Valproic acid poisoning: An evidence-based consensus guideline for out-of-hospital management

Abstract

A review of US poison center data for 2004 showed over 9000 ingestions of valproic acid. A guideline that determines the conditions for emergency department referral and prehospital care could potentially optimize patient outcome, avoid unnecessary emergency department visits, reduce health care costs, and reduce life disruption for patients and caregivers. An evidence-based expert consensus process was used to create the guideline. Relevant articles were abstracted by a trained physician researcher. The first draft of the guideline was created by the lead author. The entire panel discussed and refined the guideline before distribution to secondary reviewers for comment. The panel then made changes based on the secondary review comments. The objective of this guideline is to assist poison center personnel in the appropriate out-of-hospital triage and initial out-of-hospital management of patients with a suspected ingestion of valproic acid by 1) describing the process by which an ingestion of valproic acid might be managed, 2) identifying the key decision elements in managing cases of valproic acid ingestion, 3) providing clear and practical recommendations that reflect the current state of knowledge, and 4) identifying needs for research. This guideline applies to the acute ingestion and acute-on-chronic ingestion of immediate-release and extended-release dosage forms of valproic acid, divalproex, and valproate sodium alone. Co-ingestion of additional substances could require different referral and management recommendations depending on the combined toxicities of the substances. This review focuses on the ingestion of more than a single therapeutic dose and the effects of an overdose. Although therapeutic doses of valproic acid can cause adverse effects in adults and children, some idiosyncratic and some dose-dependent, these cases are not considered. This guideline is based on an assessment of current scientific and clinical information. The expert consensus panel recognizes that specific patient care decisions might be at variance with this guideline and are the prerogative of the patient and the health professionals providing care, considering all of the circumstances involved. This guideline does not substitute for clinical judgment. Recommendations are in chronological order of likely clinical use. The grade of recommendation is in parentheses. 1) All patients with suicidal intent, intentional abuse, or in whom a malicious intent is suspected (e.g., child abuse or neglect) should be referred to an emergency department (Grade D). 2) Patients who are symptomatic (more than somnolence or exhibiting coma or seizures) after a valproic acid ingestion should be referred to an emergency department (Grade C). 3) Asymptomatic patients with an unintentional acute ingestion of 50 mg/kg or more or asymptomatic patients who are taking the drug therapeutically and who take an additional single acute ingestion of 50 mg/kg or more of any valproic acid formulation should be referred to an emergency department for evaluatio...

Influence of Enterohepatic Recycling on the Time Course of Brain-to-Blood Partitioning of Valproic Acid in Rats

“…The present study demonstrated the various efficiencies of three different approaches to experimental ablation of VPA ER in rats. Oral administration of charcoal has been reported to eliminate more than half of the ER-related absorption of VPA in humans (Neuvonen et al, 1983), and administration of activated charcoal can be used to treat acute VPA overdose (Manoguerra et al, 2008). However, activated charcoal did not impact VPA ER in this study.…”

Review of Sodium Valproate Clinical and Biochemical Properties

“…For more than 4 decades VPA stipulate in clinical practice as an anticonvulsant to control seizures in forms of tonic-clonic (grand mal), complex partial and juvenile myoclonic. Published report by International League Against Epilepsy (ILAE) authorizes the efficiency and value of ethosuximide and VPA for children with absence seizures as initial monotherapy [2][3][4][5][6][7][8][9][10][11][12]. Karlov et al [11] reported a prescription based on valproate in dose 15 -25 mg/kg/day and levetiracetam in dose 20 -25 mg/kg/day that were used in the treatment of 23 patients with juvenile myoclonic, juvenile absence, and convulsive idiopathic generalized and children absence epilepsy.…”

“…For the treatment of absence epilepsy, it seems that older AEDs such as ethosuximide and VPA are more efficacious than newer AEDs. Due to reduced side effects, ethosuximide remains the first line treatment for childhood absence epilepsy [2][3][4].…”

“…It also increases the formation of GABA [5]. It is well known that VPA belongs to group of drugs with narrow therapeutic window and as prescription of VPA in Iranian epileptic patients continues to increase [4][5][6], an approach adjoining clinical pharmacotherapy guideline to control seizure attack was of interest that reviewed.…”

“…Two forms of drugs have extra FDA approvals. The extended-release form of drug (Depakote ER) is designated for migraine headache prophylaxis and the delayed-release product (Depakote) carries an indication for the short term management of acute manic episodes associated with bipolar disorder [1][2][3][4].…”