Anesthesia and analgesia
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Anesthesia and analgesia · Sep 2002
The prediction of defibrillation outcome using a new combination of mean frequency and amplitude in porcine models of cardiac arrest.
We estimated the predictive power with respect to defibrillation outcome of ventricular fibrillation (VF) mean frequency (FREQ), mean peak-to-trough amplitude (AMPL), and their combination. We examined VF electrocardiogram signals of 64 pigs from 4 different cardiac arrest models with different durations of untreated VF, different durations of cardiopulmonary resuscitation, and use of different drugs (epinephrine, vasopressin, N-nitro-L-arginine methyl ester, or saline placebo). The frequency domain was restricted to the range from 4.33 to 30 Hz. In the 10-s epoch between 20 and 10 s before the first defibrillation shock, FREQ and AMPL were estimated. We introduced the survival index (SI; 0.68 Hz(-1). FREQ + 12.69 mV(-1). AMPL) by use of multiple logistic regression. Kruskal-Wallis nonparametric one-way analysis was used to analyze the different porcine models for significant difference. The variables FREQ, AMPL, and SI were compared with defibrillation outcome by means of univariate logistic regression and receiver operating characteristic curves. SI increased predictive power compared with AMPL or FREQ alone, resulting in 89% sensitivity and 86% specificity. The probabilities of predicting defibrillation outcome for FREQ, AMPL, and SI were 0.85, 0.89 and 0.90, respectively. FREQ, AMPL, and SI values were not sensitive in regard to the four different cardiac arrest models but were significantly different for vasopressin and epinephrine animals. ⋯ We present a retrospective data analysis to evaluate the predictive power of different ventricular fibrillation electrocardiogram variables in pigs with respect to defibrillation outcome. We showed that our combination of variables leads to an improved forecast, which may help to reduce harmful unsuccessful defibrillation attempts.
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Anesthesia and analgesia · Sep 2002
Randomized Controlled Trial Clinical TrialThe influence of parecoxib, a parenteral cyclooxygenase-2 specific inhibitor, on the pharmacokinetics and clinical effects of midazolam.
Parecoxib, a parenteral cyclooxygenase-2 inhibitor, is undergoing clinical development as an analgesic/antiinflammatory drug for perioperative use. Parecoxib, an inactive prodrug, is hydrolyzed in vivo to valdecoxib, a substrate for hepatic cytochrome P450 (CYP) 3A4. Thus, potential exists for interactions with other CYP3A4 substrates. In this investigation, we determined the influence of parecoxib on the pharmacokinetics and clinical effects of midazolam, a CYP3A4 substrate, in volunteers. This was a randomized, balanced crossover, placebo-controlled, double-blinded clinical investigation. Twelve healthy subjects aged 23-41 yr were studied after providing IRB-approved informed consent. Midazolam 0.07 mg/kg IV infusion was administered 1 h after placebo (control) or parecoxib 40 mg IV. Venous midazolam concentrations were determined by using liquid chromatography-mass spectrometry/mass spectrometry assay. Pharmacokinetic variables were determined by noncompartmental analysis. Pharmacodynamic measurements included clinical end-points, cognitive function (memory; digit symbol substitution tests), subjective self-assessment of recovery (visual analog scales), and bispectral index. Midazolam plasma concentrations were similar between placebo and parecoxib-treated subjects. No differences were found in midazolam pharmacokinetics (maximal observed plasma concentration, clearance, elimination half-life, volume of distribution) or pharmacodynamics (clinical end-points, digit symbol substitution tests, memory, visual analog scales, bispectral index). Single-bolus parecoxib does not alter the pharmacokinetics or pharmacodynamics of midazolam infusion. Parecoxib did not affect CYP3A4 activity as assessed using midazolam clearance as the in vivo probe. ⋯ Parecoxib, a parenteral cyclooxygenase-2 inhibitor intended for perioperative use as an analgesic/antiinflammatory drug, is a substrate for hepatic cytochrome P450 3A4. The potential for a drug interaction with midazolam, an in vivo CYP3A4 probe, was tested in healthy volunteers. Single-bolus parecoxib does not alter the pharmacokinetics or pharmacodynamics of midazolam.