ASPIRIN TOXICITY

Severe intoxication

results in profound *metabolic acidosis,* *marked hyperthermia*, *cerebral edema (coma and seizure)*, *hypoglycemia,* *pulmonary edema,* *cardiovascular collapse.*

Management ?????

(1) to correct fluid deficits and acid-base abnormalities. (2) Increase excretion.

count..

*Supportive and symptomatic care :* Avoid CNS/respiratory depressants, which may decrease the respiratory alkalosis and thereby worsen the acidemia. If intubated, match the preintubation Pco2. *IV hydration* (not forced diuresis) to maintain renal perfusion.

chronic excessive use of salicylate is seen in?

*elderly* and is associated with a higher clinical toxicity for a given serum salicylate level.

Classic presentation of mild to moderate toxicity ?

*mixed acid- base picture* respiratory alkalosis, wide anion-gap metabolic acidosis, and (possibly) a metabolic alkalosis (from dehydration).

Chronic ingestion ?

- Symptoms of toxicity overlap with those of acute ingestion, but are slower in onset and often nonspecific-> difficult to dx - could be present with neurological including confusion, hallucinations, agitation, coma, or commonly with confusion, dehydration, and metabolic acidosis. or others like Pulmonary edema, cerebral edema, seizures, and renal failure

Salicylate toxicity can cause ?

- metabolic acidosis, - seizure - hyperthermia - pulmonary edema - cerebral edema, - renal failure - death.

Pathophysiology *MCQ*

-*Direct stimulation of respiratory center* → hyperventilation and respiratory alkalosis. -*Stimulation of chemoreceptor trigger zone* → vomiting. -*Uncoupling of oxidative phosphorylation* → anaerobic metabolism, lacate production, anion-gap acidosis, and hyperthermia. -*Increased fatty acid metabolism* → metabolic acidosis (ketones) -*Ototoxicity* → tinnitus and hearing loss correlate with salicylate level. -*Platelets permanently lose their ability to aggregate at therapeutic aspirin doses*. Bleeding is rare in overdose. -*Cerebral and pulmonary edema* → secondary to alterations in capillary integrity.

what also would we do

-*Early arterial blood gas* determinations in symptomatic patients rapidly assess acid-base and compensatory status. -*A serum salicylate concentration* should be measured with a second sample obtained 2 hours later. If the second concentration is greater than the first, serial concentrations should be obtained to monitor continued absorption, which may be prolonged.

count..

-*Sodium bicarbonate therapy:* 1-2 mEq/kg IV bolus, followed by drip. Goal is *urinary alkalinization* to pH 7.5-8.0. -*Correct hypokalemia*: Results from intracellular shifts and body losses. *Urinary alkalinization will not occur unless hypokalemia is corrected.* Obtain basic metabolic panel and salicylate levels every 2 hours. Monitor salicylate levels until levels have declined to near therapeutic concentration.

Initial Evaluation

-After the primary survey, a general physical examination is conducted to *assess vital signs* (including oxyhemoglobin saturation and a counted respiratory rate and reliable temperature) -*Chest auscultation* may provide evidence of pulmonary edema, and *mental status* may suggest CNS toxicity. .

MOA of aspirin ?

Salicylic acid is *a weak acid* that at normal serum pH is mostly *ionized*, therefore will *not cross the blood-brain barrier or the renal tubules* (for reabsorption).

Diagnostic Strategies

-Based on history, physical examination, and acid-base findings. -Maintain high level of suspicion in patients with: 1-Unexplained respiratory alkalosis 2-Mixed metabolic disorders 3-Metabolic acidosis 4-Elderly with altered mental status 5-Patients with hearing complaints Key labs: Salicylate level, ABG, electrolytes

Acute ingestion

-Early symptoms -Classic presentation of mild to moderate toxicity

Early symptoms

-N/V -tinnitus -hearing loss -lethargy -hyperventilation, -hyperthermia.

why the incidence of aspirin overdose has decreased over the last years ?

-pediatricians' preference for acetaminophen preparations -limiting 36 tablets of baby aspirin to each bottle -the use of child-resistant caps.

what are the indications of hemodialysis ? *MCQ*

1- Level > 100 mg/dL (*acute ingestions*), Level > 40 mg/dL (*chronic ingestions*) accompanied by clinical signs of severe intoxication. 2-Altered mental status. 3-Renal failure/anuria. 4-Severe persistent acid-base disturbance. 5-Pulmonary edema. 6-Failure to respond to intensive treatment

so you said the toxicity wouldn't develop unless the salicylate is nonionized, then how would we treat it ?

keep salicylate in the ionized form.

if the pt ingests mega dose or large dose of aspirn when do you expect to see the rising serum levels?

12hrs or more

when the peak levels occur?

2-4 hrs

toxic dose of aspirin ?

200 to 300 mg/kg, and ingestion of 500 mg/kg is potentially lethal.

So how long does it take to see the toxicity after ingestion ?

30min

*The Done nomogram* when should be performed ?

NEVER shouldn't be used

Pharmacokinetics (MCQ)

Salts of salicylic acid are rapidly absorbed intact from the gastrointestinal tract, with *appreciable serum concentrations occurring within 30 minutes.* Two thirds of a therapeutic dose is absorbed in 1 hour, and *peak levels occur in 2 to 4 hours.* Large ingestions frequently delay gastric emptying, and ingestions of enteric capsules may *cause a prolonged absorption with rising serum levels for 12 hours or more.*

So , patient with respiratory alkalosis and increased anion-gap metabolic acidosis?

Think salicylate toxicity.

which one is more difficult to diagnose acute or chronic ?

acute : easy the pt tells chronic: usually missdx

elderly on aspirin comes in with pulmonary edema and no signs CHF what is the etiology ?

alterations in capillary integrity

why is the severity of this poisoning may be underestimated ?

because of the lack of familiarity with the clinical picture

Urine ferric chloride test will be performed in purpose of ?

confirm exposure, but not toxicity (always the wrong answer)

Blood gases early on often show a respiratory alkalosis with pH > 7.5. ? *why*

cuz respiratory alkalosis respons faster than metabolic

Ototoxicity?

elderly comes in complaining of abnormality in hearing

As the blood becomes more acidemic, a more *nonionized* form develops, allowing salicylate to ?

enter the brain and be reabsorbed by the kidneys (decreasing renal excretion).

ionized and non-ionized

ionized: cant cross BBB -> less toxicity Nonionized: can cross BBB-> more toxicity