Anesthesiology
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Propofol is increasingly used for cardiac anesthesia and for perioperative sedation. Because pharmacokinetic parameters vary among distinct patient populations, rational drug dosing in the cardiac surgery patient is dependent on characterization of the drug's pharmacokinetic parameters in patients actually undergoing cardiac procedures and cardiopulmonary bypass (CPB). In this study, the pharmacokinetics of propofol was characterized in adult patients undergoing coronary revascularization. ⋯ The pharmacokinetics of propofol in adult patients undergoing cardiac surgery with CPB are dissimilar from those reported for other adult patient populations. The effect of CPB was best modeled by an increase in V1 and Cl1. Predictive accuracy of the derived pharmacokinetic parameters was excellent as measured by cross-validation and a prospective test.
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A defect in the ryanodine (Ry1) receptor Ca2+ channel has been implicated as one of the possible underlying causes of malignant hyperthermia (MH), a pharmacogenetic disorder characterized by sustained muscle contracture. The disease is triggered by common halogenated anesthetics and skeletal muscle relaxants, such as succinylcholine. This study tested whether the functional properties of the Ry1 receptor Ca2+ channel are affected by chlorocresol, a preservative added to a commercial preparation of succinylcholine (Midarine) and other parenteral compounds. ⋯ These data suggest that, in muscle from MHS individuals, the enhanced Ca2+ released from the sarcoplasmic reticulum may not be due to the effect of succinylcholine alone but rather to the action of the preservative chlorocresol added to the drug.
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Dantrolene sodium (DS) is a direct-acting skeletal muscle relaxant whose only known action is to block calcium release from intracellular storage sites. The exact site of action for DS is unknown, but its efficacy in treating and preventing anesthetic-induced malignant hyperthermia (MH) is well established. ⋯ The study results suggest that at least two binding sites for DS exist on the Ry1 receptor calcium channel. A low-affinity (microM) site is associated with reduced channel gating and open-state dwell time and may relate to the established pharmacologic muscle relaxant effect of DS. The proposed high-affinity (nM) DS binding site activates the channel, producing Ca2+ release to the myoplasm, which, under environmentally adverse conditions, could damage genetically predisposed MH muscle. Such a phenomenon, if it occurs in DS treated MH patients, could generate a recrudescence of the syndrome.
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Biodegradable microspheres are a useful method of drug delivery because they are both injectable and biodegradable, eliminating the need for surgical implantation or removal. Previous work has characterized implantable preparations of local anesthetics in polymer pellets for prolonged regional anesthesia. In this article, the authors characterize injectable suspensions of bupivacaine-polymer microspheres and examine whether they can produce prolonged blockade of the sciatic nerve in rats. ⋯ Prolonged percutaneous blockade of peripheral nerves is feasible. The recovery from blockade is complete, and plasma bupivacaine levels are far below the range associated with systemic toxicity. The mechanisms underlying the dexamethasone block-prolonging effect are under investigation.
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Barbiturates have previously been demonstrated to reduce focal cerebral ischemic brain damage. However, the dose of drug required to elicit maximal neuroprotection has not been defined. The authors' hypothesized that doses of pentobarbital substantially lower than those required to cause electroencephalographic burst suppression would result in maximal magnitudes of reduction of cerebral infarct volume. ⋯ Sodium pentobarbital administered at either dose (active electroencephalogram or burst suppression) resulted in an approximately equal to 25% reduction of cerebral infarct size, indicating that burst suppression is not required to elicit maximal neuroprotective efficacy.