Strange and Schafermeyer's Pediatric Emergency Medicine, Fourth Edition (Strange, Pediatric Emergency Medicine) 4th Ed.




Marco L. A.  Sivilotti


• Salicylate poisoning is difficult to treat, and consideration should be given to consultation with a medical toxicologist.

• Children with aspirin toxicity can rapidly develop metabolic acidosis without an apparent respiratory alkalosis.

• Initial treatment decisions should be predicated on the presence of symptoms, hearing distortion, mental status, tachypnea, and blood gas measurements rather than waiting for a salicylate concentration.

• Treatment of mild-to-moderate aspirin poisoning consists of slowing ongoing absorption, correcting volume and electrolyte deficits, alkalinizing the urine and frequent clinical and laboratory reassessments.

• Severe aspirin poisoning requires immediate fluid resuscitation, titrated bicarbonate infusion, and emergency hemodialysis.

Aspirin (acetylsalicylic acid, ASA), acetaminophen and ibuprofen are the principal nonprescription analgesic, antipyretic medications. Aspirin is the least popular, and the association with Reye syndrome decades ago led to a proscription on pediatric use for fever. The result is a much lower prevalence of nonintentional and intentional salicylate poisoning in children. This is fortunate because aspirin has much greater toxicity. The case fatality rate for aspirin poisoning is an order of magnitude greater than that of acetaminophen. Salicylate toxicity is a consequence of interference with energy production, making it a general cellular toxin that is a very difficult poisoning to treat. Management is based upon meticulous attention to fluid, electrolyte and acid–base disturbances, promoting excretion over absorption, and consideration of extracorporeal removal.


At therapeutic doses, aspirin is rapidly absorbed primarily from the small intestine. When many tablets are ingested, absorption is slowed as a consequence of delayed gastric emptying, slow tablet dissolution, mucosal adherence, and occasionally the development of concretions. The result is delayed absorption by many hours, and even longer than a day, particularly if enteric-coated aspirin has been taken in overdose.1 This delay extends the window of opportunity for gastrointestinal decontamination.

Aspirin is rapidly hydrolyzed to the active metabolite, salicylate. Metabolism and excretion of salicylate becomes saturated (zero order) at higher doses. As a result, a small increase in dose or drug absorbed will result in a large increase in serum salicylate concentration. Renal excretion becomes the dominant route of elimination when hepatic metabolism is saturated in overdose. Acidic urine increases passive reabsorption of the uncharged salicylic acid in the distal tubule. The volume of distribution of salicylate is also highly variable and dependent on dose ingested. It is, therefore, impossible to predict the trajectory of serum salicylate concentrations, and frequent measurements are necessary following overdose until the drug is undetectable.

Ingestions of <150 mg/kg are generally nontoxic.2 With ingestions of 150 to 300 mg/kg mild-to-moderate toxicity occurs, and overdoses of >300 mg/kg can be lethal. Preparations other than acetylsalicylic acid can cause measurable serum salicylate concentrations (Table 114-1). Oil of wintergreen contains nearly pure methyl salicylate (equivalent to 7000 mg salicylate per 5 mL) and can be lethal in small amounts.3

TABLE 114-1

Products Measured as Salicylates



It is best to classify salicylism in terms of mild, moderate, and severe based on clinical assessment and blood gas measurements rather than relying on the serum salicylate concentration to establish the severity of poisoning (Table 114-2). Young children have a more rapid onset of toxicity and exhibit more severe signs than adults, primarily a consequence of their decreased buffering capacity, more rapid onset of metabolic acidosis and thus, more rapid distribution into organs such as the brain. At the upper end of the therapeutic range, patients may complain of tinnitus or, more often, distorted hearing. Direct stimulation of respiratory centers causes tachypnea, which in turn results in respiratory alkalosis, the hallmark of mild poisoning. Bicarbonate excretion in the urine leads to sodium and potassium losses. At moderate toxicity, uncoupling of oxidative phosphorylation results in increased glucose, oxygen, and lipid consumption, with accumulation of lactic acid, amino acids and keto acids, as well as paradoxical aciduria and eventually hyperthermia. An osmotic diuresis results in further fluid and electrolyte losses. Thus, the characteristic anion-gap metabolic acidosis is a result of hypovolemia, impaired tissue perfusion, lactate accumulation, circulating salicylate, and other derangements of metabolism. Fluid losses from vomiting, tachypnea, and diaphoresis can be especially severe in young children. They have a more rapid onset of metabolic acidosis than adults, and the early respiratory alkalosis may not be identified.

TABLE 114-2

Severity of Salicylate Poisoning


An acidotic environment increases the nonionized fraction of salicylic acid in circulation, and facilitates shift of drug into the brain where it can cause agitation, delirium, seizures, and coma. These CNS signs, as well as respiratory acidosis, severe metabolic acidosis and hyperthermia, are manifestations of severe toxicity and impending cardiorespiratory collapse.

Patients can develop noncardiogenic pulmonary edema, most likely because of a toxic effect of salicylates on pulmonary endothelium. Risk factors for this include CNS toxicity, metabolic acidosis, and chronic salicylate ingestion. Rhabdomyolysis can occur and can cause acute renal failure. Commonly observed electrolyte abnormalities include hypo- or hypernatremia, hypokalemia, and hypocalcemia. In children, hypoglycemia is more common than hyperglycemia. Brain glucose concentrations can be low, and symptoms of hypoglycemia may develop despite a normal serum glucose concentration.


Initial laboratory studies should include a complete blood count, serum electrolytes, creatinine, glucose, and arterial or venous blood gases. Serum salicylate concentrations should be drawn upon presentation, and repeated every 2 hours to ensure that the level is decreasing. Clinical findings including pH are more predictive of toxicity than the serum salicylate concentration. Clinical decisions should not be delayed pending laboratory confirmation in patients who are symptomatic because of the risk for clinical deterioration. The reported concentration must always be interpreted in the context of the serum pH and clinical picture. A pitfall in management is assuming subsequent concentrations will be lower. Because of the known delayed and erratic absorption of this drug when taken in overdose, it is incumbent to demonstrate a near-zero salicylate concentration. Patients have been deemed “medically cleared” because of a therapeutic serum concentration several hours after ingestion, only to develop severe toxicity many hours later. When any salicylate is present, serum concentrations should be measured every 2 hours until they have clearly peaked, and then every 4 hours until undetectable.


Salicylate poisoning is difficult to treat, and consideration should be given to consultation with a medical toxicologist. The goals in the management of the salicylate-poisoned patient are fluid resuscitation, correction of metabolic disturbances, decreasing further absorption of drug and enhancement of elimination. These goals are highly time-sensitive. Because there is no antidote, the only effective treatment is to reduce the ingress of salicylate into the central nervous system.

For moderately to severely poisoned patients, intravascular volume must be restored by boluses of normal saline at doses of 10 to 20 mL/kg until adequate perfusion is assured. Intravenous bicarbonate should be administered by bolus to any patient who is acidemic using intermittent boluses of 0.5 to 1 mEq/kg every 10 minutes. Correcting acidemia decreases the entry of salicylic acid into the brain and other tissues. Dextrose, typically 2 mL/kg of D25W in young children and 1 mL/kg of D50W in adolescents, should also be administered intravenously to any patient with altered mental status or seizures unless the serum glucose exceeds 140 mg/dL.

Patients with severe toxicity may need to be intubated and mechanically ventilated. These patients will require very high minute ventilation, arterial Pco2 values below 20 mm Hg to prevent further falls in blood pH and catastrophic shift of drug into the brain.4 It is essential, for the same reason, to avoid simply sedating and restraining a patient with seizures or agitation when the cause is severe salicylate poisoning.

Severely poisoned patients need emergency hemodialysis to be arranged, usually before confirmatory concentrations are reported by the laboratory. Hemodialysis removes salicylate three to five times faster than systemic alkalinization. Indications for hemodialysis include pulmonary edema, coma, seizure, severe metabolic acidosis, and renal failure. The salicylate concentration per se is not useful as a sole criterion for dialysis due to differences between serum and tissue (brain) concentrations, delays in measurement, and the need to anticipate the need for dialysis before patients become moribund. Continuous renal replacement therapy is insufficient to remove salicylate rapidly.

All symptomatic patients and those likely to have ingested >150 mg/kg should receive gastrointestinal decontamination. While experts may disagree on the best modality,5 activated charcoal is advisable, even if many hours have passed since ingestion. Large ingestions of enteric-coated preparations may benefit from whole bowel irrigation.6 Salicylate elimination is enhanced by urinary alkalinization,7 which is indicated in any symptomatic patient (any patient with at least mild toxicity and acid–base disturbances). Serum alkalemia by itself is not a contraindication to administration of sodium bicarbonate to alkalinize the urine and to compensate for ongoing renal losses. Increasing the urine pH decreases passive reabsorption of salicylic acid in the distal tubule. The goal of alkalinization is to increase the urine pH to 7 and ensure a urine output of 1 to 2 mL/kg/h. This is accomplished by infusing sodium bicarbonate after intravascular volume resuscitation. The first step is to place a urinary catheter and measure the volume and urine pH every hour. For the infusion, 132 to 150 meq sodium bicarbonate is typically added to each liter of a D5W solution and started at a rate of twice maintenance. If hypernatremia is present, a more hypotonic solution is recommended. Potassium should also be present in the infusion at 40 mM initially.

Hypokalemia is common in salicylism, and total body potassium depletion is always present in symptomatic patients. Potassium deficits will impair attempts to alkalinize the urine since potassium is exchanged for hydrogen in the tubular fluid when serum potassium is low resulting in a paradoxical aciduria. Inadequate fluid resuscitation will also render urine alkalinization impossible. Adjustments in infusion rate, potassium supplementation, and additional boluses of sodium bicarbonate are then made based on serial (every 2–4 hours) blood gas, electrolyte and salicylate concentrations, as well as the hourly urine output and pH. Safely alkalinizing a patient requires careful attention to detail, and frequent reassessments, to avoid the complications of volume overload, excessive alkalemia (pH >7.55), hypokalemia and hypernatremia and yet optimizing elimination of salicylate commensurate with the severity of the poisoning. Pulmonary edema, cerebral edema, and oliguric renal failure all render urinary alkalinization difficult and signal the need for hemodialysis, but theoretical fears of precipitating pulmonary edema should not preclude appropriate fluid therapy.


Patients manifesting toxicity should be admitted to hospital. Those without clinical effects (particularly the absence of tachypnea) and a serum salicylate concentration less than 10 mg/dL at least 6 hours after overdose may be discharged from the emergency department, unless enteric-coated aspirin has been ingested. Repeat measurements of salicylate concentrations every 2 hours are warranted until the peak has been clearly defined. All patients with a purposeful ingestion require a mental health evaluation.


1. Rivera W, Kleinschmidt KC, Velez LI, Shepherd G, Keyes DC. Delayed salicylate toxicity at 35 hours without early manifestations following a single salicylate ingestion. Ann Pharmacother. 2004;38: 1186–1188.

2. Notarianni L. A reassessment of the treatment of salicylate poisoning. Drug Saf. 1992;7:292–303.

3. Matteucci MJ. One pill can kill: Assessing the potential for fatal poisonings in children. Pediatr Ann. 2005;34:964–968.

4. Stolbach AI, Hoffman RS, Nelson LS. Mechanical ventilation associated with acidemia in a case series of salicylate-poisoned patients. Acad Emerg Med. 2008;15:866–869.

5. Juurlink DN, McGuigan MA. Gastrointestinal decontamination for enteric-coated aspirin overdose: what to do depends on who you ask. J Toxicol Clin Toxicol. 2000;38:465–470.

6. American Academy of Clinical Toxicology and European Association of Poisons Centres and Clinical Toxicologists. Position paper: whole bowel irrigation. J Toxicol Clin Toxicol. 2004;42:843–854.

7. Prescott LF, Balali-Mood M, Critchley JAJH. Diuresis or urinary alkalinization for salicylate poisoning?. Br Med J. 1982;285:1383–1386.