Serum salicylate

Corticosteroids will reduce serum salicylate levels and may decrease their effectiveness. 

Determination in Biological Fluids and Tissues All the advances in pharmacokinetics and drug metabolism described in Sections 7 and 8 would not have been possible without the availability of the proper analytical methods. The following is a tabulation of publications in this field, most of which have already been discussed in Section 5. It should be mentioned that a few publications talk about aspirin blood levels, but really mean salicylate levels. The following tabulation covers only those papers where aspirin was differentiated from other salicylates by chromatography or other means. It seems that the "workhorse" for serum salicylate levels is still the colorimetric (ferric-nitrate) method of Brodie, Udenfriend and Coburn153 published in 1944, or modifications thereof. Simplified versions (cf. 206) may lead to erroneous results under certain conditions.207 The method is also applicable for urinary metabolites after proper hydrolysis (cf. 208). For other methods restricted to salicylic acid, see Section 5.61. 

Tinnitus may be the first indication that the serum salicylic acid concentration is reaching or exceeding the upper therapeutic range. 

The nonacetylated salicylates are administered in doses up to 3-4 g of salicylate a day and can be monitored using serum salicylate measurements. 

Salicylism and death have occurred following topical application. In an adult, 1 g of a topically applied 6% salicylic acid preparation will raise the serum salicylate level not more than 0.5 mg/dL of plasma the threshold for toxicity is 30-50 mg/dL. Higher serum levels are possible in children, who are therefore at a greater risk for salicylism. In cases of severe intoxication, hemodialysis is the treatment of choice (see Chapter 58). It is advisable to limit both the total amount of salicylic acid applied and the frequency of application. Urticarial, anaphylactic, and erythema multiforme reactions may occur in patients who are allergic to salicylates. Topical use may be associated with local irritation, acute inflammation, and even ulceration with the use of high concentrations of salicylic acid. Particular care must be exercised when using the drug on the extremities of patients with diabetes or peripheral vascular disease. 

Salicylism and death have occurred following topical application. In an adult, 1 g of a topically applied 6% salicylic acid preparation will raise the serum salicylate level not more than 0.5 mg/dL of plasma the threshold for toxicity is 30-50 mg/dL. Higher serum levels are possible in children,... 

Aspirin, especially when used chronically in geriatric populations, is known for its side effects of GI discomfort and bleeding. Therefore, serum salicylate levels with regular and enteric-coated aspirin were compared in volunteers in a chronic disease hospital and residential home for the elderly [42], It was found that there was no significant difference between the blood levels reached with conventional... 

Hansten PD, Hayton WL. Effect of antacid and ascorbic acid on serum salicylate concentrations. J Clin Pharmacol 1980 20 236-31. 

Tawashii investigated the GI absorption of two polymorphs of aspirin, the stable and metastable forms, forms I and II, respectively. He found that the metastable form produced a 70% higher total serum salicylate levels than the stable form I. 

Serum salicylate concentrations above 3.6 mmol/1 are likely to be toxic, and concentrations of 5.4 mmol/1 can easily prove fatal. 

Chronic sahcylate intoxication is commonly associated with chronic daily headaches, lethargy, confusion, or coma. Since headache is a feature, it can easily be misdiagnosed if the physician is not aware that aspirin has been over-used. Depression of mental status is usually present at the time of diagnosis, when the serum salicylate concentration is at a peak. The explanation of depression, manifested by irritability, lethargy, and unresponsiveness, occurring 1-3 days after the start of therapy for aspirin intoxication, lies in a persistently high concentration of salicylate in the central nervous system, while the serum salicylate concentration falls to non-toxic values. The delayed unresponsiveness associated with sahcylate intoxication appears to be closely associated with the development of cerebral edema of uncertain cause. The encephalopathy that ensues appears to be directly related to increased intracranial pressure, a known effect of prostaglandin synthesis inhibitors it responds to mannitol (98). 

A 50-year-old woman with chronic renal insufficiency treated with acetazolamide for simple glaucoma developed confusion, cerebellar ataxia, and metabolic acidosis 2 weeks after starting to take aspirin for acute pericarditis (30). A diagnosis of salicylism was made despite low serum salicylate concentrations. 

Mean salicylate concentrations in those who used acetyl-salicylic acid as an analgesic were 8.3 qmol/l in 1985, and 16.5 qmol/l in 1988,1991, and 1998, while salicylate concentrations in subjects who used acetylsalicylic acid as an antiplatelet drug fell from 9.8 pg/ml in 1985 to 7.8 pg/ml in 1988, 3.0 qg/ml in 1991, and 0.8 pg/ml in 1998. This fall in serum salicylate concentrations reflects changes in the usual dose of acetylsalicylic acid. 

Concomitant use of heparin and oral anticoagulants can increase the risk for bleeding due to the antiplatelet effect of aspirin. In addition, use with alcohol can increase the risk of Gl bleeding. / spirin displaces a number of drugs (e.g., tolbutamide, nonsteroidal anti-inflammatory drugs [NSAIDs], methotrexate, phenytoin, and probenecid) from protein binding sites in the blood. Corticosteroid use can reduce serum salicylate levels by increasing the clearance of aspirin. 

Chronic salicylism presents clinically in a similar fashion to the acute situation, although it is often associated with a delay in diagnosis, and a higher morbidity and mortality. Chronic salicylism is more often associated with pronounced hyperventilation, dehydration, pulmonary edema, renal failure, coma, seizures, and acidosis. Chronic salicylism can occur at serum salicylate levels as low as 15mgdl. ... 

A useful qualitative screening test for salicylic acid is performed by adding a few drops of glacial acetic acid or 0.1N hydrochloric acid to 1 ml of urine, followed by 3 drops of 10% ferric chloride solution. A burgundy red color appears and persists if salicylic acid is present (color may turn reddish brown in the presence of phenothiazines). A serum salicylate level can be obtained in most laboratories. Commerically available test strips may be used with urine as well as serum or plasma to determine the presence of salicylic acid. These tests react only with salicylic acid and therefore do not work on stomach contents or pills, but any salicylate is hydrolyzed in the body to salicylic acid and would be present as such in blood or urine (15). 

Other laboratory tests to assist in assessment and treatment include blood pH, serum C02, or PC02 (any 2) serum sodium serum potassium, BUN blood glucose and urine pH and sp gr. These determinations and the serum salicylate level should be followed serially during therapy (15). 

The manifestations of salicylate toxicity are related to the peak level rather than the level of a given moment. For single-dose ingestions of salicylate, an estimate of the relative severity of the illness can be determined by use of a nomogram, provided the approximate time of ingestion and a single serum salicylate level are known (15). 

Tang etah (54) have also reported HPLC determination of serum salicylic acid and aspirin concentrations. Serum (0.1 ml) was treated 1 fj of carbamazepine (internal standard) solution (0.65 mg/ml), 0.1 ml of 0.1 M-phosphate buffer of pH 7.4, 10 //I of 21.25% H3P04 and 1.2 ml of ethyl ether prior to centrifugation at 4000 rpm... 

The absorption of normal doses of regular aspirin from the GI tract is generally rapid, with peak serum concentration achieved within 2 hours. This peak value may be delayed for 12 hours or longer for enteric-coated or slow-release formulations. Moreover, toxic doses of aspirin may form concretions or bezoars and produce pylorospasm, thereby delaying absorption. Serum salicylate in such instances may not reach maximum concentration for 6 hours or longer, an important consideration when the assessment of the severity of toxicity is based on such measurements. 

Aspirin absorption may be delayed when overdose quantities are consumed, especially of enteric-coated or slow-release preparations. This must be considered when interpreting serum salicylate values, especially for specimens obtained earlier than 6 hours after ingestion. Repeat testing within 2 to 3 hours is recommended to ensure that absorption is complete subsequent testing provides an indication of effectiveness of therapeutic intervention. Because of the aforementioned complications, proper assessment of salicylate intoxication requires sound clinical evaluation in combination with serum salicylate levels. 

Treatment for salicylate intoxication is directed toward (1) decreasing further absorption, (2) increasing elimination, and (3) correcting add-base and electrolyte disturbances. Activated charcoal binds aspirin and prevents its absorption. Elimination of salicylate may be enhanced by alkaline diuresis and in severe cases by hemodialysis." Sodium bicarbonate may be given to alleviate metabolic acidosis. Indications for hemodialysis include serum salicylate >1000 mg/L, severe CNS depression, intractable metabolic acidosis, hepatic failure with coagulopathy, and renal failure. ... 

Karnes HT, Beightol LA. Evaluation of fluorescence polarization immunoassay for quantitation of serum salicylates. Ther Drug Monit 1985 7 351-4,... 

Pulmonary edema has occurred occasionally with salicylate overdoses. The serum salicylate concentrations are often greater than 45 mg/dL, and the patients have other signs of toxicity, although some cases have been associated with concentrations in the usual therapeutic range. ... 

NSAIDs See Table 90-4 In the osteoarthritis chapter Scr or BUN, CBC every 2-4 weeks after starting therapy for 1-2 months salicylates serum salicylate levels if therapeutic dose and no response Same as initial plus stool guaiac every 6-12 months... 

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