Respiratory Depression after Perioperative Methadone Administration: A Systematic Review and Meta-analysis.
Eduardo Nunez-Rodriguez, Guido Mazzinari, Sarah Lumsden et al.
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In 30 seconds
This systematic review and meta-analysis assessed postoperative respiratory depression after perioperative intravenous methadone versus other opioids in adult and pediatric surgical patients. Twenty-five studies involving 116,815 patients were included; 12 randomized clinical trials, with 845 participants, contributed to the primary analysis. Respiratory depression occurred in 7.7% of methadone-treated patients and 6.6% of controls, with no statistically significant increase associated with methadone (relative risk 1.22, 95% confidence interval, 0.76-1.95). The authors rated the evidence very low certainty and called for prospective studies with rigorous respiratory monitoring.
Key findings
- In the randomized-trial primary analysis, respiratory depression occurred in 7.7% with methadone and 6.6% with other opioids.
- Methadone was not associated with a significant increase in respiratory depression (relative risk 1.22, 95% confidence interval, 0.76-1.95).
- Bayesian, subgroup, and retrospective-study analyses likewise did not indicate greater respiratory-depression risk.
Why it matters
Respiratory depression is a key safety concern that may limit perioperative methadone use. These pooled findings do not show a statistically significant excess risk compared with other opioids, offering useful context for evaluating that concern. However, the very low certainty of the evidence means the results do not establish equivalent safety, particularly where respiratory events may be missed without continuous monitoring.
What to keep in mind
Evidence certainty was very low because of risk of bias and limited continuous respiratory monitoring in most included studies; the evidence was predominantly from retrospective datasets.