ASA Overdose

This morning we talked about the approach to an aspirin (ASA) overdose. This is an important topic to review since we don't see it very frequently on GIM yet its management requires time sensitive interventions to prevent morbidity and mortality.

Here's a flow chart from the BMJ. If you have access, here's a review article from Postgraduate Medicine. The Merck Manual also has a short review as does Harrison's. The Uptodate article on "Aspirin Poisoning in Adults" is also a nice summary.

We talked about urine alkalinization quite a bit today. Here's a link to a position paper published in the Journal of Toxicology that supports urinary alkalinization.

Some key points:

1) Salicylates are found not only in aspirin (acetylsalicylic acid), but also in a number of OTC/herbal products including Bismuth subsalicylate (Pepto Bismol), salicylic acid and Oil of Wintergreen.

2) In general (watch your units):
i) Therapeutic Range: 0.7-2.2mmol/L
ii) Toxic Range: >greater than 2.9mmol/L
iii) Consider dialysis when level is greater than 7.2mmol/L

3) In usual doses, aspirin is rapidly absorbed and reaches a peak concentration in 1 hour. However, in the setting of an overdose, this can be significantly delayed (5-6 hours from ingestion) due to slowed gastric emptying or enteric coated/slow-release preparations.

4) Pathophysiology of Toxicity:
i) Uncoupling of oxidative phosphorylation at the cellular level
ii) Stimulation of the respiratory centre in the medulla
iii) Metabolic acidosis (primary from salicyltes, secondary from mitochondrial poisoning)
iv) Central hypoglycemia despite normal peripheral blood glucose levels

5) Signs and Symptoms of overdose: nausea, vomiting, tinnitus, hyperventilation. More severe symptoms include: fever, decreased LOC, non-cardiogenic pulmonary edema, rhabdomyolysis, hypotension, seizures and AKI.

6) When suspecting any overdose, always check a Tylenol and ASA level.

7) Important investigations: ASA level (check q2h until two values show decreasing levels), ABG (or venous blood gas), CBC, lytes, creatinine, liver enzymes, INR, plasma glucose, extended electrolytes, urinalysis, urine pH and CXR. The blood work and urine tests should be repeated frequently during the initial period of management.

8) ASA intoxication is one of the prototypical causes of a mixed repiratory alkalosis with an anion gap metabolic acidosis (although an isolated anion gap metabolic acidosis can be seen).

9) Remember the common causes of an anion gap metabolic acidosis: methanol, uremia, diabetic/starvation/alcoholic ketoacidosis, lactic acidosis, ethylene glycol, salicylates.

10) Management:

i) Stabilize ABCs.

ii) If tolerated, activated charcoal should be given (1g/Kg up to 50g) and can be repeated q4h x 2 after the first dose. This works best if given within 1 hour of toxic ingestion. Contraindicated if level of consciousness is depressed unless the patient is intubated.

iii) Supplemental glucose should be given in patients with altered LOC due to the risk of neuroglycopenia despite normal peripheral blood glucose.

iv) Potassium must be aggressively replaced. Hypokalemia can impair urine alkalinization, and any initial hypokalemia will be exacerabted by alkalinization.

v) Urine alkalinization: This is a critical step. Here's a position paper published in the Journal of Toxicology on the topic.

Salicylic acid is a weak acid. The non-ionic form can diffuse across membranes, while the ionic form cannot. Increasing the serum pH will result in diffucion of the non-ionic form out of cells and trap it in the blood/urine in the ionic form.

Pre-existing alkalosis is not a contraindication to urinary alkalinization.

A rise in the urine pH of 1 unit can theoretically increase salicylate excretion by a factor of 10.

Start with a bolus of 1-2mEq/Kg of NaHCO3 followed by an infusion of 3amps of NaHCO3 mixed in 850cc D5W (NOT normal saline) run at 1.5-2 times maintenance. Urine pH should be checked frequently with a target of > 7.5 - 8. Failure to achieve this within 1-2 hours may be an indication for dialysis.

11) Avoid acetazolamide and any medication that depresses respiratory drive.

12) Indications for dialysis:
i) Renal failure impairing salicylate clearance
ii) Inability to alkalinize the urine
iii) Fluid overload limiting sodium bicarbonate treatment
iv) Plasma salicylate level greater than 7.2 mmol/L
v) Coma
vi) Failure of medical management

13) Always call your local poison centre for advice when managing an overdose.