Conditions: Opioid Use Shoulder Osteoarthritis Avascular Necrosis Rotator Cuff Tear Arthritis;Inflammatory
Keywords: Primary Total Shoulder Arthroplasty Reverse Total Shoulder Arthroplasty
Allocation: NON_RANDOMIZED | Intervention model: PARALLEL
Enrollment: 86
Healthy volunteers: no

Brief summary:
Purpose of Study:

To identify and provide a safe, opioid-free treatment pathway for shoulder arthroplasty with a focus on perioperative pain control and postoperative symptoms from treatment

Detailed description:
Background and Significance:

Opioid-based analgesia has been a cornerstone of patient care in the setting of acute pain for the last century and has undergone logarithmic increase over the past twenty years. Unfortunately, the rise in utilization has brought with it a rise in opioid-induced side effects. These include constipation, nausea/vomiting, hyperalgesia, delirium, addiction/withdrawal (with 67% of those prescribed a long-term opioid program still on opioids at an average of 4.8 years of follow-up), and in some cases even respiratory depression/death. Patient expectations of opioid-based pain medication has driven a rapid rise in outpatient opioid prescriptions including both short and long-acting opioids. These prescriptions have in turn become a source of significant mortality in the United States, with nearly 20,000 deaths due to opioid overdose in 2014 alone.

There have been momentous efforts made in identifying synergistic compounds to use for acute pain management in the perioperative time period to begin to minimize the opioid requirement for pain control. These studies have focused on nerve modulation with gabapentinoids, intravenous and local administration of sodium-channel blockers such as lidocaine and bupivacaine, and even increased interest in non-steroidal anti-inflammatories and acetaminophen. At this time, no study has looked at the possibility of utilizing a multi-modal acute post-surgical pain control pathway that did not include some form of opioid medication for the general population.

Arthroplasty continues to be a dominant procedure in the orthopaedic armamentarium and accounts for well over a million surgeries done in the United States per year. With the ability to utilize targeted nerve blocks by anesthesia, and the increasing data showing efficacy of multi-modal therapy for acute pain, we propose a patient care pathway that is completely free of all opioid-based medications. From the time that patients are checked in until the time the patient follows up in clinic, they will utilize a pathway designed to eliminate pain and opioid-related side effects following shoulder arthroplasty. Our hope is that a well-designed pathway for total shoulder arthroplasty can quickly be modeled for other surgical procedures in an attempt to minimize the negative effects of opioid utilization both acutely and on a societal level.

Arms:
arm 1: The observational treatment group will not have any changes from your surgeon's normal pain management process. Anesthesia will be utilized in a routine fashion with all routine perioperative medications. You will be discharged on routine postoperative medications including opioids, NSAIDS, and any other modalities typically used by the treating surgeon. arm 2: Oral dose of both gabapentin and celecoxib (toradol if sulfa allergy) in the preop area. US-guided interscalene regional block without the aid of opioid co-medication. Intra-op management by anesthesia with non-opioid modalities but should include one dose of IV acetaminophen during the procedure. Anesthetic modalities will include, but not limited to, regional block, propofol, IV lidocaine, rocuronium/vecuronium, and sevoflurane/desflurane. If the attending anesthesiologist deems it necessary to dose with opioids during procedure, it will be recorded and reported. Liposomal bupivacaine will be injected into the peri-articular soft tissues as an adjunct to the block. Post Op, cryotherapy, gabapentin, toradol. Toradol will transition to celecoxib for the duration of the hospitalization (or meloxicam for patients with sulfa allergy). As needed medications will include both oral and IV acetaminophen, as well as up to an additional 15mg of toradol per 6hr, depending on Cr clearance.

Interventions: intervention 1: Gabapentin intervention 2: Celecoxib intervention 3: toradol intervention 4: acetaminophen intervention 5: regional block intervention 6: propofol intervention 7: IV lidocaine intervention 8: rocuronium intervention 9: vecuronium intervention 10: sevoflurane intervention 11: desflurane
Intervention descriptions: intervention 1: opioid-free treatment pathway for shoulder arthroplasty with a focus on perioperative pain control and postoperative symptoms from treatment intervention 2: opioid-free treatment pathway for shoulder arthroplasty with a focus on perioperative pain control and postoperative symptoms from treatment intervention 3: opioid-free treatment pathway for shoulder arthroplasty with a focus on perioperative pain control and postoperative symptoms from treatment intervention 4: opioid-free treatment pathway for shoulder arthroplasty with a focus on perioperative pain control and postoperative symptoms from treatment intervention 5: opioid-free treatment pathway for shoulder arthroplasty with a focus on perioperative pain control and postoperative symptoms from treatment intervention 6: opioid-free treatment pathway for shoulder arthroplasty with a focus on perioperative pain control and postoperative symptoms from treatment intervention 7: opioid-free treatment pathway for shoulder arthroplasty with a focus on perioperative pain control and postoperative symptoms from treatment intervention 8: opioid-free treatment pathway for shoulder arthroplasty with a focus on perioperative pain control and postoperative symptoms from treatment intervention 9: opioid-free treatment pathway for shoulder arthroplasty with a focus on perioperative pain control and postoperative symptoms from treatment intervention 10: opioid-free treatment pathway for shoulder arthroplasty with a focus on perioperative pain control and postoperative symptoms from treatment intervention 11: opioid-free treatment pathway for shoulder arthroplasty with a focus on perioperative pain control and postoperative symptoms from treatment

Protocol document:
Prot_SAP_000.pdf: 
 
 
 
 
Opioid-Free Shoulder Arthroplasty 
 
NCT03540030 
 
 
 
Protocol Date:  July 5, 2017 


Opioid-Free Shoulder Surgery, Version 5 
 
7/5/2017 
 
Opioid-Free Shoulder Arthroplasty 
 
Protocol# SPORT049 
 
 
 
Nady Hamid, MD 
OrthoCarolina 
1915 Randolph Road 
Charlotte, NC 28207 
704-323-2000 
 
 
 
 
 
 
 
 
 
 
 
 


 
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Page 2 of 13 
 
 
1. .Title: 
Opioid-Free Shoulder Arthroplasty 
 
2. Principal Investigator: 
Nady Hamid, MD (OrthoCarolina, 1915 Randolph Road, Charlotte, NC 28207; telephone: 
704-323-2000). 
 
3. Responsible Departmental Chairperson: 
Robert B. Anderson, MD (Chairman, Research Committee, OrthoCarolina, 2001 Vail 
Avenue, Suite 200B Charlotte, NC 28207; telephone: 704-323-2000). 
 
4. Purpose of Study:  
To identify and provide a safe, opioid-free treatment pathway for shoulder arthroplasty with a 
focus on perioperative pain control and postoperative symptoms from treatment 
 
5. Background and Significance:  
Opioid-based analgesia has been a cornerstone of patient care in the setting of acute pain 
for the last century and has undergone logarithmic increase over the past twenty years.  
Unfortunately, the rise in utilization has brought with it a rise in opioid-induced side 
effects. These include constipation, nausea/vomiting, hyperalgesia [1, 2], delirium [3], 
addiction/withdrawal (with 67% of those prescribed a long-term opioid program still on 
opioids at an average of 4.8 years of follow-up [4]), and in some cases even respiratory 
depression/death.  Patient expectations of opioid-based pain medication has driven a 
rapid rise in outpatient opioid prescriptions including both short and long-acting opioids 
[4].  These prescriptions have in turn become a source of significant mortality in the 
United States, with nearly 20,000 deaths due to opioid overdose in 2014 alone. 
 
There have been momentous efforts made in identifying synergistic compounds to use for 
acute pain management in the perioperative time period to begin to minimize the opioid 
requirement for pain control.  These studies have focused on nerve modulation with 
gabapentinoids [5-7], intravenous and local administration of sodium-channel blockers 
such as lidocaine and bupivacaine [8-10], and even increased interest in non-steroidal 
anti-inflammatories and acetaminophen [11-15].  At this time, no study has looked at the 
possibility of utilizing a multi-modal acute post-surgical pain control pathway that did not 
include some form of opioid medication for the general population. 
 
Arthroplasty continues to be a dominant procedure in the orthopaedic armamentarium 
and accounts for well over a million surgeries done in the United States per year.  With 
the ability to utilize targeted nerve blocks by anesthesia [16-18], and the increasing data 
showing efficacy of multi-modal therapy for acute pain [19-24], we propose a patient 
care pathway that is completely free of all opioid-based medications.  From the time that 
patients are checked in until the time the patient follows up in clinic, they will utilize a 
pathway designed to eliminate pain and opioid-related side effects following shoulder 
arthroplasty.  Our hope is that a well-designed pathway for total shoulder arthroplasty can 
quickly be modeled for other surgical procedures in an attempt to minimize the negative 
effects of opioid utilization both acutely and on a societal level. 


 
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Page 3 of 13 
 
 
6. References: 
See part C. 
 
7. Study Design: 
 
A. Type of Study:  Prospective Cohort Study 
 
B. Study Population 
1. 
Inclusion Criteria 
a. Patient undergoing elective primary total shoulder or reverse total 
shoulder arthroplasty for osteoarthritis, avascular necrosis, cuff 
tear arthropathy, or inflammatory arthritis etiologies 
b. Age greater than or equal to 50. 
 
2. 
Exclusion Criteria 
a. Revision total shoulder arthroplasty 
b. Chronic opioid therapy – per investigator discretion 
c. Liver or renal insufficiency – per investigator discretion 
d. Arthroplasty for fracture 
e. Sickle cell disease 
f. Workers compensation 
g. Inability to receive block 
h. Intervention Arm Only:  Creatinine clearance less than 30 mL/min 
i. Intervention Arm Only: Allergy to non-steroidal anti-inflammatory 
medications (NSAIDs). 
 
C. Definition of Variables 
1. 
Primary Outcome Variable 
a. Pain at patient discharge or 24-hours, whichever comes first – 
measured on a 0-10 numeric rating scale (NRS). 
 
2. 
Secondary Outcomes Variables 
a. Pain at 6hr, 12hr, 2 weeks, and 2 months post-operatively 
measured on a 0-10 NRS 
b. Rate of nausea 
c. Rate of constipation 
d. Continued use of pain medications 
e. Delirium score 
f. Falls 
g. Morphine milli-equivalents (In-hospital operative, In-hospital post-
operative, and post-discharge) 
h. Satisfaction with overall pain 
i. American Shoulder and Elbow Surgeons (ASES) Shoulder Score 
j. Simple Shoulder Test 
k. VR-12 
 


 
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3. 
Additional Data Points 
a. Age 
b. Gender 
c. Height/Weight/Body Mass Index (BMI) 
d. Tobacco Use (current, former, never) 
e. Medical Comorbidities (based on the Charlson Comorbidiy Index) 
f. Primary Diagnosis 
g. Pre-Operative Opioid Use 
h. Pre-Operative current and average pain score (NPS) 
i. Pre-Operative creatinine level 
j. Surgeon 
k. Surgical Approach (Total Shoulder Arthroplasty, Reverse Total 
Shoulder Arthroplasty) 
l. Concomitant Procedures 
m. Date of Surgery 
n. Intraoperative Complications 
o. Date of Discharge 
p. Post-Operative opioid use 
 
4. 
Confounding Variables 
a. Patients will demonstrate some degree of recall bias when asked 
about perioperative pain control at their two week, 6-8 wk, and 1 
year follow-up 
 
D. Methods 
 
1. 
Patient Enrollment and Identification: 
Patients will be identified in clinic by the surgeon performing the shoulder 
arthroplasty.  The surgeon will introduce the concept of opioid-free 
arthroplasty with the patients, who will then choose whether to follow the 
traditional or opioid-free pathway. The surgeon will notify the study 
coordinator of the patient’s decision.  Patients participating in the 
intervention arm will have a blood draw (approximately 10 milliliters, or 
about 2 teaspoons) to determine eligibility based on creatinine clearance.  
One tube of blood will be collected in a gold serum top vaccutainer tube 
(approximately 2 teaspoons) by the research staff in the clinic during the 
screening visit.  It will be sent to the local lab for processing. Creatinine 
clearance will be calculated with the Cockcroft-Gault Formula: 
 
𝐶𝐶= [(140 −𝑎𝑔𝑒𝑦𝑒𝑎𝑟𝑠) ∗𝑤𝑒𝑖𝑔ℎ𝑡𝑘𝑔]/(72 ∗𝐶𝑟𝑒𝑎𝑡𝑖𝑛𝑖𝑛𝑒𝑆𝑒𝑟𝑢𝑚 (𝑚𝑔
𝑑𝑙)) 
 
For females, the calculated value is multiplied by 0.85 (i.e., 85% of the 
calculated value). For males, there is no additional conversion necessary. 
For convenience, an online creatinine clearance calculator will be used 
(http://www.mcw.edu/calculators/creatinine.htm) for the calculation. The 


 
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resulting creatinine clearance will be recorded. Patients with a creatinine 
clearance of less than 30 mL/min will be excluded from the interventional 
arm of the study, as NSAIDs are contraindicated. Patients with creatinine 
clearance between 30 and 60 mL/min will receive a half-dose of all 
NSAIDs if enrolled in the intervention arm of the study. Patients with 
creatinine clearance greater than 60 mL/min will be eligible to receive full 
doses of NSAIDs in the intervention arm of the study. 
   
The study consent will be scanned in the clinic and hospital chart to 
identify them as a study patient. During the screening visit, patients will be 
registered in the OrthoCarolina OBERD platform that is used to collect 
and manage patient reported outcome (PRO) data, specifically the ASES, 
Simple Shoulder Test, and VR-12 measures.   
 
Additionally, color-coded case report forms (CRFs), indicating the patient 
pathway, will be provided to the unit nurses. 
 
Online surveys containing patient reported outcomes of the ASES, Simple 
Shoulder Test, and VR-12 will be automatically sent to patients at the 1 
year post-operative interval via the OrthoCarolina OBERD platform.  
OBERD is a software platform that OrthoCarolina uses to collect clinical 
outcomes data and provide patient education. This platform is interfaced 
with OrthoCarolina’s electronic medical records and administrative claims 
system.  
 
All patients having a total shoulder replacement or reverse total shoulder 
replacement at OrthoCarolina complete these questionnaires through the 
OBERD software platform as part of the OrthoCarolina quality 
improvement process. If a patient is unable to attend the standard-of-care 1 
year postoperative clinic visit, then online and/or phone data collection of 
patient reported outcomes of the ASES, Simple Shoulder Test, VR-12, and 
questions of constipation, nausea, pain, or other complications will occur.  
Patient compliance with PRO online survey completion will be monitored 
and patients will be contacted via phone to ensure that the surveys are 
completed if they are unable to attend the standard-of-care 1 year follow 
up visit.  If patients are able to attend the 1 year follow up visit and they 
have not completed the questionnaires via the OrthoCarolina OBERD 
platform, those questionnaires will be collected at the 1 year follow up 
office visit. 
 
2. 
Randomization: N/A 
 
3. 
Treatment Administration/Intervention:  
 
Observation arm: No changes from baseline surgeon’s management 
pathway.  Anesthesia should be utilized in a routine fashion with all 


 
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routine perioperative medications.  Patients will be discharged on routine 
postoperative medications including opioids, NSAIDS, and any other 
modalities typically used by the treating surgeon.  All data collection 
points will mirror the intervention arm. 
 
Intervention arm:  
a) In the preoperative area, patients will receive an oral dose of both 
gabapentin and celecoxib (toradol if patient has sulfa allergy).  
Communication with the anesthesia team will take place the day 
before surgery to identify the patient as an opioid-free participant, 
and a reminder will be provided while patient meets with the 
anesthesiologist in pre-op.  The patient will be identified as a 
research patient on the hospital chart.  Patients will receive an 
ultrasound-guided interscalene regional block by a board certified 
anesthesiologist in standard fashion without the aid of opioid co-
medication. 
b) Intra-operative management by anesthesia will be done with non-
opioid modalities but should include one dose of intravenous 
acetaminophen during the procedure.  Anesthetic modalities will 
include, but are not limited to, regional block, propofol, IV 
lidocaine, rocuronium/vecuronium, and sevoflurane/desflurane.  If 
the attending anesthesiologist deems it necessary to dose with 
opioids during the procedure, this will be recorded and reported.  
Liposomal bupivacaine will be injected into the peri-articular soft 
tissues as an adjunct to the block performed by the anesthesia 
team.  
c) Post-operative hospital care:  
An in-service will be performed with both the recovery room staff 
and the orthopaedic care floor to the pathway. 
The presence of both the block and the liposomal bupivacaine 
should obviate the concern for pain control in the anesthesia 
recovery area.  
 
Every opioid-free patient will have: 
• Cryotherapy 
• Scheduled gabapentin (300mg q8hr)  
• Toradol (15mg IV q6hr for four doses).  Toradol will 
transition to celecoxib for the duration of the 
hospitalization (or meloxicam for patients with sulfa 
allergy).   
• PRN medications will include both oral and intravenous 
acetaminophen, as well as up to an additional 15mg of 
toradol per 6hr period (noting that the scheduled dose was 
limited to 15mg and not 30mg).  Creatinine clearance will 


 
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be checked upon admission to confirm no underlying 
chronic renal dysfunction.  
• The designed order set includes scheduled medications 
targeting multiple pain receptor targets.  Additionally, 
there are instructions to notify either the principal 
investigator (NH), or resident investigator (DL) directly if 
the patient’s pain continues to be inadequately controlled 
despite the above pathway.  After exhausting all non-
opioid modalities, either NH or DL will approve the 
administration of an opioid at the patient’s request and 
notate this patient for the record. 
 
d) Discharge medications: Upon discharge, patients will continue 
gabapentin 300mg q8hr for an additional 14 days, as well as 
celecoxib (or meloxicam for those with sulfa allergies) for an 
additional 14 days. They will additionally be allowed to continue 
utilizing acetaminophen in a PRN fashion. 
 
• NOTE: Patients with creatinine clearance between 30 and 
60 mL/min will receive a half-dose of all NSAIDs if 
enrolled in the intervention arm of the study. Patients with 
creatinine clearance greater than 60 mL/min will be eligible 
to receive full doses of NSAIDs in the intervention arm of 
the study. 
 
4. 
Data Collection 
i. Preoperative patient data:  
1. Baseline (current and average) pain score (NRS), baseline 
opioid use, baseline creatinine clearance 
2. Patient demographics: Age, Gender, Height, Weight, BMI, 
Tobacco Use, Comorbidities, and Primary Diagnosis 
3. ASES 
4. Simple Shoulder Test (SST) 
5. VR-12 
ii.  Operative chart data: 
1. Surgeon 
2. Surgical approach 
3. Concomitant procedures 
4. Date of surgery 
5. Morphine milli-equivalents (MMI) utilized during procedure 
6. Intraoperative complications 
iii. Postoperative chart data:  
1. Date of discharge 
2. Postoperative patient data: Pain score at 6hr, 12hr, and 24hr 
3. Nursing calculated delirium score at 6, 12, and 24hr: Confusion 
Assessment Method (CAM) [25] 


 
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4. Number of doses of anti-emetic/nausea 
5. Falls 
6. MMI during hospitalization 
7. Treatment failure (Y/N) 
iv. Postoperative patient diaries 
1. Pain NRS: Pain score every 8 hours for three days after 
discharge, then once per day until 2 week visit 
2. Opioid medications taken 
v. 2 week postoperative visit:  
1. Current pain NRS and average pain NRS  
2. Constipation (Y/N) 
3. Nausea (Y/N) 
4. Were you satisfied with your overall pain control? (Y/N) 
5. Have you fallen at home? (Y/N)  
6. Observational Arm: Still using opioids? (Y/N) 
7. ASES 
8. Simple Shoulder Test (SST) 
9. VR-12 
vi. 2 month postoperative visit:  
1. Current pain NRS and average pain NRS  
2. Constipation (Y/N)  
3. Nausea (Y/N)  
4. Were you satisfied with your overall pain control? (Y/N) 
5. Have you fallen at home? (Y/N)  
6. Observational Arm: Still using opioids? (Y/N) 
7. ASES 
8. Simple Shoulder Test (SST) 
9. VR-12 
vii. 1 year postoperative visit: 
1. Current pain NRS and average pain NRS  
2. Constipation (Y/N)  
3. Nausea (Y/N)  
4. Were you satisfied with your overall pain control? (Y/N) 
5. Have you fallen at home? (Y/N)  
6. Observational Arm: Still using opioids? (Y/N)  
7. ASES 
8. Simple Shoulder Test (SST) 
9. VR-12 
 
E. Risks 
• Surgical risks; patients will sign a separate surgical consent form. The 
shoulder replacement surgery risks are the same if patients choose to be in this 
study or not.  
• Loss of confidentiality 
• Risks associated with blood draws include pain, discomfort, bruising and 
infection. Rarely, a person may faint. 


 
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• As with all medications, side effects may include allergic reaction.  Allergic 
reactions may range from minor itching or rash to major reactions which can 
result in death. All of the medications being used in this study are FDA-
approved and are medications that are routinely given after total shoulder 
replacement surgery. 
 
F. Benefits 
This study may or may not improve the condition of the study subjects.  The 
information gained from subjects’ cases may benefit others with the same 
condition. 
 


 
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Proposed timeline: 
Procedure 
Preop/Screen 
Op 
6 hour 
12 hour 
24 hour 
2 week 
2 month 
1 year 
ICF 
X 
  
  
  
  
  
  
 
Demographic 
X 
  
  
  
  
  
  
 
Comorbidities 
X 
  
  
  
  
  
  
 
Creatinine Clearance 
(Intervention Arm Only) 
X 
 
Complications (nausea, 
constipation, falls) 
  
  
X 
X 
X 
X 
X 
X 
Delirium Score (CAM25) 
  
X 
X 
X 
X 
  
  
 
ConMeds (specifically anti-
emetic/nausea and pain 
medication) 
X 
X 
X 
X 
X 
X 
X 
X 
Surgical Information 
  
X 
  
  
  
  
  
 
Pain Score (NRS), current 
X 
  
X 
X 
X 
X 
X 
X 
Pain Score (NRS), average 
X 
  
  
  
  
X 
X 
X 
ASES 
X 
X 
X 
X 
Simple Shoulder Test 
X 
X 
X 
X 
VR-12 
X 
X 
X 
X 
Patient Pain (NRS) Diary± 
X 
 
Patient Pain Medication 
Diary± 
X 
 
± The diaries will be completed daily from day of discharge until the 2 week visit. They will be collected 
at the 2 week visit. 
 
8. Use of Data:  Investigators may use the data for regional and national presentation or peer 
review journal publication. 
 
9. Estimation of Sample Size:  The calculation of the sample size estimate is based on the 
primary outcomes of patient reported post-operative pain (VAS).  Statistical analysis will be 
two-sided with an alpha level of 0.05. Statistical power will be 80% for the primary outcome. 
Assuming a 2-point mean difference in pain VAS between the control and intervention 
groups with a 2.5-point standard deviation in each group [26, 27], 27 patients per group are 
required. Assuming a 30% loss to follow-up, 35 completed patients per group for a total 
sample size of 70 patients will be necessary to ensure statistical significance. 
 
10. Statistical Procedures:  Standard descriptive statistics will be reported including measures 
of central tendency, variance as well as frequencies and proportions. For bivariate analyses, 
chi-square or Fishers Exact tests will be used for categorical data to determine statistical 
differences. For normally distributed interval or continuous variables a student’s T-test will 
be used. For non-normally distributed data a Wilcoxon rank sum test will be used. 
 
11. Data Management:  Data should be entered on at least a weekly basis, via REDCap 
(http://project-redcap.org/).  REDCap is a secure web application designed exclusively to 


 
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support data capture for research studies. It allows users to build and manage online surveys 
and databases quickly and securely with site and personnel specific usernames and 
passwords. REDCap provides audit trails for tracking data manipulation and user activity, as 
well as automated export procedures for seamless data downloads to Excel, PDF, and 
common statistical packages like SPSS, SAS, and Stata. 
 
12. Data Safety Monitoring Plan:  Serious adverse events (SAEs) that are “related,” “probably 
related” or have an “unknown” relatedness to the study procedure, will be reported to the 
data safety monitoring board (DSMD) via email as they occur. Robert Anderson, M.D., 
Chairman, Research Advisory Committee will serve as the safety monitor. A data safety 
monitoring board (DSMB) will review data on a bi-monthly basis or as needed.  The DSMB 
are members of the OrthoCarolina Research Institute (OCRI) Research Advisory Committee. 
At each meeting the study will be reviewed for adverse events, serious adverse events, and 
overall feasibility issues.  
 
13. Funding: This is an investigator initiated study with funding provided by OrthoCarolina 
Research Institute. 


 
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C.  REFERENCES 
 
1. 
Fletcher, D. and V. Martinez, Opioid-induced hyperalgesia in patients after surgery: a 
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2. 
Lee, H.J. and D.C. Yeomans, Opioid induced hyperalgesia in anesthetic settings. Korean 
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McKeown, J.L., Pain Management Issues for the Geriatric Surgical Patient. Anesthesiol 
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Nir, R.R., et al., Preoperative preemptive drug administration for acute postoperative 
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Rouhani, A., et al., Effects of preoperative non-steroidal anti-inflammatory drugs on pain 
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