Evaluation of the Ability of CRRT to Remove Amino Acids According to Differences in the Hemofilter and Filtration Volume

Appropriate nutritional therapy is closely associated with
the complication rate and clinical course in critically ill patients...

state of amino acids. In this study, we evaluated the ability of CRRT to remove amino acids depending on differences in the hemofilter and filtration volume by using an experimental model of a closed circuit.

Materials and Methods
A closed circulation system of CRRT was constructed by using a high-calorie total parenteral nutrition (TPN) solution formulated with amino acids (ELNEOPA-NF No. 2 Injection, Otsuka Pharmaceutical Factory, Inc., Naruto, Japan) as a test solution.
The composition and concentrations of amino acids in ELNEOPA-NF No. 2 Injection are shown in Table 1. The modality of CRRT was continuous hemofiltration (CHF) using SUBPACK-Bi (Nipro Tokyo, Japan) as a replacement fluid, and the flow rate of the test solution was set to 100 mL/min. CRRT was performed for 4 hours with recirculation in the test solution bag, and concentrations of various amino acids were determined by liquid chromatography/ mass spectrometry. The sampling point of the test solution was just before the hemofilter, and samples were collected at 0, 15, 30, 60, 120, 180 and 240 minutes after starting recirculation. Three types of membranes including polysulfone (PS), polymethyl methacrylate (PMMA) and AN69ST membranes were used as hemofilters for the experimental CRRT. The flow rate of the replacement fluid (QF) was set to 600mL/hr (which is the amount for insurance adaptation in Japan). In addition, when using the PS membrane, changes in concentrations of amino acids were determined at a QF of 2000mL/ min.

Discussion
We evaluated the ability of CRRT to remove amino acids using a closed circuit and a high-calorie TPN solution as the test solution.
After starting CRRT, concentrations of amino acids gradually decreased, but there was no difference depending on the type of hemofilter or electric charge state of amino acids. However, decreased concentrations of amino acids at an increased filtration volume indicated that high-volume CRRT may increase the amount of amino acids removed. In this study, the ability of CRRT to remove amino acids was investigated by using three types of hemofilters: a PS membrane as a filtration membrane and PMMA and AN69ST membranes as adsorption membranes. For large molecular weight substances such as cytokines, the mechanism of removal seems to be mainly filtration in the PS membrane and adsorption in the PMMA and AN69ST membranes. The AN69ST membrane, which has been developed as a cytokine adsorption membrane, is designed to have a negatively electric charged surface itself and to have reduced ability for removal of albumin, which is negatively charged.
Since the amino acids evaluated in this study were small molecular weight substances, it was considered that the membrane material of the hemofilter and the electric charged state had no influence on the ability of CRRT to remove amino acids. On the other hand, the results suggested that the amount of amino acids removed increases with an increase in filtration volume. It has been reported that increased filtration volume up to 25mL/kg/hr may increase the therapeutic effect compared with QF of 600mL/hr (equivalent to 12mL/kg/hr for body weight of 50kg), which is the amount for insurance adaptation in Japan [11]. However, it is considered that removal of small essential substances such as amino acids cannot be overlooked if the volume of filtration is increased up to 2000mL/hr (equivalent to 40 mL/kg/hr for body weight of 50kg).
We perform tapering-CHF that increases the filtration volume in the early stage of sepsis and then gradually decrease its filtration volume according to the hemodynamic state or changes in lactate concentration [12].

Conclusions
The ability of CRRT to remove amino acids depending on the type of hemofilter and the volume of filtration was evaluated by using closed circuit models. The amount of amino acids removed as small molecules may not be different regardless of the type of hemofilter. However, caution should be taken when using highvolume CHF because the concentrations of amino acids clearly decreased with increase in the filtration volume.