Jennifer Schultheis, BCCCP, BCPS, PharmD (she/her/hers)
Clinical Pharmacist
Duke University Hospital
Durham, North Carolina
Disclosure information not submitted.
Emily Wings, PharmD
PGY-2 Infectious Diseases Pharmacy Resident
Cleveland Clinic, United States
Disclosure information not submitted.
Larissa Madden, PharmD
PGY2 Cardiology Pharmacy Resident
CHI St. Luke's Health - Baylor St. Luke's Medical Center, United States
Disclosure information not submitted.
Timothy Lassiter, PharmD, MBA
Clinical Pharmacist
Duke University Hospital, United States
Disclosure information not submitted.
Title: Assessment of Valproic Acid Level Concordance in Critically Ill Patients
Introduction:
Valproic acid (VPA) is an anticonvulsant and mood stabilizer that is extensively protein bound and susceptible to variable binding. VPA’s pharmacologically active free fraction is typically 5-10%; however, four case reports and one small observational study have described variations in the free fraction in critically ill patients. The purpose of this analysis was to characterize concordance between free and total serum VPA concentrations in critically ill patients at a quaternary care, academic medical center.
Methods:
This single-center, retrospective analysis included patients admitted to an adult ICU, between July 1, 2013 and July 1, 2019, with at least one free and total serum VPA trough level. Reference ranges for the free and total serum VPA concentrations were 5 to 17 µg/mL and 50 to 125 µg/mL, respectively. Serum concentrations were classified as “in range”, “low”, or “high” with free and total concentrations considered therapeutically concordant with the same classifications.
Conclusions:
A total of 40 patients were included in the analysis [age 56 years (IQR 44.5-66.5), ICU length of stay 13 days (IQR 6-22.5)]. The median total daily dose of VPA was 1500 mg (IQR 1000-2000). Indications for VPA in the ICU were seizures (65%), agitation (17.5%), alcohol withdrawal (10%), and mood stabilization (7.5%). Median albumin was 2.3 (IQR 1.9-2.7). Free and total concentrations were therapeutically concordant in 5 patients (12.5%). Measured free serum VPA concentrations were classified as low in 5 patients (12.5%), within reference range in 10 patients (25%), and high in 25 patients (62.5%). Total serum concentrations were low in 30 patients (70%) and within reference range in 10 patients (25%).
Although the majority of patients had total serum VPA concentrations that were classified as low, observed free serum VPA concentrations were most frequently high. These findings may be a reflection of the low albumin levels observed within the population of critically ill patients resulting in increased VPA free fractions. The low frequency of therapeutic concordance between free and total VPA serum concentrations suggests therapeutic monitoring of free serum VPA concentrations may be considered among critically ill patients.