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Heparin Coating and Cardiotomy Suction in Cardiopulmonary Bypass

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Heparin Coating and Cardiotomy Suction in Cardiopulmonary Bypass Heparin Coating and Cardiotomy Suction in Cardiopulmonary Bypass Staffan Svenmarker Department of Surgical and Perioperative Science Umeå University, Umeå, Sweden 2003 Umeå University Medical Dissertations New Series No. 855 - ISSN 0346-6612 – ISBN 91-7305-523-9 From the Department of Surgical and Perioperative Science Umeå University, Umeå, Sweden Heparin Coating and Cardiotomy Suction in Cardiopulmonary Bypass Staffan Svenmarker Fakultetsopponent: Professor Jarle Vaage Department of Surgery, Ullevål University Hospital University of Oslo, Norway Umeå 2003 Copyright 2003 Staffan Svenmarker ISBN 91-7305-523-9 Printed by Print & Media Umeå University, Sweden Hur förena tro med vetande? Frågan lär ju vara viktig. Kräva starkt arbetande, mycket ivrigt letande. Dumbom, något oförsiktig. Svarar: ”jo, när tron är riktig, är den vetande”. Gustav Fröding To my family: Barbro, Pontus, Anna and Magnus Table of Contents Abstract 7 Abbreviations 8 List of papers 9 Introduction Historical aspects of cardiopulmonary bypass 11 Introductory remarks to cardiopulmonary bypass 12 The systemic inflammatory response syndrome 14 Cardiopulmonary bypass and clinical outcome 17 The role of heparin coating 17 The role of cardiotomy suction 19 Cardiopulmonary bypass and the brain 20 Memory dysfunction 22 The protein S100 23 Aim of the investigations 27 Material & Methods Characteristics of population 28 General clinical management 30 Conduct of cardiopulmonary bypass 30 General assessments and measurements 31 Statistics 34 Results HCC and general clinical outcome 35 HCC and renal function 37 Effects of different types of HCC 37 Effect of HCC and PSB-retransfusion on release of protein S100B 37 Effect of HCC and retransfusion of PSB on memory function 38 Recycling of PSB: effects of free plasma haemoglobin 40 Recycling of PSB: general inflammatory effects 40 General Discussion 42 Conclusions 50 Acknowledgements 51 Populärvetenskaplig sammanfattning på svenska 52 References 54 Abstract Heparin Coating and Cardiotomy Suction in Cardiopulmonary Bypass Staffan Svenmarker Department of Surgical and Perioperative Science, Umeå University, Umeå Sweden. Abstract The present thesis addresses various means of reducing inflammatory responses associated with cardiopulmonary bypass (CPB) and retransfusion of pericardial suction blood (PSB) during cardiac surgery. Four (I-IV) prospective randomised controlled clinical trials comprising 475 patients were performed in the following areas: effects of heparin coating on measures of clinical outcome and memory function (I, II), inflammatory reactions in PSB and its systemic effects after retransfusion using cardiotomy suction or cell salvage (III) and effects of retransfusion of PSB on memory function and release patterns of protein S100B (IV). The use of heparin coated CPB-circuits was associated with a decrease of postoperative blood loss (I, II), transfusion requirements (II), shorter stay in hospital (I) decreased postoperative ventilator time (I), lower incidences of atrial fibrillation (II) and neurological deviations (I), reduction in releases of protein S100B (I, II) and lower postoperative creatinine elevation (I, II). PSB contained high concentrations of cytokines, complements, myeloperoxidase, free plasma haemoglobin and protein S100B (III, IV). Retransfusion using cardiotomy suction increased the systemic concentrations of free plasma haemoglobin and protein S100B, whereas retransfusion using cell salvage caused no detectable systemic effects (III, IV). CPB was associated with a small but significant release of protein S100B, despite elimination of PSB-contained protein S100B using cell salvage (IV). Subtle signs of impaired memory function were identified that were not associated with the use of heparin coated CPB-circuits (I, II) or retransfusion of PSB (IV). Key words: cardiopulmonary bypass, oxygenators, heparin, S100 proteins, blood loss, haemostasis, memory, outcome and process assessment. 7 Abbreviations Abbreviations ACT Activated Clotting Time BCI Brain Cell Injury BMI Body Mass Index CABG Coronary Artery Bypass Grafting CBAS Carmeda BioActive Surface CNS Central Nervous System CPB Cardiopulmonary Bypass CR Cardiotomy Reservoir CRP C Reactive Protein CS Cell Saver CT Computerised Tomography ECG Electrocardiogram ELISA Enzyme-Linked Immunosorbent Assay HCC Heparin Coated Circuits IL Interleukin LOS Length of Stay in Hospital MAC Membrane Attack Complex MAP Mean Arterial Pressure MODS Multi Organ Dysfunction Syndrome MPO Myeloperoxidase OFF-PUMP Cardiac surgery without heart-lung machine PHb Plasma Haemoglobin PMN Polymorphonuclear PSB Pericardial Suction Blood SCADs Small Capillary Arterial Dilatations SD Standard Deviation SEM Standard Error of the Mean SIRS Systemic Inflammatory Response Syndrome TCC Terminal Complement Complex TNF Tumour Necrosis Factor 8 Original Papers This thesis is based on the following papers referred to by their Roman numerals: I. Svenmarker S, Sandström E, Karlsson T, Jansson E, Häggmark S, Lindholm R, Appelblad M, Åberg, T. Clinical effects of the heparin coated surface in cardiopulmonary bypass. Eur J Cardiothorac Surg 1997; 11(5): 957-964. II. Svenmarker S, Sandström E, Karlsson T, Häggmark S, Jansson E, Appelblad M, Lindholm R, Åberg, T. Neurological and general outcome in low-risk coronary artery bypass patients using heparin coated circuits. Eur J Cardiothorac Surg 2001; 19(1): 47-53. III. Svenmarker S, Engström KG. The inflammatory response to recycled pericardial suction blood and the influence of cell saving. Scand Cardiovasc J 2003; 37(3): 158-164. IV. Svenmarker S, Engström KG, Karlsson T, Jansson E, Lindholm R, Åberg, T. Influence of pericardial suction blood retransfusion on memory function and release of protein S100B. Submitted. Reprints of original papers were made with approval from the publisher. 9 10 Introduction Introduction Historical Aspects of Cardiopulmonary Bypass The invention of the heart-lung machine is attributed to John Gibbon, Jr. His wife, Mary Gibbon was the first perfusionist. Dr. Gibbon invented the heart-lung machine in his laboratory at the Bullfinch Building of the Massachusetts General Hospital in the 1930’s. Originally, it was designed to serve as life support during Trendelenburg operations and pulmonary embolectomy - at that time associated with nearly 100% mortality. In 1953, the heart-lung machine was introduced in cardiac surgery, when Gibbon successfully closed an atrial septum defect in an 18-year-old woman [1]. Clarence Crafoord performed the second heart operation ever with the aid of a heart-lung machine in Sweden 1954 [2]. Inge Rygg and Erik Kyvsgaard developed a new type of integrated soft-shell bubble oxygenator in Denmark in 1956 [3]. The main body of work for the evolution of extracorporeal circulation during the 1950’s took place at the Mayo Clinic by John Kirklin and by C. Walton Lillehei at the University of Minnesota [4-6]. Kirklin performed a series of cardiac interventions using a modified Gibbon heart-lung machine with promising results [4]. However, the equipment was complex and difficult to operate and maintain. C. Walton Lillehei had at the time introduced the bubble oxygenator [5]. The device represented a tremendous step towards simplicity, making the process of extracorporeal circulation more accessible. From 1955 to 1966, C. Walton Lillehei operated on more than 2500 patients with the help of bubble oxygenators [6]. The first disposable bubble oxygenator with integrated heat exchanger came in 1955 by DeWall and colleagues [7]. Today, bubble oxygenators have been replaced by membrane oxygenation, which first was described by Wilhelm Kolf [8] in 1956 and introduced clinically by Frank Gerbode [9] and Arnold J. Lande [10] in 1966. Despite nearly half a century since the introduction of cardiopulmonary bypass (CPB) in cardiac surgery we are still confronted with similar challenges to those which occupied the pioneers. Gibbon was aware of the importance and possible deleterious effects of the contact between blood and the foreign environment represented by the extracorporeal circuit. 11 Introduction “The surface contact with blood should be inert, friendly, one might say, to the blood passing along, and this passage of blood should provide the patient with adequate circulation of undamaged properly oxygenated blood and a means for its release of carbon dioxide” [11]. The present thesis addresses a related issue to describe ways of how to modulate the blood-to-surface interaction, as well as effects generated by the use of cardiotomy suction. Introductory Remarks to Cardiopulmonary Bypass Despite recent trends in cardiac surgery to avoid CPB in attempts to simplify and to reduce complications [12], CPB will play a major role for several cardiac surgical interventions for years to come. Therefore, further refinement and improvement of the extracorporeal technique remains an important field of research. According to the Society of Thoracic Surgeons National Database, 20% or 22.000 low-risk patients develop postoperative complications after cardiac surgery [13]. Multiorgan failure occurs in 11% of cases, which increases the risks of other morbidity and mortality. In our own experience, more than 40% of cardiac surgical patients deviate in some respect from a completely normal postoperative course [14]. Since cardiac surgery is a multidisciplinary intervention, it is difficult to isolate to what extent CPB contributes to the development of organ dysfunction and poor patient outcome. The situation is further
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