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.
Highlights
Acute acidosis, lasting from minutes to a few days, can be respiratory or metabolic in nature (DuBose and Hamm, 2002; Kraut and Madias, 2014)
Acute respiratory acidosis occurs when the arterial carbon dioxide pressure PCO2 rises above its normal range (≈38 mm Hg to ≈42 mm Hg) and the arterial pH falls below its normal range, usually a result of impaired pulmonary function (Madias et al, 1979; Kraut and Kurtz, 2001; Kraut and Madias, 2010, 2012)
We have chosen Ctot = 0.15 M to be much lower than Carbicarb, which has Ctot = 0.667 M, so the resulting reduced osmolarity mixed-base (ROMB) solution would reduce the potential for adverse osmotic effects on blood cells
Summary
Acute acidosis, lasting from minutes to a few days, can be respiratory or metabolic in nature (DuBose and Hamm, 2002; Kraut and Madias, 2014). Sodium bicarbonate administration has failed to improve cellular function or to reduce mortality, even when it improves systemic acid-base balance (Cooper et al, 1990; Forsythe and Schmidt, 2000) This has been ascribed, in part, to exacerbation of intracellular acidosis in response to bicarbonate administration; administered bicarbonate ions HCO−3 react with protons to produce carbonic acid, H2CO3. By contrast to dissolved CO2, HCO−3 must enter via channels or transporters, and its movement into cells is significantly slower (Roos and Boron, 1981; Levraut et al, 1996; Hulikova and Swietach, 2014) This process, not inevitable in all circumstances in which bicarbonate is given, appears to be most frequent if the base is given when perfusion of tissues is low (Nielsen et al, 2002)
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