Effects Of Ketamine Research Articles

Sex differences in the effects of repeated ketamine infusions on bone markers in patients with unipolar and bipolar depression

BackgroundPatients with depression, especially women, are associated with low bone mineral density (BMD). Traditional antidepressants are associated with negative effects on BMD. Few studies have examined the effect of ketamine on BMD, and it remains unclear whether there are sex differences in the effects of ketamine on BMD in patients with depression.MethodsA total of 102 patients with unipolar and bipolar depression were administered six infusions of intravenous ketamine over a 12-day period. Plasma levels of eight bone markers were examined at baseline, 24 h after the sixth infusion and again 2 weeks (Days 13 and 26).ResultsLinear mixed models showed all bone markers had significant time main effect (all p < 0.05). Compared with baseline, the whole sample showed increased levels of leptin and osteoprotegerin at Days 13 and 26, as well as Dickkopf-related protein 1 at Day 13, and decreased levels of osteocalcin, sclerostin, osteopontin, parathyroid hormone and fibroblast growth factor 23 at Days 13 and 26 (all p < 0.05). Females had a higher level of leptin at Days 13 and 26, and lower levels of osteocalcin and sclerostin at Day 13 than males (all p < 0.05). Increases of leptin were associated with depressive symptom improvements at Day 13 and Day 26 in females (both p < 0.05). In males, higher baseline osteocalcin levels were associated with greater depressive symptom improvement at Day 26 (β = 0.414, p = 0.009).ConclusionsOur results suggest that repeated ketamine infusions may be associated with modulation of bone markers in patients with depression and present sex differences. Baseline osteocalcin level may be served as a predictor for the antidepressant effects of ketamine in males.Trial registration Data were derived from an open label clinical trial, which was registered at Chinese Clinical Trial Registry (ChiCTR-OOC-17012239). Registered 26 May 2017. http://www.chictr.org.cn

Comparison of airway collapsibility following single induction dose ketamine with propofol versus propofol sedation in children undergoing magnetic resonance imaging: A randomised controlled study.

Adequate sedation is essential for children undergoing magnetic resonance imaging (MRI) console. Propofol is commonly used for sedation, but it has the drawback of upper airway collapse at higher doses, which may be overcome by ketamine. This study was designed to evaluate the beneficial effect of ketamine on propofol in preventing airway collapse. Fifty-eight children undergoing MRI were randomised to Group P (propofol bolus dose followed by infusion or Group KP (bolus dose of ketamine and propofol followed by propofol infusion). The primary aim is to compare the upper airway cross-sectional area (CSA) and diameters (transverse diameter [TD] and anteroposterior diameter [APD]) obtained from MRI during inspiration and expiration. Upper airway collapse as measured by delta CSA in mean (SD) [95% confidence interval] was statistically more significant between the two groups [at the soft palate level, 16.9 mm2 (19.8) [9.3-24.4] versus 9.0 mm2 (5.50) [6.9-11.1] (P = 0.043); at the base of the tongue level, 15.4 mm2 (11.03) [11.2-19.6] versus 7.48 mm2 (4.83) [5.64-9.32] (P < 0.001); at the epiglottis level, 23.9 (26.05) [14.0-33.8] versus 10.9 mm2 (9.47) [7.35-14.5] (P = 0.014)]. A significant difference was obtained for TD at all levels and for APD at the soft palate and base of tongue level. Adding a single dose of ketamine to propofol reduced the upper airway collapse significantly, as evidenced by the MRI-based measurements of upper airway dimensions, compared to propofol alone.

Pre-adolescence repeat exposure to sub-anesthetic doses of ketamine induces long-lasting behaviors and cognition impairment in male and female rat adults

In pre-adolescence, repeated anesthesia may be required for therapeutic interventions. Adult cognitive and neurobehavioral problems may result from preadolescent exposure to anesthetics. This study examined the long-term morphological and functional effects of repeated sub-anesthetic doses of ketamine exposure on male and female rat adults during pre-adolescence. Weaned 48 pre-adolescent rats from eight mothers and were randomly divided into four equal groups: control group and the ketamine group of males and females (20 mg/kg daily for 14 days); then animals received care for 20–30 days. Repeated exposure to sub-anesthetic doses of ketamine on cognitive functions was assayed using Social discrimination and novel object tests. Besides, an elevated plus maze and fear conditioning apparatus were utilized to determine exploratory and anxiety-like behavior in adults. Toluidine blue stain was used to evaluate the number of dead neurons in the hippocampus, and the effects of ketamine on synaptic plasticity were compared in the perforant pathway of the CA1 of the hippocampus. Our study indicates that repeated exposure to sub-anesthetic doses of ketamine during pre-adolescence can result in neurobehavioral impairment in male and female rat adulthood but does not affect anxiety-like behavior. We found a significant quantifiable increase in dark neurons. Recorded electrophysiologically, repeat sub-anesthetic doses of ketamine resulted in hampering long-term potentiation and pair pulse in male adult animals. Our results showed that repeated exposure to sub-anesthetic doses of ketamine during pre-adolescence can induce hippocampus and neuroplasticity changes later in adulthood. This study opens up a new line of inquiry into potential adverse outcomes of repeated anesthesia exposure in pre-adolescent rats.

Listening to music during intranasal (es)ketamine therapy in patients with treatment-resistant depression correlates with better tolerability and reduced anxiety.

Although the effectiveness of (es)ketamine for therapy-resistant depression (TRD) has been established, potential treatment-limiting factors include side effects like dissociation, anxiety, or elevated blood pressure. Music can reduce stress and negative emotions as anxiety. This study aimed to investigate the impact of listening to music during intranasal (es)ketamine administration on both tolerability and efficacy. Records of 494 sessions (of 37 patients) with intranasal (es)ketamine administration, each containing data of blood pressure measurements, DSS-IV (dissociation symptoms scale-IV), anxiety and euphoria analogue scale, MADRS (Montgomery-Åsberg Depression Rating Scale) and BDI (Beck's Depression Inventory) were evaluated. The between-group analysis, comparing participants who listened to music with those who did not, revealed significant differences in the administered dose (p-value: 0.003, mean: 131.5 mg with music vs. 116.7 mg without music), scores on the DSS Item 1 (p-value: 0.005, mean: 3 points vs. 2.4 points), levels of anxiety (p-value: <0.001, mean: 0.4 points vs. 1.4 points), and measurements of maximal systolic blood pressure after administration (p-value: 0.017, mean: 137.9 mmHg vs. 140.3 mmHg). Listening to music had no impact on the MARDS-change score between the sessions. Key limitations include a non-randomized naturalistic design and the non-standardized selection of music, which was based on individual patient preferences. Listening to music during intranasal (es)ketamine therapy appears to be linked to reduced anxiety and lower blood pressure, stable or increased dissociation levels, and improved tolerance for higher doses. These findings could potentially contribute to the optimization of (es)ketamine therapy, both in terms of treatment efficacy and managing side effects.

Ketamine in the treatment of refractory and super-refractory status epilepticus: Experience from two centres

PurposeThere is insufficient evidence on the management of refractory status epilepticus (RSE) and super-RSE (SRSE). Ketamine is a N-methyl-d-aspartate receptor antagonist in the treatment of these entities. Our objectives were to study the effectiveness and safety of ketamine in the treatment of adult patients with RSE and SRSE, to determine the factors that can influence the response to ketamine, and to explore its use in patients without mechanical ventilation. MethodsAdult patients who had received intravenous ketamine for the treatment of RSE or SRSE at Hospital Universitario Clínico San Carlos (Madrid, Spain) or Hospital Universitari Vall d'Hebron (Barcelona, Spain) from 2017 to 2023 were retrospectively analysed. ResultsThis study included 58 adult patients, mean (standard deviation) age 60.2 (15.7) years, of whom 41 (70.7 %) were male; 33 (56.9 %) patients responded to ketamine without recurrence, with a low rate of adverse effects (8.6 %). The presence of SRSE at the time of ketamine initiation (OR 0.287, p = 0.028) and the time elapsed between status epilepticus onset and ketamine administration (OR 0.991, p = 0.034) were associated with worse response to ketamine. Patients treated without mechanical ventilation had similar rates of response without recurrence (62.5% vs 56.9 %) and lower mortality (37.5% vs 53.5 %) compared to the overall group. ConclusionKetamine is an effective drug with few adverse effects. Prompt administration should be considered in patients with RSE requiring anaesthesia, in patients with SRSE, and in patients with RSE who do not respond to standard antiseizure drugs and in whom mechanical ventilation is not advised.

Optimizing the use of ketamine to reduce chronic postsurgical pain in women undergoing mastectomy for oncologic indication: study protocol for the KALPAS multicenter randomized controlled trial

BackgroundMastectomies are commonly performed and strongly associated with chronic postsurgical pain (CPSP), more specifically termed postmastectomy pain syndrome (PMPS), with 25–60% of patients reporting pain 3 months after surgery. PMPS interferes with function, recovery, and compliance with adjuvant therapy. Importantly, it is associated with chronic opioid use, as a recent study showed that 1 in 10 patients continue to use opioids at least 3 months after curative surgery. The majority of PMPS patients are women, and, over the past 10 years, women have outpaced men in the rate of growth in opioid dependence. Standard perioperative multimodal analgesia is only modestly effective in prevention of CPSP. Thus, interventions to reduce CPSP and PMPS are urgently needed. Ketamine is well known to improve pain and reduce opioid use in the acute postoperative period. Additionally, ketamine has been shown to control mood in studies of anxiety and depression. By targeting acute pain and improving mood in the perioperative period, ketamine may be able to prevent the development of CPSP.MethodsKetamine analgesia for long-lasting pain relief after surgery (KALPAS) is a phase 3, multicenter, randomized, placebo-controlled, double-blind trial to study the effectiveness of ketamine in reducing PMPS. The study compares continuous perioperative ketamine infusion vs single-dose ketamine in the postanesthesia care unit vs placebo for reducing PMPS. Participants are followed for 1 year after surgery. The primary outcome is pain at the surgical site at 3 months after the index surgery as assessed with the Brief Pain Inventory-short form pain severity subscale.DiscussionThis project is part of the NIH Helping to End Addiction Long-term (HEAL) Initiative, a nationwide effort to address the opioid public health crisis. This study can substantially impact perioperative pain management and can contribute significantly to combatting the opioid epidemic.Trial registrationClinicalTrials.gov NCT05037123. Registered on September 8, 2021.

Analgesic and Opioid Sparing Effects of Tramadol, Ketamine, and Bupivacaine Following Wound Infiltration After Caesarean Section

Analgesic and Opioid Sparing Effects of Tramadol, Ketamine, and Bupivacaine Following Wound Infiltration After Caesarean Section

Ketamine for Adults With Treatment-Resistant Depression or Posttraumatic Stress Disorder: A 2023 Update

What Is the Issue?&#x0D; &#x0D; Many drug treatments are available for depression, but 22% of people in Canada with the condition have treatment-resistant depression (TRD). For people with TRD, standard drug treatments do not improve their symptoms or do not work for long, and their depression persists.&#x0D; Posttraumatic stress disorder (PTSD) is a disabling mental health condition that affects about 9% of people in Canada in their lifetime. Few drugs are available for treating PTSD, none of which are considered effective.&#x0D; Ketamine is a hallucinogenic drug used primarily for anesthesia. Ketamine has also been explored for other indications, such as TRD and PTSD, generating questions about whether it could be a treatment option for these conditions.&#x0D; &#x0D; What Did We Do?&#x0D; &#x0D; We conducted a review of the clinical effectiveness, cost-effectiveness, and evidence-based guidelines on the use of ketamine in adults with TRD or PTSD, to help guide decisions on the use of ketamine for managing these conditions.&#x0D; An information specialist conducted a search of peer-reviewed and grey literature sources published in March 2022 or later. One reviewer screened citations and selected and critically appraised the included studies.&#x0D; CADTH engaged a patient with lived experience of TRD who shared their experiences and perspectives on ketamine-assisted psychotherapy. These perspectives helped us to contextualize the literature and appreciate nuances of the experience.&#x0D; &#x0D; What Did We Find?&#x0D; &#x0D; Ketamine could lead to an immediate improvement in depressive symptoms and suicidal ideation compared to placebo or midazolam in adults with TRD. The longest follow-up was 90 days, and the longest lasting effect after a dose was 28 days. Serious side effects of ketamine — such as dissociation — were rare and short-lived, lasting hours, in adults with TRD.&#x0D; It is uncertain if ketamine is an effective and safe treatment for symptoms of PTSD, due to little to no evidence suggesting its effectiveness or safety against placebo, midazolam, or opioids.&#x0D; Most studies evaluated ketamine given intravenously, and we found limited evidence on intramuscular (IM), subcutaneous, and intranasal routes of administration. We found no studies on oral or sublingual administration of ketamine and no studies comparing the different ways that ketamine can be given for TRD or PTSD.&#x0D; An economic evaluation found that IV ketamine was likely to be cost-effective compared to intranasal esketamine in adults with TRD from a health care perspective in the US. However, from a patient perspective, IV ketamine was unlikely to be cost-effective compared to esketamine, due to comparable levels of clinical effectiveness and lower costs of esketamine attributable to commercial insurance coverage and manufacturer assistance programs.&#x0D; A US guideline on TRD suggests ketamine as augmentation to antidepressants. A US guideline on PTSD does not suggest the use of ketamine as therapy.&#x0D; The patient contributor CADTH engaged for this review highlighted the benefits, stigma, and barriers of ketamine therapy, including financial implications.&#x0D; &#x0D; What Does This Mean?&#x0D; &#x0D; There is some clinical effectiveness and cost-effectiveness evidence and a guideline recommendation to support the short-term use of ketamine in adults with TRD.&#x0D; Clinical effectiveness evidence and a guideline recommendation do not support the use of ketamine in adults with PTSD.&#x0D; Future research is necessary to understand the effectiveness and safety of ketamine as therapy for TRD in larger populations over longer periods and for PTSD for any follow-up duration.&#x0D; Decision-makers should consider offering ketamine in an equitable manner.&#x0D;

Effects of ketamine on rat social behavior as analyzed by DeepLabCut and SimBA deep learning algorithms.

Traditional methods of rat social behavior assessment are extremely time-consuming and susceptible to the subjective biases. In contrast, novel digital techniques allow for rapid and objective measurements. This study sought to assess the feasibility of implementing a digital workflow to compare the effects of (R,S)-ketamine and a veterinary ketamine preparation Vetoquinol (both at 20mg/kg) on the social behaviors of rat pairs. Historical and novel videos were used to train the DeepLabCut neural network. The numerical data generated by DeepLabCut from 14 video samples, representing various body parts in time and space were subjected to the Simple Behavioral Analysis (SimBA) toolkit, to build classifiers for 12 distinct social and non-social behaviors. To validate the workflow, previously annotated by the trained observer historical videos were analyzed with SimBA classifiers, and regression analysis of the total time of social interactions yielded R 2 = 0.75, slope 1.04; p < 0.001 (N = 101). Remarkable similarities between human and computer annotations allowed for using the digital workflow to analyze 24 novel videos of rats treated with vehicle and ketamine preparations. Digital workflow revealed similarities in the reduction of social behavior by both compounds, and no substantial differences between them. However, the digital workflow also demonstrated ketamine-induced increases in self-grooming, increased transitions from social contacts to self-grooming, and no effects on adjacent lying time. This study confirms and extends the utility of deep learning in analyzing rat social behavior and highlights its efficiency and objectivity. It provides a faster and objective alternative to human workflow.

Rapid-acting antidepressant drugs modulate affective bias in rats.

How rapid-acting antidepressants (RAADs), such as ketamine, induce immediate and sustained improvements in mood in patients with major depressive disorder (MDD) is poorly understood. A core feature of MDD is the prevalence of cognitive processing biases associated with negative affective states, and the alleviation of negative affective biases may be an index of response to drug treatment. Here, we used an affective bias behavioral test in rats, based on an associative learning task, to investigate the effects of RAADs. To generate an affective bias, animals learned to associate two different digging substrates with a food reward in the presence or absence of an affective state manipulation. A choice between the two reward-associated digging substrates was used to quantify the affective bias generated. Acute treatment with the RAADs ketamine, scopolamine, or psilocybin selectively attenuated a negative affective bias in the affective bias test. Low, but not high, doses of ketamine and psilocybin reversed the valence of the negative affective bias 24 hours after RAAD treatment. Only treatment with psilocybin, but not ketamine or scopolamine, led to a positive affective bias that was dependent on new learning and memory formation. The relearning effects of ketamine were dependent on protein synthesis localized to the rat medial prefrontal cortex and could be modulated by cue reactivation, consistent with experience-dependent neural plasticity. These findings suggest a neuropsychological mechanism that may explain both the acute and sustained effects of RAADs, potentially linking their effects on neural plasticity with affective bias modulation in a rodent model.

Effect of Ketamine versus Dexmedetomidine on Release of Inflammatory Mediators in Laparoscopic Hysterectomy. A Randomized Trial

Background: Surgery and anesthesia are sources of patients' stress and release of inflammatory mediators that have adverse effects on wound healing and remote organs. Objectives: To compare the effects of dexmedetomidine and ketamine on perioperative serum levels of inflammatory biomarkers (interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and C-reactive protein (CRP). Methods: We included 75 patients aged 30-60, ASA I and II, and scheduled for laparoscopic hysterectomy. Randomized patients received either intraoperative ketamine (bolus dose 0.25mg/kg then continuous infusion of 250µg/kg/h), dexmedetomidine (1µg/kg bolus dose then continuous infusion of 0.5µg/kg/h), or placebo. The primary outcome was to measure perioperative inflammatory biomarkers. Hemodynamic parameters, Recovery time, and complications were secondary outcomes. Results: At 6 and 24 hours, IL-6 significantly increased in the control group versus ketamine and dexmedetomidine groups (113.4±14.1,107.4±13.7;50.1± 8.1,48.2± 8.1;47.7±7.1, 46.01±7.1;p&lt;0.001). Similarly, At 6 and 24 hours, TNF-α significantly increased in the control group versus ketamine and dexmedetomidine groups (81.8±18.6,72.7±16.4; 40.6±7.1, 39.2±6.9;41.6± 7.6,39.9±7.6;p&lt;0.001).The same for CRP (17.4±3.6,40.0±6.0;10.2±1.3,16.2± 1.2;10.9±1.8,16.3±1.9;p&lt;0.001). Regarding hemodynamic parameters, there were significant increases in the ketamine group and decreases in the dexmedetomidine group compared to baseline. Recovery time was significantly longer in the ketamine group than in the control and dexmedetomidine group (24.3±6.4,12.6±2.0,13.5±3.3 min, respectively; P&lt;0.001). There were no significant differences between the three groups regarding agitation, nausea, and vomiting (P=1,0.126,0.776, respectively). Conclusion: Both dexmedetomidine and ketamine could attenuate the inflammatory response. However, dexmedetomidine has a shorter recovery time. Trial Registry No Trial registry at Pan African Clinical Trials Registry. The number is (PACTR201910617459894: date of registration 10/24/2019). URL https://pactr.samrc.ac.za/TrialDisplay.aspx?TrialID=9479).

The Electrographic Effects of Ketamine on Patients With Refractory Status Epilepticus After Cardiac Arrest: A Single-Center Retrospective Cohort.

To investigate the effects of ketamine on patients with refractory status epilepticus after cardiac arrest. In this retrospective cohort, selected EEG segments from patients after cardiac arrest were classified into different EEG patterns (based on background continuity and burden of epileptiform discharges) and spectral profiles (based on the presence of frequency components). For patients who received ketamine, EEG data were compared before, during, and after ketamine infusion; for the no-ketamine group, EEG data were compared at three separated time points during recording. Ketamine usage was determined by clinical providers. Electrographic improvement in epileptiform activity was scored, and the odds ratio was calculated using the Fisher exact test. Functional outcome measures at time of discharge were also examined. Of a total of 38 patients with postcardiac arrest refractory status epilepticus, 13 received ketamine and 25 did not. All patients were on ≥2 antiseizure medications including at least one sedative infusion (midazolam). For the ketamine group, eight patients had electrographic improvement, compared with only two patients in the no-ketamine group, with an odds ratio of 7.19 (95% confidence interval 1.16-44.65, P value of 0.0341) for ketamine versus no ketamine. Most of the patients who received ketamine had myoclonic status epilepticus, and overall neurologic outcomes were poor with no patients having a favorable outcome. For postarrest refractory status epilepticus, ketamine use was associated with electrographic improvement, but with the available data, it is unclear whether ketamine use or EEG improvement can be linked to better functional recovery.

The dynamic strategy shifting task: Optimisation of an operant task for assessing cognitive flexibility in rats.

Although schizophrenia is associated with a broad range of symptoms including hallucinations, delusions, and reduced motivation, measures of cognitive dysfunction, including cognitive flexibility and executive function, are the strongest predictors of functional outcomes. Antipsychotic medications are useful for reducing psychotic symptoms, but they are ineffective at improving cognitive deficits. Despite extensive investment by industry, the transition from preclinical to clinical trials has not been successful for developing precognitive medications for individuals with schizophrenia. Here, we describe the optimisation of a novel dynamic strategy shifting task (DSST) using standard operant chambers to investigate the optimal stimuli required to limit the extensive training times required in previous tasks. We determined that optimal learning by male and female Sprague Dawley rats for the flexibility task incorporated dynamic strategy shifts between spatial rules, such as following a visual cue or responding at one location, and non-spatial rules, such as responding to a central visual or auditory cue. A minimum of 6 correct consecutive responses were required to make a within-session change in the behavioural strategies. As a proof of concept, we trained and tested 84 Sprague Dawley rats on the DSST, and then assessed their cognitive flexibility using a within-subject design after an acute dose of ketamine (0, 3, 10 mg/kg). Rats made fewer premature and more perseverant responses to initiate a trial following ketamine. The effects of ketamine on trials to criterion was dependent on the rule. Ketamine induced a significant improvement on the reversal of a non-spatial visual discrimination rule. There was no significant effect of ketamine on the spatial visual or response discrimination rules. The DSST is a novel assay for studying distinct forms of cognitive flexibility and offers a rapid and adaptable means of assessing the ability to shift between increasingly challenging rule conditions. The DSST has potential utility in advancing our understanding of cognitive processes and the underlying neurobiological mechanisms related to flexibility in neuropsychiatric and neurological conditions where executive dysfunctions occur.>.

Efficacy of ketamine and thiopentone sodium with modified electroconvulsive therapy in depressive disorder: An observational study

Background: The first-line treatment for people with acute mania, mood disorders, severe depression, and catatonia is electroconvulsive therapy (ECT). The goal of anesthesia during ECT is to cause unconsciousness, and the drugs administered should not have any effect on seizures. Because all anesthetics have some ability to change seizures, the kind of anesthetic used in modified ECT becomes crucial. This study aimed to assess the hemodynamic profile during modified ECT and the effects of ketamine and thiopentone sodium on seizure duration. Aims and Objectives: The aim of the study was to compare the outcome of ECT, such as hemodynamics, improvement in depression, and duration of seizure, with ketamine versus thiopentone sodium in depressive disorder. Materials and Methods: A prospective observational study was conducted with 50 randomly selected depression patients after obtaining permission from the Institutional Ethics Committee and consent from the patients and attendants from June 2021 to November 2022. All 50 cases were equally divided into group K and group T. To obtain the data, a predesigned, semi-structured questionnaire was used along with the Hamilton rating scale for depression and ECT. The Chi-square test was used to measure the association between two categorical variables. A P &lt; 0.05 was considered statistically significant. Results: The mean heart rate, systolic blood pressure, diastolic blood pressure, mean arterial pressure, and saturation of peripheral oxygen are higher in group K than in group T, and the mean difference was significant between group K and group T. Groups had a statistically significant association with increased secretions, nausea and vomiting, and headache, but not with gender, ASA grade, and number of ECT sessions. Conclusion: Compared to ketamine, thiopentone sodium was found to have minimal hemodynamic derangements, a decrease in seizure duration, and side effects.

Effects of ketamine on penile tissues in an experimental priapism model in rats.

This study aimed to evaluate the histopathological and biochemical effects of ketamine on penile tissues following ischemia-reperfusion injury induced by priapism. Twenty-four male rats were randomized into three groups. Group 1 served as the control group. Group 2 underwent the priapism model to induce ischemia-reperfusion injury. Group 3, the treatment group, experienced a similar ischemia-reperfusion model as Group 2; additionally, 50 mg/kg of ketamine was administered intraperitoneally just before reperfusion. Blood biochemical analyses and penile histopathological evaluations were performed. In Group 3, significant improvements were observed in all histopathological scores, including desquamation, edema, inflammation, and vasocongestion compared to Group 2 (p<0.001). Blood biochemical analyses showed that the malondialdehyde (MDA) levels were recorded as 10 in Group 2, with a significant decrease in Group 3 (p=0.013). Similarly, proinflammatory cytokine levels, including interleukin-1 beta (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α), were found to be suppressed in Group 3 compared to Group 2 (p=0.003, p=0.022, and p=0.028, respectively). Antioxidant enzyme activities, such as glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD), were higher in Group 3 compared to Group 2 (p=0.016 and p=0.024, respec-tively). Ketamine is an effective anesthetic agent in alleviating the effects of penile ischemia-reperfusion injury.

Effects of ketamine, propofol and isoflurane on electrocardiographic variables in clinically healthy dogs premedicated with medetomidine and midazolam.

The purpose of this study was to investigate the effects of three anesthetic agents, with premedication of medetomidine and midazolam, on electrocardiographic variables in dogs. Ten adult mixed breed dogs were used in a crossover design study, where they received ketamine, propofol and isoflurane treatments with a one-week washout period between them. In all three groups, medetomidine was administered first followed by midazolam after 15 min. Then, after 20 min, group 1 received ketamine intravenously (IV), group 2 received propofol (IV), and group 3 received isoflurane (inhalation). In all dogs, electrocardiographs were taken before and after premedication's, as well as every 15 min during anesthesia. Medetomidine significantly decreased heart rate and P wave amplitude and increased PR interval, R wave amplitude, QT interval, and T wave amplitude. Midazolam increased the amplitude of the R and T waves. Ketamine increased the heart rate and PR interval. Propofol increased the heart rate for up to 15 min, decreased the PR interval for up to 30 min, and the QT interval for up to 45 min. Isoflurane increased the heart rate and decreased the amplitude of R and T waves. The results showed that the drugs used in this study did not have many side effects on electrocardiographic variables and could be used without serious concern. The most important side effects observed were a severe reduction in heart rate and 1st degree atrioventricular (AV) block and, to a lesser extent, 2nd degree AV block caused by medetomidine and midazolam which were masked by the anesthetics.

Antipsychotic Activity of Ethanolic Extracts of Crinum asiaticum and Crinum defixum in Animal Models.

The current study examined the antipsychotic properties of ethanolic extracts of Crinum asiaticum (EECA) and Crinum defixum (EECD). The effects of the extracts on rodents' ketamine-induced hyperactivity, amphetamine-induced stereotypy, forced swim test, conditioned avoidance response, and catalepsy were assessed. According to the findings, EECA and EECD both significantly outperformed typical antipsychotic medications in antipsychotic-like behaviours across a variety of behavioural paradigms. The extracts exhibited a 50-75% reduction in ketamine-induced hyperactivity, indicating a possible impact on glutamatergic signalling. Additionally, they greatly reduced amphetamine-induced stereotypy, suggesting a potential antagonistic interaction with the dopamine D2 receptor. Similar to haloperidol, EECD at 400 mg/kg dramatically decreased avoidance behaviour in the conditioned avoidance response test. Though less so than with haloperidol, both extracts caused catalepsy in rodents. The reversal of ketamine's effect in the forced swim test suggests that it may be effective in preventing psychosis's negative symptoms. Given that oxidative stress is a contributing factor to psychotic disorders, the antipsychotic effect of these extracts may be associated with their anti-inflammatory and antioxidant characteristics. These results bolster the long-standing usage of Crinum species in the treatment of mental illnesses and imply that they could be rich sources of new antipsychotic chemicals. To determine the active ingredients, clarify the mechanisms of action, and assess the safety and effectiveness of clinical trials, more study is necessary.

Ketamine in the Management of Acute Pain: A Comprehensive Meta-Analysis.

This review was conducted to find the effectiveness and safety of ketamine in managing acute or sudden pain in the emergency scenarios. The research was carried out using databases such as PubMed, MEDLINE, Cochrane trial registries, and EMBASE from inception up to July 2022. The meta-analysis employed using the random-effects model and presented results as pooled standardised mean difference (SMD) and risk ratio (RR) alongside their 95% confidence intervals (CIs). The pooled SMD for pain assessment within 15 minutes stood at -0.72 (95% CI: -1.55 to 0.12). At 30 minutes, SMD was -0.27 (95% CI: -0.48 to -0.05), and by 45 minutes, it was -0.04 (95% CI: -0.26 to 0.18). Between the 45-minute and 60-minute mark, the SMD was -0.03 (95% CI: -0.22 to 0.17), and after the 60-minute interval, it was registered at 0.11 (95% CI: -0.10 to 0.22). Pooled RR reflecting the requirement for supplementary analgaesics was 0.96 (95% CI: 0.65-1.41). The study found that ketamine's efficacy and safety were comparable or even superior to opioids in addressing sudden pain in the emergency contexts. Key Words: Ketamine, Meta-analysis, Opioids, Acute pain, Emergency.

Patient-reported outcomes on sleep quality and circadian rhythm during treatment with intravenous ketamine for treatment-resistant depression.

Intravenous (IV) ketamine is a rapid acting antidepressant used primarily for treatment-resistant depression (TRD). It has been suggested that IV ketamine's rapid antidepressant effects may be partially mediated via improved sleep and changes to the circadian rhythm. This study explores IV ketamine's association with changes in patient-reported sleep quality and circadian rhythm in an adult population with TRD. Adult patients (18-64 years) with TRD scheduled for IV ketamine treatment were recruited to complete patient rated outcomes measures on sleep quality using the Pittsburgh Sleep Quality Index (PSQI) and circadian rhythm using the Morningness-Eveningness Questionnaire (MEQ). Over a 4-week course of eight ketamine infusions, reports were obtained at baseline (T0), prior to second treatment (T1), prior to fifth treatment (T2), and 1 week after eighth treatment (T3). Forty participants with TRD (mean age = 42.8, 45% male) were enrolled. Twenty-nine (72.5%) had complete follow-up data. Paired t tests revealed statistically significant improvements at the end of treatment in sleep quality (PSQI) (p = 0.003) and depressive symptoms (Clinically Useful Depression Outcome Scale-Depression, p < 0.001) while circadian rhythm (MEQ) shifted earlier (p = 0.007). The PSQI subscale components of sleep duration (p = 0.008) and daytime dysfunction (p = 0.001) also improved. In an exploratory post hoc analysis, ketamine's impact on sleep quality was more prominent in patients with mixed features, while its chronobiotic effect was prominent in those without mixed features. IV ketamine may improve sleep quality and advance circadian rhythm in individuals with TRD. Effects may differ in individuals with mixed features of depression as compared to those without. Since this was a small uncontrolled study, future research is warranted.

Predicting treatment response to ketamine in treatment-resistant depression using auditory mismatch negativity: Study protocol.

Ketamine has recently attracted considerable attention for its rapid effects on patients with major depressive disorder, including treatment-resistant depression (TRD). Despite ketamine's promising results in treating depression, a significant number of patients do not respond to the treatment, and predicting who will benefit remains a challenge. Although its antidepressant effects are known to be linked to its action as an antagonist of the N-methyl-D-aspartate (NMDA) receptor, the precise mechanisms that determine why some patients respond and others do not are still unclear. This study aims to understand the computational mechanisms underlying changes in the auditory mismatch negativity (MMN) response following treatment with intravenous ketamine. Moreover, we aim to link the computational mechanisms to their underlying neural causes and use the parameters of the neurocomputational model to make individual treatment predictions. This is a prospective study of 30 patients with TRD who are undergoing intravenous ketamine therapy. Prior to 3 out of 4 ketamine infusions, EEG will be recorded while patients complete the auditory MMN task. Depression, suicidality, and anxiety will be assessed throughout the study and a week after the last ketamine infusion. To translate the effects of ketamine on the MMN to computational mechanisms, we will model changes in the auditory MMN using the hierarchical Gaussian filter, a hierarchical Bayesian model. Furthermore, we will employ a conductance-based neural mass model of the electrophysiological data to link these computational mechanisms to their neural causes. The findings of this study may improve understanding of the mechanisms underlying response and resistance to ketamine treatment in patients with TRD. The parameters obtained from fitting computational models to EEG recordings may facilitate single-patient treatment predictions, which could provide clinically useful prognostic information. Clinicaltrials.gov NCT05464264. Registered June 24, 2022.