Pharmacology 101: Acute Salicylate Poisoning, Part 2

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 Pharmacology 101! This is a continuation of our discussion of acute salicylate poisoning, specifically its pharmacokinetics, pathophysiology, and clinical manifestations. We covered those in Part 1, so in this Part 2 we will review initial management in the emergency department and beyond. While not all these therapies may be implemented in the prehospital setting, all caregivers are better served by a knowledge of treatment modalities throughout the continuum of care.

Treatment and Management

There are no antidotes available for the treatment of salicylate toxicity. Emergency care of the patient will include a continuation of the airway, breathing, and circulation assessment and stabilization started by prehospital caregivers. Due to the glucose, acid-base, and electrolyte derangements discussed in Part 1, these values must be carefully monitored, in addition to salicylate levels, which are easily obtainable upon arrival in the emergency department.^1,2

It is important to attempt to maintain euvolemia. If the patient is hypotensive and volume-depleted, fluids may be administered intravenously. This can be accomplished with normal saline or lactated Ringer’s.¹ Forced diuresis is not the goal; rather the goal is euvolemia, as too-aggressive fluid administration risks pulmonary edema.^1,2

Absorption Mitigation

Attempts to reduce gastric absorption of salicylates may be accomplished with activated charcoal, provided the patient is alert and willing to take it (activated charcoal has an aspiration risk, and many patients consider it to be unpleasant). While activated charcoal is typically considered most effective within a 1–2-hour window, large ingestions of salicylates may result in slowed gastric motility, and enteric-coated or sustained-release formulations may merit administration—thus it has been recommended to attempt charcoal administration regardless of the time of ingestion. Repeated doses may be indicated depending on evidence for absorption of salicylate. In some cases whole-bowel irrigation may be pursued.^1,2 Authors Biff Palmer, MD, and Deborah Clegg, PhD, note there are contraindications to charcoal administration: aspiration risk, poor gastric motility, and salicylate-induced gastrointestinal hemorrhage.¹

Akalinization

Alkalinization of the urine to facilitate renal elimination of salicylate will help accomplish the primary goal of minimizing salicylate distribution into the brain.³ Renal clearance can be substantially enhanced by urine alkalinization—consider that changing the pH of the urine from 5 to 8 can increase clearance by 20-fold!² Salicylic acid is a weak acid (pKa 3.0), which means that in an alkaline environment, it will be ionized and therefore “trapped.” A “three-compartment” model is often used to describe the tissues, plasma, and urine: Alkalinization of the plasma and urine shifts the equilibrium away from the tissues toward the plasma; then, in turn, from the plasma into the urine, where it is then eliminated.^1,2,4 This is generally accomplished by administering a bolus of sodium bicarbonate followed by an infusion of intravenous fluids with sodium bicarbonate while monitoring urine pH. Hypokalemia is frequently encountered when employing this strategy and should be monitored for and addressed.^1,4

Dialysis

In severe cases of salicylate toxicity, hemodialysis may be indicated. Dialysis can address many facets of toxicity, including volume status, acid-base status, and electrolyte abnormalities.^1,2,4

Summary

Acute salicylate poisoning may have significant morbidity and mortality risks and has no antidote. At least one author considers aspirin to have the poorest risk-benefit profile of all the over-the-counter analgesics.⁵ Prompt recognition of the signs and symptoms of salicylate toxicity, combined with a knowledge of treatment modalities across the continuum of care, will help improve early management.

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

2. Pearlman BL, Gambhir R. Salicylate intoxication: A clinical review. Postgrad Med, 2009; 121(4): 162–8.

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

4. Hoffman RS, Howland MA, Lewin NA, Nelson LS, Goldfrank LR. Goldfrank’s Toxicologic Emergencies, 10th edition. McGraw-Hill Education; 2014.

5. O’Malley GF. Emergency Department Management of the Salicylate-Poisoned Patient. Emerg Med Clin North Am, 2007; 25(2): 333–46.

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.