Der Anaesthesist
-
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.
-
Although ketamine has been in clinical use for 3 decades, the neuropharmacological basis of its analgesic, anaesthetic, sympathomimetic, and psychotomimetic effects is still a subject of controversial discussion and intensive investigational efforts. In recent years, however, new experimental approaches to its effects on the cellular and molecular level and the availability of pure ketamine enantiomers contributed substantially to the understanding of its complex neuropharmacology. ⋯ In contrast to the uncertainty surrounding the potential role of opioid receptors, there is now considerable evidence that NMDA antagonism is a central mechanism that contributes to the amnesic, analgesic, anaesthetic, and psychotomimetic as well as the neuroprotective actions of ketamine. Moreover, the involvement of non-NMDA glutamate receptors, muscarinic and nicotinic cholinergic transmission, interactions with 5-HT receptors, and L-Type Ca2+ channels may account for some of its anaesthetic and neuroprotective properties.
-
Almost all patients treated with opioids suffer from constipation. Numerous laxatives are used to overcome the problem, but none has yet been found to yield favourable results in all patients. Several studies have attempted to reverse opioid-induced constipation by the use of oral naloxone. Experiments carried out in rats showed that morphine-induced constipation is reduced by oral naloxone without impairment of antinociception [4]. However, evaluation of clinical studies reveals that there is uncertainty about the dosage regimen (the daily dose of naloxone ranged from 0.5% to about 60% that of morphine) and a lack of larger numbers of patients studied. ⋯ The medical history of the 3 patients in whom naloxone failed to abolish constipation revealed neurological disturbances. Treatment of these patients included the use of neuroleptics, antiemetics, and other drugs. In this context, it should be noted that oral naloxone can be expected to abolish only opioid-induced constipation. In conclusion, it was found that the treatment of opioid-induced constipation by administration of oral naloxone produced positive results. A controlled study will show, whether the side effects can be minimized by reducing the naloxone dose.
-
Closed-system anaesthesia provides the best prerequisites for optimal warming and humidification of anaesthetic gases. The PhysioFlex anaesthesia machine fascilitates quantitative closed-system anaesthesia. Furthermore, its design may improve the climatization of the anaesthetic gases by revolving the system volume at 70 l/min, using a small soda-lime canister to allow optimal usage of the heat and moisture generated by CO2 absorption and by integrating all system components in thermally isolating housing. To determine the capacity of the PhysioFlex to climatize anaesthetic gases, we evaluated the heat and humidity profile at four characteristic places in the anaesthetic circuit under standardised conditions in a model. ⋯ With the PhysioFlex anaesthesia machine employing closed-system conditions, minimal climatization of anaesthetic gases was reached within 10 min. After a period of 120 min, the anaesthetic gases were nearly climatized to the extent recommended for long-term respiratory therapy. To date, no comparable temperature and humidity level has been reported with conventional anaesthesia machines. The time course of the gradient between M1 and M2 may give an opportunity for further optimising the system in reducing heat loss after the soda-lime canister, the active heat and moisture source in the circuit. At about 32 degrees C, the temperature in the soda-lime canister is 10-15 degrees C less than in conventional anaesthesia machines. Thus, the use of thermally instable volatile anaesthetics in the PhysioFlex under closed-system conditions may be less critical than in conventional anaesthesia machines under minimal-flow conditions.