Adding a moderate dose of esketamine (0.03 mg/kg/h) to patient-controlled intravenous analgesia combined with a preoperative intercostal nerve block significantly reduced acute postoperative pain after thoracoscopic lobectomy, compared to a low dose of esketamine or sufentanil alone. Pain scores on the Numerical Rating Scale were lower at 2, 4, 24, 48, and 72 hours after surgery, and the need for rescue analgesia and opioid consumption decreased. The moderate esketamine group also had less postoperative nausea and vomiting than the sufentanil group. Low-dose esketamine did not improve pain control over sufentanil alone.
Relapse is common in remitted major depressive disorder. Arketamine, an (R)-enantiomer of ketamine, has prophylactic actions in an inflammatory model of depression, but the mechanisms are unclear. In mice, a single injection of arketamine (10 mg/kg) blocked lipopolysaccharide-induced increases in spleen genes of the heme biosynthesis II pathway (Alas2, Fech, Hmbs). Expression of these genes correlated with spleen weight and pro-inflammatory cytokines. Spleens from depressed patients showed higher ALAS2 and FECH expression. Pretreatment with a heme precursor (5-aminolaevulinic acid) worsened inflammation and depression-like behavior, while a heme inhibitor (succinyl acetone) had prophylactic effects. The heme biosynthesis pathway may be a target for preventing relapse.