AUTHOR AND EDITOR INFORMATION

Section 1 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

INTRODUCTION

Section 2 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

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

Section 3 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

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.

DIFFERENTIALS

Section 4 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Other Problems to be Considered

Caffeine toxicity

WORKUP

Section 5 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Lab Studies

• 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.
• Serum salicylate level
• • 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:
    • Acute ingestions when other salicylates have been taken within the past 24 hours
    • Acute overdoses when salicylates have been ingested over several hours
    • Chronic salicylate ingestions
    • Ingestions of enteric-coated or sustained-release preparations
    • Renal failure patients
  • 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:
    • Less than 50 mg/dL - Asymptomatic
    • 51-110 mg/dL - Mild-to-moderate toxicity
    • 110-120 mg/dL - Severe 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.
• Urinalysis
• • 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).
• Arterial blood gas
• • Repeat approximately every 2 hours until metabolic acidosis improves.
  • During urinary alkalinization therapy, the arterial pH should remain between 7.3 and 7.5.

Imaging Studies

• 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:
• • Ultrasonography
  • CT scan of the head
  • Endoscopy

Other Tests

• ECG
• The ferric chloride test and the Ames Phenistix test are sensitive but nonspecific screening tests that may be available in the ED. However, these tests are currently almost never performed because of the availability of rapid and accurate quantitative serum assays.
• • If acetylsalicylic acid is present, combining 1 mL of urine and a few drops of 10% ferric chloride causes a purple color change.
  • The Phenistix turns brown if salicylates are present in the urine, but this test lacks specificity.

TREATMENT

Section 6 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Prehospital Care

• Stabilize the airway, breathing, and circulation.

Emergency Department Care

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.
• • Ventilatory support in patients with severe hypoxemia from aspirin-induced pulmonary edema
  • Maintenance of hyperventilation (as compensation for metabolic acidosis)
  • Protection of patients who are too agitated and delirious for central line placement, hemodialysis, and other necessary medical procedures without therapeutic sedation
  • Protection of the airway against aspiration during lavage or activated charcoal administration or in obtunded patients who cannot protect their own airway.
• 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 NaHCO₃ at 1-2 mEq/kg. Follow this with a constant infusion of D5W with NaHCO₃ 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.

Consultations

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:
• • Severe manifestations of intoxication (eg, persistent neurological symptoms, pulmonary edema, renal failure)
  • Refractory or profound acidosis (ie, progressive deterioration despite conservative efforts)
  • Serum levels higher than 100 mg/dL after acute overdose or serum levels higher than 40-50 mg/dL in chronic salicylism

MEDICATION

Section 7 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Drug therapy includes activated charcoal, sodium bicarbonate, and polyethylene glycol solution.

Drug Category: GI decontaminants

Limits absorption of ingested substance.

Drug Category: Alkalinizing agent

Alkalinization of the urine enhances elimination of salicylates through ion trapping in the renal tubules.

FOLLOW-UP

Section 8 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Further Inpatient Care

• 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:
• • Infants and elderly persons
  • Individuals with chronic salicylism
  • Those with ingestions of sustained-release products

Further Outpatient Care

• 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.

Prognosis

• 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.

Patient Education

• Advise patients and their families that use or overuse of seemingly benign over-the-counter medications is sometimes dangerous. The ready availability of aspirin and aspirin-containing products does not establish the safety of aspirin.
• For excellent patient education resources, visit eMedicine's Drug Overdose Center and Poisoning - First Aid and Emergency Center. Also, see eMedicine's patient education articles Aspirin Poisoning, Drug Overdose, Activated Charcoal, and Poison Proofing Your Home.

MISCELLANEOUS

Section 9 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Medical/Legal Pitfalls

• Failure to diagnose salicylate toxicity in a patient presenting with vague signs and symptoms, such as anxiety, tachypnea, agitation, delirium, tinnitus, or a combined respiratory alkalosis and metabolic acidosis
• Failure to initiate GI decontamination in a patient with acute salicylate ingestion who, subsequently, has recurrent toxicity from a salicylate bezoar
• Failure to hyperventilate a patient with severe salicylate poisoning who has just been intubated (when acid-base status had been maintained previously by the patient's own hyperventilation) to prevent lethal acidemia
• Failure to remove any possible ingestants from a patient's access when presentation follows an intentional ingestion, such as a suicide attempt
• Failure to diagnose and treat concomitant hypoglycemia in the salicylate-intoxicated patient; more common in children than in adults
• Failure to diagnose and treat hypoxemia caused by salicylate-induced pulmonary edema
• Failure to consider co-ingestions or other diagnoses
• Failure to consider recurrent or delayed toxicity from sustained-release preparations or from an unrecognized medication bezoar

REFERENCES

Section 10 of 10

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

• Acetylsalicylic Acid. National Library of Medicine, TOXNET, Hazardous Substances Data Bank. Available at http://toxnet.nlm.nih.gov/cgi-bin/sis/search/f?./temp/~yiK5GU:1.
• Brenner BE, Simon RR. Management of salicylate intoxication. Drugs. Oct 1982;24(4):335-40. [Medline].
• Chan TY, Chan AY, Ho CS, Critchley JA. The clinical value of screening for salicylates in acute poisoning. Vet Hum Toxicol. Feb 1995;37(1):37-8. [Medline].
• Chapman BJ, Proudfoot AT. Adult salicylate poisoning: deaths and outcome in patients with high plasma salicylate concentrations. Q J Med. Aug 1989;72(268):699-707. [Medline].
• Chiaretti A, Schembri Wismayer D, Tortorolo L, et al. Salicylate intoxication using a skin ointment. Acta Paediatr. Mar 1997;86(3):330-1. [Medline].
• Danel V, Henry JA, Glucksman E. Activated charcoal, emesis, and gastric lavage in aspirin overdose. Br Med J (Clin Res Ed). May 28 1988;296(6635):1507. [Medline].
• Dargan PI, Wallace CI, Jones AL. An evidence based flowchart to guide the management of acute salicylate (aspirin) overdose. Emerg Med J. May 2002;19(3):206-9. [Medline].
• Done AK, Temple AR. Treatment of salicylate poisoning. Mod Treat. Aug 1971;8(3):528-51. [Medline].
• Dugandzic RM, Tierney MG, Dickinson GE, et al. Evaluation of the validity of the Done nomogram in the management of acute salicylate intoxication. Ann Emerg Med. Nov 1989;18(11):1186-90. [Medline].
• Gabow PA, Anderson RJ, Potts DE, Schrier RW. Acid-base disturbances in the salicylate-intoxicated adult. Arch Intern Med. Oct 1978;138(10):1481-4. [Medline].
• Gilman AG, Goodman LS, Gilman A, eds. The Pharmacological Basis of Therapeutics. 6^th ed. New York: McGraw-Hill; 1980.
• Gittelman DK. Chronic salicylate intoxication. South Med J. Jun 1993;86(6):683-5. [Medline].
• Johnson D, Eppler J, Giesbrecht E, Verjee Z, Rais A, Wiggins T. Effect of multiple-dose activated charcoal on the clearance of high-dose intravenous aspirin in a porcine model. Ann Emerg Med. Nov 1995;26(5):569-74. [Medline].
• Krause DS, Wolf BA, Shaw LM. Acute aspirin overdose: mechanisms of toxicity. Ther Drug Monit. Dec 1992;14(6):441-51. [Medline].
• O'Malley GF. Emergency department management of the salicylate-poisoned patient. Emerg Med Clin North Am. May 2007;25(2):333-46; abstract viii. [Medline].
• Proudfoot AT. Toxicity of salicylates. Am J Med. Nov 14 1983;75(5A):99-103. [Medline].
• Teece S, Crawford I. Best evidence topic report. Gastric lavage in aspirin and non-steroidal anti-inflammatory drug overdose. Emerg Med J. Sep 2004;21(5):591-2. [Medline].
• Temple AR. Acute and chronic effects of aspirin toxicity and their treatment. Arch Intern Med. Feb 23 1981;141(3 Spec No):364-9. [Medline].

Article Last Updated: Jul 11, 2008