Efficacy and safety of intrathecal adjuvants for perioperative management of cesarean delivery: a systematic review and network meta-analysis of randomized controlled trials

Abstract Background Cesarean section (CS) rates have increased globally, necessitating effective anesthesia management. Single-shot spinal anesthesia has limitations due to its duration and the dose-limiting adverse effects of local anesthetics. Objectives To evaluate the effectiveness and safety of intrathecal adjuvants combined with local anesthetics in the perioperative management of CS pain. Design Systematic review with network meta-analysis. Data sources PubMed, Cochrane Library for Clinical Trials, and Embase. Eligibility criteria We included women undergoing CS under single-shot spinal anesthesia with any intrathecal drug or placebo added to a long-acting local anesthetic. We selected single- or double-blind, parallel-group, randomized controlled trials (RCTs) reported in English. We excluded crossover, non-randomized, up-and-down dose-finding studies and clinical trials comparing the same drugs in all study arms. Results We included 166 RCTs with 14 925 patients assigned to 32 interventions. Buprenorphine and diamorphine were the highest-ranked treatments for reducing pain intensity at 24 hours, though not statistically significant. Morphine alone or in combination with meperidine, neostigmine, epinephrine, or nalbuphine significantly increased the duration of effective analgesia and reduced opioid consumption. Dexmedetomidine and morphine significantly prolonged the motor block duration. The safety profile of intrathecal adjuvants was generally adequate. Conclusions While the strength of evidence, overall, was very low to low, our study suggests that while none of the interventions significantly reduced pain intensity at 24 hours, several significantly prolonged effective analgesia and reduced postoperative opioid consumption. Dexmedetomidine and morphine prolonged the duration of motor block. None of the intrathecal adjuvants evaluated significantly increased the occurrence of severe adverse events. Future large-scale RCTs are essential to provide more robust evidence. PROSPERO registration number CRD42024479424.