Spurious Hyperchloremia in the Presence of Elevated Plasma Salicylate: A Cohort Study

Abstract

Background: Acute metabolic acidosis is rarely associated with a reduced or negative anion gap (AG), but several case reports have described such an abnormality occurring in the setting of acute salicylate intoxication. The underlying cause of this phenomenon is unclear. Methods: In this retrospective cohort study, we reviewed our institutional database to identify all patients admitted for salicylate intoxication at Mayo Clinic (Rochester, MN, USA) from January 2010 through December 2012. Serum chloride was measured with the Cobas INTEGRA 400 plus electrode (expedited laboratory test) or Cobas 6000 (routine laboratory test). We compared blood chloride levels measured by the 2 devices in the presence of positive blood salicylate level. Results: Twelve adult patients with salicylate levels >20 mg/dL had markedly elevated chloride concentrations. The median (interquartile range) chloride level at admission was 120 (107–145) mmol/L on their initial laboratory studies, resulting in reduced or even negative AGs. None of the patients had bromide toxicity, nor did they have any other identifiable cause of hyperchloremia or decreased AG. Further testing of the same blood samples with an alternative measurement system (Roche Cobas 6000) yielded normal chloride values, indicating that falsely elevated chloride values with the initial testing led to the diminished or negative AG values. Conclusion: Circulating levels of salicylate can interfere with chloride measured by using routine techniques, resulting in spurious hyperchloremia outcomes and erroneous AG values. In patients with acute metabolic acidosis and abnormally reduced or negative AG, salicylate interference with chloride measurement should be suspected.

Case report: Salicylate intoxication can present with a normal anion gap metabolic acidosis depending on method used for measuring chloride

“…Besides case reports, 2 cohort studies have described patients with salicylate poisoning presenting with a normal or low AG in the presence of pseudohyperchloraemia. In these studies, both indirect and direct Cl‐ISEs, as well as advancing electrode age, have been associated with erroneous chloride readings 6,7 . Interference due to bicarbonate concentrations was not examined in these studies.…”

“…In these studies, both indirect and direct Cl-ISEs, as well as advancing electrode age, have been associated with erroneous chloride readings. 6,7 Interference due to bicarbonate concentrations was not examined in these studies.…”

Acute Bromide Intoxication in a Patient with Preserved Renal Function

“…Although rarely acknowledged, bromide ions are usually mistaken as chloride ions by automated analysis using an ionselective electrode [7], as observed in the gas analyses at our institute. Thus, the excessive intake of bromovalerylurea, a non-benzodiazepine sedative and hypnotic of the bromoureide class that contains bromide, is known to lead to spurious hyperchloremia, although salicylate is also reported to be associated with an increased level of chloride ions [8]. Of note, direct measurement of the ion level in the serum should be considered when spurious hyperchloremia is suspected by automated analysis.…”

Pseudohyperchloremia caused by the long-term use of phenobarbital and sodium bromide compound tablets: a case report

“…The electrodes are very selective; however, they are not free from interference. Numerous substances, such as salicylate (3), bromide, iodide, nitrate, thiocyanate, can affect the accurate detection of the Cl − level (4). As bromide has gradually been removed from prescription drugs, its interference with the detection of Cl − has largely been ignored.…”