Salicylate Toxicity Workup

Initial and serial salicylate levels are important in the evaluation of salicylate toxicity. The absolute level should not detract from the importance of careful and repeated clinical evaluation. Immediately begin therapy in symptomatic patients. Do not wait for the salicylate levels to return from the laboratory.

If managing an acute or acute-on-chronic ingestion, repeat the salicylate serum level 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.

The therapeutic range of salicylate is 15-30 mg/dL. Patients are often symptomatic at salicylate concentrations higher than 40-50 mg/dL. Patients with salicylate concentrations approaching or exceeding 100 mg/dL usually have serious or life-threatening toxicity. Patients with chronic poisoning who have levels of 60 mg/dL or greater often have serious toxicity.

One cautionary note is to always confirm the units of measurement with the laboratory. Traditional units are milligrams per deciliter; however, many laboratories report salicylate concentrations in milligrams per liter or micrograms per milliliter, both of which differ by a factor of 10 from the traditional units. For example, a salicylate concentration of 100 mg/dL is seriously toxic, but a concentration of 100 mg/L is subtherapeutic. A concentration of 100 mg/L is equal to a concentration of 10 mg/dL.

Monitoring peak concentration

In overdoses, the peak serum concentration may not occur for 4-6 hours, so concentrations obtained before that time may not reflect peak levels. levels from 15-30 mg/dL are considered to be within the therapeutic range. Signs and symptoms of toxicity begin to appear at levels higher than 30 mg/dL. A 6-hour salicylate level higher than 100 mg/dL is considered potentially lethal and is an indication for hemodialysis. Chronic ingestion can increase the half-life to longer than 20 hours.

In significant ingestions, serum salicylate levels should be monitored at least every 2 hours until a peak has been reached and then every 4-6 hours until the peak falls into the nontoxic range.

Serum electrolytes and renal function studies (BUN and creatinine levels)

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 alkalization therapy. Electrolyte levels should be obtained every 2-4 hours when the patient is being alkalized, because severe hypokalemia and other electrolyte abnormalities can occur.

Urinalysis

Monitor and maintain an alkaline urine pH every 2 hours during alkalization therapy. Maintain a urine pH of 7.5-8. It is important to monitor the serum pH, as well as the urine pH. Excessive sodium bicarbonate induces severe alkalemia and/or hypernatremia. Consider obtaining a urine specimen for a qualitative toxicology screen.

Imaging studies

A chest radiograph is indicated if evidence of severe intoxication, pulmonary edema, aspiration pneumonitis, or hypoxemia is present.

Consider an abdominal radiograph if an aspirin concretion is suspected. A concretion should be suspected if salicylate levels are rising or fail to decrease despite treatment with gastric lavage and/or activated charcoal.

Other methods of identifying gastric salicylate pharmacobezoars include the following:

• Ultrasonography
• Computed tomography (CT) scanning of the abdomen
• Endoscopy

Other tests

Other studies to obtain include the following:

• Serum glucose level
• Serum acetaminophen levels - These should always be obtained in any unknown overdose
• Liver function tests
• Prothrombin time and activated partial thromboplastin time
• CBC count
• Hepatic, hematologic, and coagulation profiles - Obtain for patients with clinical evidence of moderate to severe toxicity (eg, those that need to be admitted for inpatient care)
• ECG

The toxicity of salicylates does not always correlate well with serum levels, and the levels are often less helpful in patients with long term exposure. Serum salicylate levels may correlate only moderately with clinical manifestations. In acute ingestion, levels may sometimes be high without significant clinical signs, whereas levels in patients with chronic ingestion that are in the high therapeutic range may be associated with significant clinical toxicity. Therefore, levels must always be interpreted and correlated with the history and clinical findings.

Done nomogram

The Done nomogram was formulated in 1960 to assist physicians in predicting the severity of salicylate intoxication based on a serum level and a known time of ingestion. The nomogram was based primarily on previously healthy pediatric patients with acute single-salicylate ingestion. However, clinical application of the nomogram has several limitations. The nomogram is used only to evaluate a single acute ingestion. In contrast to the Rumack-Matthew nomogram,^[6] the Done nomogram indicates severity of toxicity based on a 6-hour level of non–enteric-coated aspirin rather than the need for antidotal therapy. Currently, the Done nomogram is regarded as not very useful and is seldom used by clinicians.

Historically, qualitative determination for the presence of salicylates was rapidly performed in the emergency department by adding a few drops of 10% ferric chloride (FeCl₃) to 1 mL of urine. If salicylates are present, the solution changes to a brown/purple color. Positive results with the urine ferric chloride test only indicate that a salicylate is present; however, even very small amounts of a salicylate, such as a single ingested aspirin tablet, can give a positive test result. Most emergency departments no longer perform this test and instead obtain a plasma salicylate level because these results are now rapidly available from almost all hospital laboratories and are much more useful clinically.

Arterial blood gas (ABG) testing should be performed to evaluate for the presence of acid-base disturbances. Primary respiratory alkalosis may occur, followed by concomitant primary metabolic acidosis resulting from production of lactic acid, metabolites, and other organic acids. Therefore, the most common abnormality, especially in adults, is a mixed acid-base disturbance (a primary respiratory alkalosis plus a primary metabolic acidosis). The presence of this finding should raise the suspicion of the possibility of an aspirin overdose.

Repeated blood gases and serum salicylate levels should be done every 2 hours, until the acid-base status is improving, levels are falling, and the patient is clinically improving.