Falsely raised whole blood chloride caused by systemic absorption of cerium nitrate cream for burns

Abstract

Whole blood, serum or plasma chloride is almost exclusively measured by potentiometry with an ion-selective chloride electrode which utilizes membrane selectivity to chloride ions. Other anions such as bromide, iodide and thiosulphate can interfere but usually are not present in high enough concentration to cause significant cross reactivity. A patient from our burns unit had serial chloride measurements on a Radiometer ABL800 blood gas analyser. The results were higher in contrast to plasma measurements on the Abbott Architect Ci8200, which were within reference intervals and in line with the patient's pathophysiological status. This indicated a likely interference with the blood gas analyser chloride estimation. The chloride results on the ABL800 for 3rd, 4th and 5th day after the burn accident were 170, 137 and 119 mmol/L. Corresponding plasma chloride results on the Ci8200 were all around 105 mmol/L. Nitrate was found to be markedly elevated in these samples, and the results were 6.7, 4.9 and 1.1 mmol/L, respectively (reference limit-< 0.08 mmol/L). To further demonstrate nitrate was the causative agent, pooled plasma spiked with 7 mmol/L of sodium nitrate caused a rise in the ABL800 chloride from 105 to 202 mmol/L. Later we confirmed that the patient was topically medicated with cerium nitrate cream (Flammacerium Õ , Sinclair IS Pharma, UK) for his burns. In summary, the results clearly indicated nitrate was the interferent with the ABL800 chloride estimation and the source was the topical burns cerium nitrate cream.

Estimating blood nitrate concentration from interference on radiometer ABL800 chloride electrode

“…Sir, Nitrate species reportedly interfere with blood chloride measurement by ion selective electrodes (ISEs), which are commonly used to measure chloride in clinical laboratories. This phenomenon has been described with multiple instruments, including ABL700 and ABL800 (Radiometer Medical, Denmark), 1,2 and Cobas Integra (Roche Diagnostics, USA) 3 . There is evidence that nitrate anions do not interfere with chloride measurements on Ci8200 Architect (Abbott Diagnostics, USA).…”

“…Plasma nitrate concentrations can become significant after ingestion of sodium nitrate or from the use of topical creams containing cerium nitrate. 1 Historically, nitrite (NO 2 -) and nitrate (NO 3 -) poisonings have been rare occurrences, with few published reports. However, in recent years a number of online sources have promoted sodium nitrite ingestion as a means of committing suicide, including Exit International.…”

“…In particular, the relationship between nitrate concentration and chloride interference should be validated across ISEs of different lifespans, as this is a factor known to influence the magnitude of nitrate interference. 1 It will also be important to quantify the extent to which nitrite species interfere with chloride measurement, as it is thought to be the compound that causes methaemoglobinaemia in cases of nitrate ingestion. Samples with nitrate concentrations of 16 and 32 mmol/L were omitted because of a disproportionately high CV and measurements above the upper limit of detection, respectively.…”

Detection of Interfering Ions Using Ion Flux Phenomena in Flow-Through Cl-ISEs with Ion Exchange Membranes

“…In biological samples, such as serum, the type of relevant ionic species present is almost always the same and the concentrations of these species vary only in narrow ranges. − For this reason, calibration methods using calibrants containing interfering ions in concentration characteristic for the type of sample are sometimes used as a way to minimize effects of interfering ions on the analysis. However, even with that approach, in the case of specimens with unusual concentrations or types of interfering ions, the influence of interfering ions on high throughput analysis cannot be avoided and may affect the results of ion concentration measurements. − On the flip side, there are examples of using abnormal emf values as a means of detecting the possible presence of interfering ions . In order to deal with unusual specimens, the detection of interfering ions by using multiple electrodes for the same target ion but with different selectivities has been proposed…”