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Less is more: We are administering too much protamine in cardiac surgery.少即是多:心脏手术中我们使用了过多的鱼精蛋白。
Ann Card Anaesth. 2021 Apr-Jun;24(2):178-182. doi: 10.4103/aca.ACA_26_19.
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Individualized heparin and protamine management improves rotational thromboelastometric parameters and postoperative hemostasis in valve surgery.个体化肝素和鱼精蛋白管理可改善瓣膜手术中的旋转血栓弹力测定参数及术后止血情况。
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Can the Minimum Protamine Dose to Neutralize Heparin at the Completion of Cardiopulmonary Bypass be Significantly Lower than the Conventional Practice?体外循环结束时中和肝素所需的最小鱼精蛋白剂量能否显著低于常规用量?
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Automated protamine dose assay in heparin reversal management after cardiopulmonary by pass.体外循环后肝素逆转管理中的鱼精蛋白剂量自动检测
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Prolonged Activated Clotting Time after Protamine Administration Does Not Indicate Residual Heparinization after Cardiopulmonary Bypass in Pediatric Open Heart Surgery.鱼精蛋白给药后活化凝血时间延长并不表明小儿心脏直视手术体外循环后存在残余肝素化。
Thorac Cardiovasc Surg. 2015 Aug;63(5):397-403. doi: 10.1055/s-0035-1554998. Epub 2015 Jun 29.
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Protamine reversal of heparin affects platelet aggregation and activated clotting time after cardiopulmonary bypass.鱼精蛋白逆转肝素对体外循环后血小板聚集和活化凝血时间有影响。
Anesth Analg. 1998 Oct;87(4):781-5. doi: 10.1097/00000539-199810000-00008.
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Impact of protamine dose on activated clotting time and thromboelastography in infants and small children undergoing cardiopulmonary bypass.鱼精蛋白剂量对接受体外循环的婴幼儿活化凝血时间和血栓弹力图的影响。
Paediatr Anaesth. 2013 Mar;23(3):233-41. doi: 10.1111/pan.12109. Epub 2013 Jan 2.
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Minimum protamine dose required to neutralize heparin in cardiac surgery: a single-centre, prospective, observational cohort study.心脏手术中中和肝素所需的最低鱼精蛋白剂量:一项单中心、前瞻性、观察性队列研究。
Can J Anaesth. 2023 Feb;70(2):219-227. doi: 10.1007/s12630-022-02364-4. Epub 2022 Dec 5.

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Protamine and Heparin Interactions: A Narrative Review.鱼精蛋白与肝素相互作用:一篇叙述性综述。
Ann Card Anaesth. 2024 Jul 1;27(3):202-212. doi: 10.4103/aca.aca_117_23. Epub 2024 Jul 4.
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Management of Microvascular Bleeding after On-Pump Cardiac Surgery in a Patient with Perioperative Diagnosis of Impairment of Platelet Responses to Adenosine Diphosphate: A Case Report and a Literature Review.围手术期诊断为血小板对二磷酸腺苷反应受损的心脏搭桥术后微血管出血的管理:一例报告及文献综述
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Protamine dose to neutralize heparin at the completion of cardiopulmonary bypass can be reduced significantly without affecting post-operative bleeding.鱼精蛋白中和体外循环结束时肝素的剂量可显著减少,而不会影响术后出血。
J Extra Corpor Technol. 2023 Sep;55(3):105-111. doi: 10.1051/ject/2023026. Epub 2023 Sep 8.

本文引用的文献

1
Anticoagulant and side-effects of protamine in cardiac surgery: a narrative review.心脏手术中抗凝剂与鱼精蛋白的副作用:一篇叙述性综述。
Br J Anaesth. 2018 May;120(5):914-927. doi: 10.1016/j.bja.2018.01.023. Epub 2018 Feb 26.
2
The Society of Thoracic Surgeons, The Society of Cardiovascular Anesthesiologists, and The American Society of ExtraCorporeal Technology: Clinical Practice Guidelines-Anticoagulation During Cardiopulmonary Bypass.美国胸外科医师学会、心血管麻醉医师学会和美国体外循环技术学会:体外循环期间抗凝的临床实践指南。
Ann Thorac Surg. 2018 Feb;105(2):650-662. doi: 10.1016/j.athoracsur.2017.09.061. Epub 2018 Jan 19.
3
2017 EACTS/EACTA Guidelines on patient blood management for adult cardiac surgery.2017年欧洲心胸外科学会/欧洲心胸麻醉学会成人心脏手术患者血液管理指南。
J Cardiothorac Vasc Anesth. 2018 Feb;32(1):88-120. doi: 10.1053/j.jvca.2017.06.026. Epub 2017 Sep 30.
4
A Pharmacokinetic Model for Protamine Dosing After Cardiopulmonary Bypass.体外循环后鱼精蛋白给药的药代动力学模型。
J Cardiothorac Vasc Anesth. 2016 Oct;30(5):1190-5. doi: 10.1053/j.jvca.2016.04.021. Epub 2016 Apr 28.
5
The toxicology of heparin reversal with protamine: past, present and future.鱼精蛋白用于肝素逆转的毒理学:过去、现在与未来
Expert Opin Drug Metab Toxicol. 2016 Aug;12(8):897-909. doi: 10.1080/17425255.2016.1194395. Epub 2016 Jun 6.
6
Impact of different dosage of protamine on heparin reversal during off-pump coronary artery bypass: a clinical study.不同剂量鱼精蛋白对非体外循环冠状动脉搭桥术中肝素逆转的影响:一项临床研究
Heart Lung Vessel. 2015;7(3):238-45.
7
Pharmacokinetic model of unfractionated heparin during and after cardiopulmonary bypass in cardiac surgery.心脏手术体外循环期间及之后普通肝素的药代动力学模型
J Transl Med. 2015 Feb 1;13:45. doi: 10.1186/s12967-015-0404-5.
8
A change in anticoagulation monitoring improves safety, reduces transfusion, and reduces costs in infants on cardiopulmonary bypass.抗凝监测的改变可提高体外循环下婴儿的安全性、减少输血并降低成本。
Paediatr Anaesth. 2015 Jun;25(6):580-6. doi: 10.1111/pan.12591. Epub 2014 Dec 21.
9
Protamine overdose and its impact on coagulation, bleeding, and transfusions after cardiopulmonary bypass: results of a randomized double-blind controlled pilot study.鱼精蛋白过量及其对心肺转流后凝血、出血和输血的影响:一项随机、双盲、对照的初步研究结果。
Clin Appl Thromb Hemost. 2014 Apr;20(3):290-5. doi: 10.1177/1076029613484085. Epub 2013 Apr 4.
10
Anticoagulation monitoring during extracorporeal circulation with the Hepcon/HMS device.使用Hepcon/HMS设备在体外循环期间进行抗凝监测。
Perfusion. 2012 May;27(3):214-20. doi: 10.1177/0267659112436632. Epub 2012 Feb 2.

少即是多:心脏手术中我们使用了过多的鱼精蛋白。

Less is more: We are administering too much protamine in cardiac surgery.

机构信息

Department of Anesthesia and Intensive Care, IRCCS San Raffaele Scientific Institute, Milan, Italy.

Department of Anesthesia and Intensive Care, IRCCS San Raffaele Scientific Institute; School of Medicine, Vita-Salute San Raffaele University, Milan, Italy.

出版信息

Ann Card Anaesth. 2021 Apr-Jun;24(2):178-182. doi: 10.4103/aca.ACA_26_19.

DOI:10.4103/aca.ACA_26_19
PMID:33884973
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8253032/
Abstract

CONTEXT

Protamine is routinely administered to neutralize the anticlotting effects of heparin, traditionally at a dose of 1 mg for every 100 IU of heparin-a 1:1 ratio protamine sparing effects-but this is based more on experience and practice than literature evidence. The use of Hemostasis Management System (HMS) allows an individualized heparin and protamine titration. This usually results in a decreased protamine dose, thus limiting its side effects, including paradox anticoagulation.

AIMS

This study aims to assess how the use of HMS allows to reduction of protamine administration while restoring the basal activated clotting time (ACT) at the end of cardiac surgery.

SETTINGS AND DESIGN

A retrospective observational study in a tertiary care university hospital.

SUBJECTS AND METHODS

We analyzed data from 42 consecutive patients undergoing cardiopulmonary bypass (CPB) for cardiac surgery. For all patients HMS tests were performed before and after CPB, to determine how much heparin was needed to reach target ACT, and how much protamine was needed to reverse it.

RESULTS

At the end of cardiopulmonary bypass, 2.2 ± 0.5 mg/kg of protamine was sufficient to reverse heparin effects. The protamine-to-heparin ratio was 0.56:1 over heparin total dose (a 44% reduction) and 0.84:1 over heparin initial dose (a 16% reduction).

CONCLUSION

A lower dose of protamine was sufficient to revert heparin effects after cardiopulmonary bypass. While larger studies are needed to confirm these findings and detect differences in clinically relevant outcomes, the administration of a lower protamine dose is endorsed by current guidelines and may help to avoid the detrimental effects of protamine overdose, including paradox bleeding.

摘要

背景

鱼精蛋白通常用于中和肝素的抗凝作用,传统剂量为每 100IU 肝素给予 1mg(1:1 比例),以达到鱼精蛋白节省效果,但这更多的是基于经验和实践,而不是文献证据。使用止血管理系统(HMS)可以进行个体化肝素和鱼精蛋白滴定。这通常会导致鱼精蛋白剂量减少,从而限制其副作用,包括矛盾抗凝。

目的

本研究旨在评估 HMS 的使用如何在心脏手术后恢复基础激活凝血时间(ACT)的同时减少鱼精蛋白的给药。

设置和设计

这是在一家三级护理大学医院进行的回顾性观察性研究。

受试者和方法

我们分析了 42 例连续接受体外循环(CPB)心脏手术的患者的数据。对所有患者均在 CPB 前后进行 HMS 检测,以确定达到目标 ACT 需要多少肝素,以及需要多少鱼精蛋白来逆转其作用。

结果

CPB 结束时,需要 2.2±0.5mg/kg 的鱼精蛋白来逆转肝素的作用。鱼精蛋白与肝素总剂量的比值为 0.56:1(降低 44%),与肝素初始剂量的比值为 0.84:1(降低 16%)。

结论

CPB 后,较低剂量的鱼精蛋白足以逆转肝素的作用。虽然需要更大的研究来证实这些发现并检测临床相关结局的差异,但目前的指南支持给予较低剂量的鱼精蛋白,这可能有助于避免鱼精蛋白过量的有害影响,包括矛盾性出血。