Valproic Acid - Let’s Start Tripping

It’s 1967 and after 5 years of being meticulously studied in French laboratories, Valproic Acid is approved as an anticonvulsant in France. 53 years after that achievement, with no small amount of irony, a 53 y/o male presents to the emergency department after an intentional ingestion of anywhere between 20-40 tablets of 500 mg extended release Valproic Acid (VPA) that he had been prescribed for his Bipolar disorder.

Management of any significant drug ingestion often warrants a phone call to your local poison control center or a consultation with an in-house toxicologist. Unfortunately, our Toxicologist was not available that day, so we decided to call the poison control center. Before this call, however, we should begin initial management.

Initial management of any emergency department patient involves assessing the airway, breathing, and circulation of the patient (aka The ABCs). This patient was walking, talking, and in no acute distress without any systemic symptoms except for his persistent anxiety. The vital signs were significant only for tachycardia. From this information, we note that the patient's ABCs are indeed intact.

Now to gather the information we need for the poison control center. Some helpful information (if available) includes the dosage, route, strength, and timing of the ingestion. As stated earlier, this patient ingested 20-40 tablets of 500 mg extended release Valproic Acid just prior to arrival, meaning his total cumulative dose of VPA was between 10 and 20 grams (of the delayed release formulation).

We know, from our research and from consultation with the toxicologists at poison control, that the toxic dose of VPA is 200 mg/kg. In a 70 kg patient this means an ingestion of 14 grams (which is how much our patient may have ingested) or a VPA level >150 or 180 mcg/mL (depending on your source).

Since it was very early into his ingestion, we gave our patient activated charcoal, placed him on a monitor and drew labs. Labs important in the assessment of a VPA overdose are a VPA level (which does not correlate with toxicity, but can help guide management), Chemistries, Liver function tests, and an Ammonia level.

Symptoms of a VPA overdose include respiratory depression, hypotension, tachycardia, hyperthermia, nausea, vomiting, diarrhea, hepatitis, and a rare complication of overdose is cerebral edema and ARDS.

Ammonia level is of vital importance in a VPA overdose as VPA can cause VPA associated hepatic encephalopathy - which is due to VPA’s metabolism causing inhibition of the urea cycle. This can be seen in patients with therapeutic VPA levels and normal LFTs. These patients should be treated with L-carnitine which increases metabolism of valproate

In patients with a level greater than 500 mg/L, or those having signs of hypotension or cerebral edema should undergo dialysis.

Our patient's level was 55 mg/L - which was low enough that our poison control center recommended observation and a repeat level due to the extended release preparation he took. Our patient’s repeat VPA level increased to 192 mg/L and he was admitted to our ICU for monitoring. After one day of monitoring, the patient's levels decreased appropriately without any further intervention and he was discharged home. Our in house psychiatrists counseled the patient on living with anxiety and ensured close follow up.