Brief Report
l-carnitine was safely administered in the setting of valproate toxicity

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Abstract

Background

l-Carnitine is a carnitine replacement that has been used in carnitine deficiency states. We conducted a review of patients with acute valproate (VPA) poisoning that had an elevated ammonia level and received l-carnitine to address safety.

Methods

After a brief training of systematic chart review, reviewers blinded to the purpose of the study completed a standardized data collection sheet. Ages, outcomes, side effects, presence of hyperammonemia, and total carnitine doses were recorded.

Results

Three years of poison center charts from more than 300 000 patients were reviewed; 674 patients ingested valproic acid. The median age was 26.2 years (range, 1-58 years). l-Carnitine was routinely recommended if the ammonia level was elevated. Fifty-five doses of carnitine were administered to 19 patients who had isolated VPA ingestions and 196 doses of carnitine were administered to patients with mixed overdoses that included VPA, all with an elevated ammonia level. No patient had a documented allergic reaction or side effects.

Conclusions

Two hundred fifty-one l-carnitine doses were not associated with adverse or toxic effects in our VPA toxic patients.

Introduction

l-Carnitine is a carnitine replacement that has been used in carnitine deficiency states. Chronic valproate (VPA) toxicity may result in hyperammonemia that responds to carnitine therapy [1], [2], [3]. It has also been used with questionable benefit in the setting of acute VPA-induced hepatitis [4].

It is unclear if hyperammonemia in acute VPA toxicity is associated with lethargy. Many clinicians have adapted a practice of administering l-carnitine in this setting because it may benefit patients and is presumably safe [5], [6].

We conducted a review of patients with acute VPA poisoning that had an elevated ammonia level and received carnitine. Our objective was to evaluate safety in this setting, not efficacy.

Section snippets

Methods

After a brief training of systematic chart review, reviewers blinded to the purpose of the study completed a standardized data collection sheet. Age, outcomes, side effects, and total carnitine doses were recorded. All human exposure cases with VPA, valproic acid (generic and trade names), and others, and/or carnitine were extracted by Crystal Reports from our poison center database then manually reviewed.

We defined an adverse event as hypotension after the administration of l-carnitine or

Results

Three years of poison center charts from more than 300 000 patients were reviewed; 674 patients acutely ingested valproic acid. The median age was 26.2 years (range, 1-58 years). Fifty-five doses of carnitine were administered to 19 patients who had isolated VPA ingestions and 196 doses of carnitine were administered to patients with mixed overdoses that included VPA.

No patient developed an allergic reaction or hypotension. All charts were reviewed by at least 2 reviewers with no disagreement

Conclusions

It remains unclear if the administration of l-carnitine changes the outcome in the setting of hyperammonemia induced by valproic acid. In the chronic setting, VPA-induced hyperammonemia is treated with l-carnitine [1], [2], [3].

In chronic VPA therapy, hyperammonemia is a common side effect and patients are usually asymptomatic. This side effect can occur in the absence of other evidence of hepatic dysfunction. Valproate has been associated with exacerbation of some metabolic conditions such as

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