Aspirin Toxicity

Overview Principle of the disease Clinical features Diagnosis Management

Overview Aspirin and other salicylates are among the oldest medications remaining in clinical practice. The use of aspirin has declined due to its association with Reye's syndrome in children, and the development of other nonsteroidal antiinflammatory drugs (NSAIDs).

aspirin remains a common analgesic and a widely prescribed antiplatelet therapy for patients with cardiovascular and cerebrovascular disease, and thus aspirin toxicity remains an important clinical problem

Principle of the disease Mechanism of action: Inhibition of cyclooxygenase results in decreased synthesis of prostaglandins, prostacyclin, and thromboxanes. This will lead to platelet dysfunction and gastric mucosal injury.

Stimulation of the chemoreceptor trigger zone in the medulla causes nausea and vomiting. Activation of the respiratory center of the medulla results in hyperventilation and respiratory alkalosis.

Interference with cellular metabolism (eg, Krebs cycle, oxidative phosphorylation) leads to metabolic acidosis.

Absorption and metabolism _ rapidly absorbed Absorption and metabolism _ rapidly absorbed . _ peak blood concentrations are usually reached within one hour. _ Aspirin is metabolized in the liver. _ half-life of two to four hours.

At therapeutic levels, 90 percent of salicylate is protein bound and therefore limited to the vascular space

The drug is metabolized in the liver to salicyluric acid, which is both less toxic and more rapidly excreted by the kidney than salicylate. Only a small amount of drug is excreted unchanged in the urine.

In OVERDOSE Peak levels are frequently delayed, up to six hours In OVERDOSE Peak levels are frequently delayed, up to six hours. The degree of protein binding falls and hepatic detoxification becomes saturated.

As the normal hepatic detoxification is saturated, elimination becomes dependent upon (slow) renal excretion and drug half-life increases from 2 to 4 hours to as long as 30 hours

Clinical features

Diagnosis High index of suspicion. Vital signs Vital signs !!!

Think in ASA toxicity in any case with unexplained pulmonary edema or acute change in level of conscious.

toxic dose of aspirin 200 to 300mg/kg Lethal dose 500mg/kg

Labs CBC U&Es VBG SERUM LEVEL MSU LFTS LACTATE COAGULATIONS

Serum salicylate: Therapeutic serum salicylate concentrations fall between 10 to 30 mg/dL (0.7 to 2.2 mmol/L). values above 40 mg/dL (2.9 mmol/L) are associated with toxicity. Fatal aspirin intoxication can occur after the ingestion of 10 to 30 g by adults and as little as 3 g by children.

Although toxicity does not correlate exactly with serum salicylate concentrations and symptoms, most patients exhibit signs of intoxication when the serum concentration exceeds 40 to 50 mg/dL (2.9 to 3.6 mmol/L).

In patients with clinical signs of salicylate poisoning, serum concentrations should be measured every two hours until two consecutive levels show a continuing decrease from the peak measurement.

Monitoring serum salicylate concentrations may help assess the response to therapy and determine the need for more aggressive measures, including hemodialysis. Levels above 100 mg/dL (7.2 mmol/L) are associated with increased morbidity and mortality, and are considered an absolute indication for hemodialysis.

Acid-Base Disturbances: early respiratory acidosis High anion gap metabolic acidosis Respiratory acidosis and metabolic alkalosis can present also.

In patients with mixed acid base disturbance always think in ASA toxicity

Management Treatment of salicylate poising has two main objectives: 1st is to correct fluid deficits and acid-base abnormalities 2nd is to increase excretion.

Airway and breathing: Intubation is indicated for patients with refractory shock, pulmonary or cerebral edema, or other manifestations of severe salicylate poisoning.

Activated Charcoal: activated charcoal (AC), in a single dose or multiple doses, somewhat reduces salicylate absorption. May be used in 1st hour with large lethal dose provided the airway is well protected.

Intravenous fluids: Aggressive volume resuscitation is warranted in such patients, unless cerebral edema or pulmonary edema is present. Potassium depletion must be corrected.

Fluid administration should be guided by the patient’s apparent deficit to maintain urine output of 2 to 3 mL/kg/hr should NOT exceed the estimated replacement because overly excessive fluid administration can worsen cerebral and pulmonary edema.

Supplemental glucose: Aspirin intoxication may decrease cerebral glucose concentrations despite a normal serum glucose. supplemental glucose should be given to patients with an altered mental status regardless of the serum glucose concentration.

Urine Alkalinization: Because salicylates are weak acids and are renally excreted, alkaline urine traps the salicylate ion and increases excretion. Alkalinization with sodium bicarbonate is an essential component of management of the aspirin-poisoned patient.

Urine alkalinization is advisable in patients with salicylate levels greater than 35 mg/dL, significant acid-base disturbance, or increasing salicylate level

The usual initial dose of sodium bicarbonate is 1 to 2 mEq (or mmol) per kg given as an intravenous bolus. followed by a sodium bicarbonate infusion of 100 to 150 mEq (or mmol) in one liter of sterile water with 5 percent dextrose. The rate of the infusion is titrated to a urine pH of 7.5 to 8.

Hemodialysis

Disposition: In patients with acute intoxication, hospital admission is required for pulmonary edema, CNS symptoms , seizures ,acidosis, electrolyte disorders, dehydration, renal insufficiency, or increasing serum levels during serial testing.

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