Pearls and Pitfalls of Salicylate Toxicity in the Emergency Department

Authors: Samantha Berman, MD (EM Resident Physician, RWJMS) and Josh Bucher, MD (EMS Fellow, Morristown Medical Center) // Edited by: Alex Koyfman, MD (@EMHighAK, EM Attending Physician, UT Southwestern Medical Center / Parkland Memorial Hospital) & Justin Bright, MD (@JBright2021)


Emergency physicians commonly care for poisoned patients.  These exposures may be either intentional or unintentional.  Salicylates are commonly found in many topical and over the counter preparations, yet salicylate toxicity is often overlooked and underestimated as a potential cause for illness in our patients. Below is a condensed quick-guide of common mistakes that emergency physicians may be making with respect to salicylate overdoses and how to fix them. The goals of care to take away from this article are prevention of intestinal absorption and CNS entry of salicylates, as well as drug elimination.

Pathophysiology of Salicylate Toxicity:

Salicylate overdoses demonstrate a mixed acid-base disturbance. Salicylates have a direct stimulatory effect on the medullary respiratory center in the central nervous system, which causes an increase in carbon dioxide production. This results in an increased respiratory rate as the body attempts to rid itself of the extra acid thus causing a respiratory alkalosis. Salicylates also uncouple oxidative phosphorylation, induce lipolysis, stimulate skeletal muscle metabolism and inhibit portions of the Krebs cycle, which leads to a build up of metabolic products such as lactate, pyruvate and ketoacids. This contributes to both a rise in body temperature as well as a metabolic acidosis. Finally, salicylates inhibit gastric emptying which causes delayed, continuous absorption of the material. Therefore, a mixed respiratory alkalosis and metabolic acidosis {Pro Tip: this ABG finding will be on every EM board exam you ever take} can be expected.


Optimize electrolyte imbalances prior to intubation, correct hypokalemia to >4 mEq/L

If intubation necessary, give bicarb boluses (2 mEq/kg IV) and maintain vent settings at PRE-INTUBATION respiratory status, i.e. high minute ventilation and PCO2 < 20 mmHg à YOU CAN KILL A SALICYLATE TOXICITY PATIENT WITH INCORRECT VENTILATOR SETTINGS!

– Early hemodialysis

– Serial salicylate levels and VBGs q 2 hours

Serum alkalinization more important than urine

– Avoid acidemia!


Forced diuresis with large volume IVF has no proven benefits, increased risk of pulmonary edema in patients already at risk for this

Hyperventilation/tachypnea itself is not an indication for intubation à It is often a compensatory mechanism for the metabolic acidosis

Overreliance on serum salicylate levels

Not correcting hypokalemia

Inadequate serum alkalinization

Over-emphasizing urine alkalinization

Failure to consider hemodialysis early in the clinical course

Areas of Improvement

Over-reliance on salicylate levels: Down-trending levels can lead to a false sense of security. As the serum pH levels decrease, salicylate changes to its non-ionized form which makes it easier to cross the blood brain barrier leading to severe CNS toxicity. Additionally, falling serum pH levels allows the volume of distribution of salicylates to increase as it diffuses out of the serum and into the tissues. This creates a reported decrease in salicylate levels which can be misinterpreted by the ED physician as an improvement in clinical status. Additionally, chronic salicylate toxicity can occur at much lower levels than acute toxicity. Levels in the high-therapeutic range (i.e. 40 mg/dl) can cause significant CNS dysfunction so appropriate correlation between a patient’s clinical status, serum pH, and salicylate value is of utmost importance. Finally, because absorption is delayed in overdoses, peak levels of salicylate may also be delayed therefore treatment of salicylate poisoning should rely on the patient’s clinical factors and not solely on laboratory values.

Not optimizing volume, electrolyte, and acid-base statuses: Obtaining arterial or venous blood gases and a basic metabolic panel is key. Literature reviews from 2011 suggest that VBGs correlate well with ABGs for pH and PCO2 but not as well for PO2. For the purpose of detecting mixed acid-base disturbances in an emergent clinical setting such as salicylate poisoning, VBGs are sufficient. Additionally, ABGs have several procedural disadvantages such as increased risk of AV fistula formation, nerve injury, delay in care, and pain therefore VBGs are a suitable diagnostic alternative.

Patients presenting with salicylate toxicity are significantly volume-depleted due to diaphoresis, tachypnea, and vomiting. Hypovolemia worsens salicylate toxicity by contributing to electrolyte and acid-base disturbances. Fluid resuscitation aims to produce 3 cc/kg/hr of urine output. Resulting imbalances such as hypernatremia and hypokalemia should be aggressively repleted. Hypokalemia promotes aciduria, preventing salicylate excretion. Therefore potassium should be replenished to achieve levels >4 mEq/L as it has been shown to facilitate urinary alkalinization. Hyperglycemia from gluconeogenesis and resulting ketonemia may be seen in early toxicity but hypoglycemia occurs when the body is unable to keep up with metabolic demands. Patients will often have CNS-relative hypoglycemia as compared to the serum glucose level. Swift correction of hypoglycemia is crucial as it is a harbinger of poor outcomes. Maintain serum glucose around 150.

The use of sodium bicarbonate is necessary in patients with mild alkalemia or salicylate levels > 40 mg/dl. Alkalemia occurs as a result of hyperventilation from direct respiratory center stimulation, which produces a respiratory alkalosis. A paradoxical aciduria results as well, which also impairs salicylate excretion. The benefits of bicarbonate therapy are two-fold. It promotes alkalinization of both the serum and urine, which facilitates salicylate removal. Appropriate bicarbonate treatment creates an alkaline pH gradient, which shifts non-ionized salicylates from the tissue into the serum then into the urine where it gets trapped and eliminated. Alkalemic serum limits CNS toxicity. It may appear counterintuitive to administer bicarb to an already potentially alkalemic patient however, in the case of salicylate toxicity, patients often have a significant underlying base deficit despite the elevated serum pH. The base deficit exists due to a compensatory respiratory alkalosis combined with several mechanisms contributing to metabolic acidosis. Therefore, alkalemia is NOT a contraindication for sodium bicarbonate therapy!

Proper bicarb treatment: initial IV bolus of 1-2 mEq/kg followed by 150 mEq of bicarb in 1 L D5W running at 2x maintenance. The end-point of therapy is a serum pH 7.45 to 7.55.

Post-intubation mismanagement: Patients with severe salicylate toxicity may be at risk for respiratory decompensation due to respiratory muscle fatigue, altered mental status from CNS toxicity, or acute lung injury. However, sedation during rapid sequence intubation as well as standard weight-based ventilator settings may cause hypoventilation thus leading to respiratory acidosis. In a patient with salicylate poisoning, acidemia will cause precipitation of the non-ionized salicylate molecules which easily cross the blood brain barrier. If the situation necessitates intubation, efforts should be made to optimize alkalemia with intravenous bicarb. Even more importantly, post-intubation ventilator settings should mirror the patient’s pre-intubation respiratory status in order to maintain appropriate serum pH. High minute ventilation with high tidal volumes should be the goal with an endpoint of achieving a PCO2 < 20 mmHg. It is critically important to discuss the vent settings with your respiratory therapist.  Initial settings are often set on standard numbers – the combination of failed communication and a lack of understanding of the pathophysiology at hand can seriously harm your patient.

Delay in Hemodialysis: Many clinicians are hesitant about hemodialysis as a means of drug elimination. Earlier consideration of HD may decrease mortality in salicylate poisoning. Overreliance of salicylate levels delays definitive treatment in many patients. While it is widely accepted that levels > 100 mg/dl necessitate dialysis, chronic users may present with severe clinical symptoms with levels around 40 mg/dl. Both acute and chronic ingestions may have delayed presentations if enteric-coated tablets were involved therefore earlier dialysis should be considered. Patients who have hepatic and renal dysfunction are at particular risk for toxicity at lower than expected serum salicylate levels as the drug is metabolized via the liver and eliminated via the kidneys. Particular attention should be paid to these patients who may benefit from early dialysis. Patients presenting with acute lung injury, altered mental status, deteriorating clinical status, electrolyte imbalances, or persistent acidemia refractory to treatment, potential co-ingestions, and significant hyperthermia warrant dialysis regardless of drug level.

Lack of GI decontamination: GI decontamination is often contraindicated or becoming less favorable in toxic overdoses but benefits still apply in salicylate overdoses. Preventing further gastrointestinal absorption is imperative and activated charcoal in alert patients may accomplish that, especially if gastric bezoar formation occurs. Consider AC in alert and oriented patients who present within a few hours of ingestion as salicylate binds extremely well to charcoal. Whole bowel irrigation is controversial but may enhance transport of salicylate through the GI tract. GI decontamination should also be considered in the setting of rising salicylate levels despite bicarb therapy or while awaiting dialysis.


References / Further Reading

– Fertel, BS., Nelson, LS., Goldfarb, DS., “The Underutilization of Hemodialysis in Patients with Salicylate Poisoning.” Kidney Int. 2009 Jun; 75(12): 1349-53. Doi: 10.1038/ki.2008.443. Epub 2008 Aug 20. NYU School of Medicine, NewYork, New York

– Chhabra, Sunil K., “Agreement and Differences between Venous and Arterial Gas Analysis.” Annals of Thoracic Medicine. 2011. Jul-Sep; 6(3): 154. Doi: 10.4103/1817-1737.82454

– Soghoian, Sari MD., and Nelson, Lewis MD., “Pitfalls in the Management of Aspirin Poisoning.” Goldfrank’s Toxicologic Emergencies Ninth Edition. McGraw-Hill Medical, 2011. 508-520.

– “Guidance Document: Management Priorities in Salicylate Toxicity.” American College of Medical Toxicology.

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