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• Salicylate toxicity

  Manifested by a group of symptoms due to overdose of salicylate containing compounds
• Sources of salicylates

  • Aspirin
  • Methyl salicylate (Oil of Wintergreen)
  • Bismuth subsalicylate (Pepto-Bismol)
• Oil of Wintergreen is very concentrated - 5mL contains equivalent of 7.5g of aspirin
• Salicylates can be compounded into formulations with other classes of medications including narcotics, antihistamines, and anticholinergic medications
• Salicylates are widely available over the counter medications
• Uses of salicylates

  • Analgesic properties
  • Antipyretic properties
  • Anti-inflammatory properties
  • Anti-thrombotic properties
• Therapeutic range of salicylate concentration for anti-inflammatory effects

  15 and 30 mg/dL
• Toxicokinetics of salicylates

  • Rapid absorption
  • Highly protein bound (although in overdose this is saturated and free salicylate levels increase)
  • Volume of distribution 0.1-0.3 L/kg
  • Absorption can be delayed with enteric coated compounds but also erratic if large doses or consumed due to the formation of a bezoar
  • Hepatic metabolism with first order kinetics except in overdose it changes to zero order as the metabolic pathway becomes saturated
  • Renal excretion
• Salicylate will move into the extravascular spaces in acidaemia (e.g. the CNS)
• Alkalinizing the urine

  Promotes the salicylate to its ionised state and therefore cannot be reabsorbed across the renal tubular epithelium
• Mechanism of salicylate toxicity (pathophysiology)

  • Direct stimulation of the cerebral medulla causes hyperventilation and respiratory alkalosis
  • Uncoupling of oxidative phosphorylation in the mitochondria causes an increase in anaerobic metabolism and lactate levels
  • Metabolic acidosis from lactic acid and salicylate metabolites
  • Hyperventilation worsens in an attempt to compensate for the metabolic acidosis
  • Eventually the patient fatigues and is no longer able to compensate via hyperventilation, and metabolic acidosis prevails
• Stages of acid-base disturbances in salicylate toxicity

  • Stage I: blood pH >7.4, urine pH >6.0 respiratory alkalosis, increased urinary excretion of bicarbonate
  • Stage II: blood pH >7.4, urine pH <6.0 - metabolic acidosis with compensating respiratory alkalosis, urinary hydrogen excretion, intracellular potassium depletion
• Other effects of salicylate toxicity

  • Nausea and vomiting
  • Metabolic alkalosis (contraction alkalosis)
  • Hyperthermia
  • Altered mental status
  • Neuroglycopenia even at normal plasma glucose levels
  • Pulmonary edema
  • Fetal effects in pregnancy including increased morbidity/mortality, displacement of bilirubin, and premature closure of ductus arteriosus
• Severity of salicylate toxicity

  • Mild toxicity: acute ingestion of <150mg/kg, salicylate levels 40 to 80 mg/dL
  • Moderate toxicity: ingestion of 150-300mg/kg, salicylate levels 80 to 100 mg/dL
  • Severe toxicity: acute ingestion of >300mg/kg, salicylate levels >100 mg/dL
• Symptoms of salicylate toxicity by severity

  • Mild toxicity: Tinnitus, hearing loss, dizziness, nausea and vomiting

  Moderate toxicity: Tachypnea, hyperpyrexia, diaphoresis, ataxia, anxiety, headache

  Severe toxicity: Altered mental status, seizures, coma, cerebral edema, acute lung injury, nausea and vomiting, acute renal failure, cardiac arrhythmias, shock
• Symptoms of chronic salicylate toxicity

  • Agitation, paranoia, memory deficits, confusion, stupor, hyperventilation
• Diagnosis of salicylate toxicity

  • Salicylate level should be checked, serial levels recommended
  • Physical examination for signs and symptoms
  • Monitoring of biochemical parameters like electrolytes, liver/kidney function, urinalysis, CBC
  • Arterial blood gas to detect respiratory alkalosis early on
  • Anion-gap metabolic acidosis detected later in course
• Initial treatment for salicylate toxicity

  • Stabilize airway, breathing, circulation
  • Intravenous fluids with dextrose
  • Serum alkalization with sodium bicarbonate
  • Cooling for hyperthermia
  • Glucose administration for hypoglycemia
  • Diazepam for seizures
• Decontamination for salicylate toxicity

  • Activated charcoal
  • Gastric lavage (for large ingestions only)
  • Whole bowel irrigation
• Enhancement of elimination for salicylate toxicity

  • Alkalinizing urine with IV sodium bicarbonate
  • Hemodialysis (for severe toxicity)