Esketamine alleviates postoperative depression-like behavior through anti-inflammatory actions in mouse prefrontal cortex

Yuan

et al. 2022

Preprint

Purpose We aim to investigate the effect of S-ketamine preconditioning on postoperative depression in patients with CD undergoing bowel resection with mild to moderate depression and to observe whether it can relieve postoperative pain and anti-inflammation. Methods A total of 120 adult patients were randomised in to one of the two groups; Patients in the S-ketamine group received 0.25mg/kg S-ketamine intravenous drip under general anesthesia induction, followed by continuous infusion of S-ketamine with 0.12mg/kg/h for more than 30 minutes through target-controlled infusion. Patients in the placebo group received 0.9% saline. The patients in both groups were evaluated by depression scale, pain scale and inflammatory factors at set intervals during a total period of one month starting from the end of operation. Results There was no significant difference in preoperative age, sex, body mass index (BMI), PHQ-9, and HAMD-17 scores between the two groups (P > 0.05). The scores of PHQ-9 and HAMD-17 in the S-ketamine group were lower than those in the placebo group on the 1st, 3rd, and 7th day postoperatively (P < 0.05). There was no significant difference in PHQ-9 and HAMD-17 scores between the two groups one month postoperatively (P > 0.05). The NRS scores of PACU, 1 day and 2 days postoperatively in the S-ketamine group were lower than those in the placebo group (P < 0.05). There was no significant difference in NRS score between the two groups at 7 days postoperatively (P > 0.05). There was no significant difference in postoperative complications, hospital stay, CRP, and IL-6 levels on the 1st and 3rd day postoperatively between the two groups (P > 0.05). Conclusion In patients with Crohn’s disease undergoing bowel resection with mild to moderate depression, intraoperative infusion of low-dose S-ketamine was effective in relieving depression one week after surgery and reducing postoperative pain two-day.

Section: Discussioncontrasting

confidence: 99%

Intraoperative Low-dose S-ketamine Reduces Depressive Symptoms in Patients with Crohn’s Disease Undergoing Bowel Resection: A Randomized Controlled Trial

Yuan

et al. 2022

Preprint

“…These results are consistent with the trend of previous studies. For example, Wang et al (2022 ) reported that S-ketamine alleviates postoperative depression-like behavior through anti-inflammatory actions. Tu et al (2021) demonstrated that S-ketamine has anti-inflammatory effects, can inhibit the release of inflammatory cells, and can reduce the secretion of interleukin, tumor necrosis factor, and other cytokines by leucocytes, thus alleviating the inflammatory response.…”

Section: Discussionmentioning

confidence: 99%

S-Ketamine attenuates inflammatory effect and modulates the immune response in patients undergoing modified radical mastectomy: A prospective randomized controlled trial

Qian²,

Li³

et al. 2023

Front. Pharmacol.

Objective: This study aimed to investigate the impact of varying dosages of S-ketamine on perioperative immune-inflammatory responses in patients undergoing modified radical mastectomy (MRM).Methods: This is a prospective, randomized, controlled trial. A total of 136 patients with American Society of Anesthesiologists status I/II scheduled for MRM were enrolled and randomly assigned into groups to receive the control (C) or one of three different doses [0.25 (L-Sk), 0.5 (M-Sk), or 0.75 (H-Sk) mg/kg] of S-ketamine. The primary outcomes were the cellular immune function and inflammatory factors before anesthesia and at the end of (T1) and 24 h (T2) after the surgery. Secondary outcomes included the visual analog scale (VAS) score, opioid consumption, rate of remedial analgesia, adverse events, and patient satisfaction.Results: The percentage and absolute counts of CD3+ and CD4+ cells in groups L-Sk, M-Sk, and H-Sk were higher than those of group C at T1 and T2. Moreover, a pairwise comparison revealed that the percentage in group H-Sk was higher than those in the L-Sk and M-Sk groups (p < 0.05). The ratio of CD4+/CD8+ was lower in group C at T1 and T2 than those in groups M-Sk and H-Sk (p < 0.05). There was no significant difference in the percentage and absolute counts of natural killer (NK) cells and B lymphocytes among the four groups. However, compared with group C, the concentrations of white blood cells (WBC), neutrophils (NEUT), hypersensitive C-reactive protein (hs-CRP), the neutrophil-to-lymphocyte ratio (NLR), systemic inflammation response index (SIRI), and systemic immune-inflammation index (SII) at T1 and T2 in three different doses of S-ketamine groups were significantly low, and the lymphocytes were significantly high. The ratio of SIRI and NLR at T2 in group M-Sk was lower than that in group L-Sk (p < 0.05). Additionally, a significant decrease in VAS score, opioid consumption, rates of remedial analgesia, and adverse events was observed in the M-Sk and H-Sk groups.Conclusion: Collectively, our study demonstrates that S-ketamine could reduce opioid consumption, decrease postoperative pain intensity, exert a systemic anti-inflammatory effect, and attenuate immunosuppression in patients undergoing MRM. Moreover, we found that the effects of S-ketamine are related to the dose used, with significant differences observed in 0.5 or 0.75 mg/kg of S-ketamine.Clinical Trial Registration:chictr.org.cn, identifier ChiCTR2200057226.

“…In lipopolysaccharide-induced depression mice models, esketamine conveyed antidepressant effects by inhibiting autophagy via the mTOR- brain-derived neurotrophic factor (BDNF) pathway ( 36 ). For mice subjected to abdominal surgery, esketamine alleviated postoperative depression-like behaviors by inhibiting inflammatory effects in the prefrontal cortex ( 37 ). Preclinical studies showed that R-ketamine has greater potency and longer-lasting antidepressant effects than esketamine in animal models of depression.…”

Section: Discussionmentioning

confidence: 99%

“…For mice subjected to abdominal surgery, esketamine alleviated postoperative depression-like behaviors by inhibiting inflammatory effects in the prefrontal cortex (37). Preclinical studies showed that R-ketamine has greater potency and longer-lasting antidepressant effects than esketamine in animal models of depression.…”

Section: Discussionmentioning

confidence: 99%

Effect of esketamine on postoperative depressive symptoms in patients undergoing thoracoscopic lung cancer surgery: A randomized controlled trial

et al. 2023

BackgroundDepressive symptoms are common among patients with lung cancer. We aimed to assess the effects of esketamine on postoperative depressive symptoms after thoracoscopic lung cancer surgery.MethodsIn this randomized, double-blind, placebo-controlled trial, 156 patients undergoing thoracoscopic lung cancer surgery were randomly allocated in a 1:1 ratio to receive intravenous esketamine (intraoperatively and in patient-controlled analgesia until 48 h postoperatively) or normal saline placebo. The primary outcome was the proportion of patients with depressive symptoms at 1 month postoperatively, assessed using the Beck Depression Inventory-II (BDI-II). Secondary outcomes included depressive symptoms at 48 h postoperatively, hospital discharge and 3 months postoperatively, BDI-II scores, anxious symptoms, Beck Anxiety Inventory scores, Quality of Recovery-15 (QoR-15) scores, and 1- and 3-month mortality.Main resultsA total of 151 patients (75 in the esketamine group and 76 in the normal saline group) completed the 1-month follow-up. The esketamine group had a significantly lower incidence of depressive symptoms at 1 month compared to the normal saline group (1.3% vs. 11.8%; risk difference = −10.5, 95%CI = −19.6% to −0.49%; p = 0.018). After excluding patients without lung cancer diagnosis, the incidence of depressive symptoms was also lower in the esketamine group (1.4% vs. 12.2%; risk difference = −10.8, 95%CI = −20.2% to −0.52%; p = 0.018). The secondary outcomes were similar between groups, except that the esketamine group had higher QoR-15 scores at 1 month postoperatively (median difference = 2; 95%CI = 0 to 5; p = 0.048). The independent risk factors for depressive symptoms were hypertension (odds ratio = 6.75, 95%CI = 1.13 to 40.31; p = 0.036) and preoperative anxious symptoms (odds ratio = 23.83, 95%CI = 3.41 to 166.33; p = 0.001).ConclusionPerioperative administration of esketamine reduced the incidence of depressive symptoms at 1 month after thoracoscopic lung cancer surgery. History of hypertension and preoperative anxious symptoms were independent risk factors for depressive symptoms.Clinical trial registration: Chinese Clinical Trial Registry http://www.chictr.org.cn, Identifier (ChiCTR2100046194).