Abstract
INTRODUCTION: Intravenous methadone has shown an opioid-sparing effect in high-risk surgeries. It was hypothesized that intrathecal methadone might provide better effects than intravenous administration due to a direct action on the spinal cord.
MAIN OBJECTIVE: To search the currently published literature on the intraoperative use of intrathecal methadone in humans, a systematic review was conducted.
DESIGN: Studies from PubMed, Scopus, OVID, EMBASE, LILACS, Google Scholar, ELSERVIER, REDALYC, SciELO, Europe PubMed Central, and the Cochrane Library were searched from 1980 to June 2024. Search terms included "intrathecal methadone or spinal methadone," "methadone and spinal anesthesia," "spinal anesthesia," "intraoperative period," and "perioperative period." Randomized controlled trials (RCTs) published in English and Spanish involving human participants were considered.
MAIN OUTCOME: The quality of post-operative analgesia measured by the Visual Analog Scale (VAS).
SECONDARY OUTCOMES: Time to first opioid analgesic rescue, post-operative daily needs of morphine equivalents, and side effects.
RESULTS: Forty-one articles were identified. Good agreement intra- and intergroup was found. Four full-text articles met the inclusion criteria. Quality assessment showed an overall low to "some concern" risk of bias. Intrathecal methadone 5-10 mg provided post-operative pain for about 6 hours (VAS average of 2.4/10) after knee and hip replacements, urological, and gynecological surgeries showing minimal side effects. Twenty milligram of intrathecal methadone can produce remarkable side effects. Intrathecal morphine at 0.5-1.0 mg showed significantly lower VAS levels during the 24 hours post-operatively (p < 0.05) but showed more side effects. Intrathecal anesthesia with methadone as adjuvant showed a longer analgesic effect than fentanyl, and better effect than placebo, without differences in side effects (p < 0.05).
CONCLUSIONS: Due to the limited sample size and the small number of selected RCTs showing significant methodological differences, a meta-analysis could not be completed. Therefore, overall statistical significance was not established between the four studies, and there is not enough evidence to give recommendations. Further research is needed to evaluate whether the doses found in this review retain comparable efficacy and safety profiles in a broader range of patient cohorts. In the reviewed literature, no objective or conclusive evidence of neurotoxicity was found from the use of a single dose of perioperative intrathecal methadone.