Delayed valproic acid toxicity: A retrospective case series

Ingels, Marianne; Beauchamp, Jon; Clark, Richard F.; Williams, Saralyn R.

doi:10.1067/mem.2002.124443

Cited by 21 publications

(6 citation statements)

References 9 publications

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“…There were six level 4 articles that specifically mentioned delayed onsets of clinical effects after valproic acid ingestion (9,50,66,(72)(73)(74). On closer review, many of these patients had early symptoms followed by delayed deteriorations in their conditions.…”

Section: Onset Of Effects After Acute Ingestionmentioning

confidence: 99%

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

Manoguerra

Erdman

Woolf

et al. 2008

Clinical Toxicology

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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...

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Section: Onset Of Effects After Acute Ingestionmentioning

confidence: 99%

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

Manoguerra

Erdman

Woolf

et al. 2008

Clinical Toxicology

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“…3,4 Much like valproic acid and salicylates in acute overdose scenarios, unpredictable and random absorption may follow. 5,6 Carbamazepine ingestions may be managed by several means. AC adsorbs the drug preventing GI absorption and is a common means of decontamination.…”

Section: Discussionmentioning

confidence: 99%

Delayed Elevation in Carbamazepine Concentrations After Overdose

Patel

Schindlbeck

Bryant

2013

American Journal of Therapeutics

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An initial carbamazepine concentration may initially be supratherapeutic, therapeutic, or even subtherapeutic only to persist to rise over time. The aim of this study was to report the frequency of toxic carbamazepine concentrations continuing to rise and to estimate how often an initially therapeutic or subtherapeutic concentration misrepresents the potential toxicity of an acute carbamazepine overdose. An 8-year retrospective search of all carbamazepine exposures reported to the Illinois Poison Center (January 1, 2001 through December 31, 2008) was reviewed. Inclusion criteria were acute poisonings with a documented carbamazepine concentration of >12 μg/mL at any time. Those with initial concentrations of >12 μg/mL that subsequently increased over time were recorded. Additionally, those cases that initially had therapeutic (4-12 μg/mL) or subtherapeutic (<4 μg/mL) concentration were identified. Descriptive statistics were used to analyze the data. A total of 1424 cases were reported. Of the 523 patients with documented concentrations of >12 μg/mL, 93 patients (17.8%) had initial carbamazepine concentrations >12 μg/mL and continued to rise. Sixteen patients (3.5%) had initial carbamazepine concentrations that were therapeutic (4-12 μg/mL) and 7 patients (1.3%) had initial carbamazepine concentrations <4 μg/mL before rising >12 μg/mL. Certain patients had progressive decreases in level of consciousness corresponding to increasing carbamazepine concentrations. Additionally, several patients with initial levels of therapeutic or subtherapeutic concentration later became comatose and required ventilator management. Initial serum carbamazepine concentrations can be misleading. Serial measurements documenting a declining carbamazepine concentration or prolonged observation are recommended when managing these overdoses.

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“…However, four hours later the clinical condition worsened and, without rechecking the VPA concentration, the first haemodialysis was started. We believed that at that point the VPA level was even higher because of delayed toxicity (10). A threshold level for initiating haemodialysis is not set, but it is proposed that haemodialysis should be considered for any patient with a significantly reduced level of consciousness and elevated VPA concentration (3,4).…”

Section: Discussionmentioning

confidence: 99%

Life-threatening Valproate Overdose Successfully Treated with Haemodialysis

Meštrović¹,

Filipović²,

Polić³

et al. 2008

Archives of Industrial Hygiene and Toxicology

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Valproate (VPA) poisoning is an increasing clinical problem. The most common finding in VPA overdose is the depression of the central nervous system, which may progress to coma and death. This type of poisoning is difficult to treat, as no antidote exists. This report describes a case with a 16-year-old girl who poisoned herself with valproate. Initial treatment included naloxone, but she did not respond. She became comatose, with serum VPA concentration of 1320 µg mL -1. Three sessions of haemodialysis were performed, effectively eliminating VPA and decreasing the serum concentration. The patient regained consciousness and fully recovered. To our knowledge, this is the highest serum VPA concentration reported by now in children aged 16 or less. Haemodialysis has proved to be the treatment of choice for life-threatening acute VPA overdose in children. Me{trovi} J, et al. VALPROATE OVERDOSE TREATED WITH HAEMODIALYSIS Arh Hig Rada Toksikol 2008;59:295-298: Valproate (VPA) is used as sodium valproate to manage childhood refractory epilepsy, behavioural disorders, and migraines. Cases of VPA overdosing have been on the rise (1). The most common finding is the central nervous system depression, and management is mainly symptomatic and supportive, including activated charcoal and naloxone (2). Haemodialysis, haemoperfusion, or both, have also been reported (3, 4). Here we report a case of a 16-year-old girl with VPA-induced coma who was successfully treated with haemodialysis. KEY WORDS: central nervous system depressants, intensive care, thrombocytopenia, toxicity CASE PRESENTATIONA 16-year-old girl was admitted to the Emergency Department of the University Hospital Split eight hours after ingesting 75 g (882 mg kg -1 ) of VPA (enteric-coated formulation marketed as Apilepsin ® ) in attempted suicide. On admission, her vital signs were: blood pressure 130/70 mmHg, pulse 100 min -1 , and respiratory rate 25 min -1 and her Glasgow Coma Scale (GCS) score was 6. Initial blood analysis revealed serum VPA concentration of 1320 µg mL -1. Arterial blood gas analysis showed compensated metabolic acidosis, with an anion gap of 22.3 mmol L -1 . Complete blood count, electrolytes, creatinine, and liver enzymes were normal. Two doses of naloxone, 0.9 mg each, were given intravenously, but without notable improvement of her neurological status. Four hours after admission, she was in a deep coma (GCS 3). Breathing and circulation were stable, the patent airway was secured with the oropharyngeal (Guedel) airway, and there was no need for mechanical ventilation. Haemodialysis was considered the best possible therapeutic intervention at that moment, and the first session was immediately started through a double-lumen internal jugular vein using a NIPRO FB 130 TGA dialyser.

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Delayed valproic acid toxicity: A retrospective case series

Cited by 21 publications

References 9 publications

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

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

Delayed Elevation in Carbamazepine Concentrations After Overdose

Life-threatening Valproate Overdose Successfully Treated with Haemodialysis

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