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.

This is a preview of subscription content, access via your institution.

References

  1. Abbott, W.E., Shea, P. (1946). The treatment of temporary renal insufficiency (uremia) by peritoneal lavage.American Journal of Medical Science, 211:312–319.

    Google Scholar 

  2. Brandt, R.B., Siegel, S.A., Waters, M.G., Bloch, M.H. (1980). Spectrophotometric assay for D- (-) -lactate in plasma.Annals of Biochemistry, 102:39–46.

    Article  Google Scholar 

  3. Carr, D.B., Shih, V.E., Richter, J.M., Martin, J.B. (1982). D-lactic acidosis simulating a hypothalamic syndrome after bowel bypass.Annals Neurology, 11:195–197.

    Article  Google Scholar 

  4. Cechetto, D.F., Chen, S.J. (1990). Subcortical sites mediating sympathetic responses from insular cortex in rats.American Journal Physiology, 258:R245-R255.

    Google Scholar 

  5. Connor, H., Woods, H.F., Ledingham, J.G.G. (1983). Comparison of the kinetics and utilization of D(-)- and L(+) sodium lactate in normal man.Annals Nutrition Metabolism, 27:481–487.

    Article  Google Scholar 

  6. Ganter, G. (1924). Uber die beseitigung gifter stoffe aus dem blute durch dialyse.Münchener medinische Wochenschrifft, 70:1478–1480.

    Google Scholar 

  7. Haam, E.V., Fine A. (1932). Effect of Peritoneal Lavage in Acute Uremia. 30:396–399.

    Google Scholar 

  8. Hartmann, A.F. (1934). Theory and practice of parenteral fluid administration.Journal of American Medical Association, 103:1349–1354.

    Google Scholar 

  9. Neeley, J.R., Liebermeister, H., Battersby, E., Morgan, H.E. (1967). Effects of pressure development on oxygen consumption by the isolated rat heart.American Journal of Physiology, 212:804–814.

    Google Scholar 

  10. Nolph, K.D., Twardowski, Z.J., Khanna, R., Prowant, B.F., Ponferrada, L.P., Schmidt, L.M., Moore, H.L. (1990). Tidal peritoneal dialysis with racemic or L-lactate solutions.Peritoneal Dialysis International, 10:161–164.

    PubMed  Google Scholar 

  11. Oh, M.S., Phelps, K.R., Traube, M., Barbosa-Salyidar J.L., Boxhill, C., Carroll, H.J. (1979). D-lactic acidosis in a man with the short bowel syndrome.New England Journal of Medicine, 301:249–252.

    PubMed  Article  Google Scholar 

  12. Olendorf, W.H. (1971/72). Blood brain barrier permeability to lactate.European Neurology, 6:49–55.

    Google Scholar 

  13. Oppenheimer, S.M., Wilson, J.X., Guiradon, C., Cechetto, D.F. (1991). Insular cortex stimulation produces lethal cardiac arrhythmias: A mechanism of sudden death?Brain Research, 550:115–121.

    PubMed  Article  Google Scholar 

  14. Oppenheimer, S. (1992). The insular cortex and the pathophysiology of stroke-induced cardiac changes.Canadian Journal of Neurological Science, 19:208–211.

    Google Scholar 

  15. Oppenheimer, S.M., Cechetto, D.F., Hachinski, V.C. (1990). Cerebrogenic cardiac arrhythmias, cerebral electrocardiographic influences and their role in sudden death.Archives Neurology, 47:513–519.

    Google Scholar 

  16. Passonneau, J., Lowry, O.H. (1993).Enzymatic Analysis. Totowa, NJ: Humana, 188–190.

    Google Scholar 

  17. Pitts, F.N. Jr., McClure, J.N. (1967). Lactate metabolism in anxiety neurosis.New England Journal of Medicine, 277:1329–1336.

    PubMed  Article  Google Scholar 

  18. Reiman, E.M., Raichle, M.E., Robbins, E., Mintum, M.A., Fusselman, M.J., Fox, P.T., Price, J.L., Hackman, K.A. (1989). Neuroanatomical correlates of lactate-induced panic anxiety attack.Archives General Psychiatry, 46:493–500.

    Google Scholar 

  19. Rhoads, J.E. (1938).American Journal of Medical Science, 196:642.

    Article  Google Scholar 

  20. Rubin, J., Adair, C., Johnson, B., Bower, J.D. (1982). Stereospecific lactate absorption during peritoneal dialysis.Nephron.

  21. Slingeneyer, A., Canaud, B., Mion, C. (1983). Permanent loss of ultrafiltration capacity of the peritoneum in long-term peritoneal dialysis: An epidemiological study.Nephron, 33:133–138.

    PubMed  Article  Google Scholar 

  22. Thurn, J.R., Pierpoint, G.L., Ludvigsen, C.W., Eckfeldt, J.H. (1985). D-lactate encephalopathy.American Journal of Medicine, 79:717–721.

    PubMed  Article  Google Scholar 

  23. Tubbs, P.K. (1961). The metabolism of D-α hydroxyacids in animal tissues.Annals New York Academy of Science, 119:920–926.

    Article  Google Scholar 

  24. Veech, R.L., Fowler, R.C. (1986). Cerebral dysfunction and respiratory alkalosis during peritoneal dialysis with D-lactate containing fluids.American Journal of Medicine, 82:572–573.

    Google Scholar 

  25. Wolf, S. (1965).The Stomach. NY: Oxford University Press, 33–36, 111–112.

    Google Scholar 

  26. Wolf, S. (1967). The Jeremiah Metzer Lecture: Neural mechanisms in sudden cardiac death. American Clinical & Climatological Association, 79:158–176.

    Google Scholar 

Download references

Author information

Affiliations

Authors

Corresponding author

Correspondence to Stewart Wolf.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Chan, L., Slater, J., Hasbargen, J. et al. Neurocardiac toxicity of racemicd,l-lactate fluids. Integrative Physiological and Behavioral Science 29, 383–394 (1994). https://doi.org/10.1007/BF02691358

Download citation

Key Words

  • d,l-lactate
  • encephalopathy
  • panic reaction
  • arrhythmia