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Salicylate Overdose: Can’t See the Forest for the Willow Bark

The acute toxic dose is 150mg/kg, which works out to 10-30g in adults and 3g in children. Salicylate levels > 40 mg/dL are considered toxic. Still, serum levels can rise or fall with serum pH, reflecting changes in elimination or distribution, and cannot be used to correlate with toxicity directly.

Here's the critical chemistry you must understand to know how to treat salicylate overdose: salicylate is a weak acid. At low pH, more of the drug is uncharged, able to pass through cellular membranes. At a higher pH, more of the drug is charged and unable to pass through membranes, which make it essentially "trapped." A trapped drug is a good thing. A trapped, charged drug is unable to…

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 An Approach to Salicylate Poisoning

As always start with the ABCs: if altered and vomiting (AKA not protecting the airway) or patient appears to be tiring and therefore hypoventilating → intubate! But be careful. These patients usually have metabolic acidosis so be sure to set a HIGH respiratory rate on the vent to prevent combined metabolic and respiratory acidosis → which could cause the patient to code.

 Guidance Document: Management Priorities in Salicylate Toxicity

Salicylate toxicity is a complex problem with the potential for significant morbidity and mortality. Awareness of the differences in acute and chronic toxicity, anticipation of clinical manifestations and potential complications, appropriate interpretation of salicylate concentrations and timely initiation of enhanced elimination techniques are imperative.

Articles of Interest

Acute Salicylate Toxicity in Children: Diagnosis and Treatment of Overingestion

Various formulations with different concentrations of salicylates are available, including 81-mg ASA tablets, 325-mg ASA tablets, enteric-coated ASA capsules, and topical methyl salicylate creams and ointments. Familiar brand names of ASA-containing medications are Bufferin, Excedrin, Percodan, Anacin, and Fiorinal. Bismuth subsalicylate–containing preparations, such as Pepto-Bismol, are sold over the counter to relieve upset stomach and contain 8.7 mg of salicylate per mL. Methyl salicylate, also known as oil of wintergreen, is the most concentrated and toxic formulation of salicylate, containing 98% salicylate in its pure form.

Approach to Acute Salicylate Toxicity

Patients with accidental ingestions of < 150mg/kg and no signs of toxicity may be observed for 6 hours post ingestion and considered for discharge.

ASA Toxicity

Salicylate toxicity, while relatively rare, has fairly nuanced management. It is important for physicians to be aware of presenting features of the toxicity and also of key management steps. Some pearls from this case include:

BCE 64 Salicylate Poisoning

Serum alkalinization is more important than urine alkalinization. Bicarb 1-2 mEq/kg IV bolus, then infusion at 150 mEq in 1 L D5W at 2x maintenance to a target serum pH 7.45 to 7.55. Beware hypokalemia!

EM@3AM: Salicylate Overdose

Indications for hemodialysis for salicylate toxicity include pulmonary edema, severe metabolic acidosis, altered mental status, coagulopathy, renal failure, clinical deterioration despite supportive care, and absolute serum salicylate level > 100 mg/dL in acute poisonings and > 60 mg/dL in chronic poisonings.

EmergencyKT: Salicylate Toxicity

Avoid intubation if possible. Intubation should only be performed if patient truly has respiratory failure (worsening acidosis, hypoxemia).

Meet the salicylates

Chemically speaking, they are all variations on the same theme. Aspirin is probably the most commonly overdosed upon of the group, and so will receive the greatest attention, even though methyl salicylate is actually more toxic (and seems to have been around for longer in toxicological literature; early pioneers of the field report on the case from 1832, of a man who drank 30ml of "oil of wintergreen" and died).

Pharmacology 101: Acute Salicylate Poisoning, Part 1

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.

Salicylate intoxication

If patient is intubated and aspirin ingestion was within 1 hour, administer activated charcoal. If not intubated, don't give charcoal. (This is controversial, these patients have a tendency to lose their mental status and vomit.) Whole bowel irrigation could be considered for an intubated patient who consumed a large amount of enteric-coated tablets.

Salicylate Overdose

Salicylate toxicity can significantly affect cardiac physiology. Prolongation of the QT interval is regularly seen, which can lead to polymorphic ventricular tachycardia and/or ventricular fibrillation.

Salicylate Poisoning

Chronic Salicylate poisoning: Occurs in patients who routinely take salicylates, and sometimes to the point of excess. More common in young children and elderly patients. Symptoms may be all of the above, but the levels of salicylate may be normal or only mildly elevated. Have a lower threshold for dialysis.

Salicylate toxicity

Salicylates irreversible block the COX-1 pathway and modify the COX-2 pathway resulting in a decrease in inflammation (reduced prostaglandin synthesis) and platelet aggregation. It stimulates the respiratory centres causing hyperpnoea (one of the first signs of toxicity, although rarely seen in children), noted as a respiratory alkalosis on a gas sample.

Salicylate Toxicity

No definite cutoff for salicylate concentration requiring HD, however acute toxicity patients with concentrations greater than 80 or 100 mg/dL will likely require HD.

Salicylate Toxicity as a Sepsis-Mimic

Salicylate toxicity isn’t as common as it once was and it can look a lot like sepsis (tachycardia, tachypnea, elevated temperature, altered mental status, acidosis, etc), particularly in older adults. In this patient population, consider sending a salicylate level with the initial set of sepsis labs. Even though the test may seem ‘low-yield,’ early identification and treatment of salicylate poisoning is vital, even if it is a less common cause for suspected sepsis.

Tasty Morsels of Critical Care 055 | Salicylate poisoning

Like most ingestions, the context or the patient will often be the give away to the diagnosis. But if they haven’t told you directly, you might start by asking questions about tinnitus, dizziness and vomiting. On exam you might find fever, tachypnoea and even impaired consciousness as things get more advanced.

Unintentional overdose with over-the-counter salicylate products in an elderly patient

The most well known is aspirin, or acetyl salicylic acid. One of the most popular forms is Anacin, containing aspirin and caffeine. An old medication, it has been popular since the 1930s. Salicylates can also be found in bismuth salicylate (Pepto Bismol) and oil of wintergreen. It is imperative that emergency medicine clinicians recognize the wide array of over-the-counter substances containing salicylate, and signs and symptoms of acute ingestion to quickly prescribe the appropriate treatment.

Resources

5 Tips in Managing Acute Salicylate Poisoning

The American College of Medical Toxicology (ACMT) recently published a guidance document on management priorities in salicylate toxicity, and it’s definitely worth a read. While not an official clinical guideline, it highlights some important concepts to consider when working up and treating patients after a significant salicylate exposure, and we’ll review five major concepts here and hopefully answer some questions that may cross your mind on shift.

BC Emergency Medicine Network

Enteric coated pills can form bezoar: consider flat plate abdomen if rising ASA level despite alkalinization. ECG: usually sinus tachycardia. Ventricular dysrhythmias and AV block are reported but rare.

WikEM

Therapeutic: 10-30mg/dL, Toxicity: >40-50mg/dL. Unit Conversion 100mg/dL = 1000mg/L = 7.24 mmol/L.