Ann Thorac Surg 2011;91:608-610. doi:10.1016/j.athoracsur.2010.07.088
© 2011 The Society of Thoracic Surgeons
Case Reports
Successful On-Pump Coronary Artery Bypass Without Using Protamine
Vivek Srivastava, MRCSEda,
Palanikumar Saravanan, FRCAb,
Jeanette Abraham, ACPc,
John Au, FRCP, FRCSa,*
a Department of Cardiothoracic Surgery, Victoria Hospital, Blackpool, United Kingdom
b Department of Cardiothoracic Anesthesia, Victoria Hospital, Blackpool, United Kingdom
c Department of Clinical Perfusion, Victoria Hospital, Blackpool, United Kingdom
Accepted for publication July 22, 2010.
* Address correspondence to Mr Au, Department of Cardiothoracic Surgery, Victoria Hospital, Whinney Heys Rd, Blackpool, FY3 8N, United Kingdom (Email: mr.au{at}bfwhospitals.nhs.uk).
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Abstract
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A 48-year-old woman presented with a history of angina and breathlessness on exertion. She was diagnosed to have critical left main stem coronary artery disease along with a blocked right coronary artery. She was also allergic to protamine. After multidisciplinary consultation, it was decided to use heparin without protamine for reversal. She underwent successful on-pump coronary artery bypass grafting (CABG) without excessive blood loss. The disadvantages were a longer total operating time and the use of blood products to achieve normal coagulation. This case report describes the successful management of this complex problem.
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Introduction
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Cardiac operations using cardiopulmonary bypass (CPB) were greatly facilitated by the discovery of heparin by Jay McLean in 1915. Unfractionated heparin (UFH) has been the drug of choice for achieving anticoagulation for CPB because of the low cost, ease of administration and monitoring, and the easy reversibility by protamine. However, protamine is contraindicated in patients with known allergy or hypersensitivity to protamine. We present a patient with protamine allergy requiring urgent coronary artery bypass grafting using CPB who was successfully managed without using protamine.
A 48-year-old woman presented with angina and breathlessness. She had a history of stenting of the right coronary artery after an inferior wall myocardial infarction 4 years earlier. Comorbidities included hypertension, emphysema, and asthma. A coronary angiogram revealed critical left main coronary artery stenosis and a blocked right coronary artery, with good left ventricular function. She had a history of allergy to different species of fish that precipitated urticaria and angioedema. Fish allergy has been reported to increase the risk of protamine allergy [1], and she underwent an intradermal skin test, which was positive for protamine sensitivity. (Further immunologic tests were not performed at this point because of the urgent nature of the operation.) After multidisciplinary consultation, we decided to proceed with on-pump coronary artery bypass grafting using heparin, but without using protamine. We decided to titrate the dose of the heparin with the use of the heparin-dose-response (HDR) test.
Before commencing the case, the HDR test (Medtronic Hepcon HMS system, Medtronic, Minneapolis, MN) was used to estimate that 120 mg of heparin was the precise amount required for a target activated clotting time of 400. This level of heparinization was maintained by intermittent measurement of heparin concentration using the HDR test. Additional heparin was administered where indicated (Fig 1).
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Fig 1. The temporal relation of the activated clotting time (ACT, triangles) and heparin concentration (circles) is shown as measured using the Medtronic Hepcon system at various perioperative intervals. Heparin was added as indicated during cardiopulmonary bypass (CPB) to maintain the ACT above 400 seconds. The ACT and heparin concentration continued to reduce with time after CPB was stopped. (CSU = cardiac surgical intensive care unit.)
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The coronary artery bypass grafting was accomplished as in a routine procedure. After CPB was terminated, the HDR test was used to measure heparin levels intermittently to predict the time for heparin to wear off. Figure 1 illustrates the temporal relationship of the activated clotting time and the heparin concentration. Surgical hemostasis was achieved, and a cell-saving device was used to salvage blood, which was retransfused. The patient received 4 units of platelets and 2 units of fresh frozen plasma to correct the clotting abnormalities measured after discontinuation of CPB. Once a minimal level of heparin was measured, coinciding with formation of clots in the surgical field, the aortic cannula was removed and the chest was closed. Total CPB time was 101 minutes, and the total operating time was 380 minutes.
A cell-saving device was set up in the intensive care unit to salvage any blood from the drains. Postoperative bleeding was within acceptable limits, and subsequent management was as according to usual protocols. The patient made a good recovery and was discharged home on day 6.
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Comment
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Anaphylaxis to protamine is uncommon and is usually diagnosed when a reaction occurs during the administration of protamine. Protamine allergy is suspected in patients with known allergy to fish. Various options have been described for the management of CPB in such patients [2, 3].
Heparin substitutes that do not require protamine for reversal include bivalirudin, lepirudin, argatroban, and danaparoid [2]. Of these, bivalirudin is most researched. The management of anticoagulation with these agents during CPB is complex and requires special monitoring of the ecarin clotting time [4]. Except for bivalirudin, these agents have a prolonged half-life and are known to be associated with increased bleeding because of the unavailability of any agent for reversal of anticoagulation. Although bivalirudin is short acting, special bypass circuits are recommended to avoid stasis of blood, which results in its degradation.
Heparin-coated circuits [5] have been successfully used but have limited availability. Other options include heparin removal devices, which have been shown to be effective only in experimental settings [6], and the use of heparinase I, which has not been proven to be safe [7]. Heparin-coated circuits and heparin removal devices were not available for use in our center, and heparinase did not appear to be a safe option.
Protamine has been used in protamine allergic patients with antihistamine and steroid cover [8], but we did not choose this because of the possible risks in the event of anaphylaxis. Although the off-pump option uses a lower dose, heparin would still not be entirely excluded. These factors led us to revisit the use of heparin. The Hepcon system made it possible to monitor heparin concentration and wait for spontaneous degradation of heparin to safe levels. Supplemented by the use of blood products (fresh frozen plasma and platelets), adequate hemostasis was achieved within a reasonable time. The use of a cell-saving device to process blood lost during and after CPB is routine practice in our hospital and was continued in the intensive care unit to minimize the risk of transfusion. The patient did not experience excessive blood loss and had an uncomplicated recovery.
The disadvantages were a longer total operating time and the need for transfusion of blood products. However, we recommend this technique when protamine cannot be used safely in an urgent situation, especially when bivalirudin or ecarin clotting time monitoring are not available.
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References
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- Knape JT, Schuller JL, de Haan P, de Jong AP, Bovill JG. An anaphylactic reaction to protamine in a patient allergic to fish Anesthesiology 1981;55:324-325.[Medline]
- Murphy GS, Marymont JH. Alternative anticoagulation management strategies for the patient with heparin-induced thrombocytopenia undergoing cardiac surgery J Cardiothorac Vasc Anesth 2007;21:113-126.[Medline]
- von Segesser LK, Mueller X, Marty B, Horisberger J, Corno A. Alternatives to unfractionated heparin for anticoagulation in cardiopulmonary bypass Perfusion 2001;16:411-416.[Abstract/Free Full Text]
- Dyke CM, Smedira NG, Koster A, et al. A comparison of bivalirudin to heparin with protamine reversal in patients undergoing cardiac surgery with cardiopulmonary bypass: the EVOLUTION-ON study J Thorac Cardiovasc Surg 2006;131:533-539.[Abstract/Free Full Text]
- Mukadam ME, Pritchard P, Riddington D, et al. Case 7-2001: management during cardiopulmonary bypass of patients with presumed fish allergy J Cardiothorac Vasc Anesth 2001;15:512-519.[Medline]
- Zwischenberger JB, Tao W, Deyo DJ, et al. Safety and efficacy of a heparin removal device: a prospective randomized preclinical outcomes study Ann Thorac Surg 2001;71:270-277.[Abstract/Free Full Text]
- Stafford-Smith M, Lefrak EA, Qazi AG, et al. Efficacy and safety of heparinase I versus protamine in patients undergoing coronary artery bypass grafting with and without cardiopulmonary bypass Anesthesiology 2005;103:229-240.[Medline]
- Baraka A, Choueiry P, Taha S, et al. Hydrocortisone pretreatment for attenuation of protamine-induced adverse hemodynamic reactions J Cardiothorac Vasc Anesth 1995;9:481-482.[Medline]
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Abstract
Introduction
