Role of acidic pH of intravenous fluids in subsequent development of metabolic acidosis- may not be what it seems.

Sir,

We extend our thanks to Singh et al. for drawing attention toward the controversies surrounding the use of acidic intravenous fluids (IVFs) infusion.[1] They have rightly mentioned the propensity of 5% dextrose (D5) and 0.9% saline (NS) to cause thrombophlebitis and other deleterious effects.[1] But unlike mentioned by the authors, current literature discusses the known and putative reasons for the pH of 5.5 of NS.[2] Dissolved CO2 from atmosphere, the ionic composition of the solution and inherent properties of the packaging material in which the solutions are supplied, are thought to determine it.[2] We believe that the same set of reasons may also explain the acidic pH (4.2) of D5.

Free acid activity is indicated by pH but the nondissociated acid molecules in a solution may not be characterized by the pH value.[23] Thus solutions with high titratable acid have reservoir of hydrogen ion (H+) irrespective of pH.[3] Citing the work of Gaudry et al. the authors attribute the acidity of IVFs to their method of sterilization, Gaudry et al. in their manuscript mentioned that the titratable acidity of majority of solutions under study (e.g. D5, NS) varied between 0.063 to 9.480 meq acid/l, depending on the method used for preparation and sterilization.[14] Gaudry et al. also mention that though many have measured the pH of common IVFs, not much data are available regarding their titratable acidity.[4] The work of Gaudry et al. dates back to 1972 and a PubMed search by us with the term ‘titratable acidity fluid/titratable acidity solution/titratable acidity infusion’ revealed only two studies relevant to this discussion. These studies date back to 1973 and 2005 and only the abstracts could be retrieved by us.[35] Though the in vitro pH of D5 and NS is acidic, their effect on H+ balance is probably negligible.[24] It may be because of their low titratable acid content.[4] But metabolic acidosis accompanies infusion of these solutions.[12467] This acidosis was explained by dilution of bicarbonate content in plasma.[267] Subsequently Stewart's physiochemical approach was used to describe the in vivo effect on acid base status by IVFs.[67] According to the later concept, the acid-base effect of an IVF is determined by the strong ion deference (SID) and the total weak acid concentration (ATOT) of the fluid.[67] pH falls with decreasing SID, increasing ATOT or CO2TOT(total CO2 content) / PCO2.[67] As the IVFs equilibrate with ECF, they alter SID of ECF, as SID of these IVFs defers appreciably from that of plasma.[67] SID of D5 and NS is 0, they decrease the SID of plasma and exert an acidifying effect.[67] These crystalloids are devoid of any weak acids and decrease ATOT of plasma due to its diluting effect causing alkalosis.[67] Whereas some colloids (e.g. albumin, gelatin) itself may contribute toward ATOT of plasma, thus, acidifying it.[67] Although CO2TOT/PCO2 also independently influences the pH of a biological system, its contribution in determining in vivo acid base activity of an IVF is generally regarded to be low as the concentration of dissolved CO2 is itself low (about 0.012 mmol/l).[267] But it should be kept in mind that IVFs with high CO2TOT have impact on intracellular acid base status, more during rapid administration or low perfusion states.[67] Contrary to the prediction by Singh et al. the pH of hypertonic saline (3%) is 5.8 and it causes more acidosis than NS because of its higher osmolarity that draws more water from other body fluid compartments.[67] Although the pH of Hartmann`s solution is 5, its in vivo SID is 27 meq/l, which is close to the ideal SID of 24 meq/l.[267] And despite its pH of 5, it is known to prevent infusion-related metabolic acidosis.[267] In-depth discussion on application of the concept of quantitative physical chemistry on the in vivo effect of acid base homeostasis is available.[67] The effect on plasma pH by solutions with same pH may be different and differing pH can have similar acid-base effects.[26] Thus, the effect of an IVF on plasma/ECF SID, ATOT and CO2TOT depending on the amount infused should be considered while predicting its possible in vivo effect on acid base status, not merely its in vitro pH.[1234567]