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

c onstrued to represent any agency determination or policy. 1



# APPENDIX 2 : PROSTHETIC JOINT ARTHROPLASTY SURGERY
Draft Guideline for the Prevention of Surgical Site InfectionsDisclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminate d by the Centers for Disease Control and Prevention and should not be

c onstrued to represent any agency determination or policy. 2 

## Table of Contents

SECTION 1: SEARCH ST RATEGIES

................................ ................................ ................................ ................................ ................................ ........................ 4

SECTION A: ORTHO SEARCH

................................ ................................ ................................ ................................ ................................ ........................... 4
SECTION B. TARGETED SEARCH: TRANSFUSION

................................ ................................ ................................ ................................ ............................. 6
SECTION C. TARGETED SEARCH: IMMUNOSUPPRE SSIVE THERAPY

................................ ................................ ................................ ............................. 11
SECTION D. TARGETED SEARCH: ANTICOAGULAT ION

................................ ................................ ................................ ................................ .................. 17
SECTION E. TARGETED SEARCH: SURGICAL ATT IRE

................................ ................................ ................................ ................................ ...................... 21
SECTION F . TARGETED SEARCH: A NTIMICROBIAL PROPHYL AXIS WITH A DRAIN

................................ ................................ ................................ ........ 28
SECTION G. TARGETED SEARCH: BIOFILM

................................ ................................ ................................ ................................ ................................ .... 32

SECTION 2: EVIDENCE, GRADE AND RISK OF BI AS ASSESSMENT TABLES

................................ ................................ ................................ ......................... 37

Q11 BLOOD TRANSFUSION

................................ ................................ ................................ ................................ ................................ ........................... 37

GRADE TABLE Q11

................................ ................................ ................................ ................................ ................................ ................................ .... 37

EVIDENCE TABLE Q11

................................ ................................ ................................ ................................ ................................ ................................ 49

RISK OF BIAS ASSESSM ENTS OF STUDIES Q11

................................ ................................ ................................ ................................ .......................... 85

Q12

- 16 SYSTEMIC IMMUNOSUPPRESSIVE THERAPY

................................ ................................ ................................ ................................ .................... 86

GRADE TABLE Q12

- 16

................................ ................................ ................................ ................................ ................................ ............................... 86

EVIDENCE TABLE Q12

- 16

................................ ................................ ................................ ................................ ................................ .......................... 95

RISK OF BIAS ASSESSM ENTS OF STU DIES Q12

- 16

................................ ................................ ................................ ................................ ................... 121

Q17 ANTICOAGULATION

................................ ................................ ................................ ................................ ................................ ............................. 122

GRADE TABLE Q17

................................ ................................ ................................ ................................ ................................ ................................ .. 122

EVIDENCE TABLE Q17

................................ ................................ ................................ ................................ ................................ .............................. 128

RISK OF BIAS ASSESSM ENTS OF STUDIES Q17

................................ ................................ ................................ ................................ ........................ 158

Q18 ORTHOPAEDIC SPACE SUIT

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

c onstrued to represent any agency determination or policy. 3 

### GRADE TABLE Q18

................................ ................................ ................................ ................................ ................................ ................................ .. 159

EVIDENCE TABLE Q18

................................ ................................ ................................ ................................ ................................ .............................. 161

RISK OF BIAS ASSESSM ENTS OF STUDIES Q18

................................ ................................ ................................ ................................ ........................ 170

Q20 BIOFILM

................................ ................................ ................................ ................................ ................................ ................................ ............... 171

GRADE TABLE Q20

................................ ................................ ................................ ................................ ................................ ................................ .. 171

EVIDENCE TABLE Q20

................................ ................................ ................................ ................................ ................................ .............................. 173

RISK OF BIAS ASSESSM ENTS OF STUDIES Q20

................................ ................................ ................................ ................................ ........................ 178

SECTION 3: EVALUATION OF THE RISK OF BIAS OF AN I NDIVIDUAL STUDY

................................ ................................ ................................ ................... 179

CHECKLIST FOR SYSTEMATIC REVIEWS

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

................................ ................................ ................................ ................................ ................. 179
CHECKLIST F OR OTHER CONTROLLED STUDIES

................................ ................................ ................................ ................................ .......................... 180

SECTION 4: EVIDENCE TABLE EXTRACTION TEM PLATES

................................ ................................ ................................ ................................ ................ 181

1. SYSTEMATIC REVIEW (SR) EXTRACTION TEMPLATE

................................ ................................ ................................ ................................ ............... 181
2. RANDOMIZED CONTRO LLED TRIAL (RCT) EXT RACTION TEMPLATE

................................ ................................ ................................ ....................... 181
3. OTHER CONTROLLED STUDIES EXTRACTION TEMPLATE

................................ ................................ ................................ ................................ ........ 182

SECTION 5: STUDY TYP E DETERMINATION ALGO RITHM

................................ ................................ ................................ ................................ ................ 183

SECTION 6: REFERENCE S

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

c onstrued 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 26,888Disclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminate d by the Centers for Disease Control and Prevention and should not be

c onstrued 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 infec tion'/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* o r 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 1,059Disclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminate d by the Centers for Disease Control and Prevention and should not be

c onstrued to represent any agency determination or policy. 6 

# S ECTION 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. 164,609Disclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminate d by the Centers for Disease Control and Prevention and should not be

c onstrued 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 1,784,999Disclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminate d by the Centers for Disease Control and Prevention and should not be

c onstrued 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 (‘o rthopedic

surgery’/exp and ‘joint’/exp) 603,883

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

c onstrued 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 ‘s election 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 93,355Disclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminate d by the Centers for Disease Control and Prevention and should not be

c onstrued 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 ‘rand omly alloc ated’ 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 6Disclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminate d by the Centers for Disease Control and Prevention and should not be

c onstrued to represent any agency determination or policy. 11 

# S ECTION C

. TARGETED SEARCH : IMMUNOSUPPRESSIVE TH ERAPY

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

c onstrued 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. 2,196Disclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminate d by the Centers for Disease Control and Prevention and should not be

c onstrued 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 s tudies)).tw. or

cohort analy$.tw. or (Follow up adj (study or studies)).tw. or (observational adj (study or studies)).tw. or Lon gitudinal.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. 90,322Disclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminate d by the Centers for Disease Control and Prevention and should not be

c onstrued 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’/e xp 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 (fol low 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 44,495Disclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminate d by the Centers for Disease Control and Prevention and should not be

c onstrued 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 ‘s election 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 co ntrolled 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 ‘rand omly allocated’
or ‘allo cated 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’ o r ‘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 ‘intraar ticular 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 REVIEWSDisclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminate d by the Centers for Disease Control and Prevention and should not be

c onstrued 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 cyt oxan or

tnf or "tumor necrosis factor*" or (intra

- articular" and inject*)) and (surgery or surgical* or operat*) and (joint* or art hroplast* or prosthe* or implant*) in Title, Abstract or Keywords 21Disclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminate d by the Centers for Disease Control and Prevention and should not be

c onstrued to represent any agency determination or policy. 17 

# S ECTION 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. 13,342Disclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminate d by the Centers for Disease Control and Prevention and should not be

c onstrued 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. 2,135Disclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminate d by the Centers for Disease Control and Prevention and should not be

c onstrued 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



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

c onstrued 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 replace ment’ or (‘orthopedic

surgery’/exp and ‘joint’/exp) 603,883

8 6 and 7 69,054

9 ‘heparin’/ex p or ‘warfarin’/exp or ‘acetylsalicylic acid’/exp or ‘anticoagulant agent’/exp or ‘antithrombotic agent’/exp or anticoagul* o r ‘low

dose 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 4 4,495

13 ‘reference lists’ or bibliograph$ or ‘hand search$’ or ‘manual search$’ or ‘relevant journals’ or ‘data extraction’/exp or ‘s election 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 b lind procedure’/exp 541,923Disclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminate d by the Centers for Disease Control and Prevention and should not be

c onstrued 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 alloca tion’ 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’ o r ‘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 ‘p ost

- 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



# S ECTION E

. TARGETED SEARCH : SURGICAL ATTIRE

MEDLINE

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

c onstrued 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 1,003,206Disclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminate d by the Centers for Disease Control and Prevention and should not be

c onstrued 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. 20,833Disclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminate d by the Centers for Disease Control and Prevention and should not be

c onstrued 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 ‘s election 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. 3Disclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminate d by the Centers for Disease Control and Prevention and should not be

c onstrued 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 ‘rand omly alloc ated’ 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 ‘retrospectiv e 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 ‘p ost

- 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 2,660,483Disclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminate d by the Centers for Disease Control and Prevention and should not be

c onstrued 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 su it’ 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 21Disclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminate d by the Centers for Disease Control and Prevention and should not be

c onstrued 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 7Disclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminate d by the Centers for Disease Control and Prevention and should not be

c onstrued to represent any agency determination or policy. 28 

# S ECTION F

. TARGETED SEARCH : ANTIMICROBIAL PROPHYLAXIS WITH A D RAIN

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/ 253,375Disclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminate d by the Centers for Disease Control and Prevention and should not be

c onstrued 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"/ 118,653Disclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminate d by the Centers for Disease Control and Prevention and should not be

c onstrued 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 s tudies)).tw. or

cohort analy$.tw. or (Follow up adj (study or studies)).tw. or (observational adj (study or studies)).tw. or Lon gitudinal.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



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

c onstrued 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 ‘s election 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 ‘rand omly allocated’ or ‘allocated randomly’ or allocated and adj2 and random$ or single and blind$ or double and b lind$ 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 ‘lett er’/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’/e xp 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 (fol low and up and adj 115,089Disclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminate d by the Centers for Disease Control and Prevention and should not be

c onstrued 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 ‘inf ection’/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 replace ment’ or (‘orthopedic

surgery’/exp and ‘joint’/exp) 603,883

32 30 and 31 69,062

3 3 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



# S ECTION G

. TARGETED SEARCH : BIOFILM

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

c onstrued 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, Staphyloco ccus

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/ 247,358Disclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminate d by the Centers for Disease Control and Prevention and should not be

c onstrued 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 controlle d 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"/ 114,791Disclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminate d by the Centers for Disease Control and Prevention and should not be

c onstrued 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 studi es)).tw. or

cohort analy$.tw. or (Follow up adj (study or studies)).tw. or (observational adj (study or studies)).tw. or Longitudi nal.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



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

c onstrued 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’/e xp 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 8Disclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminate d by the Centers for Disease Control and Prevention and should not be

c onstrued to represent any agency determination or policy. 37 

# SECTION 2 : E VIDENCE
, GRADE AND RISK OF BIAS ASSESSM ENT TABLES

Q 11 BLOOD TRANSFUSION

GRADE TABLE Q 11

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 Quality Consistency Directness Precision Publication Bias Large Magnitude

Dose - response Confounders

Q 11 . 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 wi th 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

Q 11 A. 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 m eta

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

c onstrued 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 Quality Consistency Directness Precision Publication Bias Large Magnitude

Dose - response Confounders

Reoperation
due to
wound
infection* 1 OBS 7  In a large retrospective OBS (N=28,087) of primary THA, using a propensity score matche d 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 k nee 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 WB C 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 pop ulation) 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 group s (3.3% vs. 2.0 %); p=0.47 Low 0 0 0

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

c onstrued 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 Quality Consistency Directness Precision Publication Bias Large Magnitude

Dose - response Confounders

Wound

healing
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 study 3 (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 study 6 , 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 study 4 (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% C I: 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 differen ce 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 2 of hip arthroplasties subanalyis High 0 0 0

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

c onstrued 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 Quality Consistency Directness Precision Publication Bias Large Magnitude

Dose - response Confounders

(N=58), no infections were observed in either group: 0/49 vs. 0/9, but study was designed to
evaluate transfusion induc ed 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 st udy 4 of 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 study 3 (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”
transfusi ons: 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 ModerateDisclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminate d by the Centers for Disease Control and Prevention and should not be

c onstrued 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 Quality Consistency Directness Precision Publication Bias Large Magnitude

Dose - response Confounders

Autologous
Whole
Blood vs. No
Transfusion SSI* 1 RCT 2  In a small RCT of THA, subanalysis of 34 patients,
no infection s 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) f ound 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

– 0.9 2; 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 sal vage 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 (10794 2 ) 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 (10804 3 ) (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 LowDisclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminate d by the Centers for Disease Control and Prevention and should not be

c onstrued 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 Quality Consistency Directness Precision Publication Bias Large Magnitude

Dose - response Confounders

Autologous
“lower WBC
content” vs. Autologous ”higher WBC
content” SSI* 2 RCT 2

, 1  In a small RCT 2 of hip arthrop lasties (N=49), no infections were observed in either group at 7 day follow up

. The study was designed to evaluate
transfusion ind uced immunomodulation, not SSI.

 In a large RCT 1 of 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 Mo derate

Post

operative salvage only

vs. Autologous
Donated
blood

- only SSI* 1 OBS 4  In one larg e 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,

tra nsfusion 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 ModerateDisclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminate d by the Centers for Disease Control and Prevention and should not be

c onstrued 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 Quality Consistency Directness Precision Publication Bias Large Magnitude

Dose - response Confounders

Allogeneic ±

WBC depleted vs. Autologous

Not WBC depleted SSI* 2 OBS 4

, 8  Allogeneic NOT WBC Depleted: I n a large prospective study 4 of 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 study 8
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 TransfusionDisclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminate d by the Centers for Disease Control and Prevention and should not be

c onstrued 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 Quality Consistency Directness Precision Publication Bias Large Magnitude

Dose - response Confounders

Both Autologous
and Allogeneic (Any) vs. No
Transfusion SSI* 1 RCT 1

2 OBS 4

, 3  No dif ference in post

- hoc subanalysis 1 (N=470) :

0 of 39 transfused vs. 1.6% of 431 not transfused (p=0.82)

 One study 4 No 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. 1/10 1 (1%) High 0 0 0

- 1 0 0 0 0 Moderate Moderate

Both Autologous
and Allogeneic

vs. Autologous

only 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

compa red with autologous (buffy coat depleted

only) blood alone. Statistical testing was not possible (data presented in graph format).

 In 1 study 4 SSI= 8/329 (2%) vs. 11/1311 (1%); p=0.02 Low 0 0 0 0 0 0 0 0 Low Low

Q 11 B. 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 4 Increased risk among revisions: 303/362 (84%) vs. 2112/3118 (68%); p<0.001

 In one observ ational study 6 Increased risk among revisions: 274/ 350(78%) vs. 969/2555(38%); p<0.001 Low 0 0 0 0 0 +1 0 0 Moderate ModerateDisclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminate d by the Centers for Disease Control and Prevention and should not be

c onstrued 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 Quality Consistency Directness Precision Publication Bias Large Magnitude

Dose - response Confounders

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 only 4 : More allogeneic only transfusions among transfused revision hips as compared to primary hip arthroplastie s: 115/252 (46%) vs. 503/1405 (36%); p=0.003

 Autologous only 4 : More autologous only transfusions among tran sfused 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 OBS 4 Higher risk among revision THAs: 54/252 (21%) vs. 165/1405 (12%); p<0.001

 One OBS 9 Higher risk among revision THAs : 76/388 (20%) vs. 159/2016 (8%); p=0.0005 Low 0 0 0 0 0 0 0 0 Low LowDisclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminate d by the Centers for Disease Control and Prevention and should not be

c onstrued 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 Quality Consistency Directness Precision Publication Bias Large Magnitude

Dose - response Confounders

Calculated
blood loss 2 OBS 4

, 9  Meta

- analysis 2 OBS studies: significantly higher
calculated blood loss in revisio n 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 ml 4 ; 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 LowDisclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminate d by the Centers for Disease Control and Prevention and should not be

c onstrued 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 Quality Consistency Directness Precision Publication Bias Large Magnitude

Dose - response Confounders

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 only 4 : 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) procedures 4

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

c onstrued 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 Quality Consistency Directness Precision Publication Bias Large Magnitude

Dose - response Confounders

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

c onstrued to represent any agency determination or policy. 49 

## EVIDENCE TABLE Q 11

Q 11 . 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 assoc iated with more complex cases ?

Author

Year ( Data

Extractor ) Risk of Bias

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

Fri e tsch

2008 1
( SIBT ) R CT

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 (LD

AWB)

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 10 6
per unit and mean red blood cell loss (RB C) 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 puru lent 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 exudat e, 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 pa rt). Each of the additional criteria ( antimicrobial treatment, abscess drainage [local vs. general anesthesia], bacterial growth [positiveDisclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminate d by the Centers for Disease Control and Prevention and should not be

c onstrued 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 (c m)

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) level s. 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

- Non

leukodepleted AWB (non

LD 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, pleuri tis, vascular thrombophlebitis,
skin infection other than wound, gynecologic) none with statistically significant
difference

In both ITT and Per

Protocol: 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 (300mgFe 2+ orally per day)

RBC loss was calculated as the compensated RBC loss (perioperatively transfused RBC volume) plus non

compensated RBC loss estimated from

pre and postoperative (Day 3) hematocrit (Hct) levels correcting large

vessel to total body Hct:
RBC loss = ( Hct pre - Hct POD3 ) X Blood
Volume* X 0.86+RBC

- V units. RBC

- V units =RBC volume of transfused

AWB *Calculated according to Nadler)
Blood loss =RBC loss/(Hct pre - Hct POD3 )/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 disseminate d by the Centers for Disease Control and Prevention and should not be

c onstrued 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, st eroid 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,
vascula r 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 weekendsDisclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminate d by the Centers for Disease Control and Prevention and should not be

c onstrued 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 Per

Protocol : 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: 7/48 8 (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 disseminate d by the Centers for Disease Control and Prevention and should not be

c onstrued 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,
ische mic attack, respiratory insufficiencyDisclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminate d by the Centers for Disease Control and Prevention and should not be

c onstrued 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

Transfusion

induced
immunomodulatio n (TRIM) caused by autologous blood

– stored either as Whole Blood (WB) or as buffy coat

poor packed red
cells and fresh

frozen plasma (RCP)

– in patients undergoing hip arthroplasty.

M onocyte and neutrophil phagocy tic 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 coat

poor packed Red
Cells and fresh

frozen Plasma

NT

- NO Transufsion ·Age: mean±SD WB: 58±10 years RCP: 59±10 years NT: 61±8 year s ·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 5 th week
after th e 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

- c oat poor packed red cells (RC)

- Oldest blood was used
first. Monitoring intervention: hemoglobin count and leucocyte counts were determined by rou tine 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. T

test and Wilcoxon rank sum test for independent variables were used to determine statistical significance.
Other notes: Small sample size
Follow

- up: 7 days observ ation periodDisclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminate d by the Centers for Disease Control and Prevention and should not be

c onstrued 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

s tored 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 disseminate d by the Centers for Disease Control and Prevention and should not be

c onstrued 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: per formed 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 interv ention: 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
thromboe mbolism, 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 disseminate d by the Centers for Disease Control and Prevention and should not be

c onstrued 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,

reop eration due to
infection of primary THR, and mortality within 90 days of primary

THR For the propensity

matched population, there
were no substantial differences for any
of the
characteristics
related to the risk of
transfusion
Stand ardized 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

Pr ophylaxis 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 l oss. 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.

O ther 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 disseminate d by the Centers for Disease Control and Prevention and should not be

c onstrued 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

H emoglobin <138.5g/L within 3

mo. before su rgery 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 (9 5%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 eit her 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 disseminate d by the Centers for Disease Control and Prevention and should not be

c onstrued 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: Multi

center 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 Regist ry (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 t he 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 adverseDisclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminate d by the Centers for Disease Control and Prevention and should not be

c onstrued 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 tr eated 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
transfus ed 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

200 8 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 expres sed 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:
d uration of transfusion

Agent: Perioperatively salvaged WSB. The blood
was collected with non

fractionated 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 Blo od 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 disseminate d by the Centers for Disease Control and Prevention and should not be

c onstrued 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
bl ood 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 , o ne 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) Ap proach: 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:

Interv ention: 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:

Anes thesia: 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 patien ts (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 quantitativ e variables.

Other notes: none

Follow

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

c onstrued 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)
Procedur es : 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

Uncemen ted 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 disseminate d by the Centers for Disease Control and Prevention and should not be

c onstrued 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=0.001Disclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminate d by the Centers for Disease Control and Prevention and should not be

c onstrued 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
Differenc e 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 arthropla sty 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
Characte ristics: ·Age: median (IQR) No RBC: 66y (54

- 73) Autologous: 64y (55

- 70) Allogeneic : 74y (67

- 78) Both: 72y (65

- 77)

P<0.0001 Interv ention group:

Allogeneic (WBC

filtered) 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 infect ion: 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 disseminate d by the Centers for Disease Control and Prevention and should not be

c onstrued 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 saline

ademine

- glucose

- mannitol
additive solution an d kept

at 4 o C and plasma was frozen (to

- 30 o C 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

- adenine

glucose

- 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 Alloge neic 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 aft er 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: DischargeDisclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminate d by the Centers for Disease Control and Prevention and should not be

c onstrued 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)

B oth: 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 cell

saver system and processed when appropriate (>1000ml of
blood in the reservoir. Postoperatively unwashed
shed blood was also re

transfused 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

- 1 000)

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 disseminate d by the Centers for Disease Control and Prevention and should not be

c onstrued 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 st abilization 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

2005 5
( 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: year s 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 al logeneic 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 0.4x10 9 /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:
Bl ood 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 a ssessment 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 conditio nal backward and forward selection to perform multivariate analysis. Effect of variables on Length of stay wasDisclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminate d by the Centers for Disease Control and Prevention and should not be

c onstrued 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 pre

transfusio n 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 ca re 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

**B lood 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 1 st 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 disseminate d by the Centers for Disease Control and Prevention and should not be

c onstrued 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 pla nned 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
sedim entation 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. distr ibution 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 wasDisclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminate d by the Centers for Disease Control and Prevention and should not be

c onstrued 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 tr ansfused 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
Transf usion (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 two

cohort prospective study in patients undergoing Number of

patients: N=3942
evaluable Intervention group:
Received Transfusions

n= 2095 Total Orthopaedic SS I (Follow U p 90 days) Surgical wounds

Orthopedic Definitions: 2 primary outcomes of interest “ Length of stay and Infections” Length of Stay (LOS): the days betweenDisclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminate d by the Centers for Disease Control and Prevention and should not be

c onstrued 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

su rgical 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 unmodif ied RBC, but cohort included patients who received BC

RBC and/or WBC reduced RBCs ONLY IF they also
received at least 2 u
unmodified RBC.

Intervention2 : n=1098 (Orthopaedic I2 n

637) Patients receiving
transfusions after mandatory ULR (Full
cohort2 is WBC r educed 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

ac ute 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 (>38 o C) 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 p roven 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 disseminate d by the Centers for Disease Control and Prevention and should not be

c onstrued 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 RBC Cohort2:
all blood was WBC

reduced 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
O rthopaedic 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

tra nsfusions 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 dischargeDisclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminate d by the Centers for Disease Control and Prevention and should not be

c onstrued 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: Non

emergent Coronary Artery Bypass Grafting (CABG) and elective total hip replacement and/
or total knee

rep lacement (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 b efore 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 (%)

receiv ing

– 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 disseminate d by the Centers for Disease Control and Prevention and should not be

c onstrued 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: E ngland

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 Cri teria: 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 Transf usions 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 disseminate d by the Centers for Disease Control and Prevention and should not be

c onstrued 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 procedu res 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 le ast 2
units of unmod ified

RBCs. Control1: 5/871 (0.6%) Control2: 3/799 (0.4%)

A dverse 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

- on ly:

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: D etermination 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’sDisclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminate d by the Centers for Disease Control and Prevention and should not be

c onstrued 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.

Pri mary 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 m ethodology : 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
characteri stics 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 di screpancies” in the counts adding to the problem of interpretation.

Follow

- up: Until discharge from Surgery DepartmentDisclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminate d by the Centers for Disease Control and Prevention and should not be

c onstrued 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

AB D 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 disseminate d by the Centers for Disease Control and Prevention and should not be

c onstrued 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
Ad verse 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 o rthopedic ward)
All infection data was presented in bar graph Definitions Perioperative care:
MSBOS: the actual number of blood units transfused in 90% of patientsDisclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminate d by the Centers for Disease Control and Prevention and should not be

c onstrued 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

rece iving 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: 480/2 884 (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 re

infused 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 r eceiving 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: χ 2

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

c onstrued 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

re ceived intravenous iron (200mg/day) Perioperative Blood

Return: Intraoperativel y, 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

concentrat e, 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

ex ceeded 200ml during 1 st 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

In traoperative 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 patientsDisclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminate d by the Centers for Disease Control and Prevention and should not be

c onstrued 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 1 st and 3 rd
POD(p<0.0005 vs

. THA &

P<0.001 vs

. TKA)

Main Risk factors
associated with An
increased incidence of Perioperativ e 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); p

0.0001

Reoperations: NR Length of stay: Patient Discharge (days after Surgery)

THA: 12±5

TKA: 16±6

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

c onstrued 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. T HR)=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 autologo us 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 disseminate d by the Centers for Disease Control and Prevention and should not be

c onstrued 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 disseminate d by the Centers for Disease Control and Prevention and should not be

c onstrued 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 arthropl asty patients.Disclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminate d by the Centers for Disease Control and Prevention and should not be

c onstrued to represent any agency determination or policy. 85 

## RISK OF BIAS ASSESSM ENTS OF STUDIES Q 11

Randomized Controlled Trials

Author

Year K

Q Described as
randomized Randomization

appropriately performed Described

as double

blind 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
iden tified 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

2 000 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     LowDisclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminate d by the Centers for Disease Control and Prevention and should not be

c onstrued to represent any agency determination or policy. 86 

# Q 1 2

- 1 6 SYSTEMIC IMMUNOSUPPRESSIVE THERAPY

GRADE TABLE Q 1 2

- 1 6

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 Quality Consistency Directness Precision Publication Bias Large Magnitude

Dose - response Confounders

Systemic Immunosuppressive Therapy: Biologic Agents (Non

- Tumor Necrosis Factors [TNF] and Anti

- TNFs) and Disease Modifying Antirheumatic Drugs

- (DMARD)
Q1 2 . How does systemic corticosteroid or other immunosuppressive therapy impact the risk of SSI in prosthetic joint arthroplasty patie nts? Q12A. Does the type of agent impact the risk of SSI?

Biologic

agents (non

TNF 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 studies 10

, 11 , multivariate logistic regression analysis identified biologic agents as a significant risk factor SSI. Low 0 0 0 0 0 0 +1 0 Moderate

Very low PJI* 2 OBS 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 study 10

, 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 study 11

, 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 study 10

= 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 Lo w 0 0 0 0 0 +1 0 0 ModerateDisclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminate d by the Centers for Disease Control and Prevention and should not be

c onstrued 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 Quality Consistency Directness Precision Publication Bias Large Magnitude

Dose - response Confounders

 1 OBS Study 11

= 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

events

drug
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%): incr eased 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 lowDisclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminate d by the Centers for Disease Control and Prevention and should not be

c onstrued 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 Quality Consistency Directness Precision Publication Bias Large Magnitude

Dose - response Confounders

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

Q1 2 B . Does the preoperative duration of the therapy impact the risk of SSI?

Disease
duration SSI* 2 OBS 10

, 11  In a study 10 comparing RA patients on biologics (anti

- TNF) and DMARDs undergoing arthroplas ty 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 cohort 10 was a median of 14.5 years (interquartil e range 8.9

- 21) but these results were not stratified by biologic agents vs. DMARDs.

 In a study 11 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 LowDisclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminate d by the Centers for Disease Control and Prevention and should not be

c onstrued 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 Quality Consistency Directness Precision Publication Bias Large Magnitude

Dose - response Confounders

Q1 2 C

. Does the agent dose impact the risk of SSI?

Biologic

agents (anti

- Tumor
necrosis factors) vs.

DMARDs SSI* 2 OBS 11

, 10  In a retrospective 1:1 matched pair case control study 11 64 r heumatoid 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 study 10 of 420 THAs and TKAs in RA patients, multivariate logistic regression
anal ysis 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

Q1 3

. 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?
Q1 3 A. 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 study 15 , o verall SSI: 3/41 (7.3%) Low 0 0 0 0 0 0 0 0 Low LowDisclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminate d by the Centers for Disease Control and Prevention and should not be

c onstrued 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 Quality Consistency Directness Precision Publication Bias Large Magnitude

Dose - response Confounders

ely  1 OBS study 15 , n o difference: 0/26 y vs.3/15; p=0.08. 1y follow up. Methotrexate 2 weeks perioperatively

 In each of these studies 13

- 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) study 14 : 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 study 16 (N=462) in RA patients undergoing 657 THAs and TKAs, patients were receiving at least 1 DMARD within 3 months of surgery in 3 36 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 patie nt 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 lowDisclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminate d by the Centers for Disease Control and Prevention and should not be

c onstrued 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 Quality Consistency Directness Precision Publication Bias Large Magnitude

Dose - response Confounders

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

Non

communic ating

serous drainage 1 OBS 13  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: Anti

tumor
necrosis factor (anti

TNF): Stopped vs.
continued perioperativ ely PJI* 1 OBS 16  Subanalysis 16 of 50 / 462 RA patients on biologic agent (anti

- TNF) therapy (etanercept, adalimumab, infliximab, o r 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 Injections

Q15. 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 LowDisclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminate d by the Centers for Disease Control and Prevention and should not be

c onstrued 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 Quality Consistency Directness Precision Publication Bias Large Magnitude

Dose - response Confounders

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 study 17 (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 study 18 (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 study 17 (N=144) re ported 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 study 18 (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 Study 19 , SSI= 0/68 vs. 2/136

 1 OBS Study 20 , SSI= 14/224 vs. 9/224

 1 OBS Study 21 , SSI= 4/40 vs. 0/40 Low 0 0 0

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

c onstrued 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 Quality Consistency Directness Precision Publication Bias Large Magnitude

Dose - response Confounders

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 study 19 (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 study 20
(N=4448 ) in THA reported no difference: 3/224(1.33%) vs. 1/224 (0.44%) a t 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) study 21 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 study 19 found n o difference: 0/68(0%) vs. 1/136 (0.73%); p=0.80. (30 day follow up)

 One study 20 found n o difference: 11/224(4.9%) Low 0 0 0 0 0 0 0 0 LowDisclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminate d by the Centers for Disease Control and Prevention and should not be

c onstrued 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 Quality Consistency Directness Precision Publication Bias Large Magnitude

Dose - response Confounders

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 study 21 found n o infections: 0/40 vs. 0/40 (1 year follow up).

Q1 6 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 injec ted) 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 associatio n 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 dev eloped 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 IntervalDisclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminate d by the Centers for Disease Control and Prevention and should not be

c onstrued to represent any agency determination or policy. 95 

## EVIDENCE TABLE Q1 2

- 1 6
Systemic immunosuppressive therapy Q1 2 . 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?
Q1 3 . What are the most effective strategies in managing systemic corticosteroids or other immunosuppressive therapy perioperativ ely to
reduce the ri sk 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
( E S) 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

interventio n 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%) Interve ntion 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 patient s 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 d rugs (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 postopDisclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminate d by the Centers for Disease Control and Prevention and should not be

c onstrued 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 N umber 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)

Patient s 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
postopDisclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminate d by the Centers for Disease Control and Prevention and should not be

c onstrued 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

– Decemb er 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
list ed 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 0/1 6 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 monthsDisclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminate d by the Centers for Disease Control and Prevention and should not be

c onstrued 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, o r chlorambucil concurrently Control group: n=61
Patients who had never taken

MTX Standard preventive

measures: A ll 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 disseminate d by the Centers for Disease Control and Prevention and should not be

c onstrued 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: Leng th 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.
Al so 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
·Comorbidi ties: 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: 1 9 (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]

N on

- b iologic 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

wit h the use of n on

b iologic DMARDs and
b iologic DMARDs.

Other notes: NR
Follow

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

c onstrued 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 non

biologic DMARDs and biologic DMARDs, as well
as the withholding of

TNF

- blocker therapy on the

inci dence 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 Coll ege of Rheumatology (ACR) criteria
for RA who underwent THA or TKA between January 2005
and December 2009 and were treated with biologic or non

biologic 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 Non

biologic medication

IMMUNOSUPPRESIVE AGENTS MTX: 279 (66.4%) Leflunomide: 4 (1%) Tacrolimus: 31 (7.4%) Mizoribine: 15 (3.6%) Cyclophosphamide: 3 (0.7%)

IMMUNOMODULA TORY

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

c onstrued 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

a verage 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
administ ered 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:
Ti ming 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%) T KA 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 anti

TNF on wound healing
THA N=30 total TKA N= 65
total

TNF n=13 TNF n=14

Non

- TNF n=17 Non

TNF=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 per iods: body temp ≥ 37.5 o CDisclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminate d by the Centers for Disease Control and Prevention and should not be

c onstrued 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
Inflixi mab (INF) or e tanercept (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: NRDisclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminate d by the Centers for Disease Control and Prevention and should not be

c onstrued 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 1 1
( 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
b een 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 disseminate d by the Centers for Disease Control and Prevention and should not be

c onstrued to represent any agency determination or policy. 1 04 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 procedure s 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 (TN F) agents: Infliximab (INF)

or e tanercept (ETN) Monitoring intervention: NR Control group: n=64 surgeries (63 patients)
Patients treated with non

biologic 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

TNF α

- 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 Inf lammation

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, bu t 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 compare d 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/spaceDisclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminate d by the Centers for Disease Control and Prevention and should not be

c onstrued 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 numb er 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=0.03Disclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminate d by the Centers for Disease Control and Prevention and should not be

c onstrued 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

A rthritis Setting: 1 medical university
Location: Japan

Dates: May 2004

– March

2009

. Inclusion Criteria: Patients in matched pairs either treated
with anti

- TNF a gents 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 interve ntion: 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 fol lowing
were present: 1. Isolation of the same organism from ≥ 2 cultures of joint aspirates orDisclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminate d by the Centers for Disease Control and Prevention and should not be

c onstrued 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
arthro plasty (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 Hyd roxychloroquine: 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.

S tandard 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 infectio n 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 s inus 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: Leng th of FU. mean ± SD y

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

c onstrued 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

c ement: 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 stopp ed Anti

TNF therapy before surgery: 0/12 infections.

P=NS

Perioperative cortisone was
not associated with increased risk of prost hesis 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 long

term 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 contact ed 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, pri mary 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.

Q1 4 . 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 arthropla sty 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 i ncluded patients onDisclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminate d by the Centers for Disease Control and Prevention and should not be

c onstrued to represent any agency determination or policy. 109 

### immunosuppressive t herapy 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 o f 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 disseminate d by the Centers for Disease Control and Prevention and should not be

c onstrued to represent any agency determination or policy. 110 

## I ntra

- articular C orticosteroid I njections
Q1 5 . 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 intra

articular 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
Timin g 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 day

case procedure (patients were discharg ed 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 patien ts) 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; pa tients 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 culture s 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 approximati on 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 disseminate d by the Centers for Disease Control and Prevention and should not be

c onstrued 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, immune

suppressive drugs, sero

negative inflammatory
arth ropathy 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 ir rigation 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 t o the loading dose to e nsure cover for 24 hours Posto p 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

p rior 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 disseminate d by the Centers for Disease Control and Prevention and should not be

c onstrued 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 intra

articular 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

consi dered 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, sk in 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 Hospit al
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: Pre

operatively
Duration of intervention:

varia b le Agent: 40mg/dL methylprednisolone and 5mg/mL levobu p ivacaine were injected. P atients 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 trans

trochanteric. 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 Reop erations:
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

Perioperati ve 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
monthsDisclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminate d by the Centers for Disease Control and Prevention and should not be

c onstrued 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 washi ng 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 month s postop developed acute renal
shutdown and died of multi

organ 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
administratio n 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 intra

articular 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 prop hylaxis 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 persist ent 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 use d to assessDisclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminate d by the Centers for Disease Control and Prevention and should not be

c onstrued 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
preoperat ive
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. inst allation 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 superficia l 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

a nd 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 Superfici al 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:

F ollow

- 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 disseminate d by the Centers for Disease Control and Prevention and should not be

c onstrued 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

Dee p 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 disseminate d by the Centers for Disease Control and Prevention and should not be

c onstrued 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 intra

articular
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

wer e 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

Pa tients 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: Methylprednisolone

Steroid delivered via intra

articular 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 intra

articular 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 inci sion. 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 cultureDisclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminate d by the Centers for Disease Control and Prevention and should not be

c onstrued 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 preventi ve

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 fro m the deep

tissue 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

>38 o C, localized pain, or
tenderness 4) an abscess or other
evidence of i nfection involving the deep incision which was found by direct examination, during re

operation, 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 infectionsDisclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminate d by the Centers for Disease Control and Prevention and should not be

c onstrued 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 intra

articular 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 w ith
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
dis tributed 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

Receiv ed 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 foll ow 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 b etween 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
l og

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

c onstrued 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)

Mort ality: NR
Adverse events: NR



### Q1 6 . 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 i ntra

- 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

se arch 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 disseminate d by the Centers for Disease Control and Prevention and should not be

c onstrued to represent any agency determination or policy. 120 

### B. Does the corticosteroid injection dose impact the risk of SSI? Our sea rch 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 disseminate d by the Centers for Disease Control and Prevention and should not be

c onstrued to represent any agency determination or policy. 121 

## RISK OF BIAS ASSESSM ENTS OF STUDIES Q1 2

- 1 6

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 S tatistical

adjustment for potential
confounders done Funding source(s)

disclosed and no
obvious conflict of
interest Overall

Risk of
Bias

Questions 1 2

– 1 6 : Immunosuppressive Therapy Bongartz
2008 16 1 3        Low

Bridges

1991 14 1 3        Low

Carpenter
1996 15 13       Low

Desai
2009 18 15      Low

Hirano
2010 12 1 2      Low

Kaspar
2005 21 15       Low

Kawakami

2010 1 1 12        Low

McIntosh

2006 20 15       Low

Momohara

2011 10 12        Low

Papavasiliou

2006 17 15       Low

Perhala

1991 13 12       Low

Sreekumar

2007 19 15      LowDisclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminate d by the Centers for Disease Control and Prevention and should not be

c onstrued to represent any agency determination or policy. 122 

# Q 1 7 ANTICOAGULATION

GRADE TABLE Q 1 7

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 Quality Consistency Directness Precision Publication Bias Large Magnitude

Dose - response Confounders

Q1 7

. What are the most effective strategies for managing perioperative venous thromboembolism (VTE) prophylaxis to reduce the risk of SSI ?
Q1 7 A. 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 studies 27

, 28 found n o difference in THA (n=6890): 14/3453 (0. 41%) vs. 16/3437 (0.47%). SSIs were rare (30 or 0.40%)

 Two studies 29

, 30 found n o difference in TKA (n=5493): 14/2747 (0.51%) vs. 11/2746 (0.40%)

. I nfections 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 HighDisclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminate d by the Centers for Disease Control and Prevention and should not be

c onstrued 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 Quality Consistency Directness Precision Publication Bias Large Magnitude

Dose - response Confounders

 Two studies 27

, 28 found n o difference in THA: 59/3453 (1.7%) vs. 54/3437 (1.6%); p =NS

 Two studies 29

, 30 found n o 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 studies 27

, 28 found n o difference in THA: 15% both 514/3453 vs. 515/3437

 Two studies 29

, 30 found n o 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
h ours 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 anal ysis showed that

enox aparin (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 thos e on ASA or those on warfarin; this difference was significant
on the 5 th (p=0.003) but not by the 8 th
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 lowDisclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminate d by the Centers for Disease Control and Prevention and should not be

c onstrued 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 Quality Consistency Directness Precision Publication Bias Large Magnitude

Dose - response Confounders

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 iden tified 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 lo w 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 fo r 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 lowDisclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminate d by the Centers for Disease Control and Prevention and should not be

c onstrued 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 Quality Consistency Directness Precision Publication Bias Large Magnitude

Dose - response Confounders

Warfarin vs.

ASA ± mechanical prophylaxis SSI* 2 OBS 31

, 33  In a large OBS study 31 (n=2437) of primary T HA (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 logi stic 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 study 33 (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 OBS 31  Warfarin wa s 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 5 th (p=0 .003) but not by the 8 th
postoperative day. Low 0 0 0

- 1 0 0 0 0 Very low

Higher vs.
lower Mean

INR PJI* 1 OBS 35  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 lowDisclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminate d by the Centers for Disease Control and Prevention and should not be

c onstrued 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 Quality Consistency Directness Precision Publication Bias Large Magnitude

Dose - response Confounders

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 w ith 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
hematom a: 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 patient s in the PJI cohort were on anticoagulation therapy preoperatively for another condition. These patients were heparinized postoperatively until fullyDisclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminate d by the Centers for Disease Control and Prevention and should not be

c onstrued 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 Quality Consistency Directness Precision Publication Bias Large Magnitude

Dose - response Confounders

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 drainage

persistent 1 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 V ery low

Q1 7B . 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
h ours (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 statist ical
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 IntervalDisclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminate d by the Centers for Disease Control and Prevention and should not be

c onstrued to represent any agency determination or policy. 128 

## EVIDENCE TABLE Q 1 7

Q1 7

. 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 Po pulation 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/m 2
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
ade quate 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: patien ts 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

- 5 0 days postop)Disclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminate d by the Centers for Disease Control and Prevention and should not be

c onstrued to represent any agency determination or policy. 129 Author

Year (Ref ID_

Data Extractor) Risk of Bias

Score Study Objective Po pulation 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 preven ting 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
breastfeedin g, 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 disseminate d by the Centers for Disease Control and Prevention and should not be

c onstrued to represent any agency determination or policy. 130 Author

Year (Ref ID_

Data Extractor) Risk of Bias

Score Study Objective Po pulation 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 Art hroplasty 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: 66/220 9 (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.

Riv aroxaban 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 p atient 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 disseminate d by the Centers for Disease Control and Prevention and should not be

c onstrued to represent any agency determination or policy. 131 Author

Year (Ref ID_

Data Extractor) Risk of Bias

Score Study Objective Po pulation 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 w ith 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 fo r the treatment of human immunodeficiency virus infection, planned intermittent pneumatic compression, or a requirement for anticoagulant Standard preventive

me asures: NRDisclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminate d by the Centers for Disease Control and Prevention and should not be

c onstrued to represent any agency determination or policy. 132 Author

Year (Ref ID_

Data Extractor) Risk of Bias

Score Study Objective Po pulation 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: 42/123 9 (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 (fol low 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

– po stoperative
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: exc essive
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 disseminate d by the Centers for Disease Control and Prevention and should not be

c onstrued to represent any agency determination or policy. 133 Author

Year (Ref ID_

Data Extractor) Risk of Bias

Score Study Objective Po pulation 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 patien ts 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, pl anned intermittent pneumatic compression, requirement of ongoing anticoagulation 12h before surgery and was given again 6

- 8h afte r 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 disseminate d by the Centers for Disease Control and Prevention and should not be

c onstrued to represent any agency determination or policy. 134 Author

Year (Ref ID_

Data Extractor) Risk of Bias

Score Study Objective Po pulation 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:

Riva Rox : n=1228

Enox: n=1229 ·Age: mean (SD, IQR) years

Riva Rox : 61.4 (13.2, 53

- 71) Enox: 61.6 (13.7, 54

- 72) ·Gender: female (%)

Riva Rox : 667 (54.3%) Enox: 651 (53.0%) ·Obesity: BMI mean (SD, IQ R)

Riva Rox : 26.8 (4.8, 23.5

- 29.4) Enox: 27.1 (5.2, 23.6

- 30.0)
·Comorbidities: Previous history of VTE

Riva Rox : 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 wou nd
closure and continued for

31

- 39 days. Agent: Oral r ivaroxaban (10mg) once daily Monitoring intervention: Liver biochemistry and
cardiovascular adverse SSI (follow

- up 30

- 35 days) Postoperative wound
infections

Riva Rox : 8/1228 (0.7%)

Enox: 6/1229 (0.5%)

Other infections:
Infections and infestations:

Riva Rox : 88/1228 (7.2%) Enox: 87/1229 (7.1%)

Topic

- specific outcomes:

Non

- Fatal Pulmonary
Embolism n (95%CI)

Riva Rox : 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

Riva Rox : 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 re

operation, or clinically

overt extra

- surgical

- site bleeding asso ciated with a fall in hemoglobin of 20g/L or more, calculated from
the POD1 baseline value orDisclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminate d by the Centers for Disease Control and Prevention and should not be

c onstrued to represent any agency determination or policy. 135 Author

Year (Ref ID_

Data Extractor) Risk of Bias

Score Study Objective Po pulation and Setting Intervention Results Comments

“Regulation of Coagulation in Orthopaedic
surgery to prevent Deep

vein thrombosis and pulmonary embolism) (IQR) (min)

Riva Rox : 95.0 (72

- 125) Enox: 93.0(73

- 126)

Procedures: Elective Hip Arthroplasty (THA) Previous Orthopedic Surgery

Riva Rox : 225 (18.3%) Enox: 232 (18.9%) Primary
Riva Rox : 1160 (94.5%) Enox: 1157 (94.1%)

Revision
Riva Rox : 52 (4.2%) Enox: 50 (4.1%) Missing/no surgery

Riva Rox : 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.

Ex clusion 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

Riva Rox : 621 (50.6%) Enox: 608 (49.8%) Deep

- vein Thrombosis in ITT population: n (95%CI)

Riva Rox : 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)

Riva Rox : 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)

Riva Rox : 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
thromboem bolism: n (95%CI)

Riva Rox : 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 on

treatment bleeding event not adjudicated as major bleeding Hemorrhagic wound complications: composite
of excessive wound hematoma and surgical

site 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.
Safe ty 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

ven ous thromboembolism

– those valid for safety analysis and in whom the venograms were evaluableDisclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminate d by the Centers for Disease Control and Prevention and should not be

c onstrued to represent any agency determination or policy. 136 Author

Year (Ref ID_

Data Extractor) Risk of Bias

Score Study Objective Po pulation 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

sev ere 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)

Riva Rox : 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 follow

up period: n (95%CI)

Riva Rox : 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

Riva Rox : 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%) [B lood in cerebrospin al 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 two

sided p value. Unweighted
RR reduction calculated with an asymptotic
method. Sensitivity analysis: 1)
included all randomized patients with evaluable
bil ateral 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 bilat eral 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 disseminate d by the Centers for Disease Control and Prevention and should not be

c onstrued to represent any agency determination or policy. 137 Author

Year (Ref ID_

Data Extractor) Risk of Bias

Score Study Objective Po pulation and Setting Intervention Results Comments

bleeding:

Riva Rox : 80/1228 (6.5%) Enox: 67/1229 (5.5%) Clinically relevant non

- major bleeding

Riva Rox : 40/1228 (3.3%) Enox: 33/1229 (2.7%) Any bleeding after initiation of placebo or Rivaroxaban:

Riva Rox : 56/1197 (4.7%) Enox: 49/1193 (4.1%)

Patients receiving blood
transfusion:

Riva Rox : 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)

Riva Rox : 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

commit tee. 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
med icationDisclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminate d by the Centers for Disease Control and Prevention and should not be

c onstrued to represent any agency determination or policy. 138 Author

Year (Ref ID_

Data Extractor) Risk of Bias

Score Study Objective Po pulation and Setting Intervention Results Comments

Death in follow

- up period: n (95%CI)

Riva Rox : 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:
Riva Rox : 768/1228 (62.5%) Enox: 807/1229 (65.7%)

Drug related adverse events:

Riva Rox : 245/1228 (20.0%) Enox: 249/1229 (20.3%)

Drug related serious on

treatment adverse events

Riva Rox: 13/1228 (1.1%)

Enox : 17 (1.4%)

Serious on

- treatment adverse

events:
Riva Rox : 90/1228 (7.3%) Enox: 131/1229 (10.7%)

Adverse events leading to
discontinuations:

Riva Rox : 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 disseminate d by the Centers for Disease Control and Prevention and should not be

c onstrued to represent any agency determination or policy. 139 Author

Year (Ref ID_

Data Extractor) Risk of Bias

Score Study Objective Po pulation and Setting Intervention Results Comments

Edema peripheral

Riva Rox : 55/ 1228 (4.5%) Enox: 48/1229 (3.9%)

Turpie

2002 22
( ES) Meta

Analysis 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 P hase 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 i ntervention: 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 re

hospitalization: Fond: 52/3616 (1.4%) Enox: 52/3621 (1.4%)

Other infections: NR Topic

- specific out comes: 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 t o 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: NRDisclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminate d by the Centers for Disease Control and Prevention and should not be

c onstrued to represent any agency determination or policy. 140 Author

Year (Ref ID_

Data Extractor) Risk of Bias

Score Study Objective Po pulation 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 1 st
injection 12h ± 2h preoperatively 2/4 studies: enoxaparin in 30mg qd with time of 1 st
injection 1 2

- 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 a nalysis 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 disseminate d by the Centers for Disease Control and Prevention and should not be

c onstrued to represent any agency determination or policy. 141 Author

Year (Ref ID_

Data Extractor) Risk of Bias

Score Study Objective Po pulation and Setting Intervention Results Comments

injection NR Standard preventive

measures: Other thromboembolic prophylaxes: Intermittent pneumatic compression, dextran and thrombolytic or anticoagulan t agents were prohibited; centers were
instructed to avoid the use of aspirin or nonsteroidal anti

inflammatory drugs when possible; other antiplatelet agents were prohibited Graduated compression stockings: use was allowed and physiotherapy was
recommende d 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 disseminate d by the Centers for Disease Control and Prevention and should not be

c onstrued to represent any agency determination or policy. 142 Author

Year (Ref ID_

Data Extractor) Risk of Bias

Score Study Objective Po pulation 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

2 010 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). O ther 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%)

Co ntrol: 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

- discharg e. 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 disseminate d by the Centers for Disease Control and Prevention and should not be

c onstrued to represent any agency determination or policy. 143 Author

Year (Ref ID_

Data Extractor) Risk of Bias

Score Study Objective Po pulation 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 undergo ing 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%)

Co ntrol: 50 (47.6%) Bemiparin Intervention: 8 (22.2%) Control: 26 (24.8%) Fraxiparin Intervention: 7 (19.4%) Top ic

- 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 non

correlated 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 reco rds did not provide enough
information to rule out infection during the first 6 months, patients wereDisclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminate d by the Centers for Disease Control and Prevention and should not be

c onstrued to represent any agency determination or policy. 144 Author

Year (Ref ID_

Data Extractor) Risk of Bias

Score Study Objective Po pulation 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 c enter 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

Interven tion: 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
recordsDisclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminate d by the Centers for Disease Control and Prevention and should not be

c onstrued to represent any agency determination or policy. 145 Author

Year (Ref ID_

Data Extractor) Risk of Bias

Score Study Objective Po pulation 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 o utcomes: Definitions:

TKA

– ICD

- 9

- CM proce dure
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 principalDisclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminate d by the Centers for Disease Control and Prevention and should not be

c onstrued to represent any agency determination or policy. 146 Author

Year (Ref ID_

Data Extractor) Risk of Bias

Score Study Objective Po pulation and Setting Intervention Results Comments

infection (SSI), and mortality
between patients who

re ceived 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
arthro plasty (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 fo r 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 al l 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 daysDisclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminate d by the Centers for Disease Control and Prevention and should not be

c onstrued to represent any agency determination or policy. 147 Author

Year (Ref ID_

Data Extractor) Risk of Bias

Score Study Objective Po pulation and Setting Intervention Results Comments

centers are predominantly small to midsize nonteaching
facilities serv ing 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
Exclu sion 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: NRDisclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminate d by the Centers for Disease Control and Prevention and should not be

c onstrued to represent any agency determination or policy. 148 Author

Year (Ref ID_

Data Extractor) Risk of Bias

Score Study Objective Po pulation 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

Pat ient 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/m 2 (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

To tal 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: pre

and 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 give n 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)

u nless indicated otherwise

Monitoring intervention:

INR SSI (adjusted results wh en 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 infectio n 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: N R

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

c onstrued to represent any agency determination or policy. 149 Author

Year (Ref ID_

Data Extractor) Risk of Bias

Score Study Objective Po pulation 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 i njectable 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 woun d healing: 1/9

INR

Mean INR>1.5 Cases: 16 (21%) Control: 17 (11%) P=0.05; χ 2 =3.97 INR at day of Discharge>1.5 Cases: 13 (17%) Control: 12 (8%) P=0.04; χ 2 =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 variab les Multivariate stepwise logistic regression was used to perform adjusted analysis
Other notes: None
Follow

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

c onstrued to represent any agency determination or policy. 150 Author

Year (Ref ID_

Data Extractor) Risk of Bias

Score Study Objective Po pulation and Setting Intervention Results Comments

Inclusion Criteria: All patients undergoing primary or revision total knee (TKA) or total hip arth roplasty (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 infectionDisclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminate d by the Centers for Disease Control and Prevention and should not be

c onstrued to represent any agency determination or policy. 151 Author

Year (Ref ID_

Data Extractor) Risk of Bias

Score Study Objective Po pulation 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

P atient 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 Arthr oplasty (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

- Weight

Heparin(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 antimicrobial s. 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 antimicrobial s; 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 woun d 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/m 2
Overweight: BMI 25

- 29.9 kg/m 2

Obese: BMI 30.0

- 39.9 kg/m 2
Morbidly Obese: BMI ≥ 40 kg/m 2 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 wo und 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 prophylaxisDisclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminate d by the Centers for Disease Control and Prevention and should not be

c onstrued to represent any agency determination or policy. 152 Author

Year (Ref ID_

Data Extractor) Risk of Bias

Score Study Objective Po pulation 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 prophylacti c antimicrobial s (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

i nfection 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:

D rain 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 log istic 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: NRDisclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminate d by the Centers for Disease Control and Prevention and should not be

c onstrued to represent any agency determination or policy. 153 Author

Year (Ref ID_

Data Extractor) Risk of Bias

Score Study Objective Po pulation and Setting Intervention Results Comments

TKA group: every additional

100

- mL increase in postop drain output resu lted 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 ho spital 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: NRDisclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminate d by the Centers for Disease Control and Prevention and should not be

c onstrued to represent any agency determination or policy. 154 Author

Year (Ref ID_

Data Extractor) Risk of Bias

Score Study Objective Po pulation 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 low

dose 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 develop ed 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, Mann

Whitney test

Other notes: None

Follow

- up: 3 months
postopDisclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminate d by the Centers for Disease Control and Prevention and should not be

c onstrued to represent any agency determination or policy. 155 Author

Year (Ref ID_

Data Extractor) Risk of Bias

Score Study Objective Po pulation 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 undergoi ng 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
readm ission] No Prophylaxis: 2 (0.3%) [
these two events were non

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

c onstrued to represent any agency determination or policy. 156 Author

Year (Ref ID_

Data Extractor) Risk of Bias

Score Study Objective Po pulation 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 disseminate d by the Centers for Disease Control and Prevention and should not be

c onstrued to represent any agency determination or policy. 157 Author

Year (Ref ID_

Data Extractor) Risk of Bias

Score Study Objective Po pulation 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 ri sk of SSI.Disclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminate d by the Centers for Disease Control and Prevention and should not be

c onstrued to represent any agency determination or policy. 158 

## RISK OF BIAS ASSESSM ENTS OF STUDIES Q1 7

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
i ndependen
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 1 7 : Anticoagulation Turpie
2002 22 1 7   High



### Randomized Controlled Trials

Author Year (RefID) K

Q Described

as randomize
d Randomizatio

n appropriately performed Described

as double

blind 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 an d no
obvious conflict of
interest Overall

Risk of
Bias

Question 1 7 : Anticoagulation
Eriksson

2008 27 1 7         Low

Kakkar

2008 28 1 7          Low

Lassen
2008 29 1 7         Low

Turpie
200 9 30 1 7         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

conf ounders
identified Statistical

adjustment for potential
confounders done Funding source(s)

disclosed and no
obvious conflict of
interest Overall

Risk of
Bias

Question 1 7 : Anticoagulation

Asensio
2010 32 1 7         Low

Bozic
2010 33 1 7         Low

Parvizi
2007 35 1 7         Low

Patel

2007 31 1 7        Low

Sachs

2003 34 1 7       LowDisclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminate d by the Centers for Disease Control and Prevention and should not be

c onstrued to represent any agency determination or policy. 159 

# Q1 8 ORTHOPAEDIC SPACE SUIT

GRADE T ABLE Q 1 8

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 Quality Consistency Directness Precision Publication Bias Large Magnitude

Dose - response Confounders

Q1 8 . How safe and effective are orthopaedic space suits in reducing the risk of SSI in prosthetic joint arthroplasty patients an d 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%C I

, 0.20

- 0.55); RR 0.75 (95% CI,

0.34

- 1.62)

 Deep Infections identified through ICD9

- CM diagnosis codes for mu ltiple joint/bone infection, debridement , and implant removal codes (not revision total joint arthroplasty codes). In this study deep infection mi ght 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 i n 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 lowDisclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminate d by the Centers for Disease Control and Prevention and should not be

c onstrued 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 Quality Consistency Directness Precision Publication Bias Large Magnitude

Dose - response Confounders

 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 hemiarthroplast y 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 OBS 38  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 IntervalDisclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminate d by the Centers for Disease Control and Prevention and should not be

c onstrued to represent any agency determination or policy. 161 

## EVIDENCE TABLE Q 1 8

Q1 8 . How safe and effective are orthopaedic space suits in reducing the risk of SSI in prosthetic joint arthroplasty patients an d 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
self

contained
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 clini cal
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:

O steoarthritis: 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 Flow

Numbers 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 hospital s 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 Graph

details not reported in text)
Conventional OR:

Su it: ~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 Chi

squared 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 procedu res and In
2008 almost half of all procedures wereDisclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminate d by the Centers for Disease Control and Prevention and should not be

c onstrued 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 informatio n 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
Con trol 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 (wit hout 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 Su it:
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
infectio n.

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
informatio n on frequency of suit use,
members of the
team who wore them, whether practice changed depending on OR
team and whetherDisclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminate d by the Centers for Disease Control and Prevention and should not be

c onstrued 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 Graph

details 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
syste ms and whether
air is concentrated
with debris and significant numbers of colony forming
units close to the surgical site.

Follow

- up: Minimum
6 monthsDisclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminate d by the Centers for Disease Control and Prevention and should not be

c onstrued 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: O ne 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 replaceme nt 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 disseminate d by the Centers for Disease Control and Prevention and should not be

c onstrued 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 tec hnician 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: N R ·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 Interv ention 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: Intraoperati ve

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) fo r 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. Reoperat ions within 90 days Perioperative care : NR Analytical methodology: NoneDisclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminate d by the Centers for Disease Control and Prevention and should not be

c onstrued 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 lami nar 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 i n 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 ev ents: 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 use

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

c onstrued 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 d uring
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

int ervention 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: Orth opedic 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 s ystem 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 0.3 μ m 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: e ither general or spinal. Analytical methodology: Settle plate results were compared between patient and
anesthetist areas and
between conventional gowns and body exhaust suits using Mann

Whitney U tests after normality checking to establish significan t differences betweenDisclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminate d by the Centers for Disease Control and Prevention and should not be

c onstrued 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 (hig h 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

tu rnover 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 exh aust 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
monthsDisclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminate d by the Centers for Disease Control and Prevention and should not be

c onstrued 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
cefamandol e 30min before anesthesia followed by a
second dose of
cefamandol e 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 disseminate d by the Centers for Disease Control and Prevention and should not be

c onstrued to represent any agency determination or policy. 170 

## RISK OF BIAS ASSESSM ENTS OF STUDIES Q1 8

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)

disclo sed and no
obvious conflict of
interest Overall

Risk of
Bias

Question 1 8 : Surgical Attire Hooper
2011 37 1 8        Low

Miner
2007 36 1 8      Low

Pasquarella

2003 38 1 8      LowDisclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminate d by the Centers for Disease Control and Prevention and should not be

c onstrued to represent any agency determination or policy. 171 

# Q 2 0 BIOFILM

GRADE TABLE Q 2 0

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 Quality Consistency Directness Precision Publication Bias Large Magnitude

Dose - response Confounders

Q 2 0 . What are the most effective strategies to reduce the risk of biofilm formation and SSI in prosthetic joint arthroplasty pa tients?
Q 20 A . 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=4 1 8), reduc ed 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 (5841 39 ) in 350 TKA s , no n

- diabet ics : 0/178 vs. 5/162(3.1%); p=0.02 38



###  1 study (5842 40 ) in 78 TKA s, all diabet ics: 0/41 vs.5/ 37(13.5%); p=0.021

 Based on de finition d eep SSI included PJI

 All TKAs performed by same surgeon, in operating ro oms without ult raviolet 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=4 1 8), no difference (OR: 0.91; 95% CI: 0.18

– 4.55; p=0.90)

 In one study 39 of 350 TKA s for osteoarthritis
with no diabetes mellitus: 2/178 vs. 2/162; p=1.00 High 0 0 0

- 1

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

c onstrued 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 Quality Consistency Directness Precision Publication Bias Large Magnitude

Dose - response Confounders

 In one study 40 of 78 TKA s all with diabetes
mellitus : 1/41 vs. 1/37; p=0.835



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

c onstrued to represent any agency determination or policy. 173 

## EVIDENCE TABLE Q 2 0

Q 2 0 . 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) R CT

1, 5, 10 To evaluate

the efficacy
of
cefuroxime

impregnate
d cement in
the prevention of deep
infection
after primary
total knee arthroplasti

es performed
without
clean

- air

measures such as
laminar flow and body

exhaust

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 an alyzed 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 cefurox ime 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: Cefuroxime

impregnated cement; pure

ce ment 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 3 rd 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
antimicrobial s for another week.

Length of stay: Mean Stay, days (range): 8 days (5

- 15 days) Mortality: NR
Adverse event s: 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 persisten t 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 afterDisclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminate d by the Centers for Disease Control and Prevention and should not be

c onstrued 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 fo r 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 2 nd day. Continuous passive motion: used every day until discharge Weight bearing: on the
involved knee was allowed
form the second postoperative day and

crut ches 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 the n 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. Th is 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 disseminate d by the Centers for Disease Control and Prevention and should not be

c onstrued 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 ef fect 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 o f 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

pos t 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: Cefuroxime

impregnated 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 3 rd
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 post

operatively. Then every 6
months there

- after MeanDisclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminate d by the Centers for Disease Control and Prevention and should not be

c onstrued 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)
Gend er: 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

Contr ol: 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: cefuroxime

impregnated cement used on one side (Intervention n=6) and not the o ther (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 (HHS

functional)

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 antimicrobial s administered for 1 week and orally for another week. Deep Infections 3/5

– radical debridement was followed by four weeks of intravenous
antimicrobial s and then two months of
oral antimicrobial s 2/5

– deep SSIs underwent two stage re

implantation procedures

. Length of stay: Mean lengths was 8 days (Range 5

- 14 days) Mortality: NR
Adverse events: NR fo llow 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 disseminate d by the Centers for Disease Control and Prevention and should not be

c onstrued 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, malig nant 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 thei r 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 disseminate d by the Centers for Disease Control and Prevention and should not be

c onstrued to represent any agency determination or policy. 178 

## RISK OF BIAS ASSESSM ENTS OF STUDIES Q 2 0

Randomized Controlled Trials

Author Year (RefID) K

Q Described

as randomize
d Randomizatio

n appropriately performed Described

as double

blind 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 c onflict of
interest Overall

Risk of
Bias

Question 20 Biofilm
Chiu

2002 39 20    Moderate

Chiu

2001 40 20    ModerateDisclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminate d by the Centers for Disease Control and Prevention and should not be

c onstrued 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 th e 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) H eterogeneity 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 RANDOMIZE D 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) Inve stigator 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 interestDisclaimer. This document is a draft. The findings and conclusions in this draft guideline have not been formally disseminate d by the Centers for Disease Control and Prevention and should not be

c onstrued to represent any agency determination or policy. 180 

### CHECK LIST 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 ha ve not been formally disseminated by the Centers for Disease Control and Prevention and should not be

construed to represent any a gency determination or policy. 181 

# SECTION 4 : EVIDENCE TABLE EXTRA CTION 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 CONTROLLE D 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

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

construed to represent any a gency determination or policy. 182 

# 3

. OTHER CONTROLLED STU DIES 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 ha ve not been formally disseminated by the Centers for Disease Control and Prevention and should not be

construed to represent any a gency determination or policy. 183 

# SECTION 5 : STUDY TYPE DETERMINA TION ALGORITHM

Adapted from: Hartling et. al. 2010 41Disclaimer. This document is a draft. The findings and conclusions in this draft guideline ha ve not been formally disseminated by the Centers for Disease Control and Prevention and should not be

construed to represent any a gency determination or policy. 184 

# SECTION 6 : R EFERENCES

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