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Beverly, A., Ong, G., Wilkinson, KL, Doree, C., Welton, NJ, & Estcourt, LJ

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Beverly, A., Ong, G., Wilkinson, KL, Doree, C., Welton, NJ, & Estcourt, LJ Beverly, A., Ong, G., Wilkinson, K. L., Doree, C., Welton, N. J., & Estcourt, L. J. (2019). Drugs to reduce bleeding and transfusion in adults undergoing cardiac surgery: A systematic review and network meta analysis. Cochrane Database of Systematic Reviews, 2019(9), [CD013427]. https://doi.org/10.1002/14651858.CD013427 Publisher's PDF, also known as Version of record Link to published version (if available): 10.1002/14651858.CD013427 Link to publication record in Explore Bristol Research PDF-document This is the final published version of the article (version of record). It first appeared online via Cochrane Collaboration at https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD013427/full . Please refer to any applicable terms of use of the publisher. University of Bristol - Explore Bristol Research General rights This document is made available in accordance with publisher policies. Please cite only the published version using the reference above. Full terms of use are available: http://www.bristol.ac.uk/red/research-policy/pure/user-guides/ebr-terms/ Cochrane Database of Systematic Reviews Drugs to reduce bleeding and transfusion in adults undergoing cardiac surgery: a systematic review and network meta- analysis (Protocol) Beverly A, Ong G, Wilkinson KL, Doree C, Welton NJ, Estcourt LJ Beverly A, Ong G, Wilkinson KL, Doree C, Welton NJ, Estcourt LJ. Drugs to reduce bleeding and transfusion in adults undergoing cardiac surgery: a systematic review and network meta-analysis. Cochrane Database of Systematic Reviews 2019, Issue 9. Art. No.: CD013427. DOI: 10.1002/14651858.CD013427. www.cochranelibrary.com Drugs to reduce bleeding and transfusion in adults undergoing cardiac surgery: a systematic review and network meta-analysis (Protocol) Copyright © 2019 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. TABLE OF CONTENTS HEADER....................................... 1 ABSTRACT ...................................... 1 BACKGROUND .................................... 1 OBJECTIVES ..................................... 6 METHODS ...................................... 6 ACKNOWLEDGEMENTS . 12 REFERENCES ..................................... 12 ADDITIONALTABLES. 21 APPENDICES ..................................... 23 CONTRIBUTIONSOFAUTHORS . 27 DECLARATIONSOFINTEREST . 28 SOURCESOFSUPPORT . 28 Drugs to reduce bleeding and transfusion in adults undergoing cardiac surgery: a systematic review and network meta-analysis (Protocol) i Copyright © 2019 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. [Intervention Protocol] Drugs to reduce bleeding and transfusion in adults undergoing cardiac surgery: a systematic review and network meta- analysis Anair Beverly1, Giok Ong1, Kirstin L Wilkinson2, Carolyn Doree1, Nicky J Welton3, Lise J Estcourt4 1Systematic Review Initiative, NHS Blood and Transplant, Oxford, UK. 2Paediatric and Adult Cardiothoracic Anaesthesia, Southamp- ton University NHS Hospital, Southampton, UK. 3Population Health Sciences, Bristol Medical School, University of Bristol, Bristol, UK. 4Haematology/Transfusion Medicine, NHS Blood and Transplant, Oxford, UK Contact address: Lise J Estcourt, Haematology/Transfusion Medicine, NHS Blood and Transplant, Level 2, John Radcliffe Hospital, Headington, Oxford, OX3 9BQ, UK. [email protected], [email protected]. Editorial group: Cochrane Heart Group. Publication status and date: New, published in Issue 9, 2019. Citation: Beverly A, Ong G, Wilkinson KL, Doree C, Welton NJ, Estcourt LJ. Drugs to reduce bleeding and transfusion in adults undergoing cardiac surgery: a systematic review and network meta-analysis. Cochrane Database of Systematic Reviews 2019, Issue 9. Art. No.: CD013427. DOI: 10.1002/14651858.CD013427. Copyright © 2019 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. ABSTRACT This is a protocol for a Cochrane Review (Intervention). The objectives are as follows: To assess the efficacy and safety of haemostatic drugs (including antifibrinolytics) and topical agents for reducing bleeding, transfusion, and reoperation in adults undergoing cardiac surgery. BACKGROUND over the age of 35 years and is, therefore, the largest single con- tributor to global mortality (Abubakar 2015; WHO 2009). De- pending on severity and anatomy of CHD, it is treated with med- ications, percutaneous coronary intervention (PCI), or coronary Description of the condition artery bypass grafting (CABG) of one or more coronary arteries (Chang 2016; Windecker 2014). PCI has become more common since the late 1990s, now accounting for four in five CHD in- Cardiac surgery in adults terventions (Blumenfeld 2017; Ko 2012; Yeh 2015). However, Cardiac surgery treats disease of the coronary arteries, heart mus- CABG remains the most frequently performed cardiac operation cle, valves, surrounding membrane (pericardium), and great vessels in adults (SCTS 2015; STS 2018). Cardiac valve repairs or replace- flowing out from the heart (aorta). Such disease may be acquired, ments are the second most frequently performed cardiac opera- age-related (degenerative), inherited, or congenital (present at tions (SCTS 2015; STS 2018). The aortic valve, followed by the birth). Coronary heart disease (CHD) is a form of cardiovascu- mitral valve most commonly require surgery (SCTS 2015). CABG lar disease affecting the coronary arteries. Cardiovascular disease and valve surgery may be conducted in a combined operation, if is common, causing approximately one-third of deaths in people coronary artery and valvular disease coexist (Bonow 2006). Some Drugs to reduce bleeding and transfusion in adults undergoing cardiac surgery: a systematic review and network meta-analysis (Protocol) 1 Copyright © 2019 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. valve procedures can be conducted percutaneously, for example a thrombosis outweighs the risk of bleeding (Sousa-Uva 2014). An- transcatheter aortic valve implant (TAVI), rather than with open tiplatelet drugs may also not be stopped with adequate washout surgery, which decreases the risk of bleeding and other complica- times prior to emergency surgery. tions (Daubert 2017; Nishimura 2017). Surgery on the cardiac CPB facilitates surgery by providing a bloodless, motionless sur- outflow tract (ascending aorta and aortic arch) is less commonly gical field (Mulholland 2015), but can impair coagulation in sev- performed (SCTS 2015; STS 2018), and usually involves graft eral ways. First, the CPB circuit is usually primed with large vol- replacement or repair for aneurysm (dilation), dissection (a tear in umes (approximately 1.5 L) of fluid, which dilutes the circulating the vessel wall), or infection (Stamou 2015). blood by 10% to 20%, and this in turn dilutes clotting factors in Cardiac surgery can be elective, urgent, or emergency, and can be the blood (Ranucci 2017). Second, the CPB is primed with hep- primary or revision surgery (Chiu 2016; Goodwin 2003; Kurki arin (an anticoagulant) to prevent clotting within the circuit, but 2003). Cardiac operations vary in their complexity, risk, and com- heparin can enter the systemic circulation and increase bleeding plication rates, and individualised mortality risk prediction mod- (O’Carroll-Kuehn 2007). Third, contact of blood with the CPB els have been developed using large cardiac surgery registries, tubing, pumps, and gas exchange membranes can alter normal co- namely EuroSCORE and its update, EuroSCORE II (Nashef agulation pathways, causing both bleeding and blood clots (Hess 1999; Nashef 2012; Nilsson 2006). Traditionally, cardiac surgery 2005; Sato 2015). Finally, low body temperatures (hypothermia) requires a sternotomy (opening of the breastbone) and artificial using active or passive cooling are used for some cardiac opera- circulation in the form of a cardiopulmonary bypass (CPB) cir- tions because this reduces organ oxygen requirements, thus reduc- cuit. This remains standard practice but newer alternatives include ing organ damage during periods of poor or absent blood flow. minimally invasive incisions, miniature CPB, and off-pump (beat- However, hypothermia also negatively affects coagulation by slow- ing heart) surgery, though this is less widely used (Møller 2014). ing the enzyme rate of many steps in the coagulation pathway (Campos 2008). Severe bleeding can cause low blood pressure and anaemia with in- Bleeding in cardiac surgery adequate oxygen supply to organs (Pittman 2011; Sabatine 2005). Intra- or postoperative bleeding is a recognised complication of Postoperative bleeding can also cause a collection of blood and cardiac surgery, but severity of bleeding varies greatly (Bennett- clots within the fibrous membrane around the heart, preventing Guerrero 2010). Bleeding risk prediction scores, for example, the adequate blood flow through the heart (pericardial tamponade) Papworth Bleeding Risk Score, predicts higher bleeding risk using (Haneya 2015). This life-threatening complication requires emer- variables of: non-elective surgery, surgery other than CABG or gency return to theatre to reopen the chest (resternotomy) and oc- single valve surgery, presence of aortic valve disease, low body mass curs in 4% to 5% of adults undergoing cardiac surgery. It is asso- index (BMI), and older age (Vuylsteke 2011). It defines severe ciated with significantly worse outcomes, including cardiac arrest, postoperative bleeding by any of: at least 2 mL/kg/hour from chest and longer hospital admission and increased costs (Biancari 2011; drains for the first three
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