Esketamine likely ineffective as an agent for supplemental analgesia during elective cesarean delivery

1. In women undergoing cesarean delivery under epidural anesthesia, the administration of esketamine produced transient sedation and clinically insignificant analgesia, with no significant effect on neonatal depression.

Evidence Rating Level: 1 (Excellent)

Epidural anesthesia is commonly used during cesarean delivery. However, some patients still experience pain and discomfort during the surgery due to an incomplete block of the splanchnic nerve. Therefore, additional analgesics like opioids and dexmedetomidine are often administered. Given the adverse effects of these analgesics that limit their widespread use, alternative drugs are being explored. Esketamine is an isomer of ketamine that is two times more potent than its counterpart and less likely to cause adverse psychiatric reactions. This double-blinded, placebo-controlled randomized clinical trial aimed to investigate the safety and efficacy of intravenous esketamine before childbirth during cesarean delivery with epidural anesthesia.  The trial assessed the eligibility of parturients from 5 medical centers and enrolled 600 women aged 18 or older who had a full-term single pregnancy. Patients were randomly assigned to receive either 0.25 mg/kg of esketamine, or the control, the same volume of normal saline, administered intravenously 2 minutes before incision. Pain intensity immediately after fetal delivery, as measured by the NRS pain score, was found to be lower in the esketamine group than in the placebo group (P = .001). However, this difference was not clinically meaningful. This is likely because of excellent analgesia in the control group, thereby not allowing for further improvement in analgesia. Patients in the esketamine group had clinically important, deeper levels of sedation compared to the placebo group (P<0.001). While Eskatamine reduced the incidence of hypotension (4.7% compared with 8.7%  in the placebo group, p=0.047), it was associated with neurologic or mental symptoms like somnolence, nystagmus, and vertigo, along with higher incidences of hypertension, tachycardia, and postoperative nausea or vomiting. Finally, despite esketamine easily crossing the placental barrier with an umbilical vein to maternal artery ratio of 0.83 (0.09), the neonatal Apgar score was not affected. Overall, the study found that for women undergoing cesarean delivery with epidural anesthesia, esketamine did not have a meaningful effect on analgesia.

Click to read the study in JAMA Network Open

Image: PD

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