Efficacy and Safety of Intrathecal Buprenorphine for Postoperative Analgesia in Cesarean Delivery: A Systematic Review of Randomized Controlled Trials

Cesarean delivery is one of the most commonly performed surgical procedures worldwide and is most commonly conducted under neuraxial anesthesia when not contraindicated. Intrathecal morphine remains the most commonly used neuraxial opioid adjunct for cesarean delivery and is widely considered the standard of care due to its prolonged duration of postoperative analgesia. However, neuraxial morphine is associated with dose-dependent adverse effects, including pruritus, nausea, urinary retention, and delayed respiratory depression related to cephalad cerebrospinal fluid migration. Buprenorphine, a semi-synthetic opioid derived from thebaine, functions as a partial μ-opioid receptor agonist with high receptor affinity and slow dissociation kinetics, potentially offering prolonged analgesia with a favorable safety profile. This systematic review evaluates the efficacy and safety of intrathecal buprenorphine for postoperative analgesia in cesarean delivery. The review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA 2020) guidelines. PubMed and the Cochrane Central Register of Controlled Trials (CENTRAL) were searched from inception through February 22, 2026. Randomized controlled trials (RCTs) involving women undergoing cesarean delivery under spinal anesthesia comparing intrathecal buprenorphine with local anesthetic alone or alternative intrathecal regimens were included. Primary outcomes were duration of analgesia and time to first rescue analgesic. Secondary outcomes included pain scores and adverse events. Risk of bias was assessed using the Cochrane Risk of Bias 2 tool. Five randomized controlled trials involving 727 participants met the inclusion criteria. Intrathecal buprenorphine consistently prolonged postoperative analgesia and delayed time to rescue analgesic compared with the control groups. A dose-dependent pattern was observed, supported by both within-trial dose comparisons and consistent trends across studies. Analgesic duration ranged from approximately 173 minutes to 18 hours, with lower doses (≤60 µg) associated with shorter durations and higher doses (≥100 µg) producing more prolonged analgesia. Adverse events were generally mild and included nausea, vomiting, pruritus, and sedation, with higher doses associated with increased frequency of these effects. No clinically significant respiratory depression was reported in any included trial; however, reporting of respiratory monitoring protocols was inconsistent across studies. Intrathecal buprenorphine appears to be an effective and generally safe adjuvant for post-cesarean analgesia. Lower doses may provide a clinically favorable balance between analgesic efficacy and tolerability. However, heterogeneity in dosing strategies, comparator regimens, and outcome definitions, as well as small sample sizes, limits certainty. Larger high-quality randomized trials directly comparing buprenorphine with intrathecal morphine are warranted.