Anesthesiology
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Randomized Controlled Trial Clinical Trial
Pharmacokinetics of midazolam in neonates undergoing extracorporeal membrane oxygenation.
Although the pharmacokinetics of midazolam in critically ill children has been described, there are no such reports in extracorporeal membrane oxygenation. ⋯ These results reveal significantly increased volume of distribution and plasma half-life in neonates receiving extracorporeal membrane oxygenation. Altered kinetics may reflect sequestration of midazolam by components of the extracorporeal membrane oxygenation circuit.
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Randomized Controlled Trial Clinical Trial
Propofol reduces perioperative remifentanil requirements in a synergistic manner: response surface modeling of perioperative remifentanil-propofol interactions.
Remifentanil is often combined with propofol for induction and maintenance of total intravenous anesthesia. The authors studied the effect of propofol on remifentanil requirements for suppression of responses to clinically relevant stimuli and evaluated this in relation to previously published data on propofol and alfentanil. ⋯ Propofol reduces remifentanil requirements for suppression of responses to laryngoscopy, intubation, and intraabdominal surgical stimulation in a synergistic manner. In addition, remifentanil decreases propofol concentrations associated with the return of consciousness in a synergistic manner.
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To simulate the time course of drug effect, it is sometimes necessary to combine the pharmacodynamic parameters from an integrated pharmacodynamic-pharmacodynamic study (e.g., volumes, clearances, k(e0) [the effect site equilibration rate constant], C(50) [the steady state plasma concentration associated with 50% maximum effect], and the Hill coefficient) with pharmacokinetic parameters from a different study (e.g., a study examining a different age group or sampling over longer periods of time). Pharmacokinetic-pharmacodynamic parameters form an interlocked vector that describes the relationship between input (dose) and output (effect). Unintended consequences may result if individual elements of this vector (e.g., k(e0)) are combined with pharmacokinetic parameters from a different study. The authors propose an alternative methodology to rationally combine the results of separate pharmacokinetic and pharmacodynamic studies, based on t(peak), the time of peak effect after bolus injection. ⋯ T(peak) is a useful pharmacodynamic parameter and can be used to link separate pharmacokinetic and pharmacodynamic studies. This addresses a common difficulty in clinical pharmacology simulation and control problems, where there is usually a wide choice of pharmacokinetic models but only one or two published pharmacokinetic-pharmacodynamic models. The results will be immediately applicable to target-controlled anesthetic infusion systems, where linkage of separate pharmacokinetic and pharmacodynamic parameters into a single model is inherent in several target-controlled infusion designs.