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Clinical Chemistry 52: 1603-1604, 2006; 10.1373/clinchem.2006.069658
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(Clinical Chemistry. 2006;52:1603-1604.)
© 2006 American Association for Clinical Chemistry, Inc.


Letters to the Editor

Equimolar Ammonia Interference in Potassium Measurement on the Osmetech OPTI Critical Care Analyzer

Mary O. Carayannopoulos1, Timothy R. Wilhite3, Lakshmi Reddy1, Michael Landt1, Carl H. Smith1 and Dennis J. Dietzen1,2,a

Departments of1 Pediatrics and 2 Pathology and Immunology, Washington University School of Medicine, St. Louis, MO
3 St. Louis Children’s Hospital, St. Louis, MO

aAddress 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 Dietzen_D{at}kids.wustl.edu.


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+) sensor on this system consists of a macrocyclic ion-selective cryptand covalently coupled to an o-alkoxyaniline fluorophore. In the presence of K+, internal fluorescence quenching is reduced, and fluorescence emission is proportional to the K+ 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 methylmalonic acidemia (mut0 subtype) and plasma ammonia >3000 µmol/L, apparent K+ 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+ measurement observed on the OPTI CCA was the result of ammonia interference.

We obtained a plasma pool (endogenous ammonia = 150 µmol/L) and supplemented it with increasing concentrations of NH4Cl and LiCl. Subsequent K+ 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+ when measured on the OPTI CCA (Fig. 1 ). Ammonium chloride up to 5000 µmol/L had no effect on K+ measured with the Vitros 250, ABL 735, GEM, or i-STAT. LiCl had no impact on K+ measured with the OPTI or with any other platform tested (data not shown).


Figure 1
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Figure 1. Effect of ammonium on potassium measurements.

Plasma was supplemented with the indicated concentrations of NH4Cl, and subsequent potassium measurements were performed on the OPTI CCA ({blacksquare}), Vitros 250 ({blacktriangleup}), ABL 735 (•), IL Gem ({diamondsuit}), and i-STAT ({blacktriangledown}). Data shown are the means of 3 replicate measurements (respective SD is less than the size of the symbol for each point). Addition of NH4Cl was 5% of the total sample volume at each concentration indicated. Least-squares regression equation for OPTI: K+ (mmol/L) = 0.0012 x added NH4+ (µmol/L) + 4.1 (r = 0.987).

The physiologic concentrations of K+ (3.5–4.5 mmol/L) and NH4+ (10–50 µmol/L) in the circulation are drastically different, but their respective ionic radii are very similar (0.133 nm vs 0.143 nm) (6). Therefore, NH4+ has a greater potential than Li+ (ionic radius = 0.068 nm) to cross-react with various K+-selective ionophores. Valinomycin-based ion-selective electrodes display selectivity factors of 50 to 100 for K+ over NH4+ (7). With this degree of selectivity, even severe hyperammonemia would not be expected to impact K+ measurements. Our present data show that the mean (SD) selectivity factor of the OPTI K+ cryptand over NH4+ is 0.7 (0.1) (n = 20). Under normal circumstances, this lack of selectivity is not evident, as the K+ concentration exceeds NH4+ concentration by 100-fold. In cases of severe hyperammonemia, however, K+ measurements are artifactually increased to the same extent as the NH4+ concentration. K+ measurements on the OPTI CCA in patients with hyperammonemia should be interpreted with this limitation in mind.


References

  1. Bachmann C. Mechanisms of hyperammonemia. Clin Chem Lab Med 2002;40:653-662.[CrossRef][ISI][Medline] [Order article via Infotrieve]
  2. Nassogne MC, Heron B, Touati G, Rabier D, Saudubray JM. Urea cycle defects: management and outcome. J Inherit Metab Dis 2005;28:407-414.[CrossRef][ISI][Medline] [Order article via Infotrieve]
  3. Cohn RM, Roth KS. Hyperammonemia, bane of the brain. Clin Pediatr (Phila) 2004;43:683-689.[Abstract/Free Full Text]
  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;64:1544-1551.[ISI][Medline] [Order article via Infotrieve]
  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;125:1468-1469.
  6. Crystal ionic radii of the elements. Weast RC Astle MJ Beyer WH eds. CRC Handbook of Chemistry and Physics 64th ed. 1983:F-170 CRC Press Boca Raton, FL. .
  7. Eyal E, Rechnitz G. Mechanistic studies on the valinomycin-based potassium electrode. Anal Chem 1971;43:1090-1093.[CrossRef]



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C. Lin and J. K. Tusa
Equimolar Ammonia Interference in Potassium Measurement on the Osmetech OPTI CCA: A Reply.
Clin. Chem., November 1, 2006; 52(11): 2116 - 2117.
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