Esketamine prevents postoperative sleep disturbance in patients with preoperative sleep disorders: a role for oral microbiota

Patients with preexisting sleep disorders face a significantly increased risk of postoperative sleep disturbance (PSD) due to heightened sensitivity to surgical stress, anesthesia, and hospital-related environmental factors. There is a critical unmet need for effective prophylactic medications to prevent PSD, as current treatment options are limited and often inadequate. This study investigated the prophylactic effect of intraoperative esketamine (0.3 mg/kg/h) on PSD in 130 patients randomized into control and esketamine groups. Preoperative sleep quality was assessed using the Pittsburgh Sleep Quality Index, while postoperative sleep was evaluated using the Numerical Rating Scale (NRS) and Athens Insomnia Scale (AIS) on postoperative days (PODs) 1, 3, and 7. PSD was defined as an NRS or AIS score ≥6. Saliva samples were collected for 16S rRNA sequencing to analyze the oral microbiota. On POD 1, the esketamine group showed a significantly lower incidence of PSD (43.1 vs. 64.6%; OR, 0.414; P = 0.014) and reduced hydromorphone consumption. Preoperative oral microbiota profiles differed between patients with and without PSD, with specific bacterial taxa associated with sleep disturbance. These findings suggest that esketamine may alleviate postoperative sleep disruption, potentially through modulation of the oral microbiota.