Management of salicylate toxicity

Author: Robert E. Sallis
Date: Jan, 1989

Management of Salicylate Toxicity Salicylate intoxication remains a commonly encountered problem. Early measures to prevent drug absorption, along with alkaline diuresis of the drug, are essential to successful management. If initial therapy fails to produce a response or if the clinical condition rapidly deteriorates, the patient should be treated aggressively with prompt hemodialysis. Because of their widespread availability and use, salicylates have been an important cause of poisoning in adults and children for many years. During the 1960s, controls limiting the number of pills per package and the introduction of childproof caps led to a dramatic decline in accidental poisonings among children.(1) However, salicylate toxicity remains a common problem and is associated with a surprisingly large number of deaths.

In children, salicylate toxicity is most often due to accidental ingestion or unintentional overdose. Chronic toxicity may result from overzealous administration of medication by parents. The problem is compounded when the parents attribute the fever, diaphoresis and tachycardia that occur with salicylate intoxication to the underlying illness and continue to increase the salicylate dose.

In adults, acute intoxication from salicylate ingestion is often associated with a suicide attempt. Chronic toxicity in adults may occur in those using high-dose salicylates to control pain. Medications that contain salicylates are a less obvious source of toxicity.

The following cases illustrate the spectrum of severity in salicylate toxicity.

Illustrative Cases


A 44-year-old woman came to the emergency department in moderate respiratory distress. For two days, she had experienced mild respiratory difficulty and shortness of breath. Intermittent vertigo and tinnitus had been present for three days, and her children had complained to her that "she was getting deaf." Her past medical history included sciatica and bipolar disorder, which was treated with lithium. For her sciatica, the patient had been taking up to 16 aspirin tablets (325 mg each) per day, along with ibuprofen, 400 mg three times daily, and indomethacin (Indocin), 25 mg three times daily.

On admission, the patient was awake and alert. She was in moderate respiratory distress and appeared restless and diaphoretic. Her temperature was 37|C (98.6|F); blood pressure, 110/60 mm Hg; pulse, 80, and respirations, 30. Diffuse rales were heard bilaterally. Heart rhythm was regular; there were no murmurs or gallops. Abdominal and neurologic findings were normal.

The electrocardiogram revealed sinus tachycardia with nonspecific ST-T changes. A chest radiograph confirmed the presence or gastric lavage.(3) Obviously, inducing emesis is contraindicated in a patient who has a reduced level of consciousness or in whom such a state may be anticipated.

There is debate regarding the maximum time interval after ingestion in which gastric emptying should be performed. Because salicylates delay gastric emptying, emesis or lavage may be of value up to 12 hours after ingestion.(6) Emesis is induced with syrup of ipecac (15 mL in children and 30 mL in adults, taken with water or soft drinks).(8) Gastric lavage is performed through a large-bore orogastric tube using normal saline.(1) Lavage is continued until the returning contents are clear. It may be necessary to perform lavage with warm water to dissolve concretions of salicylate in the stomach.


Activated charcoal acts by adsorbing to particles of salicylate in the gastrointestinal tract, thus preventing their absorption.(9) The efficacy of charcoal depends on how soon after ingestion it is given. Charcoal is of questionable value when it is given later than one to two hours after ingestion.(6) In general, the amount of activated charcoal given depends on the amount of salicylate ingested; a ratio of 10:1 (charcoal to salicylate) produces the best results.(4) Charcoal is administered as a slurry, preferably through a gastric tube (30 g of charcoal in 125 mL of water for a child; 55 g of charcoal in 250 mL of water for an adult). This should be followed by catharsis with magnesium sulfate (generally 250 mg per kg, given as a 20 percent solution) to facilitate propulsion through the gastrointestinal tract.(5)


Alkaline diuresis, using fluids containing sodium bicarbonate, is the key component in the treatment of salicylate toxicity. It should be considered for all patients whose salicylate levels exceed 35 mg per dL (2.50 mmol per L).(4) The effects of sodium bicarbonate therapy include correcting metabolic acidosis, alkalinizing the urine to promote salicylate excretion and preventing passage of salicylate into the central nervous system and other tissues by increasing the ionized (nonreabsorbable) fraction.(10)

Alkalinization should be done parenterally, rather than orally, using sodium bicarbonate. (Although acetazolamide (Diamox) increases urinary pH, it should not be used in this situation, because it produces systemic acidosis.(4)) It is important to add potassium chloride, which is needed by the kidney to excrete acid. During this process, urinary pH should be monitored hourly and maintained between 7.5 and 8.0.(5) Arterial blood gas determinations should also be performed frequently to ensure that the arterial pH does not exceed 7.5.

Intravenous fluids are essential to correct the inevitable dehydration and allow diuresis. Volume expansion and an initial bolus of bicarbonate can both be achieved by giving 500 mL of 5 percent dextrose in half-normal saline, along with one to two ampules of sodium bicarbonate, in an infusion of 20 mL per kg over 30 to 60 minutes. The next intravenous solution can consist of 5 percent dextrose in water with bicarbonate plus up to 40 mEq per L (40 mmol per L) of potassium. This should be infused at twice the rate of normal maintenance fluids to maintain adequate urine flow and provide additional bicarbonate.(4)


In general, hemodialysis (peritoneal dialysis or hemoperfusion) is indicated for severe toxicity that is not responsive to alkaline diuresis. Specific indications for hemodialysis include a salicylate level greater than 100 mg per dL (7.25 mmol per L) or rising serial levels.(11) Clinical indications for hemodialysis include aspiration pneumonia, pulmonary edema, convulsions, coma, persistent aciduria or uncontrollable acid-base dysfunction.(11)

Done Nomogram

The Done nomogram is a widely used tool for estimating the severity of salicylate toxicity.(12) It is of value only in acute intoxication and when the time of ingestion is known.(1) In addition to the initial salicylate level, the level should be determined at least six hours after ingestion.(4)

Other Considerations

There is considerable controversy over the relationship of Reye's syndrome and salicylate use in children. Some reports in the literature suggest that many cases of Reye's syndrome may actually represent subacute therapeutic salicylate poisoning,(6) but this has not been proved.

Also, patients taking central nervous system depressants in addition to salicylates may have blunting of the reflex ventilatory response, which can significantly worsen the existing acidosis and result in greater morbidity and mortality.(13)

Final Comment

Salicylate toxicity is a serious and complicated problem. Because of its frequency, family physicians and other primary care physicians must be knowledgeable about its management. Poison control hotlines should be utilized as a source of up-to-date information and clarification. Most important, physicians need to think of the diagnosis; it can be confirmed quickly using urine salicylate screening tests. Next, physicians of extensive interstitial fluid consistent with adult respiratory distress syndrome.

Laboratory tests on admission revealed a hemoglobin level of 13.1 g per dL (131 g per L) and a white blood cell count of 18,000 per mm cube (18.0 x 10 raised to 9 per L), with 89 percent (0.89) neutrophils. Serum electrolyte levels were as follows: sodium, 145 mEq per L (145 mmol per L); potassium, 3.3 mEq per L (3.3 mmol per L); chloride, 114 mEq per L (114 mmol per L), and bicarbonate, 9 mEq per L (9 mmol per L). On room air, the Po2 was 58 mm Hg. The initial serum salicylate level was 67.9 mg per dL (4.90 mmol per L).

The patient was given intravenous fluid therapy and bicarbonate. While still in the emergency department, she became progressively more dyspneic and ultimately required intubation prior to her transfer to the intensive care unit. Vigorous diuresis was maintained, and the salicylate level dropped in four hours to 61.7 mg per dL (4.45 mmol per L). Because the patient's condition appeared to have stabilized, dialysis was not performed.

Although the salicylate level continued to decline over the next few days, the patient's respiratory status gradually worsened. Three days after admission, the patient was started on antibiotic therapy for fever and increasing yellow secretions from the endotracheal tube. Her pulmonary status continued to worsen and on the fourth day of hospitalization, she was noted to have a creatine kinase level of 547 U per L (9.12 ukat per L) with 7.8 percent (0.8) MB fraction. There were no significant electrocardiographic changes. On the fifth day, the patient suffered a cardiac arrest and died.


A 19-year-old woman came to the emergency department after taking an overdose of Midol (ingredients: 454 mg aspirin, 14.9 mg cinnamedrine hydrochloride and 32.4 mg caffeine) in a suicide attempt. She reported that she had ingested 25 to 30 Midol tablets about two hours before coming to the emergency department. She complained of severe nausea, shortness of breath, vertigo and tinnitus.

On examination, the patient was in moderate distress due to nausea and shortness of breath. The physical examination was normal, as were the electrocardiogram and chest radiograph. Laboratory results included a hemoglobin level of 14 g per dL (140 g per L); serium sodium, 145 mEq per L (145 mmol per L); potassium, 3.6 mEq per L (3.6 mmol per L); chloride, 109 mEq per L (109 mmol per L) and carbon dioxide content, 17 mEq per L (17 mmol per L). An arterial blood gas determination, obtained while the patient was breathing 2 L of oxygen per minute, showed a pH of 7.47, Po2 of 123 mm Hg, Pco2 of 19, and serum bicarbonate level of 14 mEq per L (14 mmol per L). Salicylate level at the time of admission was 38.2 mg per dL (2.75 mmol per L).

Gastric lavage was performed, with the return of several pill fragments. Lavage was followed by activated charcoal therapy and the administration of intravenous fluids containing bicarbonate. About eight hours after ingestion, the salicylate level was 23.6 mg per dL (1.70 mmol per L).

By the second day of hospitalization, the patient's symptoms had resolved and she was much improved; the salicylate level that morning was 8.1 mg per dL (0.60 mmol per L). She was discharged in stable condition with psychiatric follow-up.

Definition of Toxicity

Salicylate toxicity can result from chronic or acute ingestion. Chronic intoxication results from excessive or therapeutic use over a period of 12 hours or longer. Most commonly, this is seen in elderly patients with arthritis or other musculoskeletal problems.(2) Acute intoxication is more likely to be the result of deliberate self-poisoning.(3) Chronic intoxication is seen less frequently and generally has a poorer outcome, because of a low index of suspicion and delay in proper treatment.(3)

In general, the toxic effects of salicylates are seen at serum levels above 30 mg per dL (2.15 mmol per L).(4) Therapeutic levels needed for the anti-inflammatory effects of salicylates range from 15 to 30 mg per dL (1.10 to 2.15 mmol per L).(4) The Food and Drug Administration recommends that the maximum dose of salicylate in a 70-kg person not exceed 3,900 mg in 24 hours for more than ten days.


Salicylates are weak acids, and thus are rapidly absorbed from the gastrointestinal tract. Peak serum salicylate levels occur within 12 hours of ingestion. Salicylate-induced pylorospasm and the dosage from (effervescent, enteric coated, etc.) can affect the rate of absorption.(4)

Toxic doses of salicylates have a much longer half-life than therapeutic doses.(4) This is due to a shift from first-order to zero-order kinetics as the salicylate metabolic pathways become saturated even at therapeutic levels.(3) When the enzymes are saturated, plasma salicylate concentration rises rapidly, and toxicity occurs.

Clinical Manifestations

Salicylate toxicity should be suspected in any patient with fever, hyperventilation, seizures or coma of uncertain etiology.(5) It is not uncommon for salicylate poisoning to be misdiagnosed initially as diabetic ketoacidosis.(1)

Initial sysmptoms of salicylate toxicity include tinnitus (followed by hearing loss), vertigo, nausea, vomiting, hyperventilation and agitation. As the serum level rises, metabolic acidosis ensues, resulting in more severe hyperpnea. This is followed by central nervous system deterioration (lethargy, confusion, delirium, convulsions and, eventually, coma).(6) Fever, due to uncoupling of oxidative phosphorylation, is also a common symptom.(5)

Other manifestations of salicylate toxicity include noncardiogenic pulmonary edema, renal tubular damage, bleeding disorders and hemolysis.(1) The pathophysiology of salicylate damage to the lungs and kidneys is still unclear, but a central factor seems to be a disruption of capillary permeability to protein, producing high concentrations of protein in both pulmonary edema fluid and urine. A similar phenomenon occurs in cerebral membranes and may produce cerebral edema.(7)



As with any acutely ill patient, initial treatment should focus on establishing an adequate airway, breathing and circulation. The history should include the amount of salicylates ingested, the type of preparation and the exact time of ingestion.

Important initial laboratory tests include an arterial blood gas determination and serum salicylate level, as well as serum sodium, potassium, urea nitrogen and glucose levels and coagulation profile. There are rapid screening tests, such as the ferric chloride test, to detect the presence of salicylic acid in the urine.(8)


Gastric emptying should be performed as early as possible by either induced emesis should attemtp to prevent drug absorption by gastric emptying and the use of activated charcoal.

Central to the management of these patients is the use of intravenous fluids and bicarbonate to produce alkaline diuresis and to correct acid-base and electrolyte abnormalities. These patients should be monitored closely and treated aggressively; in some patients, hemodialysis may be necessary. REFERENCES (1)Snodgrass WR. Salicylate toxicity. Pediatr Clin North Am 1986;33:381-91. (2)Grigor RR, Spitz PW, Furst DE. Salicylate toxicity in elderly patients with rheumatoid arthritis. J Rheumatol 1987;14:60-6. (3)Proudfoot AT. Toxicity of salicylates. Am J Med 1983;75(5A):99-103. (4)Goldfrank LR, Bresnitz EA, Hartnett L. Salicylates. In: Goldfrank LR, ed. Goldfrank's Toxicologic emergencies. 3d ed. Norwalk, Conn.: Appleton-Century-Crofts, 1986:233-42. (5)Haddad L. Salicylates. In: Tintinalli JE, Rothstein RJ, Krome RL, eds. Emergency medicine. New York: McGraw-Hill, 1985:291-3. (6)Prescott LF. Clinical features and management of analgesic poisoning. Hum Toxicol 1984;3(Suppl):75S-84S. (7)Niehoff JM, Baltatzis PA. Adult respiratory distress syndrome induced by salicylate toxicity. Postgrad Med 1985;78(1):117-9,123. (8)Berkow R, ed. Aspirin and other salicylate poisoning. In: The Merck manual of diagnosis and therapy. 15th ed. Rahway, N.J.: Merck Sharp & Dohme, 1987:1991-5. (9)Mofenson HC, Caraccio TR, Greensher J, D'Agostino R, Rossi A. Gastrointestinal dialysis with activated charcoal and cathartic in the treatment of adolescent intoxications. Clin Pediatr [Phila] 1985;24:678-84. (10)McGuigan MA. Death due to salicylate poisoning in Ontario. Can Med Assoc J 1986;135:891-4. (11)McGuigan MA. A two-year review of salicylate deaths in Ontario. Arch Intern Med 1987;147:510-2. (12)Done AK. Salicylate intoxication: significance of salicylate in blood in cases of acute ingestion. Pediatrics 1960;26:800-7. (13)Prescott LF, Critchley JA. Drug interactions affecting analgesic toxicity. Am J Med 1983;75(5A):113-6.

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