BACKGROUND Drug shortages are a frequent challenge in current clinical practice. Certain drugs, (e.g., protamine) lack alternatives and inadequate supplies can limit access to services. Conventional protamine dosing uses heparin ratio-based calculations for heparin reversal following CPB and may result in excess protamine utilization, and potential harm due to its intrinsic anticoagulation. We hypothesized that a fixed 250-mg protamine dose would be comparable, as measured by the activated clotting time, to a 1:1 (1 mg for every 100 U) protamine to heparin ratio-based strategy for heparin reversal and that protamine would be conserved. METHODS In a single-center, double-blinded trial, consenting elective adult cardiac surgical patients without pre-existing coagulopathy or ongoing anticoagulation, and a calculated initial heparin dose of ≥ 27500 U were randomized to receive, following CPB, protamine as a fixed dose (250 mg) or a ratio-based dose (1 mg:100 U heparin). The primary outcome was the activated clotting time following initial protamine administration, assessed by Student's t-test. Secondary outcomes included total protamine, the need for additional protamine, and the cumulative 24-h chest tube output. RESULTS There were 62 and 63 patients in the fixed- and ratio-based dose groups, respectively. The mean post-protamine ACT was not different between groups (-2.0 s, 95% CI -7.2 to 3.3 s, P = 0.47). Less total protamine per case was administered in the fixed-dose group (2.1 50-mg vials, 95% CI -2.4 to -1.8, P < 0.0001). There was no difference in the cumulative 24-h chest tube output (difference = -77 ml, 95% CI 220 to 65 ml, P = 0.28). CONCLUSIONS A 1: 1 heparin ratio-based protamine dosing strategy compared to a fixed 250-mg dose resulted in the administration of a larger total dose of protamine no difference in either the initial ACT or the amount postoperative chest-tube bleeding.

中文翻译：

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体外循环后肝素逆转的鱼精蛋白剂量：一项比较两种策略的双盲前瞻性随机对照试验。


背景 药物短缺是当前临床实践中常见的挑战。某些药物（例如鱼精蛋白）缺乏替代品，供应不足会限制获得服务。常规鱼精蛋白给药使用基于肝素比值的计算来计算 CPB 后的肝素逆转，并可能导致鱼精蛋白的过度使用，并且由于其固有的抗凝作用而可能造成危害。我们假设固定的 250 mg 鱼精蛋白剂量与基于 1：1 （每 100 U 1 mg） 鱼精蛋白比值的肝素逆转策略相当，并且鱼精蛋白将被保留。方法 在一项单中心、双盲试验中，同意的择期成人心脏手术患者没有预先存在的凝血病或持续的抗凝治疗，并且计算出的初始肝素剂量为 ≥ 27500 U，随机接受 CPB 后，鱼精蛋白作为固定剂量 （250 mg） 或基于比率的剂量 （1 mg：100 U 肝素）。主要结果是初始鱼精蛋白给药后的活化凝血时间，通过 Student 的 t 检验进行评估。次要结局包括总鱼精蛋白、需要额外的鱼精蛋白和 24 小时累积胸管排出量。结果 固定剂量组和基于比率的剂量组分别有 62 例和 63 例患者。鱼精蛋白后 ACT 的平均组间无差异 （-2.0 s，95% CI -7.2 至 3.3 s，P = 0.47）。固定剂量组每例给药的总鱼精蛋白较少 （2.1 个 50 mg 小瓶，95% CI -2.4 至 -1.8，P < 0.0001）。累积 24 小时胸管排出量无差异 （差异 = -77 ml，95% CI 220 至 65 ml，P = 0.28）。 结论 与固定 250 mg 剂量相比，基于 1：1 肝素比率的鱼精蛋白给药策略导致鱼精蛋白总剂量的给药量更大，初始 ACT 或术后胸管出血量没有差异。