A Randomized Controlled Trial of Post-operative Acetaminophen Versus Nonsteroidal Anti-Inflammatory Drug (NSAID) Use on Lumbar Spinal Fusion Outcomes
Phase: NA
Conditions: Lumbar Osteoarthritis, Spondylosis, Lumbar Disc Disease, Spinal Stenosis
Sponsor: Hospital for Special Surgery, New York

Title:  
A Randomized Controlled Trial of Post-operative Acetaminophen versus Nonsteroidal Anti-Inflammatory 
Drug Use on Lumbar Spinal Fusion Outcomes 
 
NCT#:  
NCT02700451 
 
Document Date: 
2/23/2023 
 
Principal Investigator: 
Harvinder Sandhu, MD 
 
 
 
 

Brief Summary:  
Patients undergoing spine surgery often have considerable pain post-operatively and frequently require 
opioid medication (Percocet, Norco, oxycodone, morphine, etc.) to control their pain postoperatively. 
The widespread use of opioids, however, is associated with a number of side effects. These include: 
sedation, dizziness, nausea, vomiting, constipation, dizziness and itching amongst others. Some 
investigators have suggested that anti-inflammatory medications (the same class of medicines as advil, 
ibuprofen, etc.) and acetaminophen (Tylenol) can reduce the total dose of opioid required 
postoperatively and, as a result, lower opioid-related side effects. 
 
The purpose of this study is to test this hypothesis and determine if postoperative anti-inflammatory 
medications and postoperative acetaminophen can reduce the amount of opioid required to control 
pain following surgery. A secondary goal of this study is to examine if the change in pain medication will 
lead to decreased overall pain levels, decreased opioid-related side effects and improved function 
[quicker ambulation with physical therapy (PT), earlier return to work, etc.]. 
 
  
Detailed Description: 
 
Given the potential for non-steroidal anti inflammatory drugs (NSAIDs) and acetaminophen to decrease 
opioid requirements following spine surgery, the investigators propose a prospective, randomized, 
double-blinded clinical trial comparing the efficacy of intravenous (IV) acetaminophen (Group A) or IV 
ketorolac (Group K) versus placebo (Group P). The impact of treatment on perioperative opioid use, 
opioid-related complications, functional outcomes and rates of pseudarthrosis following 1 or 2 level 
lumbar fusion surgery will be measured in each group. The specific aims of this study are as follows: 
 
Specific Aim 1: Determine the impact of IV ketorolac or IV acetaminophen use on immediate 
postoperative opioid requirements, postoperative pain levels and opiate related symptoms using the 
Opiate-Related Symptom Distress Scale (ORSDS) 
Specific Aim 2: Determine the impact of IV ketorolac or IV acetaminophen use on functional outcomes 
defined by return to work, Oswestry Disability Index (ODI) and the Veterans Rand-12 (VR-12) Health 
Survey 
The primary outcome is to determine the total postoperative opioid dose (in oral morphine equivalents) 
in each group. The investigators hypothesize that patients in Group A and Group K will have lower total 
opioid use, suffer from fewer opiate related symptoms and have similar rates of pseudarthrosis to 
patients in Group P. The investigators hypothesize that patients in Group A and Group K will have a 
quicker return to work and improved early functional outcomes although they acknowledge that long 
term functional outcomes may be the same for all groups. 
 

This is a Randomized Controlled Clinical Trial. 
 
Arms and Interventions: 
 
Arms
Assigned Interventions
Placebo Comparator: 
Intravenous (IV) 
Placebo 
IV Placebo arm 
Drug: Placebo 
Intravenous Normal Saline every 6 hours for 48 hours in 
addition to patient-controlled analgesia and oral opioids 
as needed. 
Other Names: 
 
Normal Saline 
Experimental: IV 
Ketorolac 
IV Ketorolac arm 
Drug: Ketorolac 
Age 18-64: Intravenous Ketorolac 30 milligrams (mg) 
every 6 hours for 48 hours in addition to patient-
controlled analgesia and oral opioids as needed. 
Age 65-75: Intravenous Ketorolac 15 milligrams (mg) 
every 6 hours for 48 hours in addition to patient-
controlled analgesia and oral opioids as needed. 
Other Names: 
 
Toradol 
Experimental: IV 
Acetaminophen 
IV Acetaminophen arm
Drug: Acetaminophen 
Intravenous Acetaminophen 1000mg every 6 hours for 
48 hours in addition to patient-controlled analgesia and 
oral opioids as needed. 
Other Names: 
 
Tylenol, Ofirmev 
 
 
 
 

Eligibility: 
Minimum Age: 18 Years   
Maximum Age: 75 Years   
Sex: All   
Gender Based:
Accepts Healthy Volunteers: No 
Criteria: Inclusion Criteria: 
 Age 18-75 
 Require 1 or 2 level lumbar spinal 
fusion through posterior or lateral 
approach 
 No history of long term opioid use 
(daily or almost daily opioid use > 2 
weeks) and not on opiates at time of 
presentation to clinic 
Exclusion Criteria: 
 Documented allergy to NSAIDs or 
Acetaminophen 
 History of: Peptic Ulcer Disease, 
Congestive heart failure, Chronic liver 
disease, Elevated alanine 
aminotransferase (ALT)/ aspartate 
aminotransferase (AST) greater than 
1.5 times control, Bleeding disorder, 
Renal dysfunction (Serum creatinine 
> 1.5 mg/dL), Glucocorticoid use 
within 1 month of surgery 
 Current smokers (quite date < 30 
days ago) 
 Revision for pseudarthrosis 
 Patients who are unable to physically 
or mentally provide consent to the 
study procedures. 
 

Statistical plan: 
 
All normally distributed variables are described using mean and standard deviation (SD) for normally 
distributed continuous variables, median and interquartile range (IQR) for non-normally distributed 
continuous variables and counts and percentages for categorical data. Normal distribution was assessed 
using a q-q plot prior to statistical analysis. Groups were compared using an analysis of variation 
(ANOVA) for normally distributed variables and a Kruskal-Wallis test for non-normally distributed 
variables; a chi-squared test was used for categorically distributed variables. Post-hoc pairwise 
comparisons (adjusted and unadjusted) were also performed.  
Assessment of spinal fusion was performed by consensus read with two board-certified radiologists, 
J.L.C. with certificate of added qualification in Neuroradiology and 9 years of post-fellowship experience 
and J.A.C. with subspecialty training in musculoskeletal imaging and 20 years of post-fellowship 
experience.  Interbody and posterolateral fusion was assessed on a 4-point scale, 0 = no fusion; 1 = 
probably not fused; 2 = probably fused; 3 = definitely fused. Fusion assessment was performed on 
multiplanar CT imaging when available or dedicated lumbosacral radiographs with a minimum of 
anteroposterior and lateral views.