Intraoperative Intravenous Methadone Versus Non-Methadone Opioid Analgesia in Instrumented Spinal Fusion: A GRADE-Guided Systematic Review and Meta-Analysis
8 affiliations
- 1Department of Biochemistry and Molecular Medicine, College of Medicine, Alfaisal University, Riyadh 11533, Saudi Arabia
- 2Faculty of Medicine, Kuwait University, Jabriya 13110, Kuwait
- 3College of Medicine and Medical Sciences, Arabian Gulf University, Manama 22979, Bahrain
- 4Royal College of Surgeons in Ireland, Busaiteen 228, Bahrain
- 5Kuwait Institute for Medical Specialization, Kuwait City 13018, Kuwait
- 6School of Medicine, The University of Jordan, Amman 11942, Jordan
- 7GB—School of Medicine, Dentistry and Nursing, University of Glasgow, Glasgow G31 2ER, Scotland, UK
- 8Kuwait National Guard, Medical Services Directorate, Kuwait City 12029, Kuwait
Abstract
Background: Instrumented spinal fusion is among the most painful surgical procedures. Methadone, a long-acting μ-opioid receptor agonist with N-methyl-D-aspartate receptor antagonism, may provide more sustained analgesia than shorter-acting intraoperative opioids. Methods: PubMed, Scopus, Web of Science, and the Cochrane Library were searched through August 2026 for randomized trials in adults or adolescents undergoing instrumented spinal fusion that compared intraoperative intravenous methadone with a shorter-acting intraoperative opioid. Random-effects meta-analysis, the Cochrane Risk of Bias 2 tool, GRADE, and published minimal clinically important differences (MCIDs) were used. Results: Five trials (364 participants; three in adults and two in adolescents) were included. Methadone reduced pain intensity at 24 h (MD −1.06, 95% CI −2.03 to −0.09; three trials), 48 h (MD −1.52, 95% CI −2.36 to −0.67), and 72 h (MD −1.04, 95% CI −1.91 to −0.17; two adult trials each); point estimates approximated the 1-point MCID, but confidence intervals included clinically unimportant differences. Opioid consumption was lower at 24 h (SMD −0.50, 95% CI −0.79 to −0.21; four trials; I2 = 0%), corresponding to relative reductions of 17% to 52% in the individual trials, but not at 48 h. Vomiting did not differ (RR 1.10, 95% CI 0.72 to 1.70). Respiratory events were rare, inconsistently defined, and not pooled. Certainty was moderate for 24-h opioid consumption and low or very low for all other outcomes. Conclusions: In adults undergoing instrumented spinal fusion, a single intraoperative dose of intravenous methadone may modestly reduce postoperative pain at 24 h and opioid consumption, but the clinical importance of these effects is uncertain; the evidence in adolescents is limited to two small trials, and adverse events were insufficiently reported. Methadone should be regarded as an optional, monitored component of multimodal analgesia rather than routine practice until larger trials powered for safety and longer-term opioid use are available.
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BibTeX
@article{abuzaid2026intraoperative,
title = {{Intraoperative Intravenous Methadone Versus Non-Methadone Opioid Analgesia in Instrumented Spinal Fusion: A GRADE-Guided Systematic Review and Meta-Analysis}},
author = {Ahmed Abu-Zaid and Reem B. Alhajri and Ghalyah H. Alsuhail and Faisal R. Alabkal and Fatmah Y. Boshehri and Mohammad A. Alshammari and Naser A. Alajmi and Barrak A. Albarrak and Osamah F. Alzufairi and Abdullah F. Alenezi and Yousif T. Alhuwaimel and Abdullah Kh Alabdullah and Abdullah M. Alharran},
journal = {Journal of Clinical Medicine},
year = {2026},
month = oct,
doi = {10.3390/jcm15218470},
url = {https://www.mdpi.com/2077-0383/15/21/8470},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Intraoperative Intravenous Methadone Versus Non-Methadone Opioid Analgesia in Instrumented Spinal Fusion: A GRADE-Guided Systematic Review and Meta-Analysis
AU - Ahmed Abu-Zaid
AU - Reem B. Alhajri
AU - Ghalyah H. Alsuhail
AU - Faisal R. Alabkal
AU - Fatmah Y. Boshehri
AU - Mohammad A. Alshammari
AU - Naser A. Alajmi
AU - Barrak A. Albarrak
AU - Osamah F. Alzufairi
AU - Abdullah F. Alenezi
AU - Yousif T. Alhuwaimel
AU - Abdullah Kh Alabdullah
AU - Abdullah M. Alharran
PY - 2026
DA - 2026/10/30
JO - Journal of Clinical Medicine
DO - 10.3390/jcm15218470
UR - https://www.mdpi.com/2077-0383/15/21/8470
AB - Background: Instrumented spinal fusion is among the most painful surgical procedures. Methadone, a long-acting μ-opioid receptor agonist with N-methyl-D-aspartate receptor antagonism, may provide more sustained analgesia than shorter-acting intraoperative opioids. Methods: PubMed, Scopus, Web of Science, and the Cochrane Library were searched through August 2026 for randomized trials in adults or adolescents undergoing instrumented spinal fusion that compared intraoperative intravenous methadone with a shorter-acting intraoperative opioid. Random-effects meta-analysis, the Cochrane Risk of Bias 2 tool, GRADE, and published minimal clinically important differences (MCIDs) were used. Results: Five trials (364 participants; three in adults and two in adolescents) were included. Methadone reduced pain intensity at 24 h (MD −1.06, 95% CI −2.03 to −0.09; three trials), 48 h (MD −1.52, 95% CI −2.36 to −0.67), and 72 h (MD −1.04, 95% CI −1.91 to −0.17; two adult trials each); point estimates approximated the 1-point MCID, but confidence intervals included clinically unimportant differences. Opioid consumption was lower at 24 h (SMD −0.50, 95% CI −0.79 to −0.21; four trials; I2 = 0%), corresponding to relative reductions of 17% to 52% in the individual trials, but not at 48 h. Vomiting did not differ (RR 1.10, 95% CI 0.72 to 1.70). Respiratory events were rare, inconsistently defined, and not pooled. Certainty was moderate for 24-h opioid consumption and low or very low for all other outcomes. Conclusions: In adults undergoing instrumented spinal fusion, a single intraoperative dose of intravenous methadone may modestly reduce postoperative pain at 24 h and opioid consumption, but the clinical importance of these effects is uncertain; the evidence in adolescents is limited to two small trials, and adverse events were insufficiently reported. Methadone should be regarded as an optional, monitored component of multimodal analgesia rather than routine practice until larger trials powered for safety and longer-term opioid use are available.
SN - 2077-0383
ER -