Combined Administration of Bupivacaine and Exparel Versus Bupivacaine or Exparel Alone for Postoperative Analgesia in Posterior Lumbar Spine Surgery - A Prospective Randomized Study
Phase: PHASE4
Conditions: Low Back Pain, Lumbosacral Radiculopathy, Lumbar Disc Degeneration, Lumbar Disc Herniation, Stenosis, Spondylolisthesis, Spondylolysis, Deformity of Spine
Sponsor: Virtua Health, Inc.

V. Oct 13 2016 
IRB Application for Population Health and Quality Research Study 
Title of Study: Combined administration of Bupivacaine and Exparel versus Bupivacaine or Exparel alone 
for postoperative analgesia in posterior lumbar spine surgery - A Prospective Randomized Study  
 
Background and Statement of Context 
It is estimated that 1 million elective (inpatient and outpatient) spinal surgery procedures are performed 
each year in the US, including 464,000 spinal fusions, 342,000 discectomies, and 213,000 laminectomies 
[1, 2]. Spine surgery is thought to result in severe postsurgical pain for a variety of reasons, including the 
size of the incision, the damage that may occur to ligaments, muscles, bone, discs, and joints when 
performing the surgical procedure, the existence of preoperative pain, and opioid-induced hyperalgesia 
(OIH) that may occur with pre-operative opioid use [3]. OIH may result in sensitization of the dorsal horn 
of the spinal cord where pain signals are first processed, reducing the threshold required to perceive pain, 
thereby prolonging and magnifying its effect [4]. Pain following spine surgery is thought to be most intense 
after a few hours, gradually subsiding over a few days, as supported by pain severity scores recorded in 
studies of various approaches to managing postsurgical pain [5]. Uncontrolled postsurgical pain results in 
delayed mobilization and consequently longer length of hospital stay (LOS) and morbidity associated with 
bed rest, increased opioid usage, and lower patient satisfaction.  
A variety of approaches are currently used to manage postsurgical pain, including pre-emptive analgesia, 
systemic analgesia, regional analgesia, and local analgesia [6]. These approaches are often combined in a 
multimodal regimen intended to address the various components of postsurgical pain, including 
nociceptive, neuropathic, and inflammatory mechanisms [7]. Many of the current approaches to 
managing postsurgical pain require use of opioid analgesics such as morphine, fentanyl, hydromorphone, 
hydrocodone, or oxycodone [8]. Many of these approaches provide only temporary pain control since the 
medications used have a short duration of effectiveness [9, 10]. Repeated or continuous dosing is 
therefore necessary to extend their effectiveness, which must be administered by clinical staff (e.g. IV or 
IM bolus), Patient Controlled Analgesia (PCA) device, elastomeric pump, or taken orally when permitted 
(e.g. after regaining gastrointestinal motility).  
Although short-term opioids can be effective to manage moderate to severe pain, they are associated 
with a variety of opioid related adverse events (ORAEs), including potentially incapacitating side effects 
and serious adverse events. For postsurgical pain, patients are at greatest risk for ORAEs during the first 
24 hours after surgery when their opioid use is highest [11]. The use of opioids to manage postsurgical 
pain may be of particular concern for spine surgery, since many patients are already using opioids prior 
to their surgical procedure. This increases the possibility of ORAEs with higher perioperative doses and 
continued use beyond the perioperative period [3]. In addition, consumption of opioids is often an 
outcome measure in spine surgery, and continued or increased use is considered an indicator that the 
surgical procedure was not successful [12]. It may therefore be beneficial to minimize the amount of 
opioids consumed for postsurgical pain. 

V. Oct 13 2016 
Given the limitations of current approaches to managing postsurgical pain, as well as the consequences 
of not adequately managing pain following surgical procedures, researchers are continually developing 
and investigating new approaches that provide optimal pain management. Postsurgical pain management 
regimens are also being evaluated and refined as a component of broader enhanced recovery after 
surgery (ERAS) initiatives intended to improve outcomes, reduce hospital LOS, and promote return to 
normal activities following elective surgical procedures [13]. These initiatives generally favor approaches 
to manage postsurgical pain that may increase early ambulation and discharge (e.g. regional or local 
analgesia with local anesthetics) while discouraging those that may decrease them (e.g. IV PCA with 
opioids). 
Approved by the FDA in 2011, Exparel (liposomal bupivacaine) is a sustained-release version of the local 
anesthetic bupivacaine. While bupivacaine may last 6 to 12 hours to provide post-surgical relief, it is 
claimed that Exparel can last up to 72 hours after local infiltration at the surgical site [14]. Different studies 
have also compared the efficacy of Exparel to bupivacaine for the management of postsurgical pain 
following various surgical procedures, including inguinal hernia repair, breast augmentation, and TKA [15-
20]. While some of these studies have supported the efficacy of Exparel to provide superior relief of 
postsurgical pain, others have found bupivacaine to be just as effective [20]. There is still however, a 
paucity of literature on the efficacy of Exparel for spine surgery pain management.  
 
Study Questions/Objectives and Hypothesis 
This study is aimed at prospectively examining clinical and economic outcomes when managing 
postsurgical pain using local infiltration of Exparel for patients undergoing primary, 1 or 2 level, lumbar 
laminectomy with or without fusion. There is a growing body of evidence suggesting that combining 
Exparel with a short acting numbing medicine gives much better pain coverage. The rationale is that 
Exparel can take several hours to have anesthetic onset and conventional thinking believes that if we can 
cover the immediate postoperative pain better with an immediate acting anesthetic to bridge the onset 
gap, then better outcomes will be achieved. The combination of these medications have been used in 
various studies previously in other areas of the body both in orthopedics and non-orthopedics and no 
adverse effects of combining these medications and in similar quantities/dosing have been observed 
[22,23,24]. To this end, we hypothesize that compared to patients that only received local infiltration of 
bupivacaine or only administered Exparel, the intervention group treated to a combination of Exparel and 
bupivacaine would, during their hospital stay following surgery, experience: 
1. 
Reduced mean postoperative pain score (Wong-Baker pain faces scale of 0-no pain, to 10-extreme 
pain) 
2. 
Reduced total consumption of opioids (in mean morphine equivalents)  
3. 
Reduced overall cost of postoperative pain control medications  
4. 
Decreased incidence of ORAEs 

V. Oct 13 2016 
5. 
Reduced time to achieve physical therapy discharge criteria (criteria set according to each 
patient’s living situation, preoperative physical function, comorbidities, and other goals)  
6. 
Reduced inpatient length of stay (LOS) 
 Study Benefits to Virtua 
This study could potentially benefit Virtua in several ways. If Exparel is shown to reduce postoperative 
pain for spine surgery patients, and consequently reduce their opioid consumption for postoperative pain 
management, then there could be the potential to see an improvement in patient satisfaction with 
regards to pain management. In addition, Virtua could stand to gain some cost savings if Exparel is shown 
to support decreased incidence of ORAEs such as respiratory depression, leading to reduced time to 
physical therapy discharge criteria and consequently reduced LOS. 
If on the other hand, the study indicates that the more expensive Exparel is no more effective at managing 
postoperative pain compared to the cheaper alternatives, then Virtua stands to directly gain significant 
cost savings by adopting the use of the cheaper options as standard practice.           
Study Methodology 
Patients who meet all of the following inclusion criteria may be eligible to participate in the study if: 
1. 
Age 18 or older; 
2. 
Primary indication is low back pain, lumbosacral radiculopathy, lumbar disc degeneration, lumbar 
disc herniation, stenosis, spondylolisthesis, spondylolysis, or deformity requiring surgical 
intervention; 
3. 
Scheduled to undergo primary, 1 or 2 level, posterior lumbar laminectomy with or without fusion, 
discectomy with fusion, or fusion at Virtua Memorial Hospital; 
4. 
Willing to provide informed consent, participate in study, and comply with study protocol. 
Patients who meet any of the following criteria may not be eligible to participate: 
1. 
Hypersensitivity or allergy to local anesthetics; 
2. 
Pregnant or contemplating pregnancy prior to surgery; 
3. 
Previous surgery in lumbar spine (i.e. other than microdiscectomy); 
4. 
Prior treatment for alcohol, recreational drug, or opioid abuse; 
5. 
Serious spinal conditions (e.g. spinal cord compression, cauda equina syndrome, spinal infection, 
spinal tumor, spinal fracture, inflammatory or systemic spinal arthritis); 
6. 
Surgery involving more than 2 vertebral levels; 

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7. 
Worker’s compensation or personal injury related to lumbar spine (treatment outcomes may be 
affected by patient’s personal interests [21]; could also run into potential issues with 
reimbursement). 
8. 
Lactating women 
9.  
Patients with end stage liver disease 
During the preoperative office visit, the surgeon will inform patients that appear to meet study eligibility 
criteria, about the study, and discuss the differences between the three postoperative pain management 
alternatives, including their potential risks and benefits. The surgeon will make clear to the patient that 
consenting to be a part of the study means that the patient has agreed to be randomly assigned to one of 
the three postoperative pain management groups. The patient would be told that the random assignment 
is going to be determined by rolling a standard die. The patient would be informed that the patient’s pain 
would be controlled regardless of group assignment and that no placebos would be used.  
Patients who agree to learn more about the study will be approached by a designated and trained study 
physician assistant (PA), briefly informed about the study, and asked if they wish to complete the 
screening questionnaire (Appendix 1) to see if they may be eligible to participate. Once the screening 
questionnaire is completed by the patient, it will be reviewed by the PA to ask any required clarifying 
questions and obtain additional information to determine eligibility. Participants who appear to meet 
eligibility criteria will be reviewed by the PA with one of the study investigators prior to confirming if they 
are eligible to enroll in the study. 
Patients who are deemed eligible to participate in the study and are willing to participate will be asked by 
the PA to complete the research informed consent. This document will be summarized verbally by the PA 
and potential participants will be given the opportunity to ask questions about the protocol or their 
involvement prior to providing consent. Those who agree to participate and provide research informed 
consent will be enrolled in the study, and given a copy of the research informed consent document. The 
patient’s informed consent would be added to the patient’s chart. 
On the day of surgery, in the operating room, the circulating nurse will roll a die to randomly assign the 
patient to one of the three pain management groups. The study intervention group (die roll outcome 1 or 
2) will receive a local infiltration of EXPAREL and bupivacaine 0.5% w/v solution into the surgical site (1 
level patients – 20 mL Exparel + 30 mL bupivacaine 0.5% w/v solution; 2 level patients – 20 mL Exparel 
diluted to 40mL + 30 mL bupivacaine 0.5% w/v solution). The two medications will not be combined in the 
same syringe to minimize the possibility of a direct interaction between the two. While to date, no such 
interaction has been confirmed, we will maintain a strict “no mixing of bupivacaine and Exparel in the 
same syringe” policy throughout this study. The second group (die roll outcome 3 or 4) will only be 
administered local infiltration of Exparel (1 level patients – 20 mL Exparel; 2 level patients – 20 mL Exparel 
diluted to 40 mL). The third group will be treated to a local infiltration of 30 mL bupivacaine 0.5% w/v 
solution. Anesthesiologists will use their usual pre-operative and intra-operative techniques for all study 
participants and both study groups will receive nurse-administered rescue opioids as needed.  

V. Oct 13 2016 
The patients and all staff, including hospital nursing staff, case management, and physical therapists, will 
be blinded as to which pain management treatment the patient received. While the surgical team cannot 
be blinded because the appearance of the drugs is different, they will however, not be assessing the 
outcome measures. 
The primary outcome in this study will be the mean postoperative pain score derived from the pain scores 
recorded by the nursing staff in each participant’s clinical records using the visual analog scale of 0-no 
pain to 10-extreme pain, several times in each 24-hour period, for the entire duration of the patient’s 
hospital stay. Adopting [20] assumptions of a target reduction in mean overall postoperative pain scores 
of 1 point on the VAS and our anticipated variance of 2, it is estimated using one-way analysis of variance 
that for a statistical power of 80% and significance level of 0.05, a minimum of 40 participants will be 
required in each study group for a total of 120 study participants. To minimize the possibility of dropouts 
or incomplete data impacting the analysis, a minimum of 45 participants will be enrolled in each study 
group, for a total of 135 enrollees. 
Secondary outcome measures in this study include total opioid consumption. All opioid analgesics used in 
the hospital will be recorded in the participant’s clinical record, including: Name of medication (e.g. 
morphine); Dose administered (e.g. 10mg); Route of administration (e.g. IV, IM, oral); Reason for 
administration (e.g. surgical site pain). All opioid analgesics will be converted into oral mg morphine 
equivalent to determine the total dose of opioids used during the hospital stay using the conversion 
factors in Appendix 2. Other secondary outcome measures include mean time to achieve physical therapy 
discharge criteria, mean LOS, and incidence of ORAEs. ORAEs will be documented using the checklist 
shown in Appendix 3 with assistance from a nurse during every nursing shift (i.e. every 12 hours) until 
hospital discharge).  
Means will be compared among all the three arms using analysis of variance, proportions will be compared 
using chi-square tests, and logistic regression will be used to analyze for confounding effects. All statistical 
analyses will be conducted in Minitab 16 Statistical Software.    
 
Protection of Human Subjects 
Throughout the study, the principal investigators (Virtua Memorial spine surgeons and PAs), will be the 
only ones with access to the data collection database.  Following the completion of the study, all personal 
health information collected, including name, gender, age, significant medical comorbidities, and 
postoperative complications, will be de-identified as soon as possible prior to data analysis and any 
subsequent publications or research submissions. Patient would be told participation is purely voluntary 
with no monetary reimbursement and minimal risk of being assigned to one of the three pain 
management groups. 
 
References 

V. Oct 13 2016 
1. Centers for Disease Control and Prevention (CDC). National Hospital Discharge Survey: 2006 
Annual Summary. Vital and Health Statistics, 2010;13(168). 
2. Centers for Disease Control and Prevention (CDC), Health, United States, 2012: With Special 
Features on Emergency Care. 2012: Hyattsville, MD. 
3. Sharma S, Balireddy RK, Vorenkamp KE, Durieux ME. Beyond opioid patient-controlled analgesia: 
a systematic review of analgesia after major spine surgery. Reg Anesth Pain Med, 2012;37(1):79-
98. 
4. Khan ZH, Rahimi M, Makarem J, Khan RH. Optimal dose of pre-incision/post-incision gabapentin 
for pain relief following lumbar laminectomy: a randomized study. Acta Anaesthesiol Scand, 
2011;55(3):306-12. 
5. Yukawa Y, Kato F, Ito K, Terashima T, Horie Y. A prospective randomized study of preemptive 
analgesia for postoperative pain in the patients undergoing posterior lumbar interbody fusion: 
continuous subcutaneous morphine, continuous epidural morphine, and diclofenac sodium. Spine 
(Phila Pa 1976), 2005;30(21):2357-61. 
6. Apfelbaum JL, Silverstein JH, Chung FF, Connis RT, Fillmore RB, et al. Practice guidelines for 
postanesthetic care: an updated report by the American Society of Anesthesiologists Task Force 
on Postanesthetic Care. Anesthesiology, 2013;118(2):291-307. 
7. Yu L, Ran B, Li M, Shi Z. Gabapentin and Pregabalin in the Management of Postoperative Pain After 
Lumbar Spinal Surgery: A Systematic Review and Meta-analysis. Spine (Phila Pa 1976), 
2013;38(22):1947-52. 
8. Walder B, Schafer M, Henzi I, Tramer MR. Efficacy and safety of patient-controlled opioid 
analgesia for acute postoperative pain. A quantitative systematic review. Acta Anaesthesiol 
Scand, 2001;45(7):795-804. 
9. Becker DE, Reed KL. Local anesthetics: review of pharmacological considerations. Anesth Prog, 
2012;59(2):90-101; quiz 102-3. 
10. Argoff CE, Silvershein DI. A comparison of long- and short-acting opioids for the treatment of 
chronic noncancer pain: tailoring therapy to meet patient needs. Mayo Clin Proc, 2009;84(7):602-
12. 
11. Apfelbaum JL, Gan TJ, Zhao S, Hanna DB, Chen C. Reliability and validity of the perioperative 
opioid-related symptom distress scale. Anesth Analg, 2004;99(3):699-709, table of contents. 
12. Epter RS, Helm S, Hayek SM, Benyamin RM, Smith HS, et al. Systematic review of percutaneous 
adhesiolysis and management of chronic low back pain in post lumbar surgery syndrome. Pain 
Physician, 2009;12(2):361-78. 
13. White JJE, Houghton-Clemmey R, Marval P. Enhanced recovery after surgery (ERAS): an 
orthopaedic perspective. J Perioper Pract, 2013;23(10):228-32. 
14. Pacira Pharmaceuticals, EXPAREL Product Monograph. 2012: Parsippany, NJ. 
15. Golf M, Daniels SE, Onel E. A phase 3, randomized, placebo-controlled trial of DepoFoam(R) 
bupivacaine (extended-release bupivacaine local analgesic) in bunionectomy. Adv Ther, 
2011;28(9):776-88. 
16. Gorfine SR, Onel E, Patou G, Krivokapic ZV. Bupivacaine extended-release liposome injection for 
prolonged postsurgical analgesia in patients undergoing hemorrhoidectomy: a multicenter, 
randomized, double-blind, placebo-controlled trial. Dis Colon Rectum, 2011;54(12):1552-9. 

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17. Haas E, Onel E, Miller H, Ragupathi M, White PF. A double-blind, randomized, active-controlled 
study for post-hemorrhoidectomy pain management with liposome bupivacaine, a novel local 
analgesic formulation. Am Surg, 2012;78(5):574-81. 
18. Minkowitz HS, Onel E, Patronella CK, Smoot JD. A two-year observational study assessing the 
safety of DepoFoam bupivacaine after augmentation mammaplasty. Aesthet Surg J, 
2012;32(2):186-93. 
19. Bramlett K, Onel E, Viscusi ER, Jones K. A randomized, double-blind, dose-ranging study comparing 
wound infiltration of DepoFoam bupivacaine, an extended-release liposomal bupivacaine, to 
bupivacaine HCl for postsurgical analgesia in total knee arthroplasty. Knee, 2012;19(5):530-6. 
20. Jain RK, Porat MD, Klingenstein GG, Reid JJ, Post RE, Schoifet SD. Liposomal Bupivacaine and 
Periarticular Injection Are Not Superior to Single-Shot Intra-articular Injection for Pain Control in 
Total Knee Arthroplasty. J Arthroplasty, 2016;31(9):22-5. 
21. Atlas SJ, Tosteson TD, Hanscom B, Blood EA, Pransky GS, Abdu WA, Andersson GB, Weinstein JN. 
What Is Different About Worker’s Compensation Patients? Socioeconomic Predictors of Baseline 
Disability Status Among Patients With Lumbar Radiculopathy. Spine (Phila Pa 1976), 2007; 
32(18):2019-26. 
22. DeClaire J, Aiello P, Freeman DC. Effectiveness Of Exparel, A Bupivacaine Liposome Injectable 
Suspension, For Post-operative Pain Control In Total Knee Arthroplasty: A Prospective, 
Randomized, Double Blind Study. Orthopaedic Proceedings, 2017;99-B no. SUPP 3 95. 
23. Gadsden J, Long WJ. Time to Analgesia Onset and Pharmacokinetics After Separate and Combined 
Administration of Liposome Bupivacaine and Bupivacaine HCl: Considerations for Clinicians. Open 
Orthop J, 2016;10:94-104. 
24. Schroer WC, Diesfeld, PG, LeMarr, AR, Morton, DJ, Reedy, ME. Does Extended-Release Liposomal 
Bupivacaine Better Control Pain Than Bupivacaine After Total Knee Arthroplasty (TKA)? A 
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Appendices  
APPENDIX 1. SCREENING QUESTIONNAIRE 
 
Participant information 
Last name 
 
Date of birth 
 /  / 
First name 
 
Age 
 
 
Contact information 
Home phone 
(      )      - 
Cell phone 
(     )     - 
Home street address 
 
Home city, state, Zip 
 
Email 
 
 

V. Oct 13 2016 
Inclusion criteria 
# 
 
Yes 
No 
1 
Are you able to speak, read, and write in English? 
 
 
2 
Are you able to speak, read, and write in Spanish? 
 
 
3 
Do you have low back pain, radiculopathy, disc degeneration, disc 
herniation, stenosis, spondylolisthesis, or mild deformity? 
 
 
4 
Are you scheduled for lumbar spine surgery at Virtua Memorial Hospital 
in the next 30 days? 
 
 
5 
Are you willing to participate in the study and comply with the study 
protocol? 
 
 
 
Exclusion criteria 
# 
Question 
Feet 
Inches 
1 
What is your current height? 
 
 
2 
What is your current weight? 
    Lbs. 
 
 
Yes 
No 
3 
Have you ever been diagnosed with a mental health conditions such as 
anxiety or depression? 
 
 
4 
Are you currently taking medication for depression, anxiety, or any 
other mental health condition (e.g. Prozac, Xanax, Ativan, Zoloft)? 
 
 
5 
Have you ever been treated for alcohol, recreational drug, or narcotic 
medication abuse? 
 
 
6 
Have you ever had an allergic reaction to any type of local anesthetic 
such as lidocaine, procaine, or Marcaine®? 
 
 
7 
Have you ever had spinal fusion surgery (e.g. rods, screws, cages, 
implants) before? 
 
 
8 
Have you been taking opioid analgesics (also known as narcotics) such 
as Vicodin, Percocet, or OxyContin for more than 30 days? 
 
 
 
Females only: 
Yes 
No 
9 
If you are female are you currently pregnant, or do you plan on 
becoming pregnant before your surgery? 
 
 
 
Pain diagram 
Instructions 
Please indicate where you currently have pain in your body. 
Please use the marks below to indicate each type of symptom you may have. 
ACHE 
NUMBNESS 
PINS & NEEDLES 
BURNING 
STABBING 
^ ^ ^ ^ 
^ ^ ^ ^ 
O O O O 
O O O O 
= = = = 
= = = = 
X X X X 
X X X X 
/ / / / 
/ / / / 

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BACK 
FRONT 
Pain medication questionnaire 
 
Instructions 
Please indicate if you have taken any of the following medications for pain in the past month: 
 
Brand name 
Generic name 
Yes 
No 
Actiq 
Fentanyl transmucosal 
 
 
Advil 
Ibuprofen 
 
 
Aleve 
Naproxen 
 
 
Avinza 
Morphine extended-release 
 
 
Bayer 
Aspirin 
 
 
Butrans 
Buprenorphine transdermal 
 
 
Celebrex 
Celecoxib 
 
 
Codeine 
Codeine 
 
 
Darvocet 
Dextropropoxyphene 
 
 
Darvon 
Propoxyphene 
 
 
Demerol 
Meperidine 
 
 
Dilaudid 
Hydromorphone 
 
 
Dolophine 
Methadone 
 
 
Duragesic 
Fentanyl transdermal 
 
 
Embeda 
Morphine / naltrexone extended release 
 
 
Exalgo 
Hydromorphone extended release 
 
 
Excedrin 
Acetaminophen / aspirin / caffeine 
 
 
Fioricet 
Butalbital / acetaminophen / caffeine 
 
 

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Fiorinal 
Butalbital / aspirin / caffeine 
 
 
Flexeril 
Cyclobenzaprine 
 
 
Kadian 
Morphine extended-release 
 
 
Levo-Dromoran 
Levorphanol 
 
 
Lorcet 
Hydrocodone / acetaminophen 
 
 
Lortab 
Hydrocodone / acetaminophen 
 
 
Lyrica 
Pregabalin 
 
 
Morphine 
Morphine 
 
 
MS Contin 
Morphine controlled release 
 
 
Neurontin 
Gabapentin 
 
 
Norco 
Hydrocodone / acetaminophen 
 
 
Nucynta ER 
Tapentadol extended-release 
 
 
Opana 
Oxymorphone 
 
 
Opana ER 
Oxymorphone extended-release 
 
 
OxyContin 
Oxycodone 
 
 
OxyContin CR 
Oxycodone controlled release 
 
 
Percocet 
Oxycodone / acetaminophen 
 
 
Robaxin 
Methocarbamol 
 
 
Skelaxin 
Metaxalone 
 
 
Soma 
Carisoprodol 
 
 
Toradol 
Ketorolac 
 
 
Tylenol 
Acetaminophen 
 
 
Tylenol #3 
Acetaminophen / codeine 
 
 
Ultracet 
Tramadol / acetaminophen 
 
 
Ultram 
Tramadol 
 
 
Vicodin 
Hydrocodone / acetaminophen 
 
 
Voltaren 
Diclofenac 
 
 
   
APPENDIX 2. CONVERSION FACTORS FOR COMMON OPIOID ANALGESICS TO ORAL 
MORPHINE EQUIVALENTS 
 
Drug 
Route 
*Approximate Equianalgesic 
Dose (mg) 
**Morphine Equivalent 
Dose (MED) Factor 
Codeine 
Oral 
200 
0.15 
Fentanyl 
Parenteral 
0.1 
300 
Hydrocodone 
Oral 
30 
1.00 
Hydromorphone 
IM 
1.5 
20 
Hydromorphone 
Oral 
7.5 
4 
Morphine 
IM/IV 
10 
3 
Morphine 
Oral 
30 
1 
Oxycodone 
Oral 
20 
1.5 
Oxymorphone 
IM 
1 
30 
Methadone 
Oral 
7.5 
4 
* Equivalent to 30 mg of oral morphine (Source: http://www.globalrph.com/narcotic.htm) 

V. Oct 13 2016 
** 1mg of the drug converted to equivalent mg of oral morphine 
 
APPENDIX 3. INCIDENCE OF OPIOID RELATED ADVERSE EVENTS 
 
Instructions 
Please indicate if you have experienced any of the following symptoms in the past 12 hours: 
 
Symptom 
Yes 
No 
Comments 
Constipation 
 
 
 
Falling 
 
 
 
Hypoxia 
 
 
 
Lethargy 
 
 
 
Nausea 
 
 
 
Postoperative ileus 
 
 
 
Respiratory depression 
 
 
 
Sedation 
 
 
 
Somnolence 
 
 
 
Unsteadiness 
 
 
 
Urinary retention 
 
 
 
Vomiting