Salicylate Toxicity in Emergency Medicine



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.

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.



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.


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.

Laboratory 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:

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.

Hepatic, hematologic, and coagulation profiles

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:

Other Tests

Prehospital Care

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]

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.

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:

Medication Summary

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

Activated charcoal (Liqui-Char)

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.

Polyethylene glycol (GoLYTELY, Colyte)

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.

Class Summary

Limits absorption of ingested substance.

Sodium bicarbonate (Neut)

Clinical Context:  Alkalinizes urine, causing excretion of salicylate to increase.

Class Summary

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

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:

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.


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.


Lance W Kreplick, MD, FAAEM, MMM, Medical Director of Hyperbaric Medicine, Fawcett Wound Management and Hyperbaric Medicine; Consulting Staff in Occupational Health and Rehabilitation, Company Care Occupational Health Services; President and Chief Executive Officer, QED Medical Solutions, LLC

Disclosure: Nothing to disclose.

Specialty Editors

Mark S Slabinski, MD, FACEP, FAAEM, Vice President, EMP Medical Group

Disclosure: Nothing to disclose.

John T VanDeVoort, PharmD, Regional Director of Pharmacy, Sacred Heart & St. Joseph's Hospitals

Disclosure: Nothing to disclose.

Fred Harchelroad, MD, FACMT, FAAEM, FACEP, Chair, Department of Emergency Medicine, Director of Medical Toxicology, Allegheny General Hospital; Associate Professor, Department of Emergency Medicine, Drexel University College of Medicine

Disclosure: Nothing to disclose.

John D Halamka, MD, MS, Associate Professor of Medicine, Harvard Medical School, Beth Israel Deaconess Medical Center; Chief Information Officer, CareGroup Healthcare System and Harvard Medical School; Attending Physician, Division of Emergency Medicine, Beth Israel Deaconess Medical Center

Disclosure: Nothing to disclose.

Chief Editor

Asim Tarabar, MD, Assistant Professor, Director, Medical Toxicology, Department of Emergency Medicine, Yale University School of Medicine; Consulting Staff, Department of Emergency Medicine, Yale-New Haven Hospital

Disclosure: Nothing to disclose.


  1. Samlan SR, Jordan MT, Chan SB, Wahl MS, Rubin RL. Tinnitus as a measure of salicylate toxicity in the overdose setting. West J Emerg Med. Aug 2008;9(3):146-9. [View Abstract]
  2. [Guideline] Chyka PA, Erdman AR, Christianson G, Wax PM, Booze LL, Manoguerra AS, et al. Salicylate poisoning: an evidence-based consensus guideline for out-of-hospital management. Clin Toxicol (Phila). 2007;45(2):95-131. [View Abstract]
  3. Acetylsalicylic Acid. National Library of Medicine, TOXNET, Hazardous Substances Data Bank. Available at
  4. Brenner BE, Simon RR. Management of salicylate intoxication. Drugs. Oct 1982;24(4):335-40. [View Abstract]
  5. 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. [View Abstract]
  6. 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. [View Abstract]
  7. Chiaretti A, Schembri Wismayer D, Tortorolo L, et al. Salicylate intoxication using a skin ointment. Acta Paediatr. Mar 1997;86(3):330-1. [View Abstract]
  8. 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. [View Abstract]
  9. 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. [View Abstract]
  10. Done AK, Temple AR. Treatment of salicylate poisoning. Mod Treat. Aug 1971;8(3):528-51. [View Abstract]
  11. 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. [View Abstract]
  12. 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. [View Abstract]
  13. Gilman AG, Goodman LS, Gilman A, eds. The Pharmacological Basis of Therapeutics. 6th ed. New York: McGraw-Hill; 1980.
  14. Gittelman DK. Chronic salicylate intoxication. South Med J. Jun 1993;86(6):683-5. [View Abstract]
  15. 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. [View Abstract]
  16. Krause DS, Wolf BA, Shaw LM. Acute aspirin overdose: mechanisms of toxicity. Ther Drug Monit. Dec 1992;14(6):441-51. [View Abstract]
  17. O'Malley GF. Emergency department management of the salicylate-poisoned patient. Emerg Med Clin North Am. May 2007;25(2):333-46; abstract viii. [View Abstract]
  18. Proudfoot AT. Toxicity of salicylates. Am J Med. Nov 14 1983;75(5A):99-103. [View Abstract]
  19. 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. [View Abstract]
  20. Temple AR. Acute and chronic effects of aspirin toxicity and their treatment. Arch Intern Med. Feb 23 1981;141(3 Spec No):364-9. [View Abstract]