Case 19 – Anticonvulsants

Case #19: Anticonvulsants
Author: Alexander Kogan, MD
Peer Reviewer: Patrick Lank, MD

A 45-year-old man with a past medical history of alcoholism, post-traumatic stress disorder, seizures, and bipolar disorder was brought to the emergency department after ingestion of unknown amount of valproic acid 6 hours prior to presentation in a suicidal attempt. Upon arrival to the ED, the patient was unresponsive. His exam was significant for pupils that were 3 mm bilaterally and sluggishly responsive to light. He withdrew all extremities to deep pain. DTRs were brisk and symmetric bilaterally. There were no IV marks, cyanosis or edema. The remainder of his exam was non-focal.

Vitals: Temp: 98.6, HR: 120, RR: 12, BP: 138/85, O2 Sat: 100% on RA

What initial labs would you like on this patient?
Bedside glucose, electrolytes, kidney and liver function tests, complete blood count, serum ASA/APAP/EtOH, valproic acid concentration, phenytoin concentration, carbamazepine concentration, ammonia concentration, and an ECG.

Even in the context of a known valproic acid ingestion, it is important to assess for concomitant ingestions of ASA and APAP, as well as other anticonvulsants, as the patient may be taking more than one medication.

 Initial valproic acid concentration was 236 mg/L (normal: 50-120 mg/L), phenytoin concentration was 0 mg/L (normal: 10-20 mg/L), carbamazepine concentration was 0 mg/L (normal: 4-12 mg/L), and ammonia concentration was 45 µmol/L (normal: 9-33 µmol/L).

Four hours later, a repeat valproic acid concentration increased to 810 mg/L and ammonia concentration increased to 82 µmol/L. The patient was intubated and admitted to MICU.

What is the initial treatment for this patient?
-Multidose Activated Charcoal (MDAC). Note: This can be given via NG tube in intubated patients.
-Consult toxicology and nephrology regarding possible dialysis.
-Consider an L-carnitine IV infusion (6g bolus followed by 1g IV q4h for 24 hours).
Why is carnitine suggested as a potential treatment for valproic acid toxicity?
Valproic acid is predominately metabolized in the liver and then excreted in urine. Through multiple complex mechanisms, valproic acid leads to carnitine deficiency and inhibition of the urea cycle, resulting in elevated ammonia levels in the blood. Carnitine is a required cofactor in the urea cycle and carnitine supplementation is hypothesized to decrease valproic acid-associated hyperammonemia.
Over the next three days, the patient improved and the psychiatrist decided to convert him from valproic acid to phenytoin. An initial bolus of fosphenytoin was given. What are the advantages of fosphenytoin over phenytoin?
-IV phenytoin can cause skin necrosis due to local extravasations, which is referred to as “purple hand syndrome”.
-IV phenytoin can depress myocardial contractility due to presence of propylene glycol (40%) and ethanol (10%) diluents. This limits the infusion rate to a maximum of 50 mg/min (versus 150 mg/min for fosphenytoin).
-Fosphenytoin can be given IM in patients without IV access, whereas Phenytoin cannot.
Three days later, the patient developed persistent fever, tender lymphadenopathy, and a diffuse macular rash. Labs were significant for leukocytosis and elevated liver enzymes. CXR, UA, and blood cultures were WNL. What could be the cause and the treatment of these symptoms?

Anticonvulsant Hypersensitivity Syndrome (AHS). This is an idiosyncratic reaction occurring within the first two months of treatment, which consists of a triad of fever, skin eruption, and internal organ involvement (usually liver). The treatment is IV steroids and discontinuation of the offending agent.

What other anticonvulsants can cause this syndrome?
What are the signs and treatment of phenytoin overdose?
-Slurred speech, ataxia, nystagmus, seizures, extrapyramidal symptoms, and chorea (in children)

-Supportive care
-Activated charcoal
-Hemodialysis is not effective (and rarely indicated) because phenytoin is extensively bound to serum proteins (predominately albumin) and has not been shown to significantly affect clinical outcomes.


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Larsen JR, Larsen LS. Clinical features and management of poisoning due to phenytoin. Med Toxicol Adverse Drug Exp. 1989 Jul-Aug;4(4):229-45.

Russell S. Carnitine as an antidote for acute valproate toxicity in children. Curr Opin Pediatr. 2007 Apr;19(2):206-10.

Sztajnkrycer MD. Valproic acid toxicity: overview and management. J Toxicol Clin Toxicol. 2002;40(6):789-801.

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