Evaluating respiratory depression after methadone administration in surgical patients: protocol for a systematic review and meta-analysis

Introduction Methadone has emerged as a promising option for perioperative pain management, primarily due to its rapid onset of action and prolonged duration of effect, which provides sustained analgesic benefits. Despite its clinical advantages and minimal reported risks for postoperative respirato...

Full description

Saved in:
Bibliographic Details
Main Authors: Guido Mazzinari, Juan P. Cata, Eduardo Nunez-Rodriguez, Sarah Lumsden, Kate J. Krause, Nicolas Cortes, Evan D. Kharasch
Format: Article
Language:English
Published: BMJ Publishing Group 2025-05-01
Series:BMJ Open
Online Access:https://bmjopen.bmj.com/content/15/5/e099463.full
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1850110766539079680
author Guido Mazzinari
Juan P. Cata
Eduardo Nunez-Rodriguez
Sarah Lumsden
Kate J. Krause
Nicolas Cortes
Evan D. Kharasch
author_facet Guido Mazzinari
Juan P. Cata
Eduardo Nunez-Rodriguez
Sarah Lumsden
Kate J. Krause
Nicolas Cortes
Evan D. Kharasch
author_sort Guido Mazzinari
collection DOAJ
description Introduction Methadone has emerged as a promising option for perioperative pain management, primarily due to its rapid onset of action and prolonged duration of effect, which provides sustained analgesic benefits. Despite its clinical advantages and minimal reported risks for postoperative respiratory depression, concerns about its potential respiratory complications persist. This protocol outlines a meta-analysis aimed at evaluating the risk of respiratory depression associated with methadone administration in the perioperative setting compared with other opioids or placebo.Methods and analysis We will perform a systematic review of literature published in English from 1 January 1970 to the present using Ovid MEDLINE, Ovid Embase and Cochrane CENTRAL. Eligible studies will consist of randomised controlled trials, cohort studies and case–control studies reporting respiratory depression in surgical patients receiving intravenous methadone. Case reports, reviews and non-English studies will be excluded. The primary outcome is respiratory depression, defined as naloxone administration, a respiratory rate of fewer than 8 breaths per minute, or an arterial oxygen saturation below 90%. Secondary outcomes include the timing and dose–response effect of methadone on respiratory depression. Bias will be evaluated using the Cochrane Risk of Bias Assessment 2 and ROBINS-I tools. Meta-analyses will be performed, and effect estimates will be presented as relative risks or ORs with 95% CIs. The certainty of the evidence will be assessed using Grading of Recommendations Assessment, Development and Evaluation methodology.Ethics and dissemination Ethics approval is not necessary for this systematic review and meta-analysis. The results will be published in a peer-reviewed journal and presented at national and international conferences focused on perioperative medicine and pain management.PROSPERO registration number CRD42025630383.
format Article
id doaj-art-d3708d70913b4b95b18a464bb8b232f2
institution OA Journals
issn 2044-6055
language English
publishDate 2025-05-01
publisher BMJ Publishing Group
record_format Article
series BMJ Open
spelling doaj-art-d3708d70913b4b95b18a464bb8b232f22025-08-20T02:37:46ZengBMJ Publishing GroupBMJ Open2044-60552025-05-0115510.1136/bmjopen-2025-099463Evaluating respiratory depression after methadone administration in surgical patients: protocol for a systematic review and meta-analysisGuido Mazzinari0Juan P. Cata1Eduardo Nunez-Rodriguez2Sarah Lumsden3Kate J. Krause4Nicolas Cortes5Evan D. Kharasch62 Anesthesiology and Critical Care, Hospital la Fe, Valencia, SpainDepartment of Anesthesiology and Perioperative Medicine, MD Anderson Cancer Center, Houston, Texas, USADepartment of Anesthesiology and Perioperative Medicine, The University of Texas MD Anderson Cancer Center Department of Anesthesiology and Perioperative Medicine, Houston, Texas, USAAnesthesiology Care Line, Michael E DeBakey VA Medical Center, Houston, Texas, USAResearch Medical Library, MD Anderson Cancer Center, Houston, Texas, USADepartment of Anesthesiology and Perioperative Medicine, MD Anderson Cancer Center, Houston, Texas, USADepartment of Anesthesiology, Duke University School of Medicine, Durham, North Carolina, USAIntroduction Methadone has emerged as a promising option for perioperative pain management, primarily due to its rapid onset of action and prolonged duration of effect, which provides sustained analgesic benefits. Despite its clinical advantages and minimal reported risks for postoperative respiratory depression, concerns about its potential respiratory complications persist. This protocol outlines a meta-analysis aimed at evaluating the risk of respiratory depression associated with methadone administration in the perioperative setting compared with other opioids or placebo.Methods and analysis We will perform a systematic review of literature published in English from 1 January 1970 to the present using Ovid MEDLINE, Ovid Embase and Cochrane CENTRAL. Eligible studies will consist of randomised controlled trials, cohort studies and case–control studies reporting respiratory depression in surgical patients receiving intravenous methadone. Case reports, reviews and non-English studies will be excluded. The primary outcome is respiratory depression, defined as naloxone administration, a respiratory rate of fewer than 8 breaths per minute, or an arterial oxygen saturation below 90%. Secondary outcomes include the timing and dose–response effect of methadone on respiratory depression. Bias will be evaluated using the Cochrane Risk of Bias Assessment 2 and ROBINS-I tools. Meta-analyses will be performed, and effect estimates will be presented as relative risks or ORs with 95% CIs. The certainty of the evidence will be assessed using Grading of Recommendations Assessment, Development and Evaluation methodology.Ethics and dissemination Ethics approval is not necessary for this systematic review and meta-analysis. The results will be published in a peer-reviewed journal and presented at national and international conferences focused on perioperative medicine and pain management.PROSPERO registration number CRD42025630383.https://bmjopen.bmj.com/content/15/5/e099463.full
spellingShingle Guido Mazzinari
Juan P. Cata
Eduardo Nunez-Rodriguez
Sarah Lumsden
Kate J. Krause
Nicolas Cortes
Evan D. Kharasch
Evaluating respiratory depression after methadone administration in surgical patients: protocol for a systematic review and meta-analysis
BMJ Open
title Evaluating respiratory depression after methadone administration in surgical patients: protocol for a systematic review and meta-analysis
title_full Evaluating respiratory depression after methadone administration in surgical patients: protocol for a systematic review and meta-analysis
title_fullStr Evaluating respiratory depression after methadone administration in surgical patients: protocol for a systematic review and meta-analysis
title_full_unstemmed Evaluating respiratory depression after methadone administration in surgical patients: protocol for a systematic review and meta-analysis
title_short Evaluating respiratory depression after methadone administration in surgical patients: protocol for a systematic review and meta-analysis
title_sort evaluating respiratory depression after methadone administration in surgical patients protocol for a systematic review and meta analysis
url https://bmjopen.bmj.com/content/15/5/e099463.full
work_keys_str_mv AT guidomazzinari evaluatingrespiratorydepressionaftermethadoneadministrationinsurgicalpatientsprotocolforasystematicreviewandmetaanalysis
AT juanpcata evaluatingrespiratorydepressionaftermethadoneadministrationinsurgicalpatientsprotocolforasystematicreviewandmetaanalysis
AT eduardonunezrodriguez evaluatingrespiratorydepressionaftermethadoneadministrationinsurgicalpatientsprotocolforasystematicreviewandmetaanalysis
AT sarahlumsden evaluatingrespiratorydepressionaftermethadoneadministrationinsurgicalpatientsprotocolforasystematicreviewandmetaanalysis
AT katejkrause evaluatingrespiratorydepressionaftermethadoneadministrationinsurgicalpatientsprotocolforasystematicreviewandmetaanalysis
AT nicolascortes evaluatingrespiratorydepressionaftermethadoneadministrationinsurgicalpatientsprotocolforasystematicreviewandmetaanalysis
AT evandkharasch evaluatingrespiratorydepressionaftermethadoneadministrationinsurgicalpatientsprotocolforasystematicreviewandmetaanalysis