Acute Salicylate Toxicity

Today’s episode focuses on salicylate toxicity, specifically in the case of a teenager with abdominal pain and emesis. Join us in this discussion of symptoms, patient history, diagnosis, management, and treatment. Show Highlights:Our case: A 15-year-old female is admitted to the PICU for intentionally ingesting a large amount of aspirin tablets. She had epigastric abdominal pain with some non-biliary, non-bloody emesis when she presented to the outside emergency department twelve hours post-ingestion. She denies any neurological symptoms, including tinnitus but appears anxious and tachypneic. In the emergency department, her salicylate level was 45 mg/dL after her ingestion of about 250 aspirin tablets of 325 mg each. The patient is previously healthy, denies the use of illicit drugs and alcohol, is not sexually active, and has no allergies. To summarize the key elements of this case and patient history, she has ingested potentially toxic amounts of aspirin and has suicidal ideation but has no tinnitus or other neurological symptoms. Physical examination results show stable vital signs except for a temp of 38.8C; she has persistent tachypnea and mild epigastric tenderness but no rashes or previous cutting scars.Patient labs were consistent with a 12-hour salicylate level of 45 mg/dL, liver function, Bun/Creatinine, and coagulation profile are all normal. Her anion gap is slightly elevated, urine pH is 6, specific gravity is normal, and urine pregnancy test is negative. Based on patient history, physical exam, and labs, it appears that the patient has GI symptoms of early salicylate toxicity. Ingesting potentially toxic amounts of aspirin brings concern for life-threatening injuries to organs and possible loss of life. Let’s quiz ourselves with a short multiple-choice question:A teenager with a previous history of suicidal attempt now presents with confusion, increased respiratory rate, fever, and diaphoresis. Her physical exam including the pupillary exam is normal. Her labs are remarkable for a pH of 7.45, CO2 of 19, HCO3 of 11, serum anion gap of 20meQ/L, serum K of 2.9, and serum glucose of 180 mg/dL. There are weakly positive ketones in the urine. The next step in management of this patient is:A) NaHCO3 infusionB) Insulin infusionC) Oral activated charcoalD) Hemodialysis dialysisThe correct answer to this question is A) Sodium bicarbonate infusion.Insulin therapy is not the answer because serum glucose is low, and a patient with a pH>7.25 is unlikely to have DKA.While activated charcoal can be used, especially followed by sorbitol given with the first dose, we need to be cautious about its use with an altered mental status as in the patient above.Since we do not have a salicylate level at this stage, offering hemodialysis should not be the first step, although it can be considered later given the neurological symptoms. Remember: Any patient with a previous history of suicidal ideation who presents with confusion, fever, and diaphoresis with the above labs is suggestive of mixed respiratory alkalosis with high anion gap metabolic acidosis is highly suggestive of aspirin poisoning. Always examine the pupils in any case of poisoning, as that may point one towards a possible toxidrome. Let’s highlight how basic science correlates with ASA poisoning:Remember the mechanism of action. Aspirin is a cyclo-oxygenase inhibitor which blocks prostaglandin production and has an antithrombotic effect by inhibiting platelet generation of thromboxane A2.Salicylates are weak acids which interfere with the Krebs cycle and specifically uncouple oxidative phosphorylation. This leads to acidosis, heat production, and hypoglycemia.Although not common, neuromuscular irritability manifested as paratonia (inability to relax muscles) and extreme muscle rigidity can develop, further contributing to hyperthermia and increasing the risk of rhabdomyolysis.Salicylates induce fatty acid metabolism resulting in ketone production which can further compound the anion gap metabolic acidosis.Disruption of the electron transport chain causes a dissociative shock picture in which there is adequate oxygen delivery, however, the tissues are unable to uptake the oxygen.Considerations in the diagnostic approach to our patient with salicylate poisoning:Salicylate poisoning can happen acutely (usually in young adults with suicidal ideation) or chronically, which often happens in the elderly who are taking aspirin therapeutically but have an inadvertent overdose. Because the pathways for salicylate elimination are fully saturated in those taking the drug chronically, a higher toxicity can occur at even a lower dose. The plasma level of salicylate required to elicit symptoms tends to be lower in chronic than in acute salicylate poisoning. In cases of acute salicylate toxicity, rising plasma levels are roughly correlated with the development of expected clinical manifestations, but such correlations are notoriously absent with ...