IV Acetaminophen for Post-Operative Pain Management in Enhanced Recovery After Surgery (ERAS) Population

Study Overview
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Brief Summary
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Number of patients with unsatisfactory pain relief defined as average visual analog scale (VAS) more than 5 with or without requirement of IVPCA for pain relief during the first 48 hours postoperative period will be compared between the two groups and form the primary outcome for the study. Postoperative pain intensity will be measured by Visual Analog Scale (VAS) with 0- being no pain and 10-being maximum pain and the analgesic efficacy in both groups will also be evaluated by the amount of total narcotic consumption (measured with IV morphine equivalent doses of analgesics used to provide pain relief).

Detailed Description
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In response to an increased focus on improving patient outcomes and satisfaction with surgical care, a growing body of clinical evidence has recently been dedicated to enhanced recovery after surgery (ERAS) protocols. These evidence-based perioperative pathways aim to optimize patients undergoing surgery in the preoperative, intraoperative, and postoperative periods. ERAS protocols have incorporated the use of multimodal analgesia to minimize the use of intra- and postoperative opioid analgesics. Lidocaine, ketamine, magnesium, gabapentin, acetaminophen and non-steroidal anti-inflammatory drugs are some of the adjuvant analgesics used in combination with regional blocks to optimize analgesia and recovery. Multimodal analgesia has dependably been shown to significantly reduce postoperative opioid requirements as well as opioid-related side effects such as postoperative nausea and vomiting. Both oral and intravenous acetaminophen preparations have been shown to be useful adjuvants in multimodal analgesia. Intravenous acetaminophen has been of interest for its utility in post-surgical patients, who have not yet been cleared for oral intake. Intravenous acetaminophen should also be preferred over oral acetaminophen in patients after major abdominal surgery where absorption of medications given through oral route is erratic. Although the efficacy of intravenous acetaminophen as a postoperative pain adjunct is known, its exact role in ERAS protocols and non-narcotic multimodal analgesic regimens for major abdominal surgery has not been studied in randomized clinical trials to define its efficacy. The primary goal of this study is to assess the utility of a postoperative intravenous acetaminophen dosing schedule in minimizing postoperative pain, opioid consumption and opioid-related side effects. We also aim to study overall patient satisfaction and cost-effectiveness (direct and indirect costs) of this regimen as part of ERAS protocol at a large tertiary medical center.

Official Title
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Role of Scheduled Intravenous Acetaminophen for Postoperative Pain Management in an Enhanced Recovery After Surgery (ERAS) Population: A Prospective, Randomized, Double-Blind and Placebo-Controlled Clinical Trial

Conditions
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Abdominal Wall Hernia, Pancreatic Diseases, Bowel Disease, Gastric Disease

Intervention / Treatment
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* Drug: Acetaminophen Injectable Product
* Drug: Sodium Chloride 0.9%, Intravenous


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or Female 18 years of age or older patients scheduled for elective colorectal, pancreatic, and other major abdominal procedure. Patient consent will be obtained preoperatively for eligible study participants. Exclusion Criteria: Patients who refuse to participate in the study or part of any other enhanced recovery after surgery (ERAS) research protocol. Patients with a documented allergy to acetaminophen. Chronic alcoholism Hypovolemia Chronic malnutrition Preoperative renal insufficiency (creatinine clearance less than or equal to 30ml/min) or hemodialysis Patients with a history of hepatic impairment, history of hepatic impairment or active hepatic disease severe chronic pain condition that required daily preoperative opioid dependence Patients with pre-existing dementia and/or other neuropsychiatric conditions impeding accurate assessment of pain scores or other study measures will be excluded.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Acetaminophen Injectable Product<br>Acetaminophen group: Half of subjects enrolled will be randomized to the acetaminophen group | Drug: Acetaminophen Injectable Product<br>* The interventional group will receive 1 gram intravenous acetaminophen at the start of wound closure to be repeated every 6 hours for 48 hours postoperatively<br>* Other names: Ofirmev;|
| Placebo Comparator: Sodium Chloride 0.9%, Intravenous<br>Sodium Chloride 0.9% group: Half of subjects enrolled will be randomized to the acetaminophen group | Drug: Sodium Chloride 0.9%, Intravenous<br>* The placebo group will be given an intravenous placebo of saline solution at wound closure and repeated every 6 hours for 48 hours postoperatively.<br>* Other names: Saline;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Postoperative Pain Intensity | Number of patients with unsatisfactory pain relief defined as average numeric rating scale (NRS) more than 5 will be compared between the two groups. This may include patients using IVPCA for pain relief during the first 48 hours postoperative. | PACU admission every thirty minutes until discharge to the floor and thereafter every four hours for first 24-hour, then every six hours until 48 hours and then every twelve hours until 72 hours postoperatively. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Total Post-operative Narcotic Consumption | Rescue analgesia will be given according to institutional pain management protocol. Unit of Measure recorded as OME (Oral Morphine Equivalent) consumption in mg. | From time of PACU admission until the time of discharge and 72-hours postoperatively, whichever comes first | 
| Time to Readiness for Discharge From Post Anesthesia Care Unit (PACU) | The time from PACU admission to PACU discharge to the floor will be measured. | From time of PACU admission until the time of discharge, assessed up to 24 hours postoperatively | 
| Time to Bowel Movement | The time it takes for the first bowel movement postoperatively will be measured. | From time patient left operating room until the time of first documented bowel movement, assessed up to hospital discharge | 
| Time to Oral Intake | The time it takes for the patient to ingest orally post-surgery will be measured. | From date of randomization until the date of first documented oral intake, assessed up to 72 hours postoperatively | 
| Time to Ambulation | The time it takes for the patient to successfully ambulate post-surgery will be measured. | From date of PACU admission until the date of first documented ambulation, assessed up to 72 hours postoperatively | 
| Time to Hospital Discharge | The time it takes for the patient to be fully discharged from the hospital post-surgery will be measured. | From date of randomization until the date of hospital discharge or 30 days postoperatively, whichever comes first | 
| Number of Participants With Readmission to the Hospital | If the patient is readmitted to the hospital after being fully discharged, the event will be recorded. | From the time of consent until 30 days post-operatively | 
| Patient Satisfaction | Overall patient satisfaction as well as satisfaction relating to pain management and cost analyses will be measured. These will be measured with a numerical rating scale (NRS) with 0- being worst satisfaction and 10 - best satisfaction. | These measurements will be taken at time of discharge up to 30 days, whichever comes first | 
| Intensive Care Delirium Screening Checklist (ICDSC) | Number of patients who score greater than a 4 on the 0-8 point ICDSC scale to assess delirium scores. 8 separate levels of signs for delirium assessed (1. altered level of consciousness, 2. inattention, 3. disorientation, 4. hallucination, delusion, or psychosis, 5. psychomotor agitation or retardation, 6. inappropriate speech or mood, 7. sleep-wake cycle disturbance, 8. symptom fluctuation), with 0 points awarded when patient does not exhibit above signs of delirium and 1 point awarded per confirmed sign of delirium. Score then totaled, 0 = normal, 1-3 = subsyndromal delirium, 4-8 = delirium. | The delirium scores will first be measured every 12 hours for 72 hours after surgery. | 
| Post-operative Nausea | Nausea will be evaluated by nausea score from 0 to 10, with 0 equaling no nausea and 10 equaling the worst nausea imaginable. | These will be evaluated from the time of PACU admission until 72 hours postoperatively. | 
| Post-operative Emesis | Frequency of emesis and rescue antiemetic requirement will be documented | These will be evaluated from the time of PACU admission until 72 hours postoperatively. | 
| SF-12 Health Survey | Survey to assess patient's overall health (via a combination of mental and physical health assessment) at 30 days post-discharge. Two summary scores are reported from the SF-12 - a mental component score (MCS-12) and a physical component score (PCS-12). The scores may be reported as Z-scores (difference compared to the population average, measured in standard deviations). The United States population average PCS-12 and MCS-12 are both 50 points. The United States population standard deviation is 10 points. So each 10 increment of 10 points above or below 50, corresponds to one standard deviation away from the average | These measurements will take place at 30-days post hospital discharge | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Post-operative pain, Major abdominal surgery, Colorectal surgery, Gastric surgery