Effects of the resuscitation fluid and the hemoglobin based oxygen carrier (HBOC) excipient on the toxicity of the HBOC: Ringer's D,L-lactate, Ringer's L-lactate, and Ringer's ketone solutions

Artif Cells Blood Substit Immobil Biotechnol. 2006;34(6):601-6. doi: 10.1080/10731190600974087.

Abstract

Hemoglobin based oxygen carriers (HBOC) are resuspended in "excipients" consisting of Ringer's D,L-lactate containing antioxidants to prevent methemoglobin formation during storage. Investigators have reported cardiac arrhythmias following infusion of Ringer's D,L-lactate solution. Studies have shown that D-lactate stimulates human granulocytes to generate oxygen free radicals and L-lactate inhibits glycolysis. Patients receiving HBOC in Ringer's D,L-lactate excipient are also resuscitated or hemodiluted with Ringer's lactate solution. Oxygen-free radicals generated by Ringer's D,L-lactate and HBOC may oxidize nitric oxide in endothelial cells, causing the vasoconstrictor effects reported following HBOC infusion, and activate NF-kappab and the apoptotic cascade. The combination of Ringer's D,L-lactate and HBOC in Ringer's D,L-lactate excipient may be responsible for the severe adverse events observed in clinical studies of HBOC.Veech has recommended replacing the 27 mM of lactate in Ringer's with 27 mM D-betahydroxybutyrate (BHB). BHB reduces the generation of oxygen free radicals by mitochondria and human granulocytes.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.
  • Review

MeSH terms

  • Animals
  • Blood Substitutes / adverse effects*
  • Excipients / adverse effects*
  • Fluid Therapy
  • Humans
  • Isotonic Solutions / adverse effects*
  • Isotonic Solutions / chemistry
  • Isotonic Solutions / pharmacology
  • Rats
  • Ringer's Lactate
  • Ringer's Solution

Substances

  • Blood Substitutes
  • Excipients
  • Isotonic Solutions
  • Ringer's Lactate
  • Ringer's Solution