局部枸橼酸抗凝在肾脏替代治疗中应用的数学建模与临床验证

Mathematical modeling and clinical validation of regional citrate anticoagulation in renal replacement therapy

目的本研究建立了计算局部枸橼酸抗凝(RCA)期间钙和枸橼酸需要量的通用算法,并与传统试错法方案进行比较,以评估该算法的有效性和安全性。方法20例接受血液透析滤过的患者被随机分配至算法组和试错法组行RCA方案,每组10例。抗凝采用4%枸橼酸钠从滤器前滴入,补钙采用10%葡萄糖酸钙从外周静脉单独输注。操作前检测患者的血钙和血细胞比容(HCT),确定目标血钙值(Ca Target)。根据临床需要设定血流量,净超滤量,前、后置换液量。RCA期间每隔1~2 h测定废液量、滤器后和血离子钙(iCa)水平、血钙、废液中总钙浓度。建立一室模型,以模拟钙在滤器中混合、稀释和丢失的过程。并分别建立枸橼酸钠输注方程、钙输注方程,计算算法组的弥散系数(k Dis)值。结果在RCA期间,算法组有2例患者,试错组有8例患者的血iCa水平为0.8~<0.9 mmol/L,两组患者构成比的差异有统计学意义(P=0.007)。算法组无患者血iCa水平<0.8 mmol/L,试错法组有3例<0.8 mmol/L;算法组有2例,试错法组有1例患者的滤器后iCa水平>0.4 mmol/L,两组患者构成比的差异均无统计学意义(P值分别为0.060、0.531)。试错法组8例患者需要调整补钙速率,每例需调整2~4次;算法组则无患者需额外调整补钙速率,两组间差异有统计学意义(P=0.001)。两组患者按照治疗前血钙水平分别分为<2.0 mmol/L(低钙血症)、2.0~2.4 mmol/L(正常血钙)和>2.4 mmol/L(高钙血症)3个亚组。算法组高钙血症患者在RCA初期血钙快速下降,低钙血症患者血钙则快速上升,其后3个亚组血钙均向靶目标水平趋近。该组3个亚组患者的iCa水平变化也呈类似趋势。试错法组的3个亚组患者血钙和iCa水平均在治疗开始后第1小时明显下降,其后两者水平逐渐上升。算法组低钙血症患者起始钙输入值为正值,而高钙血症患者为负值,并逐渐向零轴靠近。试错法组,无论低钙还是高钙血症患者的钙输入值,起始皆为负值,随后低钙血症和正常血钙患者钙输入值在干预下大幅升高。肾脏替代治疗期间两组患者总的钙输入值与治疗前钙水平呈负相关。算法组的k Dis值为0.91±0.08。结论本研究提供了一种安全、有效的RCA补钙需要量的计算方法,其可协助维持RCA期间血钙和iCa水平稳定而无需额外调整补钙速率。

Objective To construct a general mathematical model for calculating the calcium and citrate requirements during regional citrate anticoagulation(RCA),and assess the safety and effectiveness of the algorithm compared to the traditional trial\|and\|error.Methods During hemodiafiltration treatments with calcium-free replacement solution,20 participants were equally randomized to receive algorithm-based or trial-and-error RCA protocol.Four percents sodium citrate was infused through prefilter for anticoagulation,and 10%calcium gluconate was infused from the peripheral vein for calcium supplement.Serum calcium and hematocrit(HCT)levels were measured before operation to determine the target value of serum calcium(Ca Target).Blood flow,net ultrafiltration volume and pre/post fluid exchange volume were set according clinical needs.The effluent volume,post-filter and plasma ionized calcium(iCa),and calcium in the sera and effluents were measured at an interval of 1 to 2 h.A model was established to simulate the mix,dilution and loss of calcium in the filter.The infusion equations of sodium citrate and calcium were established respectively,and the dispersion coefficient(k Dis)of algorithm group was calculated.Results Plasma iCa was 0.8-<0.9 mmol/L in 2 patients of algorithm group and 8 patients of trial-and-error group during RCA(P=0.007).Plasma iCa was less than 0.8 mmol/L in 3 patients of trial-and-error group and no patient of algorithm group(P=0.060).Post-filter iCa was more than 0.4 mmol/L in 2 patients of algorithm group and 1 patient of trial-and-error group(P=0.531).There was no additional adjustment of the calcium supplementary rate in algorithm group,while there was additional adjustment(2-4 times per patient)in 8 patients in trial-and-error group(P=0.001).According to plasma calcium level before treatment,the patients in the two groups were divided into three subgroups:hypocalcemia(<2.0 mmol/L),normal calcium(2.0-2.4 mmol/L)and hypercalcemia(<2.4 mmol/L).In the algorithm group,the plasma calcium of hypercalcemia patients decreased rapidly at the beginning of RCA,while that of hypocalcemia patients increased rapidly,and then the plasma calcium of three subgroups approached the target level;the change of iCa level in the three subgroups also showed a similar trend.In three trial-and-error subgroups,plasma calcium and iCa levels decreased significantly at the first hour after treatment,and then increased gradually.In the algorithm group,the initial calcium input of hypocalcemia patients was positive,while that of hypercalcemia patients was negative,and they gradually approached the zero axis.In the trial-and-error group,the calcium input of both hypocalcemia and hypercalcemia patients was negative at the beginning of treatment,and then the calcium input of hypocalcemia and normal calcium patients increased significantly.Total calcium input was negatively correlated with preoperative serum calcium level in both groups during renal replacement therapy(RRT).The value of k Dis was 0.91±0.08 in algorithm group.Conclusion A safe and effective algorithm has been constructed for calculating calcium supplement.It can help to maintain plasma calcium stability without additional adjustment during RCA.