Green T P, Isham-Schopf B, Irmiter R J, Smith C, Uden D L, Steinhorn R H
Department of Pediatrics, College of Pharmacy, University of Minnesota, Minneapolis.
Clin Pharmacol Ther. 1990 Aug;48(2):148-54. doi: 10.1038/clpt.1990.129.
Heparin anticoagulation is necessary to prevent clotting during procedures involving the extracorporeal circulation of blood. Our preliminary observations suggested that heparin was inactivated in the extracorporeal circuit during extracorporeal membrane oxygenation. We tested this hypothesis by comparing heparin pharmacokinetics in five infants during extracorporeal circulation with kinetics, respectively determined in each patient and in the isolated circuit immediately after discontinuation of the procedure. Heparin clearance was 1.6 +/- 0.5 ml/kg/min in the patient and 2.1 +/- 0.8 ml/kg/min in the separated circuit. In each patient, the total of heparin clearances in the patient and circuit, 3.7 +/- 1.0 ml/kg/min, was virtually identical with the heparin clearance during the procedure, 3.8 +/- 1.9 ml/kg/min (r = 0.94, p less than 0.01). We conclude that more than one half of the heparin administered to infants during extracorporeal membrane oxygenation is eliminated by the extracorporeal circuit itself or by blood components in the circuit. These data explain the relatively large heparin doses needed to maintain anticoagulation in infants during extracorporeal circulation. In light of these findings, a reexamination of the normal mechanisms of elimination of heparin activity appears to be warranted.
在涉及血液体外循环的手术过程中,肝素抗凝对于防止血液凝固是必要的。我们的初步观察表明,在体外膜肺氧合过程中,肝素在体外循环回路中被灭活。我们通过比较五名婴儿在体外循环期间的肝素药代动力学与在手术结束后立即分别在每个患者体内和分离的回路中测定的动力学来验证这一假设。患者体内肝素清除率为1.6±0.5 ml/kg/min,分离回路中为2.1±0.8 ml/kg/min。在每个患者中,患者体内和回路中肝素清除率之和为3.7±1.0 ml/kg/min,与手术期间的肝素清除率3.8±1.9 ml/kg/min几乎相同(r = 0.94,p<0.01)。我们得出结论,在体外膜肺氧合期间给予婴儿的肝素中,超过一半是由体外循环回路本身或回路中的血液成分清除的。这些数据解释了在体外循环期间维持婴儿抗凝所需相对大剂量肝素的原因。鉴于这些发现,似乎有必要重新审视肝素活性消除的正常机制。