Anesthesiology
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Clinical Trial
Pharmacokinetics and clinical pharmacodynamics of the new propofol prodrug GPI 15715 in volunteers.
GPI 15715 (AQUAVAN injection) is a new water-soluble prodrug which is hydrolyzed to release propofol. The objectives of this first study in humans were to investigate the safety, tolerability, pharmacokinetics, and clinical pharmacodynamics of GPI 15715. ⋯ Compared with propofol lipid emulsion, the potency seemed to be higher with respect to plasma concentration but was apparently less with respect to dose. Pharmacokinetic simulations showed a longer time to peak propofol concentration after a bolus dose and a longer context-sensitive half-time.
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In the partial CO(2) rebreathing method, monitored changes in CO(2) elimination and end-tidal CO(2) in response to a brief rebreathing period are used to estimate cardiac output. However, dynamic changes in CO(2) production during ischemia and reperfusion may affect the accuracy of these estimates. This study was designed to compare measurements of cardiac output as produced by the partial CO(2) rebreathing (NICO), bolus (BCO), and continuous thermodilution (CCO) methods of monitoring cardiac output. ⋯ Results indicate that in aortic reconstruction surgery the performance of NICO monitoring is comparable with that of CCO; however, the direction of bias in these continuous measurement devices is the opposite.
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Propofol is a common sedative hypnotic for the induction and maintenance of anesthesia. Clinicians typically moderate the dose of propofol or choose a different sedative hypnotic in the setting of severe intravascular volume depletion. Previous work has established that hemorrhagic shock influences both the pharmacokinetics and pharmacodynamics of propofol in the rat. To investigate this further, the authors studied the influence of hemorrhagic shock on the pharmacology of propofol in a swine isobaric hemorrhage model. ⋯ Hemorrhagic shock altered the pharmacokinetics and pharmacodynamics of propofol. Changes in intercompartmental clearances and an increase in the potency of propofol suggest that less propofol would be required to achieve a desired drug effect during hemorrhagic shock.
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Experimental and clinical studies have shown reduction in intrapulmonary shunt with improved oxygenation by spontaneous breathing with airway pressure release ventilation (APRV) in acute lung injury. The mechanisms of these findings are not clear. The authors hypothesized that spontaneous breathing results in better aeration of lung tissue and that improvement in oxygenation can be explained by these changes. This hypothesis was studied in a porcine model of oleic acid-induced lung injury. ⋯ The results support the hypothesis that spontaneous breathing during APRV improves oxygenation mainly by recruitment of nonaerated lung and improved aeration of the lungs.