Post-op Acetaminophen vs NSAID Use on Lumbar Spinal Fusion Outcomes

A Randomized Controlled Trial of Post-operative Acetaminophen Versus Nonsteroidal Anti-Inflammatory Drug (NSAID) Use on Lumbar Spinal Fusion Outcomes

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.].

Study Overview

• Status: Completed
• Conditions: Spinal Stenosis; Spondylosis; Lumbar Disc Disease; Lumbar Osteoarthritis
• Intervention / Treatment: Drug: Placebo; Drug: Ketorolac; Drug: Acetaminophen

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.

• Study Type: Interventional
• Enrollment (Actual): 178
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10021
      • Hospital for Special Surgery

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Perioperative Opioid Use	Measure the impact of treatment on total opioid use during the hospital stay	Hospital stay (2-4 days)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Opioid Use at 4-6 Weeks	Track opioid use after discharge for the first 4-6 weeks	4-6 weeks
Opioid Use at 3 Months	Track opioid use after discharge for the first 3 months; assess for continued opioid use	3 months
Opioid Use at 1 Year	Track opioid use after discharge for the first 1 year; assess for continued opioid use	1 year
Opioid Use at 2 Years	Track total opioid use after discharge for the first 2 years; assess for continued opioid use	2 years
Numerical Pain Rating Scale	Validated pain scale; will be completed by patient Minimum Score: 0 & Maximum score 100 A lower score is representative of a low pain level	1 days and 3 days
Brief Pain Inventory	The Brief Pain Inventory (BPI) is a self-administered questionnaire for chronic pain conditions. The BPI gives two main scores: a pain severity score and a pain interference score. The pain severity score is calculated from the four items about pain intensity. Each item is rated from 0, no pain, to 10, pain as bad as you can imagine, and contributes with the same weight to the final score, ranging from 0 to 40. The pain interference score corresponds to the item on pain interference. The seven sub-items are rated from 0, does not interfere, to 10, completely interferes, and contributes with the same weight to the final score, ranging from 0 to 70. The first item, pain drawing diagrams (painful and most painful areas) and the items on pain relief treatment or medication (list of the treatments and amount of relief) do not contribute to the scoring.	1 day and 3 days
Opioid Related Side Effects	Ileus, nausea/vomiting, first bowel movement, first flatus, treated pruritis will be identified and recorded	Hospital Stay (1-4 days)
Perioperative Complications - Drain Output	Complications such as: excessive drain output, elevation in creatinine, and the need for transfusions will be identified and recorded	Hospital Stay (1-4 days)
Perioperative Complications - Transfusion Rate	Complications such as: excessive drain output, elevation in creatinine, and the need for transfusions will be identified and recorded	Hospital Stay (1-4 days)
Days to Walk 50 ft With PT	Days needed to be able to walk 50ft with PT	Hospital Stay (1-4 days)
Length of Stay	Will record date of discharge	Hospital Stay (1-4 days)
Veterans Rand - 12	The Veterans RAND 12 Item Health Survey (VR-12) is a brief, generic, multi-use, self-administered health survey comprised of 12 items. The instrument is primarily used to measure health related quality of life, to estimate disease burden and to evaluate disease-specific benchmarks with other populations. The 12 items in the questionnaire correspond to eight principal physical and mental health domains including general health perceptions; physical functioning; role limitations due to physical and emotional problems; bodily pain; energy-fatigue, social functioning and mental health.. The 12 items are summarized into two scores, a "Physical Health Summary Measure {PCS-physical component score}" and a "Mental Health Summary Measure {MCS-mental component score}". Score range is 0 to 100, higher score denotes a better outcome. This score range apply to both PCS and MCS.	pre-operative
Oswestry Disability Index	The Oswestry Disability Index (ODI) is the most commonly used outcome-measure questionnaire for low back pain in a hospital setting. It is a self-administered questionnaire divided into ten sections designed to assess limitations of various activities of daily living. Each section is scored on a 0-5 scale, 5 representing the greatest disability. The index is calculated by dividing the summed score by the total possible score, which is then multiplied by 100 and expressed as a percentage. Thus, for every question not answered, the denominator is reduced by 5. If a patient marks more than one statement in a question, the highest scoring statement is recorded as a true indication of disability.	pre-operative
Veterans Rand - 12	The Veterans RAND 12 Item Health Survey (VR-12) is a brief, generic, multi-use, self-administered health survey comprised of 12 items. The instrument is primarily used to measure health related quality of life, to estimate disease burden and to evaluate disease-specific benchmarks with other populations. The 12 items in the questionnaire correspond to eight principal physical and mental health domains including general health perceptions; physical functioning; role limitations due to physical and emotional problems; bodily pain; energy-fatigue, social functioning and mental health.. The 12 items are summarized into two scores, a "Physical Health Summary Measure {PCS-physical component score}" and a "Mental Health Summary Measure {MCS-mental component score}". Score range is 0 to 100, higher score denotes a better outcome. This score range apply to both PCS and MCS.	3 month follow up
Oswestry Disability Index	The Oswestry Disability Index (ODI) is the most commonly used outcome-measure questionnaire for low back pain in a hospital setting. It is a self-administered questionnaire divided into ten sections designed to assess limitations of various activities of daily living. Each section is scored on a 0-5 scale, 5 representing the greatest disability. The index is calculated by dividing the summed score by the total possible score, which is then multiplied by 100 and expressed as a percentage. Thus, for every question not answered, the denominator is reduced by 5. If a patient marks more than one statement in a question, the highest scoring statement is recorded as a true indication of disability.	3 month follow up
Return to Work	Record return to work	3 month follow up
Veterans Rand - 12	The Veterans RAND 12 Item Health Survey (VR-12) is a brief, generic, multi-use, self-administered health survey comprised of 12 items. The instrument is primarily used to measure health related quality of life, to estimate disease burden and to evaluate disease-specific benchmarks with other populations. The 12 items in the questionnaire correspond to eight principal physical and mental health domains including general health perceptions; physical functioning; role limitations due to physical and emotional problems; bodily pain; energy-fatigue, social functioning and mental health.. The 12 items are summarized into two scores, a "Physical Health Summary Measure {PCS-physical component score}" and a "Mental Health Summary Measure {MCS-mental component score}". Score range is 0 to 100, higher score denotes a better outcome. This score range apply to both PCS and MCS.	1 year follow up
Oswestry Disability Index	The Oswestry Disability Index (ODI) is the most commonly used outcome-measure questionnaire for low back pain in a hospital setting. It is a self-administered questionnaire divided into ten sections designed to assess limitations of various activities of daily living. Each section is scored on a 0-5 scale, 5 representing the greatest disability. The index is calculated by dividing the summed score by the total possible score, which is then multiplied by 100 and expressed as a percentage. Thus, for every question not answered, the denominator is reduced by 5. If a patient marks more than one statement in a question, the highest scoring statement is recorded as a true indication of disability.	1 year follow up
Return to Work	Record return to work	1 year follow up
Numerical Pain Rating Scale	Validated pain scale; will be completed by patient Minimum Score: 0 & Maximum score 100 A lower score is representative of a low pain level	1 year follow up
Veterans Rand - 12	The Veterans RAND 12 Item Health Survey (VR-12) is a brief, generic, multi-use, self-administered health survey comprised of 12 items. The instrument is primarily used to measure health related quality of life, to estimate disease burden and to evaluate disease-specific benchmarks with other populations. The 12 items in the questionnaire correspond to eight principal physical and mental health domains including general health perceptions; physical functioning; role limitations due to physical and emotional problems; bodily pain; energy-fatigue, social functioning and mental health.. The 12 items are summarized into two scores, a "Physical Health Summary Measure {PCS-physical component score}" and a "Mental Health Summary Measure {MCS-mental component score}". Score range is 0 to 100, higher score denotes a better outcome. This score range apply to both PCS and MCS.	2 year follow up
Oswestry Disability Index	The Oswestry Disability Index (ODI) is the most commonly used outcome-measure questionnaire for low back pain in a hospital setting. It is a self-administered questionnaire divided into ten sections designed to assess limitations of various activities of daily living. Each section is scored on a 0-5 scale, 5 representing the greatest disability. The index is calculated by dividing the summed score by the total possible score, which is then multiplied by 100 and expressed as a percentage. Thus, for every question not answered, the denominator is reduced by 5. If a patient marks more than one statement in a question, the highest scoring statement is recorded as a true indication of disability.	2 year follow up
Return to Work	Record return to work	2 year follow up
Numerical Pain Rating Scale	Validated pain scale; will be completed by patient Minimum Score: 0 & Maximum score 100 A lower score is representative of a low pain level	2 year follow up

Collaborators and Investigators

• Sponsor: Hospital for Special Surgery, New York
• Investigators: Principal Investigator: Harvinder Sandhu, MD, Associate Professor of Orthopedic Surgery; Study Director: Catherine Himo Gang, Research Manager for Spine Research

Study record dates

Study Major Dates

• Study Start: March 1, 2016
• Primary Completion (Actual): December 31, 2021
• Study Completion (Actual): March 1, 2023

Study Registration Dates

• First Submitted: February 18, 2016
• First Submitted That Met QC Criteria: March 1, 2016
• First Posted (Estimated): March 7, 2016

Study Record Updates

• Last Update Posted (Actual): July 10, 2023
• Last Update Submitted That Met QC Criteria: June 16, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Keywords: Post-operative analgesia; Opioid use; IV acetaminophen; IV Ketorolac
• Additional Relevant MeSH Terms: Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Arthritis; Spinal Diseases; Bone Diseases; Spondylarthritis; Spondylitis; Osteoarthritis; Spinal Stenosis; Spondylosis; Osteoarthritis, Spine; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Enzyme Inhibitors; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Cyclooxygenase Inhibitors; Antipyretics; Ketorolac; Acetaminophen
• Other Study ID Numbers: 2014-333

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO