Effects Of S-ketamine Research Articles

Effect of S-Ketamine on Postoperative Nausea and Vomiting in Patients Undergoing Video-Assisted Thoracic Surgery: A Randomized Controlled Trial.

Postoperative nausea and vomiting (PONV) frequently occur in patients after surgery. In this study, the authors investigated whether perioperative S-ketamine infusion could decrease the incidence of PONV in patients undergoing video-assisted thoracoscopic surgery (VATS) lobectomy. This prospective, randomized, double-blinded, controlled study was conducted a total of 420 patients from September 2021 to May 2023 at Xuzhou Central Hospital in China, who underwent elective VATS lobectomy under general anesthesia with tracheal intubation. The patients were randomly assigned to either the S-ketamine group or the control group. The S-ketamine group received a bolus injection of 0.5 mg/kg S-ketamine and an intraoperative continuous infusion of S-ketamine at a rate of 0.25 mg/kg/h. The control group received an equivalent volume of saline. All patients were equipped with patient-controlled intravenous analgesia (PCIA), with a continuous infusion rate of 0.03 mg/kg/h S-ketamine in the S-ketamine group or 0.03 μg/kg/h sufentanil in the control group. The primary outcome was the incidence of PONV. Secondary outcomes included perioperative opioid consumption, hemodynamics, postoperative pain, and adverse events. The incidence of PONV in the S-ketamine group (9.7%) was significantly lower than in the control group (30.5%). Analysis of perioperative opioid usage revealed that remifentanil usage was 40.0% lower in the S-ketamine group compared to the control group (1414.8 μg vs 2358.2 μg), while sufentanil consumption was 75.2% lower (33.1 μg vs 133.6 μg). The S-ketamine group demonstrated better maintenance of hemodynamic stability. Additionally, the visual analogue scale (VAS) scores on postoperative day 1 (POD-1) and postoperative day 3 (POD-3) were significantly lower in the S-ketamine group. Finally, no statistically significant difference in other postoperative adverse reactions was observed between the two groups. The results of this trial indicate that perioperative S-ketamine infusion can effectively reduce the incidence of PONV in patients undergoing VATS lobectomy.

Effect of S-ketamine on Postoperative Pain in Adults Post-Abdominal Surgery: A Systematic Review and Meta-analysis

BACKGROUND: S-ketamine is the S-enantiomer of ketamine, which exerts anesthetic and analgesic effects through noncompetitive antagonism of N-methyl-D-aspartate (NMDA) receptors. OBJECTIVE: We aimed to define the relative risk of post–abdominal surgery pain in adults who were administered perioperative S-ketamine. STUDY DESIGN: Systematic review and meta-analysis. METHODS: Two reviewers independently screened the articles from the titles and abstracts based on our eligibility criteria, evaluated the risk of bias by using the Cochrane Collaboration Risk of Bias tool in randomized controlled trials, and extracted the data from the included studies according to a prespecified protocol; any disagreements were solved by consultation. The level of certainty for the main results were evaluated according to the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system RESULTS: Of the 1,621 studies identified, 9 studies were included; they were published from 2004 through 2022. Only one study involved epidural anesthesia, whereas the other 8 studies included general anesthesia. The pain at rest scores at 4 and 24 hours post–abdominal surgery were significantly lower in the S-ketamine group, respectively. However, there was no significant difference between the 2 groups in the pain at rest scores at 48 hours post–abdominal surgery. S-ketamine infusion reduced pain during movement 24 hours post-abdominal surgery, but not at 48 hours, respectively. The incidence of postoperative nausea and vomiting, as well as psychotomimetic adverse effects post-abdominal surgery were similar between the 2 groups, respectively. A subgroup analysis revealed that the pain at rest score at 4 hours post-abdominal surgery in patients in the intraoperative use group was remarkably reduced, compared with the patients who received S-ketamine perioperatively. Otherwise, the pain at rest score at 24 hours post-abdominal surgery in the perioperative use group was significantly reduced versus intraoperative use group. LIMITATION: The number of trials included was small. The remarkable heterogeneity found in the pooled results at each time point post-abdominal surgery might affect the credibility of the results. CONCLUSIONS: S-ketamine is effective in reducing the early postoperative pain of patients who received abdominal surgery, and may not increase the incidence of postoperative complications. KEY WORDS: S-ketamine, intravenous, postoperative pain, abdominal surgery, pain scores, randomized controlled trial, systematic review, meta-analysis

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

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 24h (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 0.75mg/kg of S-ketamine. Clinical Trial Registration: chictr.org.cn, identifier ChiCTR2200057226.

Effect of S-ketamine on Postoperative Quality of Recovery in Patients Undergoing Video-Assisted Thoracic Surgery

S-ketamine is associated with effective postoperative analgesia and enhanced quality of recovery (QoR). The study aimed to investigate the effect of perioperative S-ketamine on postoperative quality of recovery in patients undergoing video-assisted thoracic surgery (VATS). A prospective, randomized, double-blinded, placebo-controlled trial. Single institution, tertiary university hospital. Eighty adult patients aged 18-to-65 undergoing VATS were eligible for participation. Patients enrolled in this study were randomized to receive either S-ketamine (a bolus of 0.25 mg/kg, followed by an infusion of 0.125 mg/kg/h until 15 minutes before the end of the surgical procedure), or identical volumes and rates of 0.9% saline. Postoperative quality of recovery was measured with QoR-40 score 48 hours after surgery. The postoperative pain was assessed postoperatively using the numeric rating scale at 0.5, 6, 24, and 48 hours. Hospital Anxiety and Depression Scale Depression subscale (HADS-D) scores and other secondary outcomes also were recorded. The final analysis included 77 patients. The global QoR-40 score at 48 hours postoperatively was higher in the S-ketamine group compared with the saline group (median [interquartile range]: 181.5 [178-184] v 174.5 [169-177]), estimated median difference 7 (95% confidence interval 5-10, p < 0.001). Patients who received S-ketamine treatment had lower pain scores at rest (p=0.017 and p=0.006, respectively) and coughing (p < 0.001 and p=0.007, respectively) at 24 and 48 hours postoperatively than those who received saline treatment. The requirement and consumption of opioid for rescue analgesic were lower in the S-ketamine (p=0.045 and p=0.047, respectively). Compared with the saline group, S-ketamine reduced HADS-D scores (p=0.003) at 48 hours after surgery. The present study's findings suggested that perioperative S-ketamine enhanced the quality of recovery in patients undergoing VATS. S-ketamine also improved postoperative analgesia and postoperative depression.

Translating the immediate effects of S-Ketamine using hippocampal subfield analysis in healthy subjects-results of a randomized controlled trial

Antidepressant doses of ketamine rapidly facilitate synaptic plasticity and modify neuronal function within prefrontal and hippocampal circuits. However, most studies have demonstrated these effects in animal models and translational studies in humans are scarce. A recent animal study showed that ketamine restored dendritic spines in the hippocampal CA1 region within 1 h of administration. To translate these results to humans, this randomized, double-blind, placebo-controlled, crossover magnetic resonance imaging (MRI) study assessed ketamine’s rapid neuroplastic effects on hippocampal subfield measurements in healthy volunteers. S-Ketamine vs. placebo data were analyzed, and data were also grouped by brain-derived neurotrophic factor (BDNF) genotype. Linear mixed models showed that overall hippocampal subfield volumes were significantly larger (p = 0.009) post ketamine than post placebo (LS means difference=0.008, standard error=0.003). Post-hoc tests did not attribute effects to specific subfields (all p > 0.05). Trend-wise volumetric increases were observed within the left hippocampal CA1 region (p = 0.076), and trend-wise volumetric reductions were obtained in the right hippocampal—amygdaloid transition region (HATA) (p = 0.067). Neither genotype nor a genotype–drug interaction significantly affected the results (all p > 0.7). The study provides evidence that ketamine has short-term effects on hippocampal subfield volumes in humans. The results translate previous findings from animal models of depression showing that ketamine has pro-neuroplastic effects on hippocampal structures and underscore the importance of the hippocampus as a key region in ketamine’s mechanism of action.

S-ketamine and intranasal application: alternatives for the castration of male suckling piglets?

BackgroundThe intramuscular injection of ketamine and azaperone was proposed as a suitable anaesthesia for male suckling piglets for surgical castration. However, this can be opposed by massive defensive movements, hypothermia and tachycardia during castration and a long recovery period. The aim of the present study was to test whether the use of S-ketamine and/or a change in the route of application from intramuscular to intranasal could reduce stress responses and the duration of recovery compared to the intramuscular route and the use of racemic ketamine. Seventy-eight healthy, five-day-old male piglets were randomized to six treatment groups in a blinded experimental study, matched by litter and weight. Experimental groups were A (15 mg kg-1 S-ketamine + 2 mg kg-1 azaperone, i.m., surgical castration), B (15 mg kg-1 R/S-ketamine racemate + 2 mg kg-1 azaperone, i.m., surgical castration), C (30 mg kg-1 S-ketamine + 2 mg kg-1 azaperone, i.n., surgical castration), D (15 mg kg-1 R/S-ketamine racemate + 2 mg kg-1 azaperone, i.m.; not castrated), E (positive control group; no anesthesia, surgical castration) and F (negative control group; no anesthesia, not castrated).ResultsS-ketamine reduced the defensive movement score during castration to a similar extent to racemic ketamine when administered intramuscularly but not via the intranasal route. However, the effects of S-ketamine (both routes) on the increase in cortisol levels and decrease in body temperature were similar to those induced by racemic ketamine. A reduction of the long recovery time known for ketamine-azaperone anaesthesia could not be achieved with S-ketamine in the given dosage, regardless of the route of application. The intranasal administration of ketamine was difficult with the available formulation as the necessary amount exceeded the capacity of the nose cavity.ConclusionsNeither the use of S-ketamine nor intranasal administration can be suitable alternatives for the anaesthesia of male suckling piglets for castration.

Effect of S-ketamine as an Anesthetic Adjuvant to Propofol on Treatment Response to Electroconvulsive Therapy in Treatment-Resistant Depression

Effect of S-ketamine as an Anesthetic Adjuvant to Propofol on Treatment Response to Electroconvulsive Therapy in Treatment-Resistant Depression

P 120. Anaesthesia with S-ketamine and etomidate during electroconvulsive therapy of therapy-resistant major depression

Introduction/Objective S-ketamine is a NMDA-receptor antagonist used as anesthetic, with possibly antidepressive properties. In contrast to other anesthetics such as etomidate, propofole or meto-hexitale, it does not increase the seizure threshold. Due to its pharmacokinetic properties, S-ketamine is well suitable for short anesthesia, e.g. in electroconvulsive therapy (ECT). In our clinic we use S-ketamine and etomidate as anesthetics for ECT. The objective of this abstract is to report our clinical observations on ECT-related parameters with these two anesthetics. Methods By the time of abstract submission, the ongoing recruitment amounts to 46 patients (15 male, 31 female) treated by 639 ECT for severe therapy-resistant major depression. Patients were anesthetized either using etomidate or S-ketamine according to clinical indication. Succinylcholine was used for muscle relaxation. A Thymatron IV stimulator (Thymatron somatics Inc., Ontario/Canada) was used for seizure provocation. Generally, patients received three treatments per week. Objective parameters recorded in each session were electrode position, stimulation energy, seizure duration, postictal supression index (PSI), maximum sustained coherence (MSC), maximal heartrate and side-effects. Statistical evaluation was performed using analysis of variance implemented in SPSS software (SPSS Statistics, 19th version, IBM Germany GmbH, Ehningen). Results Seizure duration was significantly longer during S-ketamine that during etomidate anesthesia (41.75 and 36.65s respectively; p =0.009). Significantly lower number of restimulations was necessary during S-ketamine versus etomidate anesthesia (34 restimulations versus 20; p =0.00). Stimulation energy to induce a seizure was lower using S-ketamine compared to etomidate (230,63mC versus 259,66mC; p =0.08), but there was no statistically significant effect. Side effects were rare and did not differ between groups. Conclusion Our preliminary data suggest that S-ketamine might have favorable effects on seizure parameters during ECT for treatment-resistant major depression concerning stimulation energy, seizure duration and number of restimulations. This is in accordance with Kranaster et al. (2011). However, interpretation is limited by the non-randomized open design. The mechanism leading to the favorable effects of s-ketamine remain unclear so far. Improvement of seizure-quality or additive antidepressive effects of S-ketamine such as observed in Zarate CA et al. (2006) and Price et al. (2009) might explain our preliminary results.

Microglial Ca2+-Activated K+Channels Are Possible Molecular Targets for the Analgesic Effects ofS-Ketamine on Neuropathic Pain

Ketamine is an important analgesia clinically used for both acute and chronic pain. The acute analgesic effects of ketamine are generally believed to be mediated by the inhibition of NMDA receptors in nociceptive neurons. However, the inhibition of neuronal NMDA receptors cannot fully account for its potent analgesic effects on chronic pain because there is a significant discrepancy between their potencies. The possible effect of ketamine on spinal microglia was first examined because hyperactivation of spinal microglia after nerve injury contributes to neuropathic pain. Optically pure S-ketamine preferentially suppressed the nerve injury-induced development of tactile allodynia and hyperactivation of spinal microglia. S-Ketamine also preferentially inhibited hyperactivation of cultured microglia after treatment with lipopolysaccharide, ATP, or lysophosphatidic acid. We next focused our attention on the Ca(2+)-activated K(+) (K(Ca)) currents in microglia, which are known to induce their hyperactivation and migration. S-Ketamine suppressed both nerve injury-induced large-conductance K(Ca) (BK) currents and 1,3-dihydro-1-[2-hydroxy-5-(trifluoromethyl)phenyl]-5-(trifluoromethyl)-2H-benzimidazol-2-one (NS1619)-induced BK currents in spinal microglia. Furthermore, the intrathecal administration of charybdotoxin, a K(Ca) channel blocker, significantly inhibited the nerve injury-induced tactile allodynia, the expression of P2X(4) receptors, and the synthesis of brain-derived neurotrophic factor in spinal microglia. In contrast, NS1619-induced tactile allodynia was completely inhibited by S-ketamine. These observations strongly suggest that S-ketamine preferentially suppresses the nerve injury-induced hyperactivation and migration of spinal microglia through the blockade of BK channels. Therefore, the preferential inhibition of microglial BK channels in addition to neuronal NMDA receptors may account for the preferential and potent analgesic effects of S-ketamine on neuropathic pain.

Psychopathological effects of S-ketamine and dimethyltryptamine (DMT) in humans: a double-blind, cross-over human experimental study of the NMDA antagonist and the 5HT2A agonist model of psychosis

Psychopathological effects of S-ketamine and dimethyltryptamine (DMT) in humans: a double-blind, cross-over human experimental study of the NMDA antagonist and the 5HT2A agonist model of psychosis