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Equimolar ammonia interference in potassium measurement on the Osmetech OPTI Critical Care Analyzer.

To the Editor:

Ammonia is a toxic byproduct of amino acid metabolism, and increased blood concentrations of ammonia are associated with severe encephalopathy (1). In mammals, ammonia is detoxified in the liver via formation of urea (2). Hyperammonemia can result from hepatic failure, enzymatic deficiencies of the urea cycle or defects in ornithine transport [e.g., HHH syndrome (hyperornithinemia, hyperammonemia, hyperhomocitrullinuria)], or it may be secondary to other organic acidopathies (3). The hyperammonemia observed in methylmalonic acidemia is thought to arise because accumulated propionyl CoA interferes with formation of N-acetylglutamate, an obligatory activator of carbamyl phosphate synthase, the initial step in urea synthesis (4).

The Osmetech (Roswell, GA) OPTI Critical Care Analyzer (CCA) is a point-of-care instrument used to monitor electrolytes and blood gases; at our institution it is used to monitor critically ill patients during transport from outside facilities. The unique potassium ([K.sup.+]) sensor on this system consists of a macrocyclic ion-selective cryptand covalently coupled to an o-alkoxyaniline fluorophore. In the presence of [K.sup.+], internal fluorescence quenching is reduced, and fluorescence emission is proportional to the [K.sup.+] concentration in the specimen. The sensor displays negligible interference from pH, calcium, or sodium (5).

During the recent transport to our hospital of an infant with methylma-Ionic acidemia ([mut.sup.0] subtype) and plasma ammonia >3000 [micro]mol/L, apparent [K.sup.+] concentrations were increased (>8 mmol/L) when measured by the OPTI CCA but were within reference values when measured in plasma by both direct and indirect ion-specific electrodes. We hypothesized that the increased [K.sup.+] measurement observed on the OPTI CCA was the result of ammonia interference.

We obtained a plasma pool (endogenous ammonia = 150 [micro]mol/L) and supplemented it with increasing concentrations of NH4C1 and LiCl. Subsequent [K.sup.+] measurements were performed on the OPTI CCA and on the following whole-blood direct ion-selective electrode platforms: ABL 735 (Radiometer), GEM Premier (Instrumentation Laboratories), and i-STAT (Abbott Point of Care). Potassium measurements were also performed with the Vitros 250 (Ortho Clinical Diagnostics). In the presence of increasing concentrations of ammonium chloride, we observed an equimolar increase in apparent [K.sup.+] when measured on the OPTI CCA (Fig. 1). Ammonium chloride up to 5000 [micro]mol/L had no effect on [K.sup.+] measured with the Vitros 250, ABL 735, GEM, or i-STAT. LiC1 had no impact on [K.sup.+] measured with the OPTI or with any other platform tested (data not shown).


The physiologic concentrations of [K.sup.+] (3.5-4.5 mmol/L) and [NH.sub.4.sup.+] (10-50 [micro]mol/L) in the circulation are drastically different, but their respective ionic radii are very similar (0.133 rim vs 0.143 nm) (6). Therefore, [NH.sub.4.sup.+] has a greater potential than [Li.sup.+] (ionic radius = 0.068 nm) to cross-react with various [K.sup.+]-selective ionophores. Valinomycin-based ionselective electrodes display selectivity factors of 50 to 100 for [K.sup.+] over [NH.sub.4.sup.+] (7). With this degree of selectivity, even severe hyperammonemia would not be expected to impact [K.sup.+] measurements. Our present data show that the mean (SD) selectivity factor of the OPTI [K.sup.+] cryptand over [NH.sub.4.sup.+] is 0.7 (0.1) (n = 20). Under normal circumstances, this lack of selectivity is not evident, as the [K.sup.+] concentration exceeds [NH.sub.4.sup.+] concentration by 100-fold. In cases of severe hyperammonemia, however, [K.sup.+] measurements are artifactually increased to the same extent as the [NH.sub.4.sup.+] concentration. [K.sup.+] measurements on the OPTI CCA in patients with hyperammonemia should be interpreted with this limitation in mind.


(1.) Bachmann C. Mechanisms of hyperammonemia. Clin Chem Lab Med 2002;40:653-62.

(2.) Nassogne MC, Heron B, Touati G, Rabier D, Saudubray JM. Urea cycle defects: management and outcome. J Inherit Metab Dis 2005;28:40714.

(3.) Cohn RM, Roth KS. Hyperammonemia, bane of the brain. Clin Pediatr (Phila) 2004;43:683-9.

(4.) Coude FX, Sweetman L, Nyhan WL. Inhibition by propionyl-coenzyme A of N-acetylglutamate synthetase in rat liver mitochondria: a possible explanation for hyperammonemia in propionic and methylmalonic acidemia. J Clin Invest 1979; 64:1544-51.

(5.) He H, Mortellaro MA, Leiner MJ, Fraatz RJ, Tusa JK. A fluorescent sensor with high selectivity and sensitivity for potassium in water. J Am Chem Soc 2003;125:1468-9.

(6.) Crystal ionic radii of the elements. In: Weast RC, Astle MJ, Beyer WH, eds. CRC Handbook of Chemistry and Physics, 64th ed. Boca Raton, FL: CRC Press, 1983:F-170.

(7.) Eyal E, Rechnitz G. Mechanistic studies on the valinomycin-based potassium electrode. Anal Chem 1971;43:1090-3.

Mary O. Carayannopoulos [1] Timothy R. Wilhite [3] Lakshmi Reddy [1] Michael Landt [1] Carl H. Smith [1] Dennis J. Dietzen [1,2]

Departments of [1] Pediatrics and [2] Pathology and Immunology Washington University School of Medicine St. Louis, MO [3] St. Louis Children's Hospital St. Louis, MO

* Address correspondence to this author at: Department of Pediatrics, Box 8208, Washington University School of Medicine, 660 S. Euclid, St. Louis, MO 63110. Fax 314-286-2892; e-mail

DOI: 10.1373/clinchem.2006.069658
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Title Annotation:Letters
Author:Carayannopoulos, Mary O.; Wilhite, Timothy R.; Reddy, Lakshmi; Landt, Michael; Smith, Carl H.; Dietz
Publication:Clinical Chemistry
Article Type:Letter to the editor
Date:Aug 1, 2006
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