Anesthesiology
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The pharmacokinetic profiles of sufentanil available in the literature are conflicting because of methodologic differences. Length of sampling and assay sensitivity are key factors involved in accurately estimating the volumes of distribution, clearances, and elimination phase. The unit disposition function of increasing doses of sufentanil were investigated and the influence of dose administered on the linearity of pharmacokinetics was assessed. ⋯ Sufentanil pharmacokinetics were linear within the dose range studied. Drug detection up to 24 h after dosing was necessary to define the terminal elimination phase. The metabolic clearance approached liver blood flow and a large volume of distribution was identified, consistent with the long terminal elimination half-life. Simulations predicted that plasma sufentanil steady-state concentrations would rapidly decline after termination of an infusion despite the long half-lives.
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Use of long-acting local anesthetics that elicit complete neural blockade for more than 3 h often is desirable in pain management. Unfortunately, clinically available local anesthetics are in general not suitable for prolonged analgesia. This report describes the organic synthesis and functional testing of a lidocaine derivative that appears to fulfill the criteria of long-acting local anesthetics. ⋯ In an attempt to elicit prolonged local anesthesia, a quaternary ammonium derivative of lidocaine containing a permanent charge and an additional hydrophobic component was synthesized. Complete sciatic neural blockade of more than 3 h was achieved with this derivative. Of note, sensory blockade was prolonged to a greater extent than motor blockade. The approach used in this study may prove useful for developing new drugs applicable in pain management.
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Randomized Controlled Trial Clinical Trial
Desflurane slightly increases the sweating threshold but produces marked, nonlinear decreases in the vasoconstriction and shivering thresholds.
Shivering is rare during general anesthesia. This observation suggests that anesthetics profoundly impair shivering. However, the effects of surgical doses of volatile anesthetics on control of shivering have yet to be evaluated. Furthermore, the effects of desflurane on sweating and thermoregulatory vasoconstriction remain unknown. Accordingly, the authors determined the concentration-dependent effects of desflurane on sweating, vasoconstriction, and shivering. ⋯ The observed linear increase in the sweating threshold was similar in pattern and magnitude to that produced by most general anesthetics. The approximately 3 degrees C reduction in the vasoconstriction threshold by 0.8 MAC desflurane was similar to that observed previously during isoflurane and propofol anesthesia. However, the threshold was reduced less than expected at 0.5 MAC, suggesting that the dose-response relationship for vasoconstriction is nonlinear. Shivering was induced without difficulty in this study although the response is rare in surgical patients. It is likely that shivering during general anesthesia is rare because thermoregulatory vasoconstriction usually prevents body temperature from decreasing the required additional 1-1.5 degrees C.
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Randomized Controlled Trial Clinical Trial
Effects of storage time on quantitative and qualitative platelet function after transfusion.
Platelet transfusions are being used increasingly in patients with thrombocytopenia to improve hemostatic function before surgery and invasive procedures. However, there are limited data on the immediate quantitative and qualitative platelet response after transfusion. Some authors have suggested that transfused platelets require time in vivo to regain maximal function, which is dependent on the duration of platelet storage. Therefore, the timing of surgery and invasive procedures with optimal platelet function may not be occurring. ⋯ In patients with chemotherapy-induced thrombocytopenia, platelet transfusion causes an immediate increase in number and function, which is independent of storage time. This quantitative and qualitative increase persists unchanged for 2 h after transfusion, suggesting that there is no acute "warm-up-time" necessary for transfused platelets to regain maximal function. Fresh platelets demonstrate increased aggregation and dense granule release compared to 4-day stored platelets and may impart improved hemostatic function in vivo.
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It was hypothesized that stimulation of rapidly adapting airway receptors produces the transient (2-4 min) circulatory responses to rapid increases in desflurane concentrations greater than 6%. Accordingly, it was reasoned that increasing the concentration of desflurane in one lung, without altering the concentration of desflurane in systemic blood, should cause cardiovascular stimulation, whereas once the airway receptors had adapted to the stimulation, an initial increase in the systemic concentration of desflurane should have little effect. ⋯ It was concluded that at least two sites respond to a rapid increase in desflurane concentrations greater than 6%: one site in the airways and/or lungs, and at least one other in a highly perfused tissue(s). The systemic site contributes more importantly.