Pharmacology 101: Acute Salicylate Poisoning, Part 1

Pharmacology 101 is an online column designed to keep EMS providers informed on formularies, dosages, effects, applications, and current research related to medications administered and encountered in the prehospital setting. If you have a medication-related question you’d like the author to address, contact editor@emsworld.com.

Welcome to the latest in Pharmacology 101! Today we discuss acute salicylate poisoning, specifically its pharmacokinetics, pathophysiology, and clinical manifestations. While aspirin is probably the most well-known of the salicylates, other over-the-counter and prescription products exist. Examples of other salicylate products include bismuth subsalicylate, effervescent antacids, ointments, liniments, and oil of wintergreen (methyl salicylate) and alternative medication products (e.g., willow bark).¹

Poison control centers have reported tens of thousands of exposures to salicylates over the years, both intentional and unintentional.^2,3 Unfortunately, several dozens of these cases have been fatal. In the 1950s–1970s, salicylates were a leading cause of fatal childhood poisonings, but pediatric fatalities have declined over the years due to child-resistant packaging, decreased use, and improved critical care.

Salicylate toxicity can occur either acutely, through a large ingestion, or chronically, through repeated supratherapeutic exposures.²

Pharmacokinetics

Upon ingestion aspirin is rapidly absorbed, then hydrolyzed to salicylate, with significant serum concentrations within 30 minutes and peak serum concentrations often occurring within one hour. However, delayed peak levels can occur when enteric-coated formulations are ingested.^2,4 When encountering a patient with a potential aspirin overdose, clarifying the formulation (i.e., chewable vs. enteric-coated) can be very important! Enteric-coated formulations can have delayed peak levels from 4–6 hours at therapeutic doses and up to 24 hours when taken in toxic overdoses.⁵

Aspirin is rapidly converted to salicylate in the body. Salicylate in turn has a dose-dependent half-life that can be up to 12 hours when used at anti-inflammatory doses. When taken in toxic doses, the half-life can be prolonged up to 20 hours!⁵

Pathophysiology and Clinical Effects

There are five primary clinical manifestations of aspirin toxicity:^3,5,6

Gastrointestinal effects—Salicylate can alter the protective mucosal barrier protecting the stomach lining from its acidic contents. Nausea and vomiting (including hematemesis) may occur due to gastric irritation and direct stimulation of the chemoreceptor trigger zone in the brain, causing fluid and electrolyte losses. Significant dehydration is possible with fluid deficits up to 4–6 liters.

Acid-base disturbances—Tachypnea and hypercapnia occur via direct stimulation of the respiratory center. The classic presentation is that of respiratory alkalosis, as the patient “blows off” carbon dioxide. Salicylate can also interfere with oxidative phosphorylation and fatty acid metabolism, resulting in increased pyruvic and lactic acids, as well as ketone bodies. Inorganic acids accumulate, which can exacerbate an anion gap metabolic acidosis. In moderate to severe toxicity a mixed acid-base disturbance will reveal itself as the clinical course progresses—that is, a respiratory alkalosis combined with a metabolic acidosis.

Neurological effects—The Cleveland Clinic’s Simon Lam, PharmD, and colleagues note, “Central nervous system (CNS) manifestations are always an ominous finding.”⁶ The neurotoxic effects of salicylate poisoning may be the most visible, and patients may present with a spectrum of neurological disturbances ranging from lethargy to confusion and agitation to seizures and coma.

Glucose concentrations in the brain may be significantly lower than in the serum. One case report of a child with salicylate poisoning noted that cerebrospinal fluid had an undetectably low glucose level. Even in the setting of a normal serum glucose, the CNS glucose level may be significantly low, and effects of stupor, coma, and delirium have been reported to be acutely reversed by administration of dextrose. Lam and colleagues recommend dextrose be considered in any patient presenting with altered mental status and suspected salicylate toxicity.

Tinnitus (ringing in the ears) is a classic finding in salicylate poisoning, and this may ultimately progress to deafness. Even in the absence of other neurological disturbances, tinnitus may be a signal of salicylate poisoning.

Acute lung injury—Acute respiratory distress syndrome (ARDS) is a potential manifestation in acute toxicity and may even lead to death. Pulmonary edema may result from increased capillary permeability.

Hyperthermia—Extreme muscle rigidity has been demonstrated in severe salicylate poisoning, potentially leading to hyperthermia. In addition to generating excess heat, the patient may be unable to dissipate heat. The discovery of significantly elevated temperatures may be a preterminal finding.

Conclusion

Emergency service personnel should be aware of salicylate poisoning and its associated clinical manifestations. In the upcoming second part of this series, we will discuss the evaluation and management of patients with salicylate poisoning.

The views and opinions expressed in this article are those of the author and do not necessarily reflect those of people, institutions, or organizations they have been, currently are, or will be affiliated with.

References

1. American College of Medical Toxicology. Guidance Document: Management Priorities in Salicylate Toxicity. J Med Toxicol, 2015; 11(1): 149–52.

2. Chyka PA, Erdman AR, Christianson G, et al. Salicylate poisoning: An evidence-based consensus guideline for out-of-hospital management. Clin Toxicol, 2007; 45(2): 95–131.

3. Palmer BF, Clegg DJ. Salicylate Toxicity. N Engl J Med, 2020; 382(26): 2,544–55.

4. Brooks DE, Levine M, O’Connor AD, et al. Toxicology in the ICU: Part 2: Specific toxins. Chest, 2011; 140(4): 1,072–85.

5. Hoffman RS, Howland MA, Lewin NA, et al. Goldfrank’s Toxicologic Emergencies, 10th ed. McGraw-Hill Education, 2014.

6. Lam SW, Engebretsen KM, Bauer SR. Toxicology today: What you need to know now. J Pharm Pract, 2011; 24(2): 174–88.

Daniel Hu, PharmD, BCCCP, has Doctor of Pharmacy degree and is a critical care and emergency medicine pharmacist. He is a frequent speaker at conferences and has many publications in peer-reviewed journals.