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

University of Aarhus

Status: Active, not recruiting

Conditions: Postoperative Pain

Treatments: Drug: Morphine; Drug: Methadone

Study type: Interventional

Funder types: Other

Identifiers

NCT03908060

01052019

Details and patient eligibility

About

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.

Full 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.

Enrollment: 126 patients

Sex: Female

Ages: 18 to 110 years old

Volunteers: Accepts Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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126 participants in 2 patient groups

Intravenous single-dose methadone

Experimental group

Description:

A 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).

Treatment:

Drug: Methadone

Intravenous single-dose morphine

Active Comparator group

Description:

A 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).

Treatment:

Drug: Morphine