Perioperative intravenous ketamine reduces postoperative depression scores and pain scores on the first day after surgery but increases the risk of adverse effects including nausea, vomiting, headache, hallucination, and dizziness. The analysis of 15 randomized controlled trials with 1697 patients receiving ketamine and 1462 controls showed a reduction in depression scores on postoperative days 1, 3, and 7 and over the long term. Pain scores were lower only on the first postoperative day. The authors conclude that ketamine's benefits for postoperative depression and pain must be weighed against its increased adverse effects.
Arketamine, the (R)-enantiomer of ketamine, reduces damage to the myelin sheath and promotes its repair in the brains of mice treated with cuprizone, a chemical that induces demyelination. The beneficial effects occur through a mechanism dependent on transforming growth factor β1 (TGF-β1). Blocking the TGF-β1 receptor with RepSox prevented arketamine's protective effects. Directly administering TGF-β1 intranasally also reduced demyelination and enhanced remyelination in the corpus callosum. These findings suggest that arketamine's effects on myelin repair rely on TGF-β1 signaling, pointing to potential therapeutic targets for demyelinating diseases like multiple sclerosis.
Patients with preexisting sleep disorders are at higher risk for postoperative sleep disturbance (PSD). In a randomized trial of 130 patients, intraoperative esketamine (0.3 mg/kg/h) reduced the incidence of PSD on postoperative day 1 (43.1% vs. 64.6%; odds ratio, 0.414) and lowered hydromorphone use. Preoperative oral microbiota profiles differed between patients who later developed PSD and those who did not, with specific bacterial taxa linked to sleep disturbance. The findings suggest esketamine may help prevent postoperative sleep disruption, possibly by modulating the oral microbiota.
Ketamine produces rapid antidepressant-like effects in mice exposed to forced swimming stress. The stressed mice showed depression-like behavior and reduced GABA levels in the hippocampus. Ketamine increased GABA and decreased glutamate there, and GABA levels correlated with behavior. Ketamine raised levels of certain GABAergic enzymes and transporters and astrocytic proteins, but not those on glutamatergic neurons. It also decreased the GABAAR α1 subunit, boosted GABA synthesis and metabolism, altered astrocyte plasticity, and increased ATP. A GABAAR antagonist or ATP itself had rapid antidepressant-like effects, while a GABAAR agonist blocked ketamine's effects. The findings suggest ketamine works by downregulating GABAAR α1, increasing GABA, and converting GABA to ATP.