Effect of Intravenous Acetaminophen on Postoperative Opioid-related Complications

Phase 3

Completed

Conditions: Postoperative Pain

Interventions: Drug: Intravenous Acetaminophen

Registration Number: NCT02156154

Lead Sponsor: The Cleveland Clinic

Brief Summary: 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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 580

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 & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Intravenous 0.9% sodium chloride	Intravenous Acetaminophen	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.
Intravenous Acetaminophen	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.

Primary Outcome Measures

Name	Time	Method
Duration of Hypoxemia	the initial 48 hours of postoperative monitoring or for the duration of hospitalization, if shorter.	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.

Secondary Outcome Measures

Name	Time	Method
Fatigue Score on Morning of Postoperative Day 1	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.
Lowest RASS Score During Initial 48 Postoperative Hours	Initial 48 postoperative hours or duration of hospitalization (whichever comes first)	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.
Incidence of Postoperative Nausea and Vomiting	Initial 48 postoperative hours or duration of hospitalization (whichever comes first)	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.
Time Weighted Pain Score in Post Anesthesia Care Unit	Initial 48 postoperative hours or duration of hospitalization (whichever comes first)	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.
Opioid Consumption - Intravenous Morphine Equivalents	Initial 48 postoperative hours	Total opioid consumption over the initial 48 postoperative hours was extracted from patients' medical records and converted to intravenous morphine equivalents
Total Anesthetic Dose From Induction to Extubation	Induction to extubation (3 hours on average)	Total anesthetic dose is measured in minimal alveolar concentration hours.
Time-weighted Pain Score During Initial 48 Postoperative Hours	Initial 48 postoperative hours or duration of hospitalization (whichever comes first)	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
Time Spent in Sitting or Upright Position	Initial 48 postoperative hours or duration of hospitalization (whichever comes first)	Treatment effect data are reported as ratios of geometric means
Incidence of Low Respiratory Function Event	Initial 48 postoperative hours or duration of hospitalization (whichever comes first)	A low respiratory function event was defined as an episode of less than 40% of predicted minute ventilation for 2 minutes.