Discussion
fits, trauma
In this study we present a simple mathematical equation to calculate calcium-excretion in the ultrafiltrate during CVVH with citrate anticoagulation using routinely available parameters. Using this equation, we found that in a population of ICU patients treated with citrate anticoagulated CVVH, cumulative CVVH calcium balance was negative in the majority of patients even if plasma concentrations of ionized calcium were normal and well above the commonly advocated target level of 1.0 mmol/l [Our mathematical model fits the data very well. In an independent, separate population from our ICU, the mean absolute error in the estimation of calcium-loss by CVVH was 4.8 mmol/24 h (4.5% of mean daily calcium excretion). We found that the performance of our model was better in patients treated with the HF1400 filter than in patients treated with the ST150 filter, but the difference was only small (mean absolute error 4.0 ± 4.2 mmol/24 h vs. 5.6 ± 5.2 mmol/24 h, The performance of our model was better than that of two different mathematical models that were previously published [We found that in ICU patients, CVVH with citrate anticoagulation and calcium supplementation guided by the plasma ionized calcium concentration resulted in a negative CVVH calcium balance of mean − 12.5 ± 20.4 mmol/24 h. The mean cumulative CVVH calcium balance was dependent of the time on CVVH. Five percent of patients had a cumulative CVVH calcium balance that was more negative than − 475 mmol (19 g). Normal total body calcium is approximately 1000During the major part of this study we adhered to a target ionized calcium concentration of 0.9–1.1 mmol/l, in accordance with recommendations in the literature [During the last 6 months of our study, due to a change in our local CVVH protocol, we adhered to a higher ionized calcium target of 1.15–1.30 mmol/l. Interestingly, mean plasma concentrations of ionized calcium were only slightly higher compared with the period with lower target plasma calcium, but the rate of calcium supplementation was higher and CVVH calcium balance changed from negative to positive. The likely explanation for this is that plasma calcium levels were hardly determined by the rate of calcium supplementation but much more by homeostatic mechanisms of the body [Some limitations of our study should be discussed. First, from a theoretical point of view, it is likely that factors not included in our model could influence calcium excretion during CVVH. The concentration of citrate used for anticoagulation will influence the ratio of protein-bound and non protein-bound calcium in the blood of the CVVH circuit and thereby the filtration of calcium to the ultrafiltrate. Likewise, the sieving coefficient of a filter is influenced by the amount of time a filter is in use. However, citrate dose and type of filter did not add to the performance of our model, and the results of our validation show that the influence of these factors is very limited. Second, validation was performed in a separate patient population, but treated in the same ICU and using the same equipment and protocols. Before using the model in other settings, its performance should be confirmed in those circumstances. This could be easily done by direct measurement of total calcium concentration in the ultrafiltrate in a number of patients. Finally, in our calculation of calcium balance we only considered calcium losses by CVVH and calcium intake if given intravenously or as part of the CVVH substitution fluids. There is additional intake by enteral or parenteral feeding and some extra losses in the urine if there is some residual kidney function. However, in a study in trauma patients in the ICU calcium losses in urine were low (mean 0.2 mmol/day in patients on renal replacement therapy and mean 3.2 mmol/day in patients without renal replacement therapy) and negligible compared to losses in the CVVH ultrafiltrate [