In rats exposed to a combined stress model (single prolonged stress plus plantar shock), those treated with (2R,6R)-hydroxyketamine (HNK) showed reduced depression- and anxiety-like behaviors, including increased exploratory activity. The compound reversed stress-induced disruptions in the PI3K/AKT signaling pathway in the hippocampus and prefrontal cortex, but not in the amygdala. Traumatic stress itself altered PI3K/AKT signaling in all three brain regions. These results suggest that (2R,6R)-HNK may alleviate negative emotional symptoms after trauma by modulating PI3K/AKT signaling, particularly in the hippocampus.
Esketamine as an adjunct to sufentanil may reduce opioid consumption in non-surgical patients receiving mechanical ventilation in the ICU. This ongoing multicenter, single-blind, randomized controlled trial in six ICUs in China will assign 132 patients to either standard care (sufentanil alone) or an esketamine infusion at 0.2 mg/kg/hour plus sufentanil. The primary outcome is mean hourly sufentanil consumption. The trial aims to provide evidence for esketamine's efficacy and safety, addressing a gap in knowledge for this patient population.