Ketamine

Recently it became clear that opioids, besides their role in analgesia, mayalso induce hyperalgesia. Something what in the past was called opioidneurotoxicity. Hyperalgesia, or hypersensitivity to pain stimuli may berelated to well known problems of tolerance to opioids. Hyperalgesia is amajor clinical problem and its recognition and treatment are of paramountimportance. It is believed that uncoupling of opioid receptors from theGi/Go proteins and coupling them to Gs protein changes dramatically activityof opioid receptors. In this article the different aspects of diagnosis andtreatment of hyperalgesia are discussed.

Objective-To evaluate pulmonary and cardiovascular effects of a recruitment maneuver (RM) combined with positive end-expiratory pressure (PEEP) during total intravenous anesthesia in ponies. Animals-6 healthy adult Shetland ponies. Procedure-After premedication with detomidine (10 µg/kg, IV), anesthesia was induced with climazolam (0.06 mg/kg, IV) and ketamine (2.2 mg/kg, IV) and maintained with a constant rate infusion of detomidine (0.024 mg/kg/h), climazolam (0.036 mg/kg/h), and ketamine (2.4 mg/kg/h). The RM was preceded by an incremental PEEP titration and followed by a decremental PEEP titration, both at a constant airway pressure difference (∆P) of 20 cm H 2 O. The RM consisted of a stepwise increase in ∆P by 25, 30, and 35 cm H 2 O obtained by increasing peak inspiratory pressure (PIP) to 45, 50, and 55 cm H 2 O, while maintaining PEEP at 20 cm H 2 O. Hemodynamic and pulmonary variables were analyzed at every step of the PEEP titration-RM. Results-During the PEEP titration-RM, there was a significant increase in PaO 2 (+12%), dynamic compliance (+ 62%), and heart rate (+17%) and a decrease in shunt (-19%) and mean arterial blood pressure (-21%) was recorded. Cardiac output remained stable. Conclusions and Clinical Relevance-Although baseline oxygenation was high, PaO 2 and dynamic compliance further increased during the RM. Despite the use of high PIP and PEEP and a high tidal volume, limited cardiovascular compromise was detected. A PEEP titration-RM may be used to improve oxygenation in anesthetized ponies. During stable hemodynamic conditions, PEEP titration-RM can be performed with acceptable adverse cardiovascular effects. (Am J Vet Res 2006;67:152-159)

Current analytical methods used for screening drugs and their metabolites in biological samples from victims of drug-facilitated sexual assault (DFSA) or other vulnerable groups can lack sufficient sensitivity. The application of liquid chromatography, employing small particle sizes, with tandem mass spectrometry (MS/MS) is likely to offer the sensitivity required for detecting candidate drugs and/or their metabolites in urine, as demonstrated here for ketamine. Ultra-performance liquid chromatography-mass spectrometry (UPLC-MS/MS) was performed following extraction of urine (4 mL) using mixed-mode (cation and C8) solid-phase cartridges. Only 20 L of the 250 L extract was injected, leaving sufficient volume for other assays important in DFSA cases. Three ion transitions were chosen for confirmatory purposes. As ketamine and norketamine (including their stable isotopes) are available as reference standards, the assay was additionally validated for quantification purposes to study elimination of the drug and primary metabolite following a small oral dose of ketamine (50 mg) in 6 volunteers. Dehydronorketamine, a secondary metabolite, was also analyzed qualitatively to determine whether monitoring could improve retrospective detection of administration. The detection limit for ketamine and norketamine was 0.03 ng/mL and 0.05 ng/mL, respectively, and these compounds could be confirmed in urine for up to 5 and 6 days, respectively. Dehydronorketamine was confirmed up to 10 days, providing a very broad window of detection.

Ketamine is an anaesthetic compound used in human and veterinary medicine with hallucinogen properties that have resulted in its increased illicit use by teenagers at rave parties. Although several gas chromatography/mass spectrometry (GC/MS) methods have been reported for the quantification of the drug both in urine and in hair, its electron ionization (EI) fragmentation after derivatization with different reagents has been not yet fully investigated. The present work reports the study of the fragmentation of ketamine, derivatized with heptafluorobutyric anhydride (HFBA-Ket), using gas chromatography/electron ionization mass spectrometry (GC/EI-MS). The complete characterization of the fragmentation pattern represented an intriguing exercise and required tandem mass spectrometry (MS n ) experiments, high-resolution accurate mass measurements and the use of deuterated d 4 -ketamine to corroborate the proposed structures and to characterize the fragment ions carrying the unchanged aromatic moiety. Extensive fragmentation was observed, mainly located at the cyclohexanone ring followed by rearrangement of the fragment ions, as confirmed by the mass spectra obtained from the deuterated molecule. The GC/EI-MS analysis of HFBA-Ket will represent a useful tool in forensic science since high-throughput analyses are enabled, preserving both the GC stationary phase and the cleanliness of the mass spectrometer ion optics.

Excited delirium syndrome (ExDS) is a medical emergency usually presenting first in the prehospital environment. Untreated ExDS is associated with a high mortality rate and is gaining recognition within organized medicine as an emerging public safety problem. It is highly associated with male gender, middle age, chronic illicit stimulant abuse, and mental illness. Management of ExDS often begins in the field when first responders, law enforcement personnel, and emergency medical services (EMS) personnel respond to requests from witnesses who observe subjects exhibiting bizarre, agitated behavior. Although appropriate prehospital management of subjects with ExDS is still under study, there is increasing awareness of the danger of untreated ExDS, and the danger associated with the need for subject restraint, whether physical or chemical. We describe two ExDS patients who were successfully chemically restrained with ketamine in the prehospital environment, and who had good outcomes without complication. These are among the first case reports in the literature of ExDS survival without complication using this novel prehospital sedation management protocol. This strategy bears further study and surveillance by the prehospital care community for evaluation of side effects and unintended complications.

Background: Recent brain imaging studies have indicated that schizophrenia is associated with increased amphetamine-induced dopamine release in the striatum. It has long been hypothesized that dysregulation of subcortical dopamine systems in schizophrenia might result from a failure of the prefrontal cortex (PFC) to adequately control subcortical dopaminergic function. The activity of midbrain dopaminergic neurons is regulated, in part, by glutamatergic projections from the PFC acting via glutamatergic N-methyl-D-aspartate (NMDA) receptors. The goal of this study was to test the hypothesis that a pharmacologically induced disruption of NMDA transmission leads to an increase in amphetamine-induced dopamine release in humans. Methods: In eight healthy volunteers, we compared striatal amphetamine-induced (0.25 mg/kg) dopamine release under control conditions and under sustained disruption of NMDA transmission induced by infusion of the noncompetitive NMDA antagonist ketamine (0.2 mg/kg intravenous bolus followed by 0.4 mg/kg/hour intravenous infusion for 4 hours). Amphetamine-induced dopamine release was determined with single photon emission computed tomography, as the reduction in the binding potential (BP) of the radiolabeled D 2 receptor antagonist [ 123 I]IBZM. Results: Ketamine significantly enhanced the amphetamine-induced decrease in [ 123 I]IBZM BP, from Ϫ5.5% Ϯ 3.5% under control conditions to Ϫ12.8% Ϯ 8.8% under ketamine pretreatment (repeated-measures analysis of variance, p ϭ .023). Conclusions: The increase in amphetamine-induced dopamine release induced by ketamine (greater than twofold) was comparable in magnitude to the exaggerated response seen in patients with schizophrenia. These data are consistent with the hypothesis that the alteration of dopamine release revealed by amphetamine challenge in schizophrenia results from a disruption of glutamatergic neuronal systems regulating dopaminergic cell activity.

Ketamine is an N-methyl-D-aspartate (NMDA) receptor antagonist that has been found to induce schizophrenia-type symptoms in humans and is a potent and fast-acting antidepressant. It is also a relatively widespread drug of abuse, particularly in China and the UK. Acute administration has been well characterized, but the effect of extended periods of ketamine use-on brain structure in humans-remains poorly understood. We measured indices of white matter microstructural integrity and connectivity in the brain of 16 ketamine users and 16 poly-drug-using controls, and we used probabilistic tractography to quantify changes in corticosubcortical connectivity associated with ketamine use. We found a reduction in the axial diffusivity profile of white matter in a right hemisphere network of white matter regions in ketamine users compared with controls. Within the ketamine-user group, we found a significant positive association between the connectivity profile between the caudate nucleus and ...

The Selva Pascuala mural, a work of post-Paleolithic rock art in Spain, contains fungoid figures herein hypothesized to depict neurotropic fungi, especially Psilocybe hispanica, a species that occurs in a neighboring region. This hypothesis is based on features of these figures related to fungal morphology, along with ethnographic analogy, and shamanistic explanations of rock art. If correct, this interpretation would support inference of prehistoric utilization of this fungus in the region. The mural represents the first direct evidence for possible ritual use of Psilocybe in prehistoric Europe.