Methadone for Postoperative Pain

Efficacy Methadone for Management Postoperative Pain After the Use of Anesthesia Intravenous in Laparoscopic Cholecystectomy

The aim of this study is to compare the efficacy of methadone versus morphine in dealing with postoperative pain, in laparoscopic cholecystectomy under total intravenous anesthesia (TIVA); Efficacy is defined in terms of the difference of milligrams in morphine used as rescue analgesia postoperatively. Our hypothesis is that methadone is more effective than morphine for postoperative pain treatment.

Study Overview

• Status: Completed
• Conditions: Pain, Postoperative
• Intervention / Treatment: Drug: Morphine; Drug: TIVA; Drug: Methadone

Detailed Description

Patients undergo laparoscopic cholecystectomy at Almirante Nef Naval Hospital will be recruited, between March and July 2013. The sample size was calculated to obtain an average difference of 4 mg of morphine (DE 1.5) to 3 mg of morphine (DE 1.5), with a power of 80% and a significance level of 0.05. This came down to 36 randomized patients into each group, so 86 patients will be recruited considering a 15% loss to follow up.

Before signing an informed consent, we will explain to them how to classify pain intensity numerical rating scale (NRS) and this will be evaluated periodically during the first 24 hours after surgery.

General anesthesia will be based on Remifentanil and Propofol, titrated to achieve bispectral index (BIS) between 40 and 60. Patients will be randomized into methadone group (ME) and morphine group (MO), they will receive 0.08 mg / kg bolus of methadone or 0.08 mg / kg bolus of morphine as applicable at the time of beginning surgery. Postoperative analgesia will be standard for both groups. Patient´s demographic data will be filed as well as surgical timings.

All patients will remain in the anesthetic recovery room for the first two hours , to get a record taken of vital signs and measurement of NRS at 5, 15, 30, 60 and 120 minutes. If NRS is greater than or equal to 4, 1 mg of morphine ev will be used as analgesic rescue. In room measuring NRS continue hospitalized at 4, 8, 12 and 24 hours postoperatively and were used as rescue analgesia if ketorolac 30mg ev NRS is greater than or equal to 4. The amount of morphine is registered and ketorolac rescue of both groups as well as pain assessment scores. The occurrence of adverse effects such as nausea, vomiting, pruritus, urinary retention and respiratory depression is also recorded in both groups, to be compared later as a secondary objective.

• Study Type: Interventional
• Enrollment (Actual): 86
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Chile
  • Valparaiso
    • Viña del Mar, Valparaiso, Chile
      • Almirante Nef Naval Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patients undergoing laparoscopic cholecystectomy in the Almirante Nef Naval Hospital
• Patients ASA 1 or 2

Exclusion Criteria:

• Patients with renal insufficiency (creatinine> 2.0 mg / dl)
• Patients with a history of liver failure
• Patients with BMI> 35 kg/m2
• Patients with hypersensitivity to the drugs in question
• History of chronic use of opioids
• Need for conversion to open surgery

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Morphine; morphine group 0.08 mg / kg, to start surgery	Drug: Morphine; Morphine group,receive morphine 0.08 mg / kg at the start of surgery; Drug: TIVA; TIVA: General anesthesia will be based on Remifentanil and Propofol (TIVA-TCI), titrated to achieve bispectral index (BIS) between 40 and 60.
Experimental: Methadone; methadone group 0.08 mg / kg, to start surgery	Drug: TIVA; TIVA: General anesthesia will be based on Remifentanil and Propofol (TIVA-TCI), titrated to achieve bispectral index (BIS) between 40 and 60.; Drug: Methadone; Methadone group,receive methadone 0.08 mg / kg at the start of surgery

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Difference in milligrams of morphine used as rescue analgesia	Difference in milligrams of morphine used as rescue analgesia in postoperative period in both groups	First 24 hours postoperatively

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Difference in pain scores, using the Numeric Rating Scale	Difference in pain scores, using the Numeric Rating Scale at 5, 15, 30, 60 and 120 minutes postoperative. Also at 4, 8, 12 and 24 hours postoperatively, during hospitalization.	First 24 hours postoperatively

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
The different of the adverse effect	The total number of adverse effects such as nausea, vomiting, pruritus, urinary retention and respiratory depression is recorded in both groups, to be compared later as a secondary objective.	First 24 hours postoperatively

Collaborators and Investigators

• Sponsor: Universidad de Valparaiso
• Investigators: Principal Investigator: NICOLAS ARRIAZA, Physician, University Valparaiso

Publications and helpful links

General Publications

• Arriaza N, Papuzinski C, Kirmayr M, Matta M, Aranda F, Stojanova J, Madrid E. Efficacy of methadone for the management of postoperative pain in laparoscopic cholecystectomy: A randomized clinical trial. Medwave. 2021 Mar 23;21(2):e8135. doi: 10.5867/medwave.2021.02.8134. English, Spanish.

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2013
• Primary Completion (Actual): August 1, 2013
• Study Completion (Actual): September 1, 2013

Study Registration Dates

• First Submitted: March 30, 2013
• First Submitted That Met QC Criteria: April 14, 2013
• First Posted (Estimated): April 17, 2013

Study Record Updates

• Last Update Posted (Actual): September 26, 2023
• Last Update Submitted That Met QC Criteria: September 22, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Keywords: Methadone; Morphine; Pain, Postoperative; Analgesics, Opioid
• Additional Relevant MeSH Terms: Pathologic Processes; Postoperative Complications; Pain; Neurologic Manifestations; Pain, Postoperative; Physiological Effects of Drugs; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Analgesics, Opioid; Narcotics; Respiratory System Agents; Antitussive Agents; Morphine; Methadone
• Other Study ID Numbers: P03/13

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No