Anesthesiology
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Randomized Controlled Trial
Effectiveness of an Electronic Alert for Hypotension and Low Bispectral Index on 90-day Postoperative Mortality: A Prospective, Randomized Trial.
We tested the hypothesis that an electronic alert for a "double low" of mean arterial pressure less than 75 mmHg and a bispectral index less than 45 reduces the primary outcome of 90-day mortality. ⋯ Ninety-day mortality was not significantly lower in patients cared for by anesthesiologists who received automated alerts to double-low states. Prolonged cumulative double-low conditions were strongly associated with mortality.
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CW002 is a benzylisoquinolinium nondepolarizing neuromuscular-blocking drug found to be inactivated by cysteine in preclinical studies. The current study represents a dose escalation clinical trial designed to describe CW002 potency, duration, cardiopulmonary side effects, and histamine release. ⋯ In healthy subjects receiving sevoflurane/nitrous oxide, CW002 at 1.8 × estimated ED95 produces a clinical duration less than 40 min, elicits no histamine release, and has minimal cardiopulmonary side effects.
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At therapeutic concentrations, cytochrome P4502B6 (CYP2B6) is the major P450 isoform catalyzing hepatic ketamine N-demethylation to norketamine in vitro. The CYP2B6 gene is highly polymorphic. The most common variant allele, CYP2B6*6, is associated with diminished hepatic CYP2B6 expression and catalytic activity compared with wild-type CYP2B6*1/*1. CYP2B6.6, the protein encoded by the CYP2B6*6 allele, and liver microsomes from CYP2B6*6 carriers had diminished ketamine metabolism in vitro. This investigation tested whether humans with the CYP2B6*6 allele would have decreased clinical ketamine metabolism and clearance. ⋯ These results show that while the CYP2B6*6 polymorphism results in diminished ketamine metabolism in vitro, this allelic variant did not affect single, low-dose ketamine metabolism, clearance, and pharmacokinetics in vivo. While in vitro drug metabolism studies may be informative, clinical investigations in general are needed to validate in vitro observations.