Der Anaesthesist
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The present review summarises the main actions of racemic ketamine and ketamine enantiomers on central nervous system receptors. The primary CNS action of ketamine appears to be a non-competitive block of N-methyl-D-aspartate receptors. Although numerous other receptors (e.g., GABA, nicotinic acetylcholine, opiate, voltage-operated channels) have been reported to interact with ketamine, their role in inducing dissociative anaesthesia is still under discussion. ⋯ Interestingly, in contrast to many other anaesthetics, middle-latency AEP were not altered by racemic and S-(+)-ketamine. This observation may indicate insufficient suppression of auditory stimulus processing during ketamine anaesthesia. Motor evoked responses to transcranial electrical or magnetic stimulation in humans are not markedly suppressed by ketamine.
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This review focuses on the significance of S-(+)-ketamine as a neuroprotective agent. Evidence in the literature supporting or contradicting a neuroprotective or even therapeutic role of ketamine in global cerebral ischaemia is critically reviewed, and data from an ongoing study in a rat global cerebral ischaemia model (15 min ischaemia with S(+)-ketamine administered 15 min after reperfusion) are reported. ⋯ Only at higher ketamine dosages was protection found reliably, especially in models of complete forebrain ischaemia lasting over 10 min. In our own study, only after 90 mg/kg S(+)-ketamine was there significantly better preservation of cortical neurons than without treatment; 30 and 60 mg/kg did not produce this effect.
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Randomized Controlled Trial Comparative Study Clinical Trial
[Combined 3-in-1 sciatic block. Prilocaine 500 mg vs. 650 mg].
The objective of the study was to investigate the clinical effectiveness of increasing the dosage of prilocaine for a combined 3-in-1/sciatic nerve block from 500 to 650 mg (open study with 29 patients compared with 30 patients from a former study) and to validate these findings in a second stage (randomised study comparing two groups of 30 patients each). Not only was clinical effectiveness improved by increasing the dose to 650 mg, but methaemoglobinaemia and toxicity were not relevant problems. With the higher dosage, development of the block was slightly faster (onset and completion); there were fewer unsatisfactory blocks; and clinically relevant plasma levels of methaemoglobin did not occur.
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ANAESTHETICS, ENDOCRINE SYSTEM, AND STRESS: The effects of anaesthetics on the nervous system are invariably associated with endocrine reactions, which are of great importance for the general characterization of anaesthetics or anaesthetic regimens. In this context, the endocrine stress response is mainly represented by adrenaline (A), noradrenaline (NA), antidiuretic hormone/vasopressin (ADH), adrenocorticotropic hormone (ACTH), and cortisol. PHARMACOLOGICAL PROFILE AND ANAESTHETIC ACTION OF KETAMINE: The pharmacological profile of ketamine is characterized by the term "dissociative anaesthesia." At the present time, the anaesthetic action of ketamine cannot be explained by a single mechanism. ⋯ The combination of S-(+)-ketamine and midazolam has weaker sympathomimetic and general endocrine-stimulating properties, and can be used for analgosedation in patients with cardiovascular instability and exogenous catecholamine requirements. In combination with propofol, the sympathomimetic and general endocrine-stimulating effects of S-(+)-ketamine are less pronounced because of contrasting properties of both drugs. This combination might be useful in patients with endocrine deficits and for analgosedation, when rapid recovery is necessary and negative circulatory effects should be avoided.
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A key question in cellular neuroprotection is how pharmacologic agents may protect neurons when applied after injury in clinically relevant concentrations. Of special importance is the N-methyl-D-aspartate (NMDA) antagonist ketamine, which offers the potential for regulation of intracellular calcium levels and pathophysiological NO induction by blocking excessive NMDA-receptor stimulation. This may reduce progressive neuronal degeneration and cell death. ⋯ S(+)-ketamine demonstrated a unique neuroregenerative potential that was associated with greater re-outgrowth of axonal neurites after mechanical injury and increased expression of growth-associated proteins after glutamate damage. S(+)-ketamine has a two- to four-fold higher affinity for the phencyclidine receptor of the NMDA receptor complex than ketamine racemate, and it is conceivable that the induction of a differentiated pattern of genes induces cellular growth activities via ketamine-mediated NMDA-receptor activation or blockade. However, further investigations elucidating ketamine's effects in animals and humans have to be performed before final decisions regarding a potential application of ketamine as a neuroprotective agent in the clinical setting can be made.