Nonsteroidal Anti-Inflammatory Drugs

GENERAL PRINCIPLES

NSAIDs are widely prescribed as analgesics and for the management of inflammatory diseases. There are many different agents available; the discussion here relates to ibuprofen and naproxen.

Pathophysiology

• NSAIDs exert their therapeutic effects by inhibiting COX and thereby preventing the formation of prostaglandins.

• This mechanism accounts for both their therapeutic effects and toxicities, which include ulceration of the GI mucosa and renal dysfunction.

• In most cases, acute overdose is benign. In rare cases of massive overdose, mental status changes, anion gap metabolic acidosis (from accumulation of acidic metabolites), and seizures may occur.

DIAGNOSIS

Clinical Presentation

• Patients with acute NSAID overdose typically have no symptoms or signs or isolated GI distress.

• In rare cases of massive overdose, patients may present with encephalopathy, coma, seizures, and cardiovascular collapse.

Diagnostic Testing

• Obtain a BMP to evaluate renal function and acid-base status.

î Large overdoses may cause an elevated anion gap metabolic acidosis.

î Kidney injury is unusual in acute overdoses; if present, it typically resolves rapidly and spontaneously.

• Obtain an APAP concentration, as many patients confuse over-the-counter analgesics.

TREATMENT

Significant toxicity is extremely rare in NSAID overdose. Most patients require no treatment or symptomatic treatment only. In rare cases of massive overdose, substantial resuscitative care may be required.

Medications

• Patients with GI upset or dyspepsia may benefit from antiemetics and antacids.

• Intravenous fluid resuscitation for those with hypovolemia or hemodynamic instability.

• Treat seizures with benzodiazepines (or other directly GABAergic antiepileptics such as barbiturates or propofol).

• In rare cases, vasopressors and/or inotropes may be needed.

• As in most cases of elevated anion gap acidosis, indiscriminate use of sodium bicarbonate is not helpful.

Nonpharmacologic Therapies

• In rare cases, patients with massive overdoses resulting in coma may require intubation and mechanical ventilation.

• Hemodialysis may improve acid-base status but does not remove NSAIDs.