Subanesthetic dose of S-ketamine improved cognitive dysfunction via the inhibition of hippocampal astrocytosis in a mouse model of post-stroke chronic stress

Zhang, Limin; Wu, Zhi‐You; Liu, Jizhen; Li, Yan; Lv, Jin-Meng; Wang, Luying; Shan, Yu-Dong; Song, Rong‐Xin; Miao, Hui‐Tao; Zhang, Wei; Zhang, Dongxue

doi:10.1016/j.jpsychires.2022.12.010

Cited by 13 publications

(6 citation statements)

References 60 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…POCD, another potential complication of surgical interventions, has been found to be more prevalent among older adults and those undergoing cardiac surgery [20]. It was previously shown that sub-anesthetic doses of S-ketamine (10 mg/kg) improve POCD by inhibiting hippocampal astrocytosis in a mouse model of post-stroke chronic stress [21]. In a comparable manner, in another randomized controlled study, subanesthetic doses of S-ketamine (0.15 mg/kg) were found to potentially decrease the occurrence of early delayed neurocognitive recovery in postoperative stages of older adults, thereby enhancing early postoperative cognitive function.…”

Section: Discussionmentioning

confidence: 99%

The influence of low-dose s-ketamine on postoperative delirium and cognitive function in older adults undergoing thoracic surgery

Wang,

Ma,

Wang

et al. 2024

J Cardiothorac Surg

View full text Add to dashboard Cite

Background Postoperative delirium (POD) and cognitive dysfunction (POCD) are common complications following thoracic surgery, particularly in patients aged 65 years and above. These complications can significantly affect recovery and increase healthcare costs. This study investigates the effects of low-dose S-ketamine on reducing POD and POCD in this patient demographic. Methods In this retrospective cohort study, medical records of patients aged ≥ 65 years who underwent elective thoracic surgery from January 2019 to August 2023 were reviewed. Patients were categorized into S-ketamine and Control groups based on intraoperative S-ketamine exposure. POD was assessed using the Confusion Assessment Method (CAM), while cognitive function was evaluated using the Montreal Cognitive Assessment (MoCA) at baseline, 1 week, 1 month, and 6 months post-surgery. Intraoperative and postoperative parameters, including hemodynamic stability, blood loss, pain scores, and ICU stay length, were also recorded. Results The study comprised 140 participants, with 70 in each group. The S-ketamine group demonstrated a significantly lower incidence of POD at 7 days post-surgery (12.0% vs. 26.7%, P < 0.001), and reduced POCD at 1 month (18.7% vs. 36.0%, P < 0.05) and 6 months (10.7% vs. 21.3%, P < 0.05). The Ketamine group had a significantly higher median MoCA score compared to the Control group both at 1 month (P = 0.021) and 6 months (P = 0.007). Adverse events, such as infection, bleeding, and respiratory failure, showed no significant differences between the groups, suggesting a safe profile for S-ketamine. Conclusion Administering low-dose S-ketamine during thoracic surgery in patients aged 65 years and above significantly reduces the incidence of POD and POCD, highlighting its neuroprotective potential. These findings advocate for the inclusion of S-ketamine in anesthetic protocols to improve postoperative outcomes and reduce healthcare costs in this patient population.

show abstract

Section: Discussionmentioning

confidence: 99%

The influence of low-dose s-ketamine on postoperative delirium and cognitive function in older adults undergoing thoracic surgery

Wang,

Ma,

Wang

et al. 2024

J Cardiothorac Surg

View full text Add to dashboard Cite

show abstract

“…In our study, patients in the esketamine group had higher MoCA impairment by stimulating the activity of the interferon GRNES/TANK-binding kinase 1(TBK1) signaling pathway. This activity impedes trauma-induced chronic neuroinflammation, blood-brain barrier disruption, oxidative stress, and microglia activation [29,30,31,32,33,34] . In our study, we observed that postoperative nausea and vomiting and respiratory depression were also significantly less common than in the control group.…”

Section: Discussionmentioning

confidence: 99%

Safety and Efficacy of Esketamine Weak Opioid Anesthesia in Laparoscopic Gallbladder Surgery

Zhao,

Li,

Jin

et al. 2023

Preprint

View full text Add to dashboard Cite

Background: Esketamine, a non-competitive antagonist of the N-methyl-D-aspartate (NMDA) receptor, plays significance in multimodal analgesia due to its potent analgesic, sedative, and anti-inflammatory properties. Recent studies, however, contradict the belief that laparoscopic surgery notably reduces postoperative pain compared to traditional surgeries. The potential opioid-sparing effects of intravenous esketamine, along with its impact on oxidative stress, inflammatory responses, and cognitive function during laparoscopic surgery, remain unexplored. Methods: In this study, ninety patients scheduled for laparoscopic cholecystectomy were randomized into three groups, each comprising thirty patients: a normal saline control group (NS), a low-dose esketamine group (LS), and a high-dose esketamine group (HS). The LS and HS groups were administered a 0.5 mg/kg esketamine injection before the initial skin incision, followed by esketamine infusions at 2 µg/kg·min and 4 µg/kg·min respectively. Conversely, the NS control group received an intravenous dose of 0.5 mg/kg saline before the first skin incision, followed by a continuous saline infusion at a rate of 2 µg/kg·min. Subsequently, we monitored several parameters: the hemodynamic responses, levels of stress and inflammatory responses, intraoperative doses of sufentanil, remifentanil, and propofol, as well as sufentanil dosage administered in the 24 hours postoperative. We also evaluated alterations in cognitive function, perioperative indicators, and potential adverse reactions among the three groups. Results: Compared to their levels five minutes prior to anesthesia (T₀) and thirty minutes post-operation (T₄), the NS group exhibited a more significant decrease in Mean Arterial Pressure (MAP) and Heart Rate (HR) at the various time intervals: five minutes after the skin incision (T₁), thirty minutes post-incision (T₂), and at the conclusion of the operation (T₃), when compared to both the LS and HS groups (P < 0.05). Additionally, the LS and HS groups required lower doses of propofol, remifentanil, and sufentanil compared to the NS group during the operation (P < 0.05). At T₁, T₂, and T₃, the NS group exhibited elevated levels of adrenaline (AD), noradrenaline (NE), and endothelin (ET) compared to T₀ and T₄. However, the LS and HS groups had lower AD, NE, and ET levels at T₁, T₂, and T₃ compared to the NS group (P< 0.05). In all groups (NS, LS, and HS), serum levels of C-reactive protein (CRP), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) were elevated at T₁, T₂, and T₃ in comparison to levels at T₀ and T₄. Yet, the LS and HS groups had lower CRP, TNF-α, and IL-6 levels at T₁, T₂, and T₃ compared to the NS group (P < 0.05). The Montreal Cognitive Assessment (MoCA) scores of all three groups decreased 24 hours after the operation, however, they were notably higher in the LS and HS groups compared to the NS group (P < 0.05). Furthermore, the recovery time was shorter, and the incidence of nausea, vomiting, and respiratory depression was lower in the LS and HS groups compared to the NS group (P< 0.05). Conclusion: The administration of low-dose esketamine has been shown to be safe, effective, and dependable in the context of laparoscopic gallbladder surgery. It has the capacity to stabilize hemodynamic responses, ameliorate both stress and inflammatory reactions induced by surgical procedures, and expedite the recovery period from anesthesia. Furthermore, it fosters the restoration of postoperative cognitive function. Notably, when used in conjunction with nalbuphine, low-dose esketamine exhibits opioid-sparing properties, thereby reducing the incidence of postoperative adverse effects. Trial registration: The trial is registered with the China Clinical Trials Registry Registration Number: ChiCTR2300067596. Retrospectively registered (date of registration: 12/01/2023).

show abstract

“…Esketamine is known to be a psychoactive drug with hallucinogenic properties that could theoretically contribute to the occurrence and development of PND. However, previous research has reported potential neuroprotective effects of ketamine [12,13] . The US Food and Drug Administration recently approved S-ketamine nasal spray as a novel treatment for drug-resistant depression and adults with major depression associated with acute suicidal ideation or behavior [11] .…”

mentioning

confidence: 90%

Effect of low-dose esketamine on perioperative neurocognitive disorder and postoperative depressive symptoms in elderly patients undergoing major elective non-cardiac surgery for malignant tumors: A randomized clinical trial

Cuifang,

Xianlong,

Yubing

et al. 2023

Preprint

View full text Add to dashboard Cite

Background: Research on the impact of small-dose esketamine on perioperative neurocognitive disorder and postoperative depressive symptoms in elderly patients is limited. This study aimed to assess whether administering perioperative small-dose esketamine intravenously would reduce the incidence of perioperative neurocognitive disorder and postoperative depressive symptoms in elderly patients with malignant tumors undergoing elective non-cardiac major surgery. Methods: This trial included 209 patients aged 65 to 86 years undergoing tumor resection who received esketamine (Group E) or not (Group C) during and after surgery. Cognitive function was evaluated using neuropsychological tests as well as the telephone interview for cognitive status-modified (TICSm), and symptoms of depression were assessed using the 17-item Hamilton Depression Rating Scale (HAMD-17). Results: There was no significant difference in postoperative delirium incidence between patients who received esketamine during surgery and those who did not at 1-5 days post-operation. Group E had 12.0% incidence (13 out of 108 patients), while Group C had 10.9% (11 out of 101). Group E showed significantly better results than group C regarding less time required for the trail making test (Part B) during neuropsychological testing, lower incidence of depression, and lower Hamilton depression score at 3, 7, and 90 days post-surgery. Conclusions: Small doses of eketamine given perioperatively improved postoperative depression in elderly patients with malignant tumors. Adverse reactions were not significantly increased. It did not significantly affect postoperative delirium and cognitive function, but it facilitated the recovery of social executive abilities. Trial registration: The study was registered on clinicaltrials.gov.cn on 10/3/2023 (NO. ChiCTR2300069249).

show abstract

Subanesthetic dose of S-ketamine improved cognitive dysfunction via the inhibition of hippocampal astrocytosis in a mouse model of post-stroke chronic stress

Cited by 13 publications

References 60 publications

The influence of low-dose s-ketamine on postoperative delirium and cognitive function in older adults undergoing thoracic surgery

The influence of low-dose s-ketamine on postoperative delirium and cognitive function in older adults undergoing thoracic surgery

Safety and Efficacy of Esketamine Weak Opioid Anesthesia in Laparoscopic Gallbladder Surgery

Effect of low-dose esketamine on perioperative neurocognitive disorder and postoperative depressive symptoms in elderly patients undergoing major elective non-cardiac surgery for malignant tumors: A randomized clinical trial

Contact Info

Product

Resources

About