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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.
- Anesthesia, Spinal
- Analgesics, Opioid
- Acute Pain
- Injections, Spinal
- Meta-Analysis
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Footnotes
X @VinzTripodi
Contributors MO, SS, and VFT contributed substantially to the conception and design of the work; MO, SS and VFT drafted the manuscript; MO, SS, VFT, AB, and GC collected the data; SS and MO performed the analysis with contributions from VFT, AB, and GC. All the authors (MO, VFT, AB, GC, MM, MI, AC, GF, SS) gave substantial contributions to the interpretation of data for the work, revised the manuscript critically for important intellectual content, gave the final approval of the version to be published, and agreed to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. Corresponding author: SS, MD.
Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial, or not-for-profit sectors.
Competing interests None declared.
Provenance and peer review Not commissioned; externally peer-reviewed.
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