Effects Of Ketamine Research Articles

Suicide prevention and ketamine: insights from computational modeling.

Suicide is a pressing public health issue, with over 700,000 individuals dying each year. Ketamine has emerged as a promising treatment for suicidal thoughts and behaviors (STBs), yet the complex mechanisms underlying ketamine's anti-suicidal effect are not fully understood. Computational psychiatry provides a promising framework for exploring the dynamic interactions underlying suicidality and ketamine's therapeutic action, offering insight into potential biomarkers, treatment targets, and the underlying mechanisms of both. This paper provides an overview of current computational theories of suicidality and ketamine's mechanism of action, and discusses various computational modeling approaches that attempt to explain ketamine's anti-suicidal effect. More specifically, the therapeutic potential of ketamine is explored in the context of the mismatch negativity and the predictive coding framework, by considering neurocircuits involved in learning and decision-making, and investigating altered connectivity strengths and receptor densities targeted by ketamine. Theory-driven computational models offer a promising approach to integrate existing knowledge of suicidality and ketamine, and for the extraction of model-derived mechanistic parameters that can be used to identify patient subgroups and personalized treatment approaches. Future computational studies on ketamine's mechanism of action should optimize task design and modeling approaches to ensure parameter reliability, and external factors such as set and setting, as well as psychedelic-assisted therapy should be evaluated for their additional therapeutic value.

Effect of Ketamine on Postoperative Neurocognitive Disorders: A Systematic Review and Meta-Analysis.

Neurocognitive alterations in the perioperative period might be caused by a wide variety of factors including pain, blood loss, hypotension, hypoxia, micro- and macroemboli, cardiopulmonary bypass (CPB), reperfusion damage, and surgery itself, and all are risk factors for developing postoperative delirium (POD) and postoperative cognitive dysfunction (POCD). The objective of this study was to evaluate the effect of ketamine on neurocognitive dysfunction after anesthesia. We conducted a meta-analysis of randomized controlled trials (RCTs) comparing ketamine use (experimental group) with placebo (controls). The model favors the control group over the experimental group in terms of frequency of hallucinations (the risk ratio with 95% CI is 1.54 [1.09, 2.19], p-value = 0.02), the number of patients readmitted within 30 days (RR with 95% CI is 0.25 [0.09, 0.70]), and the number of adverse events (overall RR with 95% CI is 1.31 [1.06, 1.62]). In terms of morphine consumption, the model favors the experimental group. There was no statistically significant difference in incidences of postoperative delirium, vasopressor requirement, and fentanyl consumption between the ketamine and control groups. However, hallucinations were more frequently reported in the ketamine group.

Ketamine as a pre-emptive analgesia in patients undergoing caesarean delivery under spinal anesthesia

BACKGROUND & OBJECTIVES: Lower segment caesarean section (LSCS) leads to moderate to severe pain in the patient. Pain severity is directly proportional to the functional limitations and depression in the postpartum period, making it essential to provide good pain relief after surgery. Maternal wellbeing and better nursing care of newborn requires good postoperative analgesia with minimal side effects. The main objective of the study was to evaluate the analgesic effect of intravenous low-dose ketamine, when administered pre-emptively, in patients undergoing caesarean delivery under spinal anesthesia.
 METHODOLOGY: Two groups were made, each with 50 full-term pregnant females with a plan of caesarean section under spinal anesthesia. Group-A received spinal anesthesia with bupivacaine 0.5% along with intravenous placebo of 2cc normal saline, whereas group-B received 0.5mg/kg ketamine intravenously after administration of spinal anesthesia but before the start of surgical incision. Pain intensity was monitored using a visual rating pain scale (VRS), till the need for the first analgesic dose postoperatively.
 RESULTS: Both groups were comparable in terms of age and weight. Analgesia was markedly prolonged, and postoperative pain scores were significantly less in Group-B (ketamine group) as compared to Group-A; with p-value< 0.001, demonstrating analgesic properties of ketamine when administered pre-emptively as an intravenous dose.
 CONCLUSION: Our study concluded that pre-emptive analgesic dose of ketamine (administered before surgical incision), leads to prolong analgesia in post-operative period in patients who underwent LSCS under spinal anesthesia.

Review: The use of functional magnetic resonance imaging (fMRI) in clinical trials and experimental research studies for depression.

Functional magnetic resonance imaging (fMRI) is a non-invasive technique that can be used to examine neural responses with and without the use of a functional task. Indeed, fMRI has been used in clinical trials and pharmacological research studies. In mental health, it has been used to identify brain areas linked to specific symptoms but also has the potential to help identify possible treatment targets. Despite fMRI's many advantages, such findings are rarely the primary outcome measure in clinical trials or research studies. This article reviews fMRI studies in depression that sought to assess the efficacy and mechanism of action of compounds with antidepressant effects. Our search results focused on selective serotonin reuptake inhibitors (SSRIs), the most commonly prescribed treatments for depression and ketamine, a fast-acting antidepressant treatment. Normalization of amygdala hyperactivity in response to negative emotional stimuli was found to underlie successful treatment response to SSRIs as well as ketamine, indicating a potential common pathway for both conventional and fast-acting antidepressants. Ketamine's rapid antidepressant effects make it a particularly useful compound for studying depression with fMRI; its effects on brain activity and connectivity trended toward normalizing the increases and decreases in brain activity and connectivity associated with depression. These findings highlight the considerable promise of fMRI as a tool for identifying treatment targets in depression. However, additional studies with improved methodology and study design are needed before fMRI findings can be translated into meaningful clinical trial outcomes.

Baseline cognitive function predicts full remission of suicidal symptoms among patients with treatment-resistant depression and strong suicidal ideation after low-dose ketamine infusion.

Whether pretreatment working memory and response inhibition function are associated with the rapid and sustained antisuicidal effect of low-dose ketamine among patients with treatment-resistant depression (TRD) and strong suicidal ideation is unclear. We enrolled 65 patients with TRD, comprising 33 who received a single infusion of 0.5 mg/kg ketamine and 32 who received a placebo infusion. The participants performed working memory and go/no-go tasks prior to infusion. We assessed suicidal symptoms at baseline and on postinfusion Days 2, 3, 5, and 7. The full remission of suicidal symptoms persisted for 3 days after a single ketamine infusion and the ketamine-related antisuicidal effect persisted for 1 week. Lower cognitive impairment at baseline (indicated by a higher rate of correct responses on a working memory task) was associated with the rapid and sustained antisuicidal effect of low-dose ketamine in patients with TRD and strong suicidal ideation. Patients with TRD and strong suicidal ideation but low cognitive impairment may benefit the most from the antisuicidal effect of low-dose ketamine.

Comparative Study of Intra-articular Dexmedetomidine Versus Ketamine as an Adjuvant Analgesic after Arthroscopy

Abstract Background: The primary aim of this study was to evaluate the analgesic effect and safety of intra-articular Dexmedetomidine versus Ketamine in patients undergoing knee arthroscopic surgeries. Material and Methods: A total of 100 patients were allocated into two equal groups (n= 50 in each group) using random numbers, in an allocation ratio of 1:1. Syringes were labelled either D (dexmedetomidine) or K (ketamine) and study drugs were injected via intra-articular route after completion of knee arthroscopy. Analgesic effect of study drugs was compared using VAS score at 6 hrs, 12 hrs and 24 hrs. Safety of study drugs was compared using mean HR, mean BP and adverse events observed. Results: Lower VAS score, increased time for first rescue analgesic requirement and decreased need for postoperative analgesics were observed in the dexmedetomidine group as compared to ketamine group. Mean HR and Mean BP were lower in patients receiving dexmedetomine compared to those receiving ketamine. Hypotension was detected in 2 patients receiving dexmedetomedine while 1 patient on ketamine developed delirium. Conclusion: Intra-articular use of dexmedetomidine is superior to ketamine for post-operative analgesia without significant adverse effects. Key words: Knee arthroscopy, Intra-articular Dexmedetomidine, Intra-articular Ketamine

Retigabine promotes ketamine's antidepressant effect in the forced swim test in male and female C57BL/6J mice

Ketamine has been increasingly used as a rapid-onset antidepressant in specific clinical settings. However, as a psychedelic reagent, the potential of physical and psychological dependence limits its clinical use. Here, we added retigabine, a KCNQ channel opener, as an adjunctive treatment to observe its effect on ketamine's antidepressant property in a forced swim test in both male and female C57BL/6 J mice. Behavioral data demonstrated that intraperitoneal injection of ketamine exhibited a dose-dependent effect on animals' immobility performance in the forced swim test. Adding retigabine was sufficient to induce a remarkable antidepressant effect in mice treated with a relatively lower dose of ketamine which failed to be antidepressant when administrated separately. When simultaneously gave retigabine, ketamine's antidepressant effect in the forced swim test was significantly enhanced with a prolonged effective duration. Together, these results from both male and female mice indicated that adjunctive treatment with retigabine was an alternative to promote the antidepressant effect of ketamine, thus holding the possibility of encountering its possible physical and psychological dependence.

Comparison of the effect of ketamine and propofol on surgical operation patients

Background and objective: A prospective randomized controlled study was conducted to compare and evaluate the quality of anesthesia with ketamine or propofol.
 Materials and methods: 80 patients, aged 18-50 years, who were scheduled to undergo minor surgeries of short duration (less than 1 hour of expected duration) were selected and divided in two groups. The patients were randomly assigned to the first group and the second group of 40 patients in each. Group I patients were given ketamine injection 0.5 mg/kg and group II received propofol injection (1.5 μg/kg) as a co-induction agent. After 2 minutes, induction of anesthesia was given with propofol (2.5 mg/kg) and an appropriately sized laryngeal mask was inserted. Anesthesia was maintained with 60% NO in O2 and an intermittent bolus of propofol injection (0.5 mg/kg) given after significant changes in heart rate, blood pressure, lacrimation, sweating, and abnormal movements were noted.
 Results: There was a significant decrease (P < 0.05) in pulse rate, systolic and diastolic blood pressure at 1, 3 and 5 minutes in the group receiving propofol, while the change was insignificant (P > 0.05) at 10 minutes.
 Conclusion: It was noted that ketamine as a starting material was better than propofol with regard to hemodynamic stability and caused fewer adverse effects during surgery and after surgery.

The effect of ketamine on synaptic mistuning induced by impaired glutamate reuptake

Mistuning of synaptic transmission has been proposed to underlie many psychiatric disorders, with decreased reuptake of the excitatory neurotransmitter glutamate as one contributing factor. Synaptic tuning occurs through several diverging and converging forms of plasticity. By recording evoked field postsynaptic potentials in the CA1 area in hippocampal slices, we found that inhibiting glutamate transporters using DL-TBOA causes retuning of synaptic transmission, resulting in a new steady state with reduced synaptic strength and a lower threshold for inducing long-term synaptic potentiation (LTP). Moreover, a similar reduced threshold for LTP was observed in a rat model of depression with decreased levels of glutamate transporters. Most importantly, we found that the antidepressant ketamine counteracts the effects of increased glutamate on the various steps involved in synaptic retuning. We, therefore, propose that ketamine’s mechanism of action as an antidepressant is to restore adequate synaptic tuning.

Comparison of the effect of a combination of low dose ketamine and dexmedetomidine with a combination of low dose ketamine and midazolam on hemodynamic changes and pain in electroconvulsive therapy.

Background: Currently, electroconvulsive therapy (ECT) is used as an effective treatment method in many psychiatric disorders. The basis of a successful electroshock session is to create a seizure with the precise intensity, quality and duration. In addition to the appropriate method of shock induction, appropriate anesthesia methods should be used to cause such seizures. The present study compared a combination of low-dose ketamine and dexmedetomidine (Ketodex) with a combination of low-dose ketamine and midazolam (Ketomid) on hemodynamic changes in electroshocks applied to patients referred from the psychiatric ward.
 Methodology: This study was a randomized triple-blind clinical trial performed after obtaining permission from the Medical Ethics Committee of the Isfahan University of Medical Sciences. For this purpose, 70 patients were selected for electroshock therapy and randomly distributed into two groups of 35 people. In the first group, 0.04 mg/kg midazolam was combined with ketamine 0.1 mg/kg and in the second group, 0.5 μg/kg dexmedetomidine with 0.1 mg/kg ketamine. The patients were placed under complete cardiovascular monitoring. Hemodynamic changes of patients were measured and recorded before injection, after injection, after shock, and at 5 and 10 min after the end of seizures.
 Results: In this study, 70 patients who were candidates for receiving ECT were equally divided into two groups of 35: one group received a mixture of Ketodex and the second group a combination of Ketomid. The two study groups showed no significant difference in terms of systolic pressure (P = 0.883), diastolic (P = 0.443), mean arterial pressure (P = 0.443), oxygen saturation (P = 0.018), and heart rate (P = 0.286). Complications such as headache, muscular pain (P = 0.01), bradycardia, nausea and vomiting were reported in the dexmedetomidine and ketamine groups.
 Conclusion: Our study showed that although systolic, diastolic and mean arterial blood pressure, heart rate and oxygen saturation were significantly reduced in both study groups, no significant difference was observed between the two groups in terms of hemodynamic changes and neither drug group in our study population was different from the other in terms of these parameters. In addition, neither option was superior to the other. However, due to the fact that complications such as headache, muscular pain, bradycardia, nausea and vomiting were reported in the dexmedetomidine and ketamine groups, the combination of midazolam and ketamine appeared to be a more appropriate combination in patients undergoing electroconvulsive therapy.
 Key words: Electroshock therapy; Midazolam; Ketamine; Dexmedetomidine; Hemodynamic changes; Headache pain
 Citation: Nazemroaya B, Manian N. Comparison of the effect of low dose ketamine plus dexmedetomidine vs low dose ketamine plus midazolam on hemodynamic changes and pain in electroconvulsive therapy. Anaesth. pain intensive care 2023;27(3):364−370; DOI: 10.35975/apic.v27i3.1981
 Received: September 02, 2022; Reviewed: December 03, 2022; Accepted: April 23, 2023

A systematic review of the print media representation of ketamine treatments for psychiatric disorders.

Public and patient expectations of treatment influence health behaviours and decision-making. We aimed to understand how the media has portrayed the therapeutic use of ketamine in psychiatry. We systematically searched electronic databases for print and online news articles about ketamine for psychiatric disorders. The top ten UK, USA, Canadian and Australian newspapers by circulation and any trade and consumer magazines indexed in the databases were searched from 2015 to 2020. Article content was quantitatively coded with a framework encompassing treatment indication, descriptions of prior use, references to research, benefits and harms, treatment access and process, patient and professional testimony, tone and factual basis. We found 119 articles, peaking in March 2019 when the United States Food and Drug Administration approved esketamine. Ketamine treatment was portrayed in an extremely positive light (n = 82, 68.9%), with significant contributions of positive testimony from key opinion leaders (e.g. clinicians). Positive research results and ketamine's rapid antidepressant effect (n = 87, 73.1%) were frequently emphasised, with little reference to longer-term safety and efficacy. Side-effects were frequently reported (n = 96, 80.7%), predominantly ketamine's acute psychotomimetic effects and the potential for addiction and misuse, and rarely cardiovascular and bladder effects. Not infrequently, key opinion leaders were quoted as being overly optimistic compared with the existing evidence base. Information pertinent to patient help-seeking and treatment expectations is being communicated through the media and supported by key opinion leaders, although some quotes go well beyond the evidence base. Clinicians should be aware of this and may need to address their patients' beliefs directly.

Ketamine exerts dual effects on the apoptosis of primary cultured hippocampal neurons from fetal rats in vitro.

Ketamine, a noncompetitive N-methyl D-aspartate (NMDA) receptor antagonist, is widely used in pediatric clinical practice. The neuroprotective and neurotoxic effects of ketamine on brain neurons during development remain controversial. The reason may be related to the different concentrations of ketamine used in practice and the small range of concentrations used in previous studies. In this study, cultured hippocampal neurons were treated with ketamine in a wide range of concentrations to comprehensively observe the effects of different concentrations of ketamine on neurons. We demonstrated that low concentrations of ketamine (10 μM, 100 μM and 1000 μM) promoted neuronal survival (p < 0.05) and reduced neuronal apoptosis (p < 0.05) compared with those of the control group. High concentrations of ketamine (2000 μM, 2500 μM and 3000 μM) reduced neuronal survival (p < 0.05) and promoted neuronal apoptosis (p < 0.05). The p38 MAPK inhibitor SB203580 reduced neuronal apoptosis induced by high concentrations of ketamine (2500 μM) (p < 0.05). Our findings indicate that ketamine exerts a dual effect on the apoptosis of primary cultured fetal rat hippocampal neurons in vitro and that the neurotoxic effects of ketamine are related to activation of the p38 MAPK signaling pathway.

The Role of Ketamine in the Treatment of Bipolar Depression: A Scoping Review

Bipolar depression remains a clinical challenge with a quarter of patients failing to respond to initial conventional treatments. Although ketamine has been extensively studied in unipolar depression, its role in bipolar disorder remains inconclusive. The aim of our scoping review was to comprehensively synthesize the current clinical literature around ketamine use in bipolar depression. A total of 10 clinical studies (5 randomized controlled trials and 5 open label studies) were selected. The preliminary evidence, albeit weak, suggests that ketamine is a promising treatment and calls for further interest from the research community. Overall, ketamine treatment appeared to be tolerable with minimal risk for manic/hypomanic switching and showed some effectiveness across parameters of depression and suicidality. Moreover, ketamine is a potential treatment agent in patients with treatment-resistant bipolar depression with promising data extracted from extant controlled trials and real-world effectiveness studies. Future studies are needed to identify ketamine’s role in acute and maintenance treatment phases of bipolar depression. Moreover, future researchers should study the recurrence prevention and anti-suicidal effects of ketamine in the treatment of bipolar depression.

Low-Dose Ketamine-Induced Deficits in Arbitrary Visuomotor Mapping in Monkeys.

Ketamine, an NMDA antagonist, is widely used in clinical settings. Recently, low-dose ketamine has gained attention because of its promising role as a rapid antidepressant. However, the effects of low-dose ketamine on brain function, particularly higher cognitive functions of primate brains, are not fully understood. In this study, we used two macaques as subjects and found that acute low-dose ketamine administration significantly impaired the ability for arbitrary visuomotor mapping (AVM), a form of associative learning (AL) essential for flexible behaviors, including executions of learned stimuli-response contingency or learning of new contingencies. We conducted in-depth analyses and identified intrinsic characteristics of these ketamine-induced functional deficits, including lowered accuracy, prolonged time for planning and movement execution, increased tendency to make errors when visual cues are changed from trial to trial, and stronger impact on combining associative learning and another key higher cognitive function, working memory (WM). Our results shed new light on how associative learning relies on the NMDA-mediated synaptic transmission of the brain and contribute to a better understanding of the potential acute side effects of low-dose ketamine on cognition, which can help facilitate its safe usage in medical practice.

The effects of ketamine on viability, primary DNA damage, and oxidative stress parameters in HepG2 and SH-SY5Y cells.

Ketamine is a dissociative anaesthetic used to induce general anaesthesia in humans and laboratory animals. Due to its hallucinogenic and dissociative effects, it is also used as a recreational drug. Anaesthetic agents can cause toxic effects at the cellular level and affect cell survival, induce DNA damage, and cause oxidant/antioxidant imbalance. The aim of this study was to explore these possible adverse effects of ketamine on hepatocellular HepG2 and neuroblastoma SH-SY5Y cells after 24-hour exposure to a concentration range covering concentrations used in analgesia, drug abuse, and anaesthesia (0.39, 1.56, and 6.25 µmol/L, respectively). At these concentrations ketamine had relatively low toxic outcomes, as it lowered HepG2 and SH-SY5Y cell viability up to 30 %, and low, potentially repairable DNA damage. Interestingly, the levels of reactive oxygen species (ROS), malondialdehyde (MDA), and glutathione (GSH) remained unchanged in both cell lines. On the other hand, oxidative stress markers [superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase (CAT)] pointed to ketamine-induced oxidant/antioxidant imbalance.

Effects of Ketamine on Chronic Postsurgical Pain in Patients Undergoing Surgery: A Systematic Review and Meta-analysis

BACKGROUND: Chronic postsurgical pain (CPSP) has become a common complication during the perioperative period. The efficacy of one of the most potent strategies, ketamine, remains unclear. OBJECTIVES: The aim of this meta-analysis was to evaluate the effect of ketamine on CPSP in patients undergoing common surgeries.. STUDY DESIGN: Systematic review and meta-analysis. METHODS: English-language randomized controlled trials (RCTs) published in MEDLINE, Cochrane Library, and EMBASE from 1990 through 2022 were screened. RCTs with a placebo control group that evaluated the effect of intravenous ketamine on CPSP in patients undergoing common surgeries were included. The primary outcome was the proportion of patients who experienced CPSP 3 – 6 months postsurgery. The secondary outcomes included adverse events, emotional evaluation, and 48 hour postoperative opioid consumption. We followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. Pooled effect sizes were measured using the common-effects model or random-effects model, and several subgroup analyses were conducted. RESULTS: Twenty RCTs were included with 1,561 patients. Our pooled meta-analysis showed a significant difference between ketamine and placebo in the treatment of CPSP (Relative Risk [RR] = 0.86; 95% CI, 0.77 – 0.95; P = 0.02; I2 = 44%). In the subgroup analyses, our results indicated that compared with placebo, intravenous ketamine might decrease the prevalence of CPSP 3 – 6 months postsurgery (RR = 0.82; 95% CI, 0.72 – 0.94; P = 0.03; I2 = 45%). For adverse events, we observed that intravenous ketamine might lead to hallucinations (RR = 1.61; 95% CI, 1.09 – 2.39; P = 0.27; I2 = 20%) but did not increase the incidence of postoperative nausea and vomiting (RR = 0.98; 95% CI, 0.86 – 1.12; P = 0.66; I2 = 0%). LIMITATIONS: Inconsistent assessment tools and follow-up for chronic pain may contribute to the high heterogeneity and limitation of this analysis. CONCLUSIONS: We discovered that intravenous ketamine may reduce the incidence of CPSP in patients undergoing surgery, especially 3 – 6 months postsurgery. Because of the small sample size and high heterogeneity of the included studies, the effect of ketamine in the treatment of CPSP still needs to be explored in future large-sample, standardized-assessment studies. KEY WORDS: Ketamine, chronic postsurgical pain, perioperative period, meta-analysis, randomized controlled trial

Real-world study of intranasal ketamine for use in patients with refractory chronic migraine: a retrospective analysis

IntroductionSubanesthetic ketamine infusion has been used for managing refractory headache in inpatient or outpatient infusion settings. Intranasal ketamine may be an alternative option for outpatient care.MethodsA retrospective study was conducted...

Sex-Dependent Attentional Impairments in a Subchronic Ketamine Mouse Model for Schizophrenia

BackgroundThe development of more effective treatments for schizophrenia targeting cognitive and negative symptoms has been limited, partly due to a disconnect between rodent models and human illness. Ketamine administration is widely used to model symptoms of schizophrenia in both humans and rodents. In mice, subchronic ketamine treatment reproduces key dopamine and glutamate dysfunction; however, it is unclear how this translates into behavioral changes reflecting positive, negative, and cognitive symptoms. MethodsIn male and female mice treated with either subchronic ketamine or saline, we assessed spontaneous and amphetamine-induced locomotor activity to measure behaviors relevant to positive symptoms, and used a touchscreen-based progressive ratio task of motivation and the rodent continuous performance test of attention to capture specific negative and cognitive symptoms, respectively. To explore neuronal changes underlying the behavioral effects of subchronic ketamine treatment, we quantified expression of the immediate early gene product, c-Fos, in key corticostriatal regions using immunofluorescence. ResultsWe showed that spontaneous locomotor activity was unchanged in male and female subchronic ketamine–treated animals, and amphetamine-induced locomotor response was reduced. Subchronic ketamine treatment did not alter motivation in either male or female mice. In contrast, we identified a sex-specific effect of subchronic ketamine on attentional processing wherein female mice performed worse than control mice due to increased nonselective responding. Finally, we showed that subchronic ketamine treatment increased c-Fos expression in prefrontal cortical and striatal regions, consistent with a mechanism of widespread disinhibition of neuronal activity. ConclusionsOur results highlight that the subchronic ketamine mouse model reproduces a subset of behavioral symptoms that are relevant for schizophrenia.

Ketamine versus etomidate for rapid sequence intubation in patients with trauma: a retrospective study in a level 1 trauma center in Korea

BackgroundKetamine and etomidate are commonly used as sedatives in rapid sequence intubation (RSI). However, there is no consensus on which agent should be favored when treating patients with trauma. This study aimed to compare the effects of ketamine and etomidate on first-pass success and outcomes of patients with trauma after RSI-facilitated emergency intubation.MethodsWe retrospectively reviewed 944 patients who underwent endotracheal intubation in a trauma bay at a Korean level 1 trauma center between January 2019 and December 2021. Outcomes were compared between the ketamine and etomidate groups after propensity score matching to balance the overall distribution between the two groups.ResultsIn total, 620 patients were included in the analysis, of which 118 (19.9%) were administered ketamine and the remaining 502 (80.1%) were treated with etomidate. Patients in the ketamine group showed a significantly faster initial heart rate (105.0 ± 25.7 vs. 97.7 ± 23.6, p = 0.003), were more hypotensive (114.2 ± 32.8 mmHg vs. 139.3 ± 34.4 mmHg, p < 0.001), and had higher Glasgow Coma Scale (9.1 ± 4.0 vs. 8.2 ± 4.0, p = 0.031) and Injury Severity Score (32.5 ± 16.3 vs. 27.0 ± 13.3, p < 0.001) than those in the etomidate group. There were no significant differences in the first-pass success rate (90.7% vs. 90.1%, p > 0.999), final mortality (16.1% vs. 20.6, p = 0.348), length of stay in the intensive care unit (days) (8 [4, 15] (Interquartile range)), vs. 10 [4, 21], p = 0.998), ventilator days (4 [2, 10] vs. 5 [2, 13], p = 0.735), and hospital stay (days) (24.5 [10.25, 38.5] vs. 22 [8, 40], p = 0.322) in the 1:3 propensity score matching analysis.ConclusionIn this retrospective study of trauma resuscitation, those receiving intubation with ketamine had greater hemodynamic instability than those receiving etomidate. However, there was no significant difference in clinical outcomes between patients sedated with ketamine and those treated with etomidate.

Essential role of microglia in the fast antidepressant action of ketamine and hypidone hydrochloride (YL-0919).

Introduction: Intracerebral microglia play a vital role in mediating central immune response, neuronal repair and synaptic pruning, but its precise role and mechanism in fast action of antidepressants have remained unknown. In this study, we identified that the microglia contributed to the rapid action of antidepressants ketamine and YL-0919. Methods: The depletion of microglia was achieved with the diet containing the colony-stimulating factor 1 receptor (CSF1R) inhibitor PLX5622 in mice. The tail suspension test (TST), forced swimming test (FST) and novelty suppressed feeding test (NSFT) were employed to evaluate the rapid acting antidepressant behavior of ketamine and YL-0919 in the microglia depletion model. The number of microglia in the prefrontal cortex (PFC) was assayed by the immunofluorescence staining. The expressions of synaptic proteins (synapsin-1, PSD-95, GluA1) and brain-derived neurotrophic factor (BDNF) in the PFC were tested by Western blot. Results: The immobility duration in FST and the latency to feed in NSFT were shortened 24h after an intraperitoneal (i.p.) injection of ketamine (10mg/kg). The microglial depletion of PLX3397 blocked the rapid antidepressant-like effect of ketamine in mice. In addition, the immobility time in TST and FST as well as latency to feed in NSFT were reduced 24h after the intragastric (i.g.) administration of YL-0919 (2.5mg/kg), and the rapid antidepressant effect of YL-0919 was also blocked by the microglial depletion using PLX5622. About 92% of microglia in the prefrontal cortex was depleted in PLX5622 diet-fed mice, while both ketamine and YL-0919 promoted proliferation on the remaining microglia. YL-0919 significantly increased the protein expressions of synapsin-1, PSD-95, GluA1 and BDNF in the PFC, all of which could be blocked by PLX5622. Conclusion: These results suggested the microglia underlying the rapid antidepressant-like effect of ketamine and YL-0919, and microglia would likely constitute in the rapid enhancing impact of synaptic plasticity in the prefrontal cortex by YL-0919.