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A citrate concentration of 3–5 mmol/L should be attained before the filter to reach a post-filter ionised calcium level of 0.25–0.35 mmol/L (0.8–1.3 mg/dL) [15]. This is imperative to avoid coagulation inside the filter and the circuit. Correct prescription of citrate in any protocol requires, among others, dose adjustment to blood flow. Citrate is infused either separately or added to the replacement fluid. In the latter, currently most popular option, a fixed relation between citrate flow and blood flow is not guaranteed, as the flow of the replacement fluid varies with the ultrafiltration (UF) flow and the amount of removed fluid. For instance, when UF flow decreases or when a more negative fluid balance is desired, less citrate is administered and this may precipitate early filter clotting resulting in lower filter survival time. Adding citrate to the predilution fluid can overcome this problem.

Commercial citrate formulations contain tri-sodium citrate concentrations varying from 0.5 to 30%. The lower the concentration, the higher the volume infused (and thus the need for more storage space!) but also the lower the risk of citrate-related side-effects. Solutions also contain variable proportions of citric acid. Eventually, a citrate dextrose-A solution is used, which contains a fourfold higher citrate concentration than the 0.5% solutions (74.8 vs. 18 mmol/L) [15]. Equimolar citrate solutions may differ in sodium amount and buffer potential. For citrate dosing, a fixed blood flow/citrate flow relation is preferred, obviating the need for routine monitoring of anticoagulation in the extracorporeal circuit. If blood flow is kept constant and citrate dose adjusted to blood flow, metabolic control is recommended only when initiating the technique. After gaining sufficient experience, monitoring circuit anticoagulation can subsequently be limited to particular cases (e.g., unexplained early filter clotting). Some centers still prefer intensive monitoring of anticoagulation in the extracorporeal circuit and repeatedly titrate citrate dose because this, although unproven, tends to increase FLS. The anticoagulation effect is evaluated by measuring post-filter ionized calcium concentration (level below 0.35 mmol/L [0.8 and 1.3 mg/dL]), activated clotting time, or activated partial thromboplastin time [15, 17, 18]. Several algorithms for adjusting the citrate infusion rate are described in the literature. Yet, continuous monitoring of ionized calcium in the circuit remains the gold standard.