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Hypokalemia, Cardiac Failure, and Reporting NXY-059 Safety for Acute Stroke

Johns Hopkins University, Department of Neurology, Osler Medical Center, 7600 Osler Drive, Suite 307, Towson, MD 21204; heartdrug{at}aol.com

NXY-059, an alpha-phenyl-N-tert-butyl nitrone derivative, is a free radical–trapping agent presently in late clinical trials as a potential neuroprotectant limiting reperfusion injury following acute stroke. Two recent trials suggest that NXY-059 causes hypokalemia and associated cardiac disturbances. With regard to the mechanism of such association, most investigators agree that potent trapping of free radicals leads to the 11 beta-hydroxysteroid dehydrogenase blockade in kidneys, diminishing renal hydrocortisone oxidation and increasing K⁺ ion urine excretion. Importantly, potassium deficiency represents the major avoidable cause of the array of serious cardiac adverse reactions: QT-prolongation, Torsades de pointes and other life-threatening arrhythmias, and higher risks for perioperative cardiopulmonary resuscitation and cardiac death. Because a prime target for NXY-059 use will likely be acute strokes in the emergency room environment, the potential combination of the drug with intensive therapy including fluid infusions, particularly with diuretics, might be especially harmful because of the synergic depletion of potassium, which might also jeopardize the fate of the novel nitrone neuroprotectant.

Key Words: hypokalemia • NXY-059 • cardiac failures • safety • serious adverse events • clinical trials

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This Article Abstract Free Full Text (Free PDF) Free Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Saved Citations Download to citation manager Request Permissions Request Reprints Add to My Marked Citations Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Serebruany, V. L. Search for Related Content PubMed PubMed Citation Articles by Serebruany, V. L. Social Bookmarking                   What's this?