Analgesic Efficacy of Intravenous Acetaminophen After Video-assisted Thoracic Surgery

Study Overview
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Brief Summary
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We will study the efficacy of FDA approved intravenous (IV) acetaminophen (Ofirmev, © 2011 Cadence Pharmaceuticals, Inc.) in reducing opioid consumption after minimally invasive thoracic surgery in a double blind randomized trial. This drug has been shown in Europe to reduce the need for patient controlled analgesia and the total dose of opioids, which have serious side effects in thoracic surgery patients. We will compare the use of IV patient-controlled morphine (PCA) in two groups of subjects in treating postoperative pain. We will determine if IV acetaminophen reduces post-operative morphine requirements (primary end point). We will also assess subject pain scores and post-operative complications associated with pain management as secondary end points. Our hypothesis is that the study arm receiving intravenous acetaminophen will have lower total morphine consumptions compared to the placebo group.

Detailed Description
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We will study the efficacy of FDA approved intravenous (IV) acetaminophen (Ofirmev, © 2011 Cadence Pharmaceuticals, Inc.) in reducing opioid consumption after minimally invasive thoracic surgery in a double blind randomized trial. This drug has been shown in Europe to reduce the need for patient controlled analgesia and the total dose of opioids, which have serious side effects in thoracic surgery patients. We will compare the use of IV patient-controlled morphine (PCA) in two groups of subjects in treating postoperative pain. One group of subjects will receive IV acetaminophen every six hours beginning within 30 minutes before surgical end time and continuing for 24 hours plus IV morphine PCA, and the other group will receive IV placebo every six hours plus IV morphine PCA, a standard treatment for postoperative pain. We will determine if IV acetaminophen reduces post-operative morphine requirements (primary end point). We will also assess subject pain scores and post-operative complications associated with pain management as secondary end points. Our hypothesis is that the study arm receiving intravenous acetaminophen will have lower total morphine consumptions compared to the placebo group.

Official Title
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A Double-blind, Randomized, Placebo-controlled Study to Compare the Effectiveness of IV Acetaminophen Administered Intra-operatively in Reducing the Use of Opiates to Treat Post-operative Pain

Conditions
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Lung Tumor

Intervention / Treatment
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* Drug: IV Acetaminophen
* Drug: Saline Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Any elective VATS patients with low probability of conversion to thoracotomy as determined by surgery. Ages 18-99 American Society of Anesthesiologists Physical Status I-III, hemodynamically stable Male or female Exclusion Criteria: Age less than 18. Patient refusal High probability of conversion to thoracotomy as determined by surgeon Conversion of procedure to thoracotomy (subjects will be withdrawn if VATS procedure is converted to thoracotomy, as thoracotomy is more invasive and will likely require additional analgesia such as neuraxial and regional anesthesia). Scheduled procedure of VATS Pleurodesis/decortication History of Interstitial Lung Disease Emergency case Known allergy/adverse reaction to acetaminophen, morphine, or fentanyl History of drug or alcohol abuse Patients on preoperative analgesic therapy within one week of surgery Contraindication to self administered morphine (unable to understand PCA) Need for postoperative mechanical ventilation Necessary major deviation for intraoperative study protocol as per the discretion of the intraoperative attending anesthesiologist History of congestive heart failure, renal failure, liver failure Pregnant or breastfeeding women Weight less than 51 kg

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 99 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: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Saline Placebo<br>Subjects will receive a saline placebo infusion administered over 15 minutes every 6 hours for 24 hours. | Drug: Saline Placebo<br>* Normal saline placebo given every six hours for a total of four doses if randomized to the placebo arm.<br>* Other names: Normal saline solution;|
| Active Comparator: IV Acetaminophen<br>Subjects will receive an infusion of 1 g of intravenous acetaminophen administered over 15 minutes every 6 hours for 24 hours with a maximum dose of 4 grams. | Drug: IV Acetaminophen<br>* 1000mg IV Ofirmev given every six hours for a total of four doses.<br>* Other names: Paracetamol;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Total Morphine Consumption (mg) | How much morphine the subject consumes in the first 24 hours after surgery (mg). | 24 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Total Number of PCA Requests in First 24 Hours Post-Operation | The total number of Patient Controlled Analgesic (PCA) requests in the first 24 hours after the conclusion of the subject's operation | 24 hours post-operation | 
| VAS Pain Score 2 Hours Post Operation | 2 hours after the conclusion of their operation,participants were asked to draw a vertical line on the VAS to indicate their level of pain, which was then converted into millimeters for interpretations. Scores ranged from 0-100mm. VAS pain score identifies two extremes on a 10 centimeter horizontal line; the extremes are labeled No Pain (score of 0) and Worst possible pain (score of 100). | 2 Hours Post Operation | 
| VAS Pain Score 6 Hours Post-Operation | 6 hours after the conclusion of their operation, participants were asked to draw a vertical line on the VAS to indicate their level of pain, which was then converted into millimeters for interpretations. Scores ranged from 0-100mm. VAS pain score identifies two extremes on a 10 centimeter horizontal line; the extremes are labeled No Pain (score of 0) and Worst possible pain (score of 100). | 6 Hours Post-Operation | 
| VAS Score 24 Hours Post-Operation | 24 Hours after the conclusion of the subject's operation, participants were asked to draw a vertical line on the VAS to indicate their level of pain, which was then converted into millimeters for interpretations. Scores ranged from 0-100mm. VAS pain score identifies two extremes on a 10 centimeter horizontal line; the extremes are labeled No Pain (score of 0) and Worst possible pain (score of 100). | 24 hours post-operation | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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VATS, thoracic surgery, acetaminophen, ofirmev, lung surgery, thoracoscopic, intravenous acetaminophen