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 evaluation (Grade C). 4) Patients with unintentional ingestions of immediate-release valproic acid formulations, who are asymptomatic, and more than 6 hours has elapsed since the time of ingestion, can be observed at home (Grade C). 5) Patients with unintentional ingestions of delayed-release or extended-release formulations of valproic acid who are asymptomatic, and more than 12 hours has elapsed since the time of ingestion, can be observed at home (Grade C). 6) Pregnant women who ingest below the dose for emergency department referral and do not have other referral conditions should be directed to their primary care obstetrical provider for evaluation of potential maternal and fetal risk. Routine referral to an emergency department for immediate care is not required (Grade D). 7) Do not induce emesis (Grade C). 8) Activated charcoal can be administered to asymptomatic patients who have ingested valproic acid within the preceding hour (Grade C). Prehospital activated charcoal administration, if available, should only be carried out by health professionals and only if no contraindications are present. Poison centers should follow local protocols and experience with its use. Do not delay transportation in order to administer activated charcoal (Grades D). 9) In patients who have ingested valproic acid and who are comatose, naloxone can be considered for prehospital administration in the doses used for treatment of opioid overdose, particularly if the patient has respiratory depression (Grade C). 10) A benzodiazepine can be administered by EMS personnel if convulsions are present and if authorized by EMS medical direction, expressed by written treatment protocol or policy, or if there is direct medical oversight (Grade C).