Effects of intrathecal opioids on cesarean section: a systematic review and Bayesian network meta-analysis of randomized controlled trials

Purpose: We aimed to compare the beneficial and harmful effects of opioids used as adjuncts to local anesthetics in patients undergoing cesarean section under spinal anesthesia. Methods: We searched electronic databases and ClinicalTrials.gov from their inception until March, 2021 without language restrictions. The primary outcome was the complete analgesia duration (Time to VAS > 0). Data were synthesized using the Bayesian random-effects model. Evidence confidence was evaluated using the Confidence In Network Meta-Analysis. Results: We identified 66 placebo-controlled randomized controlled trials (RCTs) comprising 4400 patients undergoing elective cesarean section. Compared with the placebo, intrathecal opioids (fentanyl, sufentanil, and morphine) significantly prolonged the analgesia duration by 96, 96, and 190 min, respectively (mean difference). Despite morphine ranking first, opioid efficacy was similar; the results were inconsistent with respect to other analgesic outcomes. Except for diamorphine, all opioids were associated with significant increases in the pruritus incidence. Sufentanil and morphine were associated with increases in the respiratory depression incidence. Conclusions: We confirmed that intrathecal opioids benefit postoperative analgesia. Although morphine seems to be the most appropriate agent, some results were inconsistent, and the evidence confidence was often moderate or low, especially for adverse outcomes. Well-designed RCTs with an evidence-based approach are imperative for determining the most appropriate opioid for cesarean sections.