Valproic Acid-Associated Hyperammonemia: A Systematic Review.

BACKGROUND: Hyperammonemia is an adverse effect that poses clinical uncertainty around valproic acid (VPA) use. The prevalence of symptomatic and asymptomatic hyperammonemia and its relationship to VPA concentration is not well established. There is also no clear guidance regarding its management. This results in variability in the monitoring and treatment of VPA-induced hyperammonemia. To inform clinical practice, this systematic review aims to summarize evidence available around VPA-associated hyperammonemia and its prevalence, clinical outcomes, and management. METHODS: An electronic search was performed through Ovid MEDLINE, Ovid Embase, Web of Science, and PsycINFO using search terms that identified hyperammonemia in patients receiving VPA. Two reviewers independently performed primary title and abstract screening with a third reviewer resolving conflicting screening results. This process was repeated during the full-text review process. RESULTS: A total of 240 articles were included. Prevalence of asymptomatic hyperammonemia (5%-73%) was higher than symptomatic hyperammonemia (0.7%-22.2%) and occurred within the therapeutic range of VPA serum concentration. Various risk factors were identified, including concomitant medications, liver injury, and defects in carnitine metabolism. With VPA discontinued, most symptomatic patients returned to baseline mental status with normalized ammonia level. There was insufficient data to support routine monitoring of ammonia level for VPA-associated hyperammonemia. CONCLUSIONS: Valproic acid-associated hyperammonemia is a common adverse effect that may occur within therapeutic range of VPA. Further studies are required to determine the benefit of routine ammonia level monitoring and to guide the management of VPA-associated hyperammonemia.

Vancomycin area under the curve/minimum inhibitory concentration and trough level concordance-evaluation on an urban health unit.

Background: A vancomycin AUC/MIC (area under the curve/minimum inhibitory concentration) of 400-600 mg•h/L is associated with improved clinical outcomes for the treatment of methicillin resistant Staphylococcus aureus (MRSA) infections. Currently, there are still limited studies evaluating the relationship between vancomycin trough and AUC. Objectives: To evaluate the correlation between vancomycin trough and AUC/MIC and determine if trough-guided monitoring is an adequate predictor of AUC/MIC in the Urban Health population at St Paul's Hospital. Methods: This was a retrospective chart review of 29 patients from November 2019 to February 2021. Patient demographics and laboratory data were collected from electronic medical records. The two-level equation-based approach was used to calculate AUC/MIC. The proportion of AUC/MIC values within target (400-600 mg•h/L) despite subtherapeutic troughs, and the proportion of AUC/MIC values supratherapeutic when trough is within target (15-20 mg/L) were the primary endpoints. Main Results: Fifty-seven sets of levels were collected and 75% of vancomycin troughs and AUC24 were found to be discordant. When trough was 10-14.9 mg/L, AUC24 was > 400 mg•h/L in 94% of cases and when trough was 15-20 mg/L, AUC24 was > 600 mg•h/L in 69% of cases. There was a moderate correlation between vancomycin trough and AUC24h (R 2 = 0.57; p < 0.001). Conclusion: A vancomycin trough between 15 and 20 mg/L may result in an AUC/MIC greater than necessary for clinical efficacy. Considering these findings and the practical concerns of AUC-guided monitoring, a modest reduction in target troughs to prevent vancomycin toxicity warrants clinical consideration and further evaluation.