Analgesia materna e segurança neonatal com fentanil ou sufentanil intratecal em cesariana: Revisão sistemática e metanálise de ensaios randomizados

Abstract

Introduction: The intrathecal administration of fentanyl or sufentanil as adjuvants to spinal anesthesia has been widely reported in the literature and at scientific meetings worldwide. However, these drugs do not have explicit approval from the U.S. Food and Drug Administration (FDA) or the Brazilian National Health Surveillance Agency (ANVISA) for the intrathecal route, due to concerns related to labeled indications for safety and efficacy. In the setting of cesarean delivery, balancing maternal analgesia and neonatal safety justifies an updated synthesis of the available evidence. Therefore, this study aimed to determine whether, among women undergoing cesarean delivery under spinal anesthesia, intrathecal fentanyl or sufentanil provides effective maternal analgesia while maintaining neonatal and maternal safety. Methods: MEDLINE (via PubMed), EMBASE, CENTRAL (Cochrane Library), ClinicalTrials.gov, grey literature, and manual searches were systematically searched from inception to November 6, 2025. Randomized controlled trials with no restrictions on language, publication date, or publication status were included if they compared spinal local anesthetics (LA) alone versus LA combined with a lipophilic intrathecal opioid (fentanyl or sufentanil), or direct head-to-head comparisons of fentanyl versus sufentanil, specifically in cesarean deliveries. Outcomes included maternal analgesic efficacy and perioperative adverse events, as well as neonatal safety metrics (such as Apgar scores or umbilical cord pH). Data were pooled using random-effects or fixed-effect models according to the degree of statistical heterogeneity. Results: Thirty-six randomized controlled trials were included, comprising a total of 1,492 patients (823 in the control group and 669 in the intrathecal opioid group). The intrathecal addition of fentanyl or sufentanil to local anesthetics was associated with a significant reduction in the need for postoperative rescue analgesia (RR 0.23; 95% CI 0.16–0.35), as well as a lower incidence of postoperative nausea and vomiting (RR 0.25; 95% CI 0.13–0.50). A significantly increased incidence of pruritus was observed in groups receiving intrathecal opioids (RR 4.94; 95% CI 2.61–9.34), with no relevant differences between fentanyl and sufentanil. No statistically significant differences were found between groups regarding respiratory depression, shivering, or other serious maternal adverse events. Conclusion: The intrathecal addition of fentanyl or sufentanil to spinal anesthesia for cesarean delivery improves maternal analgesic efficacy and reduces the incidence of postoperative nausea and vomiting, without negatively affecting maternal or neonatal safety. The increased incidence of pruritus represents the main associated adverse effect. These findings support the use of these lipophilic opioids as safe and effective adjuvants to spinal anesthesia for cesarean delivery when used at appropriate doses and with adequate monitoring.