Aspirin and Other Salicylate Poisoning


ByGerald F. O’Malley, DO, Grand Strand Regional Medical Center;
Rika O’Malley, MD, Grand Strand Medical Center
Reviewed/Revised Jun 2022
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(See also General Principles of Poisoning.)

Acute ingestion of > 150 mg/kg of salicylate can cause severe toxicity. Salicylate tablets may form bezoars, prolonging absorption and toxicity. Chronic toxicity can occur after several days or more of high therapeutic doses; it is common, often undiagnosed, and often more serious than acute toxicity. Chronic toxicity tends to occur in older patients.

< 5 mL is equivalent to about 7000 milligrams (twenty-two 325-mg tablets) of aspirin

Pearls & Pitfalls

  • Ingestion of <

Pathophysiology of Salicylate Poisoning

Salicylates impair cellular respiration by uncoupling oxidative phosphorylation. They stimulate respiratory centers in the medulla, causing primary respiratory alkalosis, which is often unrecognized in young children. Salicylates simultaneously and independently cause primary metabolic acidosis. Eventually, as salicylates disappear from the blood, enter the cells, and poison mitochondria, metabolic acidosis becomes the primary acid-base abnormality.

Salicylate poisoning also causes ketosis, fever, and, even when systemic hypoglycemia is absent, low brain glucose levels. Renal sodium, potassium, and water loss and increased but imperceptible respiratory water loss due to hyperventilation lead to dehydration.

Salicylates are weak acids that cross cell membranes relatively easily; thus, they are more toxic when blood pH is low. Dehydration, hyperthermia, and chronic ingestion increase salicylate toxicity because they result in greater distribution of salicylate to tissues. Excretion of salicylates increases when urine pH increases.

Symptoms and Signs of Salicylate Poisoning

With acute overdose, early symptoms include nausea, vomiting, tinnitus, and hyperventilation. Later symptoms include hyperactivity, fever, confusion, and seizures. Rhabdomyolysis, acute renal failure, and respiratory failure may eventually develop. Hyperactivity may quickly turn to lethargy; hyperventilation (with respiratory alkalosis) progresses to hypoventilation (with mixed respiratory and metabolic acidosis) and respiratory failure.

With chronic overdose, symptoms and signs tend to be nonspecific, vary greatly, and may suggest sepsis. They include subtle confusion, changes in mental status, fever, hypoxia, noncardiogenic pulmonary edema, dehydration, lactic acidosis, and hypotension.

Pearls & Pitfalls

  • Consider salicylate poisoning in older patients with findings that are nonspecific and/or compatible with sepsis (eg, subtle confusion, changes in mental status, fever, hypoxia, noncardiogenic pulmonary edema, dehydration, lactic acidosis, hypotension).

Diagnosis of Salicylate Poisoning

  • Serum salicylate level

  • Arterial blood gases (ABGs)

Salicylate poisoning is suspected in patients with any of the following:

  • History of a single acute overdose

  • Repeated ingestions of therapeutic doses

  • Unexplained metabolic acidosis

  • Unexplained confusion and fever (in older patients)

  • Other findings compatible with sepsis (eg, fever, hypoxia, noncardiogenic pulmonary edema, dehydration, hypotension)

rhabdomyolysis is suspected, serum creatine kinase (CK) and urine myoglobin are measured.

Significant salicylate toxicity is suggested by serum levels much higher than therapeutic (therapeutic range, 10 to 20 mg/dL [0.725 to 1.45 mmol/L]), particularly 6 hours after ingestion (when absorption is usually almost complete), and by acidemia plus ABG results compatible with salicylate poisoning. Serum levels are helpful in confirming the diagnosis and may help guide therapy, but levels may be misleading and should be clinically correlated.

Usually, ABGs show primary respiratory alkalosis during the first few hours after ingestion; later, they show compensated metabolic acidosis or mixed metabolic acidosis/respiratory alkalosis. Eventually, usually as salicylate levels decrease, poorly compensated or uncompensated metabolic acidosis is the primary finding. If respiratory failure occurs, ABGs suggest combined metabolic and respiratory acidosis, and chest x-ray shows diffuse pulmonary infiltrates. Plasma glucose levels may be normal, low, or high. Serial salicylate levels help determine whether absorption is continuing; ABGs and serum electrolytes should always be determined simultaneously. Increased serum CK and urine myoglobin levels suggest rhabdomyolysis.

Treatment of Salicylate Poisoning

After volume and electrolyte abnormalities are corrected, alkaline diuresis can be used to increase urine pH, ideally to 8. Alkaline diuresis is indicated for patients with any symptoms of poisoning and should not be delayed until salicylate levels are determined. This intervention is usually safe and exponentially increases salicylate excretion. Because hypokalemiapulmonary edema, patients are monitored for respiratory findings.

metabolic acidosis and decrease blood pH. Drugs that decrease respiratory drive should be avoided if possible because they may impair hyperventilation and respiratory alkalosis, decreasing blood pH.

Fever can be treated with physical measures such as external cooling. Seizures are treated with benzodiazepines. In patients with rhabdomyolysis, adequate hydration and urine output are crucial; alkaline diuresis may also help prevent renal failure.

Hemodialysis may be required to enhance salicylate elimination in patients with severe neurologic impairment, renal or respiratory insufficiency, acidemia despite other measures, or very high serum salicylate levels (>100 mg/dL [> 7.25 mmol/L] with acute overdose or > 60 mg/dL [> 4.35 mmol/L] with chronic overdose).

Treating acid-base alterations in salicylate-poisoned patients who require endotracheal intubation and mechanical ventilation for airway protection or oxygenation can be extremely challenging. In general, intubated patients should probably be dialyzed and closely monitored by a critical care specialist.

Key Points

  • Salicylate poisoning causes respiratory alkalosis and, by an independent mechanism, metabolic acidosis.

  • Consider salicylate toxicity in patients with nonspecific findings (eg, alteration in mental status, metabolic acidosis, noncardiogenic pulmonary edema, fever), even when a history of ingestion is lacking.

  • Estimate the severity of toxicity by the salicylate level and ABGs.

  • Consider hemodialysis if poisoning is severe.

Drugs Mentioned In This Article
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