- USES: Ibuprofen is used for fever and pain control and for the treatment of several rheumatologic conditions. PHARMACOLOGY: Ibuprofen inhibits the cyclooxygenase enzyme, leading to decreased prostaglandin production and decreased pain and inflammation. TOXICOLOGY: Gastrointestinal (GI) symptoms are due to both local irritant effects and the inhibition of prostaglandins (PG), which are responsible in part for maintaining the GI mucosal barrier. Inhibition of thromboxane A2 production in platelets prolongs bleeding time and contributes to gastrointestinal bleeding. Inhibition of PGI2 and PGE2, which have vasodilatory and natriuretic activity in the kidney, can be linked to sodium and water retention and occasional acute renal failure. EPIDEMIOLOGY: Overdose is common; however, severe toxicity is very rare. MILD TO MODERATE TOXICITY: In general, patients are asymptomatic or have mild GI upset (ie, nausea, vomiting, abdominal pain). Mild CNS depression (drowsiness, lethargy) and headache are common (incidence up to 30%). Nystagmus, diplopia, headache, tinnitus, and transient deafness may also occur following overdose. SEVERE TOXICITY: With massive overdose, seizure, coma, acute renal failure, and, very rarely, cardiopulmonary arrest may occur. Upper GI bleeding may occur after acute or chronic ingestion. Elevated liver enzymes, hypoprothrombinemia, metabolic acidosis, hypokalemia, hypophosphatemia, hyponatremia, and hyperkalemia (associated with renal failure), hypotension, bradycardia, tachycardia, atrial fibrillation, dyspnea, aspiration pneumonia, rhabdomyolysis, and disseminated intravascular coagulation have also been observed in overdose. Transient episodes of apnea have been reported in young children following large ingestions. Acute pancreatitis has been reported. ONSET: Symptoms typically occur within 4 to 6 hours of ingestion. ADVERSE EFFECTS: Gastrointestinal distress, nausea, and epigastric pain are the most common findings; upper GI bleeding may occur after acute or chronic ingestion. Angioedema, hives, itching, rash, and swelling have also been reported with therapeutic use. Fluid retention, interstitial nephritis, nephritic syndrome, and acute renal failure can develop. Hematologic effects include agranulocytosis, aplastic anemia, and thrombocytopenia. Headache, asthma exacerbation, aseptic meningitis, delirium, and anaphylactoid reactions have also been reported.
Range of Toxicity:
- TOXICITY: Ingestions of less than 200 mg/kg rarely cause significant toxicity; ingestions of greater than 400 mg/kg may result in serious effects. ADULTS: Overdoses of up to 48 g have been well tolerated by healthy adults. An adult died following an overdose of 105 g of sustained-release ibuprofen. THERAPEUTIC DOSE: ADULT: OTC: 200 mg orally every 4 to 6 hours as needed; PRESCRIPTION: 400 to 800 mg orally every 6 to 8 hours as needed. PEDIATRIC: OTC: 5 to 10 mg/kg.
- Support: MANAGEMENT OF MILD TO MODERATE TOXICITY: Most ibuprofen toxicity resolves with supportive care. Otherwise healthy patients with a history of ibuprofen poisoning generally require only supportive care and fluid and electrolyte replacement. MANAGEMENT OF SEVERE TOXICITY: Maintain an open airway and support ventilation. Treat seizures with benzodiazepines, hypotension with fluids and adrenergic vasopressors, and coma with intubation. Monitor ECG and arterial blood gases in patients with severe toxicity.
- Decontamination: PREHOSPITAL: Activated charcoal can be given to patients with significant overdose (more than 200 mg/kg) who are alert and can protect their airway. HOSPITAL: Activated charcoal binds ibuprofen and should be administered after significant overdose (more than 200 mg/kg). Gastric lavage is rarely, if ever, indicated, as this drug is absorbed rapidly and severe toxicity is exceedingly rare.
- Airway management: Endotracheal intubation should be considered for patients who present with CNS depression (rare).
- Antidote: None
- Hypotensive episode: IV 0.9% NaCl 10 to 20 ml/kg, dopamine, norepinephrine.
- Anaphylaxis: Mild: antihistamines; Severe: airway management, epinephrine, ECG monitoring, fluids.
- Acidosis: Administer sodium bicarbonate 1 to 2 mEq/kg intravenously for severe acidosis (pH less than 7.1). Monitor arterial pH and blood gases to guide bicarbonate therapy.
- Monitoring of patient: Serum ibuprofen levels are not available in most hospital laboratories and are not necessary for clinical management. Measure serum electrolytes, creatinine and BUN. If significant CNS or respiratory toxicity is present, assess acid-base status. Obtain serum acetaminophen level. Monitor for gastrointestinal bleeding.
- Enhanced elimination procedure: Ibuprofen is highly protein-bound; hemodialysis is unlikely to be effective.
- Patient disposition: HOME CRITERIA: Asymptomatic children with inadvertent ingestions of less than 200 mg/kg can be managed at home with milk or water dilution and observation. OBSERVATION CRITERIA: Symptomatic children, adults with deliberate ingestion, and children ingesting more than 200 mg/kg should be referred to a health care facility for observation and treatment. Most patients who have ingested significant amounts of ibuprofen will manifest symptoms within 4 to 6 hours. ADMISSION CRITERIA: Patients who develop CNS depression, hypotension, acidosis, or gastrointestinal bleeding should be admitted.