Abstracts

Rationale: Although valproic acid (VPA) is the second most frequently used AED in nursing homes (NHs), there is little information regarding the concentrations attained and relations to outcome. Methods: We analyzed all daily Physicians Orders (POs) for antiepileptic drug doses and all Minimum Data Set (MDS) records for data on fractures for all residents living in a Beverly Enterprises NH at any time during 2000-2002 (annual census > 70,000 persons) who were ≥65 years of age on day of admission. The study cohort was comprised of those residents who were on VPA at admission and for at least 30 days following admission (N=322). Total VPA concentrations were predicted from the daily VPA dose listed in the POs. A population-based clearance estimated from a previous primary source database was used to predict each resident’s VPA concentration (Cl/F (L/hr) = 0.843 for a male on no comedication). VPA concentrations were also predicted with factors adjusting for female sex and comedicantions when indicated (Birnbaum, 2007). Clinical, functional, and demographic characteristics associated with VPA concentration levels were assessed. Associations of predicted VPA concentration with post-admission outcomes were tested with individual proportional hazards models. Results: Overall, 46% of the residents had calculated total VPA concentrations less than 40 ug/ml and 6.8% had concentrations greater than 100 ug/ml. The mean VPA concentration (standard deviation) was 59.4 (36.3) for those 65-74 years of age, 44.3 (25.8) for those 75-84, and 40.7 ug/ml (25.9) for those 85+, respectively. Older age was associated with lower VPA concentrations (p<0.001). Mean VPA concentrations were significantly higher among residents with prevalent epilepsy/seizure disorder compared to those without (55.9 vs. 44.9 ug/ml, p=0.003), but significantly lower among those with prevalent dementia compared to those without (44.6 vs. 55.6 ug/ml, p=0.003) and among those with prevalent fracture (30.3 vs. 51.0 ug/ml, p=0.0009). Higher concentrations were associated with 4% lower risk of post-admission incident indication of osteoporosis (10 events, p=0.01), but not with rarer events such as post-admission incident indication of epilepsy/seizure disorder (2 events) nor fracture (5 events).