Supplemental Esketamine During Cesarean Delivery May Raise Sedation Concerns

Esketamine administered prior to incision does not have a meaningful effect on analgesia but raises concern about sedation among women undergoing cesarean delivery under epidural anesthesia. These are the findings of a study published in JAMA Network Open.

Epidural anesthesia is the first-choice anesthetic when labor is converted to cesarean delivery, however, in the case of incomplete splanchnic nerve block, some patients can experience discomfort during delivery.

To explore the anesthetic effect of esketamine in cesarean delivery, researchers conducted a double-blind, placebo-controlled randomized clinical trial (ClinicalTrials.gov Identifier: NCT04548973) between 2021 and 2022 at 5 sites in China. Women (N=600) who were scheduled for an elective cesarean delivery after a full-term pregnancy were randomly assigned to receive either 0.25 mg/kg esketamine (n=300) or saline placebo (n=300) administered intravenously after epidural anesthesia, approximately 2 minutes prior to incision. The primary outcomes were maternal pain intensity assessed using the 11-point numeric rating scale (NRS) and sedation score assessed using the Ramsay Sedation Scale (RSS).

The intervention and control cohorts comprised parturients mean age, 30.4 (SD, 4.2) and 30.9 (SD, 4.3) years; they had a median of 2 (IQR, 1-3) and 2 (IQR, 1-2) gravidities; and they were delivering at an average of 38.7 (SD, 1.2) and 38.8 (SD, 1.2) weeks, respectively.

Immediately after fetal delivery, women who received esketamine had significantly lower NRS scores (median, 0 vs 0; P =.001) and higher RSS scores (median, 4 vs 2; P <.001) compared with control individuals, respectively.

In an exploratory analysis, fewer women who received esketamine had an NRS score greater than 2 (6.0% vs 10.7%; P =.04), and more had an RSS of 4 or greater (71.7% vs 0%; P <.001) immediately after fetal delivery compared with control individuals, respectively.

No significant group differences in secondary outcomes of neonatal Apgar score at 1 (median difference [MD], 0; P =.98) and 5 (MD, 0; P =.27) minutes, umbilical vein pH (MD, 0; P .58), and length of hospital stay (mean difference, 0.0 days; P =.76) were observed.

The esketamine intervention was associated with significantly more neurologic or mental symptoms (97.7% vs 4.7%; P <.001), nausea or vomiting (23.0% vs 11.0%; P <.001), tachycardia (27.0% vs 16.7%; P =.002), and hypertension (7.7% vs 1.3%; P <.001) compared with control, respectively.

The limitations of this study included the sufficient pain control from the epidural block and the fact that only 1 dose level of esketamine was evaluated.

The researchers concluded, “The results of this randomized clinical trial showed that, for women undergoing cesarean delivery with epidural anesthesia, a subanesthetic dose of esketamine administered before incision did not have much effect on analgesia but raised concern about sedation and mental adverse effects. The administered esketamine easily passed through the placental barrier but did not induce significant neonatal depression.”