Anesthesiology
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Randomized Controlled Trial Comparative Study Clinical Trial
Diuretic effect of clonidine during isoflurane, nitrous oxide, and oxygen anesthesia.
Because clonidine, a relative selective alpha 2-agonist, inhibits the action of arginine vasopressin (AVP), the authors examined whether clonidine as an oral preanesthetic medication would induce diuresis and also would affect AVP release and its action during general anesthesia. ⋯ Oral preanesthetic medication of clonidine 2.5 or 5 micrograms.kg-1 caused a significant diuretic effect during surgery under general anesthesia, though it did not apparently relate to AVP action. This effect of clonidine could be related to its pharmacological action as an alpha 2-adrenoceptor agonist not necessarily restricted to the kidney. The diuretic effect of clonidine implicates its clinical importance in the management of patients during anesthesia.
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Randomized Controlled Trial Clinical Trial
Repetitive rapid increases in desflurane concentration blunt transient cardiovascular stimulation in humans.
Rapid increases in desflurane concentrations above minimum alveolar concentration (MAC) can cause transient (2-4-min) circulatory changes, possibly from stimulation of rapidly-adapting airway receptors. We hypothesized that the initial increase in concentration would produce greater changes than subsequent increases. ⋯ An initial rapid increase in desflurane to 1.1 MAC produces much more stimulation than do subsequent increases, regardless of the presence of nitrous oxide. The decreased response is consistent with the hypothesis that stimulation of rapidly-adapting airway receptors produce the initial response.
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Several recent studies have suggested that the terminal half-lives of many drugs do not predict the rate of washout of drug after the relatively short durations of infusions used in anesthesia. Many anesthetic drugs fit a three-compartment mamillary model, with three volumes of distribution (central [V1] and peripheral [V2 and V3]) and three clearances (elimination or metabolic [Cl1] and distribution [Cl2 and Cl3]). It has been suggested that a large V3:Cl3 ratio contributes to rapid recovery after infusion. We investigated the role of each of these primary pharmacokinetic parameters to determine values of each that would contribute to rapid recovery after various dosing schemes. ⋯ This study proposes qualitative guidelines for pharmacokinetic properties desirable in anesthetic drugs. If a rapid decrease in plasma concentration is desired after an infusion, it is always beneficial to have a small V1 and a large Cl1. For infusions of short duration, after which only a small decrease in plasma concentration is required, it is beneficial to have a larger V2, V3, Cl2, and Cl3. For infusions of longer duration, after which a large decrease in plasma concentration is desired, it is beneficial to have a smaller V2, V3, Cl2, and Cl3. These proposals may be beneficial for planning clinical trials of new drugs.
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Levosimendan is a myofilament calcium sensitizer with phosphodiesterase III inhibiting properties which increases contractile state in vitro by stabilizing calcium-induced changes in troponin C. This latter effect may produce positive inotropic actions but may also cause deleterious negative lusitropic effects. This investigation examined the effects of levosimendan on systemic and coronary hemodynamics and left ventricular systolic and diastolic function in conscious and anesthetized dogs. ⋯ The results indicate that levosimendan causes systemic and coronary vasodilatation in conscious and anesthetized dogs during blockade of the autonomic nervous system. Levosimendan caused direct positive inotropic effects and improved rapid ventricular filling but did not alter indices of isovolumic relaxation, suggesting that levosimendan may selectively enhance systolic performance and diastolic filling without affecting left ventricular relaxation.