Treatment of Delirium During Critical Illness

Abstract

Delirium, an acute disturbance in mental status due to another medical condition, is common and morbid in the intensive care unit. Despite its clear association with multiple common risk factors and important outcomes, including mortality and long-term cognitive impairment, both the ultimate causes of and ideal treatments for delirium remain unclear. Studies suggest that neuroinflammation, hypoxia, alterations in energy metabolism, and imbalances in multiple neurotransmitter pathways contribute to delirium, but commonly used treatments (e.g., antipsychotic medications) target only one or a few of these potential mechanisms and are not supported by evidence of efficacy. At this time, the optimal treatment for delirium during critical illness remains avoidance of risk factors, though ongoing trials may expand on the promise shown by agents such as melatonin and dexmedetomidine.

Keywords: delirium; intensive care; mechanical ventilation; treatment.

Figure 1

Putative mechanisms of delirium and treatments that target these effects. Abbreviations: BBB, blood–brain barrier; GABA, gamma-aminobutyric acid.

Figure 2

Effects of haloperidol, ziprasidone, and placebo on (a) days alive without delirium or coma and (b) days with delirium. Analyses were adjusted for age, preexisting cognitive impairment, Clinical Frailty Score, and Charlson Comorbidity Index at baseline, as well as modified Sequential Organ Failure Assessment and Richmond Agitation-Sedation Scale at randomization. Analyses found no significant differences between the trial groups with respect to the primary endpoint (days alive without delirium or coma) and the secondary endpoint (days with delirium). Figure adapted with permission from Reference .

Figure 3

Prevalence of delirium while on study drug. Among all patients, those sedated with dexmedetomidine had a 70% lower likelihood of having delirium on any given day compared with patients sedated with lorazepam. Percentages of alive, non-comatose patients who were delirious each study day are represented with green bars if in the lorazepam group or blue bars if in the dexmedetomidine group. Figure adapted with permission from Reference .