The Effectiveness of IV/PO Acetaminophen in the Perioperative Period in Reducing Opiate Use After Lumbar Spine Fusion

The Effectiveness of IV/PO Acetaminophen in the Perioperative Period in Reducing Opiate Use After Lumbar Spine Fusion: a Prospective, Randomized Controlled Trial

Simple explanation and rationale:

Recovery after spine surgery is usually accompanied by severe pain which has traditionally been managed with opioids. It is common practice to supplement opioid treatment with different classes of analgesics which work through alternative pain pathways and receptors in order to achieve an additive or synergistic effect while reducing the amount of opioids necessary for pain control.

Acetaminophen can be a beneficial supplemental analgesic to opioids for postoperative pain relief.

Intervention:

Patients will be randomized to either the treatment with IV acetaminophen (A), PO acetaminophen (B), or hydromorphone control group (C).

Objective/Purpose:

Primary objective is to determine the impact of administering a supplemental non-opioid analgesic drug such as IV or PO acetaminophen on total opioid dose administered over the postoperative period.

Secondary objectives include investigating the impact of IV/PO acetaminophen on the level of postoperative pain, patient satisfaction, and side effects secondary to opioids such as nausea, vomiting, pruritus, sedation, respiratory depression, ileus, and urinary retention, and PACU (postoperative care unit) discharge time.

Study population:

126 patients will be enrolled in the study (42 for group A, 42 for group B, and 42 for control group C).

Follow-up and Endpoints / Outcomes:

Postoperative assessments will be done at 0, 30, and 60 minutes, 6 hours, 12 hours and 24 hours after surgery. Patients will be evaluated for pain (using a numeric rating scale), total opioid consumption, and for opioid side effects including drowsiness (using the Ramsey sedation scale and the Aldrete score at the time of arrival to and discharge from recovery room), respiratory depression, nausea, vomiting, and pruritus. Patient satisfaction will also be assessed using a numeric rating scale.

Study Overview

• Status: Terminated
• Conditions: Fusion of Spine, Lumbar Region
• Intervention / Treatment: Drug: Hydromorphone; Drug: Acetaminophen; Drug: Acetaminophen IV Soln 10 MG/ML

Detailed Description

Simple explanation and rationale:

Recovery after spine surgery, especially spinal fusion surgery, is usually accompanied by severe pain which has traditionally been managed with opioids. While opioids have been proven effective, they are associated with undesirable side effects including nausea, vomiting, pruritus, sedation, respiratory depression, ileus, and urinary retention leading to increased time required in recovery and a decrease in patient satisfaction. For this reason, it is common practice to supplement opioid treatment with different classes of analgesics which work through alternative pain pathways and receptors in order to achieve an additive or synergistic effect while reducing the amount of opioids necessary for pain control.

Acetaminophen is a centrally-acting cyclooxygenase inhibitor nonsteroidal anti-inflammatory medication that has minimal, if any, gastrointestinal and platelet-inhibiting side effects, and is better tolerated by patients than other cyclooxygenase inhibitors. This medication can be a beneficial supplemental analgesic to opioids for postoperative pain relief. Previously conducted studies demonstrate a rationale for the use of intravenous/PO acetaminophen in a multimodal analgesic regimen to reduce postoperative analgesia.

Intervention:

Patients will be randomized to either the treatment with IV acetaminophen (A), PO acetaminophen (B), or hydromorphone control group (C). Patients who are randomized to group A will receive 1 g of IV acetaminophen during the wound closure and every 4 to 6 hours postoperatively for a total of 4 g in 24 hours. Patients who are randomized to group B will receive 1 g of PO acetaminophen before surgery and every 4 to 6 hours postoperatively for a total of 4 g in 24 hours. Patients who are randomized to control group C will not receive acetaminophen. Post-operatively, patients in both groups will also receive IV hydromorphone PCA (patient-controlled analgesia) only for 24 hours for pain.

Objective/Purpose:

Primary objective is to determine the impact of administering a supplemental non-opioid analgesic drug such as IV or PO acetaminophen on total opioid dose administered over the postoperative period.

Secondary objectives include investigating the impact of IV/PO acetaminophen on the level of postoperative pain, patient satisfaction, and side effects secondary to opioids such as nausea, vomiting, pruritus, sedation, respiratory depression, ileus, and urinary retention, and PACU discharge time.

Study population:

126 patients will be enrolled in the study (42 for group A, 42 for group B, and 42 for control group C).

Follow-up and Endpoints / Outcomes:

Postoperative assessments will be done at 0, 30, and 60 minutes, 6 hours, 12 hours and 24 hours after surgery. Patients will be evaluated for pain (using a numeric rating scale), total opioid consumption, and for opioid side effects including drowsiness (using the Ramsey sedation scale and the Aldrete score at the time of arrival to and discharge from recovery room), respiratory depression, nausea, vomiting, and pruritus. Patient satisfaction will also be assessed using a numeric rating scale.

Statistics:

All sample size calculations with reference to:

• Specific Aim 1 reduction of opioid intake by at least 25% between the Control (Group C) and Intervention Groups A and B, and
• Specific Aim 2 improvement of Pain Score by at least 25% between the Control (Group C) and the Intervention Groups A and B,

• Study Type: Interventional
• Enrollment (Actual): 28
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90033
      • Keck Hospital of USC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• ASA (American Society of Anesthesiologists) I-III patients scheduled for elective one or two level minimally invasive lumbar fusions

Exclusion Criteria:

• Patients requiring surgery for neoplastic processes
• Allergy to acetaminophen
• Liver dysfunction and elevated Liver Function Tests (LFTs)
• Alcohol or drug dependency
• Mental retardation
• Less than 50 kg of weight
• regnant women
• Patients requiring long-acting opioid pain management (including fentanyl patch, oxycontin, etc) for over 3 weeks immediately prior to surgery

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Acetaminophen IV Soln 10 MG/ML (A); Patients in group A will receive 1 g of IV acetaminophen 15 minutes prior to wound incision, and every 4 to 6 hours postoperatively for a total of 4 grams in 24 hours.	Drug: Hydromorphone; Other Names: Dilaudid; Drug: Acetaminophen IV Soln 10 MG/ML; Other Names: Ofirmev
EXPERIMENTAL: PO acetaminophen (B); Patients in group B will receive 1 g of PO acetaminophen prior to surgery, and 1 g of oral acetaminophen every 4 to 6 hours postoperatively for a total of 4 grams in 24 hours.	Drug: Hydromorphone; Other Names: Dilaudid; Drug: Acetaminophen; Other Names: Tylenol
ACTIVE_COMPARATOR: Hydromorphone (control arm) (C); Patients in the control arm (Group C) will not receive acetaminophen for 24 hours.	Drug: Hydromorphone; Other Names: Dilaudid

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Postoperative Opioid Use	Determine the impact of administering a supplemental non-opioid analgesic drug such as IV/oral acetaminophen on total opioid dose administered over the perioperative period.	Within 24 hours after surgery

Collaborators and Investigators

• Sponsor: University of Southern California
• Investigators: Principal Investigator: Eugenia Ayrian, University of Southern California

Publications and helpful links

General Publications

• Cakan T, Inan N, Culhaoglu S, Bakkal K, Basar H. Intravenous paracetamol improves the quality of postoperative analgesia but does not decrease narcotic requirements. J Neurosurg Anesthesiol. 2008 Jul;20(3):169-73. doi: 10.1097/ANA.0b013e3181705cfb.
• Devin CJ, McGirt MJ. Best evidence in multimodal pain management in spine surgery and means of assessing postoperative pain and functional outcomes. J Clin Neurosci. 2015 Jun;22(6):930-8. doi: 10.1016/j.jocn.2015.01.003. Epub 2015 Mar 9.
• Korkmaz Dilmen O, Tunali Y, Cakmakkaya OS, Yentur E, Tutuncu AC, Tureci E, Bahar M. Efficacy of intravenous paracetamol, metamizol and lornoxicam on postoperative pain and morphine consumption after lumbar disc surgery. Eur J Anaesthesiol. 2010 May;27(5):428-32. doi: 10.1097/EJA.0b013e32833731a4.
• Garcia RM, Cassinelli EH, Messerschmitt PJ, Furey CG, Bohlman HH. A multimodal approach for postoperative pain management after lumbar decompression surgery: a prospective, randomized study. J Spinal Disord Tech. 2013 Aug;26(6):291-7. doi: 10.1097/BSD.0b013e318246b0a6.

Study record dates

Study Major Dates

• Study Start: October 1, 2016
• Primary Completion (ACTUAL): October 1, 2017
• Study Completion (ACTUAL): December 1, 2017

Study Registration Dates

• First Submitted: March 29, 2017
• First Submitted That Met QC Criteria: April 3, 2017
• First Posted (ACTUAL): April 7, 2017

Study Record Updates

• Last Update Posted (ACTUAL): October 8, 2019
• Last Update Submitted That Met QC Criteria: September 20, 2019
• Last Verified: September 1, 2019

More Information

Terms related to this study

• Keywords: Pain; Opioid; Pain management; Postoperative; Spinal; Analgesics; Ofirmev; Acetaminophen po; Acetaminophen IV; minimally invasive lumbar fusions
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Analgesics, Non-Narcotic; Antipyretics; Analgesics, Opioid; Narcotics; Acetaminophen; Hydromorphone
• Other Study ID Numbers: HS-15-00615

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: The data will kept for a minimum of 3 years after the study is completed. All documents containing identifiers will be shredded. Electronic documents will be deleted.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No