Postinduction hypotension (PIH) increases the risk of perioperative adverse events. This study aimed to test if low-dose esketamine could significantly decrease the incidence of PIH in elderly patients undergoing elective noncardiac surgery. This was a post hoc analysis of a randomized clinical trial in university-affiliated academic tertiary hospital. Patients (65 to 85 years, ASA physical status classification II or III) randomly received esketamine (0.2 mg/kg) or normal saline intravenous injection before general anesthesia induction. The primary outcome was the incidence of PIH. The secondary outcomes were the profiles of induction and adverse events during postinduction period. Several different definitions of hypotension and postinduction period were prespecified as the sensitivity analysis. The baseline characteristics were comparable between esketamine group (n = 211) and normal saline group (n = 213). The incidence of PIH was significantly lower in esketamine group than that in normal saline group (44.1 vs. 64.8%, P < 0.01). Esketamine pretreatment significantly decreased the consumption of propofol (P < 0.01) and the rate of vasoconstrictor utilization (P = 0.02). There were no significant differences in the incidence of postinduction adverse events between two groups (all P > 0.05). And, no other severe adverse events were observed. The sensitivity analysis displayed the robustness of the conclusion, though the effect size was lower than 0.2 under certain definition of PIH. A low dose of esketamine treatment before general anesthesia induction for elderly patients undergoing noncardiac surgery could significantly reduce the risk of PIH.Trial registration: www.chictr.org.cn (ChiCTR2100051179); registered 15 September 2021. Date of enrolment of the first participant to the trial: 24 February 2022.

This study investigates the effects of subclinical doses of esketamine on serum NLRP3 levels and early cognitive dysfunction in elderly ischemic stroke patients after neurointerventional procedures under general anesthesia.

A prospective cohort study included 120 elderly ischemic stroke patients undergoing general anesthesia from January 2022 to September 2023. The esketamine group received 0.25 mg/kg of esketamine. Serum levels of NLRP3, C-reactive protein, interleukin-6 (IL-6), IL-1β, and IL-17 were measured before surgery and 24 h postoperatively. Cognitive dysfunction was assessed using the Mini-Mental State Examination (MMSE).

At 24 h postoperatively, the esketamine group had significantly higher MMSE scores (p < 0.05) and lower serum levels of NLRP3, IL-17, and IL-6. Pearson's correlation showed a link between NLRP3 levels and cognitive outcomes. Logistic regression identified heart rate, mean arterial pressure, preoperative NLRP3, IL-6, IL-17, and esketamine treatment as risk factors for cognitive dysfunction.

Subclinical doses of esketamine might reduce postoperative cognitive dysfunction risk and offer neuroprotection, presenting potential therapeutic options for elderly ischemic stroke patients.

The effect of esketamine on perioperative neurocognitive dysfunction (PND) remains controversial. This systematic review and meta-analysis aimed to evaluate the impact of perioperative esketamine administration on PND.

Systematic review and meta-analysis.

PubMed, EMBASE, Web of Science and Cochrane Library were searched from their inception to 25 April 2024.

We included the randomised controlled trials (RCTs) that compared single or continuous intravenous infusion of esketamine to saline among adult surgical patients without pre-existing neurocognitive disorders.

Two reviewers independently extracted pertinent information from the included studies. Risk of bias was assessed using Cochrane's risk of bias criteria. Risk ratios (RRs) and their corresponding 95% CIs were synthesised using a random-effects model. The overall evidence quality was appraised using the Grading of Recommendations Assessment, Development and Evaluation framework.

10 RCTs were included in our meta-analysis, involving 854 surgical patients. Perioperative esketamine was associated with a reduced risk of postoperative delirium (POD) (relative risk (RR): 0.46, 95% CI: 0.30 to 0.71, p<0.001) and delayed neurocognitive recovery (dNCR) (RR: 0.41, 95% CI: 0.21 to 0.78, p<0.001). However, no statistically significant difference was found in the risk of postoperative neurocognitive disorder (post-NCD) at 3 months postsurgery between the esketamine and control groups (RR: 0.57, 95% CI: 0.19 to 1.73, p=0.40). Additionally, pain severity was reduced on postoperative day 1, with no difference in the risk of adverse events or length of hospital stay.

Perioperative esketamine reduces the risk of short-term PND, including POD and dNCR, without significantly affecting the incidence of adverse events or length of hospital stay. However, no significant differences were observed in the risk of post-NCD at 3 months following surgery. This systematic review and meta-analysis offers valuable data for PND research and clinical drug intervention strategies.

CRD42024538438.

Postoperative delirium (POD) is a frequent complication in elderly patients undergoing major surgery. Research has shown that neuroinflammation, postoperative pain and autonomic nervous system dysfunction play significant roles in its onset. Vagus nerve stimulation (VNS) has the potential to reduce inflammation, ease postoperative pain and aid in recovery by enhancing acetylcholine release and activating the cholinergic anti-inflammatory pathway. This study aims to assess the effectiveness and safety of transauricular VNS (ta-VNS) in preventing POD in elderly patients undergoing major surgery.

This multicentre, participant-blinded and assessor-blinded, randomised, parallel-group controlled trial will compare the incidence of POD in elderly patients undergoing major surgery who receive ta-VNS versus sham stimulation. A total of 300 eligible patients will be randomly assigned in a 1:1 ratio to either the active or sham stimulation group. The active stimulation group will receive electrical stimulation to the left cymba conchae at a frequency of 30 Hz and a pulse width of 250 µs, with a 30 s on/30 s off cycle. The intensity will start at 0.4V and be increased in 0.4V increments until a tingling sensation is felt, then adjusted to the highest tolerable level without pain. After obtaining informed consent and randomisation, the initial intervention will begin in the preoperative area and continue throughout the surgery. For the four postoperative days, the intervention will be administered twice daily in 2-hour sessions each morning and afternoon. The sham group will follow the same procedure, with electrodes placed on the left cymba conchae. After adjusting the stimulation intensity, the device will be switched off. The primary outcome is the incidence of POD from postoperative day 0 to day 7 or discharge. Secondary outcomes include the severity of POD, quality of recovery, sleep quality and adverse events.

The protocol was approved by Sir Run Run Shaw Hospital Affiliated to Zhejiang University School of Medicine on 9 January 2024 (Approval number: 20240014), and the trial was registered on the Chinese Clinical Trial Registry on 21 February 2024, prior to recruitment. The study will be performed according to the guidelines of the Declaration of Helsinki. Written informed consent will be obtained from all participants. The results will be submitted for publication in a refereed journal.

ChiCTR2400081078.

Perioperative neurocognitive disorders (POND) are common in older adults and are associated with adverse outcomes. This meta-analysis aimed to evaluate the efficacy and safety of esketamine for the prophylaxis of POND.

Electronic databases were comprehensively searched from inception to April 1, 2024, to identify randomized controlled trials (RCTs) exploring the impact of perioperative esketamine on POND in adult patients. The primary outcomes were the incidence of POND and the level of postoperative cognitive function. The secondary outcomes included recovery characteristics (i.e., respiratory depression, extubation time, agitation, hallucinations, and nightmares) and inflammatory markers. Subgroup and meta-regression analyses were conducted to investigate the heterogeneity and effect of esketamine dosage.

A total of 24 RCTs (n = 2,130 patients), all conducted in China with relatively short follow-up periods (≤ 3 months), were included. Esketamine was found to significantly reduce the risk of POND (risk ratio:0.53, 95%confidence interval [CI]: 0.43-0.67) and improved cognitive function on postoperative day 1 (standardized mean difference [SMD]:1.22, 95%CI:0.85-1.59) and day 3 (SMD:0.94, 95%CI: 0.46-1.43) compared with controls, without impacting recovery characteristics. Furthermore, esketamine was associated with lower pain scores, reduced risk of postoperative nausea/vomiting, and decreased levels of inflammatory markers (IL-6, TNF-α, and S100β). Subgroup and meta-regression analyses revealed that age, quality of studies, type of esketamine administration, and esketamine dosage did not have a significant impact on cognitive outcomes. The evidence showed moderate certainty for POND risk, low certainty for POD 1 cognitive function and several complications (agitation, hallucinations, PONV, respiratory issues, nightmares) and biomarkers (TNF-α, s100β), and very low certainty for POD 3 cognition, extubation time, pain, and IL-6 levels.

Perioperative esketamine is potentially effective in reducing the risk of POND and improving cognitive function in adult patients, regardless of age and dosage. Nevertheless, the certainty of evidence was low to very low for several outcomes (e.g., cognitive function on POD 3). Given that all included studies were conducted in China with relatively short follow-up periods, further high-quality RCTs with diverse populations and longer follow-up are warranted to validate these findings.

Esketamine ameliorates propofol-induced brain damage and cognitive impairment in mice. However, the precise role and underlying mechanism of esketamine in perioperative neurocognitive disorders (PND) remain unclear. Therefore, this study aimed to investigate the key genes associated with the role of esketamine in PND through animal modeling and transcriptome sequencing.

The present study established a mice model of PND and administered esketamine intervention to the model, and mice were divided into control, surgical group, and surgical group with esketamine. Behavioral assessments were conducted using the Morris water maze and Y maze paradigms, while transcriptome sequencing was performed on hippocampal samples obtained from 3 groups. Differential expression analysis and weighted gene co-expression network analysis (WGCNA) were performed on sequencing data to identify candidate genes related to esketamine treating PND. Thereafter, protein-protein interaction (PPI) network analysis was implemented to select key genes. The genes obtained from each step were subjected to enrichment analysis, and a regulatory network for key genes was constructed.

The Morris water maze and Y maze findings demonstrated the successful construction of our PND model, and indicated that esketamine exhibits a certain therapeutic efficacy for PND. Ank1, Cbln4, L1cam, Gap43, and Shh were designated as key genes for subsequent analysis. The 5 key genes were significantly enriched in cholesterol biosynthesis, nonsense mediated decay (NMD), formation of a pool of free 40s subunits, major pathway of rRNA processing in the nucleolus and cytosol, among others. Notably, the miRNAs, mmu-mir-155-5p and mmu-mir-1a-3p, functionally co-regulated the expression of Ank1, Gap43, and L1cam.

We uncovered the therapeutic efficacy of esketamine in treating PND and identified 5 key genes (Ank1, Cbln4, L1cam, Gap43, and Shh) that contribute to its therapeutic effects, providing a valuable reference for further mechanistic studies on esketamine's treatment of PND.

Emergence delirium(ED) is a common postoperative complication in children undergoing tonsillectomy and adenoidectomy under general anesthesia. There is no high-quality evidence on the relationship between esketamine and ED. The systematic review and meta-analysis was performed to investigate the effect of perioperative esketamine use on ED in children undergoing tonsillectomy and adenoidectomy.

We searched Embase, The Cochrane Library, PubMed, MEDLINE, Web of Science, China National Knowledge Infrastructure (CNKI), WanFang, VIP, and SinoMed from inception to 1 September, 2024. Two evaluators identified randomized controlled trials comparing perioperative use of esketamine with placebo or other drugs in children undergoing tonsillectomy and adenoidectomy. Incidence of ED was the primary outcome of the study. Data synthesis was performed by using Review Manager 5.4 software.

Twenty-three relevant studies involving a total of 1,996 children were identified. Perioperative use of esketamine reduced the incidence of ED in children undergoing tonsillectomy and adenoidectomy (RR = 0.33, 95% CI: [0.25, 0.44], p < 0.00001, I 2 = 0%). Scores of ED were lower in the esketamine group than in the control group (SMD = -1.20, 95% CI: [-1.56,-0.84], p < 0.00001, I 2 = 88%). Children in the esketamine group have lower postoperative pain scores (SMD = -0.51, 95% CI: [-0.80,-0.39], p < 0.00001, I 2 = 74%). Esketamine was also associated with a lower incidence of adverse events (RR = 0.75, 95% CI: [0.57, 0.99], p = 0.04, I 2 = 62%). We also found that the use of esketamine reduced the length of stay in the post-anesthetic care unit (PACU) but had no effect on the time to extubation.

Perioperative use of esketamine could significantly reduce the incidence of ED in children undergoing tonsillectomy and adenoidectomy. However, the optimal dose and timing of esketamine administration for preventing ED remains to be explored.

https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=558560, PROSPERO: CRD42024558560.

While esketamine shows promise as an adjunct in procedural sedation, its impact on postoperative cognitive recovery remains incompletely characterized. This study investigated the effects of esketamine on multiple dimensions of recovery, particularly cognition, in patients undergoing colonoscopy with propofol-based sedation.

We conducted this randomized, double-blinded, placebo-controlled trial from January 6, 2023, to May 20, 2024, at two hospitals in China. Patients were randomized in a 1:1 ratio to receive either esketamine 0.2 mg/kg (n = 126) or placebo (n = 126), followed by propofol 1 mg/kg. We administered additional propofol boluses (0.5 mg/kg) to maintain sedation. The study assessed cognitive recovery on postoperative day 3 as the primary outcome, measured by the Postoperative Quality of Recovery Scale (PostopQRS). Secondary outcomes included overall recovery, recovery in other PostopQRS domains, time to discharge, and adverse events.

Esketamine significantly enhanced cognitive recovery compared to placebo on postoperative day 3 (95.2% vs 83.3%, relative risk = 1.14; 95% confidence interval: 1.05-1.25, P = 0.002). Discharge times were comparable between groups (odds ratio = 0.70; 95% confidence interval: 0.43-1.16, P = 0.163). The esketamine group demonstrated higher satisfaction (P = 0.003) and significantly reduced incidences of hypotension (14.3% vs 36.5%, P < 0.001), bradycardia (5.6% vs 15.1%, P = 0.013), hypoxemia (2.4% vs 8.7%, P = 0.028), and injection site pain (21.4% vs 48.4%, P < 0.001).

Adding esketamine 0.2 mg/kg to propofol for colonoscopy sedation improved postoperative cognitive recovery, enhanced patient satisfaction, and reduced cardiopulmonary adverse events without prolonging discharge time. These findings establish low-dose esketamine as a beneficial adjunct to propofol in procedural sedation for colonoscopy.

To explore the effects of subanesthetic dose of esketamine on serum inflammatory factor levels and depressive mood in elderly patients with sarcopenia postoperatively.

This study retrospectively included 102 elderly patients who underwent elective total knee arthroplasty from April 2023 to June 2024 with skeletal muscle mass index (SMI) meeting the diagnostic criteria for sarcopenia (male SMI < 42.6 cm2/m2, female SMI < 30.6 cm2/m2). They were divided into two groups according to whether esketamine was used: esketamine group (ESK group, n = 51) and control group (CON group, n = 51). The Hamilton Depression Scale (HAMD) scores of the patients in the two groups were completed on preoperative day 1, postoperative day 1 and day 7, and serum ceramide (Cer), NOD-like receptor thermoprotein structural domain-related protein 3 (NLRP3) and interleukin-6 (IL-6) were detected. The length of hospital stay, time to first ambulation and pain VAS scores of 4 h, 8 h and 24 h after surgery were recorded. The incidence of adverse reactions was recorded in the postoperative period of 48 h.

There were no significant differences in HAMD scores, Cer, NLRP3 and IL-6 levels between the two groups preoperatively (P > 0.05). Compared with CON group, HAMD score, Cer, NLRP3 and IL-6 levels, and pain VAS scores (postoperative 4 h and 8 h) were significantly decreased in ESK group at postoperative day 1 and day 7 (P < 0.05). In addition, the number of postoperative remedial analgesia and length of hospital stay in the ESK group were significantly shorter than those in the CON group (P < 0.05). HAMD scores and levels of Cer, IL-6 and NLRP3 were higher at postoperative day 1 and day 7 than those preoperatively in both two groups (P < 0.05), and there was no statistically significant difference in the incidence of adverse reactions at postoperative 48 h between the two groups.

The subanesthetic dose of esketamine can effectively reduce the serum Cer, NLRP3 and IL-6 levels after knee arthroplasty in elderly patients with sarcopenia, and may improve the patients' depression in the early postoperative period.

Owing to the particularities of their physical characteristics, older patients undergoing surgery under general anesthesia experience great surgical traumas. Thus, exploring more refined and individualized nursing approaches is an urgent need to mitigate the negative effects of surgery on such patients.

To analyze the influence of preoperative comprehensive education on anxiety, depression, pain, and sleep in older patients who underwent surgery under general anesthesia.

In total, 163 older adults who underwent surgery under general anesthesia between June 2022 and November 2023 were selected, 77 of them received routine nursing care (control group), and 86 received preoperative comprehensive education (research group). Subsequently, comparative analyses were performed from the following perspectives: Surgical indicators (operation time, time to complete regain of consciousness, and temperature immediately after the procedure and upon recovery from anesthesia) before and after nursing care; negative emotions [self-rating anxiety scale (SAS)/self-rating depression scale (SDS)]; pain severity [visual analog scale (VAS)]; sleep quality [Pittsburgh sleep quality index (PSQI)]; incidence of sleep disturbances (difficulties in falling asleep for the first time, falling asleep again after waking up frequently at night, falling asleep again after waking up early, and falling asleep all night); and incidence of adverse events (airway obstruction, catheter detachment, aspiration, and asphyxia).

The research group had significantly lower operation time and time to complete regain of consciousness than the control group after nursing care and markedly better recovery of postoperative body temperature and body temperature at awakening. In addition, more notable decreases in SAS, SDS, VAS, and PSQI scores were observed in the research group than in the control group. Furthermore, the incidence rate of sleep disturbance (8.14% vs 29.87%) and adverse events (4.65% vs 19.48%) were lower in the research group than in the control group.

Preoperative comprehensive education in older patients who underwent surgery under general anesthesia can improve postoperative indicators, effectively reduce the occurrence of anxiety and depression, alleviate postoperative pain, and improve sleep quality.

Prior meta-analyses have established the potential of intravenous ketamine in safeguarding against neurocognitive impairment, but the efficacy of intravenous esketamine for the prevention of perioperative neurocognitive disorders (PND) remains uncertain. The primary aim of this meta-analysis was to conduct a comprehensive evaluation of the effects of esketamine on PND in adult surgical patients undergoing general anesthesia.

We searched several electronic databases and clinical trial registries to find relevant trials. Randomized controlled trials of perioperative use of esketamine adjuvant were included in the analysis. The main outcome measured was the risk of postoperative delirium(POD) and postoperative cognitive dysfunction (POCD). Secondary outcomes included the assessment of postoperative cognitive status, pain scores (VAS/NRS), remifentanil consumption and the occurrence of postoperative nausea and vomiting (PONV).

Thirteen studies encompassing procedures such as abdominal, thoracoscopic lung, gastrointestinal, laparoscopic gynecological, spinal surgery, and modified radical mastectomy, were included in the analysis. A cohort comprising 1068 adult patients underwent general anesthesia, with 584 patients assigned to the esketamine group and 484 patients designated to the placebo group. The administration of general anesthesia was augmented by intravenous infusion of esketamine, and a comparative analysis was conducted in relation to alternative pharmacological interventions or a placebo. The application of esketamine during the perioperative period was observed to decrease the risk of POD ( RR 0.46; 95% CI: 0.32, 0.66, p < 0.0001, GRADE = High) and exhibited a protective influence on POCD (RR = 0.50; 95%CI: 0.30, 0.84, p = 0.009, I2 = 0%, GRADE = Moderate). Significant improvements were observed at 4, 24 and 48 h post-surgery when comparing esketamine to a placebo (4 h: SMD -0.78, 95% CI: -1.24, -0.32, p = 0.0009, I2 = 58%, GRADE = Low; 24 h: SMD -0.92, 95% CI: -1.40, -0.44, p = 0.0002, I2 = 86%, GRADE = Low; 48 h: SMD -0.9, 95% CI: -1.68, -0.12, p = 0.02, I2 = 89%, GRADE = Low), and intraoperative remifentanil consumption was significantly reduced in the esketamine group (SMD -0.56; 95%CI: - 0.86, - 0.27, p = 0.0002, I2 = 62%, GRADE = moderate). A notable reduction in the risk of PONV was observed in the esketamine group(RR = 0.64; 95%CI: 0.49, 0.84, p = 0.001, I2 = 0%, GRADE = High).

The use of intravenous esketamine as an adjuvant in general anesthesia may represent a potentially beneficial strategy for reducing susceptibility to PND, with potential benefits for preventing POD and POCD. Furthermore, it can decrease intraoperative opioid consumption and alleviate postoperative pain intensity without increasing the incidence of PONV.

This meta-analysis was registered on PROSPERO (CRD42023453714).

Alveolar epithelial cell (AEC) ferroptosis contributes to the progression of acute lung injury (ALI). Esketamine (ESK) is a new clinical sedative, anesthetic, and analgesic drug that has attracted substantial attention in mental health research because of its antidepressant effects. However, the effects of ESK on ferroptosis-mediated ALI remain unclear.

This study aimed to explore the protective effect of ESK on AEC ferroptosis in ALI and its potential molecular mechanism in vivo and in vitro.

The antiferroptotic and anti-inflammatory effects of ESK were assessed in a mouse model of lipopolysaccharide (LPS)-induced ALI. In vitro, the epithelial cell lines MLE-12 and A549 were used to examine the underlying mechanism by which ESK regulates inflammation and ferroptosis.

ESK protected mice against LPS-induced ALI, significantly attenuated pathological changes in the lungs and decreased inflammation and ferroptosis. In vitro, ESK inhibited LPS-induced inflammation and ferroptosis in MLE-12 and A549 cells. Moreover, ferroptosis mediated inflammation in LPS-induced ALI in vivo and in vitro, and ESK decreased the LPS-induced inflammatory response by suppressing ferroptosis. ESK promoted the HIF-1α/HO-1 pathway in LPS-treated AECs and in the lung tissues of mice with LPS-induced ALI. Moreover, pretreatment with ESK and the HIF-1α stabilizer dimethyloxaloylglycine (DMOG) substantially attenuated lung injury and prevented changes in ferroptosis-related biochemical indicators, including glutathione (GSH) depletion, malondialdehyde (MDA) production and glutathione peroxidase 4 (GPX4) downregulation, in untreated LPS-induced mice but not in LPS-induced mice treated with the HO-1 inhibitor zinc protoporphyrin (ZNPP). Similar effects were observed in vitro in HO-1 siRNA-transfected A549 cells after LPS incubation but not in control siRNA-transfected cells.

ESK can inhibit ferroptosis-mediated lipid peroxidation by increasing the expression of HIF-1α/HO-1 pathway, highlighting the potential of ESK to treat LPS-induced ALI.

Postoperative delirium is a common neurological complication, especially in older patients undergoing surgery, which is closely related to the poor prognosis of patients. The objective was to investigate the effects of esketamine on postoperative delirium in patients with general anesthesia.

The databases of PubMed, Embase, Cochrane Library and the Chinese National Knowledge Infrastructure were searched for all available randomised controlled trials on the effects of esketamine induction on postoperative delirium in patients undergoing elective general anesthesia from inception until April 21, 2024. We used RevMan5.4 software for data analysis. Dichotomous data was analyzed by risk ratios(RR) with a 95% confidence interval(CI), and continuous data by mean differences(MD). We also evaluated the risk of literature bias using the Cochrane Bias Risk Assessment tool.

We included a total of 17 randomized controlled trials, including 1286 patients undergoing elective general anesthesia. In 17 studies, esketamine significantly reduced the incidence of postoperative delirium (RR: 0.43; 95%CI: 0.33 ~ 0.57; p < 0.001). Five studies examined the incidence of postoperative adverse events (nausea, vomiting, dizziness and resporatory depression) and showed no statistically significant difference between the esketamine group and the control group (normal saline or dexmedetomidine) (RR: 0.82; 95%CI: 0.65 ~ 1.03; p = 0.08). In addition, this study found that the esketamine group had a lower incidence of hypotension (RR: 0.24; 95%CI: 0.12 ~ 0.48; p < 0.001) and a lower score on the visual analogue scale 24 h after surgery (MD: -0.44; 95%CI: -0.54 ~ -0.33; p < 0.001).

According to our meta-analysis, the use of esketamine during anesthesia induction significantly reduced the incidence of postoperative delirium in patients undergoing elective general anesthesia without increasing the incidence of postoperative adverse reactions.

Postoperative cognitive dysfunction (POCD) is a common complication after surgery in elderly patients, and its prevalence can be up to 25.6% at one week after noncardiac surgery. This study mainly evaluates the combined effects of esketamine and dexmedetomidine on the incidence of POCD in elderly patients undergoing lumbar spine surgery and explores the underlying mechanisms.

A total of 162 elderly patients undergoing lumbar spine surgery were randomized into three groups: esketamine combined with dexmedetomidine group (ED group), esketamine group (E group), and dexmedetomidine group (D group). Primary outcome measures included the incidence of POCD on the first postoperative day. Secondary outcomes included the incidence of POCD on the third postoperative day, first postoperative day serum levels of neuron-specific enolase (NSE) and calcium-binding protein β (S100β), patient visual analog scale (VAS) scores at 2, 24, and 48 hours postoperatively, and the incidence of adverse events.

The incidence of POCD on the first postoperative day was significantly lower in the ED group compared to the E group (P = 0.017), with no significant differences when compared to the D group (P = 0.064). The levels of serum NSE in patients in the ED group on the first postoperative day were significantly lower than those in E group and D group (ED group vs E group, P = 0.028; ED group vs D group, P = 0.048). The results for the S100β were similar to those for the NSE (ED group vs E group, P = 0.005; ED group vs D group, P = 0.011).

The combination of esketamine and dexmedetomidine effectively reduces the incidence of POCD on the first postoperative day in elderly patients undergoing lumbar spine surgery.

We explored whether esketamine anesthesia during hysteroscopic surgery can reduce intraoperative hemodynamic fluctuations and improve patient benefit.

A total of 170 patients undergoing hysteroscopic surgery were enrolled, and 151 patients were finally included in the analysis, among which 19 used vasoactive drugs during surgery. Patients were randomly assigned to either the esketamine anesthesia group (E group) or the sufentanil anesthesia group (S group). The primary outcomes were blood pressure and heart rate during the surgery. Secondary outcomes included resistance to laryngeal mask insertion, demand for propofol and remifentanil, nausea and vomiting, Richmond Agitation and Sedation Scale (RASS), dizziness and pain intensity after resuscitation, vasoactive medication treatment, hospitalization time and expenses.

E group had a more stable heart rate, systolic blood pressure, diastolic blood pressure and mean blood pressure than the S group (p < 0.001). Patients in E group had a higher demand for propofol (p < 0.001) but better RASS scores (p < 0.001) after resuscitation. The incidence of intraoperative vasoactive medication use was higher in the S group (18.4% vs. 6.7%, p = 0.029). There were no statistically significant differences in terms of resistance to laryngeal mask insertion, remifentanil demand, time required for resuscitation, postoperative pain, dizziness, nausea or vomiting.

Compared with sufentanil, esketamine-induced anesthesia during hysteroscopic surgery can reduce intraoperative hemodynamic fluctuations and the incidence of intraoperative vasoactive medication. Although esketamine-induced anesthesia may increase the demand for propofol during surgery, it does not affect the anesthesia recovery time and the quality of patient recovery is better.

Sufentanil may induce hypotensive bradycardia and other adverse reactions in elderly patients during anesthesia, while esketamine exhibits sedative and analgesic effects with minimal impact on respiration and circulation. The objective of this study was to investigate the impact of these two anesthetics on vital signs in patients undergoing bronchoscopy and lavage under general anesthesia.

This study was a randomized controlled trial with a parallel design. A total of 100 patients aged ≥60 years with ASAI or II who were undergoing bronchoscopy and lavage were randomly assigned to two groups: group A (esketamine, n = 50) and group B (sufentanil, n = 50). During anesthesia induction, both groups received intravenous infusion of propofol at a dose of 1.5 mL/kg and atracurium. In group A, esketamine at a dose of 0.3 mg/kg was injected; in group B, sufentanil at a dose of 0.2 μg/kg was injected intravenously. Subsequently, a laryngeal mask was inserted and connected to an anesthesia machine for mechanical ventilation. Anesthesia maintenance involved continuous intravenous infusion of propofol at a dose of 3 mL/kg. The mean arterial pressure (MAP), heart rate (HR), and blood oxygen saturation (SpO2) were recorded at various time points: before anesthesia injection (T0), after laryngeal mask insertion (T1), 5 min after the operation started (T2), 15 min after the operation started (T3), and before the end of the operation (T4). Additionally, the recovery time was recorded.

The blood pressure of patients in the esketamine group exhibited higher levels compared to those in the sufentanil group at multiple time points during the operation, while maintaining a more stable intraoperative blood pressure and shorter postoperative recovery time than that observed in the sufentanil group. The blood pressure and heart rate of patients in the esketamine group exhibited significant fluctuations after laryngeal mask implantation compared to pre-anesthesia induction, with a statistically significant increase observed. Conversely, no significant changes were observed in the sufentanil group. The heart rate and oxygen saturation showed no significant differences between the two groups, nor did the amount of propofol administered during the procedure.

The utilization of esketamine during the induction phase of bronchoscopy and lavage under general anesthesia can enhance hemodynamic stability and reduce the occurrence of hypotension, thereby facilitating postoperative anesthetic recovery.

Perioperative neurocognitive disorder and postoperative depressive symptoms are significant complications after surgery. Studies have indicated that esketamine possesses neuroprotective and antidepressant qualities.

This trial included 209 patients aged 60 to 86 years undergoing tumor resection who received esketamine (Group E) or not (Group C) during and after surgery. In group E, patients were given an intravenous dose of 0.5 mg/kg of esketamine 10 minutes after induction of general anaesthesia. In addition, esketamine (2 mg/kg) in combination with sufentanil was used for PCIA during 48 hours postoperatively. On the other hand, saline was used as a substitute for esketamine in group C. Cognitive function was evaluated using neuropsychological tests and telephone interview for cognitive status-modified, and symptoms of depression were assessed using Hamilton Depression Rating Scale 17.

Compared to Group C, patients in Group E exhibited lower rates of depressive symptoms at 3, 7, and 90 days post-surgery (53.9% vs 67.7%, 26.3% vs 47.9%, and 13.3% vs 28.4%). Group E also showed decreased time for Trail Making Test on days 7 and 90. However, there were no significant differences in the incidence of delirium 1 to 5 days post-surgery or cognitive impairment 90 days post-surgery between the 2 groups (12.1% vs 10.9% and 8.4% vs 9.7%).

Intraoperative low-dose esketamine and postoperative low-dose esketamine combined with sufentanil for patient-controlled intravenous analgesia has been shown to improve postoperative analgesia, alleviate postoperative depressive symptoms, and aid in the recovery of social executive ability. However, this approach did not reduce the incidence of postoperative delirium or postoperative cognitive dysfunction.

To provide up to date information on postoperative delirium and neurocognitive disorders in surgical cancer patients.

Established risk factors such as age, psychosocial factors, comorbidities, frailty and preexisting cognitive decline continue to exhibit associations with perioperative neurocognitive disorders (PND); novel risk factors identified recently include microbiome composition and vitamin D deficiency. Prevention measures include cognitive prehabilitation, perioperative geriatric assessment and multidisciplinary care, dexmedetomidine and multimodal analgesic techniques. Studies investigating ciprofol, remimazolam, esketamine, ramelteon and suvorexant have shown encouraging results. Controversy remains regarding the use of inhalational versus intravenous general anesthesia. Innovative approaches to address PND are a rapidly developing area of research, but more studies are needed to identify effective prevention and management interventions. Despite challenges and controversy in the field, implementation of best practice can reduce the detrimental impact of PND on patients, caregivers, and society at large.

Postoperative delirium (POD) is a serious and common complication. The aim of present study is to investigate the diurnal variation of POD and the effects of esketamine in elderly patients.

A randomized, double-blind, placebo-controlled clinical trial with factorial design was conducted. Patients (aged 65 to 85 years) with normal Mini-Mental State Examination (MMSE) score were stratified by age (≤70 vs. >70) and American Society of Anesthesiologists physical status classification (Ⅱ vs. Ⅲ), then randomly assigned to either morning (08:00-12:00) or afternoon (14:00-18:00) noncardiac operation under general anesthesia with or without esketamine administration (0.2 mg/kg). The primary outcome was the incidence of POD (3-Minute Diagnostic Interview for Confusion Assessment Method-defined Delirium, 3D-CAM) on postoperative days 1, 3, and 7. The secondary outcomes were the scores of MMSE and Hospital Anxiety and Depression Scale. The intention-to-treat analysis of the outcomes were performed by generalized estimating equation.

Six patients who did not receive an intervention because of canceled operation were excluded after randomization. The datasets containing 426 cases were analyzed following the intention-to-treat principle after handling missing data via multiple imputation method. The incidence of POD declined from about 55% on postoperative day 1 to 31 and 18% on postoperative days 3 and 7, respectively. Afternoon operation [B=-0.583, OR (95% CI) 0.558 (0.319-0.976); P=0.041], but not esketamine, significantly decreased the incidence of POD. Both esketamine and operation time failed to significantly affect MMSE, HAD, and NRS score. There was no interaction among operation time, esketamine, and follow up time.

Elderly patients undergoing elective noncardiac surgery in the afternoon displayed lower POD incidence than those operated in the morning. A single low-dose of esketamine before general anesthesia induction failed to significantly decrease the risk of POD but decrease the risk of intraoperative hypotension and emergence agitation.

Use of sedatives and analgesics is associated with the occurrence of delirium in critically ill patients receiving mechanical ventilation. Dexmedetomidine reduces the occurrence of delirium but may cause hypotension, bradycardia, and insufficient sedation. This substudy aims to determine whether the combination of esketamine with dexmedetomidine can reduce the side effects and risk of delirium than dexmedetomidine alone in mechanically ventilated patients.

This single-center, randomized, active-controlled, superiority trial will be conducted at The First Affiliated Hospital of Nanjing Medical University. A total of 134 mechanically ventilated patients will be recruited and randomized to receive either dexmedetomidine alone or esketamine combined with dexmedetomidine, until extubation or for a maximum of 14 days. The primary outcome is the occurrence of delirium, while the second outcomes include the number of delirium-free days; subtype, severity, and duration of delirium; time to first onset of delirium; total dose of vasopressors and antipsychotics; duration of mechanical ventilation; ICU and hospital length of stay (LOS); accidental extubation, re-intubation, re-admission; and mortality in the ICU at 14 and 28 days.

There is an urgent need for a new combination regimen of dexmedetomidine due to its evident side effects. The combination of esketamine and dexmedetomidine has been applied throughout the perioperative period. However, there is still a lack of evidence on the effects of this regimen on delirium in mechanically ventilated ICU patients. This substudy will evaluate the effects of the combination of esketamine and dexmedetomidine in reducing the risk of delirium for mechanically ventilated patients in ICU, thus providing evidence of this combination to improve the short-term prognosis. The study protocol has obtained approval from the Medical Ethics Committee (ID: 2022-SR-450).

ClinicalTrials.gov: NCT05466708, registered on 20 July 2022.

Perioperative neurocognitive disorders (PNDs) affect a large percentage of people who undergo surgeries that need general anesthesia. There is an increased risk of death and a major disruption to postoperative self-care as a result of this. This study compiles all the relevant materials that the authors have found to investigate postnatal depression and its causes, as well as the methods used to determine the probability and severity of PNDs and how to reduce their risk before surgery. Postnatal depression can have many causes, and this text explores some of them. These include a history of alcohol or opiate use, immunological dysregulation, advanced age, educational background, infections, neurocognitive impairment, and pre-existing chronic inflammatory disorders. It also delves into various methods used to gauge the likelihood and severity of postpartum depression. The following assessment tools were covered: the Clock Drawing Test, Domain-Specific Tests, the Mini-Mental State Examination, and the Montreal Cognitive Assessment. In addition to biochemical markers, neuroimaging techniques play an important role in diagnosis. The Frailty Fried assessment, which measures inertia, sluggishness, lack of physical activity, fatigue, and unintentional weight loss, is a key prognostic sign that is highlighted. There is strong evidence that the index, which is derived from these five characteristics, may accurately predict the likelihood of PNDs. Risk mitigation strategies are also covered in this research. Preoperative brain plasticity-based therapies, such as physical exercise and intensive cognitive training, can significantly reduce the incidence and severity of postoperative neurocognitive disorders. A peripheral nerve block, monitoring cerebral oxygen saturation, dexmedetomidine, and a reduction in anesthesia depth are all ways to improve anesthetic procedures. Methods that lower blood pressure should be avoided, the body temperature should be kept down during surgery, or the time without liquids should be lengthened; all of these raise the risk of postoperative nausea and vomiting and make it worse. Potential approaches include a Mediterranean diet, physical activity, cognitive stimulation, smoking cessation, alcohol reduction, avoidance of anticholinergic medications, and non-steroidal anti-inflammatory drug stewardship, although there is no definitive evidence for successful postoperative neurocognitive rehabilitation procedures. More standardized diagnostic criteria, evaluation methods, and PND classification are urgently needed, according to this study. Different cases of PNDs are characterized by different combinations of tests, cutoff values, and methods because there is a broad variety of diagnostic tests used to make the diagnosis. Until now, PNDs and pre-existing neurocognitive disorders have been diagnosed using the Diagnostic and Statistical Manual of Mental Disorders (DSM-V). With an aging population comes an increase in the occurrence and prevalence of PNDs, which calls for a specific way to classify and describe the condition.

To investigate the improvement of perioperative sleep quality and neurocognitive impairment in elderly patients under general anesthesia by nasal administration of dexmedetomidine.

One hundred and twenty patients admitted to our hospital for various laparoscopic elective gynecological surgeries lasting more than 1 h under general anesthesia from July 2021 to March 2023 were selected. All subjects were divided into 3 groups according to the random number table method. From 21:00 to 21:30 every night from one day before to 5 days after surgery, group A was given alprazolam 0.4 mg orally; group B was given dexmedetomidine 1.5ug/kg nasal drip; group C was given saline nasal drip. All subjects were observed for general information, sleep quality, postoperative cognitive function, anxiety status, sleep quality, adverse effects and complication occurrence.

The difference in general information between the three groups was not statistically significant, P > 0.05; the sleep quality scores of the three groups on admission were not statistically significant, P > 0.05. At the Preoperative 1d, postoperative 1d, 3d and 5d, the RCSQ scores of the subjects in group A and group B were higher than those in groups C, and with the postoperative RCSQ scores of subjects in group B were higher as the time increased; the assessment of anxiety status in the three groups 1d before surgery was not statistically significant, P > 0.05. The cognitive function scores of subjects in the three groups were not statistically significant in the preoperative 1d, P > 0.05. The postoperative 1d (24.63 ± 2.23), 3d (25.83 ± 2.53), and 5d (26.15 ± 2.01) scores of the subjects in group B were higher than those in groups A and C (P < 0.05), and the subjects in group B had better recovery of postoperative cognitive function with increasing time; the occurrence of postoperative delirium (POD) in group B (12.5%) were lower on postoperative 5d than those in groups A (37.5%) and C (32.5%) (P < 0.05). There was no statistical significance in the evaluation of anxiety state of the three groups on the first day before operation (P > 0.05). The scores in group B were lower than those in group C on the postoperative 1d, 3d, 5 d (P < 0.05). The overall incidence of adverse reactions and complications in subjects in group B was 17.5% significantly lower than that in groups A and C (P < 0.05).

Dexmedetomidine can effectively improve the sleep disorder of elderly general anesthesia patients, reduce the damage to their neurocognitive function and the occurrence of POD, effectively reduce the anxiety of patients and the occurrence of adverse reactions and complications, and has better sedative, improve postoperative cognitive function and anti-anxiety effects, with a high drug safety, worthy of clinical application and promotion.

Postoperative delirium (POD) is an acute, transient brain disorder associated with decreased postoperative quality of life, dementia, neurocognitive changes, and mortality. A small number of trials have explored the role of S-ketamine in the treatment of POD due to its neuroprotective effects. Surprisingly, these trials have failed to yield supportive results. However, heterogeneity in delirium assessment methodologies, sample sizes, and outcome settings as well as deficiencies in S-ketamine use methods make the evidence provided by these studies less persuasive. Given the severe impact of POD on the health of elderly patients and the potential for S-ketamine to prevent it, we believe that designing a large sample size, and rigorous randomized controlled trial for further evaluation is necessary.

This is a single-center, randomized, double-blind, placebo-controlled, pragmatic study. Subjects undergoing total hip or knee arthroplasty will be randomized in a 1:1 ratio to intervention (n = 186) and placebo (n = 186) groups. This trial aims to explore the potential role of S-ketamine in the prevention of POD. Its primary outcome is the incidence of POD within 3 postoperative days. Secondary outcomes include the number of POD episodes, the onset and duration of POD, the severity and subtype of POD, pain scores and opioid consumption, sleep quality, clinical outcomes, and safety outcomes.

To our knowledge, this is the first pragmatic study that proposes to use S-ketamine to prevent POD. We reviewed a large body of literature to identify potential preoperative confounding variables that may bias associations between the intervention and primary outcome. We will use advanced statistical methods to correct potential confounding variables, improving the test's power and external validity of test results. Of note, the patient population included in this trial will undergo intraspinal anesthesia. Although large, multicenter, randomized controlled studies have found no considerable difference in the effects of regional and general anesthesia on POD, patients receiving intraspinal anesthesia have less exposure to at-risk drugs, such as sevoflurane, propofol, and benzodiazepines, than patients receiving general anesthesia. At-risk drugs have been shown to negatively interfere with the neuroprotective effects of S-ketamine, which may be the reason for the failure of a large number of previous studies. There is currently a lack of randomized controlled studies evaluating S-ketamine for POD prevention, and our trial helps to fill a gap in this area.Trial registration: http://www.chictr.org.cn, identifier ChiCTR2300075796.

The administration of analgesic drugs in elderly patients should take into account age-related physiological changes, loss of efficiency of homeostatic mechanisms, and pharmacological interactions with chronic therapies. Underestimation of pain in patients with impaired cognition is often linked to difficulties in pain assessment. In the preoperative phase, it is essential to assess the physical status, cognitive reserve, and previous chronic pain conditions to plan effective analgesia. Furthermore, an accurate pharmacological history of the patient must be collected to establish any possible interaction with the whole perioperative analgesic plan. The use of analgesic drugs with different mechanisms of action for pain relief in the intraoperative phase is a crucial step to achieve adequate postoperative pain control in older adults. The combined multimodal and opioid-sparing strategy is strongly recommended to reduce side effects. The use of various adjuvants is also preferable. Moreover, the implementation of non-pharmacological approaches may lead to faster recovery. High-quality postoperative analgesia in older patients can be achieved only with a collaborative interdisciplinary team. The aim of this review is to highlight the perioperative pain management strategies in the elderly with a special focus on intraoperative pharmacological interventions.

The aim of this study was to compare the effects of remimazolam and propofol on emergence agitation (EA) in elderly patients undergoing hip replacement.

A total of 60 elderly patients undergoing hip replacement were recruited for this prospective, single-center, clinical, randomized, controlled study from February to April 2023. They were randomly assigned to two groups: the remimazolam group (group R) and the propofol group (group P). In group R, remimazolam was administered intravenously during the induction and maintenance of anesthesia, In group P, propofol was used during the induction and maintenance of anesthesia. The incidence of EA was recorded as the primary indicator. Secondary indicators included heart rate (HR) and mean arterial pressure (MAP) values at the following moments: 5 min prior to anesthetic induction (T0), 1 min following induction (T1), 5 min after the laryngeal mask was inserted (T2), the beginning of surgery (T3), the moment the laryngeal mask was removed (T4), and the overall incidence of postoperative adverse events (bleeding or splitting of the surgical incision, removal of the intravenous infusion needle, falling off the bed, hypoxemia, and hypertension).

The incidence of EA was significantly lower in group R than in group P (10% vs 33%, P < 0.05). At T1, T2, and T3, the HR and MAP values of group R were higher than those of group P (P < 0.05). The overall incidence of postoperative adverse events was significantly lower in group R than in group P (P < 0.05).

Remimazolam further reduced the incidence of emergence agitation when compared to propofol during geriatric hip replacement. Moreover, it has a minor hemodynamic effect and lower the incidence of postoperative adverse events.