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.
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:
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.
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.
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.
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:
No scientific research has determined that outcomes of salicylate toxicity are dependent on race.
No scientific research has determined that outcomes of salicylate toxicity are dependent on sex.
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.
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.
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.
Contact dermatitis may develop from topical application.
Diaphoresis is a common sign in patients with salicylate toxicity.
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.
Obtain measurements of serum electrolytes, blood urea nitrogen (BUN), creatinine, calcium, magnesium, and glucose. Repeat these tests at least every 12 hours until the salicylate level falls and the acid-base disturbance improves. If hemodialysis is required, testing is needed more frequently. Monitor serum potassium concentrations; normal levels may be difficult to obtain during alkalinization therapy.
If managing an acute or acute-on-chronic ingestion, repeat this test every 2 hours until the salicylate level falls.
If the levels increase, consider the possibility that a sustained-release preparation was ingested or that a concretion in the GI tract has formed.
In general, the Done nomogram (noted in numerous emergency medicine and toxicology textbooks) is not as useful in salicylate ingestions as other nomograms are in other ingestions. The Done nomogram has not been proven valid in the following instances:
Many toxicologists suggest avoiding the use of the Done nomogram. The Done nomogram assumes complete absorption by 6 hours postingestion; 6-hour postingestion levels may be correlated with the following degrees of toxicity:
Serum levels determined less than 6 hours postingestion (acute overdose) do not rule out impending toxicity because salicylates are in the absorption-distribution phase. Likewise, in cases of chronic salicylism, measured toxic levels may be only 30-40 mg/d.
Monitor and maintain an alkaline urine pH every 2 hours during alkalinization therapy.
Maintain a urine pH of 7.5-8 (monitor the serum pH rather than the urine pH). Excessive sodium bicarbonate induces severe alkalemia and/or hypernatremia. Consider obtaining a urine specimen for a qualitative toxicology screen.
Obtain hepatic, hematologic, and coagulation profiles for patients with clinical evidence of moderate-to-severe toxicity (eg, those that need to be admitted for inpatient care).
Repeat approximately every 2 hours until metabolic acidosis improves.
During urinary alkalinization therapy, the arterial pH should remain between 7.3 and 7.5.
A chest x-ray is indicated if evidence of severe intoxication, pulmonary edema, or hypoxemia is present.
Consider an abdominal x-ray if an aspirin concretion is suspected. For better sensitivity, this should be performed before administration of activated charcoal.
Other methods of identifying gastric salicylate pharmacobezoars include the following:
Stabilize the airway, breathing, and circulation.
Evidence-based guidelines are available from the American Association of Poison Control Centers on management of out-of-hospital salicylate exposures.[2]
Therapeutic objectives include cardiopulmonary stabilization, prevention of absorption, correction of fluid deficits, correction of acid-base abnormalities, and enhancement of excretion and elimination.
Endotracheal intubation may be required for several reasons.
Large-bore vascular access catheters may be required to facilitate emergent hemodialysis.
Methods to prevent absorption involve emesis, gastric lavage, multidose activated charcoal, and cathartics.
The use of ipecac syrup is controversial and many studies indicate that it does not alter clinical outcome. It is most effective if given within 30 minutes of ingestion; however, it is relatively contraindicated in the presence of a severe aspirin ingestion because of the risk of seizures from aspirin. Gastric lavage may be beneficial, unless contraindicated, up to 60 minutes after salicylate ingestion. Warmed (38°C) isotonic sodium chloride solution may be used. Protect the airway before gastric lavage.
Administer activated charcoal unless contraindications are present. Current literature does not support the administration of multidose activated charcoal. A cathartic agent may be given with the first charcoal dose; however, repeat cathartic dosing generally should be avoided because of concern over resultant electrolyte imbalances.
Provide treatment for correction of fluid deficits and enhancement of excretion and elimination. Administer lactated Ringer or isotonic sodium chloride solution for volume expansion at 10-20 cc/kg/h until a 1-1.5-cc/kg/h urine flow is established. Provide maintenance fluids to maintain urinary alkalinization. Forced diuresis is not recommended. The greater the urine flow, the more difficult it is to alkalinize the urine. Be cautious of excessive fluid volumes in cases of salicylate-induced pulmonary edema.
Perform urinary alkalinization for symptomatic patients and patients with rising salicylate levels or acid-base abnormalities. Consider this treatment if the salicylate level is higher than 35 mg/dL.
One method to initiate urinary alkalinization uses a single IV bolus of NaHCO 3 at 1-2 mEq/kg. Follow this with a constant infusion of D5W with NaHCO 3 100-150 mEq/L and KCl 20-40 mEq/L at 1.5-2.5 mL/kg/h to produce a urine flow of 0.5-1 mL/kg/h. Closely monitor the serum electrolytes and urine pH, and maintain the urinary pH between 7.5-8.
The urinary excretion of salicylic acid is dependent upon hydrogen ion gradients, which are, in turn, dependent on adequate serum potassium. Alkaline urine facilitates salicylate ion trapping and excretion but can only be accomplished if adequate potassium is present.
Monitor glucose levels closely. Initial hyperglycemia may give way to hypoglycemia and worsening CNS symptoms. Tissue glucose levels may be lower than plasma glucose levels.
Consult with the regional poison control center or a local medical toxicologist for additional information and patient care recommendations. Consultation with nephrology department personnel is required if hemodialysis is indicated. This decision should be made in conjunction with the medical toxicologist.
Hemodialysis is the best method for enhanced elimination. Advantages of hemodialysis are increased salicylate clearance, correction of acid-base disturbances, and correction of fluid and electrolyte abnormalities.
Recommendations for hemodialysis include the following:
Drug therapy includes activated charcoal, sodium bicarbonate, and polyethylene glycol solution.
Clinical Context: Emergency treatment in poisoning caused by drugs and chemicals. Network of pores present in activated charcoal adsorbs 100-1000 mg of drug per gram of charcoal. Does not dissolve in water.
For maximum effect, administer within 30 min of ingesting poison.
Clinical Context: Laxative with strong electrolyte and osmotic effects that has cathartic actions in GI tract. Consider whole bowel irrigation when sustained-release products are involved. Remember that this agent does not adsorb anything but merely pushes things through the GI tract at a faster rate.
Clinical Context: Alkalinizes urine, causing excretion of salicylate to increase.
Alkalinization of the urine enhances elimination of salicylates through ion trapping in the renal tubules.
Admit patients with major signs and symptoms (eg, neurological, cardiopulmonary, metabolic) to an intensive care unit under the care of a medical toxicologist, if available. Consult psychiatric service personnel for patients with intentional overdose.
Admit patients with minor signs and symptoms (eg, tinnitus, nausea) to an extended care observational unit or medical floor.
Admit the following patients, regardless of salicylate levels:
Patients with accidental ingestions of less than 150 mg/kg and no signs of toxicity can be discharged after 6 hours postingestion. Arrange a follow-up for these patients in 24 hours.
A 16% morbidity rate and a 1% mortality rate are associated with patients presenting with an acute overdose.
The incidence of morbidity and mortality for a patient with chronic intoxication is 30% and 25%, respectively.