Prediction of Hematotoxicity in Patients with Acute Valproic Acid Intoxication

Purpose: Valproic acid is a drug used for the treatment of convulsive disorders and for mood stabilization. Acute intoxication can result in gastrointestinal disturbances, neurologic symptoms, and hematologic toxicity. This study aims to identify factors that may predict patient prognosis.Methods: In this single-center retrospective observational study, medical records from January 1, 2013, to December 31, 2022, were reviewed. The initial clinical features, laboratory results, and serum valproic acid levels of patients with acute valproic acid intoxication who presented to the emergency department were analyzed. Patients were divided into two groups: those who developed hematologic toxicity (hematotoxicity group) and those who did not (non-hematotoxicity group).Results: A total of 115 patients were included in the analysis, of whom 23 (20%) developed hematotoxicity. The median age of patients with hematotoxicity was 39 years (interquartile range [IQR], 32.0–50.5), which was significantly higher than in the non-hematotoxicity group (p=0.001). The Glasgow Coma Scale score was lower in the hematotoxicity group, with a median of 12 points (IQR, 9.0–14.5) (p=0.013). Intensive care unit admission was more frequent in the hematotoxicity group (p=0.003). Compared with the non-hematotoxicity group, patients with hematotoxicity had a higher incidence of pneumonia, acute kidney injury, rhabdomyolysis, metabolic acidosis, and hyperlactatemia (all p<0.001, except p=0.009 for hyperlactatemia). The initial serum valproic acid concentration was also higher in the hematotoxicity group, with a median of 121.6 μg/mL (IQR, 59.8–154.3) (p<0.001). Multivariate analysis showed that the odds ratio for hematotoxicity was 6.20 (p=0.018) in the presence of metabolic acidosis and 8.32 (p<0.001) when the initial valproic acid concentration exceeded 115.0 μg/mL.Conclusion: In patients with suspected acute valproic acid poisoning, early evaluation of arterial pH and serum valproic acid concentration is essential for predicting the prognosis.