Introduction
Background
Salicylates possess anti-inflammatory, analgesic, and antipyretic properties. These agents are available for ingestion as tablets, capsules, and liquids. Salicylates are also available in topical forms as creams or lotions. Acetylsalicylic acid is colorless or white in a crystalline, powder, or granular form. The chemical is odorless and is soluble in water.
It is used as an analgesic agent for the treatment of mild to moderate pain. Aspirin is used as an anti-inflammatory agent for the treatment of soft tissue and joint inflammation. The product is an antipyretic drug. Low-dose aspirin helps prevent thrombosis.
Pathophysiology
The toxic effects of salicylates are complex. Respiratory centers are directly stimulated. Salicylates cause an inhibition of the citric acid cycle and an uncoupling of oxidative phosphorylation. In addition, lipid metabolism is stimulated, while amino acid metabolism is inhibited. Catabolism occurs secondary to the inhibition of ATP-dependent reactions with the following results:
- Increased oxygen consumption
- Increased carbon dioxide production
- Accelerated activity of the glycolytic and lipolytic pathways
- Depletion of hepatic glycogen
- Hyperpyrexia
Acid-base disturbances vary with age and severity of the intoxication. Initially, a respiratory alkalosis develops secondary to direct stimulation of the respiratory centers. This may be the only consequence of mild salicylism. The kidneys excrete potassium, sodium, and bicarbonate, resulting in alkaline urine.
Metabolic effects
A severe metabolic (ketolactic) acidosis with compensatory respiratory alkalosis may develop with severe salicylate intoxication. A paradoxical aciduria (hydrogen ion excretion) occurs with the depletion of sodium bicarbonate and potassium.
Infants rarely present with a pure respiratory alkalosis. Respiratory alkalosis with a compensatory (high anion gap) metabolic acidosis defines the next stage in moderate-to-severe intoxication. Potassium moves from the intracellular space to the extracellular space. Excretion of hydrogen ions produces acidic urine.
Frequency
United States
Data from the American Association of Poison Control Centers' annual report indicate that, in 1998, a total of 14,253 exposures to salicylates were reported; of which, 3837 exposures were in patients younger that 6 years, and 5053 exposures were in patients older than 19 years. Of the total exposures for that year, 33 deaths were reported. These numbers include only pure aspirin formulations; toxic exposures to pharmaceuticals with aspirin in combination with other drugs are not included in this report.
Mortality/Morbidity
A 16% morbidity rate and a 1% mortality rate are associated with patients presenting with an acute overdose. The incidence of morbidity and mortality of a patient with chronic intoxication is 30% and 25%, respectively.
- The following 4 categories are helpful for assessing the potential severity and morbidity of an acute, single event, nonenteric-coated, salicylate ingestion:
- Less than 150 mg/kg - Spectrum ranges from no toxicity to mild toxicity
- From 150-300 mg/kg - Mild-to-moderate toxicity
- From 301-500 mg/kg - Serious toxicity
- Greater than 500 mg/kg - Potentially lethal toxicity
Race
No scientific research has determined that outcomes of salicylate toxicity are dependent on race.
Sex
No scientific research has determined that outcomes of salicylate toxicity are dependent on sex.
Age
Generally, the degree of the toxicity is more severe in elderly individuals, infants, and in persons with coexisting morbidity or chronic intoxication.
- Acid-base disturbances vary with age and severity of the intoxication.
- Infants rarely present with pure respiratory alkalosis. Respiratory alkalosis may not develop in an infant or it may be short-lived. The most common presentation for a child is metabolic acidosis.
- Factors contributing to a decline in the incidence of pediatric salicylate intoxication include increased acetaminophen utilization and child-resistant packaging.
Clinical
History
The patient who presents with an acute, witnessed, or intentional overdose usually has a history that the physician can directly obtain. Eliciting a history associated with chronic overdose in the geriatric patient or the psychiatric patient often is more obscure; thus, diagnosis can be more difficult in these patient populations.
- The chronic ingestion of salicylates may produce the appearance of anxiety with its associated tachypnea, difficulty concentrating, and hallucinations; agitated delirium also may be observed.
- Elderly individuals may present with deterioration in functional status or with concerns of pneumonia.
- Patients with underlying psychiatric illness may present with symptoms suggestive of an exacerbation of their underlying psychiatric illness (eg, mania, psychosis).
- If aspirin usage is suspected, direct questioning is useful. Many patients do not list aspirin or other over-the-counter aspirin-containing products because they may not consider such products as medications.
Physical
- Pulmonary
- Hyperventilation (common)
- Hyperpnea
- Noncardiogenic pulmonary edema
- Respiratory arrest
- Apnea
- Aspiration pneumonitis
- Auditory
- Ototoxicity
- Tinnitus
- Tinnitus is commonly encountered when serum salicylate concentrations exceed 30 mg/dL.
- Tinnitus is a nonspecific nonsensitive clinical effect of salicylism.
- Deafness
- Cardiovascular
- Tachycardia, generally with minimal hemodynamic or clinical significance
- Hypotension
- Dysrhythmias (eg, ventricular tachycardia, ventricular fibrillation, multiple PVCs)
- Asystole (with severe intoxication)
- Electrocardiogram (ECG) abnormalities (eg, U waves, flattened T waves, QT prolongation), may reflect hypokalemia
- Sudden hemodynamic deterioration secondary to respiratory depression
- Respiratory depression limits the respiratory alkalosis and causes an increase in the nonionized portion of salicylate.
- The nonionized fraction enters the tissues, especially the CNS.
- Neurologic
- CNS depression, with manifestations ranging from somnolence and lethargy to seizures and coma
- Tremor
- Blurring of vision
- Seizures
- Encephalopathy
- Encephalopathic changes may include irritability, confusion, hyperactivity, and hallucinations
- These clinical effects are usually associated with severe cases.
- Cerebral edema (with severe intoxication)
- Gastrointestinal
- Nausea and vomiting, common
- Epigastric pain
- GI hemorrhage -Most common with chronic intoxication
- Intestinal perforation
- Pancreatitis
- Hepatitis (generally in chronic toxicity, rare in acute toxicity)
- Genitourinary
- Acute renal failure is an uncommon complication of salicylate toxicity.
- Renal failure may be secondary to multisystem organ failure.
- Case reports have documented the presence of albuminuria.
- Hematologic
- Hematologic effects may include prolongation of the prothrombin and bleeding times and decreased platelet adhesiveness.
- Disseminated intravascular coagulation (DIC) may be noted with multisystem organ failure in association with chronic salicylate toxicity.
- Dermatologic
- Contact dermatitis may develop from topical application.
- Diaphoresis is a common sign in patients with salicylate toxicity.
- Electrolytes
- Dehydration
- Hypokalemia may be a severe iatrogenic complication in patients treated with urinary alkalinization if sufficient potassium supplementation is not provided.
- Hypocalcemia
- Acidemia
- SIADH
Causes
Onset of chronic salicylism may be insidious; elderly individuals may consume an increasing amount over several days to alleviate arthralgias, subsequently becoming confused because salicylate pharmacokinetics change at higher concentrations. This may lead to a perpetual spiral of increased salicylate consumption and increased confusion. Similar scenarios occur in persons with underlying psychiatric disorders.
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References
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Further Reading
Keywords
aspirin overdose, aspirin, aspirin poisoning, aspirin ingestion, salicylate toxicity, salicylate ingestion, salicylate overdose, salicylate poisoning
