Valproic Acid for Hyperactive Delirium and Agitation in Critically Ill Patients

Background: Delirium and agitation are common syndromes in critically ill patients. Valproic acid (VPA) has shown benefit in intensive care unit (ICU)-associated delirium and agitation, but further evaluation is needed.

Objective: The purpose of this study was to evaluate the effectiveness and safety of VPA for hyperactive delirium and agitation in critically ill adult patients.

Methods: A retrospective cohort study at NYU Langone Health was conducted in critically ill patients treated with VPA for hyperactive delirium or agitation from October 1, 2017 to October 1, 2022. The primary outcome was effectiveness of VPA, defined as a reduction in the total number of any concomitant psychoactive medication by day 3 of VPA treatment. Secondary outcomes included the effect of VPA on the doses of concomitant medications and adverse events.

Results: A total of 87 patients were included in the final analysis. By day 3 of VPA treatment, a 33% reduction (P < .001) in the total number of concomitant psychoactive medications was observed. VPA decreased the need for sedatives, as assessed by midazolam equivalents, but no significant changes were seen with dexmedetomidine alone, opioids, or antipsychotics. A 10 mg/kg loading dose was utilized in 36% of the cohort and its use decreased the risk for initiating additional psychoactive medications by day 3 of therapy (OR 2.8, 95% CI 1.0-7.8, P = .047), with benefits noted as early as 48 h after initiation. Adverse events were low in the total cohort (10.3%).

Conclusion and relevance: The addition of VPA to a complex pharmacologic regimen for hyperactive delirium and agitation is safe and can assist in the prevention of polypharmacy and overall workload in critically ill patients admitted primarily for cardiogenic shock and respiratory failure requiring mechanical ventilation.