Benzodiazepines in the intensive care unit

The effects of BZ drugs result from interaction at the GABA_A receptor within the CNS, producing anxiolysis, hypnosis, and amnesia in a dose-dependent fashion. These sedative effects are best titrated to reproducible clinical endpoints, using scoring systems such as the Ramsay scale. All BZs exhibit similar pharmacologic effects, but the important differences in pharmacokinetics and pharmacodynamics should be recognized to use these drugs safely and effectively within the ICU. Diazepam is the classic anxiolytic, amnestic, and sedative agent, but the presence of long-acting active metabolites that depend on the kidneys for elimination limits its use in many ICU patients. Lorazepam is the most potent BZ used in the ICU; it has stable pharmacokinetics and relatively low cost. This drug is best reserved for situations in which rapid onset is not essential and long-term sedation is anticipated. Midazolam has the shortest t_1/2 of the commonly used BZs, generates few active metabolites, and is water soluble at physiologic pH. Thus, it is well suited for continuous infusion in the ICU, and the recent introduction of generic formulations of midazolam has decreased the drugacquisition cost for many hospitals. Optimal sedation for ICU patients often requires BZ and concomitant therapy with drugs such as haloperidol, dexmedetomidine, opioids, and so forth, to reduce untoward side effects and, perhaps, overall drug costs. Flumazenil, a specific BZ antagonist, can be used for diagnostic or therapeutic reversal of BZ agonists when appropriate. Most experienced intensivists recommend an individualized approach to sedation and titration of anxiolysis to maximize efficacy, minimize side effects, and optimize cost effectiveness in the ICU. New CNS monitors of the EEG, such as the BIS or entropy EEG monitors, may refine titration algorithms further in the near future.