Can naproxen (NSAID) overdose cause severe metabolic acidosis with a high anion gap and elevated lactate levels?

Naproxen Overdose Can Cause Severe Metabolic Acidosis with High Anion Gap and Elevated Lactate

Naproxen overdose can directly cause severe metabolic acidosis with high anion gap and elevated lactate levels, as confirmed by the FDA drug label. 1

Mechanism and Clinical Presentation

Naproxen overdose affects acid-base balance through several mechanisms:

• Direct metabolic acidosis is listed as a specific complication in the FDA drug label for naproxen overdose 1
• Symptoms of significant naproxen overdose include:
  • Lethargy, dizziness, drowsiness
  • Epigastric pain and abdominal discomfort
  • Altered liver function
  • Renal dysfunction
  • Metabolic acidosis
  • Respiratory depression (in severe cases)

Evidence from Case Reports

A specific case report from 1989 documents a 15-year-old girl who developed severe metabolic acidosis and seizures shortly after naproxen sodium ingestion. The acidosis resolved within 12 hours, correlating with the known pharmacokinetics of naproxen. 2

Diagnostic Approach for High Anion Gap Metabolic Acidosis

When evaluating a patient with suspected naproxen-induced metabolic acidosis:

1. Calculate the anion gap: AG = Na⁺ - (Cl⁻ + HCO₃⁻)

   • Severe acidosis: AG >27 mmol/L
   • Moderate acidosis: AG 23-27 mmol/L 3

2. Measure lactate levels, as elevated lactate is common in drug-induced metabolic acidosis 3

3. Assess for other clinical manifestations:

   • Mental status changes (confusion, drowsiness, lethargy)
   • Respiratory compensation (Kussmaul breathing)
   • Hemodynamic instability

Management of Naproxen-Induced Metabolic Acidosis

According to the FDA drug label, treatment should focus on:

1. Supportive care - There are no specific antidotes for naproxen overdose 1

2. Gastrointestinal decontamination (if within 4 hours of ingestion):

   • Activated charcoal (60-100g in adults)
   • Consider osmotic cathartic 1

3. Acid-base management:

   • For severe acidosis (pH <7.1 or bicarbonate <10 mEq/L), IV sodium bicarbonate may be considered 3
   • Monitor arterial blood gases to assess pH and bicarbonate levels

4. Fluid resuscitation:

   • Isotonic fluids (0.9% NaCl) at 15-20 ml/kg/hr 3
   • Monitor electrolytes, particularly potassium

5. Special considerations:

   • Hemodialysis is not effective for naproxen removal due to high protein binding 1
   • Forced diuresis and alkalinization of urine are not useful for the same reason 1

Important Clinical Pearls

• Mental status changes in metabolic acidosis typically correlate with the degree of acidosis, ranging from irritability and confusion in mild cases to stupor and coma in severe cases 3

• Metabolic acidosis with elevated lactate can be a marker of severity in naproxen overdose

• Multiple mechanisms may contribute to acidosis in NSAID overdose, including direct drug effects, renal impairment, and tissue hypoperfusion

• Unlike some other toxin-induced acidoses, naproxen-induced acidosis cannot be effectively treated with hemodialysis due to high protein binding 1

• Monitor for other complications of naproxen overdose including gastrointestinal bleeding, hypertension, acute renal failure, and respiratory depression 1

The temporal relationship between naproxen ingestion and development of metabolic acidosis, along with exclusion of other causes, is key to establishing the diagnosis of naproxen-induced metabolic acidosis.