# A 29-year-old client with epilepsy takes divalproex 1,000 mg twice daily; topiramate was added 2 weeks ago for migraine prevention. The client is admitted with 2 days of vomiting, increasing lethargy, and confusion. The client is oriented to person only, has asterixis, and has no nuchal rigidity or focal weakness. Temperature is 37.0°C (98.6°F), blood pressure 124/76 mm Hg, heart rate 88/min, and respiratory rate 16/min. Laboratory results: ammonia 168 mcg/dL (reference 15 to 45), valproate level 78 mcg/mL (therapeutic 50 to 100), AST 32 U/L, ALT 28 U/L, total bilirubin 0.6 mg/dL, INR 1.0, bicarbonate 23 mEq/L, glucose 96 mg/dL, and sodium 139 mEq/L. Complete the diagram by selecting the condition the client is most likely experiencing, 2 actions the nurse should take to address that condition, and 2 parameters the nurse should monitor to assess the client's progress.

> source: MyMerci (mymerci.kr)  
> url: https://mymerci.kr/pages/nclex_q.php?qn_id=617372&lang=en  
> language: en  
> subject: Adverse Effects/Contraindications/Interactions  
> category: PPT

## Question

A 29-year-old client with epilepsy takes divalproex 1,000 mg twice daily; topiramate was added 2 weeks ago for migraine prevention. The client is admitted with 2 days of vomiting, increasing lethargy, and confusion. The client is oriented to person only, has asterixis, and has no nuchal rigidity or focal weakness. Temperature is 37.0°C (98.6°F), blood pressure 124/76 mm Hg, heart rate 88/min, and respiratory rate 16/min. Laboratory results: ammonia 168 mcg/dL (reference 15 to 45), valproate level 78 mcg/mL (therapeutic 50 to 100), AST 32 U/L, ALT 28 U/L, total bilirubin 0.6 mg/dL, INR 1.0, bicarbonate 23 mEq/L, glucose 96 mg/dL, and sodium 139 mEq/L. Complete the diagram by selecting the condition the client is most likely experiencing, 2 actions the nurse should take to address that condition, and 2 parameters the nurse should monitor to assess the client's progress.

Condition

Select 1
Valproate-induced hepatotoxicity
Topiramate-associated metabolic acidosis
Valproate hyperammonemic encephalopathy
Acute valproate overdose toxicity

Actions to take

Select 2
Hold divalproex and notify the prescriber
Administer the prescribed activated charcoal
Administer the prescribed IV levocarnitine
Administer the prescribed IV acetylcysteine
Start the prescribed sodium bicarbonate infusion

Parameters to monitor

Select 2
Serum valproate concentration
Serum bicarbonate
Serum ALT and bilirubin
Serum ammonia level
Level of consciousness

## Explanation

Encephalopathy with a high ammonia, a therapeutic valproate level, and normal liver tests is valproate-induced hyperammonemic encephalopathy, and topiramate increases that risk. The nurse holds valproate and notifies the prescriber, and levocarnitine is given to restore the carnitine that valproate depletes. Serum ammonia and level of consciousness show whether the encephalopathy is resolving.

## In-depth explanation

Quick answer
Valproate-induced hyperammonemic encephalopathy. Actions: hold divalproex and notify the prescriber; administer the prescribed IV levocarnitine. Monitor: serum ammonia level, and level of consciousness.

Why this is correct
Valproate can raise ammonia even at therapeutic levels and with normal liver function, because it depletes carnitine and inhibits the urea cycle. The Depakote label warns that combining valproate with topiramate is associated with hyperammonemia with or without encephalopathy. Asterixis, vomiting, and confusion with ammonia 168 mcg/dL fit this diagnosis, while the normal AST, ALT, bilirubin, and INR argue against hepatotoxicity.

Easy analogy or mental picture
Think of valproate as a clog in the urea-cycle drain: the sink (liver) is healthy, but ammonia backs up. Levocarnitine helps clear the clog, and stopping valproate stops adding to it.

Memory hook
Normal liver + normal level + high ammonia + confusion = valproate ammonia; stop the drug, give carnitine.

NCLEX decision rule
When a drug adverse effect is suspected, hold the suspected drug and notify the prescriber, then choose the specific treatment that matches the laboratory pattern rather than the drug name.

Why the other choices are wrong
Hepatotoxicity would show rising transaminases, bilirubin, and INR, which are normal, so acetylcysteine and an ALT trend are misdirected. Acute overdose is unlikely with a therapeutic valproate level, so charcoal and repeated valproate levels do not address the problem. Topiramate can cause a non-anion-gap acidosis, but bicarbonate is 23 mEq/L, so a bicarbonate infusion and bicarbonate trend are not indicated.

References
1DailyMed — Depakote (divalproex sodium) prescribing informationHyperammonemia and encephalopathy with normal liver tests; increased risk with concomitant topiramate.
2Systematic review: valproic acid-associated hyperammonemiaHyperammonemia occurs at therapeutic valproate levels; management includes discontinuation and L-carnitine.

## Clinical scenario

Scenario
A client on divalproex with newly added topiramate has vomiting, lethargy, confusion, and asterixis with ammonia 168 mcg/dL, a therapeutic valproate level, and normal liver tests and bicarbonate.

## Key concepts

- **Hyperammonemic encephalopathy** — Brain dysfunction from high blood ammonia, often with asterixis, lethargy, and vomiting.
- **Levocarnitine** — A carnitine supplement used to treat valproate-associated hyperammonemia and toxicity.
- **Asterixis** — A flapping tremor of the outstretched hands that signals metabolic encephalopathy.

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