Sedation for Critically Ill or Injured Adults in the Intensive Care Unit

Abstract

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.

Recalibration of the delirium prediction model for ICU patients (PRE-DELIRIC): a multinational observational study

“…Although remarkably, and in line with other studies [29,30], in our study the most sedated patients, and patients in coma within the first 24hrs after ICU admission, have the highest rate of delirium (table 1).…”

Diazepam or midazolam for orotracheal intubation in the ICU?

“…Pharmacokinetics of almost all drugs, including sedatives, are not well known in critically ill patients. 28,29 The reduction in blood pressure and the incidence of hypotension observed with midazolam and diazepam (60% of patients) may have been related to the high doses used to achieve rapid sedation in already sick patients prone to hemodynamic instability. Fifteen episodes of hypotension in this study occurred within the first 15 minutes.…”

Markov Models and Cost Effectiveness Analysis: Applications in Medical Research

“…Therapeutically, patients are sedated to maximize their comfort. A growing body of literature, however, has identified the risks of continuous sedation in the ICU, as it is associated with increased mortality, delirium, duration of mechanical ventilation and length of ICU and hospital stay [22]. To strike the right balance between maintaining sedation and mechanical ventilator support as long as the patient needs it, but also moving to extubation as soon as possible, Girard and colleagues proposed actively waking up the patients daily to assess their readiness to come off of the ventilator.…”