Postoperative pain is prevalent and severe complication in elderly surgical patients. Multiple studies propose that a small dose of esketamine administered intraoperatively can alleviate postoperative pain and curtail opioid usage. We aimed to evaluate the impact of esketamine on postoperative acute pain among elderly patients with gastrointestinal tumors. This is a prospective, parallel-group, randomized controlled trial. Ninety patients aged 60 and above, undergoing resection of gastrointestinal tumors, were randomly assigned to two groups: esketamine group (Group S, a single dose of 0.25 mg/kg and 0.1 mg/kg/h infusion) and control group (Group C, saline). Visual Analogue Scale (VAS) pain scores were the primary outcome. Remifentanil consumption, instances of rescue analgesia, delirium, sleep quality, postoperative recovery quality, serum levels of inflammatory cytokines, and adverse events within 72 h post-surgery were secondary outcomes, respectively. Data of 87 of 99 eligible patients were analyzed. VAS scores at rest in Group S were lower than those in Group C at 6 h [1.2 (0.6, 1.6) vs 1.6 (1.0, 2.0), P = 0.003], 12 h [1.4 (1.0, 2.0) vs 2.0 (1.5, 2.0), P < 0.001], and 24 h [1.8 (1.3, 2.0) vs 2.2 (1.6, 2.6), P < 0.001] postoperatively. At 6 h post-surgery, VAS score during coughing was lower in Group S than Group C [2.0 (2.0, 2.3) vs 2.0 (2.0, 3.0), P = 0.009]. The instances of rescue analgesia were fewer in group S compared to group C (P = 0.007). Furthermore, the esketamine group showed improved sleep quality and QoR-15 score (P < 0.05) postoperatively. Intravenous administration of esketamine as an adjunct to general anesthesia can decrease the intensity of pain for 24 h without additional adverse effects after laparoscopic gastrointestinal tumor surgery.

Background: Several studies have shown that excessive protein degradation is a major cause of skeletal muscle atrophy induced by sepsis, and autophagy is the main pathway participating in protein degradation. However, the role of autophagy in sepsis is still controversial. Previously, we found that neuregulin-1β (NRG-1β) alleviated sepsis-induced diaphragm atrophy through the phosphatidylinositol-3 kinase signaling pathway. Akt/mechanistic target of rapamycin (mTOR) is a classic signaling pathway to regulate autophagy, which maintains intracellular homeostasis. This study aimed to investigate whether NRG-1β could alleviate sepsis-induced skeletal muscle atrophy by regulating autophagy. Methods: L6 rat myoblast cells were differentiated using 2% fetal bovine serum into myotubes, which were divided into four groups: Con group treated with normal serum; Sep group treated with septic serum to form a sepsis cell model; septic serum + NRG-1β (SN) group treated with septic serum for 24 h followed by injection with NRG-1β and incubation for another 48 h; and serum+NRG-1β+LY294002 group, in which the PI3K inhibitor LY294002 was added 30 min before NRG-1β, and other treatments were similar to those in SN group. Effects of NRG-1β were also evaluated in vivo using Sprague–Dawley (SD) rats, in which sepsis was induced by cecal ligation and puncture (CLP). Results: In L6 myotubes treated with septic serum, the expression of autophagy-related proteins UNC-51 like kinase 1, p-Beclin-1, and Beclin-1, and the ratio of LC3B II/I were highly increased, while protein p62 expression was decreased, indicating that autophagy was excessively activated. Moreover, NRG-1 expression was decreased, as detected by confocal immunofluorescence and western blotting. Upon exogenous addition of NRG-1β, autophagy was inhibited by the activation of Akt/mTOR signaling pathway, and cell viability was also increased. These effects disappeared in the presence of LY294002. In SD rats, sepsis was induced by CLP. NRG-1β was shown to inhibit autophagy in these rats via the Akt/mTOR pathway, leading to increased body weight of the septic SD rats and alleviation of atrophy of the tibialis anterior muscle. Conclusion: NRG-1β could alleviate sepsis-induced skeletal muscle atrophy by inhibiting autophagy via the AKT/mTOR signaling pathway.

Objective: This study aimed to evaluate the effects of perioperative intravenous esketamine on the quality of postoperative recovery in adult patients. Methods: The primary outcome was post-anesthesia care unit (PACU) stay time. Secondary outcomes included extubation time, Quality of Recovery-40 (QoR-40) and Quality of Recovery-15 (QoR-15) scores, pain scores at 24 hours postoperatively, incidence of postoperative nausea and vomiting (PONV), postoperative sleep quality, anxiety and depression, and mental side effects. A comprehensive literature search was conducted in PubMed, EMBASE, Web of Science, the Cochrane Library, and China National Knowledge Infrastructure from inception through April 20, 2023, with an update on May 18, 2024. The study was registered on PROSPERO (Registration number: CRD42023399290). Mean differences (MD) or relative risks (RR) with 95% confidence intervals (CI) were used to estimate effect sizes. Meta-analysis was performed using RevMan 5.3 and Stata 16.0 software. Results: Nineteen studies involving 1,967 patients were included. No significant differences were observed between the esketamine and control groups in PACU stay time (MD = 0.99, 95% confidence interval (CI) [−2.31–4.30], P = 0.56) or extubation time (MD = 1.30, 95% CI [−1.10–3.17], P = 0.34). However, the esketamine group showed significantly higher postoperative QoR-40 scores (MD = 9.40, 95% CI [6.12–12.69], P < 0.00001) and QoR-15 scores (MD = 7.43, 95% CI [3.97–10.88], P < 0.0001) compared to the control group. Conclusion: Perioperative intravenous esketamine does not significantly affect PACU stay time, extubation time, or the incidence of postoperative mental side effects. However, it can reduce pain within 24 hours after surgery, improve sleep quality, decrease the incidence of PONV, and enhance postoperative recovery as reflected by higher QoR scores.