Analgesic Efficacy of Repeated Doses of Intravenous (IV) Acetaminophen in Post-operative Pediatric Spine Fusion Patients (IV APAP SF)

Analgesia Efficacy of Repeated Doses of Intravenous Acetaminophen (Paracetamol) in the Pediatric Spinal Fusion Population

This is a prospective, randomized, double-blinded, placebo controlled trial Potential subjects will be identified from the Pre-Surgical Anesthesia Clinic visit. Parents/legal guardians will be approached about study participation at the Anesthesia outpatient pre-visit. Attending Anesthesiologist will receive e-mail notification about potential subject participation the day before the scheduled surgery. Study lab (hepatic function panel) will be collected as soon as possible after anesthesia induction by anesthesia. Results will be reviewed by study team member and study drug will be ordered by study team if patient does not meet exclusion criteria. Study drug (IV acetaminophen or placebo) will be administered at the time of skin closure by anesthesia on completion of the surgical procedure (after randomization). Study drug will be administered every 6 hours for 2 days. Subjects will continue to receive standard of care with patient controlled analgesia (PCA) opiate therapy (morphine or hydromorphone) for analgesia as per the Pain Management Service. Pain scores, opiate (morphine equivalent) administered, requirements for treatment of opiate related side effects (treatment for nausea and itching), and certain post-operative characteristics will be measured for up to 4 days post-operatively (time to mobilization, time to diet advancement, time to discharge).

Study Overview

• Status: Completed
• Conditions: Pain, Postoperative
• Intervention / Treatment: Other: Placebo; Drug: Intravenous Acetaminophen

Detailed Description

An ideal drug as an opiate-sparing analgesic adjunct, acetaminophen, unlike some other drugs, is platelet function sparing, and thus particularly useful in the post-operative orthopedic patient population. In part because of its well established safety profile, as well as minimal drug interactions, acetaminophen is considered a cornerstone of a multimodal analgesic approach. Several studies have described the clinically significant beneficial effects of a multimodal drug approach to analgesia, citing improved pain control and a shorter recovery time. Reduced adverse events and improved pain control with multimodal analgesia drug approaches may result in shorter hospitalizations, improved recovery and function, and reduced health care costs. Opiate therapy, while effective analgesia, is associated with a variety of potential adverse side effects, including pruritus, nausea, emesis, ileus, respiratory depression, tolerance, addiction and sedation. These adverse effects may limit post-operative mobility, postpone return of bowel function, cause feeding intolerance, prolong hospitalization, and postpone post-operative recovery.

While oral acetaminophen is useful as an opiate-sparing therapy, the oral route of drug administration may not be feasible in the early post-operative period. Enteral drug absorption in the initial post-operative period may be erratic, with negative impacts on therapeutic effect. Intravenous acetaminophen may a particularly useful analgesic in these circumstances. At present, there are no pediatric studies in the United States examining the efficacy of multiple- dose IV acetaminophen in the post-operative surgical population. This study will compare analgesic efficacy, nausea and pruritus scores, time to recovery, and length of hospital stay in two subject groups who are status post spine fusion surgery: those who receive schedule IV acetaminophen and opiate for 48 hours, and those who are treated with standard opiate therapy without IV acetaminophen.

• Study Type: Interventional
• Enrollment (Actual): 67
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Children's Hospital of Philadelphia

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 10 years to 18 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

Subjects 10-18 years who are status post anterior or posterior spine fusion surgery

Exclusion Criteria:

1. All patients requiring mechanical ventilation post-operatively, continuous infusions of sedative, or continuous infusions of alternate opiates (i.e. fentanyl)
2. Patients with hepatic dysfunction
3. Patients with chronic opiate requirements
4. Pregnant or lactating females
5. Patients placed on opiates other than morphine or hydromorphone
6. Patients with opiate or acetaminophen allergies
7. Patients placed on alternate analgesic adjuncts (i.e. ketamine, etc)
8. Patients who receive intrathecal opiates

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Saline Placebo; Control subjects will receive saline as placebo at the time of skin closure intra-operatively and will continue to receive IV saline for 44 hours post-operatively. Doses will be administered every 6 hours (total of 8 doses).	Other: Placebo; Saline placebo will be given at the time of skin closure intra-operatively and will continue to receive IV saline for 44 hours post-operatively. Doses will be administered every 6 hours (total of 8 doses).
Experimental: Intravenous Acetaminophen; Subjects will receive the first dose of intravenous (IV) acetaminophen (at 15 mg/kg, with maximum doses based on patient age and weight) at the time of skin closure intra-operatively and will continue to receive IV acetaminophen for 42 hours post-operatively. Doses will be administered every 6 hours (total of 8 doses).	Drug: Intravenous Acetaminophen; Scheduled doses of 15 mg/kg of IV acetaminophen will be administered to the treatment arm of the study for a total of 8 doses over a 48 hour period post-operatively.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Total Opiate Requirement	Total opiate requirement was monitored 24 hours post-operatively. Morphine and hydromorphone measurements were totaled and recorded in mg/kg/day of morphine equivalents.	24 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Average Pain Score	Pain Scores were monitored using the numeric pain assessment scale in both treatment arms of the study and recorded and averaged for the first 24 hours after initial intra-operative dose of study drug. The numeric pain assessment scale is a verbal self-reported pain assessment that ranges between 1 (no pain) to 10 (worst pain imaginable).	24 hours
Average Nausea Score	Nausea scores were recorded by the nursing staff approximately 4 times over the first 24 hours and then averaged for the 24 hour period. Nausea Scores range from 1 (none) to 4 (severe).	24 hours
Average Pruritus Score	Pruritus scores were recorded by the nursing staff approximately 4 times over the first 24 hours and then averaged for the 24 hour period. Pruritus scores range from 1 (none) to 3 (intolerable).	24 hours

Collaborators and Investigators

• Sponsor: Children's Hospital of Philadelphia
• Investigators: Principal Investigator: Athena Zuppa, MD, Children's Hospital of Philadelphia

Study record dates

Study Major Dates

• Study Start: July 1, 2011
• Primary Completion (Actual): June 1, 2014
• Study Completion (Actual): July 1, 2015

Study Registration Dates

• First Submitted: July 13, 2011
• First Submitted That Met QC Criteria: July 13, 2011
• First Posted (Estimate): July 14, 2011

Study Record Updates

• Last Update Posted (Estimate): April 18, 2016
• Last Update Submitted That Met QC Criteria: March 17, 2016
• Last Verified: March 1, 2016

More Information

Terms related to this study

• Keywords: acetaminophen; spine fusion surgery; analgesic adjunct; opiate reduction; pain management after elective surgical operation
• Additional Relevant MeSH Terms: Pathologic Processes; Postoperative Complications; Pain; Neurologic Manifestations; Pain, Postoperative; Physiological Effects of Drugs; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Analgesics, Non-Narcotic; Antipyretics; Acetaminophen
• Other Study ID Numbers: 11-08095