Effect of Intravenous Acetaminophen on Postoperative Opioid-related Complications

Some patients have respiratory depression (decreased breaths per minute) after surgery. Acetaminophen, an FDA approved pain medication, may prevent this problem. The purpose of this study is to determine if acetaminophen decreases respiratory depression after surgery. The investigators will also evaluate the cost effectiveness of acetaminophen.

Patients having elective major abdominal surgery are being asked to participate in this research study. If eligible, a patient will have their baseline tidal volume (amount of air moved into or out of the lungs) and vital capacity (how much air the lungs are capable of holding) measured using a spirometer (apparatus for measuring the volume of air inspired and expired by the lungs) measured before surgery. Three questionnaires will also need to be completed before surgery.

The patient will then be randomized, like flipping a coin, to receive either Acetaminophen or placebo (inactive substance) as an infusion throughout surgery and for the first two days thereafter. Neither the patient nor his or her physician will know if the patient is assigned to study drug or placebo. Regardless of study assignment, both groups will receive standard pain management medications and sedation.

After surgery, the patient's blood pressure, activity, posture, respiratory rate, the electrical activity of the heart, oxygen saturation, tidal volume, minute ventilation and respiratory rate will be continuously monitored and recorded for 48 hours using a wireless pulse-oximeter and a respiratory volume monitor.

48 hours after surgery the patient will be asked to complete a patient satisfaction questionnaire, which will allow the patient to rate the satisfaction with the treatment received for pain. The patient will also be asked to complete a questionnaire about recovery.

At discharge, the patient will be given two questionnaires about pain and quality of life.

Study Overview

• Status: Completed
• Conditions: Postoperative Pain
• Intervention / Treatment: Drug: Intravenous Acetaminophen

• Study Type: Interventional
• Enrollment (Actual): 580
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic Foundation

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Written informed consent
• 18-85 years old
• above 50 kg
• American Society of Anaesthesiologists Physical Status 1-3
• Scheduled for elective open or laparoscopic abdominal surgery, including colorectal, prostate, and hysterectomy surgeries
• Patients with anticipated hospitalization of two nights
• Expected to require parenteral opioids for at least 48 hours for postoperative pain
• Able to use IV Patient-Controlled Analgesia systems

Exclusion Criteria:

• Hepatic disease, e.g. twice the normal levels of liver enzymes
• Kidney disease, e.g. twice the normal level of serum creatinine
• Epidural analgesia or regional blocks (including Transverse abdominis plane block)
• Acetaminophen sensitivity or known allergy
• Female patients who are pregnant or breastfeeding
• Patients taking warfarin

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: Intravenous 0.9% sodium chloride; 0.9% sodium chloride infusion will be initiated before the surgical incision with 100 ml and repeated every 6 hours for the earlier of 48 postoperative hours of hospital discharge.	Drug: Intravenous Acetaminophen
Experimental: Intravenous Acetaminophen; Acetaminophen infusion will be initiated before the surgical incision with 1 g and repeated every 6 hours for the earlier of 48 postoperative hours of hospital discharge.	Drug: Intravenous Acetaminophen

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Duration of Hypoxemia	Hypoxemia is measured as minutes with hypoxemia (Spo2 <90%) per hour of successful Spo2 monitoring. Patients will have nearly continuous pulseoximeter monitoring and recording. Data from the monitor will be downloaded daily for 48 hours postoperatively.	the initial 48 hours of postoperative monitoring or for the duration of hospitalization, if shorter.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time-weighted Pain Score During Initial 48 Postoperative Hours	Pain scores were calculated on a visual analog scale of 0 to 10, with 0 being no pain and 10 being the most pain imaginable; time weighted mean was calculated as the area under the curve of the pain score measurements divided by total measurement time. Pain was recorded at roughly 15-minute intervals in the postanesthesia care unit and at 4-hour intervals on surgical wards	Initial 48 postoperative hours or duration of hospitalization (whichever comes first)
Time Weighted Pain Score in Post Anesthesia Care Unit	Pain scores were calculated on a visual analog scale of 0 to 10, with 0 being no pain and 10 being the most pain imaginable; time-weighted mean was calculated as the area under the curve of the pain score measurements divided by total measurement time.	Initial 48 postoperative hours or duration of hospitalization (whichever comes first)
Fatigue Score on Morning of Postoperative Day 1	Fatigue scores were calculated on a scale of 1 to 10, with 1 being no fatigue and 10 being the worst fatigue imaginable.	Postoperative day 1
Lowest RASS Score During Initial 48 Postoperative Hours	Sedation was estimated by the RASS score and recorded at 2-hour intervals by ward nurses per clinical routine during the initial 48 postoperative hours. The Richmond Agitation-Sedation Scale (RASS) is scored from -5 to +4, with -5 being unarousable, 0 being alert and calm, and +4 being combative.	Initial 48 postoperative hours or duration of hospitalization (whichever comes first)
Time Spent in Sitting or Upright Position	Treatment effect data are reported as ratios of geometric means	Initial 48 postoperative hours or duration of hospitalization (whichever comes first)
Opioid Consumption - Intravenous Morphine Equivalents	Total opioid consumption over the initial 48 postoperative hours was extracted from patients' medical records and converted to intravenous morphine equivalents	Initial 48 postoperative hours
Incidence of Postoperative Nausea and Vomiting	Patients were asked about postoperative nausea and vomiting in the postanesthesia care unit, at 4-hour intervals while awake through the remaining initial day of surgery, and on the first and second postoperative mornings.	Initial 48 postoperative hours or duration of hospitalization (whichever comes first)
Incidence of Low Respiratory Function Event	A low respiratory function event was defined as an episode of less than 40% of predicted minute ventilation for 2 minutes.	Initial 48 postoperative hours or duration of hospitalization (whichever comes first)
Total Anesthetic Dose From Induction to Extubation	Total anesthetic dose is measured in minimal alveolar concentration hours.	Induction to extubation (3 hours on average)

Collaborators and Investigators

• Sponsor: The Cleveland Clinic

Publications and helpful links

General Publications

• Turan A, Essber H, Saasouh W, Hovsepyan K, Makarova N, Ayad S, Cohen B, Ruetzler K, Soliman LM, Maheshwari K, Yang D, Mascha EJ, Ali Sakr Esa W, Kessler H, Delaney CP, Sessler DI; FACTOR Study Group. Effect of Intravenous Acetaminophen on Postoperative Hypoxemia After Abdominal Surgery: The FACTOR Randomized Clinical Trial. JAMA. 2020 Jul 28;324(4):350-358. doi: 10.1001/jama.2020.10009.

Study record dates

Study Major Dates

• Study Start: December 1, 2014
• Primary Completion (Actual): March 1, 2019
• Study Completion (Actual): October 1, 2020

Study Registration Dates

• First Submitted: June 3, 2014
• First Submitted That Met QC Criteria: June 4, 2014
• First Posted (Estimate): June 5, 2014

Study Record Updates

• Last Update Posted (Actual): April 20, 2021
• Last Update Submitted That Met QC Criteria: March 25, 2021
• Last Verified: March 1, 2021

More Information

Terms related to this study

• 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: 14-241