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Emergency and Acute Medicine – Nonsteroidal Anti-Inflammatory Poisoning
Nonsteroidal anti-inflammatory drugs (NSAIDs) exert their effects by inhibiting cyclooxygenase (COX), thereby blocking the conversion of arachidonic acid to prostaglandins. In most cases, NSAID ingestion results in low morbidity, and toxicity is usually mild. Much of the published toxicity data involves ibuprofen, largely because of its widespread over-the-counter availability. Fatal outcomes are rare but have been reported with massive ingestions. Patients with underlying congestive heart failure or renal insufficiency are at increased risk of toxicity because NSAIDs promote sodium and water retention and reduce renal blood flow. Experience with COX-2 inhibitors such as celecoxib in overdose is limited, but management is similar to that of traditional NSAIDs. Patients may still ingest rofecoxib or valdecoxib from stored supplies despite their withdrawal from the US market.
NSAIDs are available both by prescription and over the counter and include agents such as ibuprofen, naproxen, diclofenac, ketorolac, indomethacin, meloxicam, sulindac, piroxicam, and others. Toxic effects vary slightly among agents, but the overall clinical approach remains similar.
Clinical manifestations primarily involve the gastrointestinal and central nervous systems. Gastrointestinal symptoms include nausea, vomiting, and epigastric pain. Neurologic findings range from drowsiness, dizziness, and lethargy to aseptic meningitis and seizures in severe cases. Cardiovascular effects may include hypotension and tachycardia. Pulmonary complications such as eosinophilic pneumonia, apnea, or hyperventilation are uncommon but reported. Renal effects include acute renal failure, hyperkalemia, acute tubular necrosis, and acute interstitial nephritis. Hepatic injury may present as hepatocellular damage or cholestatic jaundice, particularly with diclofenac or sulindac. Metabolic effects are usually limited to a mild, transient metabolic acidosis. Hypersensitivity reactions can occur and include asthma exacerbations, angioedema, urticaria, and aseptic meningitis.
Evaluation begins with a focused history and assessment of the specific NSAID ingested, as subtle toxicologic differences exist between agents. Most cases result in mild toxicity, but identification of the drug is helpful because aseptic meningitis is more commonly associated with ibuprofen, while liver toxicity is more frequently seen with diclofenac and sulindac.
Laboratory evaluation should include electrolytes, blood urea nitrogen, creatinine, and glucose to assess baseline renal function and metabolic status. A complete blood count and arterial blood gas are indicated in large overdoses or if metabolic acidosis is suspected. Coagulation studies may be obtained, noting that etodolac can cause false-positive bilirubin or ketone dipstick results. Acetaminophen and salicylate levels should be obtained in all suspected NSAID ingestions, as patients often confuse these medications. Toxicology screens are not useful because NSAIDs are difficult to detect and results do not alter management.
The differential diagnosis includes other causes of metabolic acidosis, gastrointestinal irritation, and altered mental status, such as salicylate poisoning, isoniazid toxicity, ethylene glycol, methanol, and isopropanol ingestion.
Management is largely supportive. Prehospital care should focus on bringing all medication containers for identification. Initial stabilization follows standard airway, breathing, and circulation principles, with administration of naloxone, thiamine, and dextrose for altered mental status when indicated. In the emergency department, activated charcoal may be administered if the patient presents early after ingestion. Enhanced elimination techniques such as hemodialysis are not effective due to the high degree of plasma protein binding of NSAIDs.
Admission is indicated for patients with persistent vomiting, hematemesis, central nervous system depression, seizures, metabolic acidosis, hypotension or hypertension, congestive heart failure, or renal failure. Asymptomatic patients with nontoxic ingestions who remain well after 6–8 hours of observation may be safely discharged. Intentional ingestions warrant psychiatric evaluation and follow-up.
Key clinical points include the generally benign nature of NSAID poisoning, the importance of evaluating for coingestions, and the routine measurement of acetaminophen and salicylate levels. Massive overdoses and patients with underlying cardiac or renal disease carry a higher risk of significant toxicity and require closer monitoring.
Nonsteroidal anti-inflammatory drugs (NSAIDs) exert their effects by inhibiting cyclooxygenase (COX), thereby blocking the conversion of arachidonic acid to prostaglandins. In most cases, NSAID ingestion results in low morbidity, and toxicity is usually mild. Much of the published toxicity data involves ibuprofen, largely because of its widespread over-the-counter availability. Fatal outcomes are rare but have been reported with massive ingestions. Patients with underlying congestive heart failure or renal insufficiency are at increased risk of toxicity because NSAIDs promote sodium and water retention and reduce renal blood flow. Experience with COX-2 inhibitors such as celecoxib in overdose is limited, but management is similar to that of traditional NSAIDs. Patients may still ingest rofecoxib or valdecoxib from stored supplies despite their withdrawal from the US market.
NSAIDs are available both by prescription and over the counter and include agents such as ibuprofen, naproxen, diclofenac, ketorolac, indomethacin, meloxicam, sulindac, piroxicam, and others. Toxic effects vary slightly among agents, but the overall clinical approach remains similar.
Clinical manifestations primarily involve the gastrointestinal and central nervous systems. Gastrointestinal symptoms include nausea, vomiting, and epigastric pain. Neurologic findings range from drowsiness, dizziness, and lethargy to aseptic meningitis and seizures in severe cases. Cardiovascular effects may include hypotension and tachycardia. Pulmonary complications such as eosinophilic pneumonia, apnea, or hyperventilation are uncommon but reported. Renal effects include acute renal failure, hyperkalemia, acute tubular necrosis, and acute interstitial nephritis. Hepatic injury may present as hepatocellular damage or cholestatic jaundice, particularly with diclofenac or sulindac. Metabolic effects are usually limited to a mild, transient metabolic acidosis. Hypersensitivity reactions can occur and include asthma exacerbations, angioedema, urticaria, and aseptic meningitis.
Evaluation begins with a focused history and assessment of the specific NSAID ingested, as subtle toxicologic differences exist between agents. Most cases result in mild toxicity, but identification of the drug is helpful because aseptic meningitis is more commonly associated with ibuprofen, while liver toxicity is more frequently seen with diclofenac and sulindac.
Laboratory evaluation should include electrolytes, blood urea nitrogen, creatinine, and glucose to assess baseline renal function and metabolic status. A complete blood count and arterial blood gas are indicated in large overdoses or if metabolic acidosis is suspected. Coagulation studies may be obtained, noting that etodolac can cause false-positive bilirubin or ketone dipstick results. Acetaminophen and salicylate levels should be obtained in all suspected NSAID ingestions, as patients often confuse these medications. Toxicology screens are not useful because NSAIDs are difficult to detect and results do not alter management.
The differential diagnosis includes other causes of metabolic acidosis, gastrointestinal irritation, and altered mental status, such as salicylate poisoning, isoniazid toxicity, ethylene glycol, methanol, and isopropanol ingestion.
Management is largely supportive. Prehospital care should focus on bringing all medication containers for identification. Initial stabilization follows standard airway, breathing, and circulation principles, with administration of naloxone, thiamine, and dextrose for altered mental status when indicated. In the emergency department, activated charcoal may be administered if the patient presents early after ingestion. Enhanced elimination techniques such as hemodialysis are not effective due to the high degree of plasma protein binding of NSAIDs.
Admission is indicated for patients with persistent vomiting, hematemesis, central nervous system depression, seizures, metabolic acidosis, hypotension or hypertension, congestive heart failure, or renal failure. Asymptomatic patients with nontoxic ingestions who remain well after 6–8 hours of observation may be safely discharged. Intentional ingestions warrant psychiatric evaluation and follow-up.
Key clinical points include the generally benign nature of NSAID poisoning, the importance of evaluating for coingestions, and the routine measurement of acetaminophen and salicylate levels. Massive overdoses and patients with underlying cardiac or renal disease carry a higher risk of significant toxicity and require closer monitoring.
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