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Delirium and Exposure to Psychoactive Medications in Critically Ill Adults: A Multi-Centre Observational Study
Burry LD, Williamson DR, Mehta S, et al. J Crit Care. 2017; 42:268-74.
Study Question: Is there a relationship between psychoactive drug exposure and delirium?
Study Description: This multicenter, prospective, observational study included critically ill adults admitted for ≥ 24 hours. Patients with acute severe head trauma or who were comatose when screened were excluded. The primary endpoint was the relationship between 24-hour prior exposure to psychoactive drugs and the development of delirium. Secondary endpoints included duration of mechanical ventilation, ICU and hospital length of stay (LOS), and ICU and hospital mortality. Psychoactive drugs included benzodiazepines, non-benzodiazepine sedatives (e.g. propofol, dexmedetomidine, and ketamine), opioids, antipsychotics, and drugs with high- (e.g. diphenhydramine, ipratropium, atropine, and scopolamine) or low- (e.g. ranitidine, trazodone, olanzapine, risperidone, and haloperidol) anticholinergic activity.
Results: A total of 520 patients were included: 260 developed delirium and 260 did not. Median time to delirium onset was 3 days and median duration was 2 days. A regression model of the 24 hours preceding drug exposure showed no association between any psychoactive drug and delirium. A post-hoc analysis of an extended 48 hours preceding drug exposure showed an association between delirium and high-potency anticholinergic drugs (HR 2.45, 95%CI 1.08-5.54) and benzodiazepines (HR 1.08 per 5mg midazolam-equivalent, 95%CI 1.04-1.12). Overall, delirious patients experienced a longer ICU and hospital LOS (p < 0.0001) as well as a higher ICU (p = 0.003) and hospital (p = 0.007) mortality.
Conclusion(s): High-potency anticholinergic drugs and benzodiazepines given in the previous 48 hours were associated with delirium.
Perspective: Literature has shown delirium is associated with many negative outcomes. Current guidelines reinforce the importance of preventing delirium as interventions shown to decrease the severity and duration of delirium are limited. This study demonstrated psychoactive medications could be a modifiable risk factor for delirium. In particular, benzodiazepines and high-potency anticholinergic drugs administered in the preceding 48 hours were associated with delirium. If psychoactive medications are necessary, the lowest dose and shortest duration should be used.