Anesthesia and analgesia
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Anesthesia and analgesia · Aug 2012
Comparative StudyPharmacological studies of methoxycarbonyl etomidate's carboxylic acid metabolite.
Methoxycarbonyl etomidate (MOC-etomidate) is a rapidly metabolized and ultrashort-acting etomidate analog that does not produce prolonged adrenocortical suppression after bolus administration. Its metabolite (MOC-ECA) is a carboxylic acid whose pharmacology is undefined. We hypothesized that MOC-ECA possesses significantly lower pharmacological activity than MOC-etomidate, accounting for the latter's very brief duration of hypnotic action and inability to produce prolonged adrenocortical suppression after bolus administration. To test this hypothesis, we compared the potencies of MOC-ECA and MOC-etomidate in 3 biological assays. ⋯ In all 3 biological assays, MOC-ECA's potency was approximately 300-fold lower than that of MOC-etomidate.
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Anesthesia and analgesia · Aug 2012
Randomized Controlled Trial WebcastsA placebo- and midazolam-controlled phase I single ascending-dose study evaluating the safety, pharmacokinetics, and pharmacodynamics of remimazolam (CNS 7056): Part II. Population pharmacokinetic and pharmacodynamic modeling and simulation.
A new benzodiazepine, remimazolam, which is rapidly metabolized by tissue esterases to an inactive metabolite, has been developed to permit a fast onset, a short, predictable duration of sedative action, and a more rapid recovery profile than currently available drugs. We report on modeling of the data and simulations of dosage regimens for future study. ⋯ Population pharmacokinetic and pharmacodynamic models developed for remimazolam and midazolam fitted the observed data well. Simulations based on these models show that remimazolam delivers extremely rapid sedation, with maximal effect being reached within 3 minutes of the start of treatment. This property will enable maintenance doses to be given more accurately than with slower-acting drugs. No covariate effects considered to be clinically relevant were observed, suggesting that dosing by body weight may offer no advantage over fixed doses in terms of consistency of exposure to remimazolam within the weight range studied (65-90 kg).
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Anesthesia and analgesia · Aug 2012
Randomized Controlled Trial WebcastsA placebo- and midazolam-controlled phase I single ascending-dose study evaluating the safety, pharmacokinetics, and pharmacodynamics of remimazolam (CNS 7056): Part I. Safety, efficacy, and basic pharmacokinetics.
A new benzodiazepine, remimazolam, metabolized by tissue esterases to an inactive compound, CNS 7054, has been developed to permit a fast onset, a short and more predictable duration of sedative action, and a more rapid recovery profile than with currently available benzodiazepines. We report on the safety and efficacy of the first human study. ⋯ Remimazolam provided sedation with rapid onset and offset, and was well tolerated. There was no supplemental oxygen or ventilation required. On the basis of these data, further studies on the potential utility of remimazolam for sedation/anesthesia are warranted.
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Anesthesia and analgesia · Aug 2012
Comparative StudyInside anesthesia breathing circuits: time to reach a set sevoflurane concentration in toddlers and newborns: simulation using a test lung.
We measured the time it takes to reach the desired inspired anesthetic concentration using the Primus (Drägerwerk, AG, Lübeck, Germany) and the Avance (GE Datex-Ohmeda, Munich, Germany) anesthesia machines with toddler and newborn ventilation settings. The time to reach 95% of inspired target sevoflurane concentration was measured during wash-in from 0 to 6 vol% sevoflurane and during wash-out from 6 to 0 vol% with fresh gas flows equal to 1 and 2 times the minute ventilation. The Avance was faster than the Primus (65 seconds [95% confidence interval (CI): 55 to 78] vs 310 seconds [95% CI: 261 to 359]) at 1.5 L/min fresh gas flow, tidal volume of 50 mL, and 30 breaths/min. ⋯ The effect of doubling fresh gas flow was variable and less than expected. The Primus is slower during newborn than toddler ventilation, whereas the Avance's response time was the same for newborn and toddler ventilation. Our data confirm that the time to reach the target-inspired anesthetic concentration depends on breathing circuit volume, fresh gas flow, and minute ventilation.
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Therapeutic hypothermia has been shown to be effective in out-of-hospital cardiac arrest, and use of this therapy has been expanded to involve in-hospital cardiac arrest. The utility of hypothermia in cardiac arrest after hemorrhage is not known. ⋯ Therapeutic hypothermia by surface cooling was initiated after acute control of the bleeding source, restoration of circulating blood volume, and hemodynamic stabilization. We believe therapeutic hypothermia use will continue to increase for in-hospital cardiac arrests.