Neurocardiac toxicity of racemic D,L-lactate fluids.
Level 5 - mechanism / opinion, no new human data
Non-human animal in vivo and ex vivo laboratory experiment.
PubMed 7696135 · doi:10.1007/BF02691358
What was done
Researchers evaluated the neurological and cardiac toxicity of D-lactate compared to L-lactate across rat models. Rats received intraperitoneal infusions of sodium D-lactate or sodium L-lactate to reach 25 mM serum concentrations to assess behavioral effects. In 48-hour fasted rats, intravenous racemic D,L-lactic acid or L-lactic acid was infused to evaluate dose-dependent cardiac rate and rhythm changes. Additionally, isolated working rat hearts were perfused with 25 mM sodium D,L-lactate to differentiate direct myocardial effects from central nervous system-mediated toxicity.
What was found
Intraperitoneal sodium D-lactate (serum concentration 25 mM) induced coma equivalent to 75 mM ethanol, while equal quantities of sodium L-lactate produced no observable neurological effect. Intravenous infusion of D,L-lactic acid in fasted rats produced progressive cardiac rhythm disturbances: bradycardia at 1–2 mM serum D-lactate, QT prolongation at 2–3 mM, AV block with ectopic escape rhythms at 6–7 mM, and death via ventricular standstill or fibrillation at 11 mM. Intravenous L-lactic acid up to 25 mM caused no cardiac rhythm changes. Perfusion of isolated working hearts with 25 mM sodium D,L-lactate caused no rhythm or physiological changes.
Why it matters
The findings demonstrate that D-lactate—a component historically present in racemic clinical fluids such as Ringer's lactate—causes neurotoxicity and fatal centrally mediated cardiac arrhythmias that do not occur with physiological L-lactate.
Limits
The study was performed entirely in rat and isolated organ models, and exact sample sizes (n) were not reported in the abstract. Results cannot be directly extrapolated to establish safe human clinical thresholds without clinical pharmacokinetic and safety data.
Cited by
- supports Lactated Ringer's solution was historically prepared as a 50/50 racemic mixture of D-lactate and L-lactate.