Acute salicylate toxicity typically results with ingestion of a total dose ≥ 150 mg/kg (approximately 7.5 to 10 g in adults). Salicylate poisoning can cause vomiting, tinnitus, confusion, hyperthermia, respiratory alkalosis, metabolic acidosis, and multiple organ failure. Diagnosis is clinical, evaluation includes measurement of the anion gap, arterial blood gases, and serum salicylate levels. Treatment is with activated charcoal and alkaline diuresis or hemodialysis.
(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 or misdiagnosed, and often more serious than acute toxicity. Chronic toxicity tends to occur in older adults.
The most concentrated and toxic form of salicylate is oil of wintergreen (methyl salicylate, a component of some liniments and solutions used in hot vaporizers); ingestion of The most concentrated and toxic form of salicylate is oil of wintergreen (methyl salicylate, a component of some liniments and solutions used in hot vaporizers); ingestion of< 5 mL is equivalent to approximately 7000 milligrams (twenty-two 325-mg tablets) of aspirin, which can kill a young child. Any exposure should be considered serious. Bismuth subsalicylate (8.7 mg salicylate/mL) is another potentially unexpected source of large amounts of salicylate., which can kill a young child. Any exposure should be considered serious. Bismuth subsalicylate (8.7 mg salicylate/mL) is another potentially unexpected source of large amounts of salicylate.
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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 or pneumonia. They include subtle confusion, changes in mental status, fever, hypoxia, noncardiogenic pulmonary edema, dehydration, lactic acidosis, and hypotension.
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Diagnosis of Salicylate Poisoning
Serum salicylate level
Arterial blood gases (ABGs) or venous blood gases (VBGs)
Salicylate poisoning is suspected in patients with any of the following:
History of a prior acute overdose
Repeated ingestions of therapeutic doses
Unexplained metabolic acidosis
Unexplained confusion and fever (in older adults)
Other findings compatible with sepsis (eg, fever, hypoxia, noncardiogenic pulmonary edema, dehydration, hypotension)
If poisoning is suspected, serum salicylate level (drawn at least a few hours after ingestion), urine pH, ABGs or VBGs, serum electrolytes, serum creatinine, plasma glucose, and blood urea nitrogen (BUN) are measured. If If poisoning is suspected, serum salicylate level (drawn at least a few hours after ingestion), urine pH, ABGs or VBGs, serum electrolytes, serum creatinine, plasma glucose, and blood urea nitrogen (BUN) are measured. Ifrhabdomyolysis 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 or VBG 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 or VBGs 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 or VBGs suggest combined metabolic and respiratory acidosis, and chest radiograph shows diffuse pulmonary infiltrates. Plasma glucose levels may be normal, low, or high. Serial salicylate levels help determine whether absorption is continuing; ABGs or VBGs and serum electrolytes should always be determined simultaneously. Increased serum CK and urine myoglobin levels suggest rhabdomyolysis.
Treatment of Salicylate Poisoning
Activated charcoal
Urine alkalinization with extra potassium chloride Urine alkalinization with extra potassium chloride
Unless contraindicated (eg, by altered mental status), activated charcoal is given as soon as possible and, if bowel sounds are present, may be repeated every 4 hours until charcoal appears in the stool (1).
After volume and electrolyte abnormalities are corrected, urine alkalinization can be used to increase and maintain urine pH between 7.5 and 8.5 (2). Urine alkalinization 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 hypokalemia may interfere with urine alkalinization, patients are given a solution consisting of 1 L of 5% D/W, 3 50-mEq (50-mmol) ampules of sodium bicarbonate, and 40 mEq (40 mmol) of potassium chloride at 1.5 to 2 times the maintenance IV fluid rate. Serum potassium is monitored. Because fluid overload can result in may interfere with urine alkalinization, patients are given a solution consisting of 1 L of 5% D/W, 3 50-mEq (50-mmol) ampules of sodium bicarbonate, and 40 mEq (40 mmol) of potassium chloride at 1.5 to 2 times the maintenance IV fluid rate. Serum potassium is monitored. Because fluid overload can result inpulmonary edema, patients are monitored for compatible respiratory findings.
Medications that increase urinary bicarbonate (eg, acetazolamide) should be avoided because they worsen Medications that increase urinary bicarbonate (eg, acetazolamide) should be avoided because they worsenmetabolic acidosis and decrease blood pH. Medications 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; urine alkalinization 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.
Treatment references
1. Levy G, Tsuchiya T. Effect of activated charcoal on aspirin absorption in man. Part I. Clin Pharmacol Ther. 1972;13(3):317-322. doi:10.1002/cpt1972133317
2. Proudfoot AT, Krenzelok EP, Vale JA. Position Paper on urine alkalinization. J Toxicol Clin Toxicol. 2004;42(1):1-26. doi:10.1081/clt-120028740
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 or VBGs.
Treat with activated charcoal and alkaline diuresis with extra KCl.
Consider hemodialysis if poisoning is severe.
