DESCRIPTION

• Salicylate poisoning is a medical emergency, with the potential for severe metabolic derangements, resulting from the accidental or intentional exposure via ingestion or topical application.
• May be acute or chronic (≤8 hours vs >8 hours)
• The degree of toxicity generally increases with the amount ingested.
  • >150 mg/kg of acetylsalicylic acid is potentially toxic.
  • >250 mg/kg is likely to cause moderate toxicity.
  • >500 mg/kg causes severe and possibly fatal toxicity.
• Salicylates are available in several forms:
  • Aspirin (acetylsalicylic acid) as chewable, regular, and enteric coated tablets
  • Bismuth subsalicylate (Pepto-Bismol^®) as chewable tablets or liquid; used as an over the counter for a variety of gastrointestinal (GI) symptoms.
  • Oil of wintergreen (methyl salicylate) is a common ingredient used in herbal medications, ointments for muscle pain, and as a flavoring agent.
  • Topical keratolytics (salicylic acid [SA]) are used for wart removal and acne.
  • Other pain relievers such as magnesium salicylate (Doan’s^®) and salsalate (Salflex^® and Disalcid^®)

EPIDEMIOLOGY

• In 1951, 3 years after St. Joseph^® aspirin became available for children, preschool-aged children accounted for 80% of aspirin deaths. The safety cap was later developed in 1958 to prevent pediatric aspirin poisonings.
• In 1960, aspirin manufacturers agreed to standardize the amount of acetylsalicylic acid in each tablet, and by the mid-1970s, aspirin mortality rates declined significantly due to The Poison Prevention Packaging Act.
• Today, there are approximately 20,000 pediatric salicylate exposures per year reported to American Association of Poison Control Centers Toxic Exposure Surveillance System.
• 28% of hospital admissions due to salicylate toxicity are in patients <20 years of age.
• Ingestion in children <5 years old is mostly accidental, whereas in children 13 to 19 years of age, ingestion is usually intentional.
• Increased use of acetaminophen and ibuprofen in children has contributed to a decline in the incidence of salicylate toxicity.

RISK FACTORS

• Young children rarely become toxic from accidental oral ingestion of aspirin but are at great risk for toxicity from highly concentrated forms of salicylates such as oil of wintergreen.
• Adolescents with mental health disorders are at risk for intentional ingestions of salicylates.
• Because salicylates are ingredients in several types of products, salicylate toxicity should be considered in unknown or multiple drug ingestions.

GENERAL PREVENTION

Over the past 40 years, several factors have led to the decline in pediatric exposures:

• Decreased use of aspirin in the pediatric population since the recognition of its association with Reye syndrome
• Child-resistant packaging
• Decreasing the dose of flavored chewable tablets to 81 mg
• Limiting the number of chewable pills per bottle to 36

PATHOPHYSIOLOGY

• Metabolism
  • At therapeutic dosages:
    • After ingestion, acetylsalicylic acid is converted to SA, its active state, and is absorbed from the jejunum, and to a lesser extent, the stomach.
    • Liquids are absorbed rapidly. For pills, serum levels peak in 1 to 2 hours for standard preparations or 4 to 6 hours for enteric coated tablets.
    • SA is metabolized by the liver and eliminated in 2 to 3 hours.
  • At toxic dosages:
    • Absorption is prolonged.
    • Tablets can form bezoars which can have erratic absorption, and the elimination half-life is prolonged.
• Acid–base effects are complex:
  • Stimulation of the respiratory center in the brain leads to hyperventilation, respiratory alkalosis, increased renal elimination of HCO₃, and increased insensible fluid loss.
  • There is an alteration of lipid and amino acid metabolism that enhances metabolic acidosis.
  • SA acts to uncouple oxidative phosphorylation, leading to accumulation of lactic acid and pyruvic acid, causing a primary elevated anion gap metabolic acidosis.
• Effects on glucose metabolism:
  • Uncoupling of oxidative phosphorylation in the mitochondria leads to increased oxygen utilization and glucose demand, increased glycogenolysis, and increased production of heat. Potential downstream effects include a metabolic acidosis, fever, fluid loss, and hypoglycemia and can result in rhabdomyolysis.
  • Inhibition of Krebs cycle enzymes such as tricarboxylic acid leads to a decrease in glucose availability and an increase in organic acids.
  • Even at normal plasma glucose levels, salicylate toxicity causes decreased brain glucose due to uncoupling of oxidative phosphorylation and compensatory stimulation of brain glycolysis. Therefore, symptoms of central nervous system (CNS) hypoglycemia (e.g., altered mental status) may occur even when blood glucose levels are within the normal range.
• GI, fluid, and electrolyte effects:
  • Nausea and vomiting are common as SA ingestion is a mucosal irritant and may cause a gastritis.
  • In addition, stimulation of the chemoreceptor trigger zone in the medulla causes nausea and vomiting.
  • Fluid and electrolyte losses are common, leading to dehydration, sodium and potassium depletion, and a loss of buffer capacity.
• Hematologic effects:
  • Inhibition of cyclooxygenase results in decreased synthesis of prostaglandins, prostacyclin, and thromboxanes.
  • Salicylates cause a dose-dependent inhibition of the activation of factors 2, 7, 9, and 10.
• Respiratory effects:
  • Salicylates cause direct and indirect stimulation of respiration.
  • Salicylate poisoning may rarely cause noncardiogenic pulmonary edema (NCPE) and acute lung injury in pediatric patients (mechanism is not well understood).

COMMONLY ASSOCIATED CONDITIONS

• Aspirin use in the setting of influenza has been associated with Reye syndrome in children.
• Multidrug overdose should be considered in the accidental or intentional ingestion in an adolescent patient.