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Salicylate Poisoning (Aspirin), Pediatric


Basics


Description


  • May occur with acute or chronic overdosage of the following:
    • Acetylsalicylic acid (aspirin)
    • Methyl salicylate (oil of wintergreen)
    • Bismuth subsalicylate (Pepto Bismol)
    • Salicylic acid (a keratolytic)
    • Other salicylate-containing drugs
  • The potentially toxic acute oral dose of acetylsalicylic acid is >150 mg/kg.

Epidemiology


  • Analgesics are the most common drugs implicated in human exposures reported to U.S. poison control centers.
  • Salicylate preparations constitute ’ ˆ Ό9% of all analgesic poisoning exposures reported to poison control centers.

Pathophysiology


  • Ingested drug is absorbed in stomach and proximal intestine.
  • With therapeutic aspirin dosing, serum levels peak in 1 " “2 hours (standard preparations) or 4 " “6 hours (enteric coated).
  • After oral overdose, absorption may be prolonged and erratic.
  • Acetylsalicylate ingestion may produce gastritis and may trigger centrally mediated vomiting.
  • After overdose, the elimination half-life of salicylate becomes prolonged.
  • As blood pH falls, the proportion of nonionized salicylate rises, and more salicylate shifts into tissues, including brain.
  • Toxic salicylate exposures uncouple mitochondrial oxidative phosphorylation and increase oxygen consumption.
  • Direct stimulation of the medullary respiratory center leads to hyperventilation and respiratory alkalosis.
  • Multiple metabolic derangements produce a wide anion gap metabolic acidosis.
  • Dehydration and electrolyte shifts are common.
  • Low cerebral glucose concentrations may exist despite normal serum glucose concentrations.
  • Pulmonary and/or cerebral edema may occur.

Commonly Associated Conditions


  • Aspirin is often marketed in combination with other pharmaceuticals, which may complicate drug overdose situations.
  • Adolescents frequently overdose on more than 1 drug preparation.
  • Therapeutic use of acetylsalicylic acid among children with influenza has been associated with the occurrence of Reye syndrome.

Diagnosis


History


  • Aspirin poisoning mimics many illnesses, and chronic overdosage often results in delayed diagnosis.
  • Enteric coating may lead to significantly delayed drug absorption.
  • Timing of ingestion allows for proper consideration of the risks versus benefits of gastrointestinal decontamination.
  • Tinnitus frequently associated with serum salicylate levels >25 mg/dL

Physical Exam


  • Hyperpnea indicates primary central hyperventilation and/or compensation for metabolic acidosis.
  • Hyperpyrexia: Presence of "fever "  may confuse salicylism with infection.
  • Hypoxia: Pulmonary edema complicates therapy of aspirin overdose.
  • Hypotension indicates severe dehydration, likely complicated by metabolic acidosis and salicylate-mediated myocardial inefficiency.
  • Encephalopathy: CNS depression or seizures represent grave toxicity.

Diagnostic Tests & Interpretation


Lab
  • Serum electrolytes: A wide anion gap metabolic acidosis is common, and hypoglycemia or hyperglycemia may occur.
  • Arterial blood gas: may show mixed respiratory alkalosis/metabolic acidosis
  • Salicylate level: Serum salicylate levels >60 " “100 mg/dL (acute) or 30 " “40 mg/dL (chronic) portend serious toxicity.
  • Urine pH: allows monitoring of adequacy of urinary alkalinization
  • Acetaminophen level: Acetaminophen may be a coingestant.
  • Ferric chloride test: A few drops of 10% ferric chloride will turn brown or purple in 1 mL of urine that contains salicylate.

Alert
  • Respiratory acidosis suggests central nervous system depression and is an ominous sign.
  • Salicylate levels after chronic or acute-on-chronic overdose correlate poorly to clinical condition.
  • Serial salicylate levels may be necessary to rule out ongoing drug absorption.

Differential Diagnosis


  • Gastroenteritis
  • Pneumonia
  • Metabolic disease
  • Ketoacidosis
  • Sepsis
  • Meningitis/encephalitis

Treatment


General Measures


  • Fluids/alkalinization
    • Intravascular volume should be repleted with intermittent boluses of 10 " “20 mL/kg of isotonic crystalloid.
    • Altered mentation may imply CNS hypoglycemia and should be treated with dextrose.
    • Acidemia should be treated with sodium bicarbonate to limit salicylate distribution to the brain. Serum pH of 7.5 is reasonable goal.
    • With significant poisoning, an IV infusion of 5% dextrose with 100 " “150 mEq/L of sodium bicarbonate and 20 " “40 mEq/L of potassium chloride should be initiated at 1.5 " “2 times maintenance requirements. Titrate fluid volume to produce urine output of 2 " “3 mL/kg/h. Titrate alkalinization to produce urine pH between 7.5 and 8, which greatly increases the urinary elimination of salicylate via "ion-trapping "  effect.
  • Hemodialysis indications
    • Acute serum salicylate level >100 mg/dL
    • Chronic serum salicylate level >60 mg/dL
    • Severe acidosis or severe electrolyte disturbance
    • Renal failure
    • Pulmonary edema
    • Persistent neurologic dysfunction
    • Progressive clinical deterioration

Alert
  • Hypokalemia may interfere with the ability to achieve urinary alkalinization.
  • Sedating a salicylate-poisoned patient may lead to respiratory depression and clinical deterioration.
  • Endotracheal intubation is dangerous and, if performed, must be accompanied by sodium bicarbonate IV bolus and hyperventilation to prevent worsening acidemia and salicylate distribution to the brain.
  • Hemodialysis equipment must be carefully primed to prevent worsening hypovolemia and cardiovascular collapse.
  • If hemodialysis is performed, adjust dialysate to maintain alkalemia.
  • Pulmonary edema and/or cerebral edema may complicate fluid management.

Inpatient Considerations


Initial Stabilization
GI decontamination ‚  
  • Activated charcoal 1 g/kg (maximum 75 g) may be administered if aspirin is judged to be present in the stomach or proximal intestine.
  • Many authorities suggest a 2nd charcoal dose 2 " “4 hours after the 1st or if salicylate levels continue to rise.
  • Whole-bowel irrigation may reduce drug absorption after large overdoses.

Ongoing Care


Follow-up Recommendations


  • Drug administration education should be offered to victims of chronic overdose.
  • Mental health services should be provided to victims of intentional overdose.

Prognosis


  • Chronic therapeutic misuse often leads to delayed diagnosis and has the most serious prognosis.
  • Single acute ingestion of >300 mg/kg acetylsalicylic acid should be considered life threatening.

Complications


  • Nausea and vomiting
  • Dehydration
  • Metabolic acidosis
  • Electrolyte abnormalities
  • Disorientation, coma, seizures
  • Noncardiogenic pulmonary edema
  • Renal failure
  • Cerebral edema and death

Additional Reading


  • Chyka ‚  PA, Erdman ‚  AR, Christianson ‚  G, et al. Salicylate poisoning: an evidence-based consensus guideline for out-of-hospital management. Clin Toxicol (Phila).  2007;45(2):95 " “131. ‚  [View Abstract]
  • Glatstein ‚  M, Garcia-Bournissen ‚  F, Scolnik ‚  D, et al. Sudden-onset tachypnea and confusion in a previously healthy teenager. Ther Drug Monit.  2010;32(6):700 " “703. ‚  [View Abstract]
  • Pearlman ‚  BL, Gambhir ‚  R. Salicylate intoxication: a clinical review. Postgrad Med.  2009;121(4):162 " “168. ‚  [View Abstract]
  • Stolbach ‚  AI, Hoffman ‚  RS, Nelson ‚  LS. Mechanical ventilation was associated with acidemia in a case series of salicylate-poisoned patients. Acad Emerg Med.  2008;15(9):866 " “869. ‚  [View Abstract]

Codes


ICD09


  • 965.1 Poisoning by salicylates
  • 276.2 Acidosis

ICD10


  • T39.014A Poisoning by aspirin, undetermined, initial encounter
  • E87.2 Acidosis
  • T39.011A Poisoning by aspirin, accidental (unintentional), init
  • T39.012A Poisoning by aspirin, intentional self-harm, init encntr

SNOMED


  • 7248001 Poisoning by salicylate (disorder)
  • 35528000 Metabolic acidosis due to salicylate (disorder)
  • 216471009 Accidental poisoning by salicylates (disorder)
  • 290148002 Intentional salicylic acid salt poisoning (disorder)

FAQ


  • Q: What amount of the candy-scented oil of wintergreen is toxic to a toddler?
  • A: Oil of wintergreen may contain as much as 98% methyl salicylate. 1 mL of methyl salicylate is the equivalent of 1,400 mg of aspirin. Therefore, 1 teaspoon of oil of wintergreen represents a very serious "aspirin "  overdose.
  • Q: Is there a prognostic nomogram for aspirin poisoning similar to that used for acetaminophen overdose?
  • A: The Done nomogram is applicable only to ingestion of non " “enteric-coated aspirin by children with normal mentation and normal blood pH, and the validity of its prognostication is suspect. Its use is not widely recommended.
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