Is there a link between naproxen (Nonsteroidal Anti-Inflammatory Drug (NSAID)) overdose and the development of metabolic acidosis, high anion gap, and elevated lactate levels?

Naproxen Overdose and Metabolic Acidosis: Evidence of Association

Yes, there is documented evidence linking naproxen overdose to metabolic acidosis with high anion gap and elevated lactate levels, as reported in a case study published in Annals of Emergency Medicine. 1

Evidence of Naproxen-Induced Metabolic Acidosis

The FDA drug label for naproxen explicitly lists metabolic acidosis as a potential complication of significant naproxen overdose, along with other symptoms such as lethargy, dizziness, drowsiness, and gastrointestinal symptoms. 2

The case report from 1989 specifically documents a 15-year-old girl who developed severe metabolic acidosis and seizures following naproxen sodium ingestion. The acidosis resolved within 12 hours, correlating with the known pharmacokinetics of naproxen. 1

Clinical Presentation and Laboratory Findings

When naproxen overdose occurs, patients may present with:

• Metabolic acidosis (specifically mentioned in the FDA label)
• Altered mental status (lethargy, disorientation, confusion)
• Gastrointestinal symptoms (epigastric pain, nausea, vomiting)
• Seizures (as reported in the case study)

Laboratory findings may include:

• High anion gap
• Elevated lactate levels
• Decreased bicarbonate
• Renal dysfunction markers

Mechanism and Differential Diagnosis

While the exact mechanism of naproxen-induced metabolic acidosis is not fully elucidated, it's important to consider that high anion gap metabolic acidosis (HAGMA) can have multiple causes:

• Lactic acidosis (common in drug overdoses)
• Ketoacidosis
• Renal failure
• Toxin-induced acidosis

When evaluating a patient with suspected naproxen overdose and metabolic acidosis, it's crucial to rule out other common causes of HAGMA, such as:

• Salicylate toxicity (which can cause a more well-documented metabolic acidosis) 3
• Acetaminophen overdose (which has been associated with early anion gap metabolic acidosis and hyperlactatemia) 4, 5
• Other toxins like methanol or ethylene glycol

Management Approach

For patients with naproxen overdose presenting with metabolic acidosis:

1. Provide supportive care (FDA label states "symptomatic and supportive care") 2
2. Consider activated charcoal (60-100g in adults) if within 4 hours of ingestion 2
3. Monitor acid-base status with serial arterial blood gases
4. Assess renal function, as naproxen can cause renal dysfunction
5. Consider hemodialysis for severe acidosis, though the FDA notes that "hemodialysis does not decrease the plasma concentration of naproxen because of the high degree of its protein binding" 2

Important Clinical Considerations

• Metabolic acidosis may be an early sign of significant naproxen toxicity
• The presence of lactic acidosis with abdominal pain should prompt consideration of early CT angiography to rule out mesenteric ischemia, as lactic acidosis and abdominal pain can be a concerning combination 6
• Mental status changes may correlate with the severity of acidosis, with confusion in mild cases and stupor/coma in severe cases 7
• Elderly patients and those with renal impairment may be at higher risk for complications

Conclusion

While naproxen overdose is not among the most common causes of high anion gap metabolic acidosis, there is documented evidence of this association in both the FDA drug label and published case reports. Clinicians should be aware of this potential complication when evaluating patients with suspected NSAID overdose, particularly when metabolic acidosis and elevated lactate levels are present.