REBEL Core Cast 120.0 – Salicylate Toxicity

REBEL Core Cast 120.0 – Salicylate Toxicity

Definition and Physiology

• The therapeutic range of salicylate concentration is between 15-30 mg/dL, with concentrations exceeding this range often associated with sign and symptoms of toxicity.
• Salicylic acid is a weak acid – at a physiologic pH, it exists as a charged (ionized) state. Under acidic conditions (dropping pH), it becomes non-ionized which means it can penetrate bodily tissues and cause end-organ damage.
• At supratherapeutic concentrations, salicylic acid does several things:
  • Stimulates respiratory drive in the medulla
  • Uncouples oxidative phosphorylation
  • Disrupts normal glucose metabolism
• Salicylate acid is renally excreted.

Clinical Manifestations

• The typical course of acute ingestions begin with non-specific GI symptoms due to local gastric irritation (nausea/vomiting) and tinnitus (cochlear COX inhibition).
• Early tachypnea and hyperpnea occur as a result of direct stimulation of medullary respiratory neurons and may lead to a respiratory alkalosis.
• The development of an anion gap metabolic acidosis soon follows.
• Hyperthermia can occur secondary to uncoupling of oxidative phosphorylation, and is often considered a pre-terminal sign.
• As the acidosis worsens, grave clinical consequences ensue: cerebral edema, coagulopathy, and ARDS.

Management

• Activated charcoal should be given to the patient who is awake, alert, and can otherwise tolerate it. Charcoal should be considered especially for aspirin ingestions, as aspirin adsorbs well to charcoal and has a propensity to form bezoars with particularly large overdoses. (Levy 1972)
• Since salicylic acid is a weak acid, in order to prevent tissue penetration and enhance urinary excretion, serum and urinary alkalinization should be performed with administration of sodium bicarbonate. (Temple 1981)
  • Start with a 1-2 mEq/kg bolus followed by an infusion at 1.5-2x maintenance
  • Goal urine pH should be maintained at 7.5-8.0
  • Resultant hypokalemia (due to induced alkalosis) must be corrected in order to achieve maximum alkalinization.
• Depressed or altered mental status should be empirically treated with dextrose, as salicylism has been demonstrated to cause “neuroglycopenia” (central hypoglycemia) even despite a normal serum glucose concentration. (Thurston 1970)
• If significant renal dysfunction is present or unable to appropriately alkalinize, hemodialysis should be considered. Consult nephrology early to ensure prompt HD.
  • Hard indications include: altered mental status, volume overload, persistent acidemia.
• Avoid intubation if possible as there is a high degree of morbidity and mortality with mechanical ventilation (Stolbach 2008). Keeping in mind that acidosis worsens systemic toxicity, any degree of apnea during the peri-intubation period or hypoventilation on the ventilator will exacerbate end organ damage.
  • If intubation is necessary, consider awake intubation or ketamine facilitated intubation to minimize/eliminate apneic time.
  • Matching pre-intubation minute ventilation is critical to prevent worsening acidosis (high tidal volumes and respiratory rates).

References

1. Levy G, Tsuchiya T. Effect of activated charcoal on aspirin absorption in man. Part I. Clin Pharmacol Ther. 1972 May-Jun;13(3):317-22. doi: 10.1002/cpt1972133317. PMID: 5026372.
2. Temple AR. Acute and chronic effects of aspirin toxicity and their treatment. Arch Intern Med. 1981 Feb 23;141(3 Spec No):364-9. doi: 10.1001/archinte.141.3.364. PMID: 7469627.
3. Thurston JH, Pollock PG, Warren SK, Jones EM. Reduced brain glucose with normal plasma glucose in salicylate poisoning. J Clin Invest. 1970 Nov;49(11):2139-45. doi: 10.1172/JCI106431. PMID: 4319971; PMCID: PMC535789.
4. Stolbach AI, Hoffman RS, Nelson LS. Mechanical ventilation was associated with acidemia in a case series of salicylate-poisoned patients. Acad Emerg Med. 2008 Sep;15(9):866-9. doi: 10.1111/j.1553-2712.2008.00205.x. PMID: 18821862.

Post Peer Reviewed By: Salim R. Rezaie, MD (Twitter/X: @srrezaie)