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Clinical Effectiveness and Safety of Intraoperative Methadone in Patients Undergoing Laparoscopic Hysterectomy

Not Applicable
Active, not recruiting
Conditions
Postoperative Pain
Interventions
Registration Number
NCT03908060
Lead Sponsor
University of Aarhus
Brief Summary

The role of a single-dose of intraoperative methadone on postoperative pain and opioid consumption in patients undergoing hysterectomy remains scarcely explored. A prospective double-blind, randomised controlled trial investigating the effect of a single-dose of intraoperative methadone in patients scheduled for same day hysterectomy is therefore conducted.

Detailed Description

Background with aim: Hysterectomy is the most common major gynaecological procedure in the world and hysterectomy on benign indications are increasingly being performed as same-day surgery. Therefore, perioperative anaesthesia has moved towards the use of very short-acting opioids with the incitement to speed up extubation and facilitate hospital discharge. However, the potential consequence is that more patients experience pain and discomfort.

Methadone has several desirable pharmacological features, and a single intraoperative dose of the long acting opioid could therefore theoretically expand the analgesic window and reduce postoperative opioid consumption compared to the more conventional use of short-acting opioids. The aim of this study is to investigate the effect of a single-dose of intravenous intraoperative methadone on postoperative opioid consumption, pain and side effects in patients scheduled for hysterectomy for benign indications. Our primary hypothesis is that intravenous perioperative methadone reduces opioid consumption (oral cumulative equivalent dose) by 30% during the first 24 postoperative hours compared to intravenous morphine.

Methods: 126 patients will be included in an investigator-initiated, prospective, randomised, double-blind, controlled trial with two arms: an intervention arm (methadone 0.2 mg/kg ideal body weight) and a control arm (morphine 0.2 mg/kg ideal body weight). The study will be GCP-monitored, and is approved by the Danish Health and Medicines Authority (2018-004351-20) and the Central Denmark Region Committees on Health Research Ethics (1-10-72-365-18).

Hypothesis: The results will probably be applicable to other types of surgery involving visceral pain, and thus the present study has the potential to improve the pain management for a large number of patients undergoing surgery.

Recruitment & Eligibility

Status
ACTIVE_NOT_RECRUITING
Sex
Female
Target Recruitment
126
Inclusion Criteria
  • Patients scheduled for elective laparoscopic hysterectomy for benign indications
Exclusion Criteria
  • American Society of Anaesthesiologists (ASA) physical status IV or V
  • prolonged QT-interval assessed by electrocardiogram (> 440 milliseconds)
  • Existing treatment with medications prolonging the QT-interval
  • Hysterectomy due to malignancy or acute bleeding disorders
  • Allergy to study drugs
  • Preoperative daily use of opioids
  • Severe respiratory insufficiency
  • Heart failure
  • Acute alcohol intoxication/delirium tremens
  • Increased intracranial pressure
  • Acute liver disease
  • Acute abdominal pain
  • Liver insufficiency
  • Kidney insufficiency
  • Treatment with rifampicin
  • Breastfeeding
  • Inability to provide informed consent.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Intravenous single-dose morphineMorphineA 10 ml syringe with 2 mg/ml of morphine will be prepared and study drug will be administered as intravenous bolus dose (0.2 mg/kg) corresponding to 1 ml for every 10 kg of ideal body weight (height (cm) - 105).
Intravenous single-dose methadoneMethadoneA 10 ml syringe with 2 mg/ml of methadone will be prepared and and study drug will be administered as intravenous bolus dose (0.2 mg/kg) corresponding to 1 ml for every 10 kg of ideal body weight (height (cm) - 105).
Primary Outcome Measures
NameTimeMethod
Opioid consumption at 24 hours after extubation (cumulative opioid consumption)24 hours

cumulative opioid consumption in oral morphine equivalents

Opioid consumption at 6 hours after extubation (cumulative opioid consumption)6 hours

cumulative opioid consumption in oral morphine equivalents

Secondary Outcome Measures
NameTimeMethod
Pain intensity (NRS, 0-10) at rest and coughing0-48 hours after extubation

Numeric Rating Scale (NRS) ranging from 0 (no pain) to 10 (worst imaginable pain)

Postoperative side effects/ adverse events (nausea and vomiting, sedation, hypoventilation, and hypoxemia)0-72 hours after extubation

Number of patients

Trial Locations

Locations (1)

Department of Anaesthesiology and Intensive Care, Horsens Regional Hospital

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Horsens, Central Denmark Region, Denmark

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