Ketamine Group Research Articles

Peri-Operative Use of Ketamine Infusion versus Dexmedetomidine Infusion for Analgesia in Obese Patients Undergoing Bariatric Surgery: A Double-Blinded Three-Armed Randomized Controlled Trial

Abstract Background The development of different techniques in bariatric surgeries has required the development of novel anesthetic techniques to reduce the incidence of complications and improve post-operative patient outcomes. Ketamine and dexmedetomidine have been used for their peri-operative analgesic profiles in different studies. Methods Ninety patients were studied and randomized equally into three groups. The Ketamine group received a bolus dose (0.3 mg/kg) of ketamine over 10 min followed by an infusion (0.3 mg/kg/h). The Dexmedetomidine group received a bolus dose (0.5 mcg/kg) of dexmedetomidine over 10 min followed by an infusion (0.5 mcg/kg/h). The control group received normal saline infusion. The total morphine dose was the primary outcome, and intra-operative fentanyl requirements, time to extubation, post-operative nausea and vomiting (PONV), Numerical Rating Scale (NRS) scores, and Modified Observer’s Agitation/Sedation Scale (MOASS) scores were secondary outcomes of the study. Results The Dexmedetomidine group showed decreased intra-operative fentanyl requirements (160.000 ± 42.345 µcg), less time to extubation (3.700 ± 0.925 min), and better scores on MOASS than the other groups. Post-operative NRS scores and the morphine requirement in the Ketamine group (1.867 ± 2.921 mg) were lower than in the other groups. The Dexmedetomidine group showed the lowest scores for PONV. Conclusions The Dexmedetomidine group showed lower total fentanyl doses, a significantly shorter time to extubation, better MOASS scores, and lower PONV. The Ketamine group showed significantly lower NRS scores and morphine doses than the other two groups. Dexmedetomidine was effective on the reduction of intraoperative fentanyl requirement with early extubation, and ketamine was effective on the reduction of postoperative pain. Trial Registration This trial has been registered on clinicaltrials.gov registry (NCT04576975) since 06/10/2020.

Impact of Sub-Anesthetic Dose of Ketamine on Post Spinal Hypotension in Cesarean Delivery

Abstract Background Spinal anesthesia is the commonest technique used in Cesarean Section (CS) and most frequently associated with maternal hypotension, for whicha lot of techniques have been described to prevent but an effective method is yet to be found. Objectives The aim was to study the effect of using a sub-anesthetic dose of ketamine to prevent post-spinal hypotension in CS delivery. Methods This double-blinded randomized controlled study was conducted on 60 participating parturients who were ASA І, П term pregnant. All the parturients received spinal anesthesia. The parturients were then randomly divided into two equal groups (n = 30 in each); ketamine group received a sub- anesthetic dose of ketamine of 0.5 mg/kg IV bolus in 3 ml saline and control group received the same volume of normal saline IV bolus. Heart Rate (HR) and Mean Arterial blood Pressure (MAP) were recorded at baseline (5 minutes prior to the intrathecal injection), at 5, 10, 15 and 20 minutes after the injection and then every 15 minutes till the end of the operation. Incidences of hypotension and severe hypotension were recorded. The total dose of ephedrine was recorded. Modified Ramsay sedation score was recorded at baseline then 5, 10, 15, 30, 45 minutes after injection and then at the end of the operation. Results The study revealed that ketamine didn’t prevent hypotension, it only delayed it for 10 min compared to control group 5 min. Also, observed that total ephidren dose significantly decreased in ketamine group compared to control group. And sedation scores in the first 30 min were higher in ketamine group. HR wasn’t affected. No changes in APGAR score were noticed between the two groups. No side effects from ketamine except for nystagmus. Conclusion This study concluded that the use of intravenous ketamine in low dose (0.5mg/kg) doesn’t prevent postspinal hypotension but it only decreases ephidren requirements.

Ketamine vs Electroconvulsive Therapy for Treatment-Resistant Depression

The ELEKT-D: Electroconvulsive Therapy (ECT) vs Ketamine in Patients With Treatment Resistant Depression (TRD) (ELEKT-D) trial demonstrated noninferiority of intravenous ketamine vs ECT for nonpsychotic TRD. Clinical features that can guide selection of ketamine vs ECT may inform shared decision-making for patients with TRD. To evaluate whether selected clinical features were associated with differential improvement with ketamine vs ECT. This secondary analysis of an open-label noninferiority randomized clinical trial was a multicenter study conducted at 5 US academic medical centers from April 7, 2017, to November 11, 2022. Analyses for this study, which were not prespecified in the trial protocol, were conducted from May 10 to Oct 31, 2023. The study cohort included patients with TRD, aged 21 to 75 years, who were in a current nonpsychotic depressive episode of at least moderate severity and were referred for ECT by their clinicians. Eligible participants were randomized 1:1 to receive either 6 infusions of ketamine or 9 treatments with ECT over 3 weeks. Association between baseline factors (including 16-item Quick Inventory of Depressive Symptomatology Self-Report [QIDS-SR16], Montgomery-Asberg Depression Rating Scale [MADRS], premorbid intelligence, cognitive function, history of attempted suicide, and inpatient vs outpatient status) and treatment response were assessed with repeated measures mixed-effects model analyses. Among the 365 participants included in this study (mean [SD] age, 46.0 [14.5] years; 191 [52.3%] female), 195 were randomized to the ketamine group and 170 to the ECT group. In repeated measures mixed-effects models using depression levels over 3 weeks and after false discovery rate adjustment, participants with a baseline QIDS-SR16 score of 20 or less (-7.7 vs -5.6 points) and those starting treatment as outpatients (-8.4 vs -6.2 points) reported greater reduction in the QIDS-SR16 with ketamine vs ECT. Conversely, those with a baseline QIDS-SR16 score of more than 20 (ie, very severe depression) and starting treatment as inpatients reported greater reduction in the QIDS-SR16 earlier in course of treatment (-8.4 vs -6.7 points) with ECT, but scores were similar in both groups at the end-of-treatment visit (-9.0 vs -9.9 points). In the ECT group only, participants with higher scores on measures of premorbid intelligence (-14.0 vs -11.2 points) and with a comorbid posttraumatic stress disorder diagnosis (-16.6 vs -12.0 points) reported greater reduction in the MADRS score. Those with impaired memory recall had greater reduction in MADRS during the second week of treatment (-13.4 vs -9.6 points), but the levels of MADRS were similar to those with unimpaired recall at the end-of-treatment visit (-14.3 vs -12.2 points). Other results were not significant after false discovery rate adjustment. In this secondary analysis of the ELEKT-D randomized clinical trial of ECT vs ketamine, greater improvement in depression was observed with intravenous ketamine among outpatients with nonpsychotic TRD who had moderately severe or severe depression, suggesting that these patients may consider ketamine over ECT for TRD.

Use of Early Ketamine Sedation and Association With Clinical and Cost Outcomes Among Mechanically Ventilated Patients With COVID-19: A Retrospective Cohort Study.

To describe the utilization of early ketamine use among patients mechanically ventilated for COVID-19, and examine associations with in-hospital mortality and other clinical outcomes. Retrospective cohort study. Six hundred ten hospitals contributing data to the Premier Healthcare Database between April 2020 and June 2021. Adults with COVID-19 and greater than or equal to 2 consecutive days of mechanical ventilation within 5 days of hospitalization. The exposures were early ketamine use initiated within 2 days of intubation and continued for greater than 1 day. Primary was hospital mortality. Secondary outcomes included length of stay (LOS) in the hospital and ICUs, ventilator days, vasopressor days, renal replacement therapy (RRT), and total hospital cost. The propensity score matching analysis was used to adjust for confounders. Among 42,954 patients, 1,423 (3.3%) were exposed to early ketamine use. After propensity score matching including 1,390 patients in each group, recipients of ketamine infusions were associated with higher hospital mortality (52.5% vs. 45.9%, risk ratio: 1.14, [1.06-1.23]), longer median ICU stay (13 vs. 12 d, mean ratio [MR]: 1.15 [1.08-1.23]), and longer ventilator days (12 vs. 11 d, MR: 1.19 [1.12-1.27]). There were no associations for hospital LOS (17 [10-27] vs. 17 [9-28], MR: 1.05 [0.99-1.12]), vasopressor days (4 vs. 4, MR: 1.04 [0.95-1.14]), and RRT (22.9% vs. 21.7%, RR: 1.05 [0.92-1.21]). Total hospital cost was higher (median $72,481 vs. $65,584, MR: 1.11 [1.05-1.19]). In a diverse sample of U.S. hospitals, about one in 30 patients mechanically ventilated with COVID-19 received ketamine infusions. Early ketamine may have an association with higher hospital mortality, increased total cost, ICU stay, and ventilator days, but no associations for hospital LOS, vasopressor days, and RRT. However, confounding by the severity of illness might occur due to higher extracorporeal membrane oxygenation and RRT use in the ketamine group. Further randomized trials are needed to better understand the role of ketamine infusions in the management of critically ill patients.

Ketamine as a treatment of stress-induced maternal depression in mice: effects on offspring behaviour

Maternal depression during pregnancy adversely affects offspring neurodevelopment and behaviour. Typical antide-pressants like selective serotonin reuptake inhibitors have limitations due to risks of crossing the placenta. Ketamine has emerged as a promising alternative treatment. This research examined ketamine's effects on offspring of mater¬nally stressed mice. Dams were divided into control, maternal adversity, fluoxetine, and ketamine groups. Open field, sucrose preference, elevated plus maze, and forced swim tests assessed offspring anxiety, anhedonia, and despair. Maternal adversity increased anxiety-like behaviours and ketamine or fluoxetine reversed some effects. However, fluoxetine more effectively mitigated despair in forced swim tests. Ketamine moderately alleviated anhedonia versus controls. Further research on dose-response and timing is needed to optimize ketamine treatment. Mitigating maternal depression is crucial for preventing maladaptive offspring neurobehavioral trajectories.

Negative emotionality shapes the modulatory effects of ketamine and lamotrigine in subregions of the anterior cingulate cortex

Neuroimaging studies have identified the anterior cingulate cortex (ACC) as one of the major targets of ketamine in the human brain, which may be related to ketamine’s antidepressant (AD) mechanisms of action. However, due to different methodological approaches, different investigated populations, and varying measurement timepoints, results are not consistent, and the functional significance of the observed brain changes remains a matter of open debate. Inhibition of glutamate release during acute ketamine administration by lamotrigine provides the opportunity to gain additional insight into the functional significance of ketamine-induced brain changes. Furthermore, the assessment of trait negative emotionality holds promise to link findings in healthy participants to potential AD mechanisms of ketamine. In this double-blind, placebo-controlled, randomized, single dose, parallel-group study, we collected resting-state fMRI data before, during, and 24 h after ketamine administration in a sample of 75 healthy male and female participants who were randomly allocated to one of three treatment conditions (ketamine, ketamine with lamotrigine pre- treatment, placebo). Spontaneous brain activity was extracted from two ventral and one dorsal subregions of the ACC. Our results showed activity decreases during the administration of ketamine in all three ACC subregions. However, only in the ventral subregions of the ACC this effect was attenuated by lamotrigine. 24 h after administration, ACC activity returned to baseline levels, but group differences were observed between the lamotrigine and the ketamine group. Trait negative emotionality was closely linked to activity changes in the subgenual ACC after ketamine administration. These results contribute to an understanding of the functional significance of ketamine effects in different subregions of the ACC by combining an approach to modulate glutamate release with the assessment of multiple timepoints and associations with trait negative emotionality in healthy participants.

Antagonistic interaction between caffeine and ketamine in zebrafish: Implications for aquatic toxicity

The coexistence of caffeine (CF) and ketamine (KET) in surface waters across Asia has been widely reported. Previous studies have implied that CF and KET may share a mechanism of action. However, the combined toxicity of these two chemicals on aquatic organisms remains unclear at environmental levels, and the underlying mechanisms are not well understood. Here we demonstrate that KET antagonizes the adverse effects of CF on zebrafish larvae by modulating the gamma-aminobutyric acid (GABA)ergic synapse pathway. Specifically, KET (10–250 ng L−1) ameliorates the locomotor hyperactivity and impaired circadian rhythms in zebrafish larvae induced by 2 mg L−1 of CF, showing a dose-dependent relationship. Additionally, the developmental abnormalities in zebrafish larvae exposed to CF are mitigated by KET, with an incidence rate reduced from 26.7% to 6.7%. The competition between CF and KET for binding sites on the GABA-A receptor (in situ and in silico) elucidates the antagonistic interactions between the two chemicals. Following a seven-day recovery period, the adverse outcomes of CF exposure persist in the fish, whereas the changes observed in the CF + KET groups are significantly alleviated, especially with KET at 10 ng L−1. Based on these results, it is imperative to further assess the environmental risks associated with CF and KET co-pollution. This pilot study underscores the utility of systems toxicology approaches in estimating the combined toxicity of environmental chemicals on aquatic organisms. Moreover, the nighttime behavioral functions of fish could serve as a sensitive biomarker for evaluating the toxicity of psychoactive substances.

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

BackgroundPostoperative 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.MethodsIn 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.ResultsThe 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.ConclusionAdministering 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.

Monitored Anesthesia Care (MAC) as an Alternative to General Anesthesia (GA): Prospective Double-Blinded Randomized Controlled Study Comparing Efficacy and Safety of Dexmedetomidine and Ketamine Infusions with Ultrasonography (USG) Guided Pectoral Nerve Block (PECs) for Postoperative Analgesia in Breast Surgery.

PECs blocks are usually combined for breast surgery under general anesthesia (GA) to provide postoperative analgesia rather than primary anesthesia technique. A prospective, interventional, single-center, double-blind, randomized, parallel-group, active-controlled, Helsinki protocol-compliant clinical study was conducted in a tertiary care teaching center after obtaining the Ethics Committee's approval and patients' written informed consent. Forty-eight American Society of Anesthesiologists physical status I/II patients aged 18-60 years, undergoing elective unilateral breast surgery were enrolled. Patients were block-randomized (computer-generated) to two equal groups (24 patients each), with one of them receiving Dexmedetomidine and the other one Ketamine. For concealment, sequentially numbered, sealed, opaque envelopes were used. The study was double-blinded for both the anesthesiologist and outcome assessor anesthesiologist. Obese patients (body mass index > 30), those with infection at block site, coagulopathy and known hypersensitivity to local anesthetics or study medications as well as individuals who refused participation in research were all excluded. The Dexmedetomidine group received a bolus of 0.5 mcg/kg over ten minutes, followed by an infusion of 0.3 mcg/kg/hour, while the Ketamine group received a bolus of 0.5 mg/kg over ten minutes, followed by an infusion of 0.3 mg/kg/hour. Postoperative analgesia was compared using a visual analogue scale (VAS) at regular intervals. When VAS exceeded four, 1 mg/kg intravenous Pethidine was administered as a rescue analgesic. Sub-anesthetic low-dose Ketamine was more effective than low-dose Dexmedetomidine in prolonging PECs block analgesia, which was statistically significant (p value < 0.001). The Ketamine group had lower rescue analgesic Pethidine consumption and longer first-rescue analgesia demand time. There was no significant hemodynamic difference between the study groups. Ketamine was more efficient than Dexmedetomidine for postoperative analgesia.

Effects of ketamine on the severity of depression and anxiety following postoperative mechanical ventilation: a single-blind randomized clinical trial in Iran.

In this study, we compare the effects of ketamine and the combination of midazolam and morphine on the severity of depression and anxiety in mechanically ventilated patients after discharge from the intensive care unit (ICU). This randomized single-blind clinical trial included 50 patients who were candidates for craniotomy and postoperative mechanical ventilation in the ICU of 5 Azar Teaching Hospital in Gorgan City, North Iran, from 2021 to 2022. Patients were allocated to two groups by quadruple block randomization. In group A, 0.5 mg/kg of ketamine was infused over 15 minutes after craniotomy and then continued at a dose of 5 µ/kg/min during mechanical ventilation. In group B, midazolam was infused at a dose of 2-3 mg/hr and morphine at a dose of 3-5 mg/hr. After patients were discharged from the ICU, if their Glasgow Coma Scale scores were ≥14, Beck's anxiety and depression inventories were completed by a psychologist within 2 weeks, 2 months, and 6 months after discharge. The mean scores of depression at 2 months (P=0.01) and 6 months (P=0.03) after discharge were significantly lower in the ketamine group than in the midazolam and morphine group. The mean anxiety scores were significantly lower in the ketamine group 2 weeks (P=0.006) and 6 months (P=0.002) after discharge. Ketamine is an effective drug for preventing and treating anxiety and depression over the long term in patients discharged from the ICU. However, further larger volume studies are required to validate these results.

Impact of Continuous Infusion Ketamine Compared to Continuous Infusion Benzodiazepines on Delirium in the Intensive Care Unit.

Purpose: The purpose of this study was to evaluate rates of delirium or coma-free days between continuous infusion sedative-dose ketamine and continuous infusion benzodiazepines in critically ill patients. Materials and Methods: In this single-center, retrospective cohort adult patients were screened for inclusion if they received continuous infusions of either sedative-dose ketamine or benzodiazepines (lorazepam or midazolam) for at least 24 h, were mechanically ventilated for at least 48 h and admitted to the intensive care unit of a large quaternary academic center between 5/5/2018 and 12/1/2021. Results: A total of 165 patients were included with 64 patients in the ketamine group and 101 patients in the benzodiazepine group (lorazepam n = 35, midazolam n = 78). The primary outcome of median (IQR) delirium or coma-free days within the first 28 days of hospitalization was 1.2 (0.0, 3.7) for ketamine and 1.8 (0.7, 4.6) for benzodiazepines (p = 0.13). Patients in the ketamine arm spent a significantly lower proportion of time with RASS -3 to +4, received significantly higher doses and longer durations of propofol and fentanyl infusions, and had a significantly longer intensive care unit length of stay. Conclusions: The use of sedative-dose ketamine had no difference in delirium or coma-free days compared to benzodiazepines.

Impact of Prolonged Continuous Ketamine Infusions in Critically Ill Children: A Prospective Cohort Study.

Ketamine has been considered as an adjunct for children who do not reach their predefined target sedation depth. However, there is limited evidence regarding the use of ketamine as a prolonged infusion (i.e., >24hours) in the pediatric intensive care unit (PICU). We sought to evaluate the safety and effectiveness of continuous ketamine infusion for >24hours in mechanically ventilated children. We conducted a prospective cohort study in a tertiary PICU from January 2020 to December 2022. The primary outcome was the incidence of adverse events (AEs) after ketamine initiation. The secondary outcome included assessing the median proportion of time the patient spent on the Richmond Agitation-Sedation Scale (RASS) goal after ketamine infusion. Patients were also divided into two groups based on the sedative regimen, ketamine-based or non-ketamine-based, to assess the incidence of delirium. A total of 269 patients were enrolled: 73 in the ketamine group and 196 in the non-ketamine group. The median infusion rate of ketamine was 1.4mg/kg/h. Delirium occurred in 16 (22%) patients with ketamine and 15 (7.6%) patients without ketamine (p=0.006). After adjusting for covariates, logistic regression showed that delirium was associated with comorbidities (odds ratio [OR] 4.2), neurodevelopmental delay (OR 0.23), fentanyl use (OR 7.35), and ketamine use (OR 4.17). Thirty-one (42%) of the patients experienced at least one AE following ketamine infusion. Other AEs likely related to ketamine were hypertension (n=4), hypersecretion (n=14), tachycardia (n=6), and nystagmus (n=2). There were no significant changes in hemodynamic variables 24h after the initiation of ketamine. Regarding the secondary outcomes, patients were at their goal RASS level for a median of 76% (range 68-80.5%) of the time in the 24hours before ketamine initiation, compared with 84% (range 74.5-90%) of the time during the 24 h after ketamine initiation (p<0.001). The infusion rate of ketamine did not significantly affect concomitant analgesic and sedative infusions. The ketamine group experienced a longer duration of mechanical ventilation and a longer length of stay in the PICU and hospital than the non-ketamine group. The use of ketamine infusion in PICU patients may be associated with an increased rate of adverse events, especially delirium. High-quality studies are needed before ketamine can be broadly recommended or adopted earlier in the sedation protocol.

Rapid Antidepressant-Like Potential of Chaihu Shugan San Depends on Suppressing Glutamate Neurotransmission and Activating Synaptic Proteins in Hippocampus of Female Mice.

To explore the rapid antidepressant potential and the underlying mechanism of Chaihu Shugan San (CSS) in female mice. Liquid chromatography mass spectrometry (LC-MS)/MS was used to determine the content of main components in CSS to determine its stability. Female C57BL/6J mice were randomly divided into 4 groups, including control (saline), vehicle (saline), CSS (4 g/kg) and ketamine (30 mg/kg) groups. Mice were subjected to irregular stress stimulation for 4 weeks to establish the chronic mild stress (CMS) model, then received a single administration of drugs. Two hours later, the behavioral tests were performed, including open field test, tail suspension test (TST), forced swimming test (FST), novelty suppression feeding test (NSF), and sucrose preference test (SPT). Western blot analysis was used to detect the expression levels of N-methyl-D-aspartate receptor (NMDA) subtypes [N-methyl-D-aspartate receptor 1 (NR1), NR2A, NR2B], synaptic proteins [synapsin1 and post synaptic density protein 95 (PSD95)], and brain-derived neurotrophic factor (BDNF). Moreover, the rapid antidepressant effect of CSS was tested by pharmacological technologies and optogenetic interventions that activated glutamate receptors, NMDA. Compared with the vehicle group, a single administration of CSS (4 g/kg) reversed all behavioral defects in TST, FST, SPT and NSF caused by CMS (P<0.05 or P<0.01). CSS also significantly decreased the expressions of NMDA subtypes (NR1, NR2A, NR2B) at 2 h in hippocampus of mice (all P<0.01). In addition, similar to ketamine, CSS increased levels of synaptic proteins and BDNF (P<0.05 or P<0.01). Furthermore, the rapid antidepressant effects of CSS were blocked by transient activation of NMDA receptors in the hippocampus (all P<0.01). Rapid antidepressant effects of CSS by improving behavioral deficits in female CMS mice depended on rapid suppression of NMDA receptors and activation of synaptic proteins.

Continuous Infusion of Ketamine in Mechanically Ventilated Patients with SARS-CoV-2.

Widespread drug shortages led to higher utilization of ketamine in our intensive care unit, especially among patients with SARS-CoV-2. To evaluate the impact of continuous infusion of ketamine on vasopressor requirements in patients with SARS-CoV-2. This was a single-center, retrospective, cohort study comparing mechanically ventilated (MV), adult patients with SARS-CoV-2 receiving either propofol or ketamine for at least 72 hours. 84 patients (mean age of 61-year-old, 68% male) were analyzed. 31 patients received ketamine, and 53 patients received propofol. Mean vasopressor doses were not significantly different between ketamine and propofol groups at prespecified timepoints. However, mean arterial pressures (MAP) were higher in the ketamine group at 24 h, 48 h, and 96 h postsedative initiation. The median opioid infusion requirements were 3 vs. 12.5 mg/hr (p < 0.0001) for ketamine and propofol groups, respectively. Comparing to propofol, C-reactive protein (CRP) values were significantly lower in the ketamine group at 24 h (7.53 vs. 15.9 mg/dL, p=0.03), 48 h (5.23 vs. 14.1 mg/dL, p=0.0083), and 72 h (6.4 vs. 12.1 mg/dL, p=0.0085). In patients with SARS-CoV-2 on MV, there was no difference in the vasopressor requirement in patients receiving ketamine compared to propofol. Nevertheless, the use of ketamine was associated with higher MAP, reductions in CRP in select timepoints, and overall lower opioid requirements.

The effect of intraoperative low-dose ketamine versus dexmedetomidine infusion on postoperative bowel recovery in patients undergoing gastrointestinal malignancy surgeries: Placebo-controlled, randomized trial

Abstract Background and Aims: No studies have compared the effects of ketamine and dexmedetomidine on bowel recovery. We evaluated the effects of intraoperative low-dose ketamine or dexmedetomidine infusion on postoperative bowel recovery in patients undergoing gastrointestinal (GI) malignancy surgeries. Material and Methods: This placebo-controlled, randomized study was carried out in 84 American Society of Anesthesiologists II patients, aged 18–70 years, of either gender, undergoing elective open GI malignancy surgeries. Patients received intraoperative infusion of ketamine @ 0.1 mg kg-1 h-1 (KET), dexmedetomidine @ 0.25 μg kg-1 h-1 (DEX), or normal saline (placebo). Primary outcome was the time to first flatus and/or stool. Secondary outcomes included time to extubation, total analgesic requirement, postoperative pain scores, time to feeds, duration of intensive care unit (ICU) and hospital stay, and the incidence of adverse events. Continuous data were analyzed by the one-way analysis of variance (ANOVA) or the Kruskal–Wallis test. Categorical data were analyzed by the Chi-square test or the Fisher’s exact test. Results: Median time to passage of flatus and/or stool was 3 [interquartile range (IQR) 2–3] days in the KET group, 2 [IQR 2–3] days in the DEX group, and 2 [IQR 2–3] days in the placebo group (P = 0.53 for placebo vs. KET, 0.81 for placebo vs. DEX, and 0.99 for KET vs. DEX). Pain scores and analgesic consumption were significantly less in the intervention groups versus placebo (P &lt; 0.001). No difference was seen in other secondary outcomes. Conclusion: Low-dose ketamine or dexmedetomidine did not result in early bowel recovery despite lower pain scores and opioid consumption in patients undergoing open GI malignancy surgeries. Key Message: What is known: Ketamine and dexmedetomidine may promote bowel recovery by improving analgesia and decreasing opioid usage.Main findings: This randomized controlled trial found no evidence of earlier bowel recovery with ketamine or dexmedetomidine versus placebo despite lower pain scores and analgesic consumption in the ketamine and dexmedetomidine groups.

Preoperative ketamine administration for prevention of postoperative neurocognitive disorders after major orthopedic surgery in elderly patients: A multicenter randomized blinded placebo-controlled trial

BackgroundPreventive anesthetic impact on the high rates of postoperative neurocognitive disorders in elderly patients is debated. The Prevention of postOperative Cognitive dysfunction by Ketamine (POCK) study aimed to assess the effect of ketamine on this condition. MethodsThis is a multicenter, randomized, double-blind, interventional study. Patients ≥60 years undergoing major orthopedic surgery were randomly assigned in a 1:1 ratio to receive preoperative ketamine 0.5 mg/kg as an intravenous bolus (n = 152) or placebo (n = 149) in random blocks stratified according to the study site, preoperative cognitive status and age. The primary outcome was the proportion of objective delayed neurocognitive recovery (dNR) defined as a decline of one or more neuropsychological assessment standard deviations on postoperative day 7. Secondary outcomes included a three-month incidence of objective postoperative neurocognitive disorder (POND), as well as delirium, anxiety, and symptoms of depression seven days and three months after surgery. ResultsAmong 301 patients included, 292 (97%) completed the trial. Objective dNR occurred in 50 (38.8%) patients in the ketamine group and 54 (40.9%) patients in the placebo group (OR [95% CI] 0.92 [0.56; 1.51], p = 0.73) on postoperative day 7. Incidence of objective POND three months after surgery did not differ significantly between the two groups nor did incidence of delirium, anxiety, apathy, and fatigue. Symptoms of depression were less frequent in the ketamine group three months after surgery (OR [95% CI] 0.34 [0.13–0.86]). ConclusionsA single preoperative bolus of intravenous ketamine does not prevent the occurrence of dNR or POND in elderly patients scheduled for major orthopedic surgery. (Clinicaltrials.gov NCT02892916).

Ketamine Sedation Decreases Survival after Extremity Trauma and Moderate Hemorrhage in Rats

Objective: Traumatic hemorrhage (HEM) is often associated with pain. The use of ketamine (KET) has increased both on the battlefield and in civilian emergency care for analgesia and sedation. We have reported that an analgesic dose of KET does not impact cardiorespiratory responses or survival after HEM (JAP 130: 1583-1593, 2021). In this study, we measured the effects of a larger, sedative, dose of KET on cardiovascular responses and survival to moderate (37% blood volume) HEM combined with extremity trauma (ET), and whether midazolam (MDZ), a drug often given in combination with KET alters these responses. Hypothesis: We hypothesized that either KET (50 mg/kg) or KET+MDZ (5 mg/kg) would compromise cardiovascular responses to HEM and thereby decrease survival. Methods: Male rats were implanted with a telemetry transmitter to measure mean arterial pressure (MAP) and heart rate (HR); buprenorphine SR was used to relieve pain associated with surgical procedures. Following 2 weeks recovery, rats were anesthetized using isoflurane, and a carotid catheter was implanted. The next day, rats were briefly anesthetized using isoflurane to perform ET (fibular fracture + hindlimb soft tissue crush injury) and were allowed to recover 90 min before starting conscious HEM (time = 0-25 min). Rats received either 1) saline vehicle (VEH, n=8); 2) KET (n=8); or 3) KET followed by MDZ (KET+MDZ; n=9) during a 15 min infusion (t = 25-40 min). The study continued for 200 minutes (time = 40-240 min). Data are mean ± SD. Results: There were no differences between groups in MAP or HR at either baseline (t = 0 min) or at end of HEM (t = 25 min). However, during the 20 min after treatment (t = 40-60 min), MAP and HR were significantly lower (P≤0.05) in KET (46 ± 3 mmHg; 220 ± 11 bpm) and KET+MDZ (45 ± 10 mmHg; 212 ± 24 bpm) compared to VEH (68 ± 20 mmHg; 297 ± 37 bpm). During this time, only 3 of 8 rats in the KET group survived HEM, while all rats survived in VEH and KET+MDZ groups. At the end of the study (t = 240 min), survival rate was significantly lower (P=0.003) in KET (37.5%) compared to VEH (87.5%) or KET+MDZ (100%). Similarly, survival time was significantly lower (P=0.004) in KET (115 ± 103 min) compared to VEH (227 ± 37 min) or KET+MDZ (240 ± 0 min). Summary of Results: A sedative dose of KET decreased survival following HEM, but the same dose of KET followed by MDZ was protective. The MDZ effect was not due to improvements in cardiovascular responses to the HEM. Conclusion: Sedation with ketamine alone after trauma and moderate HEM decreased survival. Further studies of the effects of sedation with KET alone or KET+MDZ on respiration and metabolic responses to HEM may provide insight on the overall effect on survival. Congressionally Directed Medical Research Program (CDMRP). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Dexmedetomidine versus ketamine in improving tolerance to noninvasive ventilation after blunt chest trauma: A randomized, double-blinded, placebo-controlled trial

Abstract Background and Aims: Even though patient tolerance is critical to the success of noninvasive ventilation (NIV), research on using sedation to improve tolerance to NIV after traumatic chest injuries is limited. We hypothesized that dexmedetomidine would be superior to ketamine in terms of patient tolerance and lengthening the NIV sessions after blunt chest trauma. Material and Methods: This randomized, double-blinded, placebo-controlled trial included 45 patients of both genders aged 18–60 who needed NIV after blunt chest trauma. The patients were randomly assigned to one of three groups (n = 15) for receiving dexmedetomidine, ketamine, or placebo (0.9% sodium chloride solution) infusion to maintain a Richmond Agitation Sedation Scale (RASS) score between 0 and − 3 during two successive NIV sessions. Patients were evaluated for the duration of the NIV sessions, RASS, Visual Analog Scale (VAS), and the total amount of rescue analgesia consumed. Results: The mean duration of the NIV sessions was significantly longer in patients who received dexmedetomidine (P &lt; 0.001) or ketamine (P &lt; 0.001) compared to placebo. However, the NIV durations did not differ significantly between the dexmedetomidine and ketamine groups (P &gt; 0.05). The dexmedetomidine group had a significantly lower RASS score compared to the ketamine (P &lt; 0.001) and placebo (P &lt; 0.001) groups, whereas the ketamine group had a significantly lower VAS compared to the dexmedetomidine (P = 0.005) and placebo (P = 0.022) groups and required significantly less total morphine (P = 0.001) compared to the other groups. Conclusion: The duration of the NIV sessions for patients with blunt chest trauma did not differ significantly between the dexmedetomidine and ketamine groups.

Effect of Low-dose Ketamine Infusion on Opioid Consumption in Children Undergoing Open Cardiac Surgery: A Randomized Controlled Double-Blind Study

This study was designed to evaluate the effect of low-dose ketamine infusion on the perioperative consumption of opioids in pediatric open cardiac surgery. A randomized, controlled, double-blinded single-center study was conducted. The study took place in a tertiary care children's hospital. Patients of both sexes aged 2-12 years who underwent cardiac surgery were included. Patients in the ketamine group received a bolus of 0.3 mg/kg of ketamine before skin incision followed by continuous intraoperative infusion of 0.25 mg/kg/h and postoperative infusion of 0.1 mg/kg/h for 24 h. Patients in the control groups received volumes of normal saline either bolus or continuous infusion like that of the ketamine group. The primary outcome was the total dose of fentanyl consumed over the first 24 hours postoperatively. Secondary outcomes were intraoperative fentanyl consumption, time to extubation, modified objective pain score, and incidence of vomiting, pruritus, diplopia, or hallucinations. A total of 80 patients were recruited but the final analysis was done on 35 patients in the ketamine group and 34 in the control group. Fentanyl consumption during surgery and in the first 24 hours postoperatively was significantly lower in the ketamine than the control group. Patients in both the ketamine and control groups had similar times to extubation. Modified objective pain scores were significantly lower in the ketamine group than the control group. None of the patients in either group had diplopia or hallucinations. Low-dose ketamine infusion in children undergoing open cardiac surgery reduced intra- and postoperative opioid consumption and postoperative pain scores. Moreover, ketamine did not cause diplopia or hallucinations.

The Effect of Preprocedural Low-Dose Ketamine for Pain and Anxiety in Patients during Thoracic Epidural Catheterization.

Background and Objectives: Thoracic epidural catheterization (TEC) can be both uncomfortable and fearful for patients when performed awake with the thought that the procedure may be painful. The aim of this study was to assess the effect of low-dose intravenous ketamine administration on pain and anxiety during the TEC procedure. Materials and Methods: Sixty patients were randomly divided into two groups to receive intravenous (IV) placebo (Group P) and IV low-dose (0.15 mg/kg) ketamine (LDK) (Group K) 3 min before the procedure in a double-blind manner. A visual analog scale (VAS) was used to measure anxiety (VAS-A) and pain (VAS-P) scores. Vital parameters were monitored before premedication (T1), 20 min after premedication (T2), during skin anesthesia (T3), during TEC (T4), and 5 min after TEC (T5). VAS-A values were recorded at T1, T3, T4, and T5 periods, and VAS-P levels were noted at T3, T4, and T5 periods. Results: During TEC (T4), both VAS-P and VAS-A were significantly lower in Group K (p < 0.001). The mean VAS-A value was 10.6 mm lower, and the mean VAS-P value was 9 mm lower in Group K than in Group P at the T4 time point. Additionally, the mean VAS-P value was 7.7 mm lower in Group K compared to Group P at the T3 time point (p < 0.001). Both groups showed a statistically significant difference in VAS-A measurements when compared at their respective time points (p < 0.001). However, only Group P demonstrated a statistically significant difference in VAS-P measurements (p < 0.001). VAS-P values remained stable in Group K. The number of patients who did not recall the procedure was significantly higher in Group K (p < 0.001). Furthermore, the number of patients who would consent to the same procedure in the future was significantly higher in Group K (p = 0.007). Conclusions: A preprocedural LDK (0.15 mg/kg) can effectively prevent anxiety and pain experienced by patients during the TEC procedure. Administration of LDK may provide a more comfortable procedure process without causing ketamine-induced side effects (hemodynamic, respiratory, and psychological).