1. Weeks, Susan Mace DNP, RN, CNS, FNAP, FAAN


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What are the safety and effectiveness of pharmacological options for treating delirium in critically ill adults?



A systematic review of 14 randomized controlled trials (RCTs), including 1,844 participants.



Delirium, defined as a reversible nonspecific cognitive impairment, is commonly seen in critically ill adults and is associated with many negative outcomes. Those outcomes may include increased mortality, prolonged mechanical ventilation, and increased length of stay (in the ICU and/or the hospital), as well as long-term consequences such as ongoing cognitive impairment and need for long-term care. Delirium and its outcomes can be traumatic for patients and their caregivers, and also carry a significant economic burden.



The goal of this review was to compare pharmacological interventions for the treatment of delirium in critically ill adults either with delirium or at high risk for delirium. Its primary objective was to assess the effects of these interventions on the duration of delirium. Its secondary objectives were, first, to assess the effects of these interventions on delirium-free and coma-free days, days with coma, delirium relapse, duration of mechanical ventilation, ICU and hospital length of stay, mortality, and long-term outcomes (such as cognitive, discharge disposition, or health-related quality of life), and second, to assess the safety of the pharmacological interventions.


This review included 14 RCTs with 1,844 participants. Ten RCTs were placebo controlled, while four compared different pharmacological interventions. Drugs included in the comparisons were antipsychotics, [alpha]2 agonists, statins, opioids, serotonin antagonists, and cholinesterase inhibitors. Eleven of the RCTs reported on the primary outcome (duration of delirium). While the studies were small, they were found to have a good design, and nine of the 14 had a low risk of bias.


The only drug that reduced the duration of delirium, compared with placebo, was the [alpha]2 agonist dexmedetomidine, while the cholinesterase inhibitor rivastigmine prolonged the duration. Each of these results, however, is based on findings from a single small study. When compared with placebo, the other drugs did not show a change in delirium duration.


The effect of the six drug classes on the duration of delirium was also compared using network meta-analysis, which failed to rule out the possibility of no difference between them compared with placebo. None of the drugs was found to improve coma duration, length of stay, long-term cognitive outcomes, or risk of mortality.



This review finds that the [alpha]2 agonist dexmedetomidine may shorten the duration of delirium in critically ill adults. The authors found no evidence of a difference between placebo and any other pharmacological intervention, including commonly used antipsychotics, in terms of an effect on delirium duration or any secondary outcomes. One drug, the cholinesterase inhibitor rivastigmine, was associated with a prolonged delirium duration. These findings are significant because antipsychotics-the most commonly used pharmacological intervention for delirium in critically ill adults-were not found to be effective.


Treatment options for critically ill adults experiencing delirium are a high priority for patients, caregivers, and health professionals. Future studies would benefit from standardization of study outcomes, reporting of symptom management, inclusion of long-term outcomes, and use of nonpharmacological treatment options.




Burry L, et al Pharmacological interventions for the treatment of delirium in critically ill adults. Cochrane Database Syst Rev 2019;9:CD011749.