Patients in ICUs often require pain relief and sedation to treat both the underlying medical condition and the unpleasantness associated with being in an ICU. This review provides guidance on the identification and treatment of delirium and sedation.
Patients in intensive care units (ICUs) are treated with many interventions (most notably endotracheal intubation and invasive mechanical ventilation) that are observed or perceived to be distressing. Pain is the most common memory patients have of their ICU stay. Agitation can precipitate accidental removal of endotracheal tubes or of intravascular catheters used for monitoring or administration of life-sustaining medications. Consequently, sedatives and analgesics are among the most commonly administered drugs in ICUs.
• What is the current state of evidence regarding the level of sedation used in the intensive care unit?
Evidence from randomized, controlled trials consistently supports the use of the minimum possible level of sedation. In a landmark trial that compared routine daily interruption of sedative infusions with discretionary interruption by treating clinicians, patients whose sedation was routinely interrupted received less sedation overall and spent fewer days undergoing mechanical ventilation and fewer days in the ICU. A subsequent larger multicenter trial combined the daily interruption of sedation with daily spontaneous breathing trials. Daily interruption of sedation was associated with reduced administration of benzodiazepine sedative, reduced duration of mechanical ventilation, reduced length of stay in the ICU, and significantly increased survival.
• What are specific advantages of individual sedatives commonly used in the ICU?
Sedatives that are commonly used in the ICU are the benzodiazepines midazolam and lorazepam (and to a lesser extent, diazepam), the short-acting intravenous anesthetic agent propofol, and dexmedetomidine. Remifentanil, an opioid, is also used as a sole agent due to its sedative effects. Benzodiazepines act through gamma-aminobutyric acid type A (GABAA) receptors, as in part does propofol, whereas dexmedetomidine is an alpha2-adrenoceptor agonist, and remifentanil is a mu-opioid receptor agonist. As compared with benzodiazepines, propofol has not been shown to reduce mortality but may result in a reduction in the length of stay in the ICU. Dexmedetomidine may also have advantages over benzodiazepines, since it produces analgesia, causes less respiratory depression, and seemingly provides a qualitatively different type of sedation in which the patient is more interactive and so potentially better able to communicate his or her needs.
Table 1. Sedatives and Analgesics in Common Use in the ICU.
Morning Report Questions
Q: How is delirium defined, what is its most common feature, and what is increased mortality risk of delirium in a critically ill patient?
A: The Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV), lists four domains of delirium: disturbance of consciousness, change in cognition, development over a short period, and fluctuation. Delirium is defined by the National Institutes of Health as “sudden severe confusion and rapid changes in brain function that occur with physical or mental illness.” The most common feature of delirium, thought by many to be its cardinal sign, is inattention. Delirium is a nonspecific but generally reversible manifestation of acute illness that appears to have many causes, including recovery from a sedated or oversedated state. A diagnosis of delirium in critically ill patients is associated with increased mortality (estimated as a 10% increase in the relative risk of death for each day of delirium) and decreased long-term cognitive function.
Q: How may delirium in the ICU be prevented?
A: Among patients in the ICU, the duration of delirium was cut in half with early mobilization during interruptions in sedation. Four placebo-controlled trials have evaluated pharmacologic prophylaxis of delirium; low-dose haloperidol and low-dose risperidone both reduced the incidence of delirium, as did a single low dose of ketamine during the induction of anesthesia. However, these trials were conducted among patients undergoing elective surgical procedures, and it is not clear whether their results can be extrapolated to the general ICU population. Sedation with dexmedetomidine rather than benzodiazepines appears to reduce the incidence of delirium in the ICU.