RCA for CRRT represents an established procedure in critically ill patients with contraindications for in vivo anticoagulation [1]. In view of patient safety and performance of CRRT the manufacturer Fresenius Medical Care recommends monitoring iCa concentrations in systemic and post filter samples to adjust calcium and citrate flow. However, the recommendations do not include information on the methods or devices to be used for measuring iCa concentrations. Instruments such as blood gas analyzers are frequently used in monitoring RCA due to their availability. While the iCa concentrations in the systemic samples were within or close to the physiological interval (1.12–1.32 mmol/L) the post filter samples were characterized by iCa concentrations clearly below 0.5 mmol/L [11]. We evaluated iCa measurements of 102 systemic and 116 post filter samples from patients undergoing RCA for CRRT (mulitFiltrate Ci-Ca® Continuous Veno-Venous Hemo Dialysis, CVVHD, Fresenius Medical Care, Bad Homburg, Germany) using six different commercially available blood gas analyzers.
To compensate the continuous loss of calcium and to avoid hypocalcemia during RCA in CRRT the calcium flow starts at 1.7 mmol calcium per liter of effluent. This calcium flow is then increased, left unchanged or decreased according to the systemic iCa results. The systemic iCa concentrations showed a good concordance between the different instruments indicating that they are suitable for controlling iCa substitution, indicating that they are suitable for controlling iCa substitution.
The manufacturer Fresenius Medical Care recommends to either raise, leave unchanged or lower the citrate flow depending on the measured concentration of iCa in post filter samples [7]. Our results indicate that the concentration of iCa measured in post filter samples differ considerably among the instruments as illustrated in Figs. 2 and 3. Presently available technology does not allow defining a reference method or value under post filter measuring conditions. When this ambiguity of the results of measurements is translated into clinical decisions based on the recommendations of Fresenius Medical Care the results from the same post filter sample could vary from a maximum increase of citrate flow (by 0.3 mmol/L) to a maximum decrease of citrate flow (by 0.3 mmol/L) depending on the instrument used. This is also underlined by the differing medians (Fig. 2).
For low iCa in post filter samples it is important to note that we do not know which result represents the best estimate because there is no suitable reference method or commutable reference material available. The detailed scheme given by the manufacturer needs to be adjusted according to the instrument used, and made available to all customers. It is noteworthy that the recommendations are based on a report referring to results from one single patient [7, 8] using an “ABL750” (Radiometer, Copenhagen, Denmark). Furthermore, studies refer to and confirm a target interval for post filter iCa of 0.25–0.35 mmol/L without disclosing the method used for the respective iCa measurement [12, 13].
We therefore propose not to use post filter iCa for controlling RCA in CRRT until a reference method has been established, or at least a thorough evaluation of the different measuring systems in combination with different dialysis systems has been conducted. The maximum average difference (0.33 mmol/L; 95 % CI ± 0.01 mmol/L) or the median difference (Δ 0.29 mmol/L; 0.21–0.50 mmol/L) in post filter iCa concentrations among the investigated devices are approximately as large as the complete interval of the recommendation scheme (Δ 0.30 mmol/L; 0.15–0.45 mmol/L) given by Fresenius Medical Care (Tables 1 and 2) [7, 8]. The investigated instruments are optimized for physiological iCa concentrations, which might make them less suitable for measuring the low iCa in blood with a high concentration of citrate. It has to be noted that post filter samples differ from whole blood in many respects: the material is characterized by low iCa concentrations and it contains citrate, which alters the pH and consequently affects the binding capacity of proteins for calcium. Furthermore, citrate might harm the sensors in the instruments and could affect measurements other than the iCa. As a consequence this could also harm patients not undergoing citrate dialysis and therefore should be subject to further studies.
From a clinical point of view RCA in CRRT can be controlled by using the systemic iCa and disregarding the post filter iCa. The post filter iCa should only be used to prove that the blood is anticoagulated but not to control citrate dose. Lowering citrate flow because of false low post filter iCa concentrations would increase the risk of coagulation in the extracorporeal circuit. Increasing citrate flow because of false high post iCa concentrations might provoke citrate intoxication. Both are potentially life-threatening complications in critically ill patients.