Acetylsalicylic acid poisoning

Salicylate poisoning may cause vomiting, tinnitus, confusion, hyperthermia, respiratory alkalosis, metabolic acidosis, and multiple organ failure. Diagnosis is based on clinical findings and confirmed by laboratory testing (blood electrolytes, blood gases, blood salicylate levels). Treatment includes activated charcoal, alkaline diuresis, and hemodialysis.

Acute administration of more than 150 mg/kg of the drug may cause severe poisoning. Salicylate tablets may form bezoars, prolonging absorption and poisoning. Chronic poisoning may occur several days after taking high therapeutic doses, is common, in some cases is not diagnosed, and causes a more severe condition compared to acute overdose. Chronic poisoning is more common in elderly patients.

The most concentrated and toxic form of salicylates is wintergreen oil (methyl salicylate, a component of some liniments and solutions used in perfumery), the intake of <5 ml of which can kill a child.

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Pathophysiology of acetylsalicylic acid poisoning

Salicylates disrupt cellular respiration by disrupting the oxidative phosphorylation chain. They stimulate the respiratory center of the medulla oblongata, causing primary respiratory alkalosis, which is often unrecognized in young children. At the same time and independently of respiratory alkalosis, salicylates cause primary metabolic acidosis. Ultimately, when salicylates leave the blood and enter cells, where they affect mitochondria, metabolic acidosis develops - the main disturbance of acid-base balance.

Salicylate poisoning also leads to ketosis, fever, decreased glucose levels in the brain, despite the absence of systemic hypoglycemia. Dehydration develops due to fluid and electrolyte losses (K, Na) with urine, as well as due to increased respiratory fluid losses.

Salicylates are weak acids and pass through cell membranes relatively easily, so they are more toxic at low blood pH. Dehydration, hyperthermia, and continued use increase the toxicity of salicylates due to greater distribution of the drug into tissue. Salicylate excretion increases with increasing urine pH.

Symptoms of acetylsalicylic acid poisoning

In acute overdose, early symptoms include nausea, vomiting, tinnitus, and hyperventilation. Late symptoms include hyperactivity, fever, confusion, and seizures. Over time, rhabdomyolysis, acute renal failure, and respiratory failure may occur. Hyperactivity may rapidly progress to lethargy; hyperventilation (with respiratory alkalosis) progresses to hypoventilation (mixed respiratory and metabolic acidosis) and respiratory failure.

In chronic overdose, symptoms are nonspecific and vary widely. They may include mild confusion, changes in mental status, fever, hypoxia, noncardiogenic pulmonary edema, dehydration, lactic acidosis, and arterial hypotension.

Diagnosis of acetylsalicylic acid poisoning

Salicylate poisoning should be suspected in patients with a history of a single acute overdose or multiple therapeutic doses (especially in the presence of fever and dehydration), in patients with unexplained metabolic acidosis, and in elderly patients with unexplained altered consciousness and fever. If poisoning is suspected, determination of plasma salicylate concentrations (collected at least several hours after ingestion), urine pH, blood gases, electrolytes, glucose, creatinine, and urea is necessary.

If rhabdomyolysis is suspected, it is also necessary to determine the CPK blood level and the concentration of myoglobin in the urine.

Severe salicylate poisoning is suspected when plasma concentrations significantly exceed the therapeutic range (10-20 mg/dL), especially within 6 hours of poisoning when absorption of the drug is virtually complete, and in the presence of acidemia and blood gas changes characteristic of salicylate poisoning. Typically, in the first hours after ingestion, blood gases indicate respiratory alkalosis, later - compensated metabolic acidosis or mixed metabolic acidosis/respiratory alkalosis. Ultimately, usually as salicylate concentrations decrease, the underlying acid-base disturbance becomes either subcompensated or decompensated metabolic acidosis. As respiratory failure develops, blood gases indicate mixed metabolic and respiratory acidosis, and chest radiography shows diffuse pulmonary infiltrates. Plasma glucose concentrations may be normal, elevated, or low. Repeated measurements of salicylate concentrations may establish the fact of continued absorption; blood gas composition should be determined simultaneously with this study. Increased serum CPK and urine myoglobin indicate rhabdomyolysis.

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Treatment of acetylsalicylic acid poisoning

Activated charcoal should be given as soon as possible and, if peristalsis is maintained, repeated every 4 hours until charcoal appears in the stool.

After correction of electrolyte disturbances and rehydration, alkaline diuresis can be used to increase urine pH (ideally >8). Alkaline diuresis is indicated in patients with any symptoms of poisoning and should not be delayed until salicylate concentrations are determined. The method is safe and exponentially increases salicylate excretion. Since hypokalemia may interfere with alkaline diuresis, patients are given an infusion solution consisting of 1 L of 5% glucose or 0.9% sodium chloride solution, 3 ampoules of NaHCO 50 mEq, 40 mEq KCl, at a rate exceeding the maintenance rate of intravenous infusions by 1.5-2 times. Plasma K ^{+ concentrations are monitored.}

Drugs that increase urinary HCO concentrations (acetazolamide) should be avoided because they worsen metabolic acidosis and decrease blood pH. Drugs that depress the respiratory center should be avoided because they can cause hypoventilation, respiratory alkalosis, and decreased blood pH.

Hyperthermia can be treated with physical means such as external cooling. Benzodiazepines are used for seizures. In patients with rhabdomyolysis, alkaline diuresis can prevent renal failure.

To accelerate the elimination of salicylates in patients with severe neurological impairment, renal or respiratory failure and acidemia despite other measures, as well as with very high plasma salicylate concentrations [>100 mg/dL (>7.25 mmol/L) in acute overdose or >60 mg/dL (>4.35 mmol/L) in chronic overdose], hemodialysis may be required.