Neurocardiac toxicity of racemicd,l-lactate fluids

Abstract

Racemicd,l-lactate has long been used in burn therapy as Ringer’s lactate and in peritoneal dialysis fluid for treatment of renal failure. The d-lactate component of this racemic mixture is known to cause two forms of neurological toxicity in patients: encephalopathy and, in a subset of the population, panic reaction. Here we demonstrate that coma, similar in degree to that produced by blood levels of 75 mM ethanol was induced in rats by the intraperitoneal infusion of sodiumd-lactate sufficient to raise serumd-lactate concentration to 25 mM, whereas infusion of equal quantities of sodiuml-lactate produced no observable neurological effect. We further demonstrate that the intravenous infusion of racemicd,l-lactic acid into 48-hour fasted rats produced serious disturbances of cardiac rate and rhythm leading to death. When serumd-lactate concentration had reached 1–2 mM there was bradycardia, at 2–3 mM prolongation of QT interval, at 6–7 mM AV block with ectopic escape rhythms, and at 11 mM death in ventricular standstill or fibrillation. In contrast, intravenous infusion ofl-lactic acid to blood levels of 25 mM failed to produce any change in cardiac rhythm. On the other hand, the isolated working heart, free of influence from the central nervous system, displayed no change of cardiac rhythm or physiological function when perfused with 25 mM sodiumd,l-lactate.