Volume 8, Issue 3 (9-2026)
Tabari Biomed Stu Res J 2026, 8(3): 1-11 |
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Sobhani S, Hojjati M. Intrathecal Neostigmine for Post-Cesarean Analgesia: Balancing Analgesic Efficacy Against Nausea and Vomiting—A Current Concept Review. Tabari Biomed Stu Res J 2026; 8 (3) :1-11
URL: http://tbsrj.mazums.ac.ir/article-1-3920-en.html
URL: http://tbsrj.mazums.ac.ir/article-1-3920-en.html
1- Department of Anesthesiology, Faculty of Medicine, University of Mazandaran, Sari, Iran
2- Department of Burn Surgery, Faculty of Medicine, University of Mazandaran, Sari, Iran.
2- Department of Burn Surgery, Faculty of Medicine, University of Mazandaran, Sari, Iran.
Abstract:
Cesarean delivery is followed by clinically important acute pain, but analgesic intensity must be balanced against maternal nausea, sedation, delayed mobilization, impaired oral intake, and disruption of early recovery. Intrathecal neostigmine is a reversible acetylcholinesterase inhibitor that increases spinal acetylcholine and augments cholinergic antinociception. Early human and obstetric trials established a reproducible analgesic and opioid-sparing signal. In a post-cesarean dose-ranging trial, 10-100 mcg of intrathecal neostigmine reduced 24-hour morphine consumption and hourly morphine requirement for approximately 10 hours. In another randomized trial, 25 mcg produced analgesia broadly comparable with 100 mcg of intrathecal morphine, but nausea and/or vomiting occurred in 73.7% of patients.
This efficacy-to-tolerability mismatch remains the central limitation. A perioperative/peripartum meta-analysis found approximately fivefold higher odds of nausea/vomiting, whereas an obstetric neuraxial systematic review found nearly ninefold higher odds of nausea after intrathecal neostigmine. More recent comparative evidence, including a 2026 network meta-analysis, confirms that neostigmine-containing combinations can show analgesic activity, but certainty is generally low and does not neutralize the direct emetic signal. Dose reduction, altered baricity, combination strategies, and antiemetic prophylaxis may modify adverse effects, yet no contemporary trial has established a reliably favorable therapeutic window.Meanwhile, the comparator standard has advanced: low-dose intrathecal morphine within scheduled nonopioid multimodal analgesia is effective, extensively studied, and embedded in modern PROSPECT and enhanced-recovery recommendations. Current evidence therefore supports intrathecal neostigmine as a mechanistically informative but investigational adjunct rather than routine post-cesarean therapy.
This efficacy-to-tolerability mismatch remains the central limitation. A perioperative/peripartum meta-analysis found approximately fivefold higher odds of nausea/vomiting, whereas an obstetric neuraxial systematic review found nearly ninefold higher odds of nausea after intrathecal neostigmine. More recent comparative evidence, including a 2026 network meta-analysis, confirms that neostigmine-containing combinations can show analgesic activity, but certainty is generally low and does not neutralize the direct emetic signal. Dose reduction, altered baricity, combination strategies, and antiemetic prophylaxis may modify adverse effects, yet no contemporary trial has established a reliably favorable therapeutic window.Meanwhile, the comparator standard has advanced: low-dose intrathecal morphine within scheduled nonopioid multimodal analgesia is effective, extensively studied, and embedded in modern PROSPECT and enhanced-recovery recommendations. Current evidence therefore supports intrathecal neostigmine as a mechanistically informative but investigational adjunct rather than routine post-cesarean therapy.
Keywords: cesarean delivery, intrathecal neostigmine, postoperative analgesia, nausea and vomiting, neuraxial adjuvants, opioid-sparing analgesia
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