PREMEDICATION IN HYPERIRRITABLE CHILDREN USING SUBANAESTHETIC DOSES OF INTRAMUSCULAR KETAMINE.
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ABSTRACT:
SUBMITTER: Khanduri KC
PROVIDER: S-EPMC5531787 | biostudies-other | 1999 Jan
REPOSITORIES: biostudies-other
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Project description:Ketamine is an N-methyl D-aspartate receptor antagonist used off-label to facilitate dissociative anesthesia in children undergoing invasive procedures. Available for both intravenous and intramuscular administration, ketamine is commonly used when vascular access is limited. Pharmacokinetic (PK) data in children are sparse, and the bioavailability of intramuscular ketamine in children is unknown. We performed 2 prospective PK studies of ketamine in children receiving either intramuscular or intravenous ketamine and combined the data to develop a pediatric population PK model using nonlinear mixed-effects methods. We applied our model by performing dosing simulations targeting plasma concentrations previously associated with analgesia (>100 ng/mL) and anesthesia awakening (750 ng/mL). A total of 113 children (50 intramuscular and 63 intravenous ketamine) with a median age of 3.3 years (range 0.02 to 17.6 years), and median weight of 14 kg (2.4 to 176.1) contributed 275 plasma samples (149 after intramuscular, 126 after intravenous ketamine). A 2-compartment model with first-order absorption following intramuscular administration and first-order elimination described the data best. Allometrically scaled weight was included in the base model for central and peripheral volume of distribution (exponent 1) and for clearance and intercompartmental clearance (exponent 0.75). Model-estimated bioavailability of intramuscular ketamine was 41%. Dosing simulations suggest that doses of 2 mg/kg intravenously and 8 mg/kg or 6 mg/kg intramuscularly, depending on age, provide adequate sedation (plasma ketamine concentrations >750 ng/mL) for procedures lasting up to 20 minutes.
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Project description:Several studies have documented impairments in memory processes as a result of ketamine administration; however, few studies have compared the profile of cognitive effects of ketamine to other drugs.The aim of this study was to compare the cognitive effects of ketamine with those of triazolam in healthy volunteers.Doses of ketamine (0.2, 0.4 mg/kg intramuscular (i.m.)), triazolam (0.2, 0.4 mg/70 kg p.o.), and double-dummy placebos were administered to 20 volunteers under repeated measures, counterbalanced, double-blind conditions. Peak physiological, psychomotor, subjective, and cognitive effects were examined.Ketamine impaired balance when balance was assessed early in the task order, whereas triazolam impaired psychomotor coordination and divided attention irrespective of task order. Triazolam also tended to produce greater effects on working memory and episodic memory tasks than ketamine at doses that produced lower subjective effects and higher estimates of performance.Ketamine produces less cognitive impairment than triazolam at doses that produced greater subjective effects. Thus ketamine does not produce the underestimation of cognitive impairment typically seen with triazolam.
| S-EPMC3572303 | biostudies-literature
Project description:Clinical findings show that a single subanesthetic dose of ketamine elicits rapid antidepressant effects. Accumulating data suggests that ketamine blocks the N-methyl-D-aspartate receptor and results in specific effects on intracellular signaling including increased brain-derived neurotrophic factor (BDNF) protein expression, which augments synaptic responses required for rapid antidepressant effects. To further investigate this potential mechanism for ketamine's antidepressant action, we examined the effect of increasing ketamine doses on intracellular signaling, synaptic plasticity, and rapid antidepressant effects. Given that ketamine is often used at 2.5-10 mg/kg to examine antidepressant effects and 20-50 mg/kg to model schizophrenia, we compared effects at 5, 20 and 50 mg/kg. We found that intraperitoneal (i.p.) injection of low dose (5 mg/kg) ketamine produces rapid antidepressant effects, which were not observed at 20 or 50 mg/kg. At 5 mg/kg ketamine significantly increased the level of BDNF, a protein necessary for the rapid antidepressant effects, while 20 and 50 mg/kg ketamine did not alter BDNF levels in the hippocampus. Low concentration ketamine also evoked the highest synaptic potentiation in the hippocampal CA1, while higher concentrations significantly decreased the synaptic effects. Our results suggest low dose ketamine produces antidepressant effects and has independent behavioral and synaptic effects compared to higher doses of ketamine that are used to model schizophrenia. These findings strengthen our knowledge on specific signaling associated with ketamine's rapid antidepressant effects.
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Project description:What is the level of consciousness of the psychedelic state? Empirically, measures of neural signal diversity such as entropy and Lempel-Ziv (LZ) complexity score higher for wakeful rest than for states with lower conscious level like propofol-induced anesthesia. Here we compute these measures for spontaneous magnetoencephalographic (MEG) signals from humans during altered states of consciousness induced by three psychedelic substances: psilocybin, ketamine and LSD. For all three, we find reliably higher spontaneous signal diversity, even when controlling for spectral changes. This increase is most pronounced for the single-channel LZ complexity measure, and hence for temporal, as opposed to spatial, signal diversity. We also uncover selective correlations between changes in signal diversity and phenomenological reports of the intensity of psychedelic experience. This is the first time that these measures have been applied to the psychedelic state and, crucially, that they have yielded values exceeding those of normal waking consciousness. These findings suggest that the sustained occurrence of psychedelic phenomenology constitutes an elevated level of consciousness - as measured by neural signal diversity.
| S-EPMC5396066 | biostudies-literature
Project description:Background: In the last few years, ketamine is becoming increasingly common in the treatment of mental health conditions, but there is a lack of safety data informing intramuscular and sublingual dosing in a community-focused group psychotherapy setting. The Roots To Thrive ketamine-assisted therapy (RTT-KaT) program is a unique 12-week RTT-KaT program with 12 community of practice (a form of group therapy) sessions and three ketamine medicine sessions. Objectives: This study reports on adverse effects of intramuscular and sublingual ketamine dosing in a community group psychotherapy setting among 128 participants across four cohorts. Design: Retrospective chart review. Methods: A chart review of the RTT-KaT Program was performed retrospectively on four cohorts (n = 128) that participated in 448 sessions running between September 2020 and December 2021. Baseline characteristics and adverse events were captured including medication administration before, during, and after RTT-KaT sessions. Analyses by session and by individual were conducted. Chi-square test with Yates’ continuity correction was used to assess side effects in subgroups from ketamine administration. Results: RTT-KaT was well tolerated with none of the 128 participants dropping out of the program. Primarily, of the 448 sessions, 49.16% had elevated blood pressures post-KaT session by session. In terms of other adverse effects, 12.05% of participant-sessions experienced nausea, 2.52% had an episode of vomiting, 3.35% had a headache, and seven participant-sessions experienced dizziness. Analysis by individual revealed congruent findings. Conclusion: These findings suggest good safety and tolerability for RTT-KaT among individuals seeking treatment for mental health issues. The majority of participants did not experience adverse reactions and the adverse events that were recorded involved transient symptoms that were resolved with rest and/or medications. The group therapy model described provides a comprehensive approach and presents a promising model for operating a KaT program in a community setting.
| S-EPMC10225955 | biostudies-literature
Project description:BackgroundKetamine has emerged as a promising pharmacotherapy for depression and other mental illnesses, and the intramuscular (IM) administration of ketamine is now offered at many North American outpatient psychiatric clinics. However, a characterization of the outpatient population receiving IM ketamine treatment and an evaluation of the real-world depression, anxiety, and safety outcomes of long-term psychiatric IM ketamine treatment has not been reported. This study aimed to evaluate the clinical characteristics, treatment patterns, clinical outcomes, and adverse events of patients receiving IM ketamine treatment.MethodsPatient data from the electronic health records of a private outpatient psychiatric clinic network in the United States were collected and analyzed retrospectively. Adults with any psychiatric diagnosis who received ketamine treatment only by IM administration from January 2018 to June 2021 were included. A total of 452 patients were included in the cohort.ResultsPatients receiving IM ketamine treatment had a mean of 2.8 (SD 1.4) psychiatric diagnoses. 420 (93%) patients had a diagnosis of major depressive disorder, 243 (54%) patients had a diagnosis of generalized anxiety disorder, and 126 (28%) patients had a diagnosis of post-traumatic stress disorder. Patients received a median of 4 (range 1-48) IM ketamine treatments. Median depression scores (PHQ-9) improved 38% from 16.0 (IQR 11.3-21.8) at baseline to 10.0 (IQR 6.0-15.0) at last treatment (p < .001). Median anxiety scores (GAD-7) improved 50% from 14.0 (IQR 8.0-17.0) at baseline to 7.0 (IQR 4.3-11.8) at last treatment (p < .001). With maintenance ketamine treatments, average improvements in depression (PHQ-9) and anxiety (GAD-7) scores of at least 4.7 and 4.9 points were maintained for over 7 months. An adverse event occurred during 59 of 2532 treatments (2.3%).ConclusionsIM ketamine is being utilized to treat psychiatric outpatients with multiple mental illnesses not limited to depression. Average depression and anxiety levels significantly improve throughout IM ketamine treatment and do not regress to baseline during patients' maintenance treatment phase. Prospective studies are recommended to confirm the long-term effectiveness and safety of IM ketamine.
| S-EPMC9528178 | biostudies-literature
Project description:Activity-dependent neuroprotective protein (ADNP) syndrome is a rare neurodevelopmental disorder caused by mutations in the ADNP gene, resulting in intellectual disability, developmental delay and autism spectrum disorder (ASD). Ketamine treatment has emerged as a promising therapeutic option for children with ADNP syndrome, showing safety and significant behavioral improvements. However, the underlying molecular perturbations caused by ketamine remain poorly described. We dissected the longitudinal effect of ketamine on the peripheral blood transcriptome of 10 individuals with ADNP syndrome. The blood transcriptome was profiled prior-to intravenous ketamine treatment (0.5mg/kg) and then again at five post-infusion timepoints: immediately post-infusion, day 1, week 1, week 2, and week 4. We show that a single low-dose infusion of ketamine triggers immediate and profound gene expression alterations, with specific enrichment of monocyte-related expression patterns. These alterations encompass diverse signaling pathways and co-expression networks, implicating up-regulation of immune and inflammatory-related processes and down-regulation of RNA processing mechanisms and metabolism. Notably, these changes exhibit a transient nature, returning to baseline levels 24 hours to 1 week after treatment. These findings advance our understanding of ketamine's molecular effects and provides a foundation for further research in elucidating its precise cellular and molecular targets. Moreover, the comprehensive assessment of ketamine-induced changes in ADNP syndrome contributes to the development of innovative therapeutic strategies for this challenging genetic disorder.
2023-07-02 | GSE235921 | GEO
Project description:ObjectivesTo report the experience of using intramuscular ketamine 2.0 or 2.5 mg/kg for minor painful procedures in children in a medium sized district general hospital accident and emergency department. To demonstrate the safety and acceptability of ketamine and determine if the incidence of adverse effects is related to dose or other variables.MethodsProspective data collection and analysis using Statsdirect and SPSS software.Results501 consecutive cases were collected from August 1996 to April 2002. A total of 310 children received 2.0 mg/kg and 191 received 2.5 mg/kg. Twenty six received a second dose. In seven cases oxygen saturation fell below 93%, three of these fell below 90%. There was one case of laryngospasm. Eight cases received airway suctioning, five of these were mouth or lip wounds. Seventeen per cent vomited in recovery or at home for which one child required admission. Muscle hypertonicity was observed in 6.8%, disturbed sleep or nightmares in 2%. The median time to discharge was 85 minutes. Ninety seven per cent of parents' experiences were "the same as" or "better than" expected. No children suffered any lasting or troublesome complications.Conclusions2.0 - 2.5 mg/kg intramuscular ketamine sedation is a safe and acceptable technique when used within a defined protocol. Lower dose ketamine (2 mg/kg) warrants further study in view of potentially less airway complications and quicker discharge times than previously reported.
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Project description:RATIONALE:Low-dose ketamine is a rapid-acting antidepressant, to which female rodents are more sensitive as compared to males. However, the mechanism mediating this sex difference in ketamine sensitivity remains elusive. OBJECTIVES:We sought to determine whether male and female mice differ in their behavioral sensitivity to low doses of ketamine, and uncover how ovarian hormones influence females' ketamine sensitivity. We also aimed to uncover some of the molecular mechanism(s) in mood-related brain regions that mediate sex differences in ketamine antidepressant effects. METHODS:Male and female mice (freely-cycling, diestrus 1 [D1], proestrus [Pro], or D1 treated with an estrogen receptor (ER) α, ERβ, or progesterone receptor (PR) agonist) received ketamine (0, 1.5, or 3 mg/kg, intraperitoneally) and were tested in the forced swim test (FST) 30 min later. Ketamine's influence over synaptic plasticity markers in the prefrontal cortex (PFC) and hippocampus (HPC) of males, D1, and Pro females was quantified by Western blot 1 h post-treatment. RESULTS:Males, freely cycling females, D1 and Pro females exhibited antidepressant-like responses to 3 mg/kg ketamine. Pro females were the only group where ketamine exhibited an antidepressant effect at 1.5 mg/kg. D1 females treated with an agonist for ERα or ERβ exhibited an antidepressant-like response to 1.5 mg/kg ketamine. Ketamine (3 mg/kg) increased synaptic plasticity-related proteins in the PFC and HPC of males, D1, and Pro females. Yet, Pro females exhibited an increase in p-Akt and p-CaMKIIα in response to 1.5 and 3 mg/kg ketamine. CONCLUSION:Our results indicate that females' enhanced sensitivity to ketamine during Pro is likely mediated through estradiol acting on ERα and ERβ, leading to greater activation of synaptic plasticity-related kinases within the PFC and HPC.
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Project description:The gray squirrel is one of the most common invasive species in Europe, whose presence is dangerous for the survival of the European red squirrel. To cope with this biological invasion and to safeguard biodiversity, the LIFE+U-SAVEREDS project aims to protect the red squirrel, by limiting the growth of the current population of gray squirrels and simultaneously promoting their eradication with surgical sterilization. This study compares two different anesthetic protocols, including dexmedetomidine (40 µg/kg) and midazolam (0.3 mg/kg) associated with ketamine (15 mg/kg; n = 25 squirrels) or alfaxalone (5 mg/kg; n = 22 squirrels). A blinded investigator evaluated the quality and onset of sedation, intraoperative anesthesia, and recovery, as well as the physiologic parameters for each animal. Alfaxalone provided a good quality of anesthesia with limited cardiovascular effects (p < 0.05) and good intraoperative myorelaxation. Ketamine induced complete relaxation in a shorter time (p < 0.05) and a rapid (p < 0.001) and excellent (p < 0.05) recovery. Despite the overall superiority of ketamine, alfaxalone appeared to be an adequate alternative anesthetic drug that can be administered without requiring intravascular access. It should be rapidly metabolized and excreted; however, it requires the combination of longer acting sedatives/myorelaxants to prevent a poor recovery quality.
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