Sedation for critically ill or injured adults in the intensive care unit: a shifting paradigm.

As most critically ill or injured patients will require some degree of sedation, the goal of this paper was to comprehensively review the literature associated with use of sedative agents in the intensive care unit (ICU). The first and selected latter portions of this article present a narrative overview of the shifting paradigm in ICU sedation practices, indications for uninterrupted or prolonged ICU sedation, and the pharmacology of sedative agents. In the second portion, we conducted a structured, although not entirely systematic, review of the available evidence associated with use of alternative sedative agents in critically ill or injured adults. Data sources for this review were derived by searching OVID MEDLINE and PubMed from their first available date until May 2012 for relevant randomized controlled trials (RCTs), systematic reviews and/or meta-analyses and economic evaluations. Advances in the technology of mechanical ventilation have permitted clinicians to limit the use of sedation among the critically ill through daily sedative interruptions or other means. These practices have been reported to result in improved mortality, a decreased length of ICU and hospital stay and a lower risk of drug-associated delirium. However, in some cases, prolonged or uninterrupted sedation may still be indicated, such as when patients develop intracranial hypertension following traumatic brain injury. The pharmacokinetics of sedative agents have clinical importance and may be altered by critical illness or injury, co-morbid conditions and/or drug-drug interactions. Although use of validated sedation scales to monitor depth of sedation is likely to reduce adverse events, they have no utility for patients receiving neuromuscular receptor blocking agents. Depth of sedation monitoring devices such as the Bispectral Index (BIS©) also have limitations. Among existing RCTs, no sedative agent has been reported to improve the risk of mortality among the critically ill or injured. Moreover, although propofol may be associated with a shorter time to tracheal extubation and recovery from sedation than midazolam, the risk of hypertriglyceridaemia and hypotension is higher with propofol. Despite dexmedetomidine being linked with a lower risk of drug-associated delirium than alternative sedative agents, this drug increases risk of bradycardia and hypotension. Among adults with severe traumatic brain injury, there are insufficient data to suggest that any single sedative agent decreases the risk of subsequent poor neurological outcomes or mortality. The lack of examination of confounders, including the type of healthcare system in which the investigation was conducted, is a major limitation of existing pharmacoeconomic analyses, which likely limits generalizability of their results.