ASA

Question 1

List 3 factors in overdose that affect absorption of ASA from the gut.

Answer 1

• Enteric coating
• Concretion formation
• Direct effects on gastric emptying i.e. Salicylate induced-pylorospasm

Question 2

What is the effect of pH on absorption of salicylate?

Answer 2

• Increased absorption with lower pH

- Decreased absorption in ionized form, seen at normal and high pH

Question 3

What is the significance of the pKa of salicylate and the effects of pH?

Answer 3

• At neutral pH essentially all salicylate molecules are ionized
• Acidemia increases the proportion of nonionized salicylate
• Nonionized salicylate is able to cross cell membranes including BBB
• Acidemia increases brain salicylate toxicity
• Mortality is directly related to brain salicylate level
• Avoidance of serum academia limits cellular shift and brain shift of ASA
• Urinary alkalosis will ionize salicylate in the urine and impair reabsorption and enhance elimination

Question 4

Describe the Acid Base Derangements of ASA toxicity

Answer 4

• Respiratory alkalosis: Stimulation of resp centres in brain à hyperventilation
• NAGMA:
  o Interferes with Kreb’s cycle à limits ATP production à excess H+ not used in Kreb’s
• AGMA:
  o Impair renal hemodynamics à accumulation inorganic acids
  o Uncouples oxidative phosphorylation à accumulation pyruvate + lactic acids (+Heat)
  o Induces fatty acid metabolism à ketones
  ASA weak acid (+ metabolites) à titrates 2-3mEq HCO3

Question 5

Describe the progression of acid base disorders in the course of ASA toxicity:

Answer 5

• Resp alkalosis (can have metabolic alkalosis early with ++vomiting)
• Resp alkalosis, AGMA
• Resp acidosis with ÝPCO2, metabolic acidosis
  o Pt often tiring here or CNS depression, +/- co-ingestants that also decrease LOC
  o Even small Ý PCO2 will increase the non-ionized form of ASA and increase CNS toxicity (vicious cycle)
  Peds, often skip the resp alkalosis because they are unable to generate the same degree of tachypnea from decreased resp reserve, or they present very late with a predominant acidosis.

Question 6

What are risk factors for ALI / ARDS with ASA toxicity?

Answer 6

elderly
smoker
chronic ingestion/toxicity
neuro sx
ASA level GT 2.9
metabolic acidosis

Question 7

How is urine alkalinazation achieved?

Answer 7

• Administer bicarb to goal urine pH 7.5-8, serum pH 7.5
• 2 amps at a time then infusion (3 amps in 1L bag D5W, run at 2x maint (~250cc/hr)
• HCO3 is better than hyperventilation for alkalinization, can hyperventilate in addition, but this alone should not be relied on.
  Monitor for hypocalcemia – it decreases both ionized and total serum calcium

Question 8

List indications for Dialysis in ASA toxicity

Answer 8

• Biochemical:
  o Severe acid-base disturbance despite appropriate treatment (pH <7.25)
  o Absolute level >7mmol/L in acute ingestion (4mmol/L for chronic) à based on expert concensus
• Clinical:
  o Neurotoxicity (trial of glucose first before the line!!! – CNS hypoglycemia vs edema)
  o Pulmonary edema, ALI
  o Renal or hepatic failure
  o Fluid overload impairing ability to use bicarb
  o Clinical deterioration despite aggressive care

Question 9

How are seizures in the ASA toxic patient treated?

Answer 9

• Use benzos and phenobarb NOT dilantin