Esposito R A, Culliford A T, Colvin S B, Thomas S J, Lackner H, Spencer F C
J Thorac Cardiovasc Surg. 1983 Feb;85(2):174-85.
Precise guidelines for heparin administration and neutralization during cardiopulmonary bypass (CPB) are not established. To a large extent, the uncertainty originates from a disparity between the heparin dosage, the plasma heparin concentration, and the clinical heparin effect. We investigated these relationships in 44 consecutive patients at New York University Medical Center. Following serial loading doses of heparin (2 and 4 mg/kg) there was a wide variation in both the measured clinical heparin effect (activated clotting time--ACT) and the plasma heparin concentration. When the Act was compared to the heparin concentration, there was no linear relationship noted after heparin does commonly employed for CPB. The calculated heparin sensitivity varied over a fourfold range and was not related to the baseline antithrombin III activity. At the completion of CPB, heparin was neutralized with a 2 mg/kg protamine dose regardless of the total heparin dose. Heparin levels fell from 4.17 +/- 1.29 to 0.19 +/- 0.20 units/ml. Additional protamine was given to 49% of the patients as the ACT had not returned to pre-heparin levels. The total protamine dose rarely exceeded 3 mg/kg. This technique resulted in the administration of 30% to 50% less protamine than predicted by other commonly used protocols. In the subsequent 4 hours after protamine administration, heparin levels remained insignificant. Mild heparin rebound was found in two patients (4.5%) but was not associated with excessive bleeding. Following bypass a comparison of heparin levels and ACTs demonstrated the ACT to be a poor indicator of residual circulating heparin. These data show: (1) that neither the heparin dosage nor the plasma heparin concentration can accurately predict the magnitude of the clinical heparin effect in patients undergoing CPB and emphasize the importance of the ACT as the best available measurement of safe anticoagulation, (2) heparin "rebound" was not clinically significant, and (3) heparin was neutralized with 2 to 3 mg/kg protamine in virtually all patients, regardless of the total heparin dose.
体外循环（CPB）期间肝素给药及中和的精确指南尚未确立。很大程度上，这种不确定性源于肝素剂量、血浆肝素浓度与临床肝素效果之间的差异。我们在纽约大学医学中心对44例连续患者进行了这些关系的研究。在给予肝素连续负荷剂量（2和4mg/kg）后，所测临床肝素效果（活化凝血时间——ACT）和血浆肝素浓度均存在很大差异。将ACT与肝素浓度进行比较时，在CPB常用的肝素剂量后未发现线性关系。计算出的肝素敏感性变化范围达四倍，且与基线抗凝血酶III活性无关。CPB结束时，无论肝素总剂量如何，均用2mg/kg鱼精蛋白剂量中和肝素。肝素水平从4.17±1.29单位/毫升降至0.19±0.20单位/毫升。49%的患者因ACT未恢复到肝素前水平而给予额外的鱼精蛋白。鱼精蛋白总剂量很少超过3mg/kg。与其他常用方案预测的相比，该技术使鱼精蛋白的用量减少了30%至50%。在给予鱼精蛋白后的随后4小时内，肝素水平保持较低。在两名患者（4.5%）中发现轻度肝素反跳，但与出血过多无关。体外循环后，肝素水平与ACT的比较表明，ACT是循环中残留肝素的不良指标。这些数据表明：（1）肝素剂量和血浆肝素浓度均不能准确预测接受CPB患者的临床肝素效果大小，并强调ACT作为安全抗凝最佳可用测量指标的重要性；（2）肝素“反跳”在临床上不显著；（3）几乎所有患者无论肝素总剂量如何，均用2至3mg/kg鱼精蛋白中和肝素。
