Effects of Perioperative Dronabinol Use in Total Knee Arthroplasty
Phase: PHASE4
Conditions: Total Knee Arthroplasty, Opioid Use
Sponsor: Hospital for Special Surgery, New York

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Effects of Perioperative Dronabinol Use in Total 
Knee Arthroplasty 
 
 
FUNDER: 
Department of Anesthesiology 
PROTOCOL NO.: 
2019-1416 
VERSION & DATE: 
6/6/2023 
 
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the Hospital for Special Surgery assume any responsibility for unauthorized use of this protocol. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
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TABLE OF CONTENTS 
 
TABLE OF CONTENTS ............................................ 2 
PROTOCOL SYNOPSIS ........................................... 3 
1.0 
INTRODUCTION ............................................. 5 
2.0 
OBJECTIVE(S) OF CLINICAL STUDY .......... 7 
3.0 
STUDY HYPOTHESES .................................. 7 
4.0 
STUDY DESIGN ............................................. 8 
4.1 
Endpoints ....................................................................................................................... 8 
4.1.1 Primary Endpoint ...................................................................................................... 8 
4.1.2 Secondary Endpoints ................................................................................................ 8 
4.2 
Study Sites ..................................................................................................................... 9 
5.0 
STUDY POPULATION ................................... 9 
5.1 
Number of Subjects ........................................................................................................ 9 
5.2 
Inclusion Criteria............................................................................................................. 9 
5.3 
Exclusion Criteria ........................................................................................................... 9 
6.0 
PROCEDURES ............................................... 9 
6.1 
Intraoperative Protocol ................................................................................................... 9 
6.2 
Data Collection ............................................................................................................. 11 
7.0 
STATISTICAL ANALYSIS ............................ 12 
8.0 
ADVERSE EVENT ASSESSMENT .............. 13 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
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PROTOCOL SYNOPSIS 
Protocol Title: 
Effects of Perioperative Dronabinol Use in Total Knee Arthroplasty 
Protocol Number: 
2019-1416 
Protocol Date: 
6/6/2023 
Sponsor: 
Department of Anesthesiology 
Principal Investigator: 
Kethy Jules-Elysee, MD 
Objective: 
The current study will investigate the potential therapeutic benefit of 
perioperative dronabinol use in patients undergoing unilateral total 
knee arthroplasty (TKA). With current advanced regional anesthetic 
techniques and peripheral nerve blocks, pain is generally well 
controlled following TKA on post operative day (POD) 1. There is a 
rebound pain that exists, however, on POD2 when these blocks are no 
longer effective. We aim to study a potential reduction in opioid 
consumption on POD2 with perioperative dronabinol use in TKA 
patients. 
Study Design: 
Randomized Control Clinical Trail 
Enrollment: 
114 
Subject Criteria: 
 
1) Patients aged between 18-70 years old with osteoarthrosis 
scheduled for primary unilateral knee arthroplasty with a 
participating surgeon. 
2) Planned use of regional anesthetic technique during surgery 
involving infiltration between the popliteal artery and the capsule of 
the posterior knee (IPACK), adductor canal block (ACB), and PAI 
3) Ability to follow study protocol. 
Data Collection: 
Sources: EPIC, Medical Records, and Patient Reported. 
 
Variables: Name, Email, MRN, DOB, Age, Height, Weight, Race, 
Ethnicity, Gender, BMI, ASA, Co-morbidities, Allergies, 
Surgeon/Anesthesiologist, Anesthesia events, PONV, Opioid use, 
Non-opioid analgesic consumption, side effects/adverse events, 
Patient Satisfaction, length of PACU stay, length of hospital stay, 
pulse-oximetry data, sleep actigraph data, painOUT questionnaire, 
DN4 questionnaire, ORSDS, Blinding Assessment, NRS pain scores 
(on ambulation & at rest) 
Statistical Analysis: 
• 
Two-sample test 
• 
Alpha level: 0.05 (one-sided) 
• 
Beta or power level: 80% 
• 
Primary outcome: opioid consumption 24-48 hours after 
anesthesia stop 

 
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• 
Number of groups being compared: 2 
• 
Effect size or change expected between groups: 30% 
reduction in opioid consumption 24-48 hours after anesthesia 
stop 
• 
Resulting number per group: 50 
• 
Total sample size required: 50 + ~10% to account for attrition 
= 55, total sample size is 110 with 4 additional patients added 
to account for unexpected attrition 
 
 
 

 
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1.0 INTRODUCTION 
With current emphasis on multimodal analgesia and limiting opioid consumption, the utility of 
cannabinoids as medications in treatment of acute pain have been relatively unexplored. In 
addition, the widespread legalization of medical cannabis in several states has led to use of 
cannabinoids as adjuvants and opioid substitutes for managing pain. While the use of 
medical cannabis and cannabinoids is supported by strong evidence for the management of 
chronic pain (1), the literature for use in the acute pain population has been mixed, with 
limited randomized control trials.  A systematic review of European literature by Stevens et al 
stated that on the basis of seven included RCTs, cannabinoids have no role in the 
management of acute pain (2).  However, the RCTs included had either small sample size, 
low generalizability, or are outdated, with the most recent study from 2013. Only two studies 
included in this review used oral medications, though lacked in standardized surgical 
population, postoperative analgesia, and study power with very small sample size (3, 4). 
Other meta-analyses have displayed strong animal model, pre-clinical evidence of the 
cannabinoids and reduced opioid consumption (5). Additionally, literature has shown promise 
in the lack of addictive and abuse potential in therapeutic use of dronabinol (6).  However, 
clinical studies included in this review were of low- quality evidence and heterogeneous in 
nature, with mixed surgical populations and varied anesthetic techniques. A recent study by 
Hickernell et al demonstrated reduced opioid consumption in postoperative TKA and total hip 
arthroplasty patients receiving dronabinol. These data are promising for the role of 
cannabinoids in the acute pain population. However, as a retrospective cohort study it lacked 
randomization and consisted of a varied patient population for both surgical procedure and 
anesthetic technique. In addition, the reduction in opioid consumption was a consequence of 
shorter hospital length of stay, with no difference in patient opioid consumption per day (7). 
Prior studies by this research team have demonstrated improvements in pain scores, opioid 
consumption, and patient satisfaction with novel peripheral nerve block techniques (8). With 
these recent advances in regional anesthesiology at HSS, pain is well controlled in the first 
24 hours post operatively. However, these data also revealed that 24-48 hours after block 
placement, a rebound pain existed as patients in the treatment group had notably increased 
pain scores and opioid consumption on POD2. There is a need to investigate novel, non-
opioid medications to help manage rebound pain, decrease opioid use and increase patient 
satisfaction. Additionally, there is growing risk of chronic post surgical pain (CPSP) in total 
knee arthroplasty patients. Recent data has demonstrated a much greater risk of CPSP 
development in TKA patients than previously reported, and acute post surgical pain has been 
identified as an independent risk factor for CPSP (15, 16). Aside from improvement in post 
surgical rebound pain, there is a need to mitigate the acute post surgical pain experience in 
order to hinder development of CPSP in TKA patients. Patients have expressed willingness 
to use cannabinoids as a novel therapeutic modality to manage their pain post operatively 
(9). In addition to potential therapeutic benefit in acute pain, dronabinol is a promising 
pharmacologic intervention in obstructive sleep apnea treatment. A recent phase II RCT 
demonstrated reduction in apnea-hypopnea index in OSA patients in the dronabinol 
treatment group (10). Prior literature has also suggested benefit of dronabinol as an apnea 
suppressant and respiratory stabilizer in animal models, via stimulation of central cannabinoid 
receptors (11, 12).  Improvements in the qualitative EEG sleep patterns have also been 
shown following dronabinol therapy in human models (13). The current research team has 
shown that in the TKA patient, STOP-Bang scores were unrelated to oxygen desaturation 
episodes post operatively.  Additionally, postoperative desaturations were correlated with 

 
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longer hospital length of stay in these patients. This increase may have been due to an 
increased opioid consumption that was demonstrated by these patients on POD1 and POD2 
(14). If therapeutic dronabinol can limit opioid consumption, it may attenuate the POD1-POD2 
increase in oxygen desaturation events. Therefore, in this study we chose to examine the 
efficacy of dronabinol, a readily available FDA-approved cannabinoid, in reducing opioid 
consumption in TKA patients on POD2, when rebound pain is experienced in many patients. 
The current study can generate new evidence as a randomized control trial, with potential 
benefit in decreased opioid consumption, pain on POD2, hospital length of stay, as well as 
improvements in oxygen desaturation episodes. 
References:  
1. Whiting PF, Wolff RF, Deshpande S, et al. Cannabinoids for Medical Use: A Systematic 
Review and Meta-analysis. JAMA. 2015;313(24):2456–2473. doi:10.1001/jama.2015.6358 
2. Stevens AJ, Higgins MD. A systematic review of the analgesic efficacy of cannabinoid 
medications in the management of acute pain. Acta Anaesthesiologica Scandinavica 2017 
3. Buggy, D. J., Toogood, L., Maric, S., Sharpe, P., Lambert, D. G., and Rowbotham, D. J. 
(2003). Lack of analgesic efficacy of oral delta-9-tetrahydrocannabinol in postoperative pain. 
Pain 106, 169–172. doi: 10.1016/S0304-3959(03)00331-2 
4. Beaulieu, P. Can J Anesth (2006) 53: 769. https://doi.org/10.1007/BF03022793 
5. Nielsen S, Sabioni P, Trigo JM, Ware MA, Betz-Stablein BD, Murnion B, et al. Opioid-
sparing effect of cannabinoids: a systematic review and meta-analysis. 
Neuropsychopharmacology (2017) 42:1752–65. doi: 10.1038/npp.2017.51 
6. Calhoun SR, Galloway GP, Smith DE. Abuse potential of dronabinol (Marinol®) J 
Psychoactive Drugs. 1998; 30: 187–96. 
7. Hickernell T.R., Lakra A., Berg A., Cooper H.J., Geller J.A., Shah R.P. Should 
Cannabinoids Be Added to Multimodal Pain Regimens After Total Hip and Knee 
Arthroplasty?  Journal of Arthroplasty.  (2018), 33 (12) , pp. 3637-3641. 
8. Kim DH, Beathe JC, Lin Y et al. Addition of infiltration between the popliteal artery and the 
capsule of the posterior knee and adductor canal block to periarticular injection enhances 
postoperative pain control in total knee arthroplasty: A randomized controlled trial. Anesth 
Analg 2018. 
9. Khelemsky Y, Goldberg AT, Hurd YL et al (2017) Perioperative patient beliefs regarding 
potential effectiveness of marijuana (cannabinoids) for treatment of pain: a prospective 
population survey. Reg Anesth Pain Med 42(5):652–659 
10. Carley DW, Prasad B, Reid KJ et al. Pharmacotherapy of apnea by cannabimimetic 
enhancement, the PACE clinical trial: Effects of dronabinol in obstructive sleep apnea. Sleep 
2018; 41. 

 
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11. Calik MW, Carley DW. Effects of Cannabinoid Agonists and Antagonists on Sleep and 
Breathing in Sprague-Dawley Rats. Sleep. 2017; 40(9):zsx112.     
12. Carley DW, Paviovic S, Janelidze M, Radulovacki M. Functional role for cannabinoids in 
respiratory stability during sleep. Sleep. 2002; 25 (4): 391–398. 
13. Farabi SS; Prasad B; Quinn L; Carley DW. Impact of dronabinol on quantitative 
electroencephalogram (qEEG) measures of sleep in obstructive sleep apnea syndrome. J 
Clin Sleep Med 2014;10(1):49-56. 
14. Jules-Elysée, Kethy M., et al. “Clinical Indicators of the Need for Telemetry Postoperative 
Monitoring in Patients With Suspected Obstructive Sleep Apnea Undergoing Total Knee 
Arthroplasty.” Regional Anesthesia and Pain Medicine, vol. 43, no. 1, 1 Jan. 2018, pp. 43–49 
15. Gungor S, Fields K, Aiyer R.  Persistent post-surgical pain risk after total knee 
arthroplasty: A retrospective study.  2018 World Congress on Regional Anesthesia and Pain 
Medicine.  2018 April 19-21.  New York, NY. ASRA. 2018.  
16. Buvanendran A, Delle Valle CJ, Kroin JS, et al. Acute postoperative pain is an 
independent predictor of chronic postsurgical pain following total knee arthroplasty at 6 
months: A prospective cohort study. Reg Anesth Pain Med 2018. 
2.0 OBJECTIVE(S) OF CLINICAL STUDY 
With current regional anesthetic nerve block techniques, post-operative pain is well controlled 
following TKA on Postoperative Day (POD) 1.  However, on POD2 there is typically a rebound 
pain that exists, especially with patient activity and ambulation.  The current study will examine the 
potential opioid-sparing effect of perioperative dronabinol use in total knee arthroplasty patients on 
POD2. 
Research questions/specific aims: 
a) Does perioperative dronabinol use (starting in the immediate preoperative period (enrollment 
before 1 PM) , with BID dosing concluding the evening of POD2) affect postoperative opioid 
consumption 24-48 hours following total knee arthroplasty? 
b) Is there an effect of perioperative dronabinol use in the total knee arthroplasty patient on 
POD2 pain scores with ambulation?   
c) Will hospital length of stay following total knee arthroplasty be affected in patients who use 
perioperative dronabinol as compared to control?  
d) Does the use of perioperative dronabinol affect time to reach physical therapy discharge 
goals in postoperative total knee arthroplasty patients?  
e) Is there a change in number of postoperative oxygen desaturation events in patients following 
total knee arthroplasty based on perioperative dronabinol use?  
3.0 STUDY HYPOTHESES 
We hypothesize that patients in the perioperative dronabinol treatment group will have 
decreased opioid consumption 24-48 hours postoperatively, as well as reductions in all 
secondary outcomes.   

 
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4.0 STUDY DESIGN 
4.1 
Endpoints 
4.1.1 
Primary Endpoint 
Primary Outcome: The primary outcome of the study will be patient opioid consumption 
24-48 hours post operatively, defined by total morphine equivalents (MEs). This outcome 
will be measured throughout the patient hospitalization and conclude at 48 hours 
postoperatively. 
4.1.2 
Secondary Endpoints 
1. Time to reach discharge physical therapy goals, as defined by the number of hours 
required to meet the following criteria:  stable vital signs during PT, safe independent 
transfer from bed to standing as well as transfer in and out of seated position, ability to 
walk 40 feet only with aid of crutch or walker. This outcome will be measured prior to 
patient discharge. 
2. Patient pain with ambulation on POD2, defined by patient reported Numeric Rating Scale 
(NRS) pain score.  Measurements will take place following ambulation on morning of 
POD1, 2, 7, 90, 180. 
3. Patient pain at rest upon PACU arrival, and in the morning of POD1, POD2, and POD7. 
Measurements will also be taken at POD90 and 180   
4. Patient Pain with ambulation during morning PT session on POD1, and POD2 
5. Patient opioid consumption at PACU, on POD1, POD2.  
6. Hospital length of stay from day of admission to discharge. This outcome will be measured 
on the day of patient discharge from the hospital. 
7. The number of desaturation events. Postoperative oxygen desaturation events will be 
defined as measured SpO2 of <88% for 20 seconds or longer. This outcome will be 
measured beginning in the immediate postoperative period on POD0 (in the PACU) and 
will continue until patient discharge. 
8. Cognitive assessment at PACU, on POD1, POD2 
9. painOUT score on POD1 and POD2, POD7, POD90, and POD180 
10. DN4 questionnaire score on POD1, POD2, POD7, POD90, and POD180 
11. ORSDS on POD1 and POD2. 
12. Non opioid analgesic consumption (from PACU to POD7). This outcome will be measured 
on PACU, POD1, POD2, and POD7.  
13. NRS Pain and opioid use, POD 90.  (Pain at POD 90, or 3 months, is viewed as the onset 
of chronic pain) 

 
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14. Sleep disturbance via actigraphy measurement using the ActiGraph wGT3X-BT activity 
monitor. Measured as total sleep time, wake after sleep onset, sleep efficiency, number of 
awakenings from PACU to discharge. 
 
4.2 Study Sites 
This study will take place at the main campus of the Hospital for Special Surgery (HSS). 
5.0 STUDY POPULATION 
5.1 
Number of Subjects 
114 
5.2 
Inclusion Criteria 
Subjects will be included if: 
• 
Patients >18 years old with osteoarthrosis scheduled for primary unilateral knee 
arthroplasty with a participating surgeon 
• 
Planned use of regional anesthetic technique during surgery involving infiltration 
between the popliteal artery and the capsule of the posterior knee (IPACK), adductor 
canal block (ACB), and PAI 
• 
Ability to follow study protocol 
5.3 
Exclusion Criteria 
Subjects will be excluded from the study if: 
• 
Contraindication to regional or neuraxial anesthetic  
• 
Intended use of general anesthesia 
• 
Intolerance, contraindication, or allergy to any of the study medications or excipients 
(e.g., sesame oil) 
• 
Patients <18 or >70 years of age 
• 
Chronic opioid use (for >3 months prior to surgery) 
• 
Cannabis/cannabinoid use within the last 3 months 
• 
American Society of Anesthesiology class IV or greater 
• 
Active or history of major mental illness (as defined by the Diagnostic and Statistical 
Manual of Mental Disorders 5 (DSM-5). e.g., major depressive disorder, anxiety, bipolar 
disorder, schizophrenia) 
• 
History of seizures 
• 
Use of antidepressants 
• 
Use of anticonvulsants 
• 
Non-English speakers 
• 
BMI ≥40 
• 
Sleep Apnea 
6.0 PROCEDURES 
6.1 
Intraoperative Protocol 
Preoperative Holding Area:  Study group patients will receive the first dose of dronabinol (5 
mg), and control group will receive first non-active placebo dose.  Enrollment in the study will 

 
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begin no later than 1 PM, ensuring that patients will receive intervention before 1 PM 
preoperatively and the second BID dose at 10 PM on POD0.  BID dosing will continue 
through the morning of POD2.  
 
Intraoperative:  Both groups in the study will receive IV sedation intraoperatively with IV 
midazolam (2-5 mg) bolus, as well as propofol infusion titrated to patient sedation without 
respiratory depression and stable hemodynamics.  Anti-emetics of ondansetron 4 mg IV and 
dexamethasone 10 mg IV will be administered, along with 20 mg IV famotidine for GI 
prophylaxis.  Ketorolac (15mg-30 mg) will be dosed intraoperatively, though held if patient 
baseline creatinine >2.  Intraoperative ketamine (20mg-50mg) will also be administered by 
the treating anesthesiologist, with dosage based on clinical judgment.   
All patients will receive a neuraxial anesthetic with 60 mg of 1.5% Mepivacaine dosed in the 
spinal.     
All patients will receive both adductor canal and IPACK peripheral nerve blocks.  Adductor 
canal blocks will be performed with 15 mL of 0.25% bupivacaine mixed with 2 mg of 
preservative free dexamethasone, and IPACK blocks will be performed with 25 mL of 0.25% 
bupivacaine.   
"All patients will receive both a deep and superficial component of periarticular injection (PAI). 
The deep injections will consist of Cefazolin 500mg per 10 ml with Sodium Chloride 0.9% 22 
ml, Bupivacaine-Epinephrine PF (marcaine w/EPI) 150mg, methylprednisolone acetate 
(DEPO-MEDROL) 40mg. The superficial injection will consist of bupivacaine 0.5% 20 mL with 
Sodium Chloride 0.9% 20 mL. If there are contradictions to DEPO-MEDROL, patients may 
receive deep injections that do not contain DEPO-MEDROL." 
Post-anesthesia Care Unit:   
Patients will receive a pain regimen consisting of:  
• 
Acetaminophen- intravenous, for 15 Minutes, every 6 hours for 1 Doses, For 1 Dose, 
followed by PO q6 
• 
Ketorolac 15-30 mg IV q6 x4 doses, dosed appropriately  
• 
Oxycodone immediate release 5 mg PO q4 PRN for NRS pain score 0-6 
• 
Oxycodone immediate release 10 mg PO q4 PRN for NRS pain score 7-10 
• 
Hydromorphone 0.5 mg, IV Push, every 5 min PRN Starting S For 2 Doses, 
Breakthrough Pain, in PACU, Starting S, For 2 Doses, PACU (only) 
• 
IV opioid dosing Patient controlled Analgesia for salvage therapy (NRS>6 for >2 
hours) 
Floor Care: 
• 
Continue acetaminophen 
• 
Meloxicam 7.5-15mg PO daily to start after ketorolac dosing is completed 
• 
Oxycodone immediate release 5 mg PO q4 PRN for NRS pain score 0-6 
• 
Oxycodone immediate release 10 mg PO q4 PRN for NRS pain score 7-10 

 
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6.2 
Data Collection 
The following data will be collected: 
 
Pre-operative/Baseline 
• 
Name 
• 
Email 
• 
MRN 
• 
DOB 
• 
Age 
• 
Height 
• 
Weight 
• 
Race 
• 
Ethnicity 
• 
BMI 
• 
ASA 
• 
Co-morbidities 
• 
Allergies 
 
Surgical procedure (Intra-operative) 
• 
Surgeon/Anesthesiologist 
• 
Surgery/Anesthesia events 
 
Post-Operative Day 0 (POD 0) 
• 
NRS Pain Scores (on ambulation & at rest) 
• 
Opioid consumption 
• 
Non-opioid analgesic consumption 
• 
Cognitive assessment/subjective drug effects/adverse events 
• 
Continuous O2 saturation (Masimo) 
• 
Sleep actigraphy 
 
Post-Operative Day 1 (POD 1) 
• 
NRS Pain Scores (on ambulation & at rest) 
• 
Opioid consumption 
• 
Non-opioid analgesic consumption 
• 
Cognitive assessment/subjective drug effects/adverse events 
• 
Continuous O2 saturation (Masimo) 
• 
Sleep actigraphy 
• 
painOUT questionnaire 
• 
DN4 questionnaire 
• 
ORSDS 
 
Post-Operative Day 2 (POD 2) 
• 
NRS Pain Scores (on ambulation & at rest) 
• 
Opioid consumption 
• 
Non-opioid analgesic consumption 
• 
Cognitive assessment/subjective drug effects/adverse events 
• 
Continuous O2 saturation (Masimo) 
• 
Sleep actigraphy 
• 
painOUT questionnaire 
• 
DN4 questionnaire 
• 
ORSDS 
 

 
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Discharge 
• 
Blinding assessment 
 
Post-Operative Day 7 (POD 7) 
• 
Blinding assessment 
• 
NRS pain scores (on ambulation & at rest) 
• 
Opioid consumption 
• 
Non opioid analgesic consumption 
• 
painOUT questionnaire 
• 
DN4 questionnaire 
 
Post-Operative Day 90 (POD 90) 
• 
NRS pain scores (on ambulation & at rest) 
• 
Opioid consumption 
• 
painOUT questionnaire 
• 
DN4 questionnaire 
 
Post-Operative Day 180 (POD 180) 
• 
NRS pain scores (on ambulation & at rest) 
• 
painOUT questionnaire 
• 
DN4 questionnaire 
7.0 STATISTICAL ANALYSIS 
1. Proposed analysis (e.g., student’s t-test, ANOVA, chi-square, regression, etc.): two-
sample t-test       
2. Interim analysis planned? No. 
3. Alpha level:  0.05 
4. Beta or power level: 80%   
5. Primary outcome variable estimate (mean +/- s.d. for continuous outcome, 
frequency/percentage for categorical variable): Opioid consumption 24–48 h after 
anesthesia stop, Control group= 65.7 ± 40, Treatment group=  45.99 ± 28 (Kim 2018) 
6. Number of groups being compared (use 1 for paired analysis within the same 
subjects):  2 
7. Effect size or change expected between groups:   30% reduction in Opioid consumption 
24–48 h after anesthesia stop 
8. Resulting number per group: 50 
9. Total sample size required:  50 + ~10% to account for attrition = 55, total sample size 110 
with 4 additional patients added to account for unexpected attrition 
 
The primary outcome (Opioid consumption 24–48 hours after anesthesia stop) will be compared 
between the groups using a two-sample t-test or Wilcoxon rank-sum test, depending upon the 
distribution of the data. 

 
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Secondary outcomes (listed above, Section II Q11.) measured once per patient will be analyzed by t-
test or Wilcoxon rank-sum test (continuous data) and χ2 or Fisher’s exact test (categorical data). 
Outcomes 
measured 
multiple 
times 
per 
patient 
(e.g., 
NRS 
Pain 
Scores, 
Cognitive 
assessment/Subjective drug effects/Adverse events, Continuous O2 saturation monitoring, painOUT, 
ORSDS, Opioid Consumption) will be analyzed using regression based on a generalized estimating 
equation approach.  
 
Balance on demographics and baseline characteristics will be assessed by calculating standardized 
differences (difference in means or proportions divided by the pooled standard deviation) between 
groups. An absolute value of 0.2 or greater will be interpreted as more imbalance than would be 
expected by chance (Austin 2009). 
 
All analyses will be performed on an intention-to-treat basis. 
 
For pulse-oximetry data, we will use Masimo Trace™ software to collect and visualize data: 
http://www.masimo.com/products/analytics/trace/  
 
For actigraphy data, activity monitors will be collected on the day of discharge. Raw actigraphy data 
will be extracted and analyzed using CenterPoint Study Admin System software. 
 
8.0 ADVERSE EVENT ASSESSMENT 
All Adverse Events (AEs) will be reported in the final study report.