A study of low-dose S-ketamine infusion as "preventive" pain treatment for cesarean section with spinal anesthesia: benefits and side effects

BACKGROUND: Attenuation of central sensitization with NMDA-active drugs such as S-Ketamine may play a role in postoperative analgesia and prevention of neuropathic pain. However, during cesarean section with neuraxial block, S-Ketamine might have adverse effects on the interaction between mothers and infants, including breastfeeding. METHODS: Women undergoing elective repeat cesarean section with subarachnoid anesthesia (0.5% hyperbaric bupivacaine 8-10 mg and sufentanil 5 μg) were enrolled in a double-blind, randomized study. Patients in the S-Ketamine group (N.=28) received i.v. midazolam 0.02 mg/kg and S-Ketamine 0.5 mg/kg i.m. bolus 10 minutes after birth followed by a 2 μg/kg/min i.v. continuous infusion for 12 h. The control group (N.=28) received placebo. Paracetamol and patient controlled analgesia with intravenous morphine were given postoperatively. Von Frey filaments were used to assess pain threshold on the inner forearm and T10-T11 dermatomes (supposed hyperalgesic area). RESULTS: S-Ketamine reduced morphine consumption at 4-8, 8-12, and 12-24 hours after surgery (total 31%), even after its effect has ceased, suggesting an anti-hyperalgesic action. Mild side effects were observed in the S-Ketamine group one hour after delivery. All side effects were rated as light and there were no serious adverse events. Pain threshold was not significantly different between groups. S-Ketamine patients showed a trend towards reduced pain sensitivity at the T10 dermatome, which is involved by surgical damage. After three years, patients reported no differences in residual pain, dysesthetic symptoms, or duration of breast-feeding. CONCLUSION: Preventive administration of S-Ketamine via 12-hour infusion was safe and may have anti-hyperalgesic action after cesarean section