Anesthesia and analgesia
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The accompanying articles in this issue of the journal's special collection describe attempts to improve on the dynamics of distribution and reduce side effects of analogs of etomidate and benzodiazepines. Both classes of drugs have their principal sites of action on γ-aminobutyric acid type A receptors, although at very different binding sites and by different mechanisms of action. ⋯ In addition, we describe how these drugs can interact with the nervous system at a systems level. We leave it to other reviewers to discuss whether these new drugs offer true clinical improvements.
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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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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.
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Anesthesia and analgesia · Aug 2012
Measure to quantify the influence of time from end of surgery to tracheal extubation on operating room workflow.
The impact of delays in extubation on operating room (OR) workflow are challenging to assess because such delays may or may not be a bottleneck to the patient leaving the OR. We developed an observational measure that quantifies the influence of extubation times on OR workflow. ⋯ Longer times to extubation are associated with an increased chance of at least 1 person waiting in the OR. This measure can be used in observational studies and for lean engineering projects to assess conditions when time to extubation affects workflow. Observers can combine use of this measure for extubation times with the previously developed measure for studying the influence of induction times on OR workflow.