Efficacy and safety of intrathecal adjuvants for perioperative management of cesarean delivery: a systematic review and network meta-analysis of randomized controlled trials.
Martina Ollosu, Vincenzo Francesco Tripodi, Alessandro Bonu, Guglielmo Cittadini, Mario Musu, Mariachiara Ippolito, Andrea Cortegiani, Gabriele Finco, Salvatore Sardo
Author Information
Martina Ollosu: Department of Medical Sciences and Public Health, University of Cagliari, Cagliari, Italy. ORCID
Vincenzo Francesco Tripodi: Anesthesia and Intensive Care, Human Pathology Department, "Gaetano Martino" University Hospital, Messina, Italy. ORCID
Alessandro Bonu: Department of Medical Sciences and Public Health, University of Cagliari, Cagliari, Italy.
Guglielmo Cittadini: Department of Medical Sciences and Public Health, University of Cagliari, Cagliari, Italy.
Mario Musu: Department of Medical Sciences and Public Health, University of Cagliari, Cagliari, Italy.
Mariachiara Ippolito: Department of Anesthesia, Analgesia, Intensive Care and Emergency, University Hospital Policlinic Paolo Giaccone, Palermo, Italy.
Andrea Cortegiani: Department of Anesthesia, Analgesia, Intensive Care and Emergency, University Hospital Policlinic Paolo Giaccone, Palermo, Italy.
Gabriele Finco: Department of Medical Sciences and Public Health, University of Cagliari, Cagliari, Italy.
Salvatore Sardo: Department of Medical Sciences and Public Health, University of Cagliari, Cagliari, Italy salvatore.sardo@unica.it. ORCID
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.
