Treatment of Acidified Blood Using Reduced Osmolarity Mixed-Base Solutions

Abstract

We hypothesize that reduced osmolarity mixed-base (ROMB) solutions can potentially serve as customizable treatments for acidoses, going beyond standard solutions in clinical use, such as 1.0 M sodium bicarbonate. Through in silico quantitative modeling, by treating acidified canine blood using ROMB solutions, and by performing blood-gas and optical microscopy measurements in vitro, we demonstrate that ROMB solutions having a high proportion of a strong base, such as disodium carbonate or sodium hydroxide, can be effective in reducing carbon dioxide pressure PCO2 while raising pH and bicarbonate ion concentration without causing significant osmotic damage to red blood cells, which can occur during rapid administration of hypertonic solutions of weak bases. These results suggest that a ROMB solution, which is composed mostly of a strong base, could be administered in a safe and effective manner, when compared to a hypertonic solution of sodium bicarbonate. Because of the reduced osmolarity and the customizable content of strong base in ROMB solutions, this approach differs from prior approaches involving hypertonic solutions that only considered a single molar ratio of strong to weak base. Our calculations and measurements suggest that custom-tailored ROMB solutions merit consideration as potentially efficacious treatments for specific types of acidosis, particularly acute metabolic acidosis and acute respiratory acidosis.

The therapeutic importance of acid-base balance

“…However, in practice, manifestation of the side effects associated with NaHCO 3 administration is not a foregone conclusion [61] , [62] . Alternative vehicles for intravenous alkali delivery such as Na 2 CO 3 and CaCO 3 produce less CO 2 per neutralized H + and impose less of an osmotic stress [63] . Carbicarb is a mixture of NaHCO 3 and Na 2 CO 3 that does not cause intracellular acidification [64] , [65] .…”

Intravenous Sodium Bicarbonate in Treating Patients With Severe Metabolic Acidemia

“…Development of additional bases with beneficial properties might also prove useful in the treatment of acidemia. 23 Finally, the reduction in intracellular pH during acute acidemia might impair cellular function, not only by compromising the function of critical cellular enzymes and other proteins, but also by accelerating the activity of proteins or pathways that could be deleterious. Studies in animals have indicated that activation of the myocardial sodium/hydrogen exchanger 1 (NHE1) during lactic acidosis contributes to cellular dysfunction and mortality.…”