• David J Gagnon, Gabriel V Fontaine, Kathryn E Smith, Richard R Riker, Russell R Miller, Patricia A Lerwick, F L Lucas, John T Dziodzio, Kristen C Sihler, and Gilles L Fraser.
• Department of Pharmacy, Maine Medical Center, 22 Bramhall St, Portland, ME 04102. Electronic address: dgagnon@mmc.org.
• J Crit Care. 2017 Feb 1; 37: 119-125.

PurposeThe purpose was to describe the use of valproate therapy for agitation in critically ill patients, examine its safety, and describe its relationship with agitation and delirium.Materials And MethodsThis retrospective cohort study evaluated critically ill adults treated with valproate for agitation from December 2012 through February 2015. Information on valproate prescribing practices and safety was collected. Incidence of agitation, delirium, and concomitant psychoactive medication use was compared between valproate day 1 and valproate day 3. Concomitant psychoactive medication use was analyzed using mixed models.ResultsFifty-three patients were evaluated. The median day of valproate therapy initiation was ICU day 7, and it was continued for a median of 7 days. The median maintenance dose was 1500 mg/d (23 mg/kg/d). The incidence of agitation (96% vs 61%, P < .0001) and delirium (68% vs 49%, P = .012) significantly decreased by valproate day 3. Treatment with opioids (77% vs 65%, P = .02) and dexmedetomidine (47% vs 24%, P = .004) also decreased. In mixed models analyses, valproate therapy was associated with reduced fentanyl equivalents (-185 μg/d, P = .0003) and lorazepam equivalents (-2.1 mg/d, P = .0004). Hyperammonemia (19%) and thrombocytopenia (13%) were the most commonly observed adverse effects.ConclusionsValproate therapy was associated with a reduction in agitation, delirium, and concomitant psychoactive medication use within 48 hours of initiation.Copyright © 2016 Elsevier Inc. All rights reserved.

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