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Importance: Little is known about the impact of different anesthetic agents used for routine magnetic resonance imaging (MRI) sedation on pulmonary function in children., Objective: To compare the incidence of pulmonary atelectasis after MRI sedation with propofol vs propofol-ketamine., Design, Setting, and Participants: This double-masked randomized clinical trial screened 117 consecutive pediatric patients aged 3 to 12 years with American Society of Anesthesiologists physical status I to II undergoing elective MRI under deep sedation from November 2, 2022, to April 28, 2023, at a tertiary referral center. Four patients met the exclusion criteria, and 5 patients refused to participate. The participants and outcome assessors were masked to the group allocation., Interventions: During the MRI, the propofol group received 0.2 mL/kg of 1% propofol and 2 mL of 0.9% saline followed by a continuous infusion of propofol (200 μg/kg/min) and 0.9% saline (0.04 mL/kg/min). The propofol-ketamine group received 0.2 mL/kg of 0.5% propofol and 1 mg/kg of ketamine followed by a continuous infusion of propofol (100 μg/kg/min) and ketamine (20 μg/kg/min)., Main Outcome and Measure: The incidence of atelectasis assessed by lung ultrasonography examination., Results: A total of 107 children (median [IQR] age, 5 [4-6] years; 62 male [57.9%]), with 54 in the propofol group and 53 in the propofol-ketamine group, were analyzed in this study. Notably, 48 (88.9%) and 31 (58.5%) patients had atelectasis in the propofol and propofol-ketamine groups, respectively (relative risk, 0.7; 95% CI, 0.5-0.8; P < .001). The incidence of desaturation and interruption of the MRI due to airway intervention or spontaneous movement did not significantly differ between the groups. The propofol-ketamine group showed a faster emergence time than the propofol group (15 [9-23] vs 25 [22-27] minutes in the propofol-ketamine vs propofol group; median difference in time, 9.0 minutes; 95% CI, 6.0-12.0 minutes; P < .001). No patient was withdrawn from the trial due to adverse effects., Conclusions and Relevance: In this randomized clinical trial, the propofol-ketamine combination reduced sedation-induced atelectasis while allowing for faster emergence compared with propofol alone., Trial Registration: cris.nih.go.kr Identifier: KCT0007699.

Ketamine is a potent sedative and dissociative anesthetic agent that has been used clinically for over 50 years since it was first developed in the 1960 s as an alternative to phencyclidine (PCP). When compared to PCP, ketamine exhibited a much lower incidence of severe side effects, including hallucinations, leading to its increased popularity in clinical practice. Ketamine was initially used as an anesthetic agent, especially in emergency medicine and in surgical procedures where rapid induction and recovery was necessary. However, over the last few decades, ketamine was found to have additional clinically useful properties making it effective in the treatment of a variety of other conditions. Presently, ketamine has a wide range of clinical uses beyond anesthesia including management of acute and chronic pain, as well as treatment of psychiatric disorders such as major depression. In addition to various clinical uses, ketamine is also recognized as a common drug of abuse sought for its hallucinogenic and sedative effects. This review focuses on exploring the different clinical and non-clinical uses of ketamine and its overall impact on patient care., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

(R,S)-Ketamine (ketamine) is a dissociative anesthetic that also possesses analgesic and antidepressant activity. Undesirable dissociative side effects and misuse potential limit expanded use of ketamine in several mental health disorders despite promising clinical activity and intensifying medical need. (2R,6R)-Hydroxynorketamine (RR-HNK) is a metabolite of ketamine that lacks anesthetic and dissociative activity but maintains antidepressant and analgesic activity in multiple preclinical models. To enable future assessments in selected human indications, we report the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of RR-HNK in a Phase 1 study in healthy volunteers (NCT04711005). A six-level single-ascending dose (SAD) (0.1-4 mg/kg) and a two-level multiple ascending dose (MAD) (1 and 2 mg/kg) study was performed using a 40-minute IV administration emulating the common practice for ketamine administration for depression. Safety assessments showed RR-HNK possessed a minimal adverse event profile and no serious adverse events at all doses examined. Evaluations of dissociation and sedation demonstrated that RR-HNK did not possess anesthetic or dissociative characteristics in the doses examined. RR-HNK PK parameters were measured in both the SAD and MAD studies and exhibited dose-proportional increases in exposure. Quantitative electroencephalography (EEG) measurements collected as a PD parameter based on preclinical findings and ketamine's established effect on gamma-power oscillations demonstrated increases of gamma power in some participants at the lower/mid-range doses examined. Cerebrospinal fluid examination confirmed RR-HNK exposure within the central nervous system (CNS). Collectively, these data demonstrate RR-HNK is well tolerated with an acceptable PK profile and promising PD outcomes to support the progression into Phase 2., (© 2024 The Author(s). Clinical Pharmacology & Therapeutics published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.)

Background: This Rapid Practice Guideline (RPG) aimed to provide evidence-based recommendations for ketamine analgo-sedation (monotherapy and adjunct) versus non-ketamine sedatives or usual care in adult intensive care unit (ICU) patients on invasive mechanical ventilation (iMV) and to identify knowledge gaps for future research., Methods: The RPG panel comprised 23 multinational multidisciplinary panelists, including a patient representative. An up-to-date systematic review and meta-analysis constituted the evidence base. The Grading Recommendations, Assessment, Development, and Evaluation approach, and the evidence-to-decision framework were used to assess the certainty of evidence and to move from evidence to decision/recommendation. The panel provided input on the balance of the desirable and undesirable effects, certainty of evidence, patients' values and preferences, costs, resources, equity, feasibility, acceptability, and research priorities., Results: Data from 17 randomized clinical trials (n = 898) and nine observational studies (n = 1934) were included. There was considerable uncertainty about the desirable and undesirable effects of ketamine monotherapy for analgo-sedation. The evidence was very low certainty and downgraded for risk of bias, indirectness, and inconsistency. Uncertainty or variability in values and preferences were identified. Costs, resources, equity, and acceptability were considered varied. Adjunctive ketamine therapy had no effect on mortality (within 28 days) (relative risk [RR] 0.99; 95% confidence interval [CI] 0.76 to 1.27; low certainty), and may slightly reduce iMV duration (days) (mean difference [MD] -0.05 days; 95% CI -0.07 to -0.03; low certainty), and uncertain effect on the cumulative dose of opioids (mcg/kg/h morphine equivalent) (MD -11.6; 95% CI -20.4 to -2.7; very low certainty). Uncertain desirable effects (cumulative dose of sedatives and vasopressors) and undesirable effects (adverse event rate, delirium, arrhythmia, hepatotoxicity, hypersalivation, use of physical restraints) were also identified. A possibility of important uncertainty or variability in patient-important outcomes led to a balanced effect that favored neither the intervention nor the comparison. Cost, resources, and equity were considered varied., Conclusion: The RPG panel provided two conditional recommendations and suggested (1) against using ketamine as monotherapy analgo-sedation in critically ill adults on iMV when other analgo-sedatives are available; and (2) using ketamine as an adjunct to non-ketamine usual care sedatives (e.g., opioids, propofol, dexmedetomidine) or continuing with non-ketamine usual care sedatives alone. Large-scale trials should provide additional evidence., (© 2024 Acta Anaesthesiologica Scandinavica Foundation.)

Objectives: Pediatric patients with extremity fractures often require sedation for fracture reduction in the pediatric emergency department (PED). Although orthopedic literature suggests combination sedation regimens may be more effective for fracture reduction, some pediatric literature suggests adverse events are more frequent. The primary objective of this study is to determine the comparable depth of sedation and incidence of adverse events when intravenous ketamine is used alone versus with midazolam for pediatric procedural sedation and orthopedic fracture reduction., Methods: This is a retrospective cohort study of pediatric patients 2-18 years old who underwent sedation for fracture reduction in the PED at a single level 1 trauma center over a 2-year period. Medical records were reviewed, and occurrence of adverse events, depth of sedation (Ramsey score), midazolam dose, total ketamine administration, opiate administration, total sedation time, and time to PED discharge were compared in patients who received ketamine alone versus those who received ketamine with midazolam. Logistic regression models were adjusted to evaluate for potential confounders., Results: There was a statistically significant increase in the occurrence of hypoxia with coadministration of midazolam (5% vs 0%). When hypoxia occurred, it was mild and resolved with repositioning or administration of supplemental oxygen. Length of sedation was increased in sedations with coadministration of benzodiazepines by approximately 3.5 minutes. Time to PED discharge was not significantly different. There was no significant difference in depth of sedation, ketamine dose administered, end-tidal CO 2 measurements, administration of positive pressure ventilation, vomiting, agitation, or overall occurrence of adverse events. No patients developed apnea or laryngospasm., Conclusions: This study showed a low rate of adverse events in pediatric sedation for orthopedic reduction with ketamine alone or ketamine with midazolam. There was an increased occurrence of hypoxia with coadministration of midazolam and an increase in the length of sedation. This study showed no difference in depth of sedation based on Ramsay scores when midazolam was coadministered. Information on the orthopedic reduction and provider satisfaction was not collected., Competing Interests: Disclosure: The authors declare no conflict of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Rapid sequence intubation (RSI) is a crucial step in the resuscitation process for critically ill patients, and the judicious use of sedative drugs during RSI significantly influences the clinical outcomes of patients. Ketamine is a commonly used anesthetic sedative; however, its impact on the mortality of patients undergoing RSI has yielded inconsistent findings. Therefore, we conducted a systematic review and meta-analysis investigating ketamine's role in RSI to provide insights into selecting appropriate sedatives for critically ill patients., Methods: In this systematic review and meta-analysis, we conducted a systematic search on MEDLINE (PubMed), Embase, and Cochrane Central Register of Controlled Trials, without restricting to randomized controlled trials (RCTs) or cohort studies. The search was performed from inception until Dec 12, 2023, with no language restrictions. All studies comparing the use of sedatives, including ketamine, and documenting in-hospital mortality were included in this study., Results: A total of 991 studies were identified, out of which 15 studies (5 RCTs and 10 cohort studies) involving 16,807 participants fulfilled the inclusion criteria. No significant impact on in-hospital mortality was observed with the use of ketamine compared to other drugs during RSI (OR 0.90, 95%CI 0.72 to 1.12). Low-quality evidence suggested that ketamine might reduce mortality within the first seven days of hospitalization (OR 0.42, 95%CI 0.19 to 0.93), but it may also have a potential effect on prolonging ICU-free days at day 28 (MD -0.71, 95%CI -1.38 to -0.05). There were no significant differences in the results of the other RSI-related outcomes, such as physiological function and adverse events., Conclusions: Based on existing studies, ketamine showed no significant difference compared to other sedatives in terms of in-hospital mortality, physiological impact, and side effects following RSI. However, it may reduce mortality within 7 days while probably prolong the length of stay in the ICU., Trial Registration: CRD42023478020., (© 2024. The Author(s).)

Objectives: The aim of this study was to identify the incidence of adverse events of ketamine administration in the pediatric emergency department in patients aged 90 days or younger in order to demonstrate the safety and efficacy of administration in this patient population., Methods: An 8-year retrospective chart review of patients aged 90 days or younger who received ketamine in the pediatric emergency department was conducted. All patients who met the age criteria were included in this study. Identified routes of ketamine administration included oral, intramuscular, and intravenous., Results: Fourteen patients were identified who met the inclusion criteria and were included in the final analysis. The median age was 45 days old. Indications for ketamine administration included 7 cases for procedural sedation, 5 cases for RSI, and 2 cases for postintubation sedation. The average dose amount (mg/kg) of ketamine administered was 10, 4.43, and 1.59 for oral, intramuscular, and intravenous routes, respectively. Of the 14 patients, 1 patient was identified to have an adverse event to ketamine administration. A transient desaturation and bradycardic event due to laryngospasm was observed during laryngoscopy performed for RSI that was resolved with administration of anticholinergics and paralytics as well as successful intubation and ventilation., Conclusions: In this study, 1 patient suffered an adverse event due to laryngospasm during intubation. In the pediatric population, the incidence of adverse events of ketamine administration has been found to be variable in the current literature, ranging from 0.71% to 7.26%. In our study, an adverse event occurred in 1 out of 14 administrations (7.1%). The incidence of adverse events associated with ketamine administration in our patients aged 90 days or less appeared to be similar to that reported in the general pediatric population., Competing Interests: Disclosure: The authors declare no conflicts of interest. The authors received no financial support for the research, authorship, and/or publication of this article., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Objectives: To provide guidance in the form of consensus statement in the management of ketamine uropathy., Methods: A literature review of ketamine uropathy was performed. The consensus method was of a modified nominal group technique and has been use in the previous British Association of Urological Surgeons (BAUS) consensus documents and was led by the Female, Neurological and Urodynamic Urology Section of the BAUS., Results: A number of consensus statements detailing the assessment and management of urological complications relate to the recreational use of ketamine (ketamine uropathy) in both elective and emergency urology settings., Conclusion: Comprehensive management pathway for ketamine-related urinary tract dysfunction and uropathy has been detailed., (© 2024 The Authors. BJU International published by John Wiley & Sons Ltd on behalf of BJU International.)

Objective: Varying rates of complications have been reported for prehospital sedation with ketamine, and the relationship to dosing has not been studied on a large scale. We evaluated the association between prehospital ketamine dosing and rates of intubations and other adverse events in patients with behavioral emergencies., Methods: Using the 2018/2019 ESO public-use research datasets, we included all non-traumatic, adult behavioral and drug-related EMS encounters with ketamine administration. Based on consensus guidelines, we stratified patients into "above" and "at/below" the maximum dosing for sedation (2 mg/kg IV/IO or 5 mg/kg IM) using the highest single dose of ketamine given. We created propensity scores for matched subjects using 1:1 propensity score matching. Using logistic regression, we compared rates of intubation and other airway interventions, antipsychotic coadministration, improvement reported by EMS, hypoxia, hypotension, and cardiac arrest between the two groups., Results: We included 2383 patients: 478 in the above and 1905 in the at/below dose group. Above-dose ketamine was associated with a higher rate of intubation or supraglottic airway placement (6.4% v 3.3%, OR 2.0, 95% CI 1.00-3.90). Other airway interventions were similar (40.0% v 40.0%, OR 1, 95% CI 0.80-1.30). The above-dose group also showed a higher rate of improvement noted by EMS clinicians (92.5% v 88.7%, OR 1.6, 95% CI 1.01-2.40). The rates of antipsychotic coadministration, hypoxia, hypotension, and cardiac arrest were similar between the cohorts., Conclusions: Patients given ketamine doses above consensus recommendations for sedation appeared more likely to receive prehospital intubation but not more likely to experience other adverse events.

Background: Dexmedetomidine is an alternative agent for procedural sedation in the emergency department thanks to its ability to maintain hemodynamic and respiratory stability. Dexmedetomidine must, however, be combined with a powerful analgesic., Objective: Our aim was to evaluate the quality and safety of procedural sedation using the combination of dexmedetomidine and ketamine for patients undergoing painful procedures in the emergency department., Methods: This prospective interventional single-center study was conducted in an academic emergency department of an urban hospital in Brussels, Belgium. Patients received a bolus injection of 1 µg/kg dexmedetomidine over 10 min and then a continuous infusion of 0.6 µg/kg/h followed by a bolus of 1 mg/kg ketamine. The painful procedure was carried out 1 min later. The level of pain was evaluated with a numerical rating scale from 0 (no pain) to 10 (maximal pain). The level of patient comfort for the procedure was measured using a comfort scale., Results: Thirty patients were included. Overall, 90% of patients felt little or no pain (n = 29 of 30) or discomfort (n = 28 of 30) during the procedure. One patient experienced apnea with desaturation, which was resolved by a jaw-thrust maneuver. Although 23% of patients had significant arterial hypertension, none required drug treatment., Conclusions: The combination of dexmedetomidine and ketamine provides conscious sedation, bringing comfort and pain relief to patients in optimal conditions for respiratory and hemodynamic safety. However, sedation and recovery times are longer than with conventional drug combinations. The dexmedetomidine-ketamine combination should therefore be recommended for nonurgent procedures and fragile patients., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Neurobehavioral deficits emerge in nearly 50% of patients following a mild traumatic brain injury (TBI) and may persist for months. Ketamine is used frequently as an anesthetic/analgesic and for management of persistent psychiatric complications. Although ketamine may produce beneficial effects in patients with a history of TBI, differential sensitivity to its impairing effects could make the therapeutic use of ketamine in TBI patients unsafe. This series of studies examined male C57BL/6 J mice exposed to a mild single blast overpressure (mbTBI) for indications of altered sensitivity to ketamine at varying times after injury. Dystaxia (altered gait), diminished sensorimotor gating (reduced prepulse inhibition) and impaired working memory (step-down inhibitory avoidance) were examined in mbTBI and sham animals 15 min following intraperitoneal injections of saline or R,S-ketamine hydrochloride, from day 7-16 post injury and again from day 35-43 post injury. Behavioral performance in the forced swim test and sucrose preference test were evaluated on day 28 and day 74 post injury respectively, 24 h following drug administration. Dynamic gait stability was compromised in mbTBI mice on day 7 and 35 post injury and further exacerbated following ketamine administration. On day 14 and 42 post injury, prepulse inhibition was robustly decreased by mbTBI, which ketamine further reduced. Ketamine-associated memory impairment was apparent selectively in mbTBI animals 1 h, 24 h and day 28 post shock (tested on day 15/16/43 post injury). Ketamine selectively reduced immobility scores in the FST in mbTBI animals (day 28) and reversed mbTBI induced decreases in sucrose consumption (Day 74). These results demonstrate increased sensitivity to ketamine in mice when tested for extended periods after TBI. The results suggest that ketamine may be effective for treating neuropsychiatric complications that emerge after TBI but urge caution when used in clinical practice for enhanced sensitivity to its side effects in this patient population., (Copyright © 2021 Elsevier Inc. All rights reserved.)

The black market for new psychoactive substances has been constantly evolving and the substances that appear on this market cause a considerable number of issues, in extreme cases leading to human deaths. While monitoring the drug black market, we detected a sample of a dissociative anesthetic methoxphenidine, the salt of which contained an unusual anion in the form of bromo- and chloro-zincate complex. Concerning the unknown and potentially hazardous properties of this sample, we performed an in vitro cytotoxicity screening in cell lines of various origins (e.g., kidney, liver, bladder) which was compared with the toxicity results of the methoxphenidine standard prepared for this purpose. The street methoxphenidine sample exhibited markedly higher toxicity than the standard, which was probably caused by the anion impurity. Since it is not usual to analyze anions in salts of novel psychoactive substances, but such samples may be commonly available at the drug black market, we have developed a method for their identification with X-ray powder diffraction (XRPD), which also enabled us to distinguish between different polymorphs/solvates of methoxphenidine that were crystallized in the laboratory. XRPD offers additional data about samples, which may not be discovered by routine techniques, and in some cases, they may help to find out essential information.

Although women and men are equally likely to receive ketamine following traumatic injury, little is known regarding sex-related differences in the impact of ketamine on traumatic memory. We previously reported that subanesthetic doses of an intravenous (IV) ketamine infusion following fear conditioning impaired fear extinction and altered regional brain glucose metabolism (BGluM) in male rats. Here, we investigated the effects of IV ketamine infusion on fear memory, stress hormone levels, and BGluM in female rats. Adult female Sprague-Dawley rats received a single IV ketamine infusion (0, 2, 10, or 20 mg/kg, over a 2-h period) following auditory fear conditioning (three pairings of tone and footshock). Levels of plasma stress hormones, corticosterone (CORT) and progesterone, were measured after the ketamine infusion. Two days after ketamine infusion, fear memory retrieval, extinction, and renewal were tested over a three-day period. The effects of IV ketamine infusion on BGluM were determined using 18 F-fluoro-deoxyglucose positron emission tomography ( 18 F-FDG-PET) and computed tomography (CT). The 2 and 10 mg/kg ketamine infusions reduced locomotor activity, while 20 mg/kg infusion produced reduction (first hour) followed by stimulation (second hour) of activity. The 10 and 20 mg/kg ketamine infusions significantly elevated plasma CORT and progesterone levels. All three doses enhanced fear memory retrieval, impaired fear extinction, and enhanced cued fear renewal in female rats. Ketamine infusion produced dose-dependent effects on BGluM in fear- and stress-sensitive brain regions of female rats. The current findings indicate that subanesthetic doses of IV ketamine produce robust effects on the hypothalamic-pituitary-adrenal (HPA) axis and brain energy utilization that may contribute to enhanced fear memory observed in female rats.

Background: There is a paucity of literature around sedation and anesthesia in patients with severe anorexia nervosa. Chronically malnourished patients are known to have myopathy, neuropathy, and altered neurotransmitter signaling. Ketamine is a non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist that is an established general anesthetic and short-acting dissociative analgesic agent. It generally has a reassuring adverse event profile and rarely has been reported to result in apnea. We aim to raise awareness of this untoward adverse event in patients with severe anorexia nervosa among sedation providers and those referring patients for hospitalization or sedation., Case Presentation: We describe an episode of apnea, a rare adverse event of ketamine, which was given for procedural sedation to a severely malnourished 13-year-old female with anorexia nervosa, generalized anxiety disorder, and high-functioning autism spectrum disorder. She had no history of apnea nor of ketamine sedation. She was given a standard dose of ketamine and had no other central nervous system depressants within 24 h. Within 1 min after slow medication administration, she had a 9-min period of apnea without laryngospasm. She was supported with bag-valve-mask ventilation throughout this period and did not require intubation. She returned to baseline shortly after procedural sedation., Conclusions: This case describes apnea after ketamine sedation in a patient with severe anorexia nervosa. It supports the importance of a thorough pre-procedure review of a patient's underlying medical problems and the consideration of how sedatives may interact with these conditions. We aim to alert those who care for this complex population of the possible altered neurotransmitters, myopathy, and adverse response to sedation, anesthetics, and analgesics., (© 2021. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

The history of ketamine begins in 1962, when Calvin Stevens of the pharmaceutical laboratory Parke-Davis synthesizes it from phencyclidine, a molecule with psychodysleptic, hallucinogenic and dissociative properties. Following the first administration of ketamine to humans in 1964 in Jackson prison (Michigan, USA), its dissociative effects associated with short anaesthesia were reported, and a patent for its human use was filed in 1966. In the 1990s, the discovery of opioid-induced hyperalgesia sparked interest in ketamine as an analgesic. In recent years, the human use of ketamine, and in particular its esketamine enantiomer, has shifted towards the treatment of depression. The first cases of ketamine abuse were reported in 1992 in France, leading to special surveillance by the health authorities, and its inclusion in the list of narcotic drugs in 1997. Today, ketamine has become an attractive substance for recreational use, gradually emerging from alternative techno circles to spread to more commercial party scenes. These elements represent a public health concern, associated with the risk of developing new chemically synthesized analogues, the harmful effects of which are still little known., (Copyright © 2021 Académie Nationale de Pharmacie. Published by Elsevier Masson SAS. All rights reserved.)

Backgrounds: Ketamine is a dissociative anesthetic that is currently considered for several new indications., Aim: To deduce the safety of long-term ketamine treatment using the harm of heavy recreational (non-medical) ketamine use as a proxy for maximal possible harm of ketamine treatment., Methods: Systematic literature review according to PRISMA guidelines to identify controlled studies on ketamine-related harm in heavy recreational ketamine users. Results were compared with serious adverse events (SAEs) in patients treated with ketamine according to three systematic reviews considering dosing regimen and cumulative dose., Results: The systematic search yielded 25 studies. Heavy recreational ketamine use can escalate to ketamine dependency and was often dose-dependently associated with other SAEs, including cognitive and mental disorders, and gastrointestinal and urinary tract symptoms, which disappeared upon marked reduction of ketamine use. Heavy ketamine users have a much higher cumulative exposure to ketamine than ketamine treated patients (>90 times), which may explain why SAEs in the clinical context are mostly mild and reversible and why ketamine dependence was not reported in these patients., Conclusion: Treatment of patients with ketamine is not associated with ketamine dependency or SAEs. However, caution is needed since data on long-term clinical ketamine use with a long-term follow-up is lacking.

Background: The present study was designed to evaluate the effect of dexmedetomidine and propofol on ketamine-induced recovery agitation in adults when used as co-administration with ketamine., Methods: In this prospective, randomized, and double-blind clinical trial, 93 patients aged 18 years or older who were candidates for painful procedures in the emergency department (ED) were enrolled and assigned into three equal groups to receive either ketadex (dexmedetomidine 0.7 μg/kg and ketamine 1 mg/kg), ketofol (propofol 0.5 mg/kg and ketamine 0.5 mg/kg) or ketamine alone (1 mg/kg) intravenously. Incidence and severity of recovery agitation were evaluated using the Richmond Agitation-Sedation Scale and compared between groups., Results: There were no significant differences in demographic characteristics, procedures, pain scores, pre-sedation agitation, and duration of procedure between the three groups. The incidence of recovery agitation was 26% in the Ketadex group, 29% in the Ketofol group, and 58% in the Ketamine group. The difference in incidence of recovery agitation between Ketadex group and Ketamine group was 32% (95% confidence interval (CI), 9 to 56]) and between Ketofol group and Ketamine group was 29% (95% CI, 6 to 53). The severe agitation was significantly higher in Ketamine group, with a difference between Ketamine and Ketadex group of 19% (95% CI, 6 to 33), and a difference between Ketamine and Ketofol group of 16% (95% CI, 1 to 31)., Conclusions: In this study, a combination of ketamine-dexmedetomidine and ketamine-propofol reduced the incidence and severity of ketamine-induced recovery agitation in adults undergoing procedural sedation in the ED., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: Depressive symptoms occur in over 40% of neurosurgical patients during the perioperative period. However, no measure has been suggested to have a rapid effect on depressive surgical patients during increasingly shorter stays in the hospital. This study aimed to determine whether ketamine could improve depressive symptoms rapidly and safely during the hospital stay., Methods: This was a randomized, placebo-controlled, and double-blinded trial. Patients with moderate-to-severe depressive symptoms undergoing elective supratentorial brain tumor resection were randomized to intravenously receive either (1) 0.5 mg·kg-1 ketamine for 40 minutes or (2) an identical volume of normal saline. The primary outcome was treatment response on postoperative day 3, defined as a ≥50% reduction from the baseline depressive score. The secondary outcomes included the rate of remission and safety outcomes. The Montgomery-Åsberg Depression Rating Scale was applied by trained psychiatrists to evaluate depressive symptoms., Results: A total of 84 neurosurgical patients were enrolled in the trial. The response rate was increased by the administration of ketamine (41.5% [17/41] vs 16.3% [7/43]; relative risk [RR]: 2.51, 95% confidence interval [CI], 1.18-5.50) relative to the administration of placebo at 3 days. Furthermore, the remission rate at discharge (29.3% [12/41] vs 7.0% [3/43]; RR: 4.20, 95% CI, 1.28-13.80) was also improved by ketamine. No psychotic symptoms or adverse events were reported to be substantially higher in the ketamine group., Conclusions: The trial indicates that the intraoperative administration of ketamine could alleviate moderate-to-severe depressive symptoms in neurosurgical patients without worsening safety., Competing Interests: Conflicts of Interest: See Disclosures at the end of the article., (Copyright © 2021 International Anesthesia Research Society.)

Background: Closed-loop control of propofol-remifentanil anesthesia using the processed electroencephalography depth-of-hypnosis index provided by the NeuroSENSE monitor (WAVCNS) has been previously described. The purpose of this placebo-controlled study was to evaluate the performance (percentage time within ±10 units of the setpoint during the maintenance of anesthesia) of a closed-loop propofol-remifentanil controller during induction and maintenance of anesthesia in the presence of a low dose of ketamine., Methods: Following ethical approval and informed consent, American Society of Anesthesiologist (ASA) physical status I-II patients aged 19-54 years, scheduled for elective orthopedic surgery requiring general anesthesia for >60 minutes duration, were enrolled in a double-blind randomized, placebo-controlled, 2-group equivalence trial. Immediately before induction of anesthesia, participants in the ketamine group received a 0.25 mg·kg-1 bolus of intravenous ketamine over 60 seconds followed by a continuous 5 µg·kg-1·min-1 infusion for up to 45 minutes. Participants in the control group received an equivalent volume of normal saline. After the initial study drug bolus, closed-loop induction of anesthesia was initiated; propofol and remifentanil remained under closed-loop control until the anesthetic was tapered and turned off at the anesthesiologist's discretion. An equivalence range of ±8.99% was assumed for comparing controller performance., Results: Sixty patients participated: 41 males, 54 ASA physical status I, with a median (interquartile range [IQR]) age of 29 [23, 38] years and weight of 82 [71, 93] kg. Complete data were available from 29 cases in the ketamine group and 27 in the control group. Percentage time within ±10 units of the WAVCNS setpoint was median [IQR] 86.6% [79.7, 90.2] in the ketamine group and 86.4% [76.5, 89.8] in the control group (median difference, 1.0%; 95% confidence interval [CI] -3.6 to 5.0). Mean propofol dose during maintenance of anesthesia for the ketamine group was higher than for the control group (median difference, 24.9 µg·kg-1·min-1; 95% CI, 6.5-43.1; P = .005)., Conclusions: Because the 95% CI of the difference in controller performance lies entirely within the a priori equivalence range, we infer that this analgesic dose of ketamine did not alter controller performance. Further study is required to confirm the finding that mean propofol dosing was higher in the ketamine group, and to investigate the implication that this dose of ketamine may have affected the WAVCNS., Competing Interests: Conflicts of Interest: See Disclosures at the end of the article., (Copyright © 2021 International Anesthesia Research Society.)

Introduction: Ketamine is commonly used to treat profound agitation in the prehospital setting. Early in ketamine's prehospital use, intubation after arrival in the emergency department (ED) was frequent. We sought to measure the frequency of ED intubation at a Midwest academic medical center after prehospital ketamine use for profound agitation, hypothesizing that intubation has become less frequent as prehospital ketamine has become more common and prehospital dosing has improved., Methods: We conducted a retrospective cohort study of adult patients receiving ketamine in the prehospital setting for profound agitation and transported to a midwestern, 60,000-visit, Level 1 trauma center between January 1, 2017-March 1, 2021. We report descriptive analyses of patient-level prehospital clinical data and ED outcomes. The primary outcome was proportion of patients intubated in the ED., Results: A total of 78 patients received ketamine in the prehospital setting (69% male, mean age 36 years). Of the 42 (54%) admitted patients, 15 (36% of admissions) were admissions to the intensive care unit. Overall, 12% (95% confidence interval [CI]), 4.5-18.6%)] of patients were intubated, and indications included agitation (n = 4), airway protection not otherwise specified (n = 4), and respiratory failure (n = 1)., Conclusion: Endotracheal intubation in the ED after prehospital ketamine use for profound agitation in our study sample was found to be less than previously reported.

Background: Drugs such as propofol and ketamine are used alone or in combination to provide sedation for medical procedures in children. The purpose of this systematic review was to compare the safety and effectiveness of propofol and ketamine to other drug regimens., Methods: We searched Medline, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), Cochrane Database of Systematic Reviews (CDSR), Web of Science, and the grey literature (meta-Register of Controlled Trials, ClinicalTrials.gov, and Google Scholar) for randomized controlled studies comparing intravenous propofol and ketamine to any other single or combination drug regimen administered to children undergoing diagnostic or therapeutic procedures. Meta-analyses were performed for primary (hemodynamic and respiratory adverse events) and secondary outcomes using RevMan 5.3. We assessed the risk of bias and the certainty (quality) evidence for all outcomes using Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology., Results: Twenty-nine studies were included for analysis. Based on low-to-moderate quality evidence, we concluded that the use of propofol and ketamine may result in a slight-to-small reduction in the risk of hypotension, bradycardia, and apnea, and a slight increase in the risk of tachycardia, hypertension, and other respiratory adverse events, such as cough or laryngospasm. The ratio of propofol to ketamine and comparator drug regimen subgroups effects were important for desaturation and some secondary outcomes., Conclusions: The use of propofol and ketamine had a minimal effect on the incidence of adverse events and other secondary outcomes. Large-scale studies are required to more accurately estimate adverse event rates and the effects of propofol and ketamine on patient-important outcomes., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2020 International Anesthesia Research Society.)

Objective: Prehospital intramuscular (IM) ketamine is increasingly used for chemical restraint of agitated patients. However, few studies have assessed emergency department (ED) follow-up of patients receiving prehospital ketamine for this indication, with previous reports suggesting a high rate of post-administration intubation. This study examines the rate of and reasons for intubation and other airway interventions in agitated patients who received ketamine by Emergency Medical Services (EMS)., Methods: This retrospective cohort study included patients who received prehospital ketamine for agitation and were transported to two community hospital EDs. Charts were reviewed for demographics, ketamine dose, and airway intervention by EMS or in the ED. Characteristics of patients who were intubated versus those who did not receive airway intervention were analyzed., Results: Over 28 months, 86 patients received ketamine for agitation. Fourteen (16.3%) underwent endotracheal intubation. Patients with a higher temperature and a lower Glasgow Coma Score (GCS) were more likely to require intubation. There was no age or dose-dependent association on intubation rate. Intubated patients averaged 39 years old versus 44 for patients not intubated (negative five-year difference; 95% CI, -16 to 6). The mean ketamine dose was 339.3mg in patients intubated versus 350.7mg in patients not (-11.4mg difference; 95% CI, -72.4 to 49.6). The mean weight-based ketamine dose was 4.44mg/kg in patients intubated versus 4.96mg/kg in patients not (-0.53mg/kg difference; 95% CI, -1.49 to 0.43)., Conclusions: The observed rate of intubation in patients receiving prehospital ketamine for agitation was 16.3%. Study data did not reveal an age or dose-dependent rate of intubation. Further research should be conducted to compare the airway intervention rate of agitated patients receiving ketamine versus other sedatives in a controlled fashion.

Rhesus macaques represent an important species for translational and pre-clinical research studies across a multitude of disease and injury models, including aging. Ketamine anesthesia is used in humans and non-human primates but may be associated with adverse effects, including neuromuscular reactions. The effects of aging on ketamine adverse effects is not well characterized. Urodynamic recordings and electromyography (EMG) studies were performed in aged (>20 years old) and adult (3.9-14.9 years old) female rhesus macaques under an equal and light plane of sedation by constant rate infusion (CRI) of ketamine. A total of 4 of 41 adult subjects (9.7%) showed clinical signs of ketamine-induced abnormal neuromuscular reactivity, whereas a larger portion of 14 of 26 aged subjects showed similar ketamine-induced neuromuscular reactivity (53.8%; P< 0.001). The ketamine CRI rate was 19.8±0.9 mg/kg/h in adults and lower in aged subjects at 16.5±1.4 mg/kg/h (P<0.05). The ketamine CRI rate was negatively correlated with age (r = -0.30, P<0.05, n = 64). The incidence of ketamine reactivity or CRI rate was not different between aged pre-and post-menopausal females. EMG recordings during neuromuscular reactivity showed coordinated activation of multiple muscles, suggesting a central nervous system (CNS) mechanism for ketamine-associated neuromuscular reactivity. The incidence of ketamine-induced neuromuscular reactivity is age related but not affected by the estrous cycle in female rhesus macaques. A coordinated activation of multiple muscles, innervated by different peripheral nerves, suggests that ketamine-induced neuromuscular reactivity originates in the CNS., Competing Interests: The authors have declared that no competing interests exist.

Background: The treatment of ketamine users is substantially challenged by high dropout rates, raising questions regarding contributing factors. A number of studies have highlighted the potential of greater focus on the clinical significance of cognitive impairments in ketamine users. The present study hypothesized that cognitive deficits would play a role in greater risk for treatment dropout in chronic ketamine users., Methods: Our study examined cognitive performance in the form of working memory, verbal memory, visual memory and executive function among chronic ketamine users who completed three-month treatment in residential detoxification centres (N = 165), those who dropped out prematurely (N = 121) and drug-free healthy controls (N = 111). The data collection was completed in Hong Kong among the East Asia population., Results: Compared to healthy controls, cognitive impairments were found in ketamine users, including in verbal/visual memory and executive function. Executive dysfunction was significantly associated with dropout in ketamine users within three months., Conclusion: Our findings suggest that executive dysfunction may have clinical benefits in ketamine users admitted to residential treatment programmes., Competing Interests: Declaration of Competing Interest The authors have no conflict of interest regarding the present study., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Objective: This study was conducted to determine the effect of intramuscular ondansetron on ketamine-associated vomiting in children undergoing procedural sedation., Methods: This randomized, double-blind, placebo-controlled, parallel-group clinical trial was conducted at the emergency departments of two university-affiliated tertiary care hospitals. Eligible participants included all 6-month to 16-year-old children who received IM ketamine for PSA in the ED. A convenience sampling approach was used and a block randomization method was applied (blocks of four) using a computer-generated random sequence. Patients received ketamine 4 mg/kg or ketamine 4 mg/kg plus ondansetron 0.1 mg/kg intramuscularly. All findings including the occurrence of vomiting and its frequency were then recorded in the data collection sheets., Results: Of 56 patients who received ondansetron plus ketamin, 7 (12.5%) and 1 (1.8%) experienced vomiting during recovery and before discharge and Of 65 patients in the control group, 14 (21.5%) and 6 (9.2%) experienced vomiting during recovery and before discharge, respectively. The observed differences in the rates of vomiting during recovery and at discharge were statistically significant between the two groups (P-value of 0.03 and <0.001, respectively)., Conclusion: Intramuscular ondansetron is effective in controlling ketamine-associated vomiting., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Ketamine is a valuable anaesthetic and analgesic that in recent years has gained notoriety as a recreational drug. Recently, ketamine has also been proposed as a novel treatment for depression and post-traumatic stress disorder. Beyond its anaesthetic actions, however, the effects of ketamine on brain activity have rarely been probed. Here we examined the cortical electroencephalography (EEG) response to ketamine of 12 sheep. Following ketamine administration, EEG changes were immediate and widespread, affecting the full extent of the EEG frequency spectrum measured (0-125 Hz). After recovery from sedation during which low frequency activity dominated, the EEG was characterised by short periods (2-3 s) of alternating low (<14 Hz) and high (>35 Hz) frequency oscillation. This alternating EEG rhythm phase is likely to underlie the dissociative actions of ketamine, since it is during this phase that ketamine users report hallucinations. At the highest intravenous dose used (24 mg/kg), in 5/6 sheep we observed a novel effect of ketamine, namely the complete cessation of cortical EEG activity. This persisted for up to several minutes, after which cortical activity resumed. This phenomenon is likely to explain the 'k-hole', a state of oblivion likened to a near death experience that is keenly sought by ketamine abusers.

Electroconvulsive therapy (ECT) remains the most effective treatment for major depressive disorder. Ketamine is an anesthetic gaining attention for its rapid antidepressant effect. Numerous randomized controlled trials have investigated the effect of ketamine anesthesia in ECT on various clinical outcomes. Previous systematic reviews have not found benefit for overall depression response, although some have found evidence of benefit early in the ECT course. Clear quantitative conclusions have not been established regarding other outcomes, particularly while only using data from high-quality studies. We aimed to examine all data from double-blind randomized controlled trials comparing ketamine to other anesthetics via meta-analysis, to make recommendations regarding ECT practice and future research. Data were extracted for depressive symptoms, seizure duration and electrical dose, neuropsychological performance, and adverse effects. Effect sizes were calculated using Hedge's g and odds ratios. Eighteen studies (n = 915) were included in the meta-analysis. Ketamine was not found to enhance improvement of depressive symptoms, either early in ECT course or at end of study. Ketamine had a large effect on increasing seizure duration both overall (Hedge's g = 0.71, P = 0.038) and in the subgroup receiving ketamine in combination with another anesthetic (Hedge's g = 0.78, P < 0.01), and on decreasing electrical dose (Hedge's g = 1.98, P = 0.039). There was no significant effect of ketamine on any individual neuropsychological domain. Ketamine was not associated with increased adverse effects, except for hypertension in patients receiving ketamine monotherapy. Significant heterogeneity was present for many outcomes, and sensitivity analyses suggested a relation to methodological variation in most cases. This study supports the finding that ketamine does not enhance ECT's antidepressant effect, including on early improvement, but provides substantial evidence for enhancing seizure duration and reducing electrical dose. No significant benefit was found on neurocognitive outcomes, but analysis was limited by small sample sizes and high heterogeneity. Ketamine is generally safe in ECT, particularly as a coanesthetic. Our findings provide meta-analytic support to the recommendations in ECT clinical guidelines for use of coadjuvant ketamine in ECT where seizures are suboptimal. Further studies targeting neurocognitive outcomes are encouraged.

Background: Inguinal herniotomy is one of the commonest paediatric surgical procedures at the University of Benin Teaching Hospital. Incisional infiltration with plain bupivacaine has been used to provide postoperative analgesia for this procedure but with a short duration of action, 4-6 hours., Aims/objectives: The aim of this study therefore was to evaluate the efficacy of subcutaneous ketamine on post-operative analgesia in children undergoing unilateral inguinal herniotomy., Methods: Forty-six (46) ASA I or II patients aged three to seven years scheduled for unilateral inguinal herniotomy were recruited. The patients were randomized to receive surgical wound site infiltration with plain bupivacaine plus subcutaneous injection of ketamine for group I or surgical wound site infiltration plain bupivacaine plus 2ml of saline subcutaneously for group II at the end of surgery. Data obtained were analyzed using SPSS version 20. Continuous data were compared using student t-test while categorical data were compared using Chi-square or Fisher's exact test. P-value <0.05 was considered statistically significant., Results: In group, I, the mean time to first analgesic request was 667.7 minutes (11.12 hours) and in group II, it was 371.3 minutes (6.2 hours) with p<0.001. The pain scores were better and more favourable in group I from the 8th hour and above of the assessment period. The mean post-operative analgesic consumption in 24 hours was less in group I (19.35±5.4mg) than in group II (27.32±5.8 mg) with p-value <0.001., Conclusion: The study showed that subcutaneous ketamine prolonged the analgesic effect of plain bupivacaine surgical wound site infiltration in children undergoing unilateral inguinal herniotomy., (© 2020 Oham A et al.)

Background: We conducted a randomized clinical trial to determine whether adjunctive lidocaine diminishes the incidence of adverse effects in pediatric patients sedated with ketamine., Methods: This case-control study involved 586 consecutive pediatric patients necessitating anesthesia. Then systolic blood pressure, heart rate, respiratory rate, and blood oxygen saturation were observed. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), urea nitrogen (BUN), and creatinine (Cr) levels were tested. General dose of ketamine, the time of onset and duration of anesthesia and postoperative recovery, anesthesia effect, and adverse reaction were subsequently compared. High-performance liquid chromatography was employed to detect ketamine concentration at different time points after administration, and the postoperative cognition function was further evaluated., Results: Intra- and post-operation, the rising degree of ALT, AST, BUN, and Cr in patients treated with ketamine was higher than those in patients treated with the ketamine-lidocaine complex. General dose of ketamine, the time of onset and duration of anesthesia, postoperative recovery time, and the incidence rate of adverse reaction in patients treated with ketamine-lidocaine complex were lower, but the concentration of ketamine was higher compared to the patients treated with ketamine. In patients treated with the ketamine-lidocaine complex, elimination half-life of ketamine was prolonged, the area under curve was increased, and the plasma clearance rate was decreased relative to those with ketamine alone., Conclusions: Ketamine combined with lidocaine may be beneficial in shortening the onset of anesthesia, promoting postoperative awake, prolonging elimination half-life, increasing area under curve, and decreasing plasma clearance rate and incidence of adverse reactions., (© 2019 The Authors. Journal of Clinical Laboratory Analysis published by Wiley Periodicals, Inc.)

Tau hyperphosphorylation is a major neuropathological hallmark of many neurodegenerative disorders such as Alzheimer's disease. Several anesthetics have been shown previously to induced marked tau hyperphosphorylation. Although the ketamine/xylazine mixture is one of the most commonly used anesthetic agents in animal research and veterinary practice, the effect of this anesthetic agent on tau phosphorylation still remains to be determined. Here, we found that ketamine-/xylazine-induced a rapid and robust hyperphosphorylation of tau in a dose-dependent manner under normothermic and hypothermic conditions in mice. When used together, ketamine and xylazine exerted a synergistic action on tau phosphorylation most strongly not only on epitopes S396 and S262, but also on other residues (T181, and S202/T205). We observed that activation of the calmodulin-dependent protein kinase II (CaMKII) is the major upstream molecular event leading to tau hyperphosphorylation following ketamine/xylazine anesthesia in mice. Moreover, we observed that intracerebroventricular injection of the selective CaMKII inhibitor KN93 attenuated tau hyperphosphorylation. Since ketamine/xylazine also had a marked impact on other key molecular signaling pathways involving the MAP/microtubule affinity-regulating kinase (MARK), extracellular signal-regulated kinase (ERK), and glycogen synthase kinase-3 (GSK3), our study calls for high caution and careful monitoring when using this anesthetic agent in laboratory animal settings across all fields of biological sciences in order to avoid artifactual results., (© 2019 Federation of American Societies for Experimental Biology.)

Background: Ketamine is routinely used within the context of combat casualty care. Despite early concerns that ketamine administration may be associated with elevated risk of posttraumatic stress disorder (PTSD), more recent evidence suggests no relationship. Because PTSD occurs with regular frequency in Operation Iraqi Freedom/Operation Enduring Freedom (OIF/OEF) Service Members (SMs) and combat-related injuries are associated with higher likelihood of PTSD, it is important to investigate the relationship between ketamine exposure during inpatient medical and surgical care and PTSD symptoms in OIF/OEF SMs., Methods: Medical record data from OIF/OEF SMs medically evacuated from combat (N = 1158) included demographic characteristics, injury severity, body areas injured, and PTSD Checklist (PCL) scores. The primary analysis assessed the association between ketamine versus nonketamine exposure on positive PTSD screen (logistic regression) and PCL scores (linear regression) after using 1:1 propensity score matching to adjust for available potential confounding variables. Because there were 2 primary outcomes, the binary positive PTSD screen (yes/no) and continuous PCL score, the significance level was set at P ≤ .025. In sensitivity analyses, propensity scores were used to match ketamine to nonketamine records in a 1:4 ratio, as well as to conduct inverse probability treatment weighting (IPTW). Regressions examining the relationship between ketamine exposure and outcomes were repeated for unconditional, 1:4 matching, and IPTW models., Results: In the sample, 107 received ketamine and 1051 did not. In the logistic regression, the probability of a positive PTSD screen was not significantly different between ketamine versus nonketamine patients (odds ratio [OR] = 1.28; 95% confidence interval [CI], 0.48-3.47; P = .62). In the linear regression, PCL scores were not significantly different between ketamine versus nonketamine patients (mean difference = 1.98 [95% CI, -0.99 to 4.96]; P = .19). The results were consistent in the unconditional, 1:4 matching, and IPTW models., Conclusions: No differences in PTSD screening risk or symptom levels between ketamine exposed and nonexposed were found. Given the small sample size, wide CIs of the effects, and additional confounds inherent to retrospective studies, future studies are needed to examine the complex relationships between ketamine and psychological symptoms.

Illicit drug use contributes to substantial morbidity and mortality. Drug scheduling, a legal measure in drug enforcement, is often structured as a hierarchy based on addiction tendency, abuse trends, and harm, but may lack data-driven evidence when classifying substances. Our study aims to measure addiction tendency and use trends based on real-world data. We used the open access database of National Police Agency, Ministry of the Interior in Taiwan and analyzed all daily criminal cases of illicit drugs from 2013 to 2017 and monthly illicit drug enforcement data from the same database from 2002 to 2017. We hypothesized that repeat and frequent use despite legal consequence may be a reflection of addictive behavior, and empirical mode decomposition was applied in analysis to calculate addiction tendency indices and intrinsic 15-year use trends. Our analysis showed heroin has the highest addiction index, followed by methamphetamine. 3,4-Methyl enedioxy methamphetamine, marijuana, and ketamine had lower addictive propensities. This result is consistent with most drug scheduling hierarchies. 15-year use trends of substances were consistent with previous epidemiological studies., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background: Postanesthetic shivering is a common complication of anesthesia, which accounts for much discomfort in postoperative patients and may increase postoperative complications in high-risk patients. Due to the lack of high-quality evidence, it is difficult to draw a conclusion about optimal anti-shivering medication. The main purpose of this meta-analysis was to analyze and evaluate the efficacy and safety of prophylactic use of ketamine for preventing postanesthetic shivering., Methods: We searched the following databases: Medline, Embase, and the Cochrane Central Register of Controlled Trails for randomized controlled trials. The primary outcome observed was the difference of the incidence rate of postanesthetic shivering between ketamine group and placebo group. The secondary outcomes were the sedation score and incidence of the side effects caused by ketamine and any other drugs utilized in the studies., Results: In this meta-analysis, we analyzed a total of 16 trials including 1485 patients. Ketamine reduced the incidence rate of postanesthetic shivering compared to a placebo (odds ratio [OR]: 0.13, 95% confidence interval [CI]: 0.06 to 0.26, P<0.01). Regarding side effects, there was no evident variability of the incidence of nausea and vomiting. Usage of ketamine was associated with a lower rate of hypotension and bradycardia when compared to a placebo. Hallucinations were more frequently observed in patients who received higher doses of ketamine. No significant difference was found in the incidence of postanesthetic shivering with ketamine versus other pharmacological interventions., Conclusions: Ketamine can prevent postanesthetic shivering without severe side effects. However, ketamine shows no advantage over other anti-shivering drugs.

This case series describes the clinical courses of 3 juvenile Yucatan miniature swine ( Sus scrofa ) that experienced a suspected anaphylactic reaction to ketamine hydrochloride during premedication for protocol-related surgery. All 3 swine rapidly developed diffuse erythema shortly after injection with ketamine-containing drug combinations. Clinical signs ranged from tachycardia and erythema alone to tachycardia and erythema followed by respiratory and cardiac arrest. Ketamine was considered the most likely cause of these reactions because it was the only agent in the premedication sedation combination that was used in all 3 swine. Subsequent intradermal skin testing confirmed this suspicion. With supportive care measures and standard medical interventions for anaphylaxis, all 3 animals recovered well and went on to be successful experimental subjects when an alternative anesthetic regimen that did not contain ketamine was used. To our knowledge, this report is the first description of a suspected adverse ketamine reaction of this type in swine despite the widespread use of the drug in this species. Ketamine anaphylaxis is rare in people, but the few cases described presented with symptoms similar to the clinical signs seen in the pigs in this report. In addition to highlighting a potential adverse drug reaction to ketamine in swine, this case series demonstrates the value of emergency preparedness for even the most routine of procedures.

Background: Guidelines issued by the American Society of Regional Anesthesia and Pain Medicine suggest that ketamine infusions for acute pain management are advantageous as a primary treatment or as an opioid adjunct. Despite significant data regarding its use in adult patients, there remains a paucity of information related to its quality and side effect profile in pediatrics and how it can be effectively used. We aimed to summarize our practice of utilizing ketamine for pediatric pain management in non-critical care settings., Methods: Patients aged 0-21 years receiving low-dose ketamine infusions (≤0.3 mg/kg/hour) in inpatient care units over five years were retrospectively analyzed. Demographics, specific quality metrics, and side effects were quantified., Results: About 172 patients received 270 subhypnotic ketamine infusions. The median duration of the infusions was 63.8 hours and 0.2 mg/kg/hour for the highest dose. The primary indication for ketamine was chronic pain exacerbation (83.3%). Despite similar opioid consumption, there was a significant reduction in mean verbal pain scores before (8.9 ± 1.9, P < .001) and after ketamine (6.5 ± 2.7, P < .001) use. Although there were 52 incidences of some side effect (neurologic excitability [10.4%]; over-sedation [7.4%]; rapid response team alerts [1.1%]), none resulted in termination of the infusion or escalations in care., Conclusion: Ketamine can effectively be used as part of a multimodal analgesic regimen in pediatric patients in non-critical care settings. Our five-year experience using low-dose ketamine infusions highlights an acceptable side effect profile, with no attributable escalations in care or serious adverse events., (© 2019 The Acta Anaesthesiologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.)

Retinal lesions in the posterior pole of laboratory mice occur due to native, developmental abnormalities or as a consequence of environmental or experimental conditions. In this study, we investigated the rate and extent of retinal lesions as a result of prolonged ocular exposure following general anesthesia. Following experimental preparation induction procedures (EPIP) involving general anesthesia, mydriasis/cycloplegia, and topical anesthesia to the cornea, two ocular recovery conditions (protected and unprotected) were tested within two different animal recovery chambers (open or closed). The anterior and posterior poles were evaluated for the development of retinal lesions using digital color photography, scanning laser ophthalmoscopy, and spectral-domain optical coherence during anesthesia recovery and up to 2.5 months thereafter. In some mice, electroretinograms, histological and immunohistological evaluations were performed to assess functional and structural changes that accompanied the retinal lesions detected by in vivo imaging. Our data suggests that prolonged ocular surface exposure to circulating ambient room air leads to significant anterior and posterior segment ocular complications. The most abundant, semi-reversible complication observed was the development of lesions in the outer retina, which had a 90% probability of occurring after 45 min of exposure. The lesions mostly resolved short-term, but functional and imaging evidence suggest that some perturbations to the outer retina may persist one or more months following initial development., (Copyright © 2019. Published by Elsevier Ltd.)

The objective of this study was to gain better insight into factors associated with the capture-related mortality rate in cheetahs. A link to an online questionnaire was sent to zoo and wildlife veterinarians through the Species Survival Plan Programme and European Endangered Species Programme coordinators and via the 'Wildlife VetNet' Google group forum. The questionnaire consisted of 50 questions relating to the veterinarians' country of residence and experience, the medicine combinations used, standard monitoring procedures, capture-related complications and mortalities experienced in this species under different capture conditions. In addition, necropsy data from the national wildlife disease database of the National Zoological Gardens of South Africa were examined for cases where anaesthetic death was listed as the cause of death in cheetahs. A total of 75 veterinarians completed the survey, with 38 from African countries and a combined total of 37 from Europe, the United States (US) and Asia. Of these, 24% (n = 18/75) had experienced at least one capture-associated cheetah mortality, with almost all of the fatalities (29/30) reported by veterinarians working in Africa. A lack of anaesthetic monitoring and the absence of supplemental oxygen were shown to be significant risk factors for mortality. Hyperthermia, likely to be associated with capture stress, was the most common reported complication (35%). The results suggest that free-ranging rather than habituated captive cheetahs are particularly at risk of dying during immobilisation and transport. The capture-related fatalities in this species do not appear to be associated with either the veterinarian's level of clinical experience or the immobilisation agents used.

Two anesthetic protocols in adult giraffe were compared by retrospective study. Thirteen anesthesia records for medetomidine-ketamine (MK) and seven for medetomidine-ketamine with a potent opioid (MKO) were evaluated for differences in demographic, behavioral, drug, and respiratory parameters. Giraffe stood significantly more quickly with MKO vs MK though MK animals were physically restrained to preclude premature standing as part of normal recovery practices (5.5 min vs 21.4 min, P = 0.01). Regurgitation was recorded in 5/13 and resedation in 4/13 MK animals. The range of values for blood lactate was higher in MKO (5.18-11.25 mM/L) than in MK giraffe (0.78-6.08 mM/L). Despite limitations of a retrospective study, both MK and MKO giraffe anesthesia protocols exhibit benefits and side effects. Awareness and management of these factors will improve outcomes until standardized, prospective studies of giraffe immobilization offer more comprehensive guidance on protocol selection.

Objective: Depression relapse after electroconvulsive therapy (ECT) is common (40% at 6 months). Ketamine has a robust antidepressant effect, but there are no reported studies of ketamine for depression relapse prevention. This pilot trial (NCT02414932) was designed to assess feasibility of the proposed trial protocol, including examining reasons for nonrecruitment, nonrandomization, and dropout., Methods: Patients with unipolar depression referred for ECT were monitored weekly for therapeutic response, using the 24-item Hamilton Rating Scale for Depression (monitoring phase). Those who met standard response criteria were invited to be randomized to a course of 4 once-weekly infusions of ketamine (0.5 mg/kg) or the active comparator, midazolam (0.045 mg/kg), over 40 minutes to examine trial processes (treatment phase). Participants were followed up for 6 months after ECT to assess for relapse., Results: One hundred seventy-five referrals were screened over 18 months, and 68% of eligible participants (n = 43) were recruited to the monitoring phase; 60.5% of participants met ECT response criteria (n = 26), but only 26% (6) of these consented to take part in the treatment phase. These were randomized (3 to ketamine and 3 to midazolam), and no participant completed the 4-week treatment protocol. Information was gathered on reasons for nonrecruitment, nonrandomization, and dropout, which included practical aspects of infusions and lack of interest in further treatment after response to ECT., Conclusions: The proposed treatment protocol is not suitable for a definitive trial in our center. Information collected on reasons for dropout may inform future clinical trials of intravenous ketamine., Trial Registration: www.clinicaltrials.gov NCT02414932.

Prolonged or repeated exposure to ketamine, a common anesthetic in pediatrics, has been shown to induce neurotoxicity and long-term neurocognitive deficits in the developing brain. Therefore, identification of potential therapeutic targets for preventing or alleviating such neurodegeneration and neuroapoptosis induced by ketamine is urgently needed. Remote ischemic preconditioning of the limb provides neuroprotection in different models of cerebral injury. Thus, the present study aimed to assess whether remote ischemic preconditioning could have a neuroprotective effect against neurotoxicity induced by ketamine. In our study, 96 newborn rats were assigned to one of four groups, including control, remote ischemic preconditioning, ketamine, and remote ischemic preconditioning plus ketamine. Ketamine was administered intraperitoneally in six doses of 20 mg/kg at 2-h intervals. Limb remote ischemic preconditioning comprised four ischemia (5 min)/reperfusion (5 min) cycles in the right hind limb using an elastic rubber band tourniquet. Histopathological characteristics of cerebral damage were assessed by H&E staining and transmission electron microscopy. TUNEL assay, immunohistochemical staining and immunoblot were employed to evaluate neural cell apoptosis. Learning and memory were evaluated using the Morris water maze. The results showed increased cleaved caspase-3 protein levels in the cerebral cortex and the hippocampal CA1 region, severe cell damage and DNA breakage, and decreased spatial learning and memory abilities in the ketamine group in comparison with controls. Notably, these changes were significantly reduced by remote ischemic preconditioning. These findings suggest that remote ischemic preconditioning ameliorates neuroapoptosis and neurocognitive impairment after repeated ketamine exposure in newborn rats.