Chadha Vimal, Garg Uttam, Warady Bradley A, Alon Uri S
Section of Pediatric Nephrology, The Children's Mercy Hospital, University of Missouri at Kansas City, Kansas City, Missouri, USA.
Pediatr Nephrol. 2002 Oct;17(10):819-24. doi: 10.1007/s00467-002-0963-6. Epub 2002 Sep 7.
Anticoagulation is usually indicated in patients receiving continuous renal replacement therapy (CRRT) to prevent clotting of the extra-corporeal circuit. While heparin is the most frequently used anticoagulant, regional citrate anticoagulation is becoming the preferred choice in those patients at high risk for bleeding. However, it has been widely claimed that to avoid citrate toxicity, CRRT with citrate anticoagulation should utilize diffusive clearance (e.g., continuous venovenous hemodialysis). We studied citrate clearance in five children who received citrate anticoagulation during CRRT with a COBE PRISMA machine and an M-60 (AN-69) filter. The blood flow rate ranged from 50 to 150 ml/min (2.1-8.0 ml/kg per min). Citrate was infused in the circuit circulation as an acid citrate dextrose (ACD) solution at a rate of 1.6-3.7% of the blood flow rate to maintain the circuit ionized calcium (iCa) <0.5 mmol/l. Calcium-free replacement fluid with reduced alkali (NaHCO3 20 mEq/l) was infused in pre-filter mode at a rate of 1,800-2,000 ml/h per 1.73 m(2). In a separate central line, CaCl2 (0.8%) was infused (rate 25-50% of ACD infusion) to maintain systemic iCa between 1.0 and 1.3 mmol/l. Citrate concentration was measured using an enzymatic assay. Total CRRT duration was 1,224 h. Twenty-four filters were changed due to clotting, with a mean filter life of 51 h. Mean (range) citrate levels (mmol/l) were (1) before initiating CRRT ( n=2): patient baseline 0.13 (0.1-0.15), (2) during CRRT ( n=7): circuit 4.54 (3.95-6.25), effluent 4.31 (3.95-5.46), and patient 0.69 (0.30-1.13). Sieving coefficients for urea and citrate were 0.88-0.97 and 0.88-1.0, respectively. Citrate clearance (31-38 ml/min per 1.73 m(2)) was similar to that of urea (31-38 ml/min per 1.73 m(2)), and when evaluated in two patients, remained unchanged after substituting half of the convective clearance [continuous venovenous hemofiltration (CVVH)] by diffusive clearance [continuous venovenous hemodiafiltration (CVVHDF)]. The post-filter citrate load (mean+/-SD) delivered to the five patients during CRRT was 1.06+/-0.62 mmol/kg per hour. With the exception of alkalosis in one patient, no other complications were observed. Renal function recovered in all patients. We conclude that citrate anticoagulation in children is feasible, effective, and safe. Sufficient citrate clearance to prevent its toxic accumulation is achieved by convective clearance (CVVH) alone and diffusive clearance (CVVHDF) does not appear to be mandatory when utilizing citrate anticoagulation during CRRT.
接受连续性肾脏替代治疗（CRRT）的患者通常需要进行抗凝，以防止体外循环回路凝血。虽然肝素是最常用的抗凝剂，但对于出血风险高的患者，局部枸橼酸盐抗凝正成为首选。然而，人们普遍认为，为避免枸橼酸盐中毒，采用枸橼酸盐抗凝的CRRT应采用弥散清除（如连续性静脉-静脉血液透析）。我们研究了5例在使用COBE PRISMA机器和M-60（AN-69）滤器进行CRRT期间接受枸橼酸盐抗凝的儿童的枸橼酸盐清除情况。血流速度为50至150 ml/分钟（2.1 - 8.0 ml/千克每分钟）。枸橼酸盐以酸性枸橼酸盐葡萄糖（ACD）溶液的形式以血流速度的1.6 - 3.7%注入回路循环，以维持回路游离钙（iCa）<0.5 mmol/升。无钙且碱含量降低（NaHCO₃ 20 mEq/升）的置换液以前滤器模式以每1.73 m² 1800 - 2000 ml/小时的速度注入。在一条单独的中心静脉导管中，注入CaCl₂（0.8%）（速度为ACD注入速度的25 - 50%），以维持全身iCa在1.0至1.3 mmol/升之间。采用酶法测定枸橼酸盐浓度。CRRT总时长为1224小时。因凝血更换了24个滤器，滤器平均使用寿命为51小时。枸橼酸盐水平（mmol/升）的均值（范围）为：（1）CRRT开始前（n = 2）：患者基线0.13（0.1 - 0.15）；（2）CRRT期间（n = 7）：回路4.54（3.95 - 6.25），流出液4.31（3.95 - 5.46），患者0.69（0.30 - 1.13）。尿素和枸橼酸盐的筛系数分别为0.88 - 0.97和0.88 - 1.0。枸橼酸盐清除率（每1.73 m² 31 - 38 ml/分钟）与尿素清除率（每1.73 m² 31 - 38 ml/分钟）相似，在两名患者中进行评估时，将一半的对流清除[连续性静脉-静脉血液滤过（CVVH）]替换为弥散清除[连续性静脉-静脉血液透析滤过（CVVHDF）]后，清除率保持不变。CRRT期间输送给这5例患者的滤器后枸橼酸盐负荷（均值±标准差）为每小时1.06±0.62 mmol/千克。除1例患者出现碱中毒外，未观察到其他并发症。所有患者肾功能均恢复。我们得出结论，儿童枸橼酸盐抗凝是可行、有效且安全的。仅通过对流清除（CVVH）即可实现足够的枸橼酸盐清除以防止其毒性蓄积，在CRRT期间采用枸橼酸盐抗凝时，弥散清除（CVVHDF）似乎并非必需。
