Intraoperative Methadone for Postoperative Pain in Patients Undergoing Tonsillectomy

Study Overview
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Brief Summary
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A randomized controlled trial evaluating the efficacy and safety of single-shot intraoperative methadone for postoperative pain in patients undergoing tonsillectomy. Fentanyl is used as an active comparator

Detailed Description
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This study is an investigator-initiated, prospective, randomised controlled trial with two arms: an intervention arm (methadone) and a control arm (fentanyl). Patients scheduled for tonsillectomy at Randers Regional Hospital, Denmark, will be approached for study participation. Patients are randomised in a 1:1 ratio in blocks of varying sizes (between 4 and 8) to receive either intraoperative methadone or fentanyl. The randomisation assignment will be handled by the hospital pharmacy using a web-based central randomisation procedure (www.sealedenvelope.com). The study drug will be prepared by the hospital pharmacy at Aarhus University Hospital and delivered as kits with identical appearance, marked with the randomization number (1-130). On the day of surgery, a kit will be opened and a 10 ml syringe with study drug (methadone 2 mg/ml or fentanyl 30 microgram/ml or ) will prepared by a health care professional (nurse or medical doctor not involved in the study or the treatment of patients). Once prepared, the blinded study drug will be given to and handled by one of the research team members and administered after induction of anesthesia and prior to surgery The dose of the study drug will be administered as intravenous bolus dose in equipotent doses (0.2 mg/kg / 3 μg/kg) corresponding to 1 ml for every 10 kg of ideal body weight (women: height (cm) - 105. Men: height (cm) - 100)) after induction of anaesthesia and before the start of surgery. Postoperative data will be obtained by reviewing hospital records, by interview and electronic questionnaires sent by email.

Official Title
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Intraoperative Methadone for Postoperative Pain in Patients Undergoing Tonsillectomy - a Randomized Controlled Trial

Conditions
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Postoperative Pain

Intervention / Treatment
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* Drug: Methadone
* Drug: Fentanyl


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: All patients (≥18 years) scheduled for elective tonsillectomy Exclusion Criteria: American Society of Anaesthesiologists (ASA) physical status IV or V Allergy to study drugs Daily use of opioids 7 days prior to surgery Inability to provide informed consent Severe respiratory insufficiency Heart failure Acute alcohol intoxication/delirium tremens Increased intracranial pressure Acute liver disease Liver insufficiency Kidney insufficiency Treatment with rifampicin Treatment with any drug prolonging the QT-interval Pregnancy (every female not using contraceptives will be screened with urine human choriogonadotropin) Breastfeeding

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 100 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: Methadone<br>Single-shot intravenous methadone 0.2 mg/kg administered intraoperatively | Drug: Methadone<br>* Methadone is administered as a single intravenous dose after induction of anesthesia and prior to initiation of surgery<br>|
| Active Comparator: Fentanyl<br>Single-shot intravenous fentanyl 3 microgram/kg administered intraoperatively | Drug: Fentanyl<br>* Fentanyl is administered as a single intravenous dose after induction of anesthesia and prior to initiation of surgery<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Postoperative pain | Pain at swallowing (numeric rating scale (NRS) 0-10, lower scores are better outcomes) | On arrival at the post-anesthesia care unit | 
| Opioid consumption | Cumulative postoperative opioid consumption in morphine equivalents | First 5 postoperative days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Postoperative pain | Pain at swallowing (numeric rating scale (NRS) 0-10, lower scores are better outcomes) | 1, 2, 3, 5 and 7 days after surgery | 
| Opioid consumption | Cumulative postoperative opioid consumption in morphine equivalents | 1 and 7 days after surgery | 
| Postoperative nausea and vomiting (none, mild, moderate, severe) | Nausea and/or vomiting (PONV), proportion of patients with none or mild PONV | 1, 2 and 3 days after surgery | 
| Sedation | Level of sedation (Ramsay Scale (1-4)), proportion of patients being co-operative, oriented and tranquil | 4 hours after surgery | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Postoperative pain, Methadone