Salicylate Intoxication
Joey Sweeney, PharmD, BCPS
During the current pandemic, salicylate intoxication is unlikely to be at the top of many clinicians’ differential diagnosis list. But salicylate intoxication could be misdiagnosed as COVID-19. With fever being a symptom of COVID-19, clinicians may be seeing an increased use of salicylate antipyretics such as aspirin. This presents an opportunity for pharmacists to step in and conduct a thorough medication review of patients’ previously administered medications.
Salicylates have been used medicinally for thousands of years. In the 1800s, chemists isolated various salicylates and studied their effects. During this period, their medicinal benefits, including their antipyretic and analgesic properties, as well as salicylate toxicity became well understood.
The general population may not know that salicylates can be found in various products, including the alternative medicine option oil of wintergreen. Some OTC topical pain and bismuth subsalicylate products also contain them.
Salicylates have potentially serious overdose considerations. During the 1918 pandemic, salicylate toxicity and poisoning became more common as people used greater doses of salicylates to stave the effects of the flu—often in vain. In 2018, there were 26 deaths and more than 17,000 hospitalizations related to salicylate intoxication. Signs of salicylate toxicity include fever, tachypnea, rales, and corresponding acid–base imbalances. Many clinicians would look at this constellation of symptoms and assume viral infection.
Acute intoxication
Acute intoxication from salicylates is more common in younger patients during overdose attempts (typically with a previous psychiatric diagnosis). Fortunately, upon presentation to the emergency department, most of these patients volunteer information about their overdose attempt, and diagnosis is relatively straightforward.
Within 2 hours after ingestion, point plasma levels are often greater than 40 mg/dL (2.9 mmol/L). Therapeutic levels are between 15 mg/dL and 30 mg/dL (1.1 mmol/L and 2.2 mmol/L). Clinical symptoms of intoxication include tinnitus, vertigo, nausea, vomiting, and hyperpnea.
Severe intoxication occurs after levels increase beyond 50 mg/dL (5.1 mmol/L). Clinical symptoms at this level include fever, sweating, listlessness, and incoordination.
When levels exceed 75 mg/dL (5.4 mmol/L), clinical symptoms include hallucinations, seizures, cerebral edema, coma, noncardiogenic pulmonary edema, and cardiovascular collapse.
Concomitant ingestion of other substances can affect the presentation and course of salicylate intoxication. Alcohol and/or opioids can, in tandem with the salicylate, lead to delayed gastric emptying and a longer time course until peak salicylate levels occur. This would require frequent monitoring and lab draws to ensure the patient is appropriately managed.
Chronic intoxication
Chronic intoxication usually occurs in patients taking salicylates therapeutically who accidentally overdose. In these cases, the half-life of the salicylate is lengthened due to the patient’s baseline salicylate accumulation. This would manifest with symptoms of intoxication occurring at lower-than-expected plasma levels. Relying on plasma level alone risks underestimating the degree of intoxication and corresponding therapy.
Treatment
Because a salicylate antidote does not exist, treatment should focus on care targeting appropriate respirations and cardiovascular stabilization. Contacting poison control is recommended. Mechanical ventilation should be reserved only in cases indicating hypoventilation.
For hypotensive patients, volume resuscitation is required with careful monitoring for fluid overload (cerebral or pulmonary edema). Activated charcoal can be administered if the patient is alert and cooperative and can be repeated every 4 hours until it appears in the stool. Sodium bicarbonate can be administered intravenously to raise the plasma pH, which will more rapidly clear the drug from the central nervous system. This also alkalinizes the urine, which speeds filtration of the drug into the urine. Potassium should be closely monitored during sodium bicarbonate therapy and supplemented when needed. Hemodialysis is also an efficient way to get salicylate out of the body.