion 4: Higher risk among 

revision hip arthroplasties: 252/293 (86%) vs. 

1405/2066 (68%); p<0.001 

 Allogeneic only4: More allogeneic only 

transfusions among transfused revision hips as 

compared to primary hip arthroplasties: 

115/252 (46%) vs. 503/1405 (36%); p=0.003 

 Autologous only4: More autologous only 

transfusions among transfused primary hip as 

compared to revision hip arthroplasties: 83/252

(33%) vs. 737/1405 (52%); p<0.001 

 BOTH Autologous and additional allogeneic 

blood transfusion; Higher risk among revision 

THAs- Meta-analysis (N=4061): OR 2.44; 95% CI: 

1.77 – 3.36; p<0.001

 One OBS4Higher risk among revision THAs: 

54/252 (21%) vs. 165/1405 (12%); p<0.001

 One OBS 9Higher risk among revision THAs: 

76/388 (20%) vs. 159/2016 (8%); p=0.0005

Low 0 0 0 0 0 0 0 0 Low Low
Disclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminated by the Centers for Disease Control and Prevention and should not be 

construed to represent any agency determination or policy. 46

Comparison Outcome

Quantity 

and Type 

of 

Evidence

Findings Starting 

GRADE

Decrease GRADE Increase 

GRADE

GRADE of 

Evidence 

for 

Outcome

Overall 

GRADE of 

Evidence 

Base

Study QualityConsistencyDirectnessPrecisionPublication BiasLarge MagnitudeDose-responseConfounders

Calculated 

blood loss 2 OBS 4, 9

 Meta-analysis 2 OBS studies: significantly higher 

calculated blood loss in revision hips: mean 

difference 700 ml (95% CI: 323 ml – 1076 ml); 

p=0.0003 

 Mean calculated blood loss higher for revision 

hip: 3060 ml vs. 2143 ml; p<0.001 ml4; Mean 

blood loss significantly higher for revision hip: 

1720±460ml vs. 1190±480ml; p=.0005 9

Low 0 0 0 0 0 0 0 0 Low

Procedure 

duration 1 OBS 9

 Significantly longer procedure duration for 

revision hip arthroplasty (mean ±SD): 183±64 

minutes vs. 115±38 minutes; p=0.0005

Low 0 0 0 -1 0 0 0 0 Very Low

Revision

TKA

vs.

Primary TKA

Transfusion* 1 OBS 4

 Any transfusion no difference for revision knee 

as compared to primary knee: 51/69 (74%) vs. 

707/1052 (67%); p=0.25 no difference for 

revision knee as compared to primary bilateral 

knees: 51/69 (74%) vs. 11/13 (85%); p=0.42 

 Allogeneic only: No difference- 23/51 (45%) vs. 

245/707 (35%); p=0.13 

 Autologous only: No difference -17/51 (33%) vs. 

245/707 (49%); p=0.85

 BOTH autologous and additional allogeneic 

blood transfusion higher risk of transfusion for 

revision knees: 11/51 (21%) vs. 77/707 (11%); 

p=0.02

Low 0 0 0 -1 0 0 0 0 Very Low Very low

Calculated 

blood loss 1 OBS 4  Mean calculated blood loss higher for revision 

knee: 2634 ml vs. 2072 ml; p=0.002 Low 0 0 0 -1 0 0 0 0 Very Low
Disclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminated by the Centers for Disease Control and Prevention and should not be 

construed to represent any agency determination or policy. 47

Comparison Outcome

Quantity 

and Type 

of 

Evidence

Findings Starting 

GRADE

Decrease GRADE Increase 

GRADE

GRADE of 

Evidence 

for 

Outcome

Overall 

GRADE of 

Evidence 

Base

Study QualityConsistencyDirectnessPrecisionPublication BiasLarge MagnitudeDose-responseConfounders

Primary 

THA 

vs. 

Primary

TKA

Transfusion* 2 OBS 4, 9

 Any transfusion 4: No difference- 1405/2066 

(68%) vs. 707/1052 (67%); p=0.65

 Allogeneic only 4: No difference- 503/1405 

(36%) vs. 245/707 (35%); p=0.60

 Autologous only4: No difference- 737/1405 

(52%) vs. 385/707 (54%); p=0.38

 Both Autologous and additional allogeneic 4: No 

difference- 165/1405 (12%) vs. 77/707 (11%); 

p=0.56 

 BOTH autologous and additional allogeneic 9: No 

difference-159/2016 (8%) vs. 43/480 (9%); 

p=0.44

Low 0 0 0 0 0 0 0 0 Low

Low

Calculated 

blood loss 2 OBS 4,9

 Meta-analysis 2 OBS: No difference- Mean 

difference: -19 ml (95% CI: -176 ml – 137 ml); 

p=0.81

 Mean calculated blood loss no difference: 2143 

ml vs. 2072 ml; p=0.24 4

 Mean blood loss higher in primary knee 

arthroplasty 1190±480ml vs. 1280±403; 

p=0.0001 9

 Median preoperative estimate blood loss was 

significantly lower than median calculated blood 

loss for both primary total hip (median 750 vs. 

1944ml; p<0.001) and total knee (median, 800 

vs. 1934ml; p<0.001) procedures4.

Low 0 -1 0 0 0 0 0 0 Very low

Primary 

THA: 

Unilateral 

vs. Bilateral

Transfusion* 1OBS 4

 Any transfusion -No difference: 1387/2039

(68%) vs. 18/27 (67%); p=0.88

 Allogeneic only: No difference: 496/1387 (36%) 

vs. 7/18 (39%); p=0.78

 Autologous only: No difference 728/1387 (53%) 

Low 0 0 0 -1 0 0 0 0 Very Low Very low
Disclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminated by the Centers for Disease Control and Prevention and should not be 

construed to represent any agency determination or policy. 48

Comparison Outcome

Quantity 

and Type 

of 

Evidence

Findings Starting 

GRADE

Decrease GRADE Increase 

GRADE

GRADE of 

Evidence 

for 

Outcome

Overall 

GRADE of 

Evidence 

Base

Study QualityConsistencyDirectnessPrecisionPublication BiasLarge MagnitudeDose-responseConfounders

vs. 9/18 (50%); p=0.83 

 BOTH Autologous and additional allogeneic 

blood transfusion: No difference: 163/1387

(12%) vs. 2/18 (11%); p=0.93

Primary 

TKA:

Unilateral 

vs. Bilateral

Transfusion* 1OBS 4

 Any transfusion: No difference: 696/1039 (67%) 

vs. 11/13(85%); p=0.20 

 Allogeneic only: No difference - 242/696 (35%) 

vs. 3/11(27%); p=0.61 

 Autologous only: No difference 377/696 

(54%)vs. 8/11(74%); p=0.23

 BOTH Autologous and additional allogeneic: 

Only unilateral TKA received both:- 77/696 

(11%) vs. 0/11(0%); p=0.47

Low 0 0 0 -1 0 0 0 0 Very Low Very low

*Critical outcome; OR: Odds Ratio; RR: Risk Ratio; CI: Confidence Interval
Disclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminated by the Centers for Disease Control and Prevention and should not be 

construed to represent any agency determination or policy. 49

EVIDENCE TABLE Q11

Q11. How do perioperative blood transfusions impact the risk of SSI in prosthetic joint arthroplasty patients? 

A. Are specific blood products associated with a risk of SSI? 

B. If the risk of SSI is increased, can this effect be isolated from the risk associated with more complex cases?

Author

Year

(Data 

Extractor)

Risk of Bias

Score Study Objective Population and Setting (N) Intervention Results Comments

Frietsch

2008 1

(SIBT)

RCT

1, 2, 3, 4, 5,

7, 8, 9, 10

.

To determine if 

leukoreduction of 

autologous whole 

blood (AWB) 

reduces the 

transfusion-related 

immunomodulatio

n (TRIM) effect, 

resulting in 

reduced 

perioperative 

infection rate 

and/or length of 

hospital stay.

No. patients:

ITT: N=951

Per-Protocol=481 

Patient 

Characteristics: 

Baseline 

characteristics of 

the patients were 

similar in the two 

groups (number, 

sex, age, height, 

weight, calculated 

blood volume, 

overall estimated 

perioperative blood 

loss, donated 

autologous units per 

patient, ASA score, 

Anesthesia type, 

surgery type 

[cementless, 

cemented, hybrid], 

duration of surgery, 

anesthesia and 

hypothermia. 

Age years

median (range)

Intervention:63 (28-

Intervention Group: 

Leukodepleted AWB (LDAWB)

ITT n=488

Per Protocol n=255 

(52.3%)

Timing of Intervention: 

Intra and postoperative

Duration of Intervention: 

NR

Device/ Agent: 

Intervention (LD-AWB):

double bag system with 

inline whole-blood WBC 

filter for pre-storage 

leukoreduction. Blood was 

leukoreduced after storage 

on cooling plates at 4 to 

6°C for 1-4 hours. Residual 

WBC content was 

consistently below 1 X 106

per unit and mean red 

blood cell loss (RBC) was 

less than 10%. 

Control (non-ND AWB):

single-bag system. All 

units stored at 4°C until 

transfusion or expiry

Both systems contained 

SSI (3 months)

ITT Analysis N=951

Wound Infections

Intervention: 6/488 

(1.2%);

Control: 9/463 (1.9%)

OR 0.63 (95% CI, 0.22-

1.78); p=0.27

Other infections

Overall, urinary, 

respiratory, 

fungal and Other 

(gastrointestinal, pleuritis, 

vascular thrombophlebitis, 

skin infection other than 

wound, gynecologic) none 

with statistically significant 

difference

Note: Infections occurred 

while in hospital in 87.5% 

of cases.

Per-protocol Analysis 

N=481

Wound Infections

Intervention: 3/255 (1.2%)

Control: 5/226 (2.2%) 

0.53(0.12-2.23);p=0.30

Other infections

Overall, urinary, 

Definitions: 

Wound Infection: Defined either as 

1. isolation of bacteria from fluid wound 

secretions containing pus,

2. abscesses (verified by surgical 

drainage or aspiration of pus), or 

3, arthritis by clinical symptoms 

requiring surgical drainage.

Respiratory tract infection (RTI): 1) 

positive x-ray (chest infiltration) 

together with fever, 20 dyspnea or 

cough or purulent sputum together with 

fever, or 3) isolation of bacteria in 

tracheal secretion (only intubated 

patients) together with fever. 

ASEPSIS Index: Daily wound inspections 

evaluated for the following wound 

conditions: clear exudate, erythema, 

putrid exudate, dehiscence of profound 

tissue layers with size of relative wound 

area of the total wound concerned. If 

more than one wound condition was 

existent, only the condition with the 

highest rating was scored. Wound 

inspection scores were added up 

(dynamic part). Each of the additional 

criteria (antimicrobial treatment, 

abscess drainage [local vs. general 

anesthesia], bacterial growth [positive 
Disclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminated by the Centers for Disease Control and Prevention and should not be 

construed to represent any agency determination or policy. 50

Author

Year

(Data 

Extractor)

Risk of Bias

Score Study Objective Population and Setting (N) Intervention Results Comments

82)

Control:63 (26-83)

Gender m/f: 

470/481

mean±SD(median/r

ange)

Height (cm)

Intervention:

170±8.9 (170/150-

196)

Control: 

170.3±9.0(170/140-

197)

Weight(kg)

Intervention: 

80.1 ±14.1(80/48-

126)

Control: 

80.4±14.2(80/50-

136)

ASA1=192/951 

(20.2%)

ASA2=628/951(66.0

%)

ASA3=125/951(13.1

%)

Procedure: Primary 

hip arthroplasty 

(cemented n=30, 

cementless n=642, 

hybrid n=274)

Indications: NR

Setting: 2 university 

and 1 urban 

hospital: 

Center A n=696 

70ml citrate phosphate 

dextrose adenine (CPDA-1) 

as storage medium.

Monitoring Intervention: 

Hemoglobin (Hb) levels.

Transfusion Trigger: 

Hemoglobin (Hb) 

concentration <8.0±0.5g/L 

during and after surgery 

(irrespective of whether 

autologous or allogeneic 

blood was to be 

transfused) 

Control Group- Nonleukodepleted AWB (nonLD AWB)

ITT n=463 

Per Protocol n=226 

(48.8%)

Standard preventive 

measures AMP (second 

generation cephalosporin)

, normothermia, 

normovolemia, adequate 

oxygenation

respiratory, 

fungal and Other 

(gastrointestinal, pleuritis, 

vascular thrombophlebitis, 

skin infection other than 

wound, gynecologic) none 

with statistically significant 

difference

In both ITT and PerProtocol:

Overall infection rate, 

ASEPSIS score, Length of 

Stay, antimicrobial 

treatment, multidrug use, 

fever>38°C after postop 

day 3: No significant 

difference

SUBGROUP ANALYSIS 1:

Not transfused (NOT-T; 

n=431) vs.

Autologous only 

transfused (AUT-T; n=481) 

vs.

Additionally allogeneically 

transfused (ALL-T; n=39) 

Overall infection rate: 

NOT-T: 14.2%

AUT-T: 20.6%

ALL-T: 13.2%

p=0.03

Wound infections:

NOT-T: 1.6%

AUT-T: 1.7% 

ALL-T: 0%

culture of at least 100,000 colonies of a 

single organism], and prolonged 

hospital stay (static part) could be 

added once.

Perioperative Care

Preop:

Patients were scheduled to donate 2 or 

3 units of AWB (500ml each) in weekly 

intervals with surgery planned to take 

place in weeks 3 to 5 after the first 

donation.

Hb concentration below 110g/L during 

donation period led to postponement of 

following donation by 1 week.

Patients encouraged to take oral iron 

(300mgFe2+ orally per day)

RBC loss was calculated as the 

compensated RBC loss (perioperatively 

transfused RBC volume) plus noncompensated RBC loss estimated from 

pre and postoperative (Day 3) 

hematocrit (Hct) levels correcting largevessel to total body Hct:

RBC loss= (Hctpre-HctPOD3) X Blood 

Volume* X 0.86+RBC-Vunits.

RBC-Vunits=RBC volume of transfused 

AWB

*Calculated according to Nadler)

Blood loss=RBC loss/(Hctpre-HctPOD3)/2

Transfusion rates by Center:

No transfusion; autologous only; 
Disclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminated by the Centers for Disease Control and Prevention and should not be 

construed to represent any agency determination or policy. 51

Author

Year

(Data 

Extractor)

Risk of Bias

Score Study Objective Population and Setting (N) Intervention Results Comments

(73.2%); Center B 

n=213 (22.4%) 

Center C n=42 

(4.4%)

Location: Germany

Dates: NR

Inclusion criteria: 

Patients scheduled 

for primary hip 

arthroplasty and 

preoperative 

donation of at least 

2 units of AWB 

Exclusion criteria: 

Subjects with 

contraindications 

for preoperative 

autologous blood 

donation according 

to the German 

guidelines, immune 

deficiency, steroid 

therapy and 

intended use of cell 

salvage.

p=>0.05

Urinary tract Infection:

NOT-T 11.1%

AUT-T 16.8% 

ALL-T 13.2%

p=0.02

Other infections:

Respiratory, fungal, and 

other infections 

(gastrointestinal, pleuritis, 

vascular thrombophlebitis, 

skin infection other than 

wound, gynecologic) all 

p=>0.05

Length of Stay days:

mean±SD (median)

NOT-T 13.0±2.3 (13) 

AUT-T 13.8±3.6 (14)

ALL-T 14.3±4.2 (14)

p=≤0.001

Note: significant 

difference in infection rate 

and length of stay was 

paralleled by significantly 

longer anesthesia and 

surgery duration (NR), 

suggesting dependency 

from the complexity level 

of surgery rather than 

transfusion.

SUBGROUP ANALYSIS 2: 

Micro-aggregate filtration 

of blood product at 

autologous and allogeneic

A n=696: 43%;52.7%;4.3% 

B n=213:56.8%;39.4%;3.8%

C n=42: 26.2%, 71.4%, 2.4%

Anesthesia

Spinal: Intervention: AWB 297/488 

(60.9%)

Control: Non LD AWB: 312/463 (67.4%)

General: Intervention: AWB 187/488 

(38.3%)

Control: Non LD AWB: 143/463 (30.9%)

Epidural: Intervention: AWB 2/488 

(0.4%)

Control: Non LD AWB: 1/463 (0.2%)

Other Intervention: AWB 2/488 (0.4%)

Control: Non LD AWB: 3/463 (0.6%)

Follow up: Phone, letter or an 

outpatient visit 3 months post op.

Wound inspection: daily during the first 

14 postoperative days and discharge, 

not on weekends
Disclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminated by the Centers for Disease Control and Prevention and should not be 

construed to represent any agency determination or policy. 52

Author

Year

(Data 

Extractor)

Risk of Bias

Score Study Objective Population and Setting (N) Intervention Results Comments

bedside at Centers A and

C. Subgroup analysis to 

exclude any influence of 

these microfilters on 

overall infections rate 

showed no statistical 

significant difference 

(p=0.63, two-sided). 

Topic specific outcomes: 

N/A

Reoperation:

In both ITT and PerProtocol:

antimicrobial treatment, 

multidrug use: No 

significant difference 

In ITT protocol: 

Wound infection requiring 

revision or hospitalization: 

Intervention: 1/488 (0.2%)

Control: 3/463 (0.6%)

Delayed wound healing 

requiring revision or 

hospitalization: 

Intervention: 7/488 (1.4%)

Control: 7/463 (1.5%)

Surgical wound revision:

Intervention: 3/488 (0.6%)

Control: 8/463 (1.7%)

Prosthesis infection:

Intervention: 1/488 (0.2%)

Control: 1/463 (0.2%)

Re-surgery - prosthesis 

exchange:
Disclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminated by the Centers for Disease Control and Prevention and should not be 

construed to represent any agency determination or policy. 53

Author

Year

(Data 

Extractor)

Risk of Bias

Score Study Objective Population and Setting (N) Intervention Results Comments

Intervention: 1/488 (0.2%)

Control: 1/463 (0.2%)

Length of stay: Median 

(range)

ITT

Intervention (LD AWB): 14 

days (7-36)

Control (Non-LD AWB):14 

days (8-55)

P=0.17

Per-Protocol

Intervention (LD AWB): 14 

days (7-34)

Control (Non-LD AWB):14 

days (9-55)

P=0.71

Mortality: none

Adverse events:

In ITT protocol: not 

significantly different 

between groups

Total: 

Intervention: 1/488

Control: 1/463

Relation to LD:

Possible /unlikely 

unrelated

Intervention: 3/7/3

Control: 2/2/8 

Myocardial infarction, 

bradycardic arrhythmia, 

transient cerebral, 

ischemic attack, 

respiratory insufficiency 
Disclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminated by the Centers for Disease Control and Prevention and should not be 

construed to represent any agency determination or policy. 54

Author

Year

(Data 

Extractor)

Risk of Bias

Score Study Objective Population and Setting (N) Intervention Results Comments

(sleep apnea), deep 

venous thrombosis, 

dyesthesia foot

Frietsch

2001 2

(ES)

RCT

1, 2, 5, 7, 8, 

9, 10

To address 

Transfusioninduced 

immunomodulatio

n (TRIM) caused by 

autologous blood –

stored either as 

Whole Blood (WB) 

or as buffy coatpoor packed red 

cells and freshfrozen plasma 

(RCP) – in patients 

undergoing hip 

arthroplasty. 

Monocyte and 

neutrophil 

phagocytic 

activities, rate of 

systemic and 

wound infection, 

se of 

antimicrobials and 

length of hospital 

stay (LOS) were 

evaluated.

Number of patients 

N=58 

Patient 

Characteristics

WB=Whole Blood

RCP=buffy coatpoor packed Red 

Cells and freshfrozen Plasma

NT-NO Transufsion 

·Age: mean±SD

 WB: 58±10 years

 RCP: 59±10 years

 NT: 61±8 years

·Gender: m/f

 WB: 9/16

 RCP: 10/14

 NT: 7/2

·Obesity:

Weight

 WB: 71±16 kg

 RCP: 74±15 kg

 NT: 84±10 kg

Height

 WB: 166±9 cm

 RCP: 168±7 cm

 NT: 171±5 cm

·Comorbidities: NR

3Units Predeposited

 WB: 22/25(88%)

 RCP: 22/24 (91.2%)

 NT: 9/9 (100%)

2 Units 

Intervention group: n=2

Transfused Autologous 

Blood:

Blood was donated at 

weekly intervals (450ml 

each). Surgery was 

scheduled for the 5th week 

after the first donation.

RCP: Buffy coat-poor 

packed red cells (RC) and 

fresh-frozen plasma (FFP):

n=24 donated blood was 

separated into RC and 

FFP(80-90% of leukocytes 

and >98% platelets were 

eliminated)

Timing of intervention: 

intra or postoperatively

Duration of intervention: 

Intra and/or 

postoperatively.

Agent: Autologous blood. 

Either Whole blood (WB) 

or buffy-coat poor packed 

red cells (RC) 

- Oldest blood was used 

first.

Monitoring intervention: 

hemoglobin count and 

leucocyte counts were 

determined by routine 

automated laboratory 

methods. Differential 

SSI (follow up 7 days)

None of the patients 

presented clinical signs of 

infection. Authors indicate 

“This study is not expected 

to have the statistical 

power to discriminate 

between the two types of 

storage regarding outcome 

criteria of 

immunomodulation, such 

as wound or systemic 

infection rates or LOS, as 

the infection rate in this 

type of surgery is generally 

low”

Other infections: None 

occurred in either group.

Topic-specific outcomes:

No allogeneic transfusions 

were required in any 

group.

Total Blood loss: median 

(Range) 

 WB: 1740 (820-3170) ml

 RCP: 1760 (880-3290) ml

 NT: 1530 (1120-2320) ml

Transfusion of 

predeposited units

Definitions: NR

Perioperative care:

Anesthesia: spinal/general

 WB: 17/8

 RCP: 20/4

 NT: 8/1

Analytical methodology: Shapiro-Wilk 

test used to probe for normality of 

distribution (P>0.4). For repeated 

measurements, baseline corrected area 

under curve (AUC) was calculated. Ttest and Wilcoxon rank sum test for 

independent variables were used to 

determine statistical significance. 

Other notes: Small sample size

Follow-up: 7 days observation period
Disclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminated by the Centers for Disease Control and Prevention and should not be 

construed to represent any agency determination or policy. 55

Author

Year

(Data 

Extractor)

Risk of Bias

Score Study Objective Population and Setting (N) Intervention Results Comments

Predeposited

 WB: 3/25 (12%)

 RCP: 2/24 (8.8%)

 NT: 0

Storage period 

(days)

 WB: 27.9±2.9 

 RCP: 28.4±2.0 

 NT: 28.2±1.6

Length of Surgery

 WB: 102±17 

minutes

 RCP: 89±21 

minutes

 NT: 92±25 minutes

Procedures: Hip 

arthroplasty

Indications: NR

Setting: 1 university 

hospital

Location: Germany

Dates: NR

Inclusion Criteria: 

patients who had 

donated autologous 

blood and were 

scheduled for hip 

arthroplasty

Exclusion Criteria: 

contraindication for 

autologous blood 

donations and 

diseases associated 

with impaired 

immune defense. 

blood cell count was 

measured by depolarized 

orthogonal light scattering

Control group: n=32

WB Whole Blood n=25 

donated blood units stored 

as whole blood

Non-transfused patients 

(NT)

NT 7 had donated blood 

stored as WB vs. 2 as RCP.

Standard preventive 

measures 

Thromboembolic 

Prophylaxis: 40mg 

subcutaneous enoxaparin 

administered 1/day 

starting 12h prior to 

surgery.

AMP: cefuroxime 

administered 

intravenously prior to 

surgery.

Cemented, cementless, 

and hybrid prostheses 

were implanted.

Volume replacement: 

modified ringer’s solution 

and gelatin solution were 

used.

Postop_ autologous 

plasma was re-transfused 

for volume replacement 

primarily in the RCP group. 

Analgesic: diclofenac & 

prirtarmid.

3units

 WB: 3/25

 RCP[(RC/FFP)/n]: (9/7)/24

 NT: 0

2 units

 WB: 8/25

 RCP[(RC/FFP)/n]: (6/6)/24

 NT: 0

1unit

 WB: 14/25

 RCP[(RC/FFP)/n]: (9/4)/24

 NT: 0

P≤0.05 for all transfusion 

of unit values (3, 2, 1) for 

WB vs. RC

Volume replacement (ml)

Modified Ringer’s Solution

 WB: 4376±802 

 RCP: 4604±642

 NT: 4422±1190 

Colloid Solution

 WB: 1540±628 

 RCP: 1333±602 

 NT: 1417±530 

Patients with Cell Salvage

 WB: 12/25 (48%)

 RCP: 8/24 (33.3%)

 NT: 1/9 (11.1%)

Volume transfused: 

median(range)

 WB: 510 (240-1200) ml

 RCP: 610 (4-1600) ml

 NT: 360 ml

Laboratory Analysis:
Disclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminated by the Centers for Disease Control and Prevention and should not be 

construed to represent any agency determination or policy. 56

Author

Year

(Data 

Extractor)

Risk of Bias

Score Study Objective Population and Setting (N) Intervention Results Comments

Cell salvage: performed in 

all groups if a patient had 

<3 units and/or presented 

for surgery with Hb 

concentration <12g/dl. 

Blood collected was 

processed and 

retransfused with drain 

blood measured and 

sponged blood estimated

Transfusion Triggers: Hb, 

9g/dl or clinical signs of 

myocardial ischemia.

Regarding hemoglobin 

concentration, 

neutrophils, monocytes, 

phagocytic activity, and 

oxidation activity:

There were no significant 

differences in values 

between the three groups.

Reoperations: NR

Length of stay: (mean±SD)

 WB: 15.3±0.8 days

 RCP: 15.3±0.6 days

 NT: 15.0±1.0 days

Mortality: NR

Adverse events: NR

Pedersen

2009 7

(ES)

Retrospecti

ve 

concurrent 

control

1, 2, 3, 4, 5, 

6, 7, 8

To determine 

whether allogeneic

red blood cell 

transfusion was 

associated with 

increased odds of 

complications 

following primary 

total hip 

replacement (THR). 

Complications 

included 

hospitalization 

with cardiovascular 

and/or 

cerebrovascular 

events, venous 

thromboembolism, 

Number of 

patients: N=28087 

Matched group 

N=4508

Patient 

Characteristics: 

For total group, 

Transfused patients 

were older & had 

more comorbid 

conditions. They 

also were more 

likely to be female, 

receive a cemented 

prosthesis, and to 

have a THR 

procedure of more 

than 2 hours.

Intervention group: 

Receiving Transfusion

Intervention1: n=9063 

(32.3%)

Patients received ≥1 unit 

red blood cell (RBC) 

transfusion within 8 days 

of surgery 

Intervention2: n=2254

Patients receiving ≥1 unit 

RBC allogeneic transfusion 

within 8 days of surgery 

(matched by propensity 

scoring to the control2 

group

Timing of intervention: 

intraoperative &/or 

SSI (Follow Up 90Days)

(Adjusted) 

Reoperation due to 

infection

 Intervention2: 5/2254 

(0.2%)

 Control2: 5/2254 (0.2%)

OR (95%CI): 0.57 (0.11-

2.93)

Other infections:

Pneumonia: adjusted

 Intervention2: 36/2254 

(1.6%)

 Control2: 17/2254 (0.8%)

OR (95%CI): 2.1 (1.2-3.8)

Topic-specific outcomes: 

Definitions 

Outcomes (within 90 days of index 

procedure):

1. Death,

2. Hospitalization with cardiovascular 

events including myocardial infarction, 

congestive heart failure, peripheral 

vascular disease, or cerebrovascular 

events,

3. hospitalization with venous 

thromboembolism, including deep 

venous thrombosis and/or pulmonary 

embolism,

4. hospitalization with pneumonia and

5. reoperation due to infection.

Perioperative care: 

Regional Anesthesia:
Disclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminated by the Centers for Disease Control and Prevention and should not be 

construed to represent any agency determination or policy. 57

Author

Year

(Data 

Extractor)

Risk of Bias

Score Study Objective Population and Setting (N) Intervention Results Comments

pneumonia, 

reoperation due to 

infection of 

primary THR, and 

mortality within 90 

days of primary 

THR

For the propensitymatched 

population, there 

were no substantial 

differences for any 

of the 

characteristics 

related to the risk of 

transfusion

Standardized mean 

difference 

(SMD)>0.1 is 

indicative of 

significant 

imbalance between 

groups

·Age: Age groupings 

were similar 

between groups 

except for 

80+ years

 Intervention2: 

404/2254 (17.9%)

 Control2: 

411/2254 (18.2%)

 SMD= 0.18397

·Gender: female n 

(%)

 Intervention2: 

1490/2254 (66.1%)

 Control2: 

1439/2254 (63.8%)

 SMD=0.11293

Postoperative 

Duration of intervention: 

within 8 days of surgery

Agent: Allogeneic red 

blood cells.

Intervention1:

 Median: 2units/patient

 Range: 1-20 units

Monitoring intervention: 

NA

Control group:

No Transfusion

Control1: n=19024

Patients who received no 

transfusion

Control2: n=2254

Patients who received no 

transfusion and were 

matched by propensity 

scoring to Intervention2

Standard preventive 

measures: NR

Non-standard preventive 

measures:

Anti-rheumatic drug 

Prophylaxis for 

heterotropic bone 

formations:

 Intervention2: 195/2254 

(8.7%)

Median (range) number of 

units transfused:

Intervention1: 2 (1-20)

Control: 0

Duration of operation: 

Similar between matched 

groups except for Longer 

surgeries:

>121 minutes:

 Intervention2: 151 (6.7%)

 Control2: 157 (7.0%)

 SMD: 0.20997

Preoperative Hemoglobin 

concentration w/in 3 

months prior to surgery:

<138.5 g/L

 Intervention2: 1410 

(62.6%)

 Control2: 1362 (60.4%)

 SMD: 0.25041

Length of stay: NR

Mortality: (within 90 days 

of primary THR) - adjusted

 Intervention2: 39/2254 

(1.7%)

 Control2: 18/2254 (0.8%)

OR (95%CI) 2.17 (1.24-

3.80)

Adverse events: 

Deep venous thrombosis/ 

 Intervention2: 1753/2254 (77.8%)

 Control2: 1757/2254 (78.0%)

 SMD=0.18378

Analytical methodology: To overcome 

bias due to confounding, they matched 

patients not receiving transfusions with 

patients receiving transfusion with a 1:1 

ratio using propensity score matching. 

The propensity score for each patient 

was calculated using logistic regression. 

Patients were matched for baseline 

characteristics.

Information on blood lost during 

surgery was not available for this 

dataset.

They adjusted for hemoglobin 

concentration 1-7 days postoperative as 

a surrogate measure of blood loss.

Information on smoking status, 

obesity/BMI, prior history of 

transfusion, and preoperative history of 

increased perioperative bleeding and 

pre-operative history of chronic anemia 

was also not available and not included 

in propensity matching score.

Other notes: Data utilized in this study 

is from 

1) The Danish Hip Arthroplasty Registry 

(DHR). This registry of all primary THR 

consists of data recorded prospectively 

by the operating surgeons using 

standardized forms. (pre-, peri- and 

postoperative data). Reoperation data 

was also obtained here.
Disclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminated by the Centers for Disease Control and Prevention and should not be 

construed to represent any agency determination or policy. 58

Author

Year

(Data 

Extractor)

Risk of Bias

Score Study Objective Population and Setting (N) Intervention Results Comments

·Obesity: NR

·Comorbidities: 

Diabetes

 Intervention2: 

134/2254 (5.9%)

 Control2: 

115/2254 (5.1%)

 SMD=0.05238

Preoperative 

Hemoglobin 

<138.5g/L within 3 

mo. before surgery

 Intervention2: 

1410/2254 (62.6%)

 Control2: 

1362/2254 (60.4%)

 SMD=0.25041

Procedures: Primary 

Total Hip 

Replacement (THR)

Indications:

Primary arthrosis

 Intervention2: 

1647/2254 (73.1%)

 Control2: 

1633/2254 (72.5%)

 SMD=0.23293

Trauma

 Intervention2: 

323/2254 (14.3%)

 Control2: 

319/2254 (14.2%)

 SMD=0.28662

Other

 Intervention2: 

 Control2: 208/2254 

(9.2%)

 SMD=0.06109

pulmonary embolism –

adjusted

 Intervention2: 28/2254 

(1.2%)

 Control2: 23/2254 

(71.0%)

OR (95%CI): 1.17 (0.67-

2.06)

Cardiovascular or 

cerebrovascular disease –

adjusted

 Intervention2: 54/2254 

(2.4%)

 Control2: 39/2254 (1.7%)

OR (95%CI): 1.42 (0.93-

2.15)

Composite outcome –

adjusted

OR (95% CI): 1.67 (1.23-

2.26)

Subanalysis of composite 

outcome risk by Number 

of transfusions/ patient: 

Adjusted OR (95%CI) 

≥6 transfusions:3.4 (1.3-

9.2)

3-4 transfusions: 1.5 (0.8-

2.9)

2-3 transfusions: 1.2 (0.8-

1.9)

1 transfusion: 2.7 (1.2-5.7)

Subgroup analysis for 

2) The Danish Transfusion Database. 

Data included all allogeneic red blood 

cell transfusions administered to 

included patients within 8 days of 

primary THR surgery. Patients were 

classified as having received either no or 

one or more units.

3) The Civil Registration System was 

utilized for data on mortality.

4) The Danish National Registry of 

Patients was used for hospitalization 

data. Diagnoses were classified 

according to the Danish version of the 

International Classification of Diseases 

(ICD. The ninth edition (ICD-8) was used 

from 1977 to 1993 and the tenth edition 

(ICD-10) has been used hereafter. The 

physician who diagnosed the patient 

assessed all discharge codes.

Odds estimates may partly reflect 

unmeasured bias due to blood loss

Limitation: No information on 

intraoperative blood loss which may 

have impacted postop transfusions. 

Information on pre/post-operative 

hemoglobin concentration used as a 

surrogate measure of blood loss.

Follow-up: until the occurrence of 

death, hospitalization for cardiovascular 

or cerebrovascular events, venous 

thromboembolism, pneumonia, 

reoperation due to infection or 90 days 

after surgery.
Disclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminated by the Centers for Disease Control and Prevention and should not be 

construed to represent any agency determination or policy. 59

Author

Year

(Data 

Extractor)

Risk of Bias

Score Study Objective Population and Setting (N) Intervention Results Comments

284/2254 (12.6%)

 Control2: 

302/2254 (13.4%)

 SMD=0.00682

Setting: Multicenter 20 hospitals 

in North Jutland, 

Aarhaus, Funen, and 

Copenhagen). 

These 20

orthopaedic 

departments serve 

~45% of the Danish 

population (nearly 

2.3 million people).

Location: Denmark

Dates: January 1, 

1999 – December 

31, 2007

Inclusion Criteria: 

Patients with 

primary THR 

procedures 

registered in the 

Danish Hip 

Arthroplasty 

Registry (DHR) and 

performed at the 

hospitals reporting 

to the Danish 

Transfusion 

Database during the 

study dates. This 

includes patients 

who sustained right 

history of cardiovascular 

events

With History (matched)

 Intervention2: 407/2254 

(18.1%)

 Control2: 407/2254 

(18.1%)

- Red blood cell 

transfusion was associated 

with odd of the composite 

adverse outcome within 

90 days of surgery: 1.2 

(0.8-1.9)

Without History (matched)

 Intervention2: 1834/2254 

(81.4%)

 Control2: 1834/2254 

(81.4%)

In THR patients without 

cardiovascular events prior 

to surgery, OR of 

composite outcome: 1.7 

(1.1-2.7)

Subgroup analysis 

postoperative hemoglobin 

(matched)

Hemoglobin 

concentration <105g/L

 Intervention2: 729/2254 

(32.3%)

 Control2: 729/2254 

(32.3%)

- Adjusted OR: for 

composite adverse 
Disclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminated by the Centers for Disease Control and Prevention and should not be 

construed to represent any agency determination or policy. 60

Author

Year

(Data 

Extractor)

Risk of Bias

Score Study Objective Population and Setting (N) Intervention Results Comments

and left THR during 

the study period as 

long as surgery was 

not performed on 

the same day (those 

were treated as 

independent 

operations)

Exclusion Criteria: 

Patients without 

possibility for follow 

up and bilateral 

primary THR 

procedures 

performed during 

the same surgery.

outcome w/in 90 days of 

surgery: 1.1 (0.5-2.7) for 

transfused vs. non 

transfused

Hemoglobin 

concentration>105g/L

 Intervention2: 1505/2254 

(66.8%)

 Control2: 1505/2254 

(66.8%)

- Adjusted OR: for 

composite adverse 

outcome w/in 90 days of 

surgery: 1.6 (1.0-2.5) for 

transfused vs. non 

transfused

Monte del 

Trujillo

2008 8

(ES)

Prospective 

concurrent 

control

1, 3, 4, 5, 6, 

7, 8

To prospectively 

evaluate the utility 

of a new device 

that automatically 

provides washed 

salvaged blood to 

reduce exposure to 

Allogeneic Blood 

Transfusions (ABT) 

in elective Total 

Hip Replacement 

(THR) patients. 

End-points include 

the impact of 

Washed Salvaged 

Blood (WSB) return 

on both the rate of 

postoperative 

infection and the 

Number of patients 

N=108

Patient 

Characteristics:

There were no 

differences in 

characteristics 

between groups 

except age and 

Hypertension.

Data expressed as 

mean ±SD or n (%)

·Age (y): 

 Intervention: 

62±14

 Control: 67±9

 P= 0.027

·Gender: f/m

 Intervention: 

Intervention group: n=60

Utilization of the blood 

processing device designed 

to wash autologous blood 

and re-infuse the blood.

Timing of intervention: 

intraoperative and/or 

postoperative

Duration of intervention: 

duration of transfusion

Agent: Perioperatively 

salvaged WSB. The blood 

was collected with nonfractionated heparin and 

was re-infused within the 

first 6h from the beginning 

of blood salvage.

SSI (Follow up - NR) 

Unadjusted:

Total Infection: 

 Intervention: 1 (2%)

 Control: 5 (10%)

 P=0.086

Wound Infection

 Intervention: 0 (0%)

 Control: 2 (4%)

Infection Rate

ABT: 12.2% (4/32)

No ABT: 2.6% (2/76)

p=0.046

Other infections: 

Urinary Infection

 Intervention: 1 (2%)

 Control: 2 (4%)

Definitions:

Postoperative Infectious Complications 

(urinary tract, respiratory tract, and 

wound infections): CDC definitions.

Adverse reactions to WSB reinfusion:

Shivers, fever, bradycardia, hypotension

Estimated blood volume: calculated 

using gender and body weight 

[Gross1983]

Total Perioperative Blood Loss (CBL 

(ml)) = [Uncompensated RBC loss (ml) = 

Compensated RBC loss (ml)]/0.35

Uncompensated RBC loss (ml)= 

(preoperative Hct – postoperative day 4 

Hct) x Estimated Blood Volume (EBV)

Compensated RBC Loss (ml) = [Packed 

allogeneic red cell units x 165 (ml/unit) 

= [washed autologous blood volume x 

washed autologous blood Hct]
Disclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminated by the Centers for Disease Control and Prevention and should not be 

construed to represent any agency determination or policy. 61

Author

Year

(Data 

Extractor)

Risk of Bias

Score Study Objective Population and Setting (N) Intervention Results Comments

length of hospital 

stay.

27/33

 Control: 31/17

·Obesity: weight 

(kg) 

 Intervention: 79±9

 Control: 80±11

·Comorbidities

Diabetes

 Intervention: 7 

(12%)

 Control: 12 (25%)

Anemia (Hb<130g/l)

 Intervention: 4 

(7%)

 Control: 2 (4%)

Hypertension

 Intervention: 16 

(27%)

 Control: 32 (67%)

 P=0.001

Patient distribution 

according to 

preoperative Hb 

levels, perioperative 

Hb levels, and 

calculated total 

blood loss were no 

different in both 

groups.

Preoperative Hb 

(g/dl)

Cemented THR: 

 Intervention: 

14.4±1.2

 Control: 13.6±1.2

Device: A blood processing 

device designed 

specifically to adapt to the 

intermittent blood loss of 

orthopedic surgical 

patients.

Monitoring intervention: 

NR

Control group n=48

Patients received normal 

allogeneic blood 

transfusions (ABT) if 

necessary, one unit of 

leukodepleted packed red 

blood cell was considered 

to have a RBC mass of 

165ml.

Standard preventive 

measures:

Surgical Team: All patients 

were operated on by the 

same surgical team (senior 

surgeons) and each 

attending surgeon 

performed two operations 

in each surgical session (1 

intervention and 1 control)

Approach: All patients 

were positioned supine 

and anterolateral 

approach was used to the 

hip. 

Antimicrobials: surgery 

Respiratory Infection:

Intervention: 0 (0%)

 Control: 1 (2%)

Topic-specific outcomes:

Intervention: Enough WSB 

blood volume obtained to 

be returned: 49/60 (82%)

 Mean: 336±205

 Hct: 63±5%

 RBC: 205±151ml RBC

 U/patient: 1.3±0.9

**Calculated and total 

perioperative blood loss 

was not significantly 

different between groups 

according to age, gender, 

anesthesia type or 

hypertension.

Calculated Blood Loss (ml)

Cemented THR: 

 Intervention: 1943±906

 Control: 2091±747

 P=0.634

Uncemented THR: 

 Intervention: 2336±1015

 Control: 2347±971

 P=0.966

ABT rate,

Total

 Intervention: 15% (n=9)

 Control: 48% (n=23)

RR:0.31; P=0.001

Acute Anemia: hypotension, 

tachycardia, tachypnea, dizziness, 

fatigue.

Perioperative care:

Anesthesia: standard general or regional

Cemented THR: Regional/General 

Anesthesia

 Intervention: 6/6

 Control: 8/9

 P=0.876

Uncemented THR: Regional/General 

Anesthesia

 Intervention: 27/21

 Control: 13/18

 P=0.119

Cemented components: 73% of patients 

(79 patients)

Oral Iron Supplement

 Intervention: 32 (53.3%)

 Control: 24 (50%)

 P=0.338

Analytical methodology: Chi-square or 

Fisher’s Exact test for qualitative 

variables. Parametric one-way ANOVA 

or non-parametric Mann-Whitney for 

quantitative variables.

Other notes: none

Follow-up: NR
Disclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminated by the Centers for Disease Control and Prevention and should not be 

construed to represent any agency determination or policy. 62

Author

Year

(Data 

Extractor)

Risk of Bias

Score Study Objective Population and Setting (N) Intervention Results Comments

 P=0.067

Uncemented THR: 

 Intervention: 

14.5±1.6

 Control: 14.6±1.4

 P=0.823

(note: p<0.05 within 

control group)

Procedures: 

Unilateral Total Hip 

Replacement (THR)

Indications: NR

Setting: 1 Center

Location: Spain

Dates: January 2005 

– June 2006

Inclusion Criteria:

Patients undergoing 

THR

Exclusion Criteria: 

Patients with 

hematological 

diseases or 

coagulation 

disorders, hepatic 

or renal diseases, 

those receiving 

anticoagulant 

therapy or with 

known infection or 

malignancy. Also, 

patients with any 

other blood-saving 

performed under 

antimicrobial prophylaxis

Anticoagulant: surgery 

performed under 

antithrombotic prophylaxis 

(low molecular weight 

heparin)

Analgesia: Postop.

Components: Same 

acetabular and femoral 

components were used in 

all hips. 

Drains: 2 suction drains 

were used in all 

procedures. Removed on 

POD 2.

Transfusion was indicated 

when patient’s Hb level 

decreased to less than 

8g/dL or when the patient 

had symptoms of acute 

anemia (hypotension, 

tachycardia, tachypnea, 

dizziness, fatigue, etc.) 

Preoperative Hb≥13g/dl

RR: 0.32; P=0.003

Preoperative Hb3g/dl

RR: 1.47; P=0.091

Age<60yo

RR: 0.47; P=0.021

Age≥60yo

RR: 0.17; P=0.027

ABT rate n (%)

Cemented THR: 

 Intervention: 1 (8%)

 Control: 10 (59%)

 P=0.008

Uncemented THR: 

 Intervention: 8 (17%)

 Control: 13 (42%)

 P=0.013

Total ABT units

Cemented THR: 

 Intervention: 2

 Control: 20

 P=0.017

Uncemented THR: 

 Intervention: 13

 Control: 28

 P=0.005

Transfusion Index (ml RBC/ 

transfused patient)

Allogeneic

Overall

 Intervention: 53±117

 Control: 371±154

 P=0.001

Cemented THR: 
Disclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminated by the Centers for Disease Control and Prevention and should not be 

construed to represent any agency determination or policy. 63

Author

Year

(Data 

Extractor)

Risk of Bias

Score Study Objective Population and Setting (N) Intervention Results Comments

strategy (e.g. 

preoperative 

autologous blood

donation or 

erythropoietin 

treatment).

 Intervention: 49±129

 Control: 378±142

 P=0.001

Uncemented THR: 

 Intervention: 54±118

 Control: 366±168

 P=0.001

Autologous

Cemented THR: 

 Intervention: 163±77

 Control: 0

Uncemented THR: 

 Intervention: 218±153

 Control: 0

Overall

Total

 Intervention: 263±189

 Control: 371±154

 P=0.022

Cemented THR: 

 Intervention: 212±167

 Control: 378±142

 P=0.049

Uncemented THR: 

 Intervention: 272±192

 Control: 366±168

 P=0.001

Reoperations: NR

Length of stay (days):

 Intervention: 10.1±3.1

 Control: 11.6±7.4

 P=0.201

ABT:13.5±7.9days

No ABT: 9.6±3.1 days

Difference 3.9 days; 95%CI 

(1.8-6.0); P=0.001
Disclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminated by the Centers for Disease Control and Prevention and should not be 

construed to represent any agency determination or policy. 64

Author

Year

(Data 

Extractor)

Risk of Bias

Score Study Objective Population and Setting (N) Intervention Results Comments

Mortality: NR

Adverse events: 

DVT

 Intervention: 0 (0)

 Control: 1 (2%)

Ability to walk (days)

 Intervention: 4.6±1.4

 Control: 5.1±3.4

NoABT:4.4±1.6 days

ABT: 5.7±3.5 days

Difference 1.3d; 95%CI 

(0.3-2.3) P=0.013

Innerhofe

r

2005 3

(ES)

Prospective 

concurrent 

control

1, 2, 3, 4, 5, 

6,

To determine that 

the use of White 

Blood Cell (WBC) 

filtered blood 

components 

should cause 

allogeneic

recipients to 

exhibit 

postoperative 

infection rates 

similar to those of 

patients receiving 

autologous blood 

during elective 

primary hip or 

knee arthroplasty 

using the incidence 

of postoperative 

infection as an 

endpoint

Number of 

patients: N=308

Preoperative 

Autologous Blood 

Donation (PAD): 

n=143

No PAD: n=165

No transfusion: 

n=101

Autologous: n=85

Allogeneic, WBC 

filtered= n=100

Both, n=22

Patient 

Characteristics:

·Age: median (IQR)

No RBC: 66y (54-

73)

Autologous: 64y 

(55-70)

Allogeneic: 74y 

(67-78)

Both: 72y (65-77)

 P<0.0001

Intervention group: 

Allogeneic (WBCfiltered)n=100

Timing of intervention: 

Intraoperative and/or 

postop

Duration of intervention: 

duration of transfusion

Agent: all blood 

components produced by 

hospital

Autologous or Allogeneic

whole blood was collected 

in top and bottom bags; 

citrate phosphate dextrose 

adenine-1 was used as 

anticoagulant. WBC 

reduction was provided by 

pre-storage inline WBC 

filtration of whole blood. 

SSI (Follow up- discharge) 

Wound infection (total=4 

(1.2%)

Allogeneic: 3/100 (3%)

No RBC: 1/101 (1.0%)

Autologous: 0

Both: 0

Other infections:

Total infections (UTI, 

pneumonia, wound, 

purulent dermatitis):

22/308 (6.82%) resulting in 

antimicrobial therapy for 

treatment

Allogeneic: 12/100 (12%)

No RBC: 7/101 (6.9%)

Autologous: 1/85 (1.2%)

Both: 1/22 (4.6%)

 P=0.03

 Allogeneic compared with 

Autologous transfusions: 

P=0.0053

Definitions:

Urinary Tract Infection (UTI): diagnosed 

by orthopedic surgeon, established 

from positive results of microbiologic 

cultures and clinical signs of UTI

Pneumonia: when signs of fever, 

leukocytosis, and chest infiltrate were 

observed

Wound infection: clinically in the case of 

purulent secretion and painful 

erythema.

Purulent Dermatitis (bacterial dermal 

infection distinct from operation site):

confirmed by positive microbiologic 

results.

Perioperative care: NR

Analytical methodology: Chi-square 

and U test to compare baseline data of 

patients. 

Univariate analysis was performed for 

factors associated with postoperative 

infection and transfusion supply. 
Disclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminated by the Centers for Disease Control and Prevention and should not be 

construed to represent any agency determination or policy. 65

Author

Year

(Data 

Extractor)

Risk of Bias

Score Study Objective Population and Setting (N) Intervention Results Comments

·Gender: f/m

No RBC: 43/58

Autologous: 44/41

Allogeneic: 73/27

Both: 15/7

 P=0.0001

·Obesity: BMI

No RBC: 28 (25-31)

Autologous: 27 (24-

30)

Allogeneic: 26 (23-

29)

Both: 26 (24-32)

 P=0.009

·Comorbidities:

Existing Disease 

(including Coronary 

artery disease, 

congestive heart 

failure, COPD, 

Diabetes mellitus, 

renal and liver 

disease, chronic 

polyarthritis, intake 

of corticosteroids, 

malignant disease)

No RBC: 37.6% 

(n=38)

Autologous: 29.4% 

(n=25)

Allogeneic: 58% 

(n=58)

Both: 36.4% (n=8)

 P=0.0007

·Hb at admission 

(g/dl):

Separated RBCs were 

stored in 100ml of salineademine-glucose-mannitol 

additive solution and kept 

at 4oC and plasma was 

frozen (to -30oC core 

temp) within 2 hour of 

separation.

Autologous blood was 

donated by means of 

apheresis, at 400ml of 

RBCs 3-4 weeks before 

surgery. It was divided into 

2 units re-suspended in 

100ml saline-adenineglucose-mannitol each. 

RBCs were not WBC 

filtered and the WBC 

content was 2,000-30,000 

WBCs/μL

Monitoring intervention: 

NR

Control group: n=208

Control1: n=101

No RBCs/ no Transfusion

Control2: n=85 

Autologous

Control 2: n=22

Both Autologous and 

Allogeneic RBCs

Standard preventive 

measures:

Transfusion trigger: bHb 

 No transfusion compared 

with compared to 

autologous: P=0.06

Allogeneic + Both: 10.7% 

(13/122)

Autologous + None: 4.3% 

(8/186)

 P=0.03

**Incidence of infection 

increased significantly with 

the number of transfused 

allogeneic WBC-filtered 

RBCs (p=0.01, data not 

shown)

Statistically significant 

Multivariate analysis of 

variables predicting postop 

infection

Allogeneic WBC-filtered 

RBCs

OR (95%CI): 23.66 (1.33-

422.06) P=0.02

Foley catheter (days)

OR (95%CI): 1.23 (1.1-1.4)

 P=0.002

UTI

Allogeneic: 7/100 (7.0%)

 No RBC: 5/101 (5.0%)

Autologous: 1/85 (1.2%)

Both: 0/22 

Pneumonia

Allogeneic: 3/100 (3.0%)

Chi-square and Kruskall-Wallis test were 

applied to analyze predictive factors of 

infection after allogeneic transfusion.

Logistic regression model for evaluating 

risk factors for postoperative infection.

Other notes: As expected, Fresh Frozen 

Plasma (FFP) was seldom necessary to 

correct coagulopathy (15/308 patients) 

and intraoperatively salvaged blood was 

processed for 44/308 (14%) of patients 

only and therefore was not analyzed 

further.

Follow-up: Discharge
Disclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminated by the Centers for Disease Control and Prevention and should not be 

construed to represent any agency determination or policy. 66

Author

Year

(Data 

Extractor)

Risk of Bias

Score Study Objective Population and Setting (N) Intervention Results Comments

No RBC: 14.3 (13.7-

15.1)

Autologous: 12.8 

(12.3-13.9)

Allogeneic: 13.1 

(12.1-13.8)

Both: 12.2 (11.4-

12.5)

 P<0.0001

·Hb at discharge 

(g/dl):

Not significantly 

different between 

groups.

Procedures: 

Primary Hip 

Replacement: 189

Primary Knee 

Replacement: 119

Indications: NR

Setting: 1 center

Location: Austria

Dates: 10 months

Inclusion Criteria: 

Patients undergoing 

primary hip or knee 

replacement 

surgery

Exclusion Criteria: 

Any infection 

(including UTI), 

medical reason for 

not donating 

autologous blood, 

surgery for 

metastatic process, 

levels below 8g/dl and/or 

physiologic signs of anemia

Warming: all patients were 

actively warmed with fluid 

warmer and a convective 

warming system. 

Transfusions: fluid 

warmers and 40-μm blood 

filters were used

AMP: single dose of 

second-generation 

cephalosporin before 

incision.

Anticoagulant: Enoxaparin 

administered 12h before 

operation.

Catheters: all patients 

received Foley catheters 

on the morning of the day 

of surgery.

Non-standard preventive 

measures:

Blood Aspiration: blood 

was aspirated into a cellsaver system and 

processed when 

appropriate (>1000ml of 

blood in the reservoir.

Postoperatively unwashed 

shed blood was also retransfused within 6h

FFP: was only used to treat 

coagulopathy 15/308 

(4.9%)

 No RBC: 0/101 

Autologous: 0/85 

Both: 1/22 (4.5%)

Purulent Dermal infection

Allogeneic: 0/100 

 No RBC: 1/101 (1.0%)

Autologous: 0/85 

Both: 0/22 

Topic-specific outcomes:

·Total RBCs (units 

transfused):

Allogeneic: 2 (2-4)

No RBC: 0

Autologous: 2 (1-2)

Both: 4 (3-4)

 P<0.0001

·Shed Blood (ml):

Allogeneic: 500 (300-700)

 No RBC: 550 (500-900)

Autologous: 500 (450-

1000)

Both: 500 (300-1000)

 P=NS

Reoperations: NR

Length of stay:

With Infection: 16.8±4.2d

No Infection: 14.0±2.1d

P=0.0004

Mortality: NR

Adverse events:
Disclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminated by the Centers for Disease Control and Prevention and should not be 

construed to represent any agency determination or policy. 67

Author

Year

(Data 

Extractor)

Risk of Bias

Score Study Objective Population and Setting (N) Intervention Results Comments

or stabilization of 

acute fractures.

·Foley Catheter (days)

Allogeneic: 3 (3-4)

No RBC: 3 (2-4)

Autologous: 3 (2-3)

Both: 4 (3-5)

 P=0.006

Weber

20055

(ES)

Prospective 

concurrent 

control

1, 2, 3, 4,

To determine the 

effects of 

allogeneic blood 

transfusion on 

length of hospital 

stay in patients 

undergoing 

elective total hip 

arthroplasty by 

examining the 

frequency of 

allogeneic blood 

transfusion, 

wound-healing 

disturbances, 

superficial and 

deep wound 

infections, and 

length of hospital 

admission.

Number of 

patients: N=444

Patient 

Characteristics: 

mean (SEM) or n 

(%)

·Age: years

Intervention: 64.2 

(14.5)

Control: 63.1 (11.2)

·Gender: %male

Intervention: 13% 

(34)

Control: 39% (49

P<0.01

·Obesity

Height (cm)

Intervention: 167 

(8.6)

Control: 171 (8.9)

P<0.05

Weight (kg)

Intervention: 72 

(15.4)

Control: 79 (13.8)

P<0.001

Intervention group: n=92

Received allogeneic blood 

transfusion.

Timing of intervention: 

Intraoperative and 

postoperative

Duration of intervention: 

Intraoperative with 

different triggers either 

before or after 4 hours 

postop.

Agent: Packed red blood 

cells were supplied by local 

blood bank and consisted 

of buffy coat-depleted 

cells, mean vol. 320ml, Hb 

17.8g/dl, Hct=0.58, and 

Leukocytes 0.4x109/L

Monitoring intervention: 

Info collected

1. At POD 0 - all routine 

clinical postop 

assessments, name of 

SSI (follow up 6 weeks) 

Unadjusted results.

Deep Infection 

(mean(SEM))

Intervention: 1% (10%)

Control: 1% (8%)

P=NS

Positive Wound Culture 

(mean(SEM))

Intervention: 3.3% (18%)

Control: 2.0% (14%)

P=NS

Wound Disturbance 

(mean(SEM))

Intervention: 31% (47%)

Control: 18% (39%)

P<0.05

To determine impact of 

perioperative blood loss, 

they divided the group 

into 3 subgroups: 

Blood loss 1-700mL

Blood loss 101-1000mL

Blood loss >1000mL.

For each subgroup they 

Definitions:

Wound and urinary tract infections:

defined by the presence of a positive 

culture. Wounds were examined daily 

by orthopedic surgeons who were 

trained to the assessment protocol but 

not blinded to transfusion.

Deep infection: requires joint 

involvement

Wound-healing disturbance:

erythematous inflammation of >1cm, 

wound fluid discharge, purulent suture, 

wound dehiscence, blister, or any 

degree of wound necrosis.

Perioperative care: NR

Analytical methodology: Occurrence of 

wound disturbance factors in relation to 

blood transfusion and other potentially 

related factors were calculated using 

logistic regression

Risk variables were calculated using 

stepwise conditional backward and 

forward selection to perform 

multivariate analysis.

Effect of variables on Length of stay was 
Disclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminated by the Centers for Disease Control and Prevention and should not be 

construed to represent any agency determination or policy. 68

Author

Year

(Data 

Extractor)

Risk of Bias

Score Study Objective Population and Setting (N) Intervention Results Comments

·Comorbidities: 

Diabetes mellitus

Intervention: 2/92 

(2.2%)

Control: 18/352 

(5.1%)Pulmonary 

disease

Intervention: 9/92 

(9.8%)

Control: 29/352 

(8.2%)Steroids

Intervention: 1/92 

(1.1%)

Control: 12/352 

(3.4%)

Rheumatoid 

Arthritis

Intervention: 6/92 

(6.5%)

Control: 16/352 

(4.5%)

Procedures: Elective 

primary total hip 

arthroplasty

Indications: NR

Setting: 1 hospital

Location: The 

Netherlands

Dates: October 29, 

1998 – October 27, 

1999

surgeon, Hb level.

2. POD1 - blood loss, 

transfusion data (including 

units and type of blood 

products given and Hb 

before transfusion) any 

blood-saving techniques 

used, and medications 

used

3. POD4 – serum 

prealbumin and pretransfusion Hb (only if 

transfused)

4. Discharge – blood loss, 

transfusion data (number 

of units and type of blood 

product) and length of 

hospitalization.

Control group: n=352

No transfusion received

Standard preventive 

measures: 

All patients received 

standard care acceding to 

standard protocol by using 

active body warming and 

so on. Therefore, fraction 

of inspired oxygen, body 

temperature, and so on 

was comparable between 

groups. Because of the 

length of study period, 

group of surgeons was 

limited and their 

observed “essentially the 

same proportion in the 

incidence of wound 

disturbances as was found 

for the groups as a whole.” 

(Study not powered for 

this analysis so correlation 

between transfusion and 

wound disturbances did 

not reach significance in 

these subgroups)_

Unadjusted predictors of 

Wound healing 

disturbances: OR 

(95%CI)

Blood Transfusion

 OR: 2.1 (1.2-3.5); P=0.03

All other variables not 

significant

**Blood transfusion was 

also the only significant 

variable using multivariate 

analysis

Other infections: 

Urinary Tract Infection 

(mean(SEM))

Intervention: 3.3% (18%)

Control: 3.7% (19%)

P<0.01

Topic specific outcomes:

Preop ESR (mm 1st h)

calculated with linear regression 

analysis. Then log-normalized.

Other notes: None

Follow-up: at least 6weeks 

postoperatively.
Disclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminated by the Centers for Disease Control and Prevention and should not be 

construed to represent any agency determination or policy. 69

Author

Year

(Data 

Extractor)

Risk of Bias

Score Study Objective Population and Setting (N) Intervention Results Comments

Inclusion Criteria: 

Patients undergoing 

planned elective 

primary total hip 

arthroplasty, ≥18yo, 

living in The 

Netherlands, or 

otherwise available 

for follow up for at 

least 6 wk postop

Exclusion Criteria: 

Any infection of any 

body-system at 

screening, as 

determined by 

symptoms or 

erythrocyte 

sedimentation rate 

(ESR)>20mm (unless 

known to be 

preexistent); any 

blood transfusion 

received within 6wk 

before surgery; and 

any other operation 

within 6wk preop. 

Also, patients who 

donated autologous 

blood 

preoperatively.

distribution was 

comparable between 

groups.

Non-standard preventive 

measures

Transfusion Trigger: 

Hb<8.1 g/dl (5.0mmol/l) 

during surgery and until 4h 

postop and Hb<8.9 g/dl 

(5.5mmol/l) more than 4h 

postop. For patients with 

cardiovascular disease, all 

triggers were increased by 

0.8g/dl (0.5mmol/l)

Gentamycin cement used 

(%) (SEM)

Intervention: 21% (41)

Control: 14% (34)

P=NS

Intervention: 18.3 (13.8)

Control: 14.5 (11.1)

P<0.05

Preop prealbumin 

(mmol/L)

Intervention: 266 (51.4)

Control: 285 (56.2)

P<0.05

Preop Hb (mmol/L)

Intervention: 8.0 (0.8)

Control: 8.6 (0.7)

P<0.001

Operation time (min)

Intervention:80 (31.6)

Control: 71 (19.5)

P<0.05

Perioperative blood loss 

(mL)

Intervention: 789 (551)

Control: 540 (274)

P<0.001

Total Blood Loss (mL)

Intervention: 1185 (716)

Control: 922 (431)

P<0.001

Reoperations: NR

Length of stay: mean 

(SEM) d

Intervention: 12.3 (5.3)

Control: 9.8 (3.5)

P<0.001

Evaluation to determine if 

length of stay was affected 

by perioperative blood loss 

showed that duration of 

hospitalization was 
Disclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminated by the Centers for Disease Control and Prevention and should not be 

construed to represent any agency determination or policy. 70

Author

Year

(Data 

Extractor)

Risk of Bias

Score Study Objective Population and Setting (N) Intervention Results Comments

essentially unaffected by 

blood loss and a similar 

difference in 

hospitalization duration 

between transfused and 

nontransfused was 

maintained among the 

subgroups. (Study not 

powered to detect 

significant differences in 

sub-analysis but did reach 

significance in patients 

who lost more than 700mL 

of blood perioperatively)

Regression model to 

predict length of stay 

(days) (β (95%CI) (How 

much each variable adds 

to length of stay)

Age (days per 10yr)

 0.9 (0.6-1.2); P<0.001

Operation time (days per 

10 min)

 0.2 (0.1-0.4); P=0.011

Wound disturbance (days 

if present)

 1.3 (0.4-2.1); P=0.006

Transfusion (days if given)

 2.2 (1.3-3.1); P<0.001

Mortality: NR

Adverse events: NR

Llewelyn

2004 6

(ES)

Prospective 

Pre-Post

1, 2, 3, 4, 8

To conduct a twocohort prospective 

study in patients 

undergoing 

Number of 

patients: N=3942 

evaluable

Intervention group: 

 Received Transfusions 

n= 2095

Total Orthopaedic 

SSI (Follow Up 90 days)

Surgical wounds

 

Orthopedic

Definitions:

2 primary outcomes of interest “ Length 

of stay and Infections”

Length of Stay (LOS): the days between 
Disclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminated by the Centers for Disease Control and Prevention and should not be 

construed to represent any agency determination or policy. 71

Author

Year

(Data 

Extractor)

Risk of Bias

Score Study Objective Population and Setting (N) Intervention Results Comments

elective coronary 

artery bypass graft 

or total hip and/or 

knee replacement 

surgery before and 

after universal 

leukoreduction 

(ULR) to examine 

the effects of ULR 

on a large group of 

surgical patients 

who received 

transfusion(s).

Patient 

Characteristics: 

using evaluable 

populations:

Transfusions: n=

 Before ULR: n= 997

 Ortho before 

n=606

 After ULR: n=1098

 Ortho after: n=637

No Transfusion

 Before ULR: n=956

 Ortho before: 

n=871

 After ULR: n=891

 Ortho after: n=799

·Age: years

Transfusions:

Before 

ULR:68.6±11.1

After ULR:69.2±10.2

No Transfusion

Before ULR: 

68.0±10.4

After ULR:68.1±10.3

·Gender: male (%)

Transfusion:

Before ULR: 471 

(47.2%)

After ULR: 600 

(54.6%)

P = 0.001

No Transfusion

Before ULR: 422 

(44.1%)

After ULR: 423 

received transfusion: 1243

Intervention1: n=997 

(Orthopaedic I1 n=606)

Patients receiving 

transfusions before 

mandatory ULR. These 

transfusions were 

intended to be unmodified 

RBC, but cohort included 

patients who received BCRBC and/or WBC reduced 

RBCs ONLY IF they also 

received at least 2 u 

unmodified RBC.

Intervention2: n=1098 

(Orthopaedic I2 n637)Patients receiving 

transfusions after 

mandatory ULR (Full 

cohort2 is WBC reduced 

allogeneic RBCs)

Timing of intervention:

intraoperative and 

postoperative

Duration of intervention: 

intraoperative and 

postoperative

Agent:

Cohort1: Unmodified RBCs 

or unmodified RBC and 

RBCs with Buffy coat 

removal (BC-RBCs), or 

WBC-reduced RBCs only if 

 Intervention1: 43/606 

(7.1%)

 Intervention2: 32/637 

(5.0%)

 Control1: 31/871 (3.6%)

 Control2: 22/799 (2.8%)

Proven Infections

Orthopedic

 Intervention1: 50/606 

(8.3%)

 Intervention2: 26/637 

(4.1%)

 AOR:0.45 (0.28-0.74); 

p=0.002

 Control1: 21/871 (2.4%)

 Control2: 29/799 (3.6%)

Other infections

Lower Respiratory 

Infections

 Orthopedic

 Intervention1: 21/606 

(3.5%)

 Intervention2: 26/637 

(4.1%)

 Control1: 20/871 (2.3%)

 Control2: 22/799 (2.8%)

Urinary Tract Infections

Orthopedic

 Intervention1: 22/606 

(3.6%)

 Intervention2: 16/637 

(2.5%)

the operation and discharge form the 

acute care ward. (Days on intensive care 

unit and/or high dependency unit plus 

orthopedic or cardiac ward) 

Infections: new suspected and proven 

postop infections for which 

antimicrobial s were prescribed 

(excluding topical antimicrobials and 

antimicrobials given as perioperative 

antimicrobial prophylaxis) plus local 

signs and symptoms as follows:

UTI: two or more of following:

1) fever with no other recognized cause

2) urgency

3) frequency 

4) dysuria

Lower Respiratory Tract Infection: LRTI: 

new or increased production of sputum 

and/or fever (>38oC) with appropriate 

chest signs including consolidation 

and/or chest x-rays showing new or 

progressive infiltrate

Wound infections: with purulent 

discharge in or exuding from the 

wound.

Secondary outcomes:

Hospital proven postop infections: 

required clinical symptoms above 

leading to antimicrobial prescription 

PLUS positive microbio culture (except 

physician’s diagnosis of pneumonia 

sufficed as confirmation of LRTI) 

Major non-infectious postop 

complications: one or more of the 

following: cardiac arrest, infarction, 

renal impairment requiring dialysis, 
Disclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminated by the Centers for Disease Control and Prevention and should not be 

construed to represent any agency determination or policy. 72

Author

Year

(Data 

Extractor)

Risk of Bias

Score Study Objective Population and Setting (N) Intervention Results Comments

(47.5%)

·Obesity (weight 

(kg))

Transfusion:

Before ULR: 

75.1±15.7

After ULR: 

75.7±14.8

No Transfusion

Before ULR: 

79.6±15.6

After ULR: 

80.6±16.0

·Comorbidity (%)

Transfusion:

Before ULR: 318 

(31.8%)

After ULR: 341 

(31.1%)

No Transfusion

Before ULR: 309 

(32.3%)

After ULR: 249 

(28.0%)

Infection (%)

Transfusion:

Before ULR: 65 

(6.5%)

After ULR: 45 (4.1%)

P=0.013

No Transfusion

Before ULR: 29 

(3.0%)

After ULR: 32 (3.6%)

Hb level (g/dl)

Transfusion:

they received at least 2u 

unmodified RBCCohort2:

all blood was WBCreduced within 48 hours of 

collection by filtration 

either of whole blood or of 

BC-RBCs. 

Monitoring intervention: 

Transfusion recorded.

Control group: 

 No Transfusions n= 

1847

Total Orthopaedic No 

Transfusion: n=1670

Control1: n=956

Orthopaedic C1 n=871

Patients not receiving 

transfusions before 

mandatory ULR 

Control2: n=891 

Orthopaedic C2:n=799

Patients not receiving 

transfusions with 

leukocyte reduction (after 

mandatory ULR)

Standard preventive 

measures 

Non-standard preventive 

measures:

Transfusion Triggers; Each 

hospital followed its own 

transfusion protocols

 Control1: 19/871 (2.0%)

 Control2: 26/799 (3.3%)

Bacteremia/ Septicemia

Orthopedic

 Intervention1: 3/606 

(0.5%)

 Intervention2: 1/637 

(0.2%)

 Control1: 4/871 (0.5%)

 Control2: 0

Other Site Infections

Orthopedic

 Intervention1: 17/606 

(2.8%)

 Intervention2: 13/637 

(2.0%)

 Control1: 13/871 (1.5%)

 Control2: 13/799 (1.6%)

Topic-specific outcomes

Drain Losses (mL)

Unchanged in orthopaedic 

patients who received 

transfusions vs. those who 

did not

Lowest Hb Level (g/dL)

Data not stratified by 

procedure type

Discharge Hb level (g/dL)

Data not stratified by 

procedure type

Subgroup analysis: of 

storage age and dose of 

confirmed deep vein thrombosis and/or 

pulmonary embolism, respiratory 

failure, and return to operating room 

for bleeding from surgical wound site.

Perioperative care: NR

Analytical methodology: 80% power 

and 5% significance, a sample size of 

400-500 patients receiving transfusion 

was adequate to allow the study to 

detect an effect size of 0.125.

T-test or chi square.

Binary outcomes required logistic 

regression 

Time-dependent variables were 

analyzed by Cox proportional hazards 

method

Other notes: Data were collected by 

research nurses or audit staff by review 

of hospital notes and computer 

information systems after the patient’s 

discharge.

Follow-up: 90 days after discharge
Disclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminated by the Centers for Disease Control and Prevention and should not be 

construed to represent any agency determination or policy. 73

Author

Year

(Data 

Extractor)

Risk of Bias

Score Study Objective Population and Setting (N) Intervention Results Comments

Before ULR: 

13.2±1.4

After ULR: 13.3±1.4

No Transfusion

Before ULR: 

13.7±151.2

After ULR: 13.8±1.2

Procedures: Nonemergent Coronary 

Artery Bypass 

Grafting (CABG) and 

elective total hip 

replacement and/ 

or total knee 

replacement 

(Primary and 

revisions)

Primary Procedure:

Orthopedic 

Procedures Redos 

(includes bilateral 

and THR plus TKR)

Transfusion:

Before ULR: 145 

(23.9%)

After ULR: 129 

(20.2%)

 P=0.118

No Transfusion

Before ULR: 58 

(6.7%)

After ULR: 26 (3.3%)

P=0.001

TKR (%)

Transfusion:

Before ULR: 194 

blood on primary 

outcomes before and after 

ULR (including postop 

infections, and postop 

LOS) found no statistically 

significant comparisons.

TRANSFUSION DATA

Number RBC units/patient

 

Orthopedic

 Before ULR: 2.7±1.5

 After ULR: 2.9±2.0

 P=0.115

Number of patients (%) 

receiving – THIS IS 

CABG+ORTHO

1 unit of RBCs

 Before ULR: 114/997 

(11.4%)

 After ULR: 78/1098 

(7.1%)

2-3 units of RBCs

 Before ULR: 476/997 

(47.7%)

 After ULR: 540/1098 

(49.2%)

>3 units RBCs

 Before ULR: 407/997 

(40.8%)

 After ULR: 480/1098 

(43.7%)

 P=0.003

FFP/cryoprecipitate

 Before ULR: 84/997 

(8.4%)
Disclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminated by the Centers for Disease Control and Prevention and should not be 

construed to represent any agency determination or policy. 74

Author

Year

(Data 

Extractor)

Risk of Bias

Score Study Objective Population and Setting (N) Intervention Results Comments

(32.0%)

After ULR: 242 

(38.0%)

 P=0.027

No Transfusion

Before ULR: 443 

(50.9%)

After ULR: 408 

(51.1%)

P=0.934

Indications: variable

Setting: Multicenter 

(CABG at 4 hospitals 

and Arthroplasty at 

7 hospitals)

Location: England

Dates: 

Cohort1 (pre-ULR): 

Began January –

May 1999 and 

continued until 

enough patients 

were recruited 

(approx. 5 months)

Cohort2 (Post ULR): 

Began January –

May 2000 and 

continued until 

enough patients 

were recruited 

(approx. 5 months)

Inclusion Criteria: 

CABG patients 

undergoing 

nonemergency, 

whether primary or 

 After ULR: 108/1098 

(12.1%)

 P=0.008

PLTs

 Before ULR: 75/997 

(7.5%)

 After ULR: 110/1098 

(12.3%)

 P=0.0004

Reoperations: NR

Length of stay: postop 

LOS: mean (SD) days

Received Transfusions

Orthopedic

 Before ULR: 2.8±1.56

 After ULR: 3.3±2.98

AR 1.16 (1.04-1.30); 

p=0.010

No Transfusions

Orthopedic

 Before ULR: 8.3±3.4

 After ULR: 7.9±3.8

AR 1.11 (1.00-1.22); 

p=0.042

Mortality (in hospital and 

up to 90 days after 

discharge home):

 

Orthopedic

 Intervention1: 7/606 

(1.2%)

 Intervention2: 7/637 

(1.1%)
Disclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminated by the Centers for Disease Control and Prevention and should not be 

construed to represent any agency determination or policy. 75

Author

Year

(Data 

Extractor)

Risk of Bias

Score Study Objective Population and Setting (N) Intervention Results Comments

redo procedures, 

with or without 

aortic or mitral 

valve replacement 

or endarterectomy. 

Orthopedic patients 

undergoing elective 

THR or TKR whether 

primary or redo 

operations. Bilateral 

procedures were 

included if 

performed during 

the same operation

Exclusion Criteria: 

Patients receiving 

previously donated 

autologous 

transfusions

Cohort1: patients 

receiving BR-RBC & 

WBC-reduced 

transfusions unless 

they had also 

received at least 2 

units of unmodified 

RBCs.

 Control1: 5/871 (0.6%)

 Control2: 3/799 (0.4%)

Adverse events:

Major Complications

Orthopedic

 Intervention1: 40/606 

(6.6%)

 Intervention2: 39/637 

(6.1%)

AOR: 0.85 (0.28-2.61); 

P=0.775

 Control1: 34/871 (3.9%)

 Control2: 15/799 (1.9%)

 AOR: 0.44 (0.24-0.82); 

p=0.010

Rosencher

2003 4

(ES)

Prospective 

Concurrent 

Cohort

1, 3, 4, 5,

To examine blood 

management 

practices before, 

during and after 

elective total knee 

and total hip 

arthroplasties in 

Europe (including 

revisions and 

Number of 

patients: N=3996

Patient 

Characteristics

·Age mean±SD

 69±11.2 years

 Allogeneic-only: 

71±10.7

Intervention group: 

Received 

Transfusions:2762

Allogeneic Only (±WBC 

filtration)

=1024/2762 (37%) 

Autologous Only

=1393/2762 (50%)

 Autologous Blood 

SSI (Follow up discharge 

from Surgery Department) 

Unadjusted:

Overall wound infection 

rate: 81/3996 (2%)

Allogeneic-only: 36/999 

(4%)

Autologous-only: 11/1311 

(1%)

Definitions: 

Infection: Determination of infection 

was made using physical clinical 

judgment.

Overall Infection Rates: includes wound 

infections, urinary tract infection, 

respiratory tract infection, septicemia, 

and “other” infections

Estimated blood Loss: Physician’s 
Disclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminated by the Centers for Disease Control and Prevention and should not be 

construed to represent any agency determination or policy. 76

Author

Year

(Data 

Extractor)

Risk of Bias

Score Study Objective Population and Setting (N) Intervention Results Comments

bilateral 

procedures) and to 

determine factors 

predictive of the 

risk associated 

with allogeneic 

transfusion.

Factors examined 

included blood 

wastage; pre- and 

postoperative Hb 

evolution; 

transfusion 

associated 

complications; and 

predictors of 

allogeneic 

transfusion.

 Autologous-only: 

66±11.6

 P<0.001

·Gender: m/f

 1393/2431 (sex 

data missing for 172 

patients)

·Obesity: NR

·Comorbidities: 

Hypertension: 1631 

(41%)

Coronary Artery 

Disease: 469 (12%)

 Significant 

differences between 

transfusion method

groups: χ

2

(3)=13.82; 

P<0.001

Diabetes: 382 (10%)

COPD: 317 (8%)

Rheumatic: 149 

(4%)

 Significant 

differences between 

transfusion method 

groups: χ

2

(3)=13.29; 

P<0.001

Hematologic: 106 

(3%)

Procedures: Elective 

total hip and total 

knee arthroplasties.

Primary unilateral 

hip: 2027 (51%)

Primary bilateral 

Donation (ABD) = 

1290/1393 (93%)

 Acute Normovolemic 

Hemodilution=82/1393 

(6%)

 Cell saver=329

 Postop salvage=264

Allogeneic and 

Autologous: n=345/2762 

(13%)

Timing of intervention: 

Intraoperative/postoperati

ve

Duration of intervention: 

Intraoperative/postoperati

ve

Device/agent: Transfused 

blood

Monitoring intervention: 

CRF=case report forms 

were utilized to report, 

scan then analyze the 

perioperative data 

including transfusion type 

and amount.

Control group: n=1234

No transfusions

Standard preventive 

measures: NR

 Χ

2

(1) = 19.26; p<0.001 

(allogeneic only vs. 

autologous only)

Allogeneic & Autologous: 

8/329 (2%)

No Transfusion: 22/1180 

(2%)

ABD Transfusions only: 

4/615 (1%)

Allogeneic Transfusion

 WBC-Depleted: 18/637 

(3%)

 Not WBC-Depleted: 

18/464 (4%)

No statistically significant 

difference between WBC 

depleted and non WBC 

depleted allogeneic 

transfusions

Knee Patients only

 ABD only: 0/148

 Postop salvage only: 

5/122 (4%) 

Χ

2

(1) = 5.97; p<0.05 (Knee 

ABD vs. Postop Salvage)

Hip Patients Only 

 ABD only: 4/462 (1%)

 Postop salvage only: 

3/69 (4%)

Χ

2

(1) = 5.60; p<0.05 (Hip 

ABD vs. Postop Salvage)

Overall Infection Rates: 

Allogeneic-only: 110/999 

(11%)

estimates of EBL were recorded before 

the surgery.

Baseline Hb level: Hb level collected 

during the assessment office visit when 

the surgery was planned - 21±7 days 

before surgery.

Perioperative care: NR 

Analytical methodology: Logistic 

regression was used for modeling the 

probability of transfusion based on 

selected predictor variables. Otherwise, 

descriptive statistics or Parametric and 

nonparametric statistical tests after 

consideration of distributional 

characteristics and statistical test 

assumptions were utilized.

Other notes: The tables and data were 

not uniformly presented. Numbers & % 

were frequently mislabeled leading to 

problems interpreting the data. Missing 

data from every table resulted in 

“apparent discrepancies” in the counts 

adding to the problem of interpretation.

Follow-up: Until discharge from 

Surgery Department
Disclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminated by the Centers for Disease Control and Prevention and should not be 

construed to represent any agency determination or policy. 77

Author

Year

(Data 

Extractor)

Risk of Bias

Score Study Objective Population and Setting (N) Intervention Results Comments

hip: 27 (1%)

Primary unilateral 

knee: 1036 (26%)

Primary bilateral 

knee: 13 (0%)

Hip revision: 292 

(7%)

Knee revision: 69 

(2%)

Indications: 

Variable

Setting: 225 Centers

Location: Europe --

France, Germany, 

Greece, Italy, the 

Netherlands, and 

Spain

Dates: NR

Inclusion Criteria: 

All patients 

undergoing total hip 

or total knee 

replacement. 

Enrollment of 

consecutive 

patients was 

requested with a 

limit of 20 patients 

per center.

Exclusion Criteria: 

Autologous-only: 93/1311 

(7%)

Allogeneic & Autologous: 

30/329 (9%)

No Transfusion: 94/1180 

(8%)

ABD transfusion only: 

25/615 (4%)

Allogeneic Transfusion

 WBC-Depleted: 82/637 

(13%)

 Not WBC-Depleted: 

42/464 (9%)

Knee Patients only

 ABD only: 6/148(4%)

 Postop salvage only: 

13/122 (11%)

Hip Patients Only 

 ABD only: 19/462 (4%)

 Postop salvage only: 

12/69 (17%)

Other infections: SEE 

ABOVE

Topic-specific outcomes: 

Donated Blood: n=

Baseline Hb Level was 

linearly regressed with the 

probability of allogeneic 

transfusion:

WOMEN: 

Base Hb level of 8.0 = 75% 

prob of transfusion

Base Hb level of 16.0=12% 

prob of transfusion

MEN:
Disclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminated by the Centers for Disease Control and Prevention and should not be 

construed to represent any agency determination or policy. 78

Author

Year

(Data 

Extractor)

Risk of Bias

Score Study Objective Population and Setting (N) Intervention Results Comments

NR Base Hb level of 8.0 = 70% 

prob of transfusion

Base Hb level of 16.0=8% 

prob of transfusion

Reoperations: NR

Length of stay: days

 Allogeneic: 13.0±8.1

 Autologous: 12.3±10.5

Autologous-only collected 

via ABD method: 11.9±7.7

and No transfusion: 

10.7±12.3

vs. Allogeneic (allogeneic 

only or allogeneic and 

autologous): 13.5±10.2

 P<0.001

Mortality: NR

Adverse events: 

Fluid volume overload: 

Ranged from 3-4% across 

transfusion methods: NS

Suspected Clinical DVT: 

Ranged from 2-3% across 

transfusion methods 

including no transfusion. 

NS

Transfusion Reactions: 

Recorded not reported

Borghi

2000 9

(ES)

Prospective 

concurrent 

control

1, 2, 3, 4, 5, 

To evaluate the 

incidence and risk 

factors for 

allogeneic blood 

Number of patients 

N=2884

Patient 

Characteristics

Intervention group: n= 

278

Patients receiving 

allogeneic concentrated 

SSI (follow up: discharge 

from orthopedic ward) 

All infection data was 

presented in bar graph 

Definitions 

Perioperative care: 

MSBOS: the actual number of blood 

units transfused in 90% of patients 
Disclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminated by the Centers for Disease Control and Prevention and should not be 

construed to represent any agency determination or policy. 79

Author

Year

(Data 

Extractor)

Risk of Bias

Score Study Objective Population and Setting (N) Intervention Results Comments

8 transfusion (after 

autologous blood 

transfusion) in 

patients scheduled 

for primary hip, 

primary knee or 

revision hip 

arthroplasties and 

receiving an 

aggressive 

autotransfusion 

regimen

·Age: (mean±SD) 

years

THA: 61±12 

TKA: 68±8

HR: 64±11

·Gender m/f

THA: 726/1290 

TKA: 125/355

HR: 124/264

·Obesity

Weight (kg)

THA: 68±11

TKA: 70±10

HR: 68±10

Height (cm)

THA: 162±9 

TKA: 160±8

HR: 161±8

·Comorbidities: NR

Duration of Surgery 

(min)

THA: 115±38 

TKA: 117±44

HR: 183±64

P (THA vs.

HR)=0.0005

P (TKA vs.

HR)=0.0005

Procedures: 

Total hip 

arthroplasty: 

2016/2884 (69.9%)

Total knee 

arthroplasty: 

480/2884 (16.6%)

red blood cell (ARBC) 

transfusions after all 

autologous blood (both 

pre-donations and blood 

recovered intra and 

postoperatively.

Timing of intervention

Duration of intervention

Agent: 

Autologous Blood 

Collected: According to the 

Maximum surgery blood 

order on Schedule, 2 units 

of pre-donated blood were 

collected for THA and TKA 

and 3 units for Revision of 

Hip Arthroplasty. 

Autologous blood was 

separated into RBC and 

FFP. FFP re-infused at end 

of surgery or within 24h; 

pre-donated RBCs 

transfused during 3d 

postop.

Monitoring intervention: 

NR

Control group: n=2606

Patients receiving 

autologous blood 

transfusion (pre-donation 

separated into RBC and 

FFP) plus intraoperative reinfused cell-salvage and 

postoperative closed 

system drain(see details 

below)

form. The below numbers 

are percentages inferred.

Statistical Significance of 

difference between ARBC 

PLUS Autologous and No 

ARBC across each group is 

as follows

GROUP THA: p=0.0005

GROUP TKA: p=0.008

GROUP HR: p=0.005

Infection:

THA: 

 ARBC plus autologous: 1%

 No ARBC: 0.5%

TKA: 

 ARBC plus autologous: 2%

 No ARBC: 0.5%

HR: 

 ARBC plus autologous: 1%

 No ARBC: 0.5%

Wound Hematoma

THA: 

 ARBC plus autologous: 

11%

 No ARBC: 2%

TKA: 

 ARBC plus autologous: 

11%

 No ARBC: 5%

HR: 

 ARBC plus autologous: 8%

 No ARBC: 2%

Other infections: NR

receiving one individual surgical 

procedure.

Anesthesia: either balanced general, 

regional or integrated epidural/general 

anesthesia. The type was freely decided 

by the attending anesthesiologist with 

no randomization. 

Analytical methodology: Continuous 

variables: Analysis of variance

Post hoc comparisons: Tukey’s test and 

student’s t-test with Bonferroni’s 

correction.

Categorical variables: χ2-square or 

Fisher’s exact test. Multivariate analysis 

of variance for repeated measures with 

Wilks’ λ-test for changes over time

After univariate analysis, partial risk 

factors associated with the response 

were further evaluated by multiple 

logistic regression analyses.

Other notes: None 

Follow-up: Discharge from orthopedic 

ward
Disclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminated by the Centers for Disease Control and Prevention and should not be 

construed to represent any agency determination or policy. 80

Author

Year

(Data 

Extractor)

Risk of Bias

Score Study Objective Population and Setting (N) Intervention Results Comments

Hip revision of 

arthroplasty: 

388/2884 (13.5%)

Indications: variable

Setting: 1 

orthopedic institute

Location: Italy

Dates: NR (5 year 

period)

Inclusion Criteria: 

Patients undergoing 

Total Hip 

Arthroplasty (THA) 

Total Knee 

Arthroplasty (TKA) 

or Hip Revision of 

Arthroplasty (HR)

Exclusion Criteria: 

NR

Standard preventive 

measures

Iron Supplement: during 

each pre-donation of 

autologous blood and the 

first 4 POD, all patients 

received intravenous iron 

(200mg/day)

Perioperative Blood 

Return: Intraoperatively, 

uncoagulated blood was 

collected from wound into 

a reservoir using an 

aspirator and collection 

bag connected to the 

inferior edge of the 

surgical wound in order to 

concentrate, wash and 

infuse red cells. These 

were immediately 

returned to the patient.

Postoperatively, 

uncoagulated blood lost 

from the surgical wound 

was monitored and 

collected using a closed 

recovery system 

connected to the surgical 

drains. If blood losses 

exceeded 200ml during 1st

8h postop, the units of 

fresh frozen plasma were 

re-infused at the end or 

within the first 24h of 

surgery.

Autologous Transfusion 

Topic-specific outcomes: 

Perioperative Blood Losses 

(ml)

THA: 1190±480

TKA: 1280±403

HR: 1720±460

P (THA vs. HR)=0.0005

P (TKA vs. HR)=0.0005

Intraoperative Blood 

recovery (ml)

THA: 267±168

TKA: 162±92

HR: 524±387

P (THA vs. TKA)=0.0005

P (THA vs. HR)=0.0005

P (TKA vs. HR)=0.0005

Postoperative Blood 

recovery (ml)

THA: 387±237

TKA: 541±294

HR: 465±287

P (THA vs. TKA)=0.0005

P (THA vs. HR)=0.0005

P (TKA vs. HR)=0.0005

Patients receiving ABRC 

plus autologous 

Transfusion

THA: 159 (8%) 

TKA: 43 (9%)

HR: 76 (20%)

P (THA vs. HR)=0.0005

P (TKA vs. HR)=0.0005

(number of patients 
Disclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminated by the Centers for Disease Control and Prevention and should not be 

construed to represent any agency determination or policy. 81

Author

Year

(Data 

Extractor)

Risk of Bias

Score Study Objective Population and Setting (N) Intervention Results Comments

Trigger: if Hb <11g/dl

Allogeneic concentrated 

Red Blood cells 

Transfusion Trigger:

presence of asymptomatic 

anemia (vertigo, dizziness, 

postural hypotension, 

headache, insomnia, 

confusion, tachycardia, 

angina, dyspnea) or when 

Hb<6g/dl (10g/dl in 

patients with 

cerebrovascular or 

coronary artery disease)

receiving ABRC 

transfusions was not 

significantly different 

across anesthesia types for 

each surgery type)

Hb concentration: 

Baseline Hb concentration 

was significantly lower for 

HR than for THR and TKR 

at 1st and 3rd

POD(p<0.0005 vs. THA & 

P<0.001 vs. TKA)

Main Risk factors 

associated with An 

increased incidence of 

Perioperative transfusion 

of Allogeneic blood:

Preoperative Hb<10g/dl: 

 OR: 8.8 (6.5-16.8); 

p=0.004

Hip Revision Arthroplasty

 OR: 5.8 (3.9-8.5); 

p=0.0001

No MSBOS pre-donation:

 OR: 3.4 (2.7-4.1); p0.0001

Reoperations: NR

Length of stay:

Patient Discharge (days 

after Surgery)

THA: 12±5

TKA: 16±6

HR: 15±7
Disclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminated by the Centers for Disease Control and Prevention and should not be 

construed to represent any agency determination or policy. 82

Author

Year

(Data 

Extractor)

Risk of Bias

Score Study Objective Population and Setting (N) Intervention Results Comments

P (THA vs. TKA)=0.0005

P (THA vs. THR)=0.0005

Patients not receiving 

ARBC’s log-rank curve 

showed significantly 

shorter durations of stay 

than the log-rank curve for 

patients receiving ARBC 

plus autologous 

transfusion (p=0.0005)

Mortality: NR

Adverse events: 

No severe adverse effects 

were reported during 

either preoperative 

collection of autologous 

blood or iv iron 

administration

Statistical Significance of 

difference between ARBC 

plus autologous blood and 

No ARBC across each 

group is as follows

GROUP THA: p=0.0005

GROUP TKA: p=0.008

GROUP HR: p=0.005

Dysrhythmia

THA: 

 ARBC plus autologous: 3%

 No ARBC: 0.5%

TKA: 

 ARBC plus autologous:9%
Disclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminated by the Centers for Disease Control and Prevention and should not be 

construed to represent any agency determination or policy. 83

Author

Year

(Data 

Extractor)

Risk of Bias

Score Study Objective Population and Setting (N) Intervention Results Comments

 No ARBC: 1%

HR: 

 ARBC plus autologous: 7%

 No ARBC: 1.5%

Respiratory Failure

THA: 

 ARBC plus autologous: 2%

 No ARBC: 0.5%

TKA: 

 ARBC plus autologous: 0

 No ARBC: 1%

HR: 

 ARBC plus autologous: 4%

 No ARBC: 1%

Myocardial Ischemia

THA: 

 ARBC plus autologous: 6%

 No ARBC: 0.5%

TKA: 

 ARBC plus autologous: 0

 No ARBC: 0.5%

HR: 

 ARBC plus autologous: 4%

 No ARBC: 0.5%

Pulmonary Embolism

THA: 

 ARBC plus autologous: 1%

 No ARBC: 0.5%

TKA: 

 ARBC plus autologous: 2%

 No ARBC: 0

HR: 

 ARBC plus autologous: 5%
Disclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminated by the Centers for Disease Control and Prevention and should not be 

construed to represent any agency determination or policy. 84

Author

Year

(Data 

Extractor)

Risk of Bias

Score Study Objective Population and Setting (N) Intervention Results Comments

 No ARBC: 0.5%

Deep Vein Thrombosis

THA: 

 ARBC plus autologous: 

0.4%

 No ARBC: 0.5%

TKA: 

 ARBC: 2%

 No ARBC: 1.5%

HR: 

 ARBC plus autologous: 0%

 No ARBC: 0.5%

C. How does the volume of transfused blood product impact the risk of SSI? Our search did not identify data that evaluated differences in 

the volume of transfused blood product and their impact on the risk of SSI in prosthetic joint arthroplasty patients.

D. How safe and effective is withholding blood transfusion to reduce the risk of SSI? Our search did not identify data that both evaluated 

the safety and effectiveness of withholding blood transfusions and its impact on the risk of SSI in prosthetic joint arthroplasty patients. 
Disclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminated by the Centers for Disease Control and Prevention and should not be 

construed to represent any agency determination or policy. 85

RISK OF BIAS ASSESSMENTS OF STUDIES Q11

Randomized Controlled Trials

Author

Year 

K

Q

Described as 

randomized

Randomization 

appropriately 

performed

Described 

as doubleblind

Outcome 

assessor 

blinded

Study 

participant 

blinded

Investigato

r blinded

Attrition 

described

Attrition smaller 

than 10-15% of 

assigned patients

Attrition 

appropriately 

analyzed

Funding source(s) 

disclosed and no 

obvious conflict of 

interest

Overall 

Risk of 

Bias

Question 11: Blood Transfusion

Frietsch

2008 1 11          Low

Frietsch

2001 2 11        Low

Other Controlled Studies

Author

Year KQ

All study groups 

derived from similar 

source/reference 

populations

Attrition not 

significantly 

different across 

study groups

Measure of 

exposure is 

valid

Measure of 

outcome is valid

Investigator 

blinded to 

endpoint 

assessment

Potential 

confounders 

identified

Statistical 

adjustment for 

potential 

confounders done

Funding source(s) 

disclosed and no 

obvious conflict of 

interest

Overall 

Risk of 

Bias

Question 11: Blood Transfusion

Borghi

2000 9 11       Low

Del Trujillo

2008 8 11        Low

Innerhofer

2005 3 11       Low

Llewelyn

2004 6 11      Low

Pedersen

2009 7 11         Low

Rosencher

2003 4 11     Low

Weber

2005 5 11     Low
Disclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminated by the Centers for Disease Control and Prevention and should not be 

construed to represent any agency determination or policy. 86

Q12-16 SYSTEMIC IMMUNOSUPPRESSIVE THERAPY

GRADE TABLE Q12-16

Comparison Outcome

Quantity 

and Type 

of 

Evidence

Findings Starting 

GRADE

Decrease GRADE Increase 

GRADE

GRADE of 

Evidence for 

Outcome

Overall 

GRADE 

of 

Evidence 

Base

Study QualityConsistencyDirectnessPrecisionPublication BiasLarge MagnitudeDose-responseConfounders

Systemic Immunosuppressive Therapy: Biologic Agents (Non-Tumor Necrosis Factors [TNF] and Anti-TNFs) and Disease Modifying Antirheumatic Drugs-(DMARD)

Q12. How does systemic corticosteroid or other immunosuppressive therapy impact the risk of SSI in prosthetic joint arthroplasty patients?

Q12A. Does the type of agent impact the risk of SSI?

Biologicagents (nonTNF and 

anti-TNF)

vs.

DMARDs

SSI* 2 OBS 10, 11

 In meta-analysis of 2 OBS studies (N=528) , 

biologic agents were associated with a higher 

risk for SSI: OR: 5.90; 95% CI: 2.68 – 12.99; 

p<0.0001 

 In each of these studies10, 11, multivariate logistic 

regression analysis identified biologic agents as a 

significant risk factor SSI.

Low 0 0 0 0 0 0 +1 0 Moderate

PJI* 2 OBS Very low 10,11

 In a meta-analysis of 2 OBS (N=528), biologic 

agents were not associated with a higher risk for 

PJI (OR: 3.59; 95% CI: 0.52 – 24.88; p=0.20)

 In one study10, 3(0.7%) total organ/space SSIs 

among 420 RA patients undergoing THA or TKA: 

1/48(2.08%) vs. 2/372(0.54%); p=0.27 

 In the other study11, 1/54(1.85%) vs. 0/54 (0%); 

p=0.50 

Low 0 0 0 -1 0 0 0 0 Very low

Superficial 

SSI* 2 OBS 10,11

 In a meta-analysis of 2OBS (N=528), biologic 

agents associated with increased risk for 

superficial SSI (OR: 5.80; 95% CI: 2.55 – 13.18; 

p<0.0001)

 1 OBS study10= 24(5.7%) total superficial SSIs 

among 420 RA patients undergoing THA or TKA: 

9/48 (18.75%) vs. 15/372(4.03%); p=0.0002

Low 0 0 0 0 0 +1 0 0 Moderate
Disclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminated by the Centers for Disease Control and Prevention and should not be 

construed to represent any agency determination or policy. 87

Comparison Outcome

Quantity 

and Type 

of 

Evidence

Findings Starting 

GRADE

Decrease GRADE Increase 

GRADE

GRADE of 

Evidence for 

Outcome

Overall 

GRADE 

of 

Evidence 

Base

Study QualityConsistencyDirectnessPrecisionPublication BiasLarge MagnitudeDose-responseConfounders

 1 OBS Study11= 7/54(12.96%) vs. 1/54(1.85%); 

p=0.06

Adverse 

events of 

surgical 

wounds

1 OBS 12

 1 small study (N= 113): 2/39 (5.1%) vs. 5/74 

(6.8%);OR 0.7459 (95%CI, 0.1380-

4.0336);p=1.0000 (results include 4 ankle 

fusions)

 No difference on subanalysis (30 THAs and 65 

TKAs- THA: none in either group; TKA: 4/51 

(7.8%) vs. 1/14 (7.1%); OR 0.90 (95%CI, 0.09-

8.80). 92.3% of all patients on biologic agents 

(infliximab and etanercept) were also on 

methotrexate (DMARD).

Low 0 0 0 -1 0 0 0 0 Very low

Adverse 

eventsdrug 

related

1 OBS 11

 1 small (N=90) retrospective 1:1 pair-matched 

case-control study of deep venous thrombosis 

(DVT) in joint arthroplasty (96%) and other joint 

procedures (4%): increased incidence of DVT 

with biologic agents 23/45(51%) vs. 12/45 (26%); 

p=0.015.

 On multivariate logistic regression analysis 

biologic agents (anti-TNF) were the only risk 

factor for DVT: OR 2.83 (95% CI, 1.10-7.25); 

p=0.03

Low 0 0 0 -1 0 0 0 0 Very low

DMARD: 

methotrexat

e vs. 

No DMARD 

therapy

PJI* 1 OBS 13

 No difference in 1 study (N=202) total joint 

replacements in RA patients: 3/92 (3.26%) vs. 

2/110 (1.81%); p=0.66 at 6m follow-up

 Revision total joint replacements: 1/9 (11.1%) vs. 

0/16; p=0.26

 Bilateral TKA: 0/3 vs. 1/11 (9.09%); p=1.00 

Low 0 0 0 -1 0 0 0 0 Very low Very low
Disclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminated by the Centers for Disease Control and Prevention and should not be 

construed to represent any agency determination or policy. 88

Comparison Outcome

Quantity 

and Type 

of 

Evidence

Findings Starting 

GRADE

Decrease GRADE Increase 

GRADE

GRADE of 

Evidence for 

Outcome

Overall 

GRADE 

of 

Evidence 

Base

Study QualityConsistencyDirectnessPrecisionPublication BiasLarge MagnitudeDose-responseConfounders

Deep 

wound 

abscess*

1 OBS 13

 No difference: 0/92 vs. 1/110 (0.91%); p=0.57 Low 0 0 0 -1 0 0 0 0 Very low

Infected 

Hematom

a*

1 OBS 13

 No difference: 2/92 (2.2%) vs. 1/110 (0.9%); 

p=0.47

 Bilateral TKA 1/3 (33%) vs. 0/11; p=0.14

Low 0 0 0 -1 0 0 0 0 Very low

Necrotic 

eschar 1 OBS 13

 No difference: 2/92 (2.17%) vs. 0/110; p=0.24 Low 0 0 0 -1 0 0 0 0 Very low

Serous 

drainage 1 OBS 13

 No difference: 1/92 (1.09%) vs. 1/110 (0.91%) Low 0 0 0 -1 0 0 0 0 Very low

Q12B. Does the preoperative duration of the therapy impact the risk of SSI?

Disease 

duration SSI* 2 OBS 10, 11

 In a study10 comparing RA patients on biologics 

(anti-TNF) and DMARDs undergoing arthroplasty 

surgery, multivariate logistic regression analysis 

comparing infected to non-infected patients 

showed years of disease duration was a risk 

factors for SSI (OR 1.09; CI 1.04-1.14; p=0.003). 

 Disease duration for the cohort10 was a median 

of 14.5 years (interquartile range 8.9-21) but 

these results were not stratified by biologic 

agents vs. DMARDs.

 In a study11 comparing RA patients on biologic 

(anti-TNF) and DMARDs undergoing arthroplasty 

surgery multivariate logistic regression analysis 

also suggested disease duration as a risk factor 

for SSI: OR 1.17: 95%CI, 1.03-1.33; p=0.015.

Low 0 0 0 0 0 0 0 0 Low Low
Disclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminated by the Centers for Disease Control and Prevention and should not be 

construed to represent any agency determination or policy. 89

Comparison Outcome

Quantity 

and Type 

of 

Evidence

Findings Starting 

GRADE

Decrease GRADE Increase 

GRADE

GRADE of 

Evidence for 

Outcome

Overall 

GRADE 

of 

Evidence 

Base

Study QualityConsistencyDirectnessPrecisionPublication BiasLarge MagnitudeDose-responseConfounders

Q12C. Does the agent dose impact the risk of SSI?

Biologicagents 

(anti-Tumor 

necrosis 

factors) vs. 

DMARDs

SSI* 2 OBS 11, 10

 In a retrospective 1:1 matched pair case control 

study11 64 rheumatoid arthritis patients on

biologic agents (anti-TNF) were matched to 64 

patients on DMARDs. Patients in the biologic 

agent (anti-TNF) group were on significantly 

higher daily doses of prednisone (5mg/day; 

range 2-7) than the DMARD patients (3mg/day, 

range 0-5); p=0.006. Multivariate logistic 

regression analysis showed that prednisone dose 

(OR 1.433:95%CI, 1.007-2.040; p=0.046) was a 

risk factor for SSI. 

 In a retrospective study10 of 420 THAs and TKAs 

in RA patients, multivariate logistic regression 

analysis comparing infected to non-infected 

patients did not show prednisone dose to be a 

risk factor for SSI. Both patients with SSI (n=27) 

and those without SSI (n=393) were on 

prednisone doses of 3mg/day, range 0-5); 

p=0.27. Results were not stratified by biologic 

agents vs. DMARDs.

Low 0 -1 0 0 0 0 0 0 Very low Very low

Q13. What are the most effective strategies in managing systemic corticosteroids or other immunosuppressive therapy perioperatively to reduce the risk of SSI in prosthetic joint 

arthroplasty patients?

Q13A. How safe and effective is the discontinuation of these agents preoperatively and when should they be resumed?

DMARD: 

Methotrexat

e stopped 

vs. 

continued 

perioperativ

PJI*

4 OBS 14,13, 

15, 16

 In a meta-analysis (N=180) of 3 small 

observational studies, the data suggests that 

stopping methotrexate is associated with lower 

risk for PJI, but the result is not significant (OR: 

0.20; 95% CI: 0.04 – 1.03; p=0.05)

 1 small OBS study15, overall SSI: 3/41 (7.3%)

Low 0 0 0 0 0 0 0 0 Low Low
Disclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminated by the Centers for Disease Control and Prevention and should not be 

construed to represent any agency determination or policy. 90

Comparison Outcome

Quantity 

and Type 

of 

Evidence

Findings Starting 

GRADE

Decrease GRADE Increase 

GRADE

GRADE of 

Evidence for 

Outcome

Overall 

GRADE 

of 

Evidence 

Base

Study QualityConsistencyDirectnessPrecisionPublication BiasLarge MagnitudeDose-responseConfounders

ely  1 OBS study15

, no difference: 0/26 y vs.3/15; 

p=0.08. 1y follow up. Methotrexate 2 weeks 

perioperatively

 In each of these studies13- No difference: 1/47 

(2.1%) vs. 2/45 (4.44%); p=0.54; 6m follow up. 

Methotrexate stopped indefinitely

 No difference in one small (N=47) study14: 0/32 

vs.1 /15 (6.67%); p=0.25. No PJIs reported 

among 32 patients who stopped methotrexate 

therapy 4 or more weeks preoperatively as 

compared to 1 among the 15 patients who were 

one methotrexate within 4 weeks of surgery: 

 In 1 OBS study16 (N=462) in RA patients 

undergoing 657 THAs and TKAs, patients were 

receiving at least 1 DMARD within 3 months of 

surgery in 336 of those 657 procedures. DMARD 

therapy was withheld in 192/336 (57%) of these 

procedures. Stopping DMARD therapy at the 

time of surgery lowered the risk of subsequent 

PJI: HR 0.65 (95% CI, 0.09-4.95) but this was not 

statistically significant.

RA Flare 1 OBS 15  “No patient in either group experienced a 

postoperative flare of their rheumatoid arthritis” Low 0 0 0 -1 0 0 0 0 Very low

Infected 

Hematom

a

1 OBS 13

 No difference: 2/47 (4.25%) vs. 0/45; p=0.30 Low 0 0 0 -1 0 0 0 0 Very low
Disclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminated by the Centers for Disease Control and Prevention and should not be 

construed to represent any agency determination or policy. 91

Comparison Outcome

Quantity 

and Type 

of 

Evidence

Findings Starting 

GRADE

Decrease GRADE Increase 

GRADE

GRADE of 

Evidence for 

Outcome

Overall 

GRADE 

of 

Evidence 

Base

Study QualityConsistencyDirectnessPrecisionPublication BiasLarge MagnitudeDose-responseConfounders

Necrotic 

eschar 1 OBS 13

 No difference: 2/47 (4.25%) vs. 0/45; p=0.30 Low 0 0 0 -1 0 0 0 0 Very low

Noncommunic

ating 

serous 

drainage

1 OBS13

 No difference: 0/47 vs. 1/45 (2.22%);p=0.48 Low 0 0 0 -1 0 0 0 0 Very low

Biologic 

agent: Antitumor 

necrosis 

factor (antiTNF): 

Stopped vs. 

continued 

perioperativ

ely 

PJI* 1 OBS16

 Subanalysis16 of 50/462 RA patients on biologic 

agent (anti-TNF) therapy (etanercept, 

adalimumab, infliximab, or anakinra) who 

underwent hip or knee arthroplasties, suggested 

an increase in incidence of PJIs among those in 

whom anti-TNF therapy was continued 

perioperatively, but the findings were not 

statistically significant: 0/12(0%) vs. 3/38 (7.9%).

Low 0 0 0 -1 0 0 0 0 Very low Very low

Intra-articular Corticosteroid InjectionsQ15. How do preoperative intra-articular corticosteroid injections impact the risk of SSI in prosthetic joint arthroplasty patients?

History of 

corticosteroi

d Injection 

vs.

no injection

SSI* 5 OBS 17, 18, 

19, 20, 21

 Meta-analysis (N=1146) 5 OBS studies; OR: 1.91; 

95% CI: 1.01 – 3.61; p=0.05 

 35/476 (7.4%) vs. 26/670 (3.9%)

Low 0 0 0 0 0 0 0 0 Low Low

TKA: 

Injection vs. 

No Injection

SSI* 2 OBS 17,18

 In a meta-analysis of 2 studies (N=414), no 

difference between groups (OR: 1.89; 95% CI: 

0.53 – 6.76; p=0.33)

Low 0 0 0 -1 0 0 0 0 Very low Very Low
Disclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminated by the Centers for Disease Control and Prevention and should not be 

construed to represent any agency determination or policy. 92

Comparison Outcome

Quantity 

and Type 

of 

Evidence

Findings Starting 

GRADE

Decrease GRADE Increase 

GRADE

GRADE of 

Evidence for 

Outcome

Overall 

GRADE 

of 

Evidence 

Base

Study QualityConsistencyDirectnessPrecisionPublication BiasLarge MagnitudeDose-responseConfounders

PJI* 2 OBS 17, 18

 In a meta-analysis of 2 studies (N=414), no 

difference between groups (OR: 12.30; 95% CI: 

0.62 – 242.88; p=0.10)

 1 study17 (N=144) reported significant risk of PJI 

for TKA patients injected prior to surgery: 3/54 

(5.6%) vs. 0/90 (0%); p<0.025 at 1yr follow up. 

All 3 had received a steroid injection within 

11mo of surgery; mean (range): 9.6mo (8-11)

 One study18 (N=270) matched 90 injected 

patients to 180 patients not injected prior to 

TKA and reported no infections in either group at 

1 year follow up: 0/90 vs. 0/180. Half were 

injected within 1yr prior to surgery.

Low 0 -1 0 -1 0 0 0 0 Very low

Superficial 

SSI* 2 OBS 18,17

 In a meta-analysis of 2 studies (N=414): no 

difference between groups (OR: 1.71; 95% CI: 

0.68 – 4.31; p=0.26)

 One study17 (N=144) reported 22 (15.3%) total 

superficial SSIs and no difference at 30 day 

follow up: 12/54 (22.2%) vs. 10/90 (11.1%); 

p=0.1 

 One study18 (N=270) reported 7(2.6%) total 

superficial SSIs and no difference at 30 day 

follow up: 2/90(2.2%) vs. 5/180(2.7%); RR 0.80 

(95% CI, 0.16-4.03);p=1.0

Low 0 0 0 0 0 0 0 0 Low

THA: 

Injection vs. 

No Injection

SSI* 3 OBS 19, 20, 

21

 In a meta-analysis of 3 studies (N=732), no 

difference between groups: 18/332 vs. 11/400; 

p=0.07; OR: 1.70; 95% CI: 0.58 – 4.96; p=0.34)

 1 OBS Study19, SSI= 0/68 vs. 2/136

 1 OBS Study20, SSI= 14/224 vs. 9/224

 1 OBS Study21, SSI= 4/40 vs. 0/40

Low 0 0 0 -1 0 0 0 0 Very low Very Low
Disclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminated by the Centers for Disease Control and Prevention and should not be 

construed to represent any agency determination or policy. 93

Comparison Outcome

Quantity 

and Type 

of 

Evidence

Findings Starting 

GRADE

Decrease GRADE Increase 

GRADE

GRADE of 

Evidence for 

Outcome

Overall 

GRADE 

of 

Evidence 

Base

Study QualityConsistencyDirectnessPrecisionPublication BiasLarge MagnitudeDose-responseConfounders

PJI* 3 OBS 19, 20, 

21

 In a meta-analysis of 3 studies (N=732), no 

difference between groups7/332 (2.1%) vs. 

2/400 (0.5%); (OR: 2.95; 95% CI: 0.61 – 14.18; 

p=0.18)

 One study19 (n=202) found 66 injected patients 

(68 THAs) to 136 not-injected patients (136 

THAs): no difference: 0/68 (0%) vs. 

1/136(0.73%); p=0.80. Methylprednisolone 

40mg/dL injections were administered an 

average of 14 months before surgery (median, 

11months)

 One retrospective matched cohort study20

(N=4448) in THA reported no difference: 

3/224(1.33%) vs. 1/224 (0.44%) at 2y follow up. 

Hazard ratio: 3 (95%CI, 0.3-29.8). Cumulative 

risk of deep infection at 5yr was 3% (95% CI, 0-

7%) for the injection group and 0.6% (95%CI, 0-

1.7%) for the no-injection group. Steroid dose 

average 20.47mg (range, 6-40)

 1 small (N=80) study21 in joint infections 

requiring revision THA reported no difference: 

4/80 (5%); 4/40(10%) vs. 0/40(0%); p=0.13 at 1y 

follow up (used methylprednisolone 80mg/dL)

Low 0 0 0 -1 0 0 0 0 Very Low

Superficial 

SSI*

3OBS 19, 20, 

21

 In a meta-analysis of 3 studies (N=732), no 

difference between groups (OR: 1.32; 95% CI: 

0.54 – 3.22; p=0.55)

 One study19 found no difference: 0/68(0%) vs. 

1/136 (0.73%); p=0.80. (30 day follow up)

 One study20 found no difference: 11/224(4.9%) 

Low 0 0 0 0 0 0 0 0 Low
Disclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminated by the Centers for Disease Control and Prevention and should not be 

construed to represent any agency determination or policy. 94

Comparison Outcome

Quantity 

and Type 

of 

Evidence

Findings Starting 

GRADE

Decrease GRADE Increase 

GRADE

GRADE of 

Evidence for 

Outcome

Overall 

GRADE 

of 

Evidence 

Base

Study QualityConsistencyDirectnessPrecisionPublication BiasLarge MagnitudeDose-responseConfounders

vs. 8/224(3.6%) 2 year follow up; Hazard ratio 

1.5 (95% CI, 0.6-3.6); Cumulative risk of 

superficial SSI at 5 years: 4.5% (95% CI, 2.4-8.4) 

vs. 3.7% (95% CI, 1.1-6.1) 

 One study21 found no infections: 0/40 vs. 0/40 (1 

year follow up).

Q16 What are the most effective strategies for managing the preoperative use of intra-articular corticosteroid injections to reduce the risk of SSI in prosthetic joint arthroplasty 

patients?

Q16A. Does the length of time between intra-articular corticosteroid injection and prosthetic joint arthroplasty impact the risk of SSI?

THA:

Length of 

time 

between 

most recent 

injection 

and surgery

SSI* 2 OBS 21

, 

20

 In a small (N=80) matched, cohort (injected: not 

injected) study: neither the total number of 

injections (p=0.891) before THA nor the time 

interval between the injection and the operation 

(p=0.878) differed. For this particular measure, 

the study was underpowered (0.052 and 0.053, 

respectively)

 No association between the average time from 

intra-articular corticosteroid injection to primary 

THA and the development of superficial SSI or 

PJI 

 Mean time between injection and THA: 112 days 

(SD=81days).

 Mean time between injection and THA for 3 

patients who developed PJI was less than half 

the length of time for those who developed 

superficial SSI (n=11): 44 days (SD=23) vs. 

112days (SD=94d). 

Low 0 0 0 0 0 0 0 0 Low Low

*Critical outcome; OR: Odds Ratio; RR: Risk Ratio; CI: Confidence Interval
Disclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminated by the Centers for Disease Control and Prevention and should not be 

construed to represent any agency determination or policy. 95

EVIDENCE TABLE Q12-16

Systemic immunosuppressive therapy

Q12. How does systemic corticosteroid or other immunosuppressive therapy impact the risk of SSI in prosthetic joint arthroplasty patients? 

A. Does the type of agent impact the risk of SSI?

B. Does the preoperative duration of the therapy impact the risk of SSI?

C. Does the agent dose impact the risk of SSI?

Q13. What are the most effective strategies in managing systemic corticosteroids or other immunosuppressive therapy perioperatively to 

reduce the risk of SSI in prosthetic joint arthroplasty patients?

A. How safe and effective is the discontinuation of these agents preoperatively and when should they be resumed?

Author

Year

(Data 

Extractor)

Risk of Bias 

Score Study Objective Population and Setting Intervention Results Comments

Bridges

1991 14

(ES)

Retrospecti

ve 

concurrent 

control

1, 2, 3, 4, 6, 

7, 8

To compare the 

surgical 

outcomes of 

patients with 

Rheumatoid 

Arthritis (RA) in 

whom 

methotrexate 

(MTX) was 

stopped more 

than 4 weeks 

preoperatively 

with those in 

whom MTX was 

stopped less 

than 4 weeks 

preoperatively. 

All orthopedic 

surgeries were 

included.

Number of patients: N=38 

patients (6 patients in both 

groups) and 47 procedures

Patient Characteristics: no 

statistically significant 

differences between the 

patients in control and 

intervention groups with 

regard to any of the 

characteristics examined.

·Age: 

·Gender: 

·Obesity: 

·Comorbidities: 

Procedures: n/N procedures

TJA of hip or knee (n)

 MTX-on: 12/19 (63.2%)

 MTX-off: 32/34 (94.1%)

MCP arthroplasty

 MTX-on: 2/19 (10.5%)

 MTX-off: 0/34 

Metatarsal head resection 

 MTX-on: 1/19 (5.3%)

Intervention group: n=19 (6 

patients in both groups) [19 

procedures] 

MTX-On - Patients who 

received MTX within 4 weeks 

of surgery

Timing of intervention: NA

Duration of intervention: NA

Device/agent: NA

Monitoring intervention: NA

Control group: n=25 (6 

patients in both groups) [34 

procedures]

MTX-Off – patients in whom 

MTX was discontinued 4 or 

more weeks before the 

surgery, and those in whom 

surgery was performed before 

or after the MTX treatment 

period and who were taking no 

disease modifying anti 

rheumatic drugs (DMARDs) for 

at least 3 months prior to 

SSI (6 weeks) 

PJI

 MTX-on: 1/15 procedures 

(6.7%)

 MTX-off: 0/32 

 P=0.25

Other infections: NR

Topic-specific outcomes: 

Flares NR

Reoperations: NR

Length of stay: NR

Mortality: 

MTX-on: 6/19 (31.6%)

 MTX-off: 4/25 (16.7%)

 One (1) patient death 

overlapped both groups.

Adverse events: NR

Definitions: 

Complications: prosthetic 

joint infection or would 

dehiscence or infection 

documented in the 

medical record within 6 

weeks after surgery

Perioperative care: NR

Analytical methodology:

student’s t test, chi-square 

test, or Fisher’s exact, 2-

tailed as appropriate.

Other notes: none

Follow-up: 6 weeks postop
Disclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminated by the Centers for Disease Control and Prevention and should not be 

construed to represent any agency determination or policy. 96

Author

Year

(Data 

Extractor)

Risk of Bias 

Score Study Objective Population and Setting Intervention Results Comments

 MTX-off: 1/34 (2.9%)

Shoulder arthroplasty

 MTX-on: 1/19 (5.3%)

 MTX-off: 0/34 

Other 

 MTX-on: 3/19 (15.8%)

 MTX-off: 1/34 (2.9%)

Indications: Rheumatoid 

Arthritis (RA)

Setting: 1 University hospital

Location: USA

Dates: 1981-1989

Inclusion Criteria: Patients 

with RA who began MTX 

therapy and who underwent 

elective primary orthopedic 

surgery before January 1990.

Exclusion Criteria: Patients 

undergoing revision Total 

Joint Arthroplasty.

surgery.

Standard preventive 

measures: NR

Carpenter

1996 15

(ES)

Prospective 

Concurrent 

control

1, 2, 3, 4, 6, 

7

To prospectively 

follow all 

rheumatoid 

arthritis (RA) 

patients 

receiving 

Methotrexate 

(MTX) who 

underwent total 

joint 

arthroplasty to 

determine if 

continuing or 

stopping MTX 

during the 

perioperative 

Number of patients: N=32 

patients (41 procedures)

Patient Characteristics: no 

significant differences in 

patient characteristics 

between groups

Procedures: 

THA:

 MTXon – 8/26 (30.8%)

 MTXoff – 4/16 (25%)

TKA:

 MTXon – 7/26 (26.9%)

 MTXoff – 3/16 (18.8%)

TWA:

 MTXon – 3/26 (11.5%)

 MTXoff – 3/16 (18.8%)

Intervention group: n=19 (26 

procedures)

Patients assigned to 

discontinue MTX the week 

prior and during the week of 

surgery (total of 2 weeks)

Timing of intervention: NA

Duration of intervention: NA

Device/agent: Methotrexate

Monitoring intervention: NA

Control group: n=13 (15 

procedures)

Patients assigned to continue 

MTX through the perioperative 

period.

Standard preventive 

SSI (1 year) 

PJI

MTX-on: .3/15 procedures 

(20%) 

MTX-off: 0/26 procedures 

p=0.08

Other infections: NR

Topic-specific outcomes: 

Flares: no flares reported in 

either group

Reoperations: NR

Length of stay: NR

Mortality: NR

Adverse events: NR

Definitions: none

Perioperative care: NR

Analytical methodology:

two-sample t test. 

Bonferroni correction was 

used for multiple 

comparisons. Fisher’s 

exact test.

Other notes: none

Follow-up: at least 1 year 

postop
Disclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminated by the Centers for Disease Control and Prevention and should not be 

construed to represent any agency determination or policy. 97

Author

Year

(Data 

Extractor)

Risk of Bias 

Score Study Objective Population and Setting Intervention Results Comments

period 

influenced the 

rate of 

postoperative 

infections.

TMCPA:

 MTXon – 7/26 (26.9%)

 MTXoff – 4/16 (25%)

TEA

 MTXon – 0/26

 MTXoff – 1/16 (6.25%)

Indications: Rheumatoid 

Arthritis

Setting: 1 army medical 

center

Location: USA

Dates: January 1982 –

December 1991

Inclusion Criteria: All RA 

patients receiving MTX at the 

time they were to undergo 

total joint arthroplasty or joint 

fusion during study dates.

Exclusion Criteria: patients on 

azathioprine concurrently

measures: NR

Perhala

1991 13

(ES)

Study 

Design

1, 2, 3, 4, 6, 

7

To assess 

whether the risk 

of local 

infectious 

complications or 

poor wound 

healing is 

increased during 

the 

postoperative 

course in 

Rheumatoid 

arthritis (RA) 

patients treated 

with 

Methotrexate 

Number of patients: N=121 

patients (202 procedures)

Patient Characteristics: unless 

listed below, no statistically 

significant differences in 

characteristics existed 

between groups.

·Age: mean (Y)

 MTX: 54.6

 NoMTX: 59.0

 P=0.03

·Gender: 

·Obesity: 

·Comorbidities: 

Daily prednisone dose: 

mean(mg)

Intervention Group: n=60 

patients (92 procedures) 

Patients who had taken MTX:

Intervention group1: 

MTXoff: Patients who had 

taken MTX but stopped more 

than 4 weeks prior to the 

surgery

Intervention group2:

MTXon: patients who had 

taken MTX but who took MTX 

within 4 weeks of surgery

Timing of intervention: NA

Duration of intervention: NA

Device/agent: Methotrexate

Monitoring intervention: NA

SSI (6 months)

PJI

MTX VS NO MTX

All Total Joint Replacements

MTX: 3/92 (3.26%) 

NoMTX: 2/110 (1.81%)

 p=0.66 

Revision total joint 

replacements: MTX: 1/9 

(11.1%) 

NoMTX 0/16

p=0.26

Bilateral TKA

MTXon 0/3 

NoMTX: 1/11 (9.09%)

p=1.00

Definitions: NR

Perioperative care: NR

Analytical methodology:

Student’s t test, Chi square 

analysis.

Other notes: None

Follow-up: 6 months
Disclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminated by the Centers for Disease Control and Prevention and should not be 

construed to represent any agency determination or policy. 98

Author

Year

(Data 

Extractor)

Risk of Bias 

Score Study Objective Population and Setting Intervention Results Comments

(MTX) MTX: 4.87

 NoMTX: 3.69

 P=0.08

Procedures: THA And TKA

Indications: Rheumatoid 

Arthritis

Setting: 1 hospital

Location: USA

Dates: January 1, 1978 –

December 31, 1987

Inclusion Criteria: Patients 

who underwent Total hip or 

total knee replacement at the 

center during the study dates. 

And who were classified by 

the American Rheumatism 

Association criteria as having 

classic or definite RA (30).

Exclusion Criteria: Patients 

who had undergone apheresis 

or total lymphoid irradiation 

or had been treated with 

azathioprine, 

cyclophosphamide, or 

chlorambucil concurrently 

Control group: n=61

Patients who had never taken 

MTX

Standard preventive 

measures: All patients received 

antimicrobial s perioperatively 

(Cefazolin or vancomycin)

Continuous MTX vs. Pausing 

MTX

PJI

 MTXon: 2/45 (4.44%)

 MTXoff: 1/47 (2.12%) 

 p=0.54

Other infections: 

MTX vs. No MTX

Deep Wound Abscess

MTX: 0/92 

NoMTX: 1/110 (0.91%)

p=0.57

Infected Hematoma

 MTX: 2/92 (2.17%) 

 NoMTX: 1/110 (0.91%)

 p=0.47

 Bilateral TKA 

 MTX: 1/3 (33%) 

 NoMTX 0/11

 p=0.14

Necrotic eschar

MTX: 2/92 (2.17%) 

noMTX: 0/110

p=0.24

Serous Drainage

MTX: 1/92 (1.09%)

NoMTX: 1/110 (0.91%)

Continuous MTX vs. Paused

MTX

Infected Hematoma

 MTXoff: 2/47 (4.25%) 

 MTXon: 0/45;

p=0.30 

Necrotic eschar

MTXoff: 2/47 (4.25%) 
Disclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminated by the Centers for Disease Control and Prevention and should not be 

construed to represent any agency determination or policy. 99

Author

Year

(Data 

Extractor)

Risk of Bias 

Score Study Objective Population and Setting Intervention Results Comments

 MTXon: 0/45

 p=0.30 

Serous Drainage

 MTXoff: 0/47

 MTXon: 1/45 (2.22%)

 p=0.48 

Topic-specific outcomes: 

Reoperations: 

Length of stay: 

Mortality: 

Adverse events: 

Momohar

a 

2011 10

(ES)

Retrospecti

ve 

concurrent 

control

1, 2, 3, 4, 5, 

6, 7,

To analyze the 

risk ratios of SSI 

after total hip 

arthroplasty 

(THA) or total 

knee 

arthroplasty 

(TKA) in 

Rheumatoid 

Arthritis (RA) 

patients treated 

with biologic 

DMARDs (mainly 

TNF blockers) 

compared with 

RA patients 

treated with 

non-biologic 

DMARDs.

Also to 

determine 

whether 

perioperative 

interruption of 

Number of patients: N=420

 THA = 81 (19.3%)

 TKA = 339 (80.7%)

Patient Characteristics: given 

for total population given as n 

(%) or median (IQR)

·Age: 61 (54.8-68) y

·Gender % female: 382 

(91.0%)

·Obesity: 21.4 (19.4-23.8) BMI

·Comorbidities:

Diabetes: 34 (8.1%)

Smoking (ever): 67 (16.0%)

Surgical history: 193 (46.0%)

Disease Duration: 14.5 (8.9-

21.0)y

Preop CRP: 0.98 (0.25-2.19)

Preop Hb: 10.9 (10.2-11.8)

Preop WBC: 7.25 (6.1-9.0)

Revision: 16 (3.8%)

Procedures: Total Hip 

Arthroplasty (THA) or Total 

Knee Arthroplasty (TKA)

Intervention group: n= 48

Biologic DMARDS

 THA = 11

 TKA= 37

IFX: 19 (4.5%)

ETN: 23 (5.5%)

ADA: 2 (0.5%)

TCZ: 4 (1.0%)

Timing of intervention: For 

TNF-blockers was performed in 

accordance with British Society 

for Rheumatology and Japan 

College of Rheumatology 

Guidelines.: That TNF-blocker 

treatment should be withheld 

2-4 weeks prior to major 

surgical procedures: specifically 

ETN & ADA: 2-4 weeks

IFX & TCZ: 4 weeks (TCZ was 

restarted 4 weeks after 

surgery)

Duration of intervention:

variable 

SSI (Follow Up NR)

TOTAL INFECTIONS

27 total Postop Complications 

(6.4%)

Superficial incisional SSI: 24 

(5.7%) – [treated with 

antimicrobials]

Organ/Space SSI: 3 (0.7%) –

[required surgical treatment 

to remove the artificial joint 

prosthesis]

 Non-biologic DMARDs: 2/3 

(66.7%)

 IFX: 1/3 (33.3%)

Statistically significant risk 

factors

Disease Duration (years)

 SSI: 23.3 (17.6-26.4)

 No-SSI: 14.1 (8.1-19.6)

 OR: 1.09 (1.04-1.14); p=0.003

Biologic DMARDs

 SSI: 10/27 (37.0%)

 No-SSI: 38/393 (9.7%)

Definitions:

SSI: diagnosed by surgeon 

according to CDC SSI 

Guideline 1999. 

Perioperative care: 

General, lumbar and/or 

epidural anesthesia were 

all utilized 

Analytical methodology:

Multivariate logistic 

regression to test the 

association of SSI with 

putative risk factors and 

with the use of nonbiologic DMARDs and 

biologic DMARDs. 

Other notes: NR

Follow-up: NR
Disclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminated by the Centers for Disease Control and Prevention and should not be 

construed to represent any agency determination or policy. 100

Author

Year

(Data 

Extractor)

Risk of Bias 

Score Study Objective Population and Setting Intervention Results Comments

TNF blockers 

decreases SSI.

FROM 

DISCUSSION

The aims of this 

study were to 

assess the 

influence of nonbiologic DMARDs 

and biologic 

DMARDs, as well 

as the 

withholding of 

TNF-blocker 

therapy on the 

incidence of SSI.

Indications: Rheumatoid 

Arthritis (RA)

Setting: 1 Medical University 

Institute of Rheumatology

Location: Japan

Dates: January 2005 and 

December 2009

Inclusion Criteria: Patients 

who full the 1987 revised 

American College of 

Rheumatology (ACR) criteria 

for RA who underwent THA or 

TKA between January 2005 

and December 2009 and were 

treated with biologic or nonbiologic DMARDs

Exclusion Criteria: NR

Agent: biologic Disease 

Modifying Antirheumatic DrugS 

(bDMARDS)

Monitoring intervention: NR

Control group: n=372

 THA=70

 TKA=302

Non-biologic DMARDs. As a 

rule were continued 

perioperatively but were 

administered cautiously in 

individual patients if there 

were comorbidities or were 

elderly.

Patients in this group received 

one or more 

immunosuppressive and/or 

immunomodulatory Nonbiologic medication 

IMMUNOSUPPRESIVE AGENTS

MTX: 279 (66.4%)

Leflunomide: 4 (1%)

Tacrolimus: 31 (7.4%)

Mizoribine: 15 (3.6%)

Cyclophosphamide: 3 (0.7%)

IMMUNOMODULATORY 

AGENTS

Salazosulfapyridine: 93 (22.1%)

Bucillamine: 52 (12.4%)

Minocycline: 7 (1.7%)

Actarit: 9 (2.1%)

Auranofin: 4 (1.0%)

Gold Sodium Thiomalate: 1 

(0.2%)

ᴅ-penicillamine: 16 (3.8%)

 OR: 5.69 (2.07-15.61); 

p=0.0007

Prednisone dose not a 

statistically significant risk 

factor

 SSI: 3 (0-5

 No-SSI: 3 (0-5

 OR: 1.09 (0.93-1.28); p=0.27

Statistically significant 

Medications as SSI risk factors 

(where n>10 administered 

patients)

IFX

 SSI: 4/27 (14.8%)

 No-SSI: 15/393 (3.8%)

 OR: 9.8 (2.41-39.82); p=0.001

ETN

 SSI: 6/27 (22.2%)

 No-SSI: 17/393 (4.3%)

 OR: 9.16 (2.77-30.25); 

p=0.0003

Other infections: NR

Topic-specific outcomes: NR

Reoperations:

3 Organ/Space SSI (0.7%) 

required removal of artificial 

joint prosthesis

Length of stay: NR

Mortality: NR

Adverse events: No cases of 

sever delayed wound healing 

requiring additional sutures 
Disclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminated by the Centers for Disease Control and Prevention and should not be 

construed to represent any agency determination or policy. 101

Author

Year

(Data 

Extractor)

Risk of Bias 

Score Study Objective Population and Setting Intervention Results Comments

Glucocorticoids: 296 (70.4%) at 

average dose of 3.0mg/day

Standard preventive 

measures:

All surgeries were performed 

with protective clothing against 

infection, in a bioclean room.

AMP: cefazolin or 

ampicillin/cloxacillin were 

given intravenously twice 

before surgery and 2h after the 

start of surgery. AMP was not 

administered regularly after 

the day of surgery.

were observed.

Hirano

2010 12

(ES)

Retrospecti

ve 

Concurrent 

Cohort

2, 3, 4, 5, 8

To investigate 

the influences of 

anti-Tumor 

Necrosis Factor 

(TNF) agents on 

the 

postoperative 

recovery in 

patients with 

Rheumatoid 

Arthritis (RA) 

and the effects 

of biologics on 

wound healing.

Number of patients: N=113

Patient Characteristics: mean 

± SD (Range) or n (%)

·Age: year (range)

 TNF: 58.9±9.0 (31-73)

 Non-TNF: 62.6±9.1 (30-77)

 P=0.0308

·Gender: Female (%)

 TNF: 32 (82.1%)

 Non-TNF: 65 (87.8%)

·Obesity: NR

·Comorbidities:

RA Duration: years (Range):

 TNF: 13.5±7.8 (4-32)

 Non-TNF: 16.5±11.7 (1-51)

Steinbrocker Stage III vs. IV

 TNF: 18.8% vs. 81.2%

 Non-TNF: 52.7% vs. 47.3%

 P=0.0249

%MTX use

Intervention group: n=39

INF: 24/39 (61.5%)

ETA: 15/39 (38.5%)

Tumor Necrosis Factor (TNF) 

group: patients treated with 

anti-TNF agents from both 

centers

Administration of agents were 

stopped prior to surgery and 

restarted after complete 

wound healing:

Timing of intervention: Pre 

and postoperatively

Duration of intervention: 

variable

 INF: agent stopped 3-4 weeks 

prior to surgery. (mean 29.8 

days preop)

 ETA: agent stopped 1-2 

SSI (follow-up NR) 

Infection

 TNF: 1 (2.6%) TKA

 Agents administered – INF, 

MTX and oral prednisone

 Non-TNF: 5 (6.8%)

OR: 0.7459 (0.138-4.0336) 

P=0.7459

Other infections: NR

Topic-specific outcomes: 

Subanalysis: influence of antiTNF on wound healing 

THA N=30 total TKA N= 65 

total

TNF n=13 TNF n=14

Non-TNF n=17 NonTNF=51

AE Occurrence rate for 

Definitions:

Adverse events (AEs) of 

surgical wounds included 

wound dehiscence and 

continuation of discharge 

that were healed by 

conservative treatment 

Wound dehiscence: wound 

which is not completely 

healed in 14 POD or which 

requires secondary suture.

Infection: positive culture 

results

Time for complete wound 

healing: the period from 

the date of operation to 

the removal of surgical 

staples.

Postop Febrile periods: 

body temp≥37.5oC
Disclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminated by the Centers for Disease Control and Prevention and should not be 

construed to represent any agency determination or policy. 102

Author

Year

(Data 

Extractor)

Risk of Bias 

Score Study Objective Population and Setting Intervention Results Comments

 TNF: 92.3%

 Non-TNF: 50.0%

 P=0.001

Procedures: Ankle arthrodesis 

and total arthroplasty of the 

hip, knee, elbow, shoulder 

and ankle. Only the first 

operation for each patient 

was included.

TKA

 TNF: 14 (35.9%)

 Non-TNF: 51 (68.9%)

THA

 TNF: 13 (38.2%)

 Non-TNF: 17 (23.0%)

TEA

 TNF: 8 (20.5%)

 Non-TNF: 4 (5.4%)

AD

 TNF: 3 (7.7%)

 Non-TNF: 1 (1.4%)

TSA

 TNF: 1 (2.6%)

 Non-TNF: 0

TAA

 TNF: 0

 Non-TNF: 1 (1.4%)

Indications: Rheumatoid 

Arthritis (RA)

Setting: 1 University Hospital 

and 1 medical center

Location: Japan

Dates: April 2004 – July 2007

Inclusion Criteria: Patients 

weeks prior to the surgery. 

(mean 9.6 days preop)

Agents: Anti-TNF

Infliximab (INF) or etanercept 

(ETA)

Monitoring intervention: NR

Control group: n=74

Non-TNF Group (traditional 

DMARDs) consisting of patients 

only from the University 

Hospital.

Standard preventive 

measures: NR

surgical wounds:

THA = 0 .0% in both TNF and 

non-TNF groups.

TKA

 TNF: 1 (7.1%)

 Non-TNF: 4 (7.8%)

OR= 0.9038 (0.0928-8.7992) 

p=NS

Febrile Period

THA

 TNF: 3.5±2.0 days

 Non-TNF: 3.1±1.9days

OR= 0.9038 (0.0928-8.7992) 

p=NS

TKA

TNF: 2.6±2.5 days

Non-TNF: 2.9±1.7 days

%Hb, %TP, %Alb: The only 

statistically significant 

difference between TNF and 

non-TNF groups occurred in 

the THA subgroup for %Hb

TNF: 101.0±14.4%

Non-TNF: 83.8±10.0%

P=0.0016

Reoperations: 

TNF infection was treated 

with surgical debridement 

without implant removal;

antimicrobials were 

administered for 4 weeks.

Length of stay: NR

Mortality: NR

% recovery of hemoglobin 

(%Hb), % recovery of total 

protein (%TP), and % 

recovery of serum albumin 

(%Alb): 

Perioperative care: NR

Analytical methodology: 

Continuous variables 

evaluated with Mann 

Whitney U Test. Or Fisher’s 

exact test to evaluate the 

difference in Proportions.

Other notes: Data was 

collected from medical 

records.

Follow-up: NR
Disclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminated by the Centers for Disease Control and Prevention and should not be 

construed to represent any agency determination or policy. 103

Author

Year

(Data 

Extractor)

Risk of Bias 

Score Study Objective Population and Setting Intervention Results Comments

with RA undergoing Ankle 

arthrodesis and total 

arthroplasty of the hip, knee, 

elbow, shoulder and ankle

Exclusion Criteria: revision 

surgery and other minor 

operations such as foot 

operations and wrist 

operations

Adverse events: 

Adverse Events (AEs) of 

surgical wounds

 TNF: 2 (5.1%)

 Non-TNF: 5 (6.8%)

OR: 0.7459 (0.138-4.0336) 

P=0.7459

Time to Complete Wound 

Healing

TNF: 10.9±1.2 days

Non-TNF: 10.8±1.3 days

PostOp Febrile Periods:

TNF: 2.6±2.2 days

Non-TNF: 2.9±1.7 days

%Hb

TNF: 96.3±14.3%

Non-TNF: 90.1±11.5%

P=0.0156

%TP

TNF: 100.8±9.5%

Non-TNF: 100.8±9.2%

%Alb

TNF: 98.9±13.5%

Non-TNF: 98.0±11.3%

Kawakami

2010 11

(ES)

Retrospecti

ve 

Concurrent 

control

1, 2, 3, 4, 5, 

6, 7

To validate that 

perioperative 

interruption of 

Tumor Necrosis 

Factor (TNF)

blocker therapy 

decreases 

complications 

utilizing the 

British Society 

for 

Rheumatology 

Number of patients: N=128 

surgeries (112 patients)

Patient Characteristics: 

Patients were matched for 

type of surgery and gender 

between groups.

·Age: years 

 TNF: 57.0 (51.8-64.0)

 DMARDs: 57.0 (47.0-64.0)

·Gender: male/female

 TNF: 13/51

 DMARDs: 13/51

Intervention group: n=64 

surgeries (49 patients)

Anti-TNF group

IFX = 35

ETN = 29

NOTE: 56 (87.5%) of TNF group 

was also on MTX and 53 

(82.8%) were on prednisone 

5mg/day (range 2-7) (see 

patient characteristics)

Timing of intervention: 

ETN was withheld 2-4 weeks 

SSI (follow up If using CDC 

criteria then all superficial 

30d and anything with an 

implant wound be 1yr for 

deep and organ/space) 

Superficial SSI

TNF: 7/64 (10.9%) requiring 

the use of antimicrobials

 DMARDs: 1/64 (1.6%)

 P=0.016

Deep SSI:

Definitions:

SSI: CDC SSI Guideline 

criteria (1999) 

Flare-ups: Arthralgia was 

evaluated using subjective 

patient assessments. 

Serological markers like 

CRP and ESR have not 

been deemed suitable for 

measuring the disease 

activity during the 

perioperative period. 
Disclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminated by the Centers for Disease Control and Prevention and should not be 

construed to represent any agency determination or policy. 104

Author

Year

(Data 

Extractor)

Risk of Bias 

Score Study Objective Population and Setting Intervention Results Comments

guidelines and 

the Japanese 

College of 

Rheumatology 

recommendatio

ns for 

withholding 

infliximab (IFX) 

and etanercept 

(ETN) for 2-4 

week prior to 

major surgical 

procedures then 

restarting 

treatment once 

there is no 

evidence of 

infection and 

once wound 

healing is 

satisfactory. 

Wound 

complications, 

Deep Venous 

Thrombosis and 

flare-ups 

following joint 

surgery were 

assessed.

·Obesity (BMI)

 TNF: 21.2 (20.3-22.7)

 DMARDs: 21.2 (20.1-23.9)

·Comorbidities

Disease Duration (y)

 TNF: 10.6 (8.0-19.8)

 DMARDs: 13.4 (8.9-19.1)

Methotrexate (MTX)

 TNF: 56 (87.5%)

 DMARDs: 48 (75%)

 P=0.06

DMARDs

 TNF: 8 (12.5%)

 DMARDs: 31 (48.4%)

 P=7.99E-06

Prednisone (PSL)

 TNF: 53 (82.8%)

 DMARDs: 40 (62.5%)

 P=0.008

PLS, dose, mg/day

 TNF: 5 (2-7)

 DMARDs: 3 (0-5)

 P=0.006

Baseline characteristics for 

DVT Subanalysis (Listed below 

are only those factors that 

demonstrated statistically 

significant differences 

between groups

Methotrexate (MTX)

 TNF: 39 (86.7%)

 DMARDs: 32 (71.1%)

 P=0.06

DMARDs

 TNF: 7 (15.6%)

before surgery inflixamaub

(IFX) was withheld 4 weeks 

before surgery.

Both were restarted after there 

was no evidence of infection 

and once wound healing was 

satisfactory.

Duration of intervention: Pre 

and postoperative

Agent: 

Anti-Tumor Necrosis Factor 

(TNF) agents: Infliximab (INF) 

or etanercept (ETN)

Monitoring intervention: NR

Control group: n=64 surgeries 

(63 patients)

Patients treated with nonbiologic DMARDs. Some 

patients took more than 1 

DMARD

Methotrexate (MTX): n=48

Salazosulphapyridine: n=18

Bycillamine: n=6

ᴅ=penicillamine: n=4

NOTE: 40 (62.5%) of DMARD 

patients were on prednisone 

3mg/day (range 0-5) (see 

patient characteristics)

Standard preventive 

measures: None

 TNF 1/64 (1.6%) – IFX and 

 required prosthesis 

removal

 DMARD: 0

Multivariate analysis of 

putative risk factors for SSI: 

OR (90%CI)

Disease duration (y): 1.169 

(1.030-1.326); P=0.015

TNFα-blocker: 21.8 (1.231-

386.1) p=0.036

PSL dosage: 1.433 (1.007-

2.040) p=0.046

 

Other infections: 

Urinary Tract Infection:

 TNF: 1/64 (1.6%)

 DMARD: 0

Respiratory Inflammation

 TNF: 0

 DMARD: 1/64 (1.6%)

Topic-specific outcomes: 

Flare-ups due to interruption 

of anti-TNF: 

Arthralgia (+):

 IFX: 2/35 (5.7%)

 ETN: 9/29 (31.0%)

 P=0.009

The ETN patients experienced 

difficulty for a while during 

post-op rehab, but recovered 

after resumption of ETN 

Recurrences of Arthralgia 

were considered Flare-ups.

Venous thromboembolism 

of lower extremities: 

diagnosed by 3 

experienced medical 

technologists using 

ultrasonography

Perioperative care: 

All surgery was performed 

under general or epidural 

anesthesia

Analytical methodology 

Multivariate logistic 

regression was performed 

to test the association of 

SSI & DVT with putative 

risk factors

Baseline characteristics 

were compared using 

Mann-Whitney U-test or 

Fisher’s exact test.

Other notes

Follow-up: If using CDC 

criteria then all superficial 

30d and anything with an 

implant wound be 1yr for 

deep and organ/space
Disclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminated by the Centers for Disease Control and Prevention and should not be 

construed to represent any agency determination or policy. 105

Author

Year

(Data 

Extractor)

Risk of Bias 

Score Study Objective Population and Setting Intervention Results Comments

 DMARDs: 24 (53.3%)

 P=1.54E-04

Prednisone (PSL)

 TNF: 38 (84.4%)

 DMARDs: 29 (64.4%)

 P=0.026

PLS, dose, mg/day

 TNF: 5 (2-7)

 DMARDs: 3 (0-5)

 P=0.041

Procedures: 

1:1 pair-matched case 

control study so numbers 

below are number of 

procedure PER STUDY GROUP

Arthroplasty procedures: 

n=54 (84%)

Shoulder Arthroplasty (SA): 1

Unilateral, elective elbow 

arthroplasty: 2

Implant replacement 

arthroplasty of the MCP 

joints: 2

Wrist arthroplasty:6

Unilateral, Elective THA: 8

Unilateral, elective TKA: 33

Total ankle arthroplasty (TAA): 

1

Bipolar hip hemiarthroplasty: 

1 Non Arthroplasty 

procedures: n=10 (16%)

Arthroscopic synovectomy of 

the knee: 3

Foot surgery: 5

Ankle arthrodesis:1

Open reduction and internal 

Treatment.

Majority of IFX patients 

underwent surgery in the 

middle of an 8-week infusion 

treatment.

Reoperations:

1 deep SSI (TNF group (IFX)) 

required removal of artificial 

joint prosthesis.

Length of stay NR

Mortality NR

Adverse events: 

Postoperative complication of 

delayed wound healing was 

absent in both groups.

DVT Subgroup analysis

DVT Positive

 TNF: 23/45 (51%) 

 DMARDs: 12/45 (26%)

 P=0.015

Multivariate logistic 

regression showed that TNF 

blockers were the only 

statistically significant risk 

factor for DVT.

OR= 2.83 (1.10-7.25) p=0.03
Disclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminated by the Centers for Disease Control and Prevention and should not be 

construed to represent any agency determination or policy. 106

Author

Year

(Data 

Extractor)

Risk of Bias 

Score Study Objective Population and Setting Intervention Results Comments

fixation (ORIF): 1

Indications: Rheumatoid 

Arthritis

Setting: 1 medical university

Location: Japan

Dates: May 2004 – March 

2009.

Inclusion Criteria: Patients in 

matched pairs either treated 

with anti-TNF agents or 

conventional DMARDS and 

who underwent joint surgery 

for RA. All patients fulfilled 

the 1987 revised ACR Criteria 

for RA

Exclusion Criteria: Surgery in 

which TNF agent adalimumab 

(ADA) was used

Bongartz

2008 16

(ES)

Retrospecti

ve 

concurrent 

cohort

1, 2, 3, 4, 5, 

6, 7

To determine 

the cumulative 

and 1-year 

incidence of 

prosthetic joint 

infection (PJI) in 

total hip 

arthroplasty 

(THA) and total 

knee 

arthroplasty 

(TKA) in a 

modern cohort 

of patients with 

RA and to 

further explore 

potential risk 

factors for these 

Number of patients

Patient Characteristics

·Age: mean±SD y

 RA: 63.6±13.3

 OA: 67.2±10.8

 P<0.001

·Gender: n% female

 RA: 363 (78.6%)

 OA: 338 (73.2%)

 P=0.06

·Obesity: NR

·Comorbidities: 

At least 1 comorbidity

 RA: 337 (73.0%)

 OA: 383 (83.0%)

 P<0.0001

Mean disease Duration: 21.1 

years

Intervention group: n=462 

patients with 657 surgeries.

Patients with RA undergoing 

either THA or TKA.

Timing of intervention: Pre or 

post operatively

Duration of intervention: If 

DMARD therapy was withheld 

around the time of surgery, the 

stop and start dates were 

abstracted based on 

pharmacokinetic half-life 

and/or data on the biologic 

activity of each DMARD. 

According to the information 

below, the DMARD use was 

judged as either withheld or 

maintained.

SSI (mean follow up 4.3 

years) 

PJI in matched cohorts at 5 

years

 RA: 15/462 (4.2%)

 OA: 4/ 462 (1.4%)

 Log rank p=0.005

 HR: 4.08 (1.35-12.33) 

After adjusting for previous 

infection in the index joint:

 HR: 3.74 (1.23-11.33) [age, 

sex, functional class, and 

comorbidity were not 

significant predictors of 

infection)

PJI in matched cohorts at 1 

year

 RA: 10/462 (2.3%)

Definitions 

RA Diagnosis: verified by 

using validated RA 

classification criteria. 

According to the American 

College of Rheumatology 

classification criteria.

OA Diagnosis: verified 

during chart review using 

physician’s diagnosis of hip 

and/or knee OA and 

absence of RA

PJI: diagnosed when at 

least 1 of the following 

were present:

1. Isolation of the same 

organism from ≥2 cultures 

of joint aspirates or 
Disclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminated by the Centers for Disease Control and Prevention and should not be 

construed to represent any agency determination or policy. 107

Author

Year

(Data 

Extractor)

Risk of Bias 

Score Study Objective Population and Setting Intervention Results Comments

infections. 

Additionally, the 

frequency of this 

complication of 

patients with RA 

as compared 

with patients 

with OA who 

undergo the 

same type of 

surgery was 

assessed.

Previous PJI in index joint

 RA: 43 (9.3%)

 OA: 24 (5.2%)

Steinbrocker functional 

classification at time of 

surgery (p<0.0001)

Class1 (patient normally 

active): 

 RA: 4 (0.9%)

 OA: 6 (1.3%)

Class2 (patient able to 

maintain occupation but less 

active): 

 RA: 183 (39.6%)

 OA: 338 (73.2%)

Class3 (unable to maintain 

occupation): 

 RA: 184 (39.6%)

 OA: 108 (23.4.2%)

Class4 (largely or wholly 

incapacitated): 

 RA: 86 (18.6%)

 OA: 8 (1.7%)

Unknown: 

 RA: 6 (1.3%)

 OA: 2 (0.4%)

Procedures: Total knee 

arthroplasty (TKR) or total hip 

arthroplasty (THA)

Primary THA: 164 (25.0%)

Revision THA: 164 (25.0%)

Primary TKA: 238 (36.2%)

Revision TKA: 91 (13.8%)

Indications: Rheumatoid 

Arthritis (RA) or Osteoarthritis 

Duration of days medication 

was withheld:

Methotrexate:8

Leflunomide: 85 days or 14 

days with cholestyramine 

wash-out

Oral gold: 8

Intramuscular gold: 29

Sulfasalazine: 8

Hydroxychloroquine: 85

Azathioprine: 8

Cyclosporine: 8

Cyclophosphamide: 8

ᴅ-penicillamine: 15

Etanercept: 8

Adalimumab: 15

Infliximab: 57

Anakinra:8

Agent: See above

Monitoring intervention: NR

Control group: n=462 patients

Matched cohort of patients 

with OA instead of RA. Patients 

were listed in the registry as 

having a diagnosis of OA and 

no diagnosis of RA. Matching 

was performed according to 

age (±5 years), site (hip or 

knee), type (revision or primary 

arthroplasty), and time point of 

first surgery.

Standard preventive 

 OA: 1/ 462 (1.4%)

 p=deemed statistically 

significant, but P=NR

 OR: 10.30 (1.31-80.26) 

PJI in RA population

RA: 23/657 (3.7%) (14[2.2%] 

infected w/in first year)

 Revision: 15/255 (5.9%)

 Primary: 8/402 (2.0%)

 THA: 12/328 (3.7%)

 TKA: 11/329 (3.3%)

Previous PJI: 7/67 (10.4%)

Statistically significant risk 

factors for SSI (univariate) HR 

(95%CI) [p=NR]

Revision arthroplasty: 2.99 

(1.02-8.75)

Previous infection of index 

joint: 5.49 (1.87-16.14)

Operation Time: 1.36 per 60-

min increase (1.02-1.81

** NOTE** - Patients in this 

study who had a previous PJI 

had a risk of another infection 

of only 3.5% as compared 

with 29.2% after revision of 

the previously infected joint.

DMARD

Stopping DMARD therapy at 

the time of surgery lowered 

the Risk of subsequent PJI: HR 

0.65 (0.09-4.95) but not 

intraoperative tissue 

specimens.

2. Acute inflammation 

consistent with infection 

on histopathologic 

examination (as 

determined by the 

pathologist).

3. Cutaneous sinus tract 

communicating with the 

joint prosthesis

4. Purulence in the joint 

space (as determined by 

the surgeon).

Perioperative care 

Analytical methodology: 

Proportion of surgeries 

complicated by a PJI was 

estimated by Kaplan-Meier 

Techniques.

Cox proportional hazards 

models were used to 

examine the association 

between the risk of 

prosthetic joint inspection 

for explanatory variables. 

Also used to compare the 

risk of infection between 

the RA and OA cohorts. 

Other notes: None

Follow-up: 

Length of FU. mean±SD y

 RA: 3.1±2.4
Disclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminated by the Centers for Disease Control and Prevention and should not be 

construed to represent any agency determination or policy. 108

Author

Year

(Data 

Extractor)

Risk of Bias 

Score Study Objective Population and Setting Intervention Results Comments

(OA)

Setting: 1 hospital

Location: USA

Dates January 1, 1996 – June 

30, 2004

Inclusion Criteria: All patients 

with a diagnosis of RA or OA 

who underwent THA or TKA 

during the study dates.

Exclusion Criteria: NR

measures:

AMP: Preop AMP: 656 (99.9%)

Nonstandard preventive 

measures:

Antimicrobial impregnated 

cement: 209 (31.8%) surgeries 

were performed with 

antimicrobial impregnated 

cement

statistically significant.

 Patients who did not stop 

anti-TNF therapy before 

surgery:3/38 (7.9%) infections 

 Patients who stopped AntiTNF therapy before surgery: 

0/12 infections.

 P=NS

Perioperative cortisone was 

not associated with increased 

risk of prosthesis infections

Other infections: NR

Topic-specific outcomes: NR

Reoperation : 

16/23 (69.6%)infections were 

treated with prosthesis 

removal. 6/16 had 

subsequent reimplantation

7/23 (30.4%) were treated 

with debridement and longterm antimicrobial

suppression therapy.

Length of stay: NR

Mortality: NR

Adverse events: NR

 OA: 3.8±2.6

All patients were followed 

up by surgeon examination 

at least twice in the first 

postsurgical year and then 

at least every 5 years 

thereafter. If in-person 

follow up was not possible, 

patients were contacted 

by letter and/or phone and 

asked to complete a 

standardized form

For outstanding or unclear 

issues as well as for a 

follow-up <1 year, primary 

physicians were contacted.

B. Should the agent dose be adjusted, and if so, for how long? Our search did not identify data that evaluated perioperative I

mmunosuppressive therapy dose adjustment and its impact on the risk of SSI in prosthetic joint arthroplasty patients.

Q14. What is the optimal duration of postoperative AMP to reduce the risk of SSI in prosthetic joint arthroplasty patients who are on systemic 

corticosteroid or other immunosuppressive therapy? Our search did not identify data that specifically evaluated differences in duration of 

postoperative AMP in prosthetic joint arthroplasty patients who were on systemic corticosteroids or other immunosuppressive agents and its 

impact on the risk of SSI. However, multiple procedures examined in the Core section, Q1.E: Postoperative AMP duration that included patients on 
Disclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminated by the Centers for Disease Control and Prevention and should not be 

construed to represent any agency determination or policy. 109

immunosuppressive therapy showed no benefit of continuing AMP after closing the surgical incision in the operating room. Therefore, the broader

recommendation for duration of postoperative AMP should be applied to prosthetic joint arthroplasty procedures irrespective of use if systemic 

corticosteroid or other immunosuppressive therapy.
Disclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminated by the Centers for Disease Control and Prevention and should not be 

construed to represent any agency determination or policy. 110

Intra-articular Corticosteroid Injections

Q15. How does preoperative intra-articular corticosteroid injection impact the risk of SSI in prosthetic joint arthroplasty patients?

Author

Year

(Data 

Extractor)

Study 

Design Study Objective Population and Setting Intervention Results Comments

Desai

2009 18

(ES)

Retrospecti

ve 

Concurrent 

Control

1, 2, 3, 4, 5

To compare the 

incidence of 

infection in 

patients who 

had an intraarticular steroid 

infiltration prior 

to a knee 

replacement, 

with those who 

hadn’t. SSI and 

Number of patients: N=360 

knees (250 patients)

Patient Characteristics

·Age: mean (Range) years

 Injection: 68 (49-87)

 No Injection: 72 (51-88)

·Gender: m/f

 Injection: 26/54

 No Injection: 74/96

Knee of TKR: right/left

 Injection: 42/48

 No Injection: 82/98

·Obesity: NR

·Comorbidities: NR

Procedures: Total Knee 

Arthroplasty (TKR)

Indications:

Osteoarthritis

 Injection: 58/80 (72.5%)

 No Injection: 133/170 

(78.2%)

Rheumatoid arthritis 

 Injection: 22/80 (27.5%)

 No Injection: 37/170 (21.7%)

Setting: 1 hospital

Location: England

Dates: 1997 - 2005

Inclusion Criteria: Patients 

who had total knee 

Intervention group: n=90 

knees (80 patients)

Patients who had an injection 

prior to undergoing knee 

replacement surgery.

45/80 (56.3%) patients had a 

TKR within 12 months after the 

injection

Timing of intervention: 

preoperative

Duration of intervention: 

Variable

Agent: (40mg/dL

methylprednisolone and 

5mg/mL levobupivacaine) 

intra-articular steroids. 

Infiltration was conducted in 

the operating theater as a daycase procedure (patients were 

discharged later the same day). 

Injection was conducted under 

strict aseptic precautions. 

30 knees (the earlier surgeries) 

were performed as out-patient 

procedures with strict aseptic 

precautions.

Monitoring intervention: NR

Control group: n=180 knees 

(170 patients) 

Knees undergoing TKR that had 

no injection prior to TKR 

surgery. Knees were matched 

SSI (Follow up at least 1 year) 

Unadjusted Results

Superficial Infection (All 

treated with antimicrobials & 

no further complications)

 Injection: 2/90 (2.2%) [both 

patients received injections 18 

months prior to surgery as an 

outpatient procedure]

 No Injection: 5/180 (2.7%)

RR 0.80 (0.16-4.03) P=1.0

6/7 Infections occurred in 

patients with Osteoarthritis.

Deep Infection: No Cases in

either group

Other infections: NR

Topic-specific outcomes: 

None

Reoperations: None

Length of stay: NR

Mortality: NR

Adverse events: NR

Definitions:

Superficial Infections: 

cases which had discharge 

from superficial layers 

within one moth of 

surgery; patients who 

received antimicrobial

cover for more than 1 

week delayed wound 

healing and cases which 

had positive cultures form 

superficial layers which 

settled and did not require 

further surgery for the 

knee

Deep Infection: cases with 

positive swab cultures or 

tissue biopsy from the 

deep tissues, patients who 

under-went exploration 

and wash out of the 

wound with positive 

culture report and cases 

which underwent revision 

surgery for infection.

Perioperative care: NR

Analytical methodology: 

Normal approximation 

method was utilized to 

assess non-inferiority of 

injection on risk of 

infection.
Disclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminated by the Centers for Disease Control and Prevention and should not be 

construed to represent any agency determination or policy. 111

Author

Year

(Data 

Extractor)

Study 

Design Study Objective Population and Setting Intervention Results Comments

replacement within the study 

dates with a minimum 1-year 

follow-up including patients 

with diabetes mellitus and a 

history of smoking.

Exclusion Criteria: A history of 

malignancy, immunesuppressive drugs, seronegative inflammatory 

arthropathy or a previous 

infection in the ipsolateral 

knee. 

two control knees to one 

Intervention knee. Matching 

was done on the basis of age, 

sex and year of operation. Age 

selection was done by 10 

yearly intervals and year of

operation was done by 3-yearly 

intervals

Standard preventive 

measures: 

Prosthesis: All TKR were 

cemented, fixed bearing knee 

systems.

Approach: midvastus approach 

under tourniquet

Suction: usage was kept to a 

minimum and only used during 

pulsed lavage irrigation prior to 

cementation.

Irrigation: prior to wound 

closure and with 0.05 

chlorhexidine.

Hemostatis: meticulously 

achieved before closure over 

drains

Tourniquet was released after 

wound closure

AMP: 3 doses of Cefuroxime 

postoperatively in addition to 

the loading dose to ensure 

cover for 24 hours Postop

Other notes: Patients were 

retrospectively identified 

by analysis of the notes in 

a prospective database of 

TKRs performed by the 

primary author.

Cohort matching was done 

prior to any evaluation of 

patient notes with respect 

to infection rates.

Authors estimate that 

given low infection rate, 

sample size of ~2000 

patients per group needed 

to rule out (with 95% CI) a 

50% increase in infection 

rate among those injected.

Follow-up: At least 1 year 

follow up. Mean follow-up 

was 48 months. Range 1-

6years)
Disclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminated by the Centers for Disease Control and Prevention and should not be 

construed to represent any agency determination or policy. 112

Author

Year

(Data 

Extractor)

Study 

Design Study Objective Population and Setting Intervention Results Comments

Sreekuma

r

2007 19

(ES)

Retrospecti

ve 

Concurrent 

Control

1, 2, 3, 4, 5

To determine if 

intra-articular 

steroid injection 

prior to joint 

(hip) 

replacement 

increases the risk 

of injection in 

replaced joints 

relative to 

patients who 

had no intraarticular 

injection prior to 

the same 

surgery.

Number of patients

Patient Characteristics

·Age: avg. (range) median, y

 Injection: 62.2 (32-89) 62.62

 No-injection: NR (39-89) 

64.09

·Gender: m/f

 Injection: 15/51

 No-injection: 32/104

·Obesity: Any patient 

considered overweight 

(BMI>35) was advised to lose 

weight prior to surgery. The 

operation was deferred until 

the patient achieved target 

weight.

·Comorbidities

Infections: patients were 

critically assessed for any 

focus of sepsis, including form 

the bladder, skin and lungs.

Time between injection and 

operation for Injection 

Cohort: Mean 14 months 

(median 11 months)

Procedures: Hip replacement

Right/left

 Injection: 41/27

Bilateral Procedure:

 Injection: 2/66 

Indications: NR

Setting: 1 Tertiary Referral 

Hospital

Location: England

Dates: 1997 - 2004

Inclusion Criteria: Patients 

Intervention group: n=66 

patients (68 hips)

Injection Cohort: received 

intra-articular injection of 

steroids prior to hip 

replacement surgery

Timing of intervention: Preoperatively

Duration of intervention: 

variable

Agent: 40mg/dL

methylprednisolone and 

5mg/mL levobupivacaine were 

injected. Patients were 

discharged the same day.

Monitoring intervention: NR

Control group: n=136 patients 

(136 hips) who received no 

intra-articular injection prior to 

surgery

Each hip in the intervention 

was matched to two hips in the 

control (non-injection) group

Matching was done on the 

basis of age (10-year intervals), 

gender, and year of operation 

(3-year intervals). When exact 

matches were unavailable, the 

next closest match was chosen.

Standard preventive 

measures: 

Surgeon: all surgeries were 

performed by the senior 

author

Approach: by the transtrochanteric. Trochanteric 

SSI (F-U at least 1 year) 

Infection at most recent 

follow up

Total Infections: 

 Injection: 0

 No Injection: 2/136 (1.4%)

 Difference in incidence: 1.4% 

(-0.5%-3.3%)

Superficial: 

 Injection: 0

 No Injection: 1/136 (0.7%) 

noticed at 4 weeks postop 

and responded to 

antimicrobials.

Deep Infection 

 Injection: 0 

 No Injection: 1/136 (0.7%) 

presented 2 months postop 

with pyrexia and severe pain. 

Patient was 75yo. Hip was 

aspirated and antimicrobials

were started.

Other infections: NR

Topic-specific outcomes: NR

Reoperations: 

Reattachment of trochanter

 Injection: 1/66 (1.5%) 

occurred at 2 years Postop 

due to persisting pain

 No Injection: 0

Length of stay: NR

Mortality: 

 Injection: 0

 No Injection: 1/136 (0.7%) 

Patient with joint infection 

Definitions: None

Perioperative care: NR 

Analytical methodology: 

Statistical analysis was 

performed using Stata. 

95%CI was obtained by the 

normal approximation 

method

Other notes: All 

procedures performed by 

single surgeon

Follow-up: at least 1 year

Average Follow Up:

 Injection: 25.33 months

 No Injection: 22.28 

months
Disclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminated by the Centers for Disease Control and Prevention and should not be 

construed to represent any agency determination or policy. 113

Author

Year

(Data 

Extractor)

Study 

Design Study Objective Population and Setting Intervention Results Comments

who underwent hip 

replacement surgery after 

steroid filtration. A matched 

cohort of patients was 

created of patients who 

underwent hip replacement 

without steroid infiltration 

prior to surgery.

Exclusion Criteria: Patients 

who had previous operations 

on the same hip and patients 

who had malignancy or were 

on immune-suppressive 

drugs. Patients with a 

previous infection in the same 

hip were excluded.

osteotomy was done and the 

hip was exposed.

Suction: kept to a minimum 

used only during pulsed lavage 

to reduce the suction catheter 

sucking air towards the patient.

Irrigation: regular washing of 

the wound was done with 

chlorhexidine 0.05%.

Hemostatis: meticulous 

hemostasis was achieved 

before closure of the drains

AMP: 3 doses of cefuroxime, 

postoperatively, in addition to 

the loading dose to ensure 

coverage for 24h postop.

presented at 2 months postop 

developed acute renal 

shutdown and died of multiorgan system failure at 3 

months.

Adverse events: 

Aching hip postop

 Injection: 3/66 (4.5%) [had 

absence of infection 

confirmed by ESR, CRP Levels 

& isotope scans]

McIntosh

2006 20

(ES)

Retrospecti

ve 

Concurrent 

Control

1, 2, 3, 4, 5, 

8

To determine if 

the 

administration of 

an intra-articular 

steroid injection 

into an 

osteoarthritic 

hip within 1 year 

of subsequent 

primary THA 

would increase 

the rate of 

superficial and 

deep 

periprosthetic 

infection when 

compared with a 

matched control 

group who did 

Number of patients: N=448

Patient Characteristics

·Age: mean (SD) years

 Injection: 70 (9.8)

 No Injection: 69 (9.6)

·Gender m/f

 Injection: 93/131

 No Injection: 92/132

·Obesity: Calculated from 

mean height/weight reported:

Injection: 30.1

No injection: 29.8

Height: mean (SD) cm

 Injection: 167 (24)

 No Injection: 168 (9.7)

Weight: mean (SD) kg

 Injection: 84 (19.9)

 No Injection: 84 (19.9)

·Comorbidities: NR

Intervention group: n=224

Patients who received intraarticular steroid injection 

within 1 year prior to total hip 

arthroplasty

Timing of intervention: 

Preoperative

Duration of intervention: 

Variable

Agent: (Agent-Not 

standardized) Steroids 

delivered via intra-articular 

injection. All injections were 

performed by members of the 

radiology department within 1 

year prior to the THA using 

standard aseptic protocols. Hip 

penetration was confirmed 

fluoroscopically by the 

SSI (follow-up minimum 2 

years) 

Superficial Infections

 Injection: 11 (4.9%)

 No Injection: 8 (3.6%)

Hazard Ratio: 1.5 (0.6-3.6)

Cumulative Risk of superficial 

infection at 5 years: 

 Injection 4.5% (2.4-8.4)

 No Injection: 3.7% (1.1-6.1)

15/19 superficial infections 

were treated with local 

wound care and 7/15 were 

also treated with a course of 

oral antimicrobial prophylaxis

Deep infections (developed at 

a mean of 1.69 years)

 Injection: 3 (1.3%)

 No Injection: 1 (0.4%)

Definitions: 

Superficial Infection: any 

wound infection that did 

not penetrate the deep 

fascia and included any 

patients with persistent 

postoperative wound 

drainage, superficial 

wound dehiscence, or 

suture abscess formation.

Perioperative care: NR

Analytical methodology: 

Kaplan-Meier method was 

used to estimate the 

cumulative risk of 

infections.

Cox proportional hazard 

model was used to assess 
Disclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminated by the Centers for Disease Control and Prevention and should not be 

construed to represent any agency determination or policy. 114

Author

Year

(Data 

Extractor)

Study 

Design Study Objective Population and Setting Intervention Results Comments

not receive a 

preoperative 

intra-articular 

steroid injection.

Time from injection to THA: 

mean (SD) days

 Injection: 112 (81)

 No Injection: NA

Operative Time: mean (SD) 

minutes:

 Injection: 182 (47)

 No Injection: 182 (48.1)

Procedures: Total Hip 

Arthroplasty

Indications: Osteoarthritis

Setting: I Research Hospital

Location: USA

Dates: January 1998 – May 

2002

Inclusion Criteria: Patients 

with OA of the hip during the 

study dates.

Exclusion Criteria: Diagnosis 

of inflammatory arthritis, 

connective tissue disorders, 

any history of acetabular or 

femoral fracture, any previous 

surgery on the index hip, or 

tumor of the acetabulum or 

femur.

installation of radiopaque dye 

before steroid administration. 

Type and amount of steroid 

dispensed was left to the 

discretion of the performing 

radiologist.

Monitoring intervention: NR

Control group: n=224

Patients who did not receive 

intra-articular steroid injections 

prior to Total Hip Arthroplasty. 

Patients were matched to the 

Injection Group (intervention)

Standard preventive 

measures: NR

Hazard Ratio: 3 (0.3-29.8)

Cumulative Risk of deep 

infection at 5 years:

 Injection: 3% (0-7%)

 No Injection: 0.6% (0-1.7%)

None of the superficial 

infections had deep infections 

develop.

2/4 deep infections were 

preceded by multiple 

recurrent dislocations (both in 

injection group)

2/4 deep infections also had a 

chronic medical condition 

 1/2 had a tracheostomy for 

sever obstructive sleep apnea 

and was on chronic 

anticoagulation for atrial 

fibrillation & DVT and/or 

pulmonary embolism.

 1/2 had type II diabetes 

mellitus

No association was found 

between the average time 

from intraarticular injection to 

primary THA and the 

development of Superficial or 

Deep Infections

Overall average time between 

steroid injection and THA for 

injection group: 112 (SD 81) 

days

 Superficial: 112 (SD 94) days

 Deep: 44 (SD 23) days

the difference in survivals 

between groups. Taking 

into account the timing of 

injection and the length of 

follow-up.

Other notes: 

Follow-up: at 3 months, 1 

year, 2 years, and 5 years. 

Or until THA revision for 

instability, loosening, 

implant resection for deep 

infection, or death. 

Minimum 2 years

Average follow up (years)

 Injection: 2.7 (1.4)

 No Injection: 2.6 (1.6)
Disclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminated by the Centers for Disease Control and Prevention and should not be 

construed to represent any agency determination or policy. 115

Author

Year

(Data 

Extractor)

Study 

Design Study Objective Population and Setting Intervention Results Comments

Probability value could not be 

calculated because of limited 

number of patients with deep 

infections

Other infections: NR

Topic-specific outcomes: NR

Reoperations: 

Superficial infections

2/15 had surgical removal of 

retained drains

2/15 had wounds incised 

followed by irrigation and 

debridement with 

documentation of fascial 

integrity

Deep Infections

3/3 treated with two-stage 

exchange 

1/3 treated by debridement 

with prosthesis retention and 

chronic suppression with oral 

antimicrobial therapy

Length of stay: NR

Mortality: 

Unrelated to THA:

 Injection: 12 (5.4%)

 No Injection: 13 (5.8%)

Adverse events: 

Revision for aseptic loosening:

 Injection: 5 (2.2%)

 No Injection: 4 (1.8%)

Dislocations

 Injection: 6 (2.7%)

 No Injection: 5 (2.2%)

Mean time to dislocation: (yr.)
Disclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminated by the Centers for Disease Control and Prevention and should not be 

construed to represent any agency determination or policy. 116

Author

Year

(Data 

Extractor)

Study 

Design Study Objective Population and Setting Intervention Results Comments

 Injection: 1.41 (0.02-3.13)

 No Injection: 1.54 (0.02-5)

4/11: demonstrated hip 

stability with conservative 

treatment

7/11: reoperations

 Injection: 4 (1.8%)

 No Injection: 3 (1.3%)

Papavasili

ou

2006 17

(ES)

Retrospecti

ve 

Concurrent 

Control

1, 2, 3, 4, 5, 

8

To determine 

the rate of 

infection in 

patients who 

had undergone 

TKR and to 

correlate this 

rate with the 

pre-operative 

use of intraarticular 

steroids.

Number of patients: N=144

Patient Characteristics: 

·Age: NR

·Gender: NR

·Obesity: NR

·Comorbidities: NR

Procedures: Total knee 

replacement 

Indications: See exclusion 

criteria

Setting: 1 hospital

Location: England

Dates: February 2002 –

October 2004

Inclusion Criteria: All patients 

who underwent TKR during 

the study dates

Exclusion Criteria: If records 

were incomplete, patients 

who had previous surgery on 

the affected knee (other than 

arthroscopy), a diagnosis of 

inflammatory arthritis, 

immunosuppression, and a

Intervention group: n=54

Patients who had received one 

or more intra-articular 

injection of steroid in their 

operated knee

Timing of intervention: 

variable preoperatively

Duration of intervention: 

variable

Agent: MethylprednisoloneSteroid delivered via intraarticular injection in an 

orthopedic clinic, 

rheumatology clinic, or general 

practice setting before surgery.

Monitoring intervention: NA

Control group: n=90

Patients with no record of 

having received an intraarticular injection of steroid 

before surgery.

SSI 

Superficial: 30 days

Superficial wound infection:

 Injection: 12/54 (22.2%)

 No injection: 10/90 (11.1%)

 P=0.1

Deep wound infection: 1 year

 Injection: 3/54 (5.6%)

 No injection: 0

 P<0.025

All 3 deep infections were 

treated with long-term 

antimicrobial therapy and 

revision surgery.

All 3 deep infections had 

injections within 12 months.

No relationship was found 

between the number or 

timing of injections and the 

risk of postoperative infection

Other infections: NR

Topic-specific outcomes: NR

Definitions: 

Superficial incisional 

infection: an SSI which 

occurred within 30 days of 

surgery and involved only 

the skin or subcutaneous 

tissue around the incision. 

One of the following 

criteria had to be met:

1) purulent drainage from 

the incision

2) cultured organisms 

from a swab or tissue 

biopsy from the superficial 

wound layers.

Deep Incisional infection: 

an SSI which occurred 

within 30 days of surgery 

and involved only the skin 

or subcutaneous tissue 

around the incision.

One of the following 

criteria had to be met:

1) purulent drainage from 

the depths of the incision

2) microbiological culture 
Disclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminated by the Centers for Disease Control and Prevention and should not be 

construed to represent any agency determination or policy. 117

Author

Year

(Data 

Extractor)

Study 

Design Study Objective Population and Setting Intervention Results Comments

previous history of infection 

around the knee, smoking and 

diabetes.

Standard preventive 

measures: Recorded but not 

reported.

Reoperations: 

Revision surgery for deep 

infection

 Injection: 3/54 (5.6%)

 No injection: 0

 P<0.025

Length of stay: NR

Mortality: NR

Adverse events: 

Postoperative investigations 

for deep infection due to 

symptoms of persistent pain 

or swelling.

 Injection: 5/54 (9.3%)

 No injection: 0 

from aseptically-aspirated 

fluid, a swab or a tissue 

biopsy from the deeptissue layers or pus cells 

present on microscopy

3) a deep incision which 

spontaneously dehisced or 

was deliberately opened 

by a surgeon when the 

patient had a temperature 

>38oC, localized pain, or 

tenderness

4) an abscess or other 

evidence of infection 

involving the deep incision 

which was found by direct 

examination, during reoperation, or by 

histopathological or 

radiological examination

5) Diagnosis of a deep 

incisional SSI by an 

attending physician

Perioperative care: NR

Analytical methodology: 

Chi-squared test

Other notes: 

A pilot study of 420 

patients who had received 

a TKR was performed by 

reviewing the records 

looking for incidences of 

deep infection: 6/420 

(1.4%) deep infections 

occurred. 5/6 infections 
Disclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminated by the Centers for Disease Control and Prevention and should not be 

construed to represent any agency determination or policy. 118

Author

Year

(Data 

Extractor)

Study 

Design Study Objective Population and Setting Intervention Results Comments

had received an intraarticular injection of 

steroid prior to surgery.

Follow-up: NR

Kaspar

2005 21

(ES)

Retrospective 

Concurrent 

Control

1, 2, 3, 4, 5, 

8

To determine 

the influence of 

intra-articular 

steroid injection 

on the rate of 

surgical site 

infection in 

patients with 

osteoarthritis 

undergoing 

subsequent THA 

Number of patients: N=80 

(entire database 979)

Patient Characteristics

·Age mean ±SEM (Range) y

 Injection: 71.03±1.53 (45-87)

 No Injection: 70.55±1.50 (46-

87)

·Gender: m/f

 Injection: 25/15

·Obesity: BMI

 Injection: 28.58±0.72 (17-39)

 No Injection: 29.94±0.77 (21-

43)

·Comorbidities: Mean ASA 

score for both groups was 2.2 

indicating most patients had 

few comorbidities

Problems with the spine were 

present in approximately half 

of the population evenly 

distributed across groups. 

Procedures: Total hip 

arthroplasty

Cemented: 19 in each group

Non-Cemented: 21 in each 

group

Indications: 

Osteoarthritis

 Injection: 1/40 (2.5%)

 No Injection: 1/40 (2.5%)

Intervention group: n=40

Received intra-articular 

steroids prior to THA. Details of 

injections were found from an 

examination of patients 

receiving injections in the 

fluoroscopy suite.

Timing of intervention: 

Preoperatively

Duration of intervention: 

variable

Agent: Methylprednisolone 

80mg with 1-5ml of 

bupivacaine. Steroids 

delivered via intra-articular 

injection. Injections were 

performed in a fluoroscopy 

suite under aseptic technique

Monitoring intervention: NR

Control group: n=40

Did not receive intra-articular 

steroid injections prior to THA. 

Matched cohort.

Patients were matched in 

descending order of priority by 

gender, cemented or 

cementless THA, age, BMI, ASA 

pre-op score, year of 

SSI (mean follow up 29.8 

months) 

Deep Infection

 Injection: 4/40 (10%)

 No Injection: 0

 P=0.01

Overall rate of established 

infections and possible 

infections

 Injection: 12/40 (30%)

 No Injection: 3/40 (7.5%)

Other infections: NR

Topic-specific outcomes: 

Time between most recent 

injection and THA: mean 

±SEM (95%CI)

Infection and/or infection 

test: 11.38±3.03 (5.6-17.2)

No Infection/ no infection 

Test: 10.86±1.74 (7.2-14.5) 

P=0.878

Power: 0.053

Total number of injections 

before THA mean ±SEM

Infection and/or infection 

test: 1.43±0.25 

No Infection/ no infection 

Test: 1.46±0.11

P=0.891

Power: 0.052

Definitions 

Perioperative care

Analytical methodology: 

Descriptive statistics, 

unpaired t-test, Fisher’s 

exact test for categorical 

data, Kaplan-Meier 

survival analysis, and 

comparison of survival 

plots by Mantel-Cox type 

log-rank testing. 

Power analysis performed 

by univariate modeling.

Other notes: Study was 

underpowered 

Follow-up: 

Mean length of follow up: 

29.8±0.4 months

Injection: 33.2±2.1 months

No Injection: 30.2±1.6 

months
Disclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminated by the Centers for Disease Control and Prevention and should not be 

construed to represent any agency determination or policy. 119

Author

Year

(Data 

Extractor)

Study 

Design Study Objective Population and Setting Intervention Results Comments

Inflammatory Arthritis

 Injection: 39/40 (97.5%)

 No Injection: 39/40 (97.5%)

Setting: 1 hospital

Location: USA

Dates:1995 - 1998

Inclusion Criteria: Patients 

undergoing THA during the 

study dates.

Exclusion Criteria: prostatic 

malignancy, previous 

ipsilateral fracture of the hip 

or earlier surgery on the 

affected side. Also patients 

who were 

immunocompromised, 

previously or presently 

infected, affected with cancer 

in the hip or suspected 

tumors around the hip or who 

had been given an initial 

diagnosis of osteoarthritis.

operation, and surgeon.

Standard preventive 

measures: Recorded but not 

reported

Reoperations: 

Overall rate of revision

 Injection: 5/40 (12.5%)

 No Injection: 1/40 (2.5%)

Note: Authors report revision 

rate of 1.02% (10/979) for all 

unmatched controls/primary 

THAs performed at their 

hospital over the study time 

period (excludes those with 

primary THA performed 

elsewhere or before the 

database was established).

Length of stay: 

 Injection: 6.58±0.49 (2-18)

 No Injection: 7.26±0.96 (4-

36)

Mortality: NR

Adverse events: NR

Q16. What are the most effective strategies for managing the preoperative use of intra-articular corticosteroid injections to reduce the risk of 

SSI in prosthetic joint arthroplasty patients?

Our search did not identify data that evaluated preoperative strategies for managing the use of intra-articular corticosteroid injections in prosthetic 

joint arthroplasty patients and their impact on risk of SSI.

A. Does the length of time between intra-articular corticosteroid injection and prosthetic joint arthroplasty impact the risk of SSI? Our 

search did not identify data that evaluated different lengths of time between preoperative intra-articular corticosteroid injection 

administration and its impact on the risk of TKA. 
Disclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminated by the Centers for Disease Control and Prevention and should not be 

construed to represent any agency determination or policy. 120

B. Does the corticosteroid injection dose impact the risk of SSI? Our search did not identify data that evaluated different doses of 

preoperative intra-articular corticosteroid injections and their impact on the risk of SSI. 
Disclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminated by the Centers for Disease Control and Prevention and should not be 

construed to represent any agency determination or policy. 121

RISK OF BIAS ASSESSMENTS OF STUDIES Q12-16

Other Controlled Studies

Author

Year (RefID)

KQ All study groups 

derived from similar 

source/reference 

populations

Attrition not 

significantly 

different across 

study groups

Measure of 

exposure is 

valid

Measure of 

outcome is valid

Investigator 

blinded to 

endpoint 

assessment

Potential 

confounders 

identified

Statistical 

adjustment for 

potential 

confounders done

Funding source(s) 

disclosed and no 

obvious conflict of 

interest

Overall 

Risk of 

Bias

Questions 12 – 16: Immunosuppressive Therapy

Bongartz

200816 13        Low

Bridges

1991 14 13        Low

Carpenter

199615 13       Low

Desai

200918 15      Low

Hirano

201012 12      Low

Kaspar

2005 21 15       Low

Kawakami

201011 12        Low

McIntosh

200620 15       Low

Momohara

201110 12        Low

Papavasiliou

200617 15       Low

Perhala

1991 13 12       Low

Sreekumar

200719 15      Low
Disclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminated by the Centers for Disease Control and Prevention and should not be 

construed to represent any agency determination or policy. 122

Q17 ANTICOAGULATION 

GRADE TABLE Q17

Comparison Outcome

Quantity 

and Type 

of 

Evidence

Findings Starting 

GRADE

Decrease GRADE Increase 

GRADE

GRADE of 

Evidence for 

Outcome

Overall 

GRADE 

of 

Evidence 

Base

Study QualityConsistencyDirectnessPrecisionPublication BiasLarge MagnitudeDose-responseConfounders

Q17. What are the most effective strategies for managing perioperative venous thromboembolism (VTE) prophylaxis to reduce the risk of SSI? 

Q17A. Does the risk of SSI differ by individual VTE prophylaxis agent? 

enoxaparin 

vs.

fondaparinu

x 

SSI* 1 SR 22

 No difference in a meta-analysis of 4 RCTs 23, 24, 25, 

26 (N=7237) in primary or revision THA, TKA, or 

hip fracture surgery: group: 29/3621 (0.8%) vs. 

37/3616 (1.0%). (11 day follow up)

High -1 0 -1 0 0 0 0 0 Low

Low

Drug 

related 

adverse 

events

1 SR 22  No episode of decreased platelet count was 

reported in either group High -1 0 -1 0 0 0 0 0 Low

enoxaparin 

vs.

rivaroxaban 

SSI* 4 RCT 27, 28, 

29, 30

 No difference in a meta-analysis of 4 RCTs 

(N=12,383): 28/6200 (0.5%) vs. 27/6183 (0.4%); 

OR: 1.03; 95% CI: 0.60 – 1.76; p=0.92); 30-35 day 

follow up

 Two studies27, 28 found no difference in THA 

(n=6890): 14/3453 (0.41%) vs. 16/3437 (0.47%). 

SSIs were rare (30 or 0.40%)

 Two studies29, 30 found no difference in TKA 

(n=5493): 14/2747 (0.51%) vs. 11/2746 (0.40%). 

Infections were rare (25 or 0.46%)

High 0 0 0 0 0 0 0 0 High

High

Hemorrha

gic wound 

complicati

ons

4 RCT 27, 28, 

29, 30

 No difference in 4 RCTs (THA and TKA combined 

data) composite of excessive wound hematoma 

and reported surgical site bleeding: 105/6200 

(1.7%) vs. 100/6183 (1.6%); p=NS

High 0 0 0 0 0 0 0 0 High
Disclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminated by the Centers for Disease Control and Prevention and should not be 

construed to represent any agency determination or policy. 123

Comparison Outcome

Quantity 

and Type 

of 

Evidence

Findings Starting 

GRADE

Decrease GRADE Increase 

GRADE

GRADE of 

Evidence for 

Outcome

Overall 

GRADE 

of 

Evidence 

Base

Study QualityConsistencyDirectnessPrecisionPublication BiasLarge MagnitudeDose-responseConfounders

 Two studies27,28 found no difference in THA:

59/3453 (1.7%) vs. 54/3437 (1.6%); p =NS

 Two studies29, 30 found no difference in TKA: 

46/2747 (1.7%) vs. 46/2746 (1.7%); p=NS

Drug 

related 

adverse 

events

4 RCT 27, 28, 

29, 30

 No difference in 4 RCTS modified intention to 

treat analysis: 970/6200 (15.6%) vs. 971/6183 

(15.7%)

 Two studies27, 28 found no difference in THA: 15% 

both 514/3453 vs. 515/3437

 Two studies29, 30 found no difference in TKA: 

(17% both) 456/2747 vs. 456/2746

High 0 0 0 0 0 0 0 0 High

enoxaparin 

vs. ASA and 

mechanical 

prophylaxis

SSI* 1 OBS 31

 1 large OBS study (N=2437) Logistic regression 

analysis showed that enoxaparin (started 12-24 

hours postoperatively) was not associated with 

increased risk of SSI in primary THA; OR 2.11 

(95%CI, 0.24-18.5); p=0.499; or primary TKA: OR 

1.07 (95% CI, 0.23-4.95); p=0.932.

Low 0 0 0 -1 0 0 0 0 Very low

Very Low

Time until 

wound 

was dry

1 OBS 31

 Logistic regression analysis showed that 

enoxaparin (started 12-24 hours postoperatively) 

was associated with longer time until wound was 

dry for primary THA (p=0.027) but not for 

primary TKA (p=0.623)

 Patients on enoxaparin had longer time until 

wound was dry as compared to those on ASA or 

those on warfarin; this difference was significant 

on the 5th (p=0.003) but not by the 8th

postoperative day.

Low 0 0 0 -1 0 0 0 0 Very low

enoxaparin 

vs. 

bemiparin 

PJI* 1 OBS 32

 In a nested case-control study of TKA patients 

(n=36 infections, 106 controls) specific 

anticoagulation agents were not associated with 

Low 0 0 0 -1 0 0 0 0 Very low Very low
Disclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminated by the Centers for Disease Control and Prevention and should not be 

construed to represent any agency determination or policy. 124

Comparison Outcome

Quantity 

and Type 

of 

Evidence

Findings Starting 

GRADE

Decrease GRADE Increase 

GRADE

GRADE of 

Evidence for 

Outcome

Overall 

GRADE 

of 

Evidence 

Base

Study QualityConsistencyDirectnessPrecisionPublication BiasLarge MagnitudeDose-responseConfounders

vs. 

fraxiparin

vs. 

fondaparinu

x

increased risk of SSI: p=0.97 

 Only 50 of 5496 (0.91%) patients developed an 

SSI; (95% CI, 0.68%-1.20%). 

 Hematoma identified as an independent risk 

factor for PJI. Adjusted OR 4.2; 95%CI, 1.1-16.6

enoxaparin, 

dalteparin, 

tinzaparin or 

fondaparinu

x

vs. ASA ±

mechanical 

prophylaxis

SSI* 1 OBS 33

 No difference in retrospective study (N=41,917) 

using administrative data from a national sample 

of primary TKAs: 4366/37,198 (12%) vs. 

559/4719 (12%); adjusted OR 1.08 (95%CI, 0.95-

1.24).

 Authors indicated that subtherapeutic dosing 

and/or inappropriate timing of the LMWHs or 

synthetic Factor Xa inhibitor may have impacted 

the results.

Low 0 0 0 -1 0 0 0 0 Very low Very low

Warfarin vs. 

No 

pharmacolo

gic or 

mechanical 

prophylaxis

SSI* 1 OBS 34

 In a large (n=1742) study in primary unilateral 

TKA, infections were rare 14/1742 (0.8%) and did 

not differ between groups: 9/957 (0.9%) vs. 

5/785 (0.6%)

 Goal INR: 1.6-2.2 for 6 weeks. Follow up was 3 

months.

 Study excluded patients already on preoperative 

anticoagulation therapy for other conditions.

Low 0 0 0 -1 0 0 0 0 Very low

Very low

Deep 

Incisional 

SSI

1 OBS 34

 Deep SSIs were rare 8/1742 (0.5%) and did not 

differ between groups: 6/957 (0.6%) vs. 2/785 

(0.3%)

Low 0 0 0 -1 0 0 0 0 Very low

Superficial 

Incisional 

SSI

1 OBS 34  Superficial SSIs were rare 7/1742 (0.4%) and did 

not differ between groups: 3 (0.3%) vs. 3 (0.4%) Low 0 0 0 -1 0 0 0 0 Very low
Disclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminated by the Centers for Disease Control and Prevention and should not be 

construed to represent any agency determination or policy. 125

Comparison Outcome

Quantity 

and Type 

of 

Evidence

Findings Starting 

GRADE

Decrease GRADE Increase 

GRADE

GRADE of 

Evidence for 

Outcome

Overall 

GRADE 

of 

Evidence 

Base

Study QualityConsistencyDirectnessPrecisionPublication BiasLarge MagnitudeDose-responseConfounders

Warfarin vs. 

ASA ± 

mechanical 

prophylaxis

SSI* 2 OBS 31,33

 In a large OBS study31 (n=2437) of primary THA 

(n=1211) and TKA (n=1226), logistic regression 

analysis among THAs showed that warfarin with 

a target INR of 2.0, started on the day of surgery, 

was not associated with an increased risk of 

wound infection OR 7.47 (95%CI, 0.62-89.3); 

p=0.112. On logistic regression analysis, 

warfarin does not appear as one of the variables 

influencing wound infection after TKA. Follow up 

was not reported

 In a large OBS study33 (N=93, 840) of 

administrative data on primary TKA, subanalysis 

(n=56,642), showed no difference; 6349/51923 

(12%) vs. 559/4719 (12%); adjusted OR: 1.10 

(95%CI, 0.96-1.26). Target INR not reported. SSIs 

were detected at the time of admission or on 

readmission within 30 days of index procedure.

Low 0 0 0 0 0 0 0 0 Low

Low

Time until 

wound 

was dry

1 OBS31

 Warfarin was not associated with longer time 

with wound drainage after neither THA (p=0.834) 

nor TKA (p=0.197)

 Patients on enoxaparin had longer time until 

wound was dry as compared to those on SAS or 

those on warfarin; this difference was significant 

on the 5th (p=0.003) but not by the 8th

postoperative day.

Low 0 0 0 -1 0 0 0 0 Very low

Higher vs. 

lower Mean 

INR PJI* 1 OBS35

 In a 2:1 case control study (N=154) of 78 cases 

who underwent revision THA or TKJA for septic 

failure compared to 156 non-infected controls 

who underwent the same procedure, all on 

postoperative warfarin (target INR=1.5) found 

that while the mean INR at all time-points was 

Low 0 0 0 -1 0 0 0 0 Very low Very low
Disclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminated by the Centers for Disease Control and Prevention and should not be 

construed to represent any agency determination or policy. 126

Comparison Outcome

Quantity 

and Type 

of 

Evidence

Findings Starting 

GRADE

Decrease GRADE Increase 

GRADE

GRADE of 

Evidence for 

Outcome

Overall 

GRADE 

of 

Evidence 

Base

Study QualityConsistencyDirectnessPrecisionPublication BiasLarge MagnitudeDose-responseConfounders

higher in the infected group, it was not 

statistically significant (p=0.06). 

 INR level was significantly higher in patients with 

wound-related problems who later developed 

infection (p=0.03)

 Twice as many infected patients with mean INR 

>1.5 as compared to controls: 22% vs. 11%; 

p=0.05

 Infected patients were more likely to have 

INR>1.5 at time of hospital discharge; 17% vs. 

8%; p=0.04

 INR>1.5 at time of hospital discharge was more 

prevalent in group with wound complications vs. 

those with uncomplicated postoperative wound 

healing; 22% vs. 8%; p=0.005

 Multivariate logistic regression analysis showed 

the following were significant risk factors for PJI:

 Wound complications including development of 

hematoma: OR 27.02; (95% CI, 11.04-91.59); 

p=0.0002 

 Persistent wound drainage: OR 32.20; (95% CI, 

8.7-119.17); p<0.0001

 ASA comorbidities: OR 2.07; (95% CI, 1.08-0.97); 

p=0.03

 Postoperative transfusion: PR 1.63; (95%CI, 1.14-

2.33); p=0.007

 13/78 (17%) of patients in the PJI cohort were on 

anticoagulation therapy preoperatively for 

another condition. These patients were 

heparinized postoperatively until fully 
Disclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminated by the Centers for Disease Control and Prevention and should not be 

construed to represent any agency determination or policy. 127

Comparison Outcome

Quantity 

and Type 

of 

Evidence

Findings Starting 

GRADE

Decrease GRADE Increase 

GRADE

GRADE of 

Evidence for 

Outcome

Overall 

GRADE 

of 

Evidence 

Base

Study QualityConsistencyDirectnessPrecisionPublication BiasLarge MagnitudeDose-responseConfounders

coagulated with warfarin (target INR = 2-3). 9/13 

(69%) developed wound complications including 

hematoma (n=3), persistent wound drainage 

(n=5) and delayed wound healing (n=1) 

Wound 

hematom

a

1 OBS 35

 Infected patients had a higher incidence of 

wound hematomas: 11(14%) vs. 2(1%); 

p=0.0001.

Low 0 0 0 -1 0 0 0 0 Very low

Wound 

drainagepersistent1 OBS 35  Infected patients had a higher incidence of 

wound drainage: 24(31%) vs. 4 (3%); p=0.0001. Low 0 0 0 -1 0 0 0 0 Very low

Q17B. What is the optimal timing and duration of perioperative VTE prophylaxis that also reduces the risk of SSI?

Prophylaxis 

started 

preoperativ

ely vs. 

postoperativ

ely

PJI* 1 OBS 32

 In a nested case-control study of TKA patients

(n=36 infections, 106 controls), infected patients 

received the first dose of anticoagulant within 12

hours (before or after) of surgery more 

frequently than those not infected: OR 1.5; 

(95%CI, 0.73-3.0). 

 After adjusting by main risk factors, no statistical 

association was found between close 

perioperative timing of the first dose of 

anticoagulant and risk of PJI.

 Hematoma formation identified as an 

independent risk factor for PJI. Adjusted OR 4.2

(95%CI, 1.1-16.6)

Low 0 0 0 -1 0 0 0 0 Very low Very low

*Critical outcome; OR: Odds Ratio; RR: Risk Ratio; CI: Confidence Interval
Disclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminated by the Centers for Disease Control and Prevention and should not be 

construed to represent any agency determination or policy. 128

EVIDENCE TABLE Q17

Q17. What are the most effective strategies for managing perioperative venous thromboembolism (VTE) prophylaxis to reduce the risk of SSI?

A. Does the risk of SSI differ by individual VTE prophylaxis agent? 

B. What is the optimal timing and duration of perioperative VTE prophylaxis that also reduces the risk of SSI?

Author

Year

(Ref ID_

Data 

Extractor)

Risk of Bias 

Score Study Objective Population and Setting Intervention Results Comments

Turpie

2009 30

(ES)

RECORD 4

RCT

1, 2, 3, 4, 5, 7, 

8, 9

To assess the 

efficacy and 

safety of oral 

rivaroxaban 

(RivaRox) 10mg 

once daily 

compared with 

30mg 

enoxaparin

(Enox) given 

subcutaneously 

every 12h for the 

prevention of 

venous 

thromboembolis

m after elective 

total knee 

arthroplasty.

Number of patients: N=3034

Patient Characteristics

·Age: mean (SD) y

 RivaRox: 64.4 (9.7)

 Enox: 64.7 (9.7)

·Gender: Female n (%)

 RivaRox: 1007/1526(66.0%)

 Enox: 1508/1508 (64.1%)

·Obesity: mean (SD) kg/m2

 RivaRox: 30.9 (6.2)

 Enox: 30.7 (6.0)

·Comorbidities

History of VTE:

 RivaRox: 38/1526(2.5%)

 Enox: 28/1508 (1.9%)

Procedures: Total Knee 

Arthroplasty: n (%)

Primary:

 RivaRox: 1488/1526 (97.5%)

 Enox: 1479/1508 (98.1%)

Revision:

 RivaRox: 37/1526 (2.4%)

 Enox: 28/1508 (1.9%)

None or missing data

 RivaRox: 1/1526 (0.1%)

 Enox: 1/1508 (0.1%)

Indications: NR

Setting: Multi-Center 

Intervention group: n=1584

RivaRox: Patients assigned to 

receive 10 mg 1x/day 

rivaroxaban PO.in the 

evening beginning 6-8h after 

wound closure or after 

adequate hemostasis was 

achieved. Plus placebo 

injection

Timing of intervention: 

Preop

Duration of intervention: 

Postop until the evening 

before venography on POD 

11-15 

Device/agent: Rivaroxaban

Monitoring intervention: NA

Control group: n=1564

Enox: patients assigned to 

receive 30mg 

subcutaneously every 12h 

beginning 12-24h post 

wound closure. Plus placebo 

tablet

Standard preventive 

measures: NR

SSI (follow up 41-50 days)

Postoperative wound 

infection:

 RivaRox: 4/1526 (0.3%)

 Enox: 3/1508 (0.2%)

Other infections: NR

Topic-specific outcomes

Hemorrhagic wound 

complications:

 RivaRox: 21/1526(1.4%)

 Enox: 22/1508 (1.5%)

Reoperations: NR

Length of stay: days mean 

(SD)

 RivaRox: 8.0 (6.1)

 Enox: 7.9 (6.3)

Mortality:

 RivaRox: 6/1526 (0.4%)

 Enox: 6/1508 (0.4%)

Adverse events:

Drug related Adverse Events:

 RivaRox: 310/1526 (20.3%)

 Enox: 295/1508 (19.6%)

Definitions 

SSI-NR

Perioperative care: NR 

Other notes: None

Follow-up: for 30-35 days 

after last dose of 

anticoagulant. (41-50 days 

postop)
Disclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminated by the Centers for Disease Control and Prevention and should not be 

construed to represent any agency determination or policy. 129

Author

Year

(Ref ID_

Data 

Extractor)

Risk of Bias 

Score Study Objective Population and Setting Intervention Results Comments

Location: Bulgaria, Canada, 

Denmark, India, Israel, 

Lithuania, Pakistan, Poland, 

Sri Lanka, Sweden, USA, 

Dates: June 2006 – October 

2007

Inclusion Criteria: Patients 18 

and older scheduled for total 

knee arthroplasty

Exclusion Criteria: Patients 

with active bleeding or a high 

risk of bleeding, or any 

disorder contraindicating the 

use of enoxaparin or that 

might necessitate enoxaparin 

dose adjustment. Also 

disorders preventing bilateral 

venography, clinically 

significant liver disease, 

severe renal impairment 

(creatinine clearance 

<30ml/min), concomitant use 

of drugs that strongly inhibit 

cytochrome P450 such as 

protease inhibitors or 

ketoconazole, pregnancy or 

breastfeeding, planned 

intermittent pneumatic 

compression or the 

requirement for ongoing 

anticoagulant therapy.
Disclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminated by the Centers for Disease Control and Prevention and should not be 

construed to represent any agency determination or policy. 130

Author

Year

(Ref ID_

Data 

Extractor)

Risk of Bias 

Score Study Objective Population and Setting Intervention Results Comments

Eriksson

2008 27

(ES)

RECORD 1

RCT

1, 2, 3, 4, 5, 7, 

8, 9

To assess the 

efficacy and 

safety of a 

postoperative 

10-mg dose of 

rivaroxaban 

(Rivarox) given 

once daily as 

compared with a 

40mg 

subcutaneous 

dose of 

enoxaparin (a 

low-molecular 

weight heparin), 

with the first 

[Enox]dose given 

the evening 

before surgery 

and subsequent 

doses given once 

daily, for 

extended 

thromboprophyl

axis after Total 

Hip Arthroplasty

Number of patients: N=4433

Patient Characteristics

·Age: mean (range) y

 Rivarox: 63.1 (18-91)

 Enox: 63.3 (18-93)

·Gender: female n (%)

 Rivarox: 1220/2209 (55.2%)

 Enox: 1242/2224 (55.8%)

·Obesity: BMI mean (range) 

 Rivarox: 27.8 (16.2-53.4)

 Enox: 27.9 (15.2-50.2)

·Comorbidities

History of VTE

 Rivarox: 47/2209 (2.1%)

 Enox: 55/2224 (2.5%)

Procedures: Total Hip 

Arthroplasty

Primary

 Rivarox: 2127/2209 (96.3%)

 Enox: 2118/2224 (95.2%)

Revision

 Rivarox: 66/2209 (3.0%)

 Enox: 86/2224 (3.9%)

Missing Data

 Rivarox: 16/2209 (0.7%)

 Enox: 20/2224 (0.9%)

Indications: NR

Setting: Multi center

Location: International: 

Argentina, Australia, Austria, 

Belgium, Brazil, Canada, Chile, 

Colombia, Czech Republic, 

Denmark, France, Finland, 

Germany Greece, Hungary, 

Intervention group: n=2266

Patients who received 10mg 

oral rivaroxaban 1x/day. 

Rivaroxaban was started 6-

8h after wound closure and 

administered every 22-26h in 

the evening. Plus placebo 

injection

Timing of intervention: 

Postop for Rivaroxaban & 

pre and postop for 

Enoxaparin

Duration of intervention: 36 

days postop (range 30-42) 

until patient had a 

mandatory bilateral 

venography. Although 

further thromboprophylaxis 

was continued at the 

investigator’s discretion.

Device/agent: 10mg oral 

rivaroxaban or 40mg 

subcutaneous injections of 

enoxaparin.

Monitoring intervention: NA

Control group: n=2224

Patients who received 40mg 

subcutaneous injections of 

enoxaparin administered 

1x/day. It was initiated 12h 

before surgery and restarted 

6-8h after wound closure 

then administered every 22-

26h in the evening. Plus 

placebo tablet

SSI (follow up 66-77 days)

Postoperative wound 

infection

 Rivarox: 8/2209 (0.4%)

 Enox: 8/2224 (0.4%)

Other infections: NR

Topic-specific outcomes: 

Hemorrhagic wound 

complications:

 Rivarox: 34/2209 (1.5%)

 Enox: 38/2224 (1.7%)

Reoperations: NR

Length of stay

Mortality: 

Death possibly related to 

study drug

 Rivarox: 3/2209 (0.01%)

 Enox: 1/2224 (0.04%)

Adverse events:

Drug related adverse events

 Rivarox: 270/2209 (12.2%)

 Enox: 265/2224 (11.9%)

Definitions: 

SSI - none

Perioperative care: NR

Other notes: None

Follow-up: 30-35 days 

after the last dose of the 

study drug. (60-77 days)
Disclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminated by the Centers for Disease Control and Prevention and should not be 

construed to represent any agency determination or policy. 131

Author

Year

(Ref ID_

Data 

Extractor)

Risk of Bias 

Score Study Objective Population and Setting Intervention Results Comments

Israel, Italy, Lithuania, the 

Netherlands, Norway, Poland, 

Slovakia, South Africa, Spain, 

Sweden, Turkey, United 

States.

Dates: February 2006 – March 

2007

Inclusion Criteria: men and 

women at least 18 years of 

age who were scheduled to 

undergo elective total hip 

arthroplasty.

Exclusion Criteria: Those 

scheduled to undergo staged 

bilateral THA, were pregnant 

or breast-feeding, had active 

bleeding or a high risk of 

bleeding, or had a 

contraindication for 

prophylaxis with enoxaparin 

or a condition that might 

require an adjusted dose of 

enoxaparin. Also conditions 

preventing bilateral 

venography, substantial liver 

disease, severe renal 

impairment (creatinine 

clearance <30ml/min), 

concomitant use of protease 

inhibitors for the treatment of 

human immunodeficiency 

virus infection, planned 

intermittent pneumatic 

compression, or a 

requirement for anticoagulant 

Standard preventive 

measures: NR
Disclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminated by the Centers for Disease Control and Prevention and should not be 

construed to represent any agency determination or policy. 132

Author

Year

(Ref ID_

Data 

Extractor)

Risk of Bias 

Score Study Objective Population and Setting Intervention Results Comments

therapy that could not be 

stopped.

Lassen

2008 29

(ES)

RECORD 3

RCT

1, 2, 3, 4, 5, 7, 

8, 9

To conduct a 

multicenter, 

randomized, 

double-blind trial 

that compares 

the efficacy and 

safety of oral 

rivaroxaban 

(Rivarox) 10mg 

once daily 

administered 

postoperatively, 

with those of 

enoxaparin

(Enox), 40mg 

given 

subcutaneously 

once daily 

administered 

preoperatively, 

for the 

prevention of 

venous 

thromboembolis

m after elective 

Number of patients: N=1459

Patient Characteristics

·Age: mean (Range) y

 Rivarox: 67.6 (28-91)

 Enox: 67.6 (30-90)

·Gender: female n (%)

 Rivarox: 857/1220 (70.2%)

 Enox: 821/1239 (66.3%)

·Obesity: BMI Mean (RANGE)

 Rivarox: 29.5 (16.3-51.1)

 Enox: 29.8 (16.0-54.3)

·Comorbidities 

History of VTE

 Rivarox: 48/1220 (3.9%)

 Enox: 42/1239 (3.4%)

Procedures: Elective total 

knee arthroplasty

Primary:

 Rivarox: 1176/1220 (96.4%)

 Enox: 1186/1239 (95.7%)

Revision

 Rivarox: 24/1220 (2.0%)

 Enox: 30/1239 (2.4%)

None/Missing data

Intervention group: n=1220

Rivarox: Patients who 

received once daily oral 

rivaroxaban in a 10-mg 

tablet. Treatment was 

initiated 6-8h after wound 

closure. Then administered 

every 24h until POD10-14. 

Further thromboprophylaxis 

was given at investigator’s 

discretion according to local 

practice.

Timing of intervention: 

Postop

Duration of intervention: 

from 6-8h after wound 

closure until POD10-14

Device/agent: Rivaroxaban 

10mg tablets

Monitoring intervention: NA

Control group: n=1239

Enox: Patients who received 

a once-daily subcutaneous 

injection of 40mg enoxaparin 

sodium. This was initiated 

SSI (follow up 40-49 days):

Postoperative infection of 

wound

 Rivarox: 7/1220 (0.6%)

 Enox: 11/1239 (0.9%)

Other infections: NR

Topic-specific outcomes:

Hemorrhagic Wound 

Complications

 Rivarox: 25/1220 (2.0%)

 Enox: 24/1239 (1.9%)

Reoperations: NR

Length of stay: 

 Rivarox: 48/1220 (3.9%)

 Enox: 42/1239 (3.4%)

Mortality: 

Death

 Rivarox: 0/1201 (3.9%)

 Enox: 6/1217 (3.4%)

Adverse events: 

Drug related adverse events:

Definitions: 

SSI – postoperative 

infection of wound was 

classified according to the 

Medical dictionary for 

Regulatory Activities 

(MEdDRA a registered 

trademark of the 

International Federation of 

Pharmaceutical 

Manufacturers and 

Associations)

Hemorrhagic wound 

complication: excessive 

wound hematoma or 

bleeding at the surgical 

site.

Perioperative care: NR

Other notes: None

Follow-up. 30-35 days 

after the last dose of 

medication. (POD 40-49?)
Disclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminated by the Centers for Disease Control and Prevention and should not be 

construed to represent any agency determination or policy. 133

Author

Year

(Ref ID_

Data 

Extractor)

Risk of Bias 

Score Study Objective Population and Setting Intervention Results Comments

total knee 

arthroplasty

 Rivarox: 20/1220 (1.6%)

 Enox: 23/1239 (1.9%)

Indications: NR

Setting: Multi-center

Location: Austria, Belgium, 

Canada, China, Colombia, 

Czech Republic, Denmark, 

France, Germany, Israel, Italy, 

Mexico, the Netherlands, 

Poland, Peru, South Africa, 

Spain, Sweden.

Dates: February 2006 –

November 2006

Inclusion Criteria: Patients 

who were 18 years of age or 

older and scheduled for Total 

knee arthroplasty. 

Exclusion Criteria: Patients 

with active bleeding or a high 

risk of bleeding that 

contraindicated the use of 

low-molecular-weight-heparin 

and patients with any 

contraindication necessitating 

adjustment of its dose. Also, 

conditions preventing 

bilateral venography, clinically 

significant liver disease, 

concomitant use of protease 

inhibitors of the human 

immunodeficiency virus or 

fibrinolytic agents, planned 

intermittent pneumatic 

compression, requirement of 

ongoing anticoagulation 

12h before surgery and was 

given again 6-8h after wound 

closure, then administered 

every 24h. Study 

medications were continued 

until at least POD 10 and up 

to POD 14. Further 

thromboprophylaxis was 

given at investigator’s 

discretion according to local 

practice.

Standard preventive 

measures: NR

 Rivarox: 146/1220 (12.0%)

 Enox: 161/1239 (13.0%)
Disclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminated by the Centers for Disease Control and Prevention and should not be 

construed to represent any agency determination or policy. 134

Author

Year

(Ref ID_

Data 

Extractor)

Risk of Bias 

Score Study Objective Population and Setting Intervention Results Comments

therapy, and pregnancy or 

breastfeeding. 

Kakkar

2008 28

(ES)

RECORD 2

RCT

1, 2, 3, 4, 5, 6, 

7, 8, 9

To assess the 

efficacy of 

extended 

thromboprophyl

axis with an oral 

factor Xa 

inhibitor, 

rivaroxaban

(RivaRox), for 31-

39 days, 

compared with a 

short-term 

LMWH 

enoxaparin 

(Enox) regimen 

for 10-14 days 

followed by 

placebo in 

patients 

undergoing total 

hip arthroplasty 

(THA)

This is known as 

the RECORD 2 

study

Number of patients: N=2457 

(Safety population)

N=1923 – population for 

major VTE

N=1733 – ITT population for 

Primary Efficacy

Patient Characteristics: this 

information is for the safety 

population: 

 RivaRox: n=1228

 Enox: n=1229

·Age: mean (SD, IQR) years

 RivaRox: 61.4 (13.2, 53-71)

 Enox: 61.6 (13.7, 54-72)

·Gender: female (%)

 RivaRox: 667 (54.3%)

 Enox: 651 (53.0%)

·Obesity: BMI mean (SD, IQR)

 RivaRox: 26.8 (4.8, 23.5-29.4)

 Enox: 27.1 (5.2, 23.6-30.0)

·Comorbidities:

Previous history of VTE

 RivaRox: 10 (0.8%)

 Enox: 20 (1.6%)

Duration of surgery: median 

Intervention group: n=1228; 

VTE= 961; Primary 

Efficacy=864

RivaRox: Patients receiving 

extended duration 

rivaroxaban as 

thromboprophylaxis for 5 

weeks. Starting 6-8 hours 

after wound closure and 

continued for 31-39 days. In 

addition, they received 

placebo injections for 10-14 

days starting 12h before 

surgery.

Timing of intervention: pre 

and postoperative

Duration of intervention: 

begun 6-8 hours after wound 

closure and continued for 

31-39 days. 

Agent: Oral rivaroxaban 

(10mg) once daily

Monitoring intervention: 

Liver biochemistry and 

cardiovascular adverse 

SSI (follow-up 30-35 days) 

Postoperative wound 

infections

 RivaRox: 8/1228 (0.7%)

 Enox: 6/1229 (0.5%)

Other infections: 

Infections and infestations:

 RivaRox: 88/1228 (7.2%)

 Enox: 87/1229 (7.1%)

Topic-specific outcomes: 

Non-Fatal Pulmonary 

Embolism n (95%CI)

 RivaRox: 1/864 (0.1%, <0.1-

0.6)

 Enox: 4/869 (0.5%, 0.1-1.2)

Absolute Risk Reduction: 

(95%CI)

0.3% (-0.2-1.1), p=0.37

Deep vein thrombosis in 

Safety Population

 RivaRox: 37/1228 (3.0%)

 Enox: 86/1229 (7.0%)

Definitions: 

Deep vein thrombosis was 

assessed and confirmed by 

ascending bilateral 

venography. 

In cases of suspected 

pulmonary embolism, 

pulmonary angiography, 

perfusion/ventilation lung 

scintigraphy with chest 

radiography or spiral 

computed tomography 

was done.

Major bleeding: bleeding 

that was fatal, into a 

critical organ (e.g. 

retroperitoneal, 

intracranial, intraocular, 

intra-spinal), required reoperation, or clinically 

overt extra-surgical-site 

bleeding associated with a 

fall in hemoglobin of 20g/L 

or more, calculated from 

the POD1 baseline value or 
Disclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminated by the Centers for Disease Control and Prevention and should not be 

construed to represent any agency determination or policy. 135

Author

Year

(Ref ID_

Data 

Extractor)

Risk of Bias 

Score Study Objective Population and Setting Intervention Results Comments

“Regulation of 

Coagulation in 

Orthopaedic 

surgery to 

prevent Deepvein thrombosis 

and pulmonary 

embolism)

(IQR) (min)

 RivaRox: 95.0 (72-125)

 Enox: 93.0(73-126)

Procedures: Elective Hip

Arthroplasty (THA)

Previous Orthopedic Surgery

 RivaRox: 225 (18.3%)

 Enox: 232 (18.9%)

Primary

 RivaRox: 1160 (94.5%)

 Enox: 1157 (94.1%)

Revision

 RivaRox: 52 (4.2%)

 Enox: 50 (4.1%)

Missing/no surgery

 RivaRox: 16 (1.3%)

 Enox: 22 (1.8%)

Indications: NR

Setting: Multicenter (123 

centers)

Location: Multinational (21 

countries worldwide)

Dates: February 2006 – April 

2007

Inclusion Criteria: Patients 

enrolled during the study 

dates aged 18 years or older, 

scheduled to undergo elective 

THA.

Exclusion Criteria: Those 

scheduled to undergo staged 

bilateral hip arthroplasty, who 

had active bleeding or a high 

events were monitored 

throughout the treatment 

and follow-up periods. 

Mandatory bilateral 

venography the day after the 

last dose of the study 

mediation (day 32-40)

Control group: n=1229; VTE: 

962; Primary Efficacy=869

Enox: Patients receiving the 

heparin-based 

thromboprophylaxis 

Enoxaparin for 2 weeks. It 

was initiated 12h before 

surgery and restarted 6-8

hours after wound closure. 

And continued for 10-14 

POD. Patients also received 

placebo tablets for 31-39 

days starting 6-8h after 

surgery.

Standard preventive 

measures: NR

Nonstandard preventive 

measures: 

Use of cement

 RivaRox: 621 (50.6%)

 Enox: 608 (49.8%)

Deep-vein Thrombosis in ITT 

population: n (95%CI)

 RivaRox: 14/864 (1.6%, 0.9-

2.7)

 Enox: 71/869 (8.2%, 6.4-

10.2)

Absolute Risk Reduction: 

(95%CI)

6.5% (4.3-8.5), p<0.0001

Proximal DVT: n (95%CI)

 RivaRox: 5/864 (0.6%, 0.2-

1.3)

 Enox: 44/869 (5.1%, 3.7-6.7)

Absolute Risk Reduction: 

(95%CI)

4.5% (2.9-6.0), p<0.0001

Distal DVT: n (95%CI)

 RivaRox: 9/864 (1.0%, 0.5-

2.0)

 Enox: 27/869 (3.1%, 2.1-4.5)

Absolute Risk Reduction: 

(95%CI)

2.0% (0.7-3.3), p=0.0025

Major venous 

thromboembolism: n (95%CI)

 RivaRox: 6/961 (0.6%, 0.2-

1.4)

 Enox: 49/962 (5.1%, 3.8-6.7)

Absolute Risk Reduction: 

(95%CI)

4.5% (3.0-6.0), p<0.0001

requiring infusion of two 

or more units of whole 

blood or packed cells.

On-treatment non-major 

bleeding – any ontreatment bleeding event 

not adjudicated as major

bleeding

Hemorrhagic wound 

complications: composite 

of excessive wound 

hematoma and surgicalsite bleeding

Any post-operative 

bleeding: bleeding starting 

after the first tablet intake 

and ending up to 2 days 

after the last intake of 

study medication.

Safety Analysis: patients 

who received at least 1 

dose of medication

Modified ITT population: 

patients who were valid 

for safety analysis, had 

undergone planned 

surgery, and had adequate 

assessment of 

thromboembolism.

Patients valid for 

assessment of major 

venous thromboembolism 

– those valid for safety 

analysis and in whom the 

venograms were evaluable 
Disclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminated by the Centers for Disease Control and Prevention and should not be 

construed to represent any agency determination or policy. 136

Author

Year

(Ref ID_

Data 

Extractor)

Risk of Bias 

Score Study Objective Population and Setting Intervention Results Comments

risk of bleeding, or had any 

condition contraindicating the 

use of enoxaparin, or that 

might require enoxaparin 

dose adjustment, including 

severe renal impairment. Also 

including significant liver 

disease, pregnancy or 

breastfeeding, concomitant 

use of HIV protease inhibitors, 

use of fibrinolytic therapy or 

planned intermittent 

pneumatic compression 

during the study period, 

conditions preventing

bilateral venography, or the 

requirement for an 

anticoagulant that could not 

be discontinued.

Symptomatic venous 

thromboembolism: n (95%CI)

 RivaRox: 3/1212 (0.2%, <0.1-

0.7)

 Enox: 15/1207 (1.2%, 0.7-

2.0)

Absolute Risk Reduction: 

(95%CI)

1.0% (0.3 -1.8), p=0.0040

Symptomatic venous 

thromboembolism in followup period: n (95%CI)

 RivaRox: 1/1212 (0.1%, <0.1-

0.5)

 Enox: 2/1207 (0.2%, <0.1-

0.6)

Absolute Risk Reduction: 

(95%CI)

0.1% (-0.2-0.4), p=0.62

Major on-treatment bleeding

 RivaRox: 1/1228 (<0.1%) 

[hemorrhagic diarrhea and 

hematemesis and resulted in 

discontinuation of 

rivaroxaban; patient received 

acetylsalicylic acid w/o gastric 

protection before surgery]

 Enox: 1/1229 (<0.1%) [Blood 

in cerebrospinal fluid.

Deemed not related to study 

drug but enoxaparin was 

discontinued]

Non-Major on-treatment 

for the proximal veins, 

irrespective of whether 

they were valid for distal 

veins

Perioperative care: NR 

Analytical methodology:

Mantel-Haenszel 

weighting stratified by 

country with 

corresponding asymptotic 

two-sided 95%CI and twosided p value. Unweighted 

RR reduction calculated 

with an asymptotic 

method. 

Sensitivity analysis: 1) 

included all randomized 

patients with evaluable 

bilateral venography 

(irrespective of whether it 

was in the time window) 

or a confirmed 

symptomatic/asymptomati

c event/death irrespective 

of the time window. 2) All 

randomized participants 

included in Sensitivity 

analysis 1. Plus those who 

had evaluable bilateral 

venography/ 

ultrasonography as done 

by the investigator, 

irrespective of the time 

window, or a 

symptomatic/ 
Disclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminated by the Centers for Disease Control and Prevention and should not be 

construed to represent any agency determination or policy. 137

Author

Year

(Ref ID_

Data 

Extractor)

Risk of Bias 

Score Study Objective Population and Setting Intervention Results Comments

bleeding: 

 RivaRox: 80/1228 (6.5%)

 Enox: 67/1229 (5.5%)

Clinically relevant non-major 

bleeding

 RivaRox: 40/1228 (3.3%)

 Enox: 33/1229 (2.7%)

Any bleeding after initiation of 

placebo or Rivaroxaban:

 RivaRox: 56/1197 (4.7%)

 Enox: 49/1193 (4.1%)

Patients receiving blood 

transfusion:

 RivaRox: 485/1228 (39.5%)

 Enox: 514/1229 (41.8%)

Reoperations: No major 

bleeding events leading to 

reoperation in either group

Length of stay: NR

Mortality up to day 30-42:

Death: n (95%CI)

 RivaRox: 2/864 (0.2%, <0.1-

0.8) (both of cardiovascular 

cause)

 Enox: 6/869 (0.7%, 0.3-1.5) 

(one of pulmonary embolism, 

4 unrelated to venous 

thromboembolism, one 

unexplained)

Absolute Risk Reduction: 

(95%CI)

0.5% (-0.2-1.1), p=0.29

asymptomatic event/ 

death, irrespective of the 

time window, provided the 

symptomatic event was 

not adjudicated. To be a 

non-event by the 

committee.

Other notes: Sample size 

based on event rate of 

11% in Enoxaparin group. 

And a RR of 40% in 

rivaroxaban. Thus 914 

patients per group would 

be enough to demonstrate 

a Reduction in RR with a 

power of 90%

Follow-up: 30-35 days 

after the last dose of 

medication
Disclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminated by the Centers for Disease Control and Prevention and should not be 

construed to represent any agency determination or policy. 138

Author

Year

(Ref ID_

Data 

Extractor)

Risk of Bias 

Score Study Objective Population and Setting Intervention Results Comments

Death in follow-up period: n 

(95%CI)

 RivaRox: 0/1228 (0.0%, 0.0-

0.3)

 Enox: 2/1229 (0.2%, <0.1-

0.6)[one to pulmonary 

embolism, one unexplained]

Absolute Risk Reduction: 

(95%CI)

0.2% (-0.1-0.6), p=0.50

Adverse events

Any on treatment adverse 

event:

 RivaRox: 768/1228 (62.5%)

 Enox: 807/1229 (65.7%)

Drug related adverse events:

 RivaRox: 245/1228 (20.0%)

 Enox: 249/1229 (20.3%)

Drug related serious ontreatment adverse events

RivaRox: 13/1228 (1.1%) 

Enox: 17 (1.4%)

Serious on-treatment adverse 

events:

 RivaRox: 90/1228 (7.3%)

 Enox: 131/1229 (10.7%)

Adverse events leading to 

discontinuations:

 RivaRox: 46/1228 (3.8%)

 Enox: 64/1229 (5.2%)
Disclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminated by the Centers for Disease Control and Prevention and should not be 

construed to represent any agency determination or policy. 139

Author

Year

(Ref ID_

Data 

Extractor)

Risk of Bias 

Score Study Objective Population and Setting Intervention Results Comments

Edema peripheral

 RivaRox: 55/1228 (4.5%)

 Enox: 48/1229 (3.9%)

Turpie

2002 22

(ES)

MetaAnalysis

3, 4,

To perform a 

meta-analysis of 

4 randomized, 

double-blind 

trials using the 

same 

comparative 

drug (Enoxaparin

[Enox] and 

Fondaparinux

[Fond]), end 

points (venous 

thromboembolis

m, and proximal 

deep vein 

thrombosis), and 

adjudication 

committee and 

to report the 

results of the 

meta-analysis.

Study types and number: N=4

Phase III clinical trials: 4/5

Number of total patients in 

the review: N=7344

 Efficacy Population: N=5385

Inclusion criteria: 4 

multicenter, randomized, 

double blind studies.

Exclusion criteria: NR

Databases searched: NA –

Studies were all conducted as 

a part of the Phase 3 studies 

in a clinical trial program.

Aggregate summary score: 

NR

Eriksson 2001– Hip Fracture

Lassen 2002– Hip 

Replacement

Turpie 2002 – Hip 

Replacement

Bauer 2001 – Major Knee 

Surgery

Intervention group: n=3668

Efficacy population: = 2682

Fond: Patients administered 

Fondaparinux as an 

anticoagulant

4/4 studies: fondaparinux 

was administered at2.5mg 

qd with the time of first 

injection 6h±2h postop and 

the time to second injection 

≥12h after first dose.

Timing of intervention: 

Postoperatively

Eriksson: 2001 if surgery was 

delayed 24-48h after 

admission, fondaparinux was 

initiated 12±2h 

preoperatively (68/626 

(19.9%)). Omission of preop 

injections was recommended 

in both cohorts if spinal or

epidural anesthesia, or 

catheterization was planned.

Lassen: Fondaparinux was 

initiated a mean of 6.25h 

SSI: 

Wound infection (by day 11)

 Fond: 37/3616 (1.0%)

 Enox: 29/3621 (0.8%)

Complications at surgical site 

leading to prolonged 

hospitalization or rehospitalization:

 Fond: 52/3616 (1.4%)

 Enox: 52/3621 (1.4%)

Other infections: NR

Topic-specific outcomes: 

Patients treated for VTE by 

day 11:

 Fond: 199/3616 (5.5%)

 Enox: 351/3621 (9.7%)

 P<0.001

Venous thromboembolism:

 Fond: 182/2682 (6.8%)

 Enox: 371/2703 (13.7%)

Any deep vein thrombosis

 Fond: 174/2677 (6.5%)

Definitions 

VTE: deep vein 

thrombosis, pulmonary 

embolism or both up to 

day 11. 

Bleeding index: the sum of 

the number of units of 

packed red blood cells or 

whole blood transfused 

and the difference of the 

hemoglobin values (g/dL) 

before and after the 

bleeding occurrence (i.e.

bleeding index=units of 

transfusion + hemoglobin

before bleeding –

hemoglobin after 

bleeding)

Fatal bleeding: bleeding 

that was retroperitoneal, 

intracranial, intraspinal or 

involved any other critical 

organ, 

Perioperative care: NR 
Disclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminated by the Centers for Disease Control and Prevention and should not be 

construed to represent any agency determination or policy. 140

Author

Year

(Ref ID_

Data 

Extractor)

Risk of Bias 

Score Study Objective Population and Setting Intervention Results Comments

Eriksson 2003 – Hip Fracture after surgery in 86% of 

patients

Turpie: Fondaparinux was 

initiated a mean of 6.5h after 

surgery in 92% of patients.

Bauer: Fondaparinux was 

initiated a mean of 6.25h in 

94% of patients

Duration of intervention: for 

5-9 days postoperatively or 

until a mandatory bilateral 

venography was performed 

to assess for a new VTE after 

a minimum 5-day hospital 

stay

Agent: Fondaparinux

Monitoring intervention: NR

Control group: n=3676

Efficacy population = 2703

Enox: Patients administered 

enoxaparin as an 

anticoagulant.

2/4 Studies: enoxaparin in 

40mg qd with time of 1st

injection 12h±2h 

preoperatively

2/4 studies: enoxaparin in 

30mg qd with time of 1st

injection 12-24h 

postoperatively

1/4 studies: Time to second 

injection 12-2h postop

3/4 studies: time to second 

 Enox: 363/2698 (13.5%)

Any Proximal Deep Vein 

Thrombosis

 Fond: 35/2756 (1.3%)

 Enox: 81/2775 (2.9%)

Distal Deep Vein Thrombosis

 Fond: 141/2704 (5.2%)

 Enox: 293/2709 (10.8%)

All odds ratios favor 

Fondaparinux regarding 

Surgery type, Obesity, age, 

gender, type of anesthesia, 

use of cement or duration of 

surgery with no significant 

difference seen in odds ratios 

for variations in these factors.

Common Odds Ratio between 

studies favors Fondaparinux 

with regards to VTE:

-55.2 (-63.1 to -45.8); p<0.001

Post-hoc analysis of timing of 

Fondaparinux injection:

A statistically significant 

relationship was shown 

between the timing (between 

3-9 hours postop) of the first 

fondaparinux injection and 

major bleeding (p=0.008)

A statistically significant 

relationship also existed 

between the incidence of 

overt bleeding associated 

Other notes: None

Follow up: 

wound infection: 11 days 

(wound infection and VTE)

entire study: 49 days (PE)
Disclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminated by the Centers for Disease Control and Prevention and should not be 

construed to represent any agency determination or policy. 141

Author

Year

(Ref ID_

Data 

Extractor)

Risk of Bias 

Score Study Objective Population and Setting Intervention Results Comments

injection NR

Standard preventive 

measures: 

Other thromboembolic 

prophylaxes: Intermittent 

pneumatic compression, 

dextran and thrombolytic or 

anticoagulant agents were 

prohibited; centers were 

instructed to avoid the use of 

aspirin or nonsteroidal antiinflammatory drugs when 

possible; other antiplatelet 

agents were prohibited

Graduated compression 

stockings: use was allowed 

and physiotherapy was 

recommended

Length of administration: 

investigators could extend 

prophylaxis during follow-up 

with any currently available 

therapy, but only after a 

venography was performed.

VTE: after occurrence, 

treatment was left to the 

surgeon’s discretion.

with a bleeding index ≥2 and 

the timing of the first 

fondaparinux injection 

(p=0.008)

Efficacy was not affected by 

this timing: p=0.67

Re-operations: See Infections

Length of stay: See infections

Mortality

Fatal bleeding

 Fond: 0/3616

 Enox: 1/3621 (0.0%)

Death from any cause

 Fond: 15/3616 (0.4%)

 Enox: 21/3621 (0.6%)

Death from any cause up to 

49 days

 Fond: 48/3616 (1.3%)

 Enox: 52/3621 (1.4%)

Adverse events: 

Adjudicated bleeding events 

up to day 11:

 Fond: 96/3616 (2.7%)

 Enox: 63/3621 (1.7%)

 P=0.008

Bleeding into critical organ

 Fond: 0/3616

 Enox: 1/3621 (0.0%)

Bleeding leading to another 

operation

 Fond: 12/3616 (0.3%)

 Enox: 8/3621 (0.2%)
Disclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminated by the Centers for Disease Control and Prevention and should not be 

construed to represent any agency determination or policy. 142

Author

Year

(Ref ID_

Data 

Extractor)

Risk of Bias 

Score Study Objective Population and Setting Intervention Results Comments

Bleeding with a bleeding 

index≥2

 Fond: 84/3616 (2.3%)

 Enox: 53/3621 (1.5%)

Any Transfusions

 Fond: 1950/3616 (53.9%)

 Enox: 1864/3621 (51.5%)

 P=0.04

Asenio

2010 32

(ES)

Prospective 

concurrent 

control with 

a nested case 

control

1, 2, 3, 4, 5, 6, 

7, 8

To investigate 

the independent 

effect of Low 

Molecular 

Weight Heparin 

(LMWH) timing 

for Deep Venous 

Thrombosis 

(DVT) 

prophylaxis 

related to the 

start of surgery 

on the risk of 

prosthesis 

infection among 

patients 

undergoing Total 

Knee 

Arthroplasty 

(TKA). Other 

objectives were 

to establish the 

risk of prosthesis 

infection and 

their 

Number of patients: N=5496

Nested Case Control: N=142

Patient Characteristics: for 

case control patients

·Age: mean±SD y

 Intervention: 71.3±6.1

 Control: 71.4±8.5

·Gender male n (%)

 Intervention: 13 (36.1%)

 Control: 30 (28.3%)

·Obesity

 Intervention: 23 (63.9%)

 Control: 66 (62.3%)

·Comorbidities

Diabetes mellitus

 Intervention: 10 (27.8%)

 Control: 13 (12.3%)

 OR:2.83 (1.08-7.38) p=0.03

Hypertension:

 Intervention: 27 (75%)

 Control: 64 (60.4%)

 OR: 2.07 (0.86-5.0); p=0.10

Procedures: Total knee 

arthroplasty (TKA)

Intervention group: n=36

Patients who underwent TKA 

and developed a prosthetic 

joint infection. 

Timing of intervention

First Dose of LMWH

Preoperatively

≥48h

 Intervention: 0 

 Control: 2 (1.9%)

24-48h

 Intervention: 0

 Control: 1 (1%)

 13-24h

 Intervention: 12 (33.3%)

 Control: 31 (29.8%)

7-12h

 Intervention: 3 (8.3%)

 Control: 6 (5.8%)

≤6h

 Intervention: 0

 Control: 1 (1%)

POSTOPERTIVELY

≤6h

 Intervention: 3 (8.3%)

SSI (Follow up 6 months 

postop) 

For total population of 5496:

Prosthetic infection incidence 

rate: 0.91 cases/100 patients 

operated (95%CI 0.68-1.2)

Infection rate ranged from 

0.25%-2.34% by center 

(p=0.14)

68% of infections were 

identified post-discharge. 

Time from procedures to 

infection median: 37 days 

(IQR: 16-63)

Early Postoperative Infection: 

46% 

Adjusted OR for independent 

risk factors for infection:

Diabetes: 3.2 (95%CI:1.2-8.8)

Hematoma formation: 4.2 

95%CI (1.1-16.5)

Other infections: NR

Definitions: 

Prosthesis infection: CDC 

definitions – an infection 

involving the 

periprosthetic tissues and 

Infection: Occurring within 

the first 6 months postop 

and meeting at least 1 of 

the following criteria:

1. an organism was 

isolated from a culture of 

fluid or tissue aseptically 

obtained from an incision 

deliberately opened by the 

surgeon

2. an abscess or other 

evidence of infection was 

detected on direct 

examination, either during 

reoperation or by 

histopathological or 

radiographic examination, 

3. prosthesis infection was 

diagnosed by a surgeon or 

attending physician.
Disclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminated by the Centers for Disease Control and Prevention and should not be 

construed to represent any agency determination or policy. 143

Author

Year

(Ref ID_

Data 

Extractor)

Risk of Bias 

Score Study Objective Population and Setting Intervention Results Comments

microbiological 

characteristics 

and to evaluate 

the relative 

effect of other 

potential risk 

factors.

Non-Primary Arthroplasty

 Intervention: 2 (5.7%)

 Control: 4 (4.0%)

Surgery duration

 Intervention: 112.8±34.2

 Control: 121.4±43.1

Indications: NR

Setting: Multicenter (13 

Spanish hospitals)

Location: Spain

Dates: January 1, 2005 –

December 31, 2006

Inclusion Criteria: All patients 

undergoing primary TKA or 

total knee replacement in 13 

Spanish traumatology surgical 

units during the study dates.

Exclusion Criteria: Patients 

with infected prostheses.

 Control: 6 (5.8%)

7-12h

 Intervention: 10 (27.8%)

 Control: 29 (27.9%)

13-24h

 Intervention: 4 (11.1%)

 Control: 17 (16.4%)

24-48h

 Intervention: 4 (11.1%)

 Control: 11 (10.6%)

Timing of any dose of LMWH

Within 24h preop

 Intervention: 15(41.7%)

 Control: 41 (38.7%)

Within 24h postop

 Intervention: 31 (86.1%)

 Control: 89 (84.0%)

Duration of intervention: 

variable

Agent: Low Molecular 

Weight Heparin (LMWH). 

Doses received were 

stratified related to the time 

of surgery, and the time 

interval relative to surgical 

time.

Enoxaparin

 Intervention: 19 (52.8%)

 Control: 50 (47.6%)

Bemiparin

 Intervention: 8 (22.2%)

 Control: 26 (24.8%)

Fraxiparin

 Intervention: 7 (19.4%)

Topic-specific outcomes: 

Bleeding

 Intervention: 12 (33.3%)

 Control: 32 (30.2%)

Wound Hematoma

 Intervention: 19 (52.8%)

 Control: 50 (47.6%)

 OR:3.58 (0.96-13.40) p=0.06

Reoperations: NR

Length of stay: NR

Mortality: NR

Adverse events: NR

Early prosthesis infection: 

an organ/space wound 

infection that developed 

within 1 month 

postoperatively.

Late Prosthesis infection: a 

prosthesis infection that 

developed between 1-6

months postop.

Perioperative care: NR

Analytical methodology 

Univariate logistic 

regression, paired t-test, 

multiple conditional 

logistic regression modal 

was developed from a 

saturated model 

containing all noncorrelated risk factors that 

were significant at the .1 

level. Only cases that could 

be matched to controls 

were included in the risk 

factor analysis.

Other notes: None

Follow-up: Active 

surveillance by surgeons 

and/or hospital 

epidemiologists during the 

6 months post-op

When clinical records did 

not provide enough 

information to rule out 

infection during the first 6 

months, patients were 
Disclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminated by the Centers for Disease Control and Prevention and should not be 

construed to represent any agency determination or policy. 144

Author

Year

(Ref ID_

Data 

Extractor)

Risk of Bias 

Score Study Objective Population and Setting Intervention Results Comments

 Control: 23 (21.9%)

Fondaparinux- NOT a LMWH; 

synthetic pentasaccharide 

factor Xa inhibitor

 Intervention: 2 (5.6%)

 Control: 6 (5.7%)

 P=0.97

Monitoring intervention: NA

Control group: n=106

For every intervention 

patient who developed an 

infection, 3 control patients 

were chosen who did not 

develop an infection within 

the first 6 postoperative 

months. Patients were 

matched by medical center 

and date of index case 

procedures ±2 weeks.

Standard preventive 

measures:

AMP: AMP were given across 

patients, however, timing 

was not standard and breaks 

down as follows:

>2h preop

 Intervention: 2 (5.6%)

 Control: 12 (11.3%)

≤2h preop

 Intervention: 29 (80.6%)

 Control: 84 (79.2%)

Postop

 Intervention: 5 (3.9%)

 Control: 10 (9.4%)

interviewed by telephone. 

Investigators extracted all 

information from medical 

records
Disclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminated by the Centers for Disease Control and Prevention and should not be 

construed to represent any agency determination or policy. 145

Author

Year

(Ref ID_

Data 

Extractor)

Risk of Bias 

Score Study Objective Population and Setting Intervention Results Comments

Non-Standard preventive 

measures: 

Hair Removal P=0.07 

between groups

Shaving not done

 Intervention: 6 (22.2%)

 Control: 25 (28.7%)

Blade Razor

 Intervention: 8 (29.6%)

 Control: 12 (13.8%)

 OR:3.3 (0.26-42.1)

Electrical Clipper

 Intervention: 13 (48.1%)

 Control: 50 (57.5%)

 OR: 0.18 (0.02-2.24)

Normothermic Blanket

 Intervention: 8 (22.2%)

 Control: 38 (35.8%)

 OR: 0.30 (0.09-1.01) p=0.05

Bozic

2010 33

(ES)

Retrospectiv

e concurrent 

cohort

1, 2, 3, 4, 5, 6, 

7, 8

To utilize

administrative 

data from a large 

national sample 

of patients 

undergoing 

primary total 

knee 

arthroplasty 

(TKA) to 

compare the risk 

of venous 

thromboembolis

m (VTE), surgical 

site bleeding, 

surgical site 

Number of patients: N=93840

Patient Characteristics

·Age: mean (SD) y

 Aspirin: 66.4 (10.7)

 Injectable: 66.5 (10.5)

 Warfarin: 67.3 (10.4)

P<0.001

·Gender: male n (%)

 Aspirin: 1679 (36%)

 Injectable: 12,505 (34%)

 Warfarin: 18,085 (35%)

·Obesity: 

 Aspirin: 833 (18%)

 Injectable: 5105 (14%)

 Warfarin: 6454 (12%)

·Comorbidities

Intervention group: 

Aspirin (n=4719): Patients 

who received aspirin ±

mechanical prophylaxis and 

no other pharmacologic 

VTEP agent

Timing of intervention: NR

Duration of intervention: NR

Agent: Aspirin, Warfarin, or 

Injectable VTEPs (LMWH 

Enoxaparin] or fondaparinux 

[Factor Xa inhibitor]

Monitoring intervention: NA

Control group: 

Warfarin (n=51,923): 

patients who received 

SSI (30 days) 

Wound infection

 Aspirin: 559/4719 (12%) 

 Injectable: 4366/37.198 

(12%)

 Warfarin: 6349/51,923 

(12%)

SSI population: n=1037

Adjusted ORs (95%CI)

Aspirin as referent

 Injectable: 1.08 (0.95-1.24)

 Warfarin: 1.10 (0.96-1.26)

Other infections: NR

Topic-specific outcomes: 

Definitions:

TKA – ICD-9-CM procedure 

code 81.45

Postoperative 

complications, including 

venous thromboembolism 

(any thromboembolic 

event including proximal 

or distal DVT as well as PE), 

proximal DVT and PE only; 

surgical site bleeding; and 

surgical site infection were 

defined using ICD-9-CM 

diagnosis codes recoded 

during the index admission 

as well as principal 
Disclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminated by the Centers for Disease Control and Prevention and should not be 

construed to represent any agency determination or policy. 146

Author

Year

(Ref ID_

Data 

Extractor)

Risk of Bias 

Score Study Objective Population and Setting Intervention Results Comments

infection (SSI), 

and mortality 

between 

patients who 

received aspirin, 

warfarin, or 

injectable 

(LMWH and 

fondaparinux) 

VET Prophylaxis 

(VETP)

Diabetes:

 Aspirin: 754 (16%)

 Injectable: 6561 (18%)

 Warfarin: 8839 (17%)

Deficiency anemia

 Aspirin: 456 (10%)

 Injectable: 5056 (14%)

 Warfarin: 5824 (11%)

Aspirin patients had lower 

baseline VTE risk score than 

warfarin or 

LMWH/fondaparinux patients 

(p<0.001)

Aspirin Patients had fewer 

medical comorbidities than 

Injectable (p<0.001) but 

similar to Warfarin Patients 

(p=0.69)

Aspirin patients less likely to 

have a charge for sequential 

compression devices in 

perioperative period:

Aspirin 38%

LMWH/fondaparinux 48%

Warfarin 55%

(p<0.001)

Procedures: Total knee 

arthroplasty (TKA)

Indications: NR

Setting: Multicenter (307 

Hospitals participating in a 

proprietary database 

developed for measuring 

quality and healthcare use in 

hospitalized patients) The 

Warfarin as the VTEP

Injectable (n=37,198): 

Patients who received VTEP 

with injectable agents (e.g. 

LMWHs or fondaparinux)

Standard preventive 

measures: NR

Any thromboembolism 

 Aspirin: 110 (2.3%)

 Injectable: 1152 (3.1%)

 Warfarin: 2009 (4%)

 P<0.01 for all comparisons

Adjusted ORs (95%CI) n=3271

Aspirin as referent

 Injectable: 1.03 (0.76-1.39)

 Warfarin: 1.36 (1.02 -1.82)

 P<0.01 for all comparisons

Proximal DVT or PE

 Aspirin: 77 (1.6%)

 Injectable: 901 (2.4%)

 Warfarin: 1632 (3%)

 P<0.01 for all comparisons

Adjusted ORs (95%CI) n=2610

Aspirin as referent

 Injectable: 0.99(0.76-1.28)

 Warfarin: 1.34 (1.05 -1.70)

 P<0.01 for all comparisons

Bleeding related to wound 

site

 Aspirin: 30 (0.6%)

 Injectable: 459 (1%)

 Warfarin: 548 (1%)

 P<0.01 for all comparisons

Adjusted ORs (95%CI) n=1037

Aspirin as referent

 Injectable: 1.11 (0.77-1.60)

 Warfarin: 0.97 (0.65 -1.47)

Ultrasound or venogram any 

time after operative day (n, %)

diagnosis associated with 

any readmissions occurring 

w/in 30 days of discharge.

Perioperative care: NR

Analytical methodology 

Alternating logistic 

regression models were 

used to assess the 

independent association 

between the 3 VTEP 

strategies and the risk of 

complications or death.

A Propensity score was 

used in all models due to 

the threat of bias from 

group allocation. The 

resultant c-statistic was 

0.725 which was included 

in all core multivariable 

models as a covariate 

intended to adjust for 

allocation bias.

In a secondary analysis, 3 

propensity scores, 

including assignment to 

injectable VTEP vs. other 

VETP, etc. These scores did 

not substantially nor 

directionally alter the 

results, thus the first 

propensity score was used.

Other notes: None

Follow-up: 30 days 
Disclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminated by the Centers for Disease Control and Prevention and should not be 

construed to represent any agency determination or policy. 147

Author

Year

(Ref ID_

Data 

Extractor)

Risk of Bias 

Score Study Objective Population and Setting Intervention Results Comments

centers are predominantly 

small to midsize nonteaching 

facilities serving a largely 

urban patient population.

Location: USA

Dates: October 2003 -

September 2005

Inclusion Criteria: Patients 

admitted during the study 

dates, were ≥18 years old, and 

had primary TKA as their 

principal procedure during 

their hospitalization

Exclusion Criteria: Patients 

with no charges for any VTEP 

treatments, and those who 

had charges for VTEP 

treatments in formulations 

representing therapeutic 

rather than prophylactic 

anticoagulation.

 Aspirin: 1 (0.02%)

 Injectable: 73 (0.20%)

 Warfarin: 28 (0.05%)

Use of pneumatic 

compression 

devices

 Aspirin: 1795 (38%)

 Injectable: 17,756 (48%)

 Warfarin: 28,757 (55%)

Reoperations: NR

Length of stay: median (IQR)

 Aspirin: 1 (3-4)

 Injectable: 4 (3-4)

 Warfarin: 3 (3-4)

 P<0.001

Patients on Aspirin also more 

likely to be discharged home 

(vs. an extended care facility)

Aspirin 30%

LMWH/fondaparinux 23%

Warfarin: 21%

P<0.001

Mortality: 

 Aspirin: 9 (0.2%)

 Injectable: 45 (0.1%) 

 Warfarin: 54 (0.1%)

Adjusted ORs (95%CI) n=109

Aspirin as referent

 Injectable: 0.63 (0.30-1.34)

 Warfarin: 0.54 (0.25-1.15)

Adverse events: NR
Disclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminated by the Centers for Disease Control and Prevention and should not be 

construed to represent any agency determination or policy. 148

Author

Year

(Ref ID_

Data 

Extractor)

Risk of Bias 

Score Study Objective Population and Setting Intervention Results Comments

Parvizi

2007 35

(ES)

Retrospectiv

e Case 

Control

1, 2, 3, 5, 6, 7, 

8

To determine 

whether patients 

receiving 

excessive 

anticoagulation 

(an international 

normalized ratio 

[INR] of greater 

than clinically 

intended level) 

were at risk for 

developing 

wound-related 

problems, which 

in turn, 

predisposes 

them to 

periprosthetic 

infection. 

Ultimately, this 

study is to 

examine the 

correlation 

between 

anticoagulation 

and 

periprosthetic 

infection.

Number of patients: N=234

Patient Characteristics

·Age: mean±SD (years)

 Cases: 66±10

 Controls: 66±10

·Gender: female (%)

 Cases: 36 (46%)

 Control: NR

·Obesity: BMI >30 kg/m2

 Cases: 44 (56%)

 Control: 80 (51%)

BMI 9kg/m2 (mean±SD)

Cases: 32±9

Controls: 32±7

·Comorbidities:

ASA Score (mean±SD)

 Cases: 2.6±0.57

 Controls: 2.4±0.56

 P=0.01

Diabetes mellitus

 Cases: 14 (18%)

 Control: 22 (14%)

Steroid Therapy

 Cases: 8 (10%)

 Control: 5 (3%)

 P=0.03

NNIS≥1

 Cases: 50 (64%)

 Control: 73 (47%)

 P=0.01

SURGICAL DATA

Total Transfusion: mean±SD

 Cases: 0.78±1.15

 Controls: 0.39±0.79

 P=0.002

Intervention group: n=78

Cases: Patients who 

developed periprosthetic 

infection

Timing of intervention: preand postoperatively

Duration of intervention: 

given on the day of surgery 

and continued for a period of 

6 weeks. 

If patient a) was on 

anticoagulation before 

surgery for other conditions 

b) had known allergy to 

warfarin, or c) developed 

thromboembolism in the 

postoperative period; the 

patient was given either 

subcutaneous and/or 

intravenous heparin as the 

sole or the bridging agent 

until adequate and full 

anticoagulation (goal INR-2-

3) with oral agent could be 

established

Agent: All patients in both 

groups were given low-dose 

warfarin (goal INR=1.5) 

unless indicated otherwise

Monitoring intervention: 

INR

SSI (adjusted results when 

possible; unadjusted 

otherwise) 

Mean duration between index 

joint arthroplasty and 

development of infection was 

256 days (range 4-1890 days)

Multivariate analysis: Risk 

factors for periprosthetic 

infection (OR (95%CI)

ASA score

 2.07 (1.08-0.97); p=0.03

Postoperative Transfusions:

 1.63 (1.14-2.33); P=0.007

Postoperative wound 

complications including 

development of hematoma:

 27.02 (11.04-91.59); 

p=0.0002

Wound Drainage:

 32.20 (8.7-119.17); 

p<0.0001

Other infections: NR

Topic-specific outcomes: 

Wound Hematoma

 Cases: 11 (14%)

 Control: 2 (1%)

 P=0.0001

Wound Drainage

 Cases: 24 (31%)

 Control: 4 (3%)

 P=0.0001

Other Complications 

Definitions: 

Periprosthetic infection: 

patient has at least 3 of 5 

of the following criteria:

1) abnormal serology 

(erythrocyte 

sedimentation rate of 

>30mm/h; C-reactive 

protein level of >1mg/dL)

2) Strong clinical and 

radiographic suspicion for 

periprosthetic infection

3) positive joint aspiration 

culture for infection

4) evidence of purulence 

during the subsequent 

surgical intervention

5) Positive intraoperative 

culture.

Wound discharge beyond 

POD 7 was deemed 

clinically significant and 

abnormal.

Perioperative care: NR

Analytical methodology:

Wilcoxon procedure: to 

perform unadjusted 

analysis to compare means 

across continuous 

variables.

Fisher exact test: compare 

proportions across 

categorical variables.

T-statistics for continuous 
Disclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminated by the Centers for Disease Control and Prevention and should not be 

construed to represent any agency determination or policy. 149

Author

Year

(Ref ID_

Data 

Extractor)

Risk of Bias 

Score Study Objective Population and Setting Intervention Results Comments

Allogeneic Transfusion

 Cases: 10 (13%)

 Control: 3 (2%)

 P=0.0006

Autologous Transfusion

 Cases: 47 (60%)

 Control: 111 (71%)

 P=0.09

Procedures: 

Primary TKA: 

 Cases: 33/78 (%)

 Controls: NR

Revision TKA: 

 Cases: 10/78 (%)

 Controls: NR

Primary THA:

 Cases: 12/78 (%)

 Controls: NR

Revision THA

 Cases: 23/78 (%)

 Controls: NR

Indications: Degenerative 

joint arthritis was the most 

common diagnosis in both 

groups.

Posttraumatic arthritis: 4/234 

(1.7%)

Inflammatory arthropathy: 

2/234 (0.9%)

Setting: 1University Hospital

Location: USA

Dates: 2000 - 2005

Control group: n=156

Controls: Patients 

undergoing TKA or THA who 

underwent same index 

procedure but did not 

develop a subsequent 

infection.

Standard preventive 

measures 

AMP: Cephalosporin or an 

alternative for patients with 

penicillin allergies was 

administered within 60 

minutes of arthroplasty 

procedure and continued for 

24h postop. Antimicrobial

was administered at a mean 

of 39 min pre-incision.

(including PE, DVT & UTI)

 Cases: 18 (23%)

 Control: 18 (12%)

 P=0.02

Received injectable 

anticoagulant in addition to 

oral

 Cases: 13/78 (16.7%) 

(including 1 LMWH)

Received intravenous heparin:

 Cases: 13/74 (16.7%)

9/13 heparinized resulted in 

would complications 

 Hematoma: 3/9

 Persistent wound drainage: 

5/9

 Delayed wound healing: 1/9

INR

Mean INR>1.5

 Cases: 16 (21%)

 Control: 17 (11%)

 P=0.05; χ2=3.97

INR at day of Discharge>1.5

 Cases: 13 (17%)

 Control: 12 (8%)

 P=0.04; χ2=4.39

INR>1.5 on day of discharge

 Wound complications:22%

 No Wound Complications: 

8%

 P=0.005

INR level was statistically 

higher in patients with 

wound-related problems who 

variables

Χ

2

for categorical variables

Multivariate stepwise 

logistic regression was 

used to perform adjusted 

analysis

Other notes: None

Follow-up: NR
Disclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminated by the Centers for Disease Control and Prevention and should not be 

construed to represent any agency determination or policy. 150

Author

Year

(Ref ID_

Data 

Extractor)

Risk of Bias 

Score Study Objective Population and Setting Intervention Results Comments

Inclusion Criteria: All patients 

undergoing primary or 

revision total knee (TKA) or 

total hip arthroplasty (THA) 

for an aseptic diagnosis.

Exclusion Criteria: NR

later developed infection 

compared with patients who 

did not develop infection 

(p=0.03)

Reoperations:

 Cases: 14 (18%)

 Control: 3 (2%)

OR: 11.2; p<0.0001

Indications for reoperations 

included:

CASES:

Evacuation of hematoma: 

9/14 (64.3%)

Debridement and wash out of 

draining wound: 3/14 (21.4%)

Debridement and closure for 

wound dehiscence: 2/14 

(14.3%)

CONTROLS

Evacuation of hematoma: 2/3

(66.7%)

Delayed wound healing: 1/3: 

(1%)

Length of stay:

 Cases: 6 (Range 1-11) days

 Controls: 4 (range 2-6) days

 P=0.006

Mortality: NR

Adverse events

Wound dehiscence developed 

in 2 patients both of whom 

later developed infection
Disclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminated by the Centers for Disease Control and Prevention and should not be 

construed to represent any agency determination or policy. 151

Author

Year

(Ref ID_

Data 

Extractor)

Risk of Bias 

Score Study Objective Population and Setting Intervention Results Comments

Patel

2007 31

(ES)

Retrospectiv

e concurrent 

control

1, 2, 3, 5, 6, 7, 

8

The purpose of 

this study is to 

identify 

pharmacologic 

factors 

(prophylaxis 

against deep 

venous 

thrombosis), 

surgical factors 

(estimated blood 

loss and surgical 

time), and 

patient specific 

factors (BMI and 

drain output) 

that are 

associated with 

the time until 

postoperative 

wound is dry 

following 

primary total 

joint 

arthroplasty, and 

to determine 

whether 

prolonged 

wound drainage 

results in a 

longer hospital 

stay or increases 

the risk of early 

postoperative 

wound infection.

Number of patients: N=2437

Patient Characteristics

·Age: mean (years)

 Infected THA: 59.1

 Uninfected THA: 60.1

 Infected TKA: 63.1

 Uninfected TKA: 66.5

·Gender: m/f

 Infected THA: 0.6%/1.2%

 Infected TKA: 0.3%/1.0%

·Obesity: NR

·Comorbidities: NR

Procedures: 

Total Hip Arthroplasty 

(THA):1211

Total knee arthroplasty (TKA): 

1226

Indications: NR

Setting: 1 tertiary care 

teaching hospital.

Location: USA

Dates: January 1997 – July 

2004

Inclusion Criteria: Primary 

unilateral total hip and total 

knee arthroplasties in who 

closed suction drains had 

been utilized and who had a 

normal coagulation profile.

Intervention group: n=25 

Patients undergoing 

THR(n=15) or TKR (n=10) 

assigned to receive Warfarin, 

LMWH or aspirin at the 

surgeon’s preference who 

developed a postoperative 

wound infection

Timing of intervention: 

postoperative

Duration of intervention: 

variable

Agent: 

Warfarin: target 

international normalized 

ratio (INR)= 2.0

Low-Molecular-WeightHeparin(LMWH): started 

between 12-24 hours postop

Aspirin (ASA): 325mg in 

conjunction with pneumatic 

compression devices started 

the morning after surgery.

Monitoring intervention: NA

Control group: n=2412 

Patients undergoing THR 

(n=1196) or TKR (n=1216) 

assigned to receive Warfarin, 

LMWH or aspirin at the 

surgeon’s preference who 

SSI (unadjusted Follow Up 

NR) 

Overall: 25/2412 (1.0%)

THA: 15/1211 (1.2%) 

 [ 5/15 had cellulitis which

resolved with antimicrobials. 

10/15 had persistent drainage 

despite 3 days IV

antimicrobials and underwent 

operative irrigation and 

debridement]

TKA: 10/1226 (0.8%) 

 [7/10 had cellulitis which 

resolved with antimicrobials; 

2/10 required component 

removal due to persistent 

infection; 1/10 underwent 

operative irrigation and 

debridement due to infected 

hematoma but joint 

components were retained]

Logistic regression analysis of 

variables influencing wound 

infection after THA: 

OR(95%CI)

Time until wound dry: 

1.42 (1.18-1.71); p<0.001

Coumadin vs. aspirin and 

pneumatic compression 

devices:

7.47 (0.62-89.3); p=0.112

LMWH vs. aspirin and 

pneumatic compression 

devices:

2.11 (0.24-18.5); p=0.499

Definitions: 

Normal Weight: BMI ≤24.9 

kg/m2

Overweight: BMI 25-29.9 

kg/m2

Obese: BMI 30.0-39.9 

kg/m2

Morbidly Obese: BMI ≥40 

kg/m2

Length of stay: time/date 

of admission to time/date 

of discharge (as 

determined by the 

surgeon) either to home or 

to a rehabilitation setting.

The surgical wound was 

inspected daily with 

notation made of when 

the wound appeared dry 

according to the definition 

of Weiss and Krackow. 

Wound was considered 

actively draining if a ≥2x2-

cm area of gauze covering 

the wound was wet or if 

fluid was noted to be 

originating from the site. 

(spotting on gauze was not 

considered to be actively 

draining)

Perioperative care: NR

Analytical methodology: 

Multiple linear regression 

analysis was used to model 

the effects of prophylaxis 
Disclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminated by the Centers for Disease Control and Prevention and should not be 

construed to represent any agency determination or policy. 152

Author

Year

(Ref ID_

Data 

Extractor)

Risk of Bias 

Score Study Objective Population and Setting Intervention Results Comments

Exclusion Criteria: NR developed a postoperative 

infection

Standard preventive 

measures: 

Drains: were removed at 36 

hours postop or whenever 

drain output during any 8-h 

shift fell below 25mL.

AMP: routine preoperative 

and postoperative 

prophylactic antimicrobials 

(cefazolin if patient was not 

allergic to penicillin, 

otherwise, clindamycin) 

including at least 30min prior 

to initial incision.

Logistic regression analysis of 

variables influencing wound 

infection after TKA: OR(95%CI)

BMI: 1.08 (1.01-1.16); p=0.018

LMWH vs. aspirin and 

pneumatic compression 

devices:

1.07 (0.23-4.95); p=0.932

Other infections: NR

Topic-specific outcomes: 

Regression Analysis of 

variables influencing Time 

until wound was dry after 

THA:

LMWH: Coefficient = 0.318

 P=0.027 (compared with 

aspirin group)

Morbidly Obese: Coefficient = 

0.667; P=0.001

Drain Output: Coefficient –

0.002;

 P=<0.001

Statistically Significant 

variables influencing Time 

until wound was dry after 

TKA:

Drain Output: coefficient = 

0.0003; P=0.023

Drain output: 

THA group: every additional 

100-mL increase in postop 

drain output resulted in an 

additional 0.20 day of wound 

drainage time. 

against deep venous 

thrombosis (DVT), BMI, 

age, & type of anesthesia 

on time to a dry wound. 

Multiple logistic regression 

analysis was used to 

calculate the OR between 

postop infection and the 

time to a dry wound while 

controlling for DVT 

prophylaxis, BMI, surgical 

time, EBL 7 Drain output.

Other notes: None

Follow-up: NR
Disclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminated by the Centers for Disease Control and Prevention and should not be 

construed to represent any agency determination or policy. 153

Author

Year

(Ref ID_

Data 

Extractor)

Risk of Bias 

Score Study Objective Population and Setting Intervention Results Comments

TKA group: every additional 

100-mL increase in postop 

drain output resulted in an 

additional 0.03 day of wound 

drainage time.

Reoperations: 

THA: 10/1211 (0.8%) 

 10/15 underwent operative 

irrigation and debridement

TKA: 3/1226 (0.2%) 

 2/3 required component 

removal due to persistent 

infection; 1/3 underwent 

operative irrigation and 

debridement due to infected 

hematoma but joint 

components were retained

Length of stay: 

There was a strong positive 

correlation between the 

length of hospital stay and the 

number of days until surgical 

wound was dry: r=0.29; 

p<0.001

 THA: r=0.34; p<0.001

 TKA: r=0.26; p<0.001

Mortality: NR

Adverse events: NR
Disclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminated by the Centers for Disease Control and Prevention and should not be 

construed to represent any agency determination or policy. 154

Author

Year

(Ref ID_

Data 

Extractor)

Risk of Bias 

Score Study Objective Population and Setting Intervention Results Comments

Sachs

2003 34

(ES)

Retrospectiv

e concurrent 

control

1, 2, 3, 4, 5, 6,

To determine 

the safety and 

efficacy of 6 

weeks of lowdose warfarin 

when compared 

with no 

thromboprophyl

axis in total knee 

arthroplasty 

using infection 

and complication 

rates as the 

primary 

outcome 

measures

Number of patients: N=1742

Patient Characteristics

·Age: Median Age for both 

groups was 70 years.

·Gender: both groups included 

approximately 44% men and 

56% women

·Obesity: NR

·Comorbidities: NR

Procedures: Unilateral, 

Primary Total Knee 

Arthroplasty (TKA)

Indications: NR

Setting: Multicenter

Location: USA

Dates: 1995 - 2000

Inclusion Criteria: Patients 

who were treated with 

postoperative warfarin as 

recorded in the records of the 

“warfarin clinic” during the 

study dates. Patients 

underwent total knee 

arthroplasty and were 

operated on by one of 4 

surgeons who were using 

warfarin on an unselected 

basis for several years. 

Controls were identified who 

were treated without any 

Intervention group: n=957

Received low-dose warfarin 

as thromboprophylaxis

Timing of intervention: 

Postoperative

Duration of intervention: 6 

weeks

Agent: low-dose warfarin 

maintained at an 

international normalized 

ration (INR) from 1.6-2.2 for 

6 weeks

Monitoring intervention: NR

Control group: n=785

Patients received no 

thromboprophylaxis. While 

in the hospital, this group did 

not receive any aspirin or 

NSAIDs and were not placed 

on any type of venous 

compression device.

Standard preventive 

measures: 

Postoperative protocol: 

Continuous passive motion 

(CPM), physical therapy, and 

weight bearing, as well as 

most orders for pain control 

and nausea were essentially 

SSI (follow-up 3 months) 

Overall:

Warfarin: 9/957 (0.94%)

No Prophylaxis: 5/785 (0.64%)

Superficial infection

 Warfarin: 3 (0.4%) [two 

required readmission and IV 

antimicrobial therapy; one 

treated with an oral 

antimicrobial and developed 

wound necrosis and required 

readmission and plastic 

surgery]

 No Prophylaxis: 3 (0.3%) 

[two required readmission 

and IV antimicrobials]

Deep Wound Infection

 Warfarin: 6 (0.6%) [6 

required surgery, 5 with 

successful resolution; 1 

required 5 subsequent 

surgeries without resolution; 

1 developed necrosis 

requiring readmission and 

surgery for wound coverage 

and closure]

 No Prophylaxis: 2 (0.3%) 

[both required readmission 

and surgery]

Wound Necrosis(described 

above)

 Warfarin: 2 (0.2%) 

 No Prophylaxis: 0 (0%)

Total Complication Rate 

Definitions: NR

Perioperative care: 

Patients were encouraged 

to undergo spinal 

anesthesia 

Analytical methodology: 

Chi-square analysis, MannWhitney test

Other notes: None

Follow-up: 3 months 

postop
Disclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminated by the Centers for Disease Control and Prevention and should not be 

construed to represent any agency determination or policy. 155

Author

Year

(Ref ID_

Data 

Extractor)

Risk of Bias 

Score Study Objective Population and Setting Intervention Results Comments

chemical or mechanical 

thromboprophylaxis and were 

operated on by 1 of 3 

surgeons whose routine was 

to avoid thromboprophylaxis 

during TKA

Exclusion Criteria: Patients 

undergoing bilateral or 

revision TKA, patients on 

warfarin prophylaxis for 

previous chronic arterial 

fibrillation or thromboembolic 

events 

the same for all patients.

Both groups received initial 

wound care from a small 

group of orthopedic “special 

care nurses” who performed 

dressing changes, suture 

removal and wound 

observations for the first 

month after surgery.

(including infections)

 Warfarin: 17 (2.2%)

 No Prophylaxis: 45 (4.7%)

 P<0.01

One or more complication

 Warfarin: 5%

 No Prophylaxis: 2%

Other infections: 

Pneumonia

 Warfarin: 5 (0.5%)

 No Prophylaxis: 1 (0.1%)

Topic-specific outcomes: 

DVT

 Warfarin: 2 (0.2%) [two calf 

vein DVTs]

 No Prophylaxis: 0 (0%)

PE

 Warfarin: 1 (0.1%) [required 

readmission]

 No Prophylaxis: 2 (0.3%) [ 

these two events were nonfatal occurring within initial 

hospitalization and resolved 

with treatment

Reoperations: 

Subsequent surgeries

 Warfarin: 11 (1.1%)

 No Prophylaxis: 2 (0.3%)

 Χ

2

=4.66; P<0.01

Length of stay- NR

Mortality: 

Deaths (within 90 days)

 Warfarin: 1 (0.1%); patient 

admitted 1w postop with GI 

bleed, unsuccessful attempts 
Disclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminated by the Centers for Disease Control and Prevention and should not be 

construed to represent any agency determination or policy. 156

Author

Year

(Ref ID_

Data 

Extractor)

Risk of Bias 

Score Study Objective Population and Setting Intervention Results Comments

to control resulted in 

myocardial infarction and 

death

 No Prophylaxis: 2 (0.3%); 1 

in 91yo patient who sustained 

a fata myocardial infarction 

5w postop; 1 in a 73yo patient 

without prior history of 

cardiac disease readmitted in 

congestive heart failure 11 

days postoperatively, 

contracted pneumonia and 

expired

None due to thromboembolic 

disease

Adverse events:

New Arrhythmia

 Warfarin: 6 (0.6%)

 No Prophylaxis: 1 (0.1%)

All recovered

Angina

 Warfarin: 5 (0.5%)

 No Prophylaxis: 0 (0%)

MI

 Warfarin: 3 (0.3%)

 No Prophylaxis: 2 (0.3%)

TIA

 Warfarin: 1 (0.1%)

 No Prophylaxis: 1 (0.1%)

CVA

 Warfarin: 2 (0.2%)

 No Prophylaxis: 1 (0.1%)

GI Bleeding

 Warfarin: 3 (0.3%)

 No Prophylaxis: 0 (0%)
Disclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminated by the Centers for Disease Control and Prevention and should not be 

construed to represent any agency determination or policy. 157

Author

Year

(Ref ID_

Data 

Extractor)

Risk of Bias 

Score Study Objective Population and Setting Intervention Results Comments

Other

 Warfarin: 7 (0.7%)

 No Prophylaxis: 4 (0.5%)

C. How safe and effective is modifying the dose of the perioperative VTE prophylaxis agent to reduce the risk of SSI? Our search did not 

identify data that evaluated the safety and effectiveness of modifying perioperative VTE prophylaxis and its impact on the risk of SSI. 
Disclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminated by the Centers for Disease Control and Prevention and should not be 

construed to represent any agency determination or policy. 158

RISK OF BIAS ASSESSMENTS OF STUDIES Q17

Systematic Reviews

Author

Year (RefID)

KQ Search 

terms 

describe

d

Databases 

described 

and two 

or more 

databases 

searched

Inclusion/ 

exclusion 

criteria 

described

Number of 

included/ 

excluded 

studies 

along with 

reasons of 

exclusion 

described

Studies 

screened 

by two 

independen

t reviewers 

for inclusion

Data 

extracted 

by two 

independen

t reviewers

Individu

al study 

quality 

assessed

Heterogeneity 

between study 

results 

assessed 

qualitatively 

and/or 

quantitatively

Publication 

bias 

assessed

Characteristics 

of included 

studies 

reported in 

evidence table

Funding 

source(s) 

disclosed 

and no 

obvious 

conflict of 

interest

Overall 

Risk of 

Bias

Question 17: Anticoagulation

Turpie

2002 22 17   High

Randomized Controlled Trials

Author

Year (RefID)

K

Q

Described 

as 

randomize

d

Randomizatio

n 

appropriately 

performed

Described 

as 

doubleblind

Outcom

e 

assessor 

blinded

Study 

participant 

blinded

Investigato

r blinded

Attrition 

described

Attrition smaller 

than 10-15% of 

assigned patients

Attrition 

appropriately 

analyzed

Funding source(s) 

disclosed and no 

obvious conflict of 

interest

Overall 

Risk of 

Bias

Question 17: Anticoagulation

Eriksson

2008 27 17         Low

Kakkar

2008 28 17          Low

Lassen

2008 29 17         Low

Turpie

2009

30 17         Low

Other Controlled Studies

Author

Year (RefID)

KQ All study groups 

derived from similar 

source/reference 

populations

Attrition not 

significantly 

different across 

study groups

Measure of 

exposure is 

valid

Measure of 

outcome is valid

Investigator 

blinded to 

endpoint 

assessment

Potential 

confounders 

identified

Statistical 

adjustment for 

potential 

confounders done

Funding source(s) 

disclosed and no 

obvious conflict of 

interest

Overall 

Risk of 

Bias

Question 17: Anticoagulation

Asensio

2010 32 17         Low

Bozic

2010 33 17         Low

Parvizi

2007 35 17         Low

Patel

2007 31 17        Low

Sachs

2003 34 17       Low
Disclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminated by the Centers for Disease Control and Prevention and should not be 

construed to represent any agency determination or policy. 159

Q18 ORTHOPAEDIC SPACE SUIT 

GRADE TABLE Q18

Comparison Outcome

Quantity 

and Type 

of 

Evidence

Findings Starting 

GRADE

Decrease GRADE Increase 

GRADE

GRADE of 

Evidence 

for 

Outcome

Overall 

GRADE of 

Evidence 

Base

Study QualityConsistencyDirectnessPrecisionPublication BiasLarge MagnitudeDose-responseConfounders

Q18. How safe and effective are orthopaedic space suits in reducing the risk of SSI in prosthetic joint arthroplasty patients and then which healthcare personnel should wear 

them?

Space Suit 

vs. No suit 

Deep SSI 

requiring 

reoperati

on*

1 OBS 36

 One retrospective study (N=8288) in TKA using 

Medicare claims data, found no difference in 

risk of deep SSI requiring reoperation within 

90 days of surgery: 0.28% (95%CI, 0.11-0.46) 

vs. 0.38% (95%CI, 0.20-0.55); RR 0.75 (95% CI, 

0.34-1.62) 

 Deep Infections identified through ICD9-CM

diagnosis codes for multiple joint/bone 

infection, debridement, and implant removal 

codes (not revision total joint arthroplasty 

codes). In this study deep infection might be 

referring to PJI.

 Use of laminar flow varied between groups.

Low 0 0 0 -1 0 0 0 0 Very low

Very low

Deep SSI 

requiring 

revision*

1 OBS 37

 One study large joint registry study 

(N=88,311) with multiple subgroup analyses, 

found use of space suits was associated with 

an increased number of deep SSIs requiring 

revision surgery within 6 months of THA or 

TKA (P<0.001) but this evidence is limited in 

size (only 96 events or 0.109%): 

 The results did not differ in the presence or 

absence of laminar flow

 Deep SSI in this study might be referring to 

PJI.

Low 0 0 0 -1 0 0 0 0 Very low
Disclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminated by the Centers for Disease Control and Prevention and should not be 

construed to represent any agency determination or policy. 160

Comparison Outcome

Quantity 

and Type 

of 

Evidence

Findings Starting 

GRADE

Decrease GRADE Increase 

GRADE

GRADE of 

Evidence 

for 

Outcome

Overall 

GRADE of 

Evidence 

Base

Study QualityConsistencyDirectnessPrecisionPublication BiasLarge MagnitudeDose-responseConfounders

 60% of primary procedures used antimicrobial 

impregnated cement.

Deep 

SSI* 1 OBS 38

 One small study (N=62) evaluating 

contamination using space suit or 

conventional gowns with single hood plus 

surgical mask, during THA or hip 

hemiarthroplasty reported only 1 deep SSI in 

the exhaust suit group (11 days postop) but 

this evidence is limited in size: 1/31 (3.2%) vs. 

0/31. (24 month follow up). 

 Statistical significance was not reported.

 HEPA filtration was present in both study 

groups.

 Deep SSI was not defined-in this study might 

be referring to incisional SSI

 Study was designed to evaluate 

contamination

Low 0 0 0 -1 0 0 0 0 Very low

Superfici

al SSI 1 OBS38

 One study (14484) found no difference in risk 

of superficial SSI for patients undergoing THA 

or hip hemiarthroplasty: 1(3.2%) superficial 

SSI in each group at 16 and 15 days 

postoperatively, respectively. Follow up 24 

months.

 Statistical significance was not reported.

 HEPA filtration was present in both study 

groups.

Low 0 0 0 -1 0 0 0 0 Very low

*Critical outcome; OR: Odds Ratio; RR: Risk Ratio; CI: Confidence Interval
Disclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminated by the Centers for Disease Control and Prevention and should not be 

construed to represent any agency determination or policy. 161

EVIDENCE TABLE Q18

Q18. How safe and effective are orthopaedic space suits in reducing the risk of SSI in prosthetic joint arthroplasty patients and then which 

healthcare personnel should wear them?

Author

Year

(Ref ID_

Data 

Extractor)

Risk of Bias 

Score

Study 

Objective

Population and 

Setting Intervention Results Comments

Hooper 

2011 37

(ES)

Retrospecti

ve 

concurrent 

control

1, 2, 3, 4, 5, 

6, 8

To review the 

New Zealand 

Joint Registry 

to determine 

if the use of 

laminar flow 

and 

protective 

suits with 

hoods and 

selfcontained 

exhaust 

systems 

(space suits) 

would reduce 

the rate of 

early deep 

infection 

requiring a 

revision 

procedure 

following 

total hip 

(THR) and 

knee (TKR) 

replacements 

at 10 years

Number of patients: 

N=88,311

Primary THR: 51,485

Primary TKR: 36,826

Patient 

Characteristics: 

recorded, not 

reported but narrative 

details that there 

were no significant 

differences in clinical 

details between the 

groups and there was 

similar duration of 

operations

·Age: NR

·Gender: NR

·Obesity: NR

·Comorbidities: NR

Procedures: Total Hip 

replacement (THR) 

and total knee 

replacement (TKR) 

and revisions due to 

early infections.

Indications: 

Osteoarthritis: 94% for 

both THR and TKR

Inflammatory 

Arthritis:

THR: 3%

Intervention group: 

Intervention1: Space Suit 

n=20,385

 THR: 21% (n=10,811)

 TKR: 26% (n=9,574)

Intervention2: Laminar Flow 

Theater: n=30,983

 THR: 33% (n=16,990)

 TKR: 38% (n=13,993)

Note: Authors only provide 

percentages; “n” was 

calculated.

Intervention3: Both Space 

Suit and Laminar FlowNumbers not reported (See 

Other Notes)Timing of 

intervention: intraoperative

Duration of intervention: 

intraoperative

Device: either laminar air 

flow or protective suits with 

hoods and self-contained 

exhaust systems (space 

suits) or both. 

Laminar Flow: All hospitals 

confirmed that they had a 

regular maintenance 

program for filters. There 

were no hospitals which 

used laminar flow 

combined with a complete 

SSI (Follow up: ≥ 6 months) 

Unadjusted results:

THR

Early revision for deep 

infection:

46/51485 (0.089%)

 Intervention1- Space Suit: 

0.186%

 Control1-No Space Suit: 

0.064%

 P<0.0001

Intervention2- Laminar Flow 

theater: 0.148%

 Control2-conventional 

theater: 0.061%

 P<0.003

Intervention3-BothSpace suit 

+ laminar flow: 0.198%

 Control3 -Neither No Space 

suit in a conventional OR: 

0.053%

 P<0.001

From Figure 1c (Bar Graphdetails not reported in text)

Conventional OR:

 Suit: ~0.15%

 No Suit: 0.053%

Laminar Flow OR:

 Suit: 0.198%

 No Suit:~ 0.10%

P values for above NR

Definitions:

SSI- deep (joint 

space)

Revision due to early 

infection: any such 

procedure performed 

within 6months of 

the initial operation

Perioperative care: 

NR

Analytical 

methodology: 

Percentages with 

revision for deep 

infection were 

compared between 

groups using the Chisquared test or 

Fisher’s exact test 

when expected 

frequencies were 

low. A p-value of 

<0.05 was considered 

significant

Other notes:

There was a steady 

increase in the use of 

intervention 

procedures and In 

2008 almost half of 

all procedures were 
Disclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminated by the Centers for Disease Control and Prevention and should not be 

construed to represent any agency determination or policy. 162

Author

Year

(Ref ID_

Data 

Extractor)

Risk of Bias 

Score

Study 

Objective

Population and 

Setting Intervention Results Comments

TKR: 4%

Setting: Multi-center 

(64 hospitals)

Location: New 

Zealand

Dates: 1999-2008

Inclusion Criteria: All 

primary THR & TKR 

and revisions due to 

early infections with 

full information on 

theater environment 

and a minimum follow 

up of 6 months.

Specifically surgeons 

who had experience in 

both conventional and 

laminar-flow 

operating theaters 

and who had 

performed at least 50 

procedures in both. 

Also surgeons who 

had used space-suits 

in both settings and 

who had completed at 

least 50 procedures in 

each

Exclusion Criteria: NR

surgical enclosure.

Space Suits: All the suits 

were contemporary in 

design and no surgeon 

worked in a fully-enclosed 

space. No surgeon worked 

with all staff in the theater. 

Monitoring intervention: 

NR

Control group: n=NR

Control1: (n=67,926) THR or 

TKR performed without 

Space Suit

THR: 79% (n=40,674)

TKR: 74% (n=27,252)

Control2: (n=57,328)THR or 

TKR performed In 

Conventional theater

THR: 67% (n=34,495)

THR:62% (n=22,833)

Control3: in conventional 

theater with no space suit

Standard preventive 

measures: 

Non-standard preventive 

measures:

AMP: in New Zealand, 

prophylactic antimicrobials

are given for most THR and 

TKR procedures. (Registry 

shows 96%)

Antimicrobial agent in 

cement: Registry data 

shows 60% utilization rate

SURGEON SPECIFIC 

SURGICAL PRACTICE 

INFECTION RATES

33 surgeons did or did not 

wear space suits

 Intervention1 (with space 

suit): 0.082%

 Control1 (without space 

suit) :0.057%

 P=0.755

43 surgeons performed more 

than 50 operations in both 

operating environments 

 Intervention2(Laminar 

Flow): 0.110%

 Control2 (Conventional OR): 

0.028%

 P<0.03

30 surgeons used both space 

suit AND laminar flow or 

neither

 Intervention3 (space suit 

AND laminar flow): 0.1035%

 Control3 (NO space suit 

AND conventional OR): 

0/3598 procedures

 P=0.09

TKR

Early revision for deep 

infection:

50/36826 (0.136%)

 Intervention1- Space Suit: 

0.243%

 Control1-No Space Suit: 

0.098%

performed in 

laminar-flow theaters 

with space suits

The registry captures 

98% of both primary 

and revision 

arthroplasties 

performed in New 

Zealand and records 

revision procedures 

secondary to deep 

infection. 

Surgeon 

Questionnaire: They 

compared rates for 

surgeons who used 

space suits in both 

operating room 

settings (laminar flow 

and conventional) 

and completed at 

least 50procedures in 

each (similar surgical 

practices). 

Questionnaire 

requested 

information on 

frequency of suit use, 

members of the 

team who wore 

them, whether 

practice changed 

depending on OR 

team and whether 
Disclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminated by the Centers for Disease Control and Prevention and should not be 

construed to represent any agency determination or policy. 163

Author

Year

(Ref ID_

Data 

Extractor)

Risk of Bias 

Score

Study 

Objective

Population and 

Setting Intervention Results Comments

 P<0.001

Intervention2- Laminar Flow 

theater: 0.193%

 Control2-conventional 

theater: 0.100%

 P<0.019

Intervention3-Both Space 

suit AND Laminar Flow: 

0.25%

 Control3-Neither (No Space 

suit AND Conventional OR): 

0.087%

 P<0.001

From Figure 2c (Bar Graphdetails not reported in text)

Conventional OR:

 Suit: ~0.25%

 No Suit:0.087 %

Laminar Flow OR:

 Suit: 0.25%

 No Suit:~0.12 %

P values for above NR

SURGEON RELATED 

INFECTION RATES

23 surgeons ± space suits:

 Intervention1 (Space suit): 

0.251%

 Control1 (No Space 

suit):0.028%

 P=0.016

32 surgeons performed more 

than 50 operations in both 

operating environments 

 Intervention2 (Laminar 

Flow): 0.147%

they wore full suits 

or just hood/exhaust 

system.

Discussion comments 

regarding potential 

reasons for increased 

rate of infection with

use of space suit 

include:

Observers in OR have 

noted surgeons often 

adjust suit or hood 

during procedure 

and subsequently 

unknowingly 

contaminate their 

gloves.

Exhaust system –

there is no 

information as to the 

flow of the expelled 

air from exhaust 

systems and whether 

air is concentrated 

with debris and 

significant numbers 

of colony forming 

units close to the 

surgical site.

Follow-up: Minimum 

6 months
Disclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminated by the Centers for Disease Control and Prevention and should not be 

construed to represent any agency determination or policy. 164

Author

Year

(Ref ID_

Data 

Extractor)

Risk of Bias 

Score

Study 

Objective

Population and 

Setting Intervention Results Comments

 Control2 (Conventional OR): 

0.189%

 P=0.597

NOTE: One hospital of 64 

was identified as having a 

significantly increased rate of 

revision for early deep 

infection when the use of a 

conventional theater and no 

space suit was compared 

with laminar flow with a 

space suit. The hospital 

contributed only a small

number to the database and 

when these were removed 

from the analysis, there was 

no change in the significance 

of the results.

Other infections: NR

Topic-specific outcomes:

Surgeon Questionnaire

35/60 (58.3%) response rate 

Space suit used in all 

replacement procedures: 

35/35 

Surgical technique the same 

regardless of laminar flow vs. 

conventional OR: 35/35

Full space suit: 28/31

OR team members wearing 

full suit: surgeon, assistant 

and scrub nurse.

OR team members NOT 

wearing space suit: 
Disclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminated by the Centers for Disease Control and Prevention and should not be 

construed to represent any agency determination or policy. 165

Author

Year

(Ref ID_

Data 

Extractor)

Risk of Bias 

Score

Study 

Objective

Population and 

Setting Intervention Results Comments

anesthetist or technician

Reoperations: All infections 

were reoperations

Length of stay: NR

Mortality: NR

Adverse events:

Surgeon Questionnaire:

Spatial awareness limited by 

hood (space suit)

“Easier to contaminate 

themselves while wearing 

space suit since there was an 

apparent false sense of 

security within it”

Miner

2007 36

(ES)

Retrospecti

ve 

concurrent 

control

1, 2, 3, 5, 8

To assess the 

current 

effects of 

laminar 

airflow 

systems and 

body exhaust 

suits on the 

risk of 

postoperativ

e infections 

via a 

secondary 

analysis of 

data 

collected for 

a larger study 

of hospital 

characteristic 

and patient 

outcomes 

Number of patients: 

N=8288 procedures

Patient 

Characteristics: NR

·Ag: NR

·Gender: NR

·Obesity: NR

·Comorbidities: NR

Procedures: Unilateral 

primary total knee 

replacement (TKR)

Indications: NR

Setting: 256 centers in 

Illinois, Ohio, North 

Carolina and 

Tennessee that 

submitted a claim for 

Intervention group: 

Intervention1: n=3538 

Patients in Hospitals which 

used exhaust suits in more 

than 75% of procedures

Intervention2: n=3513

Patients in Hospitals which 

used laminar air flow in 

more than 75% of 

procedures

Timing of intervention:

Intraoperative

Duration of intervention: 

Intraoperative

Device: Laminar air flow or 

Exhaust suits.

Laminar air flow: horizontal 

and vertical laminar airflow 

SSI (follow up 90 days) 

Unadjusted results

Overall 90-day cumulative 

incidence of deep infection 

requiring reoperation: 

 28/8288 TKR 

(0.34%)BODY EXHAUST SUIT

Intervention1: 10/3538 

(0.28% (95%CI: 0.11-0.46))

Control1: 18/4750 (0.38 

(95%CI: 0.20-0.55))

Risk Ratio (95%CI) for Body 

Exhaust Suit: 0.75 (0.34-1.62)

LAMINAR AIR FLOW

Intervention2: 15/3513 

(0.43% (95%CI: 0.21-0.64))

Control2: 13/4750 (0.27 

(95%CI: 0.12-0.42))

Definitions: 

SSI-deep prosthetic 

joint infection

Infection: 

International 

Classification of 

Diseases, Ninth 

revision (ICD-9) 

diagnosis and 

procedures codes for 

evidence of 

postoperative deep 

infection that 

required additional 

operation. 

Reoperations within 

90 days 

Perioperative care: 

NR 

Analytical 

methodology: None
Disclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminated by the Centers for Disease Control and Prevention and should not be 

construed to represent any agency determination or policy. 166

Author

Year

(Ref ID_

Data 

Extractor)

Risk of Bias 

Score

Study 

Objective

Population and 

Setting Intervention Results Comments

after total 

knee 

replacement 

(TKR)

TKR during 2000

Location: USA

Dates: January 1 –

August 30, 2000

Inclusion Criteria: 

Data from Medicare 

claims parts A and B 

to identify unilateral 

primary TKRs. For 

patients with a second 

TKR during a separate 

hospitalization, only 

the first procedure 

was considered.

Hospitals had to meet 

the following criteria: 

1. The orthopedic 

administrator 

returned the survey 

on use of laminar 

airflow systems 

(horizontal or vertical) 

and body exhaust 

suits during TKR in 

year 2000, 2. The 

survey contained 

information regarding 

use of laminar airflow 

systems and body 

exhaust suits as 

systems were combined 

into a single group that 

represented regular use of 

laminar air flow.

Exhaust Suit: Not indicated 

who wore exhaust suits, 

specifics of design. OR Flow 

or traffic not described

Monitoring intervention: 

NR

Control group: 

Control1: n=4750

Patients in Hospitals which 

used exhaust suits at 

frequencies of “not at all”, 

“used in less than 26% of 

procedures,” “used in 26%-

75% of 

procedures”Control2: 

n=4775

Patients in Hospitals which 

used Laminar Air Flow at 

frequencies of “not at all”, 

“used in less than 26% of 

procedures,” “used in 26%-

75% of procedures”

Standard preventive 

measures:

Use of laminar air flow and 

exhaust suit was distributed 

roughly independently 

among hospitals. Most 

hospitals reported that 

28 TKR were performed in 25 

hospitals.

Other infections: NR

Topic-specific outcomes:

30% of hospitals in analysis 

reported regular use of 

laminar airflow systems

41% of hospitals in this 

analysis reported regular use 

of body exhaust suits.

Reoperations: All incidences 

of infection were 

reoperations within 90 days.

Length of stay: NR

Mortality: NR

Adverse events: NR

Did not adjust for 

clustering of events 

within hospitals bb/c 

22/25 hospitals with 

infections reported 

only a single 

infection and 

because no hospital 

reported more than 

2 infections.

Other notes: 

UV Light usecollected data on use 

of UV lights but this 

was used only at 

13/256 hospitals and 

did not allow analysis 

of effect on 

infectious outcomes. 

Low number of 

events (n=28) yielded 

low power to exclude 

potential benefits. 

Also precluded 

analysis of subgroups 

and interactions 

between infection 

control techniques. 

Also potential for 

misclassification of 

individual procedures 

(focus on hospital 

standard practice)-

infections associated 

with hospitals 
Disclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminated by the Centers for Disease Control and Prevention and should not be 

construed to represent any agency determination or policy. 167

Author

Year

(Ref ID_

Data 

Extractor)

Risk of Bias 

Score

Study 

Objective

Population and 

Setting Intervention Results Comments

infection control 

measures, and 3. 

There was evidence of 

at least 1 Medicare 

claim for a TKR 

performed during 

January 1 and August 

1, 2000

Exclusion Criteria: 

Bilateral TKR during 

the same 

hospitalization.

these methods were either 

part of their standard 

infection control practices 

(used>75% of time) or not 

at all.

classified as using 

intervention 

technique most of 

the time, could have 

occurred in patients 

for whom the 

technique was not 

use.

Follow-up: 90 days

Pasquarell

a

2003 38

(ES)

Prospective 

Concurrent 

control

1, 2, 3, 4, 5,

To evaluate 

the effect on 

aerobic 

bacterial 

sedimentatio

n of a mixed 

operating 

theater 

ventilation 

with separate 

operating 

and 

anesthetic 

areas and to 

compare the 

contaminatio

n using body 

exhaust 

gowns or 

conventional 

clothing 

during hip 

Number of patients: 

N=62 operations

Patient 

Characteristics

·Age: mean 70.80 

years range= 30-95 

years SD=12.39

·Gender: m/f: 33/29

·Obesity: NR

·Comorbidities: NR

Procedures: Total hip 

replacements (THR) or 

hemiarthroplasties 

Indications:

Hemiarthroplasties: 

either coxoarthrosis or 

fracture (trauma)

THR: NR

Setting: Orthopedic 

department in 1 

hospital

Location: Switzerland

Intervention group: n=31

Body exhaust suits were 

worn by one surgeon, the 

first assistant and the scrub 

nurse who remained seated 

throughout the whole 

operation. The circulating 

nurse wore a conventional 

gown. Operation was 

conducted in a diluted 

airflow system with 

separation zones.

Timing of intervention: 

Intraoperative

Duration of intervention: 

Intraoperatively

Device:

Diluted airflow system with 

separation zones: 

Unidirectional airflow 

system where the air is 

forced through a 0.3μm H14 

SSI (follow up 24 months) 

Unadjusted:

Total: 3/61 (4.8%)

Deep: 1/61 (1.6%)

Superficial: 2/61 (3.2%)

Intervention (Exhaust suit):

 Deep: 1/31 (3.2%) 

 postop day 11

 Superficial: 1/31 (3.2%) 

 postop day 16

Control (conventional gown):

 Deep: 0/31

 Superficial: 1/31 (3.2%) 

 postop day 15

Other infections: NR

Topic-specific outcomes: NA

Reoperations: NR

Length of stay: NR

Mortality: NR

Definitions:

Deep and superficial 

wound infections not 

defined but 

recorded.

Perioperative care:

Anesthesia: either 

general or spinal. 

Analytical 

methodology: 

Settle plate results 

were compared 

between patient and 

anesthetist areas and 

between 

conventional gowns 

and body exhaust 

suits using MannWhitney U tests after 

normality checking to 

establish significant 

differences between 
Disclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminated by the Centers for Disease Control and Prevention and should not be 

construed to represent any agency determination or policy. 168

Author

Year

(Ref ID_

Data 

Extractor)

Risk of Bias 

Score

Study 

Objective

Population and 

Setting Intervention Results Comments

joint 

Arthroplasty 

(THR and 

hemiarthropl

asty)

Dates: December 

1997-January 1998

Inclusion Criteria: 

Patients scheduled for 

THR or 

hemiarthroplasties for 

either coxoarthrosis or 

fracture between the 

study dates

Exclusion Criteria: NR

99.995% HEPA (high 

efficiency particulate air) 

filter and supplied through 

eight air ceiling diffusers 

located over the operating 

table and the instrument 

table. The air is extracted by 

means of two floor-level 

return air grilles in the walls 

of the anesthetic area. Air 

turnover rate ≈24 air 

changes /h with a positive 

pressure of 2 Pa. A 

plexiglass barrier separates 

the OR into the patient area 

and the anesthetic area. 

The Patient’s head and the 

anesthesiologist remain 

outside the patient area 

during the operation.

Body exhaust suit:

Manufacturer named but 

suit not described. 

Conventional Gowns: 65% 

polyester 35% cotton with 

the head cover consisting of 

a single hood plus surgical 

mask and the neck 

remaining partially exposed.

Monitoring intervention:

NA

Control group: n=31 

Conventional gowns worn 

by all surgical staff during 

operation in diluted airflow 

Adverse events: NR variables.

Other notes: None

Follow-up: 24 

months
Disclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminated by the Centers for Disease Control and Prevention and should not be 

construed to represent any agency determination or policy. 169

Author

Year

(Ref ID_

Data 

Extractor)

Risk of Bias 

Score

Study 

Objective

Population and 

Setting Intervention Results Comments

system with separation 

zones

Standard preventive 

measures:

AMP: IV injection of 

cefamandole 30min before 

anesthesia followed by a 

second dose of 

cefamandole in operations 

lasting longer than 2h.

Operating Room Traffic:

Operating Team (1 surgeon, 

2 assistants, 2 nurses) same 

for all procedures. Surgeon 

first assistant and scrub 

nurse remained seated 

entire operation (second 

assistant stood at opposite 

end of room and circulating 

nurse moved around). 

Extraneous personnel were 

excluded from the OR. 

Swing doors were closed to 

all personnel after the final 

preparation of the patient 

on the operating table.
Disclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminated by the Centers for Disease Control and Prevention and should not be 

construed to represent any agency determination or policy. 170

RISK OF BIAS ASSESSMENTS OF STUDIES Q18

Other Controlled Studies

Author

Year (RefID)

KQ All study groups 

derived from similar 

source/reference 

populations

Attrition not 

significantly 

different across 

study groups

Measure of 

exposure is 

valid

Measure of 

outcome is valid

Investigator 

blinded to 

endpoint 

assessment

Potential 

confounders 

identified

Statistical 

adjustment for 

potential 

confounders done

Funding source(s) 

disclosed and no 

obvious conflict of 

interest

Overall 

Risk of 

Bias

Question 18: Surgical Attire

Hooper

2011 37 18        Low

Miner

2007 36 18      Low

Pasquarella

2003 38 18      Low
Disclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminated by the Centers for Disease Control and Prevention and should not be 

construed to represent any agency determination or policy. 171

Q20 BIOFILM 

GRADE TABLE Q20

Comparison Outcome

Quantity 

and Type 

of 

Evidence

Findings Starting 

GRADE

Decrease GRADE Increase 

GRADE

GRADE of 

Evidence 

for 

Outcome

Overall 

GRADE of 

Evidence 

Base

Study QualityConsistencyDirectnessPrecisionPublication BiasLarge MagnitudeDose-responseConfounders

Q20. What are the most effective strategies to reduce the risk of biofilm formation and SSI in prosthetic joint arthroplasty patients?

Q20A. How effective are cement modifications (i.e., antimicrobial and nanoparticle loading)?

Cefuroxime 

loaded 

cement vs. 

plain 

cement; 

both groups 

with 

perioperativ

e AMP

Deep 

SSI* 2 RCT 39, 40

 Meta-analysis 2 RCTs (N=418), reduced risk for 

deep SSI in primary hybrid TKA (cemented 

tibial and patellar components) with 

cefuroxime 2g in 40g polymethylmethacrylate

loaded cement: OR: 0.08; (95% CI: 0.01 –

0.59); p=0.01

 1 study (584139) in 350 TKAs, non-diabetics: 

0/178 vs. 5/162(3.1%); p=0.0238

 1 study (584240) in 78 TKAs, all diabetics: 0/41 

vs.5/ 37(13.5%); p=0.021

 Based on definition deep SSI included PJI

 All TKAs performed by same surgeon, in 

operating rooms without ultraviolet light, 

laminar flow, or orthopaedic space suit

 AMP included parenteral cefazolin and 

gentamycin preoperatively then every 6 and 

12 hours, respectively postop for 36 hours 

followed by cefazolin orally for 7 more days.

High 0 0 0 0 -1 0 0 0

Low

Low

Superfici

al SSI 2 RCT 39, 40

 Meta-analysis 2 RCT (N=418), no difference 

(OR: 0.91; 95% CI: 0.18 – 4.55; p=0.90)

 In one study39 of 350 TKAs for osteoarthritis 

with no diabetes mellitus: 2/178 vs. 2/162; 

p=1.00

High 0 0 0 -1 -1 0 0 0 Low
Disclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminated by the Centers for Disease Control and Prevention and should not be 

construed to represent any agency determination or policy. 172

Comparison Outcome

Quantity 

and Type 

of 

Evidence

Findings Starting 

GRADE

Decrease GRADE Increase 

GRADE

GRADE of 

Evidence 

for 

Outcome

Overall 

GRADE of 

Evidence 

Base

Study QualityConsistencyDirectnessPrecisionPublication BiasLarge MagnitudeDose-responseConfounders

 In one study40 of 78 TKAs all with diabetes 

mellitus: 1/41 vs. 1/37; p=0.835

*Critical outcome; OR: Odds Ratio; RR: Risk Ratio; CI: Confidence Interval
Disclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminated by the Centers for Disease Control and Prevention and should not be 

construed to represent any agency determination or policy. 173

EVIDENCE TABLE Q20

Q20. What are the most effective strategies to reduce the risk of biofilm formation and SSI in prosthetic joint arthroplasty patients?

A. How effective are cement modifications (i.e., antimicrobial and nanoparticle loading)?

Author

Year

(Data 

Extractor)

Risk of Bias 

Score

Study 

Objective Population and Setting Intervention Results Comments

Chiu 

2002 39

(ES)

RCT

1, 5, 10

To evaluate 

the efficacy 

of 

cefuroximeimpregnate

d cement in 

the 

prevention 

of deep 

infection 

after 

primary 

total knee 

arthroplasti

es 

performed 

without 

clean-air 

measures 

such as 

laminar flow 

and bodyexhaust 

suits.

Number of patients: 

N=285 patients

 (340 knees)

Patient Characteristics: 

Age, tourniquet time, 

operative time, amount 

of blood transfusion, The 

Hospital for Special 

Surgery Knee Score (pre 

& post operatively), sex, 

side of operation, and 

preoperative diagnosis 

were all analyzed and 

were found to be similar 

between groups.

Age: Mean ±SD

 Intervention :70±7.4yr

 Control:68±6.9yr

Gender: (m/f)

 Intervention :69%/31%

 Control:70%/30%

Obesity: NR

Comorbidities: NR

Operation Side: 

(left/right)

 Intervention :51%/49%

 Control:55%/45%

Procedures: Primary total 

knee arthroplasties with 

cementless fixation of the 

femoral component and 

cement fixation (mixing 

Intervention group: n=178 

knees

Cefuroxime-impregnated 

cement ( 2g of cefuroxime in 

40 g cement) was utilized for 

fixation of the tibial an 

patellar components only

Timing of intervention: Intra 

and postoperatively 

Duration of intervention: 

The duration of implantation 

(indefinitely).

Device: Cefuroximeimpregnated cement; pure 

cement without cefuroxime; 

prosthetic knee

Monitoring intervention: 

Radio graphic evaluation at 

every visit & functional 

evaluation (Hospital for 

Special Surgery score) 

performed at every visit 

starting with the 3rd postop 

visit.

Control group: n= 162 knees

Cement did not contain 

cefuroxime. Only tibial and 

patellar components were 

fixed with cement.

Bilateral TKAs: n=55 patients 

; one knee treated with 

intervention, the other with 

SSI: (range 26-80 months)

Early Superficial Infections: 

 Intervention: 2/178 (1.1%)

 Control: 2/162 (1.2%)

 P=1

Early or Intermediate Deep Infections:

 Intervention: 0/178

 Control: 5/162 (3.1%) 

 Early: 3/5 (60%)

 Intermediate: 2/5 (40%)

P=0.0238

No deep infections in bilateral 

procedures

Other infections: NR

Topic-specific outcomes: NR

Re-operations attributable to SSI:

All four early superficial wound 

infections were treated with wound 

debridement & intravenous 

antimicrobials for 1 week then oral 

antimicrobials for another week.

Length of stay: Mean Stay, days (range):

 8 days (5-15 days)

Mortality: NR

Adverse events:

Loose femoral component at 2 years:

Intervention: 1/178 (0.6%) –underwent 

revision of the femoral component

Not significant statistically with 

available numbers

Definitions: (McQueen 

1990)

Superficial Infection –

infection superficial to the 

deep fascia with positive 

or negative cultures and 

no delays in wound 

healing.

Deep Infection – Infection 

extending deep to the 

deep fascia, with 

persistent wound 

discharge or joint pain, 

positive or negative 

cultures from deep tissues 

and delays in wound 

healing.

 Deep Infections also 

confirmed by laboratory 

parameters (the 

erythrocyte sedimentation 

rate & level C-reactive 

protein) & positive culture 

of joint fluid.

Early Infections: 

Developing <2 months 

after operation

Intermediate Infections: 

Developing 2-24 months 

after operation

Late Infections: Developing 

>24 months after 
Disclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminated by the Centers for Disease Control and Prevention and should not be 

construed to represent any agency determination or policy. 174

Author

Year

(Data 

Extractor)

Risk of Bias 

Score

Study 

Objective Population and Setting Intervention Results Comments

method of cement NR) of 

the patellar and tibial 

components. 

Indications: 

Osteoarthritis:

Control: 146/162 (90.1%)

Intervention: 154/178 

(86.5%)

Rheumatoid Arthritis

Control: 6/162 (3.7%)

Intervention: 10/178 

(5.6%)

Posttraumatic arthritis:

Control: 6/162 (3.7%)

Intervention: 10/178 

(5.6%)

Gouty arthritis

Control: 2/162 (1.2%)

Intervention: 1/178 

(0.6%)

Osteonecrosis:

Control: 1/162 (0.6%)

Intervention: 3/178 

(1.7%)

Setting: 1 Hospital

Location: Taiwan, China

Dates: 1994-1998

Inclusion Criteria: 

Patients undergoing 

primary total knee 

arthroplasty

Exclusion Criteria: 

Patients with diabetes 

mellitus, peripheral 

arterial occlusive disease, 

psoriasis, prior knee 

controls

Standard preventive 

measures:

Environmental: No 

ultraviolet light for 

disinfection; no laminar flow 

nor body-exhaust suits were 

used.

AMP Preop: intravenous 

bolus injections of cefazolin 

& gentamicin.

AMP Postop: Intravenous 

injections of cefazolin every 

6hrs for 36 hours; 

Intravenous injections of 

gentamicin every 12hrs for 

36 hours; and oral cefazolin 

every 6hrs for 7 days.

Drain: Used routinely and 

removed on the 2nd day.

Continuous passive motion: 

used every day until 

discharge

Weight bearing: on the 

involved knee was allowed 

form the second 

postoperative day and 

crutches were used as 

needed

Patellar fracture after traumatic 

episode:

Control: 1/162 (0.6%) – treated with 

ORIF with tension band wiring

operation.

 (Rand 1993)

Follow-up: at 3 weeks, 8 

weeks, and 6 months then 

every 6 months thereafter. 

Average was 49 months 

(Range 26-80 months)

Perioperative care: NR

Other notes:

All surgeries performed by 

1 surgeon

The authors report the 

operating room was not 

modern like more 

developed countries with 

better facilities. This study 

was an effort to show that 

antimicrobial impregnated 

cement could be utilized 

as part of a bundle to 

reduce SSI without clean 

air facilities. 
Disclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminated by the Centers for Disease Control and Prevention and should not be 

construed to represent any agency determination or policy. 175

Author

Year

(Data 

Extractor)

Risk of Bias 

Score

Study 

Objective Population and Setting Intervention Results Comments

surgery, any kind of 

lower-extremity 

infection, osteomyelitis, 

or a malignant tumor 

who were being treated 

with immunosuppressive 

agents.

Chiu 

2001 40

(ES)

RCT

1, 5, 10

To evaluate 

the effect of 

antimicrobia

l

(cefuroxime)

impregnate

d cement on 

the 

prevention 

of deep 

infection 

after 

primary 

total knee 

arthroplasty 

(TKA) in 

patients 

with 

diabetes 

mellitus 

(DM).

Number of patients: 

N=78

Patient Characteristics: 

Age; sex; side of 

operation; type of 

diabetes; type of diabetic 

treatment; duration of 

diabetes mellitus; 

tourniquet time; 

operation time, volume 

of blood transfusion; 

preoperative fasting 

blood sugar; preoperative 

“2 hours post meal” 

blood sugar; 

postoperative fasting 

blood sugar, 

postoperative “2 hours 

post meal” blood sugar; 

preoperative knee score; 

and postoperative knee 

score were all analyzed 

and found to be similar 

between groups except 

postoperative knee score 

(HHS-functional)

Age: mean (range)

 Intervention: 72y (56-

90)

Intervention group: n=41 

knees (35 patients-6 Bilateral 

TKA)

Cefuroxime-impregnated 

cement (2g of cefuroxime in 

40 g cement) was utilized for 

fixation of the tibial and 

patellar components only. 

Timing of intervention: Intra 

and post-operatively

Duration of intervention: 

The duration of implantation 

(indefinitely).

Device: Cefuroximeimpregnated cement; pure 

cement without cefuroxime; 

prosthetic knee

Monitoring intervention: 

Patients were examined at 3 

weeks, 8 weeks & 6 months 

post-operatively. Then every 

6 months there-after. Radio 

graphic evaluation at every 

visit & functional evaluation 

(Hospital for Special Surgery 

score) performed at every 

visit starting with the 3rd

postop visit.

Control group: n= 37 knees 

SSI: (range 26-88 months)

Early superficial wound infection:

 Intervention: 1/ 41 (2.4%)

 Control: 1/37 (2.7%)

 P= 0.835

Deep infection

 Intervention: 0/41

 Control: 5/37 (13.5%)

 P=0.021

Relative probability of not developing a 

deep infection in intervention group

0.865 (95%CI 0.769-0.973)

All deep infections were in unilateral 

TKAs

All deep infections were considered late 

(1-6mo postop) and were deemed 

healing satisfactorily until after the first 

follow-up visit.

No deep infections occurred in bilateral 

surgeries.

Other infections: NR

Topic-specific outcomes: 

Deep infections

Type 1 Diabetes: 

1/5 6mo postop 70yoMale

Type 2 Diabetes: 

4/5 (1,2,3 and 6 mo. postop in 67-73yo 

Definitions:

SSI

Classified according to 

(McQueen et al 1990) and 

confirmed by 

measurement of the ESR & 

level of C-reactive protein 

and culture of joint fluid.

Perioperative care: 

Authors report patients 

had poor control of blood 

glucose and the operating 

room was “not modern”. 

Also used 7 day course of a

systemic antimicrobial

because operating 

environment was poor and 

patients were in poor state 

of hygiene. They report 

trying to shorten regimen 

by using antimicrobial

impregnated cement

Other notes: All surgeries 

performed by 1 surgeon

Follow-up: Patients were 

examined at 3 weeks, 8 

weeks & 6 months postoperatively. Then every 6 

months there-after Mean 
Disclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminated by the Centers for Disease Control and Prevention and should not be 

construed to represent any agency determination or policy. 176

Author

Year

(Data 

Extractor)

Risk of Bias 

Score

Study 

Objective Population and Setting Intervention Results Comments

 Control: 69y (54-81)

Gender: m/f (%)

 Intervention: 80/20

 Control: 67/33

Obesity: NR

Comorbidities:

NIDDM/IDDM:

 Intervention: 32/3

 Control: 28/4

Duration of Diabetes: y 

(SD)

 Intervention: 12y (8.7)

 Control: 10y (7.8)

Left/right: (%)

 Intervention: 80/20

 Control: 52/48

Procedures: Total knee 

arthroplasty with 

cementless fixation of the 

femoral component and 

cement fixation (mixing 

method of cement NR) of 

the patellar and tibial 

components. 

Indications: 

Osteoarthritis

Setting: 1 hospital

Location: Taiwan, China

Dates: 1993-1998

Inclusion Criteria: 

Patients with diabetes 

mellitus undergoing total 

knee arthroplasty

Exclusion Criteria: 

Patients with rheumatoid 

arthritis, psoriasis, 

(32 patients-5 Bilateral TKA)

Cement did not contain 

cefuroxime. Only the tibial 

and patellar components 

were fixed with cement.

Bilateral TKAs: cefuroximeimpregnated cement used 

on one side (Intervention 

n=6) and not the other 

(Control n=5). All 

undertaken in sequence 

under difference anesthetics

Standard preventive 

measures: 

Environmental: No 

ultraviolet light for 

disinfection; no laminar flow 

nor body-exhaust suits were 

used.

AMP Preop: intravenous 

bolus injections of cefazolin 

& gentamicin.

AMP Postop: Intravenous 

injections of cefazolin every 

6hrs for 36 hours; 

Intravenous injections of 

gentamicin every 12hrs for 

36 hours; and oral cefazolin 

every 6hrs for 7 days.

Drain: (not vacuum) Were 

used for 36 hours

Continuous passive motion: 

Prescribed immediately and 

used every day until 

discharge

Weight bearing: on the 

Males)

Infecting organism in deep infections:

Staphylococcus aureus: 3/5

Staphylococcus epidermis: 2/5

Postoperative knee score (HHSfunctional)

 Intervention: 91 (SD 2.8)

 Control: 86 (SD 9.2)

 P= 0.0093

Caused by five cases of deep infection in 

control group

Re-operations: Both early superficial 

wound infections were successfully 

treated with debridement and 

intravenous antimicrobials administered 

for 1 week and orally for another week.

Deep Infections

3/5 – radical debridement was followed 

by four weeks of intravenous 

antimicrobials and then two months of 

oral antimicrobials

2/5 –deep SSIs underwent two stage reimplantation procedures. 

Length of stay: Mean lengths was 8 

days (Range 5-14 days)

Mortality: NR

Adverse events: NR

follow up was 50 months 

(Range 26-88 months)
Disclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminated by the Centers for Disease Control and Prevention and should not be 

construed to represent any agency determination or policy. 177

Author

Year

(Data 

Extractor)

Risk of Bias 

Score

Study 

Objective Population and Setting Intervention Results Comments

previous knee surgery, 

any type of infection of 

the lower limb, 

osteomyelitis, malignant 

tumor or those who were 

undergoing 

immunosuppressive 

therapy.

operated knee was allowed 

immediately & crutches used 

as needed.

B. How effective are prosthesis surface modifications (i.e., antimicrobial coating, galvanic couples, “printing” technologies, and 

nanotechnology)? Our search did not identify in vivo studies that evaluated the safety and effectiveness of prosthesis modifications and 

their impact on biofilm formation and the risk of SSI.

C. How effective are vaccines? Our search did not identify in vivo studies that evaluated the safety and effectiveness of vaccines and their 

impact on biofilm formation and the risk of SSI.

D. How effective are other biofilm control agents (e.g., biofilm dispersants, quorum-sensing inhibitors, novel antimicrobial agents)? Our 

search did not identify in vivo studies that evaluated the safety and effectiveness of biofilm control agents and their impact on biofilm 

formation and the risk of SSI.
Disclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminated by the Centers for Disease Control and Prevention and should not be 

construed to represent any agency determination or policy. 178

RISK OF BIAS ASSESSMENTS OF STUDIES Q20

Randomized Controlled Trials

Author

Year (RefID)

K

Q

Described 

as 

randomize

d

Randomizatio

n 

appropriately 

performed

Described 

as 

doubleblind

Outcom

e 

assessor 

blinded

Study 

participant 

blinded

Investigato

r blinded

Attrition 

described

Attrition smaller 

than 10-15% of 

assigned patients

Attrition 

appropriately 

analyzed

Funding source(s) 

disclosed and no 

obvious conflict of 

interest

Overall 

Risk of 

Bias

Question 20 Biofilm

Chiu

2002 39 20    Moderate

Chiu

2001 40 20    Moderate
Disclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminated by the Centers for Disease Control and Prevention and should not be 

construed to represent any agency determination or policy. 179

SECTION 3: EVALUATION OF THE RISK OF BIAS OF AN INDIVIDUAL STUDY

Instructions

Check off each item in the appropriate checklist if it is present in the study

Divide the total number of checked items by the total number of questions on the checklist 

Rate the risk of bias as follows: 

% of Items Present in Study Risk of Bias

< 25% High

> 25% and < 50% Moderate

> 50% Low

CHECKLIST FOR SYSTEMATIC REVIEWS

1) Search terms described

2) Databases searched described and two or more databases searched

3) Inclusion/exclusion criteria described

4) Number of included/excluded studies along with reasons of exclusion described

5) Studies screened by two independent reviewers for inclusion

6) Data extracted by two independent reviewers

7) Individual study quality assessed

8) Heterogeneity between study results assessed qualitatively and/or quantitatively

9) Publication bias assessed

10) Characteristics of included studies reported in evidence table

11) Funding source(s) disclosed and no obvious conflict of interest

CHECKLIST FOR RANDOMIZED CONTROLLED TRIALS

1) Described as randomized

2) Randomization appropriately performed (e.g. random number table, computerized scheme)

3) Described as double-blind

4) Outcome assessor blinded

5) Study participant blinded (e.g. interventions identical in appearance)

6) Investigator blinded (e.g. opaque sealed envelopes)

7) Attrition described

8) Attrition smaller than 10-15% of assigned patients

9) Attrition appropriately analyzed (e.g. intention to treat analysis)

10) Funding source(s) disclosed and no obvious conflict of interest
Disclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminated by the Centers for Disease Control and Prevention and should not be 

construed to represent any agency determination or policy. 180

CHECKLIST FOR OTHER CONTROLLED STUDIES

1) All study groups derived from similar source/reference populations

2) Attrition not significantly different across study groups

3) The measure of exposure is valid

4) The measure of outcome is valid

5) Investigators blinded to endpoint assessment

6) Potential confounders identified

7) Statistical adjustment for potential confounders done

8) Funding source(s) disclosed and no obvious conflict of interest

TRANSLATING RISK OF BIAS INTO GRADE TABLES

When the risk of bias was rated as “High” for >75% of studies making up the evidence base for a given outcome, one point was deducted for Study Quality in the GRADE table.
Disclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminated by the Centers for Disease Control and Prevention and should not be 

construed to represent any agency determination or policy. 181

SECTION 4: EVIDENCE TABLE EXTRACTION TEMPLATES

1. SYSTEMATIC REVIEW (SR) EXTRACTION TEMPLATE

Author

Year

(Ref ID_

Data 

Extractor

Study 

Design

Quality 

Score

Study Objective Population and Setting Intervention(s) Results (by intervention) Comments

SR

Quality 

Score

Narrative Study types and number

Number of total patients in 

the review

Inclusion criteria

Exclusion criteria

Databases searched

Aggregate summary score 

Intervention group

Timing of intervention

Duration of intervention

Device

Monitoring intervention

Control group

Standard preventive measures 

SSI 

Other infections

Topic-specific outcomes

Re-operations 

Length of stay

Mortality

Adverse events

Definitions 

Perioperative care 

Other notes

Follow up

2. RANDOMIZED CONTROLLED TRIAL (RCT) EXTRACTION TEMPLATE

Author

Year

(Ref ID_

Data 

Extractor

Study 

Design

Quality 

Score

Study Objective Population and Setting Intervention Results Comments

RCT

Quality 

Score

Narrative Number of patients

Patient Characteristics

·Age

·Gender

·Obesity

·Comorbidities

Procedures

Indications

Setting

Location

Dates

Inclusion Criteria

Exclusion Criteria

Intervention group

Timing of intervention

Duration of intervention

Device/agent

Monitoring intervention

Control group

Standard preventive measures 

SSI 

Other infections

Topic-specific outcomes

Reoperations 

Length of stay

Mortality

Adverse events

Definitions 

Perioperative care 

Other notes

Follow-up 
Disclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminated by the Centers for Disease Control and Prevention and should not be 

construed to represent any agency determination or policy. 182

3. OTHER CONTROLLED STUDIES EXTRACTION TEMPLATE

Author

Year

(Ref ID)

Data 

Extractor

Study Design

Quality Score

Study 

Objective Population and Setting Intervention Results Comments

Study Design

Quality Score

Narrative Number of patients:

Patient Characteristics: 

·Age: 

·Gender: 

·Obesity: 

·Comorbidities: 

Procedures: 

Indications: 

Setting: 

Location: 

Dates: 

Inclusion Criteria: 

Exclusion Criteria: 

Intervention group: 

Timing of intervention: 

Duration of intervention: 

Device/agent: 

Monitoring intervention: 

Control group: 

Standard preventive measures: 

SSI () 

Other infections: 

Topic-specific outcomes: 

Reoperations: 

Length of stay: 

Mortality: 

Adverse events: 

Definitions: 

Perioperative care: 

Analytical 

methodology:

Other notes: 

Follow-up: 
Disclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminated by the Centers for Disease Control and Prevention and should not be 

construed to represent any agency determination or policy. 183

SECTION 5: STUDY TYPE DETERMINATION ALGORITHM

Adapted from: Hartling et. al. 201041

Was there some kind of comparison? Case series: the study describes the clinical course of a group of individuals with a particular diagnosis, condition, or exposure; if the group is <5 individuals, it is called a case report instead

Was information on the intervention/ exposure and the outcome(s) gathered at the same time? Cross-sectional study: the study assesses the exposure/intervention and outcome(s) concurrently. Temporal cause and effect cannot be determined.

Did the investigators have control over study conditions such as: allocation to groups, timing of interventions/ exposures, and timing of outcome assessments?

Were interventions/ exposures assigned randomly?

Randomized controlled trial Non-randomized controlled trial

No Yes

No

Yes

Yes

Yes

No Did all of the enrolled patients receive the same intervention/ exposure? No

No

Were groups defined by the intervention/ exposure? Was the intervention/ exposure information collected prior to the outcome occurring? No Case-control study: participants are selected based on known outcome. Exposure/intervention status is compared between groups of those who have the outcome of interest (cases) and those who do not have the outcome of interest (controls). Nested case-control study: Participants are selected from a single-source population (consecutive patients from the same setting, all patients during a particular time period) and exposure/intervention status noted at baseline. The participants are then followed over time and the outcome of interest is noted.

No

Yes

Yes

Were there more than 3 measurements of outcomes both before and after the intervention/ exposure?

Pre-post study: the outcome of interest is measured both before and after the intervention/exposure in the same group of individuals. Interrupted time series: multiple observations over time in the same group of individuals are “interrupted” by an exposure or intervention No

Yes

Yes Were participants selected from a single-source (consecutive patients from the same setting, all patients during a particular time period)? Yes Cohort study: can be either prospective or retrospective. Individuals are identified on the basis of a common feature (such as setting) and are classified according to exposure/intervention status, and then followed over time to measure outcomes.

Were the groups concurrent? No Non-concurrent cohort study: groups of patients are identified on the basis of common features at different time points. The participants are classified according to exposure/intervention status, and then followed over time to measure outcomes No

Yes

Were there more than 3 measurements of outcomes both before and after the intervention/ exposure? Yes Controlled interrupted time series: multiple observations over time are “interrupted” by an exposure or intervention in a group compared to a group with no intervention/ exposure

No Controlled pre-post study: the outcome of interest is measured both before and after an intervention/exposure in a group compared to group with no intervention/ exposure
Disclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminated by the Centers for Disease Control and Prevention and should not be 

construed to represent any agency determination or policy. 184

SECTION 6: REFERENCES

1. Frietsch T, Karger R, Scholer M, et al. Leukodepletion of autologous whole blood has no impact on perioperative infection rate and length of hospital 

stay. Transfusion. Oct 2008;48(10):2133-2142.

2. Frietsch T, Krombholz K, Tolksdorf B, Nebe T, Segiet W, Lorentz A. Cellular immune response to autologous blood transfusion in hip arthroplasty: whole 

blood versus buffy coat-poor packed red cells and fresh-frozen plasma. Vox Sanguinis. Oct 2001;81(3):187-193.

3. Innerhofer P, Klingler A, Klimmer C, Fries D, Nussbaumer W. Risk for postoperative infection after transfusion of white blood cell-filtered allogeneic or 

autologous blood components in orthopedic patients undergoing primary arthroplasty. Transfusion. Jan 2005;45(1):103-110.

4. Rosencher N, Kerkkamp HEM, Macheras G, et al. Orthopedic Surgery Transfusion Hemoglobin European Overview (OSTHEO) study: blood management 

in elective knee and hip arthroplasty in Europe. Transfusion. Apr 2003;43(4):459-469.

5. Weber EW, Slappendel R, Prins MH, van der Schaaf DB, Durieux ME, Strumper D. Perioperative blood transfusions and delayed wound healing after hip 

replacement surgery: effects on duration of hospitalization. Anesthesia and Analgesia. May 2005;100(5):1416-1421, table of contents.

6. Llewelyn CA, Taylor RS, Todd AAM, et al. The effect of universal leukoreduction on postoperative infections and length of hospital stay in elective 

orthopedic and cardiac surgery. Transfusion. Apr 2004;44(4):489-500.

7. Pedersen AB, Mehnert F, Overgaard S, Johnsen SP. Allogeneic blood transfusion and prognosis following total hip replacement: a population-based 

follow up study. BMC Musculoskeletal Disorders. Dec 29 2009;10.

8. del Trujillo MM, Carrero A, Munoz M. The utility of the perioperative autologous transfusion system OrthoPAT (R) in total hip replacement surgery: a 

prospective study. Archives of Orthopaedic and Trauma Surgery. Oct 2008;128(10):1031-1038.

9. Borghi B, Casati A, Anaesthesia tRSGoO. Incidence and risk factors for allogenic blood transfusion during major joint replacement using an integrated 

autotransfusion regimen. European Journal of Anaesthesiology. Jul 2000;17(7):411-417.

10. Momohara S, Kawakami K, Iwamoto T, et al. Prosthetic joint infection after total hip or knee arthroplasty in rheumatoid arthritis patients treated with 

nonbiologic and biologic disease-modifying antirheumatic drugs. Modern Rheumatology. Oct 2011;21(5):469-475.

11. Kawakami K, Ikari K, Kawamura K, et al. Complications and features after joint surgery in rheumatoid arthritis patients treated with tumour necrosis 

factor-alpha blockers: perioperative interruption of tumour necrosis factor-alpha blockers decreases complications? Rheumatology. Feb 2010;49(2):341-

347.

12. Hirano Y, Kojima T, Kanayama Y, et al. Influences of anti-tumour necrosis factor agents on postoperative recovery in patients with rheumatoid arthritis. 

Clinical Rheumatology. May 2010;29(5):495-500.

13. Perhala RS, Wilke WS, Clough JD, Segal AM. Local infectious complications following large joint replacement in rheumatoid arthritis patients treated with 

methotrexate versus those not treated with methotrexate. Arthritis & Rheumatism. Feb 1991;34(2):146-152.
Disclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminated by the Centers for Disease Control and Prevention and should not be 

construed to represent any agency determination or policy. 185

14. Bridges SL, Jr., Lopez-Mendez A, Han KH, Tracy IC, Alarcon GS. Should methotrexate be discontinued before elective orthopedic surgery in patients with 

rheumatoid arthritis? J Rheumatol. Jul 1991;18(7):984-988.

15. Carpenter MT, West SG, Vogelgesang SA, Casey Jones DE. Postoperative joint infections in rheumatoid arthritis patients on methotrexate therapy. 

Orthopedics. Mar 1996;19(3):207-210.

16. Bongartz T, Halligan CS, Osmon DR, et al. Incidence and risk factors of prosthetic joint infection after total hip or knee replacement in patients with 

rheumatoid arthritis. Arthritis & Rheumatism-Arthritis Care & Research. Dec 15 2008;59(12):1713-1720.

17. Papavasiliou AV, Isaac DL, Marimuthu R, Skyrme A, Armitage A. Infection in knee replacements after previous injection of intra-articular steroid. Journal 

of Bone and Joint Surgery-British Volume. Mar 2006;88B(3):321-323.

18. Desai A, Ramankutty S, Board T, Raut V. Does intraarticular steroid infiltration increase the rate of infection in subsequent total knee replacements? 

Knee. Aug 2009;16(4):262-264.

19. Sreekumar R, Venkiteswaran R, Raut V. Infection in primary hip arthroplasty after previous steroid infiltration. International Orthopaedics. Feb 

2007;31(1):125-128.

20. McIntosh AL, Hanssen AD, Wenger DE, Osmon DR. Recent intraarticular steroid injection may increase infection rates in primary THA. Clinical 

Orthopaedics and Related Research. Oct 2006;451:50-54.

21. Kaspar S, de Beer JD. Infection in hip arthroplasty after previous injection of steroid. Journal of Bone and Joint Surgery-British Volume. Apr 

2005;87B(4):454-457.

22. Turpie AGG, Bauer KA, Eriksson BL, Lassen MR, Studies SCotPOP. Fondaparinux vs enoxaparin for the prevention of venous thromboembolism in major 

orthopedic surgery - A meta-analysis of 4 randomized double-blind studies. Archives of internal medicine. Sep 9 2002;162(16):1833-1840.

23. Bauer KA, Eriksson BI, Lassen MR, Turpie AG, Study SCotPiMKS. Fondaparinux compared with enoxaparin for the prevention of venous 

thromboembolism after elective major knee surgery. The New England journal of medicine. Nov 1 2001;345(18):1305-1310.

24. Eriksson BI, Bauer KA, Lassen MR, Turpie AG, Study SCotPiH-FS. Fondaparinux compared with enoxaparin for the prevention of venous 

thromboembolism after hip-fracture surgery. The New England journal of medicine. Nov 1 2001;345(18):1298-1304.

25. Lassen MR, Bauer KA, Eriksson BI, Turpie AG, Committee EPESSS. Postoperative fondaparinux versus preoperative enoxaparin for prevention of venous 

thromboembolism in elective hip-replacement surgery: a randomised double-blind comparison. Lancet. May 18 2002;359(9319):1715-1720.

26. Turpie AG, Bauer KA, Eriksson BI, Lassen MR, Committee PSS. Postoperative fondaparinux versus postoperative enoxaparin for prevention of venous 

thromboembolism after elective hip-replacement surgery: a randomised double-blind trial. Lancet. May 18 2002;359(9319):1721-1726.

27. Eriksson BI, Borris LC, Friedman RJ, et al. Rivaroxaban versus enoxaparin for thromboprophylaxis after hip arthroplasty. The New England journal of 

medicine. Jun 26 2008;358(26):2765-2775.

28. Kakkar AK, Brenner B, Dahl OE, et al. Extended duration rivaroxaban versus short-term enoxaparin for the prevention of venous thromboembolism after 

total hip arthroplasty: a double-blind, randomised controlled trial. Lancet. Jul 5 2008;372(9632):31-39.
Disclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminated by the Centers for Disease Control and Prevention and should not be 

construed to represent any agency determination or policy. 186

29. Lassen MR, Ageno W, Borris LC, et al. Rivaroxaban versus enoxaparin for thromboprophylaxis after total knee arthroplasty. The New England journal of 

medicine. Jun 26 2008;358(26):2776-2786.

30. Turpie AG, Lassen MR, Davidson BL, et al. Rivaroxaban versus enoxaparin for thromboprophylaxis after total knee arthroplasty (RECORD4): a randomised 

trial. Lancet. May 16 2009;373(9676):1673-1680.

31. Patel VP, Walsh M, Sehgal B, Preston C, Dewal H, Di Cesare PE. Factors associated with prolonged wound drainage after primary total hip and knee 

arthroplasty. Journal of Bone and Joint Surgery-American Volume. Jan 2007;89A(1):33-38.

32. Asensio A, Antolin FJ, Sanchez-Garcia JM, et al. Timing of DVT prophylaxis and risk of postoperative knee prosthesis infection. Orthopedics. Nov 

2010;33(11):800.

33. Bozic KJ, Vail TP, Pekow PS, Maselli JH, Lindenauer PK, Auerbach AD. Does aspirin have a role in venous thromboembolism prophylaxis in total knee 

arthroplasty patients? Journal of Arthroplasty. Oct 2010;25(7):1053-1060.

34. Sachs RA, Smith JH, Kuney M, Paxton L. Does anticoagulation do more harm than good? A comparison of patients treated without prophylaxis and 

patients treated with low-dose warfarin after total knee arthroplasty. Journal of Arthroplasty. Jun 2003;18(4):389-395.

35. Parvizi J, Ghanem E, Joshi A, Sharkey PF, Hozack WJ, Rothman RH. Does "excessive" anticoagulation predispose to periprosthetic infection? Journal of 

Arthroplasty. Sep 2007;22(6):24-28.

36. Miner AL, Losina E, Katz JN, Fossel AH, Platt R. Deep infection after total knee replacement: impact of laminar airflow systems and body exhaust suits in 

the modern operating room. Infection Control and Hospital Epidemiology: The Official Journal of the Society of Hospital Epidemiologists of America. Feb 

2007;28(2):222-226.

37. Hooper GJ, Rothwell AG, Frampton C, Wyatt MC. Does the use of laminar flow and space suits reduce early deep infection after total hip and knee 

replacement? The ten-year results of the New Zealand Joint Registry. Journal of Bone and Joint Surgery-British Volume. Jan 2011;93B(1):85-90.

38. Pasquarella C, Pitzurra O, Herren T, Poletti L, Savino A. Lack of influence of body exhaust gowns on aerobic bacterial surface counts in a mixedventilation operating theatre. A study of 62 hip arthroplasties. The Journal of hospital infection. May 2003;54(1):2-9.

39. Chiu FY, Chen CM, Lin CF, Lo WH. Cefuroxime-impregnated cement in primary total knee arthroplasty: a prospective, randomized study of three hundred 

and forty knees. The Journal of bone and joint surgery. American volume. May 2002;84-A(5):759-762.

40. Chiu FY, Lin CF, Chen CM, Lo WH, Chaung TY. Cefuroxime-impregnated cement at primary total knee arthroplasty in diabetes mellitus. A prospective, 

randomised study. The Journal of bone and joint surgery. British volume. Jul 2001;83(5):691-695.

41. Agency for Healthcare Research and Quality, Hartling L, Bond K, et al. Developing and Testing a Tool for the Classification of Study Designs in Systematic 

Reviews of Interventions and Exposures 2010; AHRQ Publication No. 11-EHC-007. :http://www.ncbi.nlm.nih.gov/books/NBK52670/; Last Accessed: 

August 26, 2013.