A relatively large dose of the opioid remifentanil given during surgery triggers increased pain sensitivity after the operation, a phenomenon called secondary hyperalgesia. In a trial of 75 patients undergoing major abdominal surgery, those who received a high intraoperative dose of remifentanil (0.40 µg/kg/min) had greater pain sensitivity around the surgical wound and required more morphine for pain relief than patients who received a low dose (0.05 µg/kg/min). Adding a small dose of the drug ketamine during surgery prevented this heightened pain sensitivity, suggesting that remifentanil-induced hyperalgesia involves an N-methyl-d-aspartate pain-facilitator process. No significant differences were seen in overall pain scores, pressure pain thresholds, breathing tests, cognitive function, or side effects among the groups.
A single low dose of esketamine given after childbirth reduces the risk of a major depressive episode at 42 days postpartum by about three quarters in mothers with prenatal depression. In a randomized trial of 364 mothers with at least mild prenatal depression, 6.7% of those receiving esketamine experienced a major depressive episode compared with 25.4% in the placebo group. Depression scores were also lower in the esketamine group at 7 and 42 days. Neuropsychiatric side effects were more common with esketamine (45.1% vs 22.0%) but were transient and resolved without drug treatment.
A single dose of 0.25 mg/kg esketamine given during breast cancer surgery did not significantly increase the proportion of women who achieved a 50% reduction in depression scores within three days after surgery. Among 104 women with preoperative depressive symptoms, 27% in the esketamine group reached this threshold versus 13% in the placebo group, a difference that was not statistically significant. However, esketamine did produce significantly lower depression scores on postoperative days one through five, with a mean additional decrease of 2.5 points on the Montgomery-Åsberg scale compared to placebo. No significant effects were seen on anxiety, pain, or adverse events.