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

Postoperative Pain Clinical Trial

Official title:

Clinical Effectiveness and Safety of Intraoperative Methadone in Patients Undergoing Laparoscopic Hysterectomy: a Prospective, Double-blind, Randomised Controlled Trial

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03908060
• Other study ID #: 01052019
• Status: Active, not recruiting
• Phase: N/A
• Start date: May 6, 2019
• Est. completion date: December 1, 2022

Study information

• Verified date: October 2022
• Source: University of Aarhus
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Active, not recruiting
• Enrollment: 126
• Est. completion date: December 1, 2022
• Est. primary completion date: July 8, 2022
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 18 Years to 110 Years

Eligibility

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.

Related Conditions & MeSH terms

• Pain, Postoperative
• Postoperative Pain

Intervention

Drug:
• Methadone
One intravenous administration of methadone (0.2 mg/kg ideal body weight)
• Morphine
One intravenous administration of morphine (0.2 mg/kg ideal body weight)

Locations

Country	Name	City	State
Denmark	Department of Anaesthesiology and Intensive Care, Horsens Regional Hospital	Horsens	Central Denmark Region

Sponsors (1)

Lead Sponsor	Collaborator
University of Aarhus

Country where clinical trial is conducted

Denmark, 

References & Publications (5)

Chui PT, Gin T. A double-blind randomised trial comparing postoperative analgesia after perioperative loading doses of methadone or morphine. Anaesth Intensive Care. 1992 Feb;20(1):46-51. — View Citation

Gottschalk A, Durieux ME, Nemergut EC. Intraoperative methadone improves postoperative pain control in patients undergoing complex spine surgery. Anesth Analg. 2011 Jan;112(1):218-23. doi: 10.1213/ANE.0b013e3181d8a095. Epub 2010 Apr 24. — View Citation

Murphy GS, Szokol JW, Avram MJ, Greenberg SB, Marymont JH, Shear T, Parikh KN, Patel SS, Gupta DK. Intraoperative Methadone for the Prevention of Postoperative Pain: A Randomized, Double-blinded Clinical Trial in Cardiac Surgical Patients. Anesthesiology. 2015 May;122(5):1112-22. doi: 10.1097/ALN.0000000000000633. — View Citation

Murphy GS, Szokol JW, Avram MJ, Greenberg SB, Shear TD, Deshur MA, Vender JS, Benson J, Newmark RL. Clinical Effectiveness and Safety of Intraoperative Methadone in Patients Undergoing Posterior Spinal Fusion Surgery: A Randomized, Double-blinded, Controlled Trial. Anesthesiology. 2017 May;126(5):822-833. doi: 10.1097/ALN.0000000000001609. — View Citation

Richlin DM, Reuben SS. Postoperative pain control with methadone following lower abdominal surgery. J Clin Anesth. 1991 Mar-Apr;3(2):112-6. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Opioid consumption at 24 hours after extubation (cumulative opioid consumption)	cumulative opioid consumption in oral morphine equivalents	24 hours
Primary	Opioid consumption at 6 hours after extubation (cumulative opioid consumption)	cumulative opioid consumption in oral morphine equivalents	6 hours
Secondary	Pain intensity (NRS, 0-10) at rest and coughing	Numeric Rating Scale (NRS) ranging from 0 (no pain) to 10 (worst imaginable pain)	0-48 hours after extubation
Secondary	Postoperative side effects/ adverse events (nausea and vomiting, sedation, hypoventilation, and hypoxemia)	Number of patients	0-72 hours after extubation