Anesthesiology
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Randomized Controlled Trial Clinical Trial
Simultaneous assessment of drug interactions with low- and high-extraction opioids: application to parecoxib effects on the pharmacokinetics and pharmacodynamics of fentanyl and alfentanil.
Parecoxib is a parenteral cyclooxygenase-2 (COX-2) inhibitor intended for perioperative analgesia. It is an inactive prodrug hydrolyzed in vivo to the active inhibitor valdecoxib, a substrate for hepatic cytochrome P450 3A4 (CYP3A4); hence, a potential exists for metabolic interactions with other CYP3A substrates. This study determined the effects of parecoxib on the pharmacokinetics and pharmacodynamics of the CYP3A substrates fentanyl and alfentanil compared with the CYP3A inhibitor troleandomycin. Alfentanil is a low-extraction drug with a clearance that is highly susceptible to drug interactions; fentanyl is a high-extraction drug and, thus, is theoretically less vulnerable. We therefore also tested the hypothesis that the extraction ratio influences the consequence of altered hepatic metabolism of these opioids. ⋯ Single-dose parecoxib does not alter fentanyl or alfentanil disposition or clinical effects and does not appear to cause significant CYP3A drug interactions. CYP3A inhibition decreases alfentanil clearance more than fentanyl clearance, confirming that the extraction ratio influences the consequence of altered hepatic drug metabolism. Modified cassette, or "cocktail," dosing is useful for assessing drug interactions in humans.
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Randomized Controlled Trial Clinical Trial
Noninvasive cardiac output measurement using partial carbon dioxide rebreathing is less accurate at settings of reduced minute ventilation and when spontaneous breathing is present.
Although evaluation of cardiac output by the partial carbon dioxide rebreathing technique is as accurate as thermodilution techniques under controlled mechanical ventilation, it is less accurate at low tidal volume. It is not clear whether reduced accuracy is due to low tidal volume or low minute ventilation. The effect of spontaneous breathing on the accuracy of partial carbon dioxide rebreathing measurement has not been fully investigated. The objectives of the current study were to investigate whether tidal volume or minute ventilation is the dominant factor for the accuracy, and the accuracy of the technique when spontaneous breathing effort is present. ⋯ During controlled mechanical ventilation, minute ventilation rather than tidal volume affected the accuracy of cardiac output measurement using the partial carbon dioxide rebreathing technique. When spontaneous breathing is present, the carbon dioxide rebreathing technique is less accurate and increases spontaneous tidal volume and respiratory rate.
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Randomized Controlled Trial Clinical Trial
The effects of hydration on core temperature in pediatric surgical patients.
Reduced vascular volume might influence body temperature by diverting heat flow from peripheral tissues to the central organs. We therefore tested the hypothesis that mild hypovolemia helps to prevent intraoperative hypothermia in pediatric patients. ⋯ Conservative fluid management, which decreased body weight by only 1%, prevented reduction in core body temperature, presumably by reducing dissipation of metabolic heat from the core thermal compartment to peripheral tissues.
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Women are at higher risk for stroke after cardiac surgery than men. Prior analysis of risk profiles for perioperative stroke that have mostly combined data from women and men may fail to identify gender-specific risks. The purpose of this study was to evaluate whether patient gender impacts adjusted risk for stroke after cardiac surgery. ⋯ These data show that prior stroke before surgery is strongly and independently associated with susceptibility for stroke after cardiac surgery, particularly for men. Other risk factors for perioperative stroke, though, do not appear to be influenced by patient gender.