Situation: A mental health day program at a government hospital serves adults with mood disorders. During the weekly clinic, the nurse reviews each client's treatment plan. A 28-year-old woman taking valproate for bipolar I disorder has had drowsiness, confusion, and vomiting for 2 days. Her valproate level is 85 mcg/mL (therapeutic range for mania 50–125 mcg/mL), and her liver function tests and serum lipase are normal. Which test should the nurse ask the prescriber to order?

Valproate can raise blood ammonia and cause lethargy, vomiting, and confusion even with a therapeutic drug level and normal liver tests. Normal lipase makes pancreatitis less likely. An ammonia level is checked when a client on valproate becomes lethargic or confused.

Clinical context
A 28-year-old woman with bipolar I disorder is taking valproate. She now has drowsiness, confusion, and vomiting for 2 days. Her valproate level is 85 mcg/mL, which is inside the therapeutic range for mania (50–125 mcg/mL). Liver function tests and serum lipase are normal. The key point is that a therapeutic drug level and normal liver tests do not rule out a serious valproate-related neurotoxicity.

Why the answer is serum ammonia
Valproate can raise blood ammonia even when the valproate level is therapeutic and liver enzymes are normal ^[1][2]. The clinical picture of drowsiness, confusion, and vomiting matches valproate-induced hyperammonemic encephalopathy (VHE). In VHE, the patient develops a decreasing level of consciousness, cognitive slowing, lethargy, vomiting, and drowsiness ^[1]. The main biochemical driver is hyperammonemia, not a high valproate level or hepatocellular injury ^[1][2].

A normal valproate level and normal liver function tests do not exclude hyperammonemic encephalopathy. Valproate-associated hyperammonemia can occur in people with normal liver function, despite normal doses and serum levels of VPA ^[2]. Therefore, when a patient on valproate becomes lethargic or confused, the prescriber should order a serum ammonia level.

Why the other options are less appropriate

Option	Why it is not the priority
1. Platelet count	Valproate can cause thrombocytopenia, but drowsiness, confusion, and vomiting are not typical presenting features of low platelets. Bleeding or bruising would be more relevant.
2. TSH level	Valproate may affect thyroid function over time, but acute drowsiness, confusion, and vomiting do not point to hypothyroidism or hyperthyroidism as the immediate cause.
3. Serum sodium level	Hyponatremia can cause confusion and vomiting, but valproate is not a common cause of acute hyponatremia. The symptom cluster and drug exposure make hyperammonemia far more likely.
4. Serum ammonia level	Directly evaluates the suspected mechanism of valproate-induced encephalopathy. This is the correct test when a patient on valproate becomes lethargic or confused.

Pathophysiology and clinical reasoning
Valproate increases blood ammonia through several mechanisms. It can reduce hepatic urea cycle activity and increase renal ammonia production. The resulting hyperammonemia crosses the blood–brain barrier and causes cerebral edema and neurotoxicity. The clinical syndrome includes vomiting, drowsiness, lethargy, cognitive slowing, and focal neurological deficits ^[1]. Because the valproate level is therapeutic and liver enzymes are normal, the patient does not have simple valproate toxicity or valproate-induced hepatitis. Normal serum lipase makes pancreatitis less likely, which is important because valproate can also cause pancreatitis.

Watch out! Hyperammonemic encephalopathy can occur with a normal valproate level and normal liver tests. Do not wait for an elevated valproate level or abnormal LFTs before checking ammonia.

Key point! In a patient on valproate with new drowsiness, confusion, and vomiting, the first metabolic test to request is a serum ammonia level, regardless of the valproate concentration.

Clinical application for nursing practice
The nurse should recognize that valproate-related neurotoxicity is a clinical diagnosis supported by an elevated ammonia level. The nurse should ask the prescriber to order a serum ammonia level and should monitor the patient’s level of consciousness, orientation, and vital signs. If ammonia is elevated, the prescriber may reduce or discontinue valproate and consider treatments such as lactulose or L-carnitine ^[1]. Early recognition prevents progression to coma.

The priority nursing action is to identify the likely cause of altered mental status in a patient taking valproate by requesting a serum ammonia level. This test directly evaluates the suspected mechanism of valproate-induced hyperammonemic encephalopathy ^[1][2].