Salicylates are used widely for their analgesic and anti-inflammatory properties. They are found in a variety of prescription and over-the-counter analgesics, topical keratolytic products (methyl salicylate), and even Pepto-Bismol (bismuth subsalicylate). Before the introduction of child-resistant containers, aspirin (acetylsalicylic acid) overdose was one of the leading causes of accidental death in children. Two distinct syndromes of intoxication may occur, depending on whether the exposure is acute or chronic.

Salicylates have a variety of toxic effects.

1. Central stimulation of the respiratory center results in hyperventilation, leading to respiratory alkalosis. Secondary consequences from hyperventilation include dehydration and compensatory metabolic acidosis.
2. Intracellular effects include uncoupling of oxidative phosphorylation and interruption of glucose and fatty acid metabolism, which contribute to metabolic acidosis.
3. The mechanism by which cerebral and pulmonary edema occurs is not known but may be related to an alteration in capillary integrity.
4. Salicylates alter platelet function and may also prolong the prothrombin time.
5. Pharmacokinetics. Salicylates are well absorbed from the stomach and small intestine. Large tablet masses and enteric-coated products may dramatically delay absorption (hours to days). The volume of distribution of salicylate is about 0.1-0.3 L/kg, but this can be increased by acidemia, which enhances movement of the drug into cells. Elimination is mostly by hepatic metabolism at therapeutic doses, but renal excretion becomes important with overdose. The elimination half-life is normally 2-4.5 hours but can be as long as 18-36 hours after overdose. Renal elimination is dependent on urine pH.

The average therapeutic single dose of aspirin is 10 mg/kg, and the usual daily therapeutic dose is 40-60 mg/kg/d. Each tablet of aspirin contains 325-650 mg of acetylsalicylic acid. One teaspoon of concentrated oil of wintergreen contains 5 g of methyl salicylate, equivalent to about 7.5 g of aspirin. Each gram of bismuth subsalicylate contains 0.38 g of salicylate, equivalent to approximately 0.5 g of aspirin.

1. Acute ingestion of 150-200 mg/kg of aspirin will produce mild intoxication; severe intoxication is likely after acute ingestion of 300-500 mg/kg. Fatalities have been reported in children with ingestion of 5 mL or less of oil of wintergreen.
2. Chronic intoxication with aspirin may occur with ingestion of more than 100 mg/kg/d for 2 days or more.

Patients may become intoxicated after an acute accidental or suicidal overdose or as a result of chronic repeated overmedication for several days.

1. Acute ingestion. Vomiting occurs shortly after ingestion, followed by hyperpnea, tinnitus, and lethargy. Mixed respiratory alkalemia and metabolic acidosis are apparent on blood gases. With severe intoxication, coma, seizures, hypoglycemia, hyperthermia, and pulmonary edema may occur. Death is caused by CNS failure and cardiovascular collapse.
2. Chronic intoxication. Victims are usually confused elderly persons who are taking salicylates therapeutically. The diagnosis is often overlooked because the presentation is nonspecific; confusion, dehydration, and metabolic acidosis are often attributed to sepsis, pneumonia, or gastroenteritis. However, morbidity and mortality rates are much higher than after an acute overdose. Cerebral and pulmonary edema is more common than with acute intoxication, and severe poisoning occurs at lower salicylate levels.

Is not difficult if there is a history of acute ingestion accompanied by typical signs and symptoms. In the absence of a history of overdose, diagnosis is suggested by the characteristic arterial blood gases, which reveal a mixed respiratory alkalemia and metabolic acidosis.

1. Specific levels. Obtain stat and serial serum salicylate concentrations. Systemic acidemia increases brain salicylate concentrations, worsening toxicity. Monitor serum pH frequently via arterial or venous blood gas determinations.
   1. Acute ingestion. Serum salicylate levels greater than 90-100 mg/dL (900-1,000 mg/L, or 6.6-7.3 mmol/L) are usually associated with severe toxicity. A single level is not sufficient because of the possibility of prolonged or delayed absorption from sustained-release tablets or a tablet mass or bezoar (especially after massive ingestion). Obtain salicylate levels every 3-4 hours (or more frequently during the initial stages of an acute overdose) until the levels have peaked and are clearly declining.
   2. Chronic intoxication. Symptoms correlate poorly with serum levels. Chronic therapeutic concentrations in arthritis patients range from 10 to 30 mg/dL (100 to 300 mg/L). A level greater than 60 mg/dL (600 mg/L, or 4.4 mmol/L) accompanied by acidosis and altered mental status is considered very serious.
2. Other useful laboratory studies include electrolytes (anion gap calculation), glucose, BUN, creatinine, prothrombin time, arterial or venous blood gases, acetaminophen (often confused with salicylates), and chest radiography.

1. Emergency and supportive measures
   1. Maintain an open airway and assist ventilation if necessary. Warning: Ensure adequate ventilation to prevent respiratory acidosis and do not allow controlled mechanical ventilation to interfere with the patient's need for compensatory efforts to maintain the serum pH. Administer supplemental oxygen. Obtain serial blood gases and chest radiographs to observe for pulmonary edema (more common with chronic or severe intoxication).
   2. Treat coma, seizures, pulmonary edema, and hyperthermia if they occur.
   3. Treat metabolic acidosis with IV sodium bicarbonate. Do not allow the serum pH to fall below 7.4.
   4. Replace fluid and electrolyte deficits caused by vomiting and hyperventilation with IV crystalloid solutions. Be cautious with fluid therapy because excessive fluid administration may contribute to pulmonary edema.
   5. Administer supplemental glucose, and treat hypoglycemia if it occurs. Note: Salicylate-poisoned patients may have low brain glucose levels despite normal measured serum glucose. It is prudent to routinely administer glucose-containing IV fluids.
   6. Monitor asymptomatic patients for a minimum of 6 hours (longer if an enteric-coated preparation or a massive overdose has been ingested and there is suspicion of a tablet bezoar). Admit symptomatic patients to an intensive care unit.
2. Specific drugs and antidotes. There is no specific antidote for salicylate intoxication. Sodium bicarbonate is given frequently both to prevent acidemia and to promote salicylate elimination by the kidneys (see Item D.1. below).
3. Decontamination . Decontamination is not necessary for patients with chronic intoxication.
   1. Administer activated charcoal orally if conditions are appropriate (see Table I-37,). Gastric lavage is not necessary after small-to-moderate ingestions if activated charcoal can be given promptly.
   2. Note: With large ingestions of salicylate (eg, 30-60 g), very large doses of activated charcoal (300-600 g) are theoretically necessary to adsorb all the salicylate. In such cases, the charcoal can be given in several 25- to 50-g doses at 3- to 5-hour intervals. whole-bowel irrigation is recommended to help move the pills and charcoal through the intestinal tract.
4. Enhanced elimination
   1. Urinary alkalinization enhances urinary excretion of salicylate, although it is often difficult to achieve in dehydrated or critically ill patients. The goal is to maintain a urine pH of 7.5 or higher. Fluid and bicarbonate administration is potentially dangerous in patients at high risk for pulmonary edema (eg, chronic intoxication).
      1. Initial bolus. Start with an intravenous bolus of sodium bicarbonate, 1-2 mEq/kg. If the patient is volume depleted, also give normal saline 10-20 mL/kg.
      2. Maintenance solution. Add 100 mEq of sodium bicarbonate to 1 L of 5% dextrose in quarter-normal saline (or add 150 mEq of sodium bicarbonate to 1 L of 5% dextrose in water) and infuse intravenously at 150-200 mL/h (2-3 mL/kg/h). Adjust flow rate to achieve a urinary pH of 7.5-8.
      3. Unless renal failure is present, also add potassium, 30-40 mEq, to each liter of IV fluids (potassium depletion inhibits alkalinization). Caution: Watch for hyperkalemia in patients with poor urine output. Do not give boluses of potassium-containing IV fluid.
      4. Alkalemia is not a contraindication to bicarbonate therapy as patients often have a significant base deficit despite the elevated serum pH.
   2. Hemodialysis is very effective in rapidly removing salicylate and correcting acid-base and fluid abnormalities. Indications for urgent hemodialysis are as follows:
      1. Patients with acute ingestion and serum levels higher than 90-100 mg/dL (900-1000 mg/L) with severe acidosis and other manifestations of intoxication.
      2. Patients with chronic intoxication and serum levels higher than 60 mg/dL (600 mg/L) accompanied by acidosis, confusion, or lethargy, especially if they are elderly or debilitated or have renal insufficiency.
      3. Any patient with severe acidemia and other manifestations of intoxication.
   3. Repeat-dose activated charcoal therapy effectively reduces the serum salicylate half-life, but it is not as rapidly effective as dialysis, and frequent stooling may contribute to dehydration and electrolyte disturbances.
   4. Continuous renal replacement therapy (CRRT) was reported to be effective in some cases, and may be an acceptable alternative if hemodialysis is not available.