Valproate for agitation in critically ill patients: A retrospective study.
The 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.



This 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.



Fifty-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.



Valproate therapy was associated with a reduction in agitation, delirium, and concomitant psychoactive medication use within 48 hours of initiation.
Department of Pharmacy, Maine Medical Center, 22 Bramhall St, Portland, ME 04102. Electronic address: dgagnon@mmc.org.
David J
DJ
Gagnon
Department of Pharmacy and Neurosciences Institute, Intermountain Medical Center, 5121 South Cottonwood St, Murray, UT 84107. Electronic address: fontaine.gabe@gmail.com.
Gabriel V
GV
Fontaine
Department of Pharmacy, Maine Medical Center, 22 Bramhall St, Portland, ME 04102. Electronic address: smithk17@mmc.org.
Kathryn E
KE
Smith
Neuroscience Institute, Maine Medical Center, 22 Bramhall St, Portland, ME 04102; Department of Critical Care Medicine, Maine Medical Center, 22 Bramhall St, Portland, ME 04102. Electronic address: rriker@cmamaine.com.
Richard R
RR
Riker
Department of Critical Care Medicine, Intermountain Medical Center, 5121 South Cottonwood St, Murray, UT 84107. Electronic address: russ.millerIII@imail.org.
Russell R
RR
Miller
Department of Critical Care Medicine, Maine Medical Center, 22 Bramhall St, Portland, ME 04102. Electronic address: lerwip@mmc.org.
Patricia A
PA
Lerwick
Center for Outcomes Research & Evaluation, 509 Forest Ave, Suite 200, Portland, ME 04101. Electronic address: flucas@mmc.org.
F L
FL
Lucas
Department of Critical Care Medicine, Maine Medical Center, 22 Bramhall St, Portland, ME 04102. Electronic address: dziodj@mmc.org.
John T
JT
Dziodzio
Department of Surgical/Trauma Critical Care, Maine Medical Center, 22 Bramhall St, Portland, ME 04102. Electronic address: sihlek@mmc.org.
Kristen C
KC
Sihler
Department of Pharmacy, Maine Medical Center, 22 Bramhall St, Portland, ME 04102; Department of Critical Care Medicine, Maine Medical Center, 22 Bramhall St, Portland, ME 04102. Electronic address: fraseg@mmc.org.
Gilles L
GL
Fraser
D000328:Adult; D000368:Aged; D000701:Analgesics, Opioid / Q000627:therapeutic use; D016638:Critical Illness; D003693:Delirium / Q000453:epidemiology*; D020927:Dexmedetomidine / Q000627:therapeutic use; D005260:Female; D005283:Fentanyl / Q000627:therapeutic use; D018682:GABA Agents / Q000627:therapeutic use*; D006801:Humans; D006993:Hypnotics and Sedatives / Q000627:therapeutic use; D008140:Lorazepam / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D011595:Psychomotor Agitation / Q000188:drug therapy* / Q000453:epidemiology; D012189:Retrospective Studies; D014635:Valproic Acid / Q000627:therapeutic use*
D000701:Analgesics, Opioid; D018682:GABA Agents; D006993:Hypnotics and Sedatives; D014635:Valproic Acid; D020927:Dexmedetomidine; D008140:Lorazepam; D005283:Fentanyl
Agitation; Critical care; Delirium; Sedation; Valproate; Valproic acid