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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In human skeletal muscles, the phosphodiesterase-III inhibitor enoximone induces in vitro contracture development, and it has been suggested that enoximone could trigger malignant hyperthermia (MH). In this study, the in vitro and in vivo effects of enoximone in MH-normal (MHN) and MH-susceptible (MHS) swine were investigated. ⋯ The cumulative enoximone doses used in this study were 30- to 50-fold higher than therapeutic doses in humans. Enoximone does not trigger MH in genetically determined swine. However, enoximone might be useful for in vitro diagnosis of MH.
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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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Clinical Trial
Influence of erythrocyte concentrate storage time on postsurgical morbidity in cardiac surgery patients.
The transfusion of erythrocytes that have been stored for long periods of time can produce visceral ischemia and favor the acquisition of postsurgical infections. To estimate the role of the duration of storage of erythrocytes on morbidity in cardiac surgery, we performed an observational study. ⋯ Prolonged storage of erythrocytes does not increase morbidity in cardiac surgery. However, storage for longer than 28 days could be a risk factor for the acquisition of nosocomial pneumonia.