Welcome to today's POTD: Aspirin overdose, and by extension, salicylate poisoning!
Background: Salicylates are found in a lot of over the counter drugs and "natural" remedies. Most commonly in the form of Aspirin (acetylsalicylic acid, or ASA), it also exists in Pepto-Bismol, Maalox, Alka-seltzer, and the classic stem question, Oil of Wintergreen. Aspirin is rapidly converted to salicylic acid in the body. Fun fact: Aspirin used to exist as Aspergum, with each stick dosed at 227mg of aspirin. You even had your choice between orange and cherry flavors. Discontinued in 2006.
Normally, at therapeutic levels, aspirin is ingested and absorbed in the stomach. It makes its way to the blood stream, and almost all of it is bound to protein. It is first metabolized by the liver, and these metabolites are then excreted by the kidneys into the urine.
This method of metabolism is quickly overwhelmed in overdose. More free salicylate exists unbound by protein, and the liver's ability to detox becomes saturated. Elimination then proceeds via renal elimination, which is much slower.
Pathophysiology and Symptoms:
The effects salicylates have on specific organs and generalized metabolism are what produce its toxicity.
Acid Base Abnormality
-Salicylates directly stimulates the medullary respiratory center, causing hyperventilation. This hyperventilation blows off CO2 and leads to a respiratory alkalosis. This is usually the first acid-base disturbance.
-This is followed by an anion gap metabolic acidosis. Salicylates uncouple oxidative phosphorylation in the mitochondria, leading to a reliance on anaerobic metabolism and a resultant increase in lactic acid. Build up of organic acids lead to a metabolic acidosis. This is on top of the original respiratory alkalosis, leading to a mixed acid-base picture.
Uncoupling oxidative phosphorylation produces heat; patients are usually hyperthermic.
Tinnitus: Salicylate is ototoxic, and can cause temporary hearing loss and reversible tinnitus. Symptoms usually subside 1-3 days following cessation of salicylate cessation.
Vomiting:
Aspirin and salicylates are gastric irritants, and in overdose, leads to direct stimulation of the chemoreceptor trigger zone in the medulla that causes vomiting. Large amounts of emesis may also create a metabolic alkalosis.
AMS and seizures: Salicylates can cross the blood brain barrier, and can build up in the CNS. This can cause AMS in three different ways: through direct toxicity to CNS through acidemia, neuroglycopenia (through increased demand in CNS), and cerebral edema.
Pulmonary edema and acute lung injury: Salicylate toxicity leads to increased pulmonary vascular permeability.
Arrhythmia: Acidosis and electrolyte disturbances lead to cardiac arrhythmia through altering membrane permeability of cardiac myocytes.
Bleeding: Acidosis lead to thrombocytopenia and platelet dysfunction.
Word to the wise: Aspirin as a means to suicide is often accompanied by a coingestion of one or more medications. Have a low threshold to check levels/treat for other common overdoses.
Workup:
ASA, Acetaminophen, and levels of any other suspected measureable coingestant
BGM, CBC, BMP, repeated blood gas, mag, phos, UA, utox, coags, LFTs
CT head, EKG, CXR, KUB
Treatment:
These patient are potentially SICK. As always, start with you ABCs.
Airway and Breathing: These patients are tachypneic and may go on to develop respiratory distress when they can no longer compensate for their metabolic acidosis. However, for similar reasons to your DKA patients, avoid intubating if possible. It will be difficult to match the patient's respiratory drive, and the short period of apnea occurring when intubating may spell disaster for your patient.
Circulation: These patients are usually volume down from insensible losses and from vomiting. Help them out with some IVF. Be wary if there are signs of cerebral edema pulmonary edema.
Consider activated charcoal and whole bowel irrigation for decontamination.
Administer glucose. There is a real risk of neuroglycopenia, even if plasma levels are normal.
Alkalinize that urine: Providing sodium bicarb helps alkalinize the urine, facilitating renal clearance and also helps with decrease in CNS/plasma levels of salicylic acid. Alkalinization (increasing pH) increases conversion of salicylic acid to its base form.
Dosing is 1-2meq per kg bolus followed by infusion of 100 to 150meq in 1L sterile water with 5% dextrose.
Correct electrolyte abnormalities.
DIALYSIS: Indications are as follows:
AMS or cerebral edema, pulmonary edema, AKI/chronic kidney disease as this will impair salicylate clearance, salicylate level >90, pH <7, or if patient continues to get worse despite care.
Keep your nephro, tox, and ICU friends handy.
Special notes:
AVOID ACETAZOLAMIDE: though it may make sense to try to alkalinize urine via acetazolaminde, it does it at the cost of reducing bicarb reabsorption.
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.
Sources:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3341117/
https://wikem.org/wiki/Salicylate_toxicity
https://www.uptodate.com/contents/salicylate-aspirin-poisoning-in-adults