Читать книгу Current Perspectives in Kidney Diseases - Группа авторов - Страница 32

Even though citrate is primarily used for extracorporeal anticoagulation, it has a significant effect on the acid-base balance as well. Anticoagulant and acid-base effects are not directly related. The degree of anticoagulation depends on the citrate dose and hypocalcemia (in the extracorporeal circuit), while the effect on the acid-base status depends on citrate metabolism.

The citrate metabolic load to the patient is the difference between the citrate infused into the CRRT circuit and the quantity of citrate lost in the effluent. In fact there is a direct positive correlation between the effluent volume and the amount of citrate lost [7]. With the more commonly reported citrate protocols, the citrate load is approximately 10–20 mmol/h. This citrate load to the patient is quickly metabolized through the aerobic pathways of the Krebs cycle in the liver, skeletal muscle, and kidney. For each 1 mmol citrate metabolized in the Krebs cycle, 3 mmol hydrogen ions are consumed and 3 mmol bicarbonate is generated, assuming that the citrate is completely metabolized. The resulting bicarbonate produced from citrate metabolism along with bicarbonate in replacement/dialysis fluids provides the buffer supply to the patient [8].

But the buffer power of a citrate solution also depends on the proportion of strong cations in the fluid counterbalancing the citrate anion. Generally, citrate is available at various concentrations of trisodium salt, but in some commercial solutions hydrogen is used (citric acid) instead of sodium. Hydrogen does not act as a buffer. The Stewart approach to the acid-base equilibrium [21] provides an interesting tool for a deeper comprehension of the buffering effect of citrate. After metabolism of citrate, the remaining sodium increases the strong ion difference (SID) in body fluids: SID = (Na⁺ + K⁺ + Ca²⁺ + Mg²⁺) – (Cl⁻ + lactate⁻). An increased SID produces alkalosis, while the infusion of a zero-SID fluid (such as saline) decreases the SID of body fluids and causes acidosis. As the citrate anion contrasts the cation load, the citrate solution has per se a zero SID (SID = [Na⁺ + K⁺ + Ca²⁺ + Mg²⁺] – [Cl⁻ + citrate³⁻]) and is therefore potentially acidifying. As a result of citrate metabolism, there appears an alkalizing effect due to the strong cation load.

Fig. 2. Change in the CRRT anticoagulation modality from 2011 to 2015 in our Nephrological Department and relative change in the difference between the prescribed and delivered dialysis doses. Columns represent the ratio of different anticoagulation modalities per each year (light grey stands for no anticoagulation; medium grey for heparin; dark grey for citrate). Over the years, we progressively increased the number of treatments with regional citrate anticoagulation modality, which, in 2015, reached near half of the overall number of CRRT performed in the intensive care units. Thanks to the reduction of the down-time due to filter clotting, the discrepancy between the prescribed and delivered dialysis doses (arrows) could be progressively reduced, from 22% in 2011 to 7% in 2015. For the same reason, we could effectively increase the prescribed dose.

Indeed, in conditions where citrate metabolism is reduced (severe liver failure, severe tissue hypoxia/hypoperfusion) even trisodium citrate can first cause some acidosis as a zero SID solution, but if citrate is metabolized, free strong cations produce their alkalinizing effect.

So, by the same anticoagulant effect, commercial solutions containing citric acid at least in part will have a lower alkalizing effect, and need to be taken into account in the prescription. In addition, the Stewart approach to acid-base equilibrium, is able to offer an explanation of the fact that different citrate formulations, although infused at similar flow rates and thus giving the patient the same citrate load, may exhibit divergent capacity and speed in correcting acidosis because of a substantial difference in solution SID, and in particular in the chloride content [22].