Transfusion Reduction in High-Bleeding-Risk Cardiac Surgery With Desmopressin

Summary

Rationale Bleeding after cardiac surgery is a complication that might result in increased morbidity, mortality, and cost of cardiac surgery by 1.76 (confidence interval (CI), 1.64-1.90) times and a median increase in costs by Australian $33,338 (CI, $21,943-$38,415) \[1\]. Strategies and techniques to reduce postoperative bleeding in identified high-risk patients for bleeding after cardiac surgery might improve outcomes and resource utilization. Desmopressin (DDAVP) is used as a hemostatic agent to prevent and treat bleeding in patients with mild hemophilia patients with von Willebrand's deficiency through stimulating the release of von Willebrand factor from endothelial cells. Previous studies showed controversial results in terms of reduced transfusion requirements in patients with low risk for bleeding with post cardiopulmonary bypass (CPB) bleeding following prophylactic infusing desmopressin over 10 to 15 minutes after induction of anesthesia or protamine administration due to its positive effects on the coagulation system responsible for such bleeding. Contradictory, prophylactic desmopressin use demonstrated fewer transfusion requirements in patients treated with antiplatelets, which raises the need to examine its efficacy in high-risk cardiac surgery patients for perioperative bleeding. These controversial results might be attributed to delayed administration of desmopressin after evolving CPB-associated thrombocytopenia, platelet dysfunction, coagulation factor consumption and dilution, hyperfibrinolysis, and hypofibrinogenemia \[2\] Concerns were raised about the associated transient decreases in systemic vascular resistance and blood pressure after desmopressin administration following discontinuing CPB and administering protamine, which might be related to the rapid infusion rate during the critical surgery stage. The cost of a single dose of Desmopressin 0.3 ug/kg for a patient with an average weight of 70 Kg is about 82US$ which is cheaper than the alternative hemostatic agents proved to be effective in reducing bleeding and transfusion needs after cardiac surgery (e.g., fibrinogen concrete (average of 3 g = 1,167US$) and prothrombin complex concentrate (6,255US$ considering low fixed dosfixed-doseof 1040 IU F IX). It is yet unclear if extended infusions of desmopressin started earlier before the development of CPB-associated coagulopathy and platelets dysfunction from anesthesia induction time and continued to the end of CPB before protamine administration would offer an "efficacy," "safety, and "cost-effective" benefits over placebo in patients with high risks for bleeding after cardiac surgery terms of the need for transfusion, cumulative postoperative 48-hour chest tube outputs, need for reoperation, thrombotic complications, 30-day mortality, hemodynamic stability, and urine output during and after completing infusion, and costs of the study drug and allogenic transfusion requirement. That raises the need to examine its impact on these crucial clinical outcomes. Objective The primary objective of this prospective multicentre randomized clinical trial (RCT) is, compared with placebo, to examine the impact of prolonged infusion desmopressin on reducing postoperative bleeding and the need for allogenic allogeneic transfusion in high-bleeding-risk cardiac surgery patients scheduled for elective cardiac surgical procedures using CPB. Secondary objectives include comparing placebo and desmopressin in terms of safety and cost-effectiveness. Hypothesis It is hypothesized that extended 'desmopressin' infusion compared to 'placebo' results in less postoperative bleeding and transfusion needs (more effective) and leads to less hemodynamic compromise (safer) and cheaper (cost-effective) in high-risk cardiac surgery patients.

Timeline

Start

2025-07

Primary completion

2027-07

Completion

2027-08

Publications

• Background Redfern RE, Fleming K, March RL, Bobulski N, Kuehne M, Chen JT, Moront M. Thrombelastography-Directed Transfusion in Cardiac Surgery: Impact on Postoperative Outcomes. Ann Thorac Surg. 2019 May;107(5):1313-1318. doi: 10.1016/j.athoracsur.2019.01.018. Epub 2019 Feb 12.
• Background Khalil MA, El Tahan MR, Khidr AM, Fallatah S, Abohamar AD, Amer MM, Makhdom F, El Ghoneimy Y, Al Bassam B, Alghamdi T, Abdulfattah D. Effects of norepinephrine infusion during cardiopulmonary bypass on perioperative changes in lactic acid level (Norcal). Perfusion. 2023 Nov;38(8):1584-1599. doi: 10.1177/02676591221122350. Epub 2022 Aug 22.
• Background Vuylsteke A, Pagel C, Gerrard C, Reddy B, Nashef S, Aldam P, Utley M. The Papworth Bleeding Risk Score: a stratification scheme for identifying cardiac surgery patients at risk of excessive early postoperative bleeding. Eur J Cardiothorac Surg. 2011 Jun;39(6):924-30. doi: 10.1016/j.ejcts.2010.10.003. Epub 2010 Nov 19.
• Background Petricevic M, Petricevic M, Pasalic M, Golubic Cepulic B, Raos M, Vasicek V, Goerlinger K, Rotim K, Gasparovic H, Biocina B. Bleeding risk stratification in coronary artery surgery: the should-not-bleed score. J Cardiothorac Surg. 2021 Apr 21;16(1):103. doi: 10.1186/s13019-021-01473-3.
• Background Baryshnikova E, Di Dedda U, Ranucci M. Are Viscoelastic Tests Clinically Useful to Identify Platelet-Dependent Bleeding in High-Risk Cardiac Surgery Patients? Anesth Analg. 2022 Dec 1;135(6):1198-1206. doi: 10.1213/ANE.0000000000006231. Epub 2022 Oct 13.
• Background Orlov D, McCluskey SA, Callum J, Rao V, Moreno J, Karkouti K. Utilization and Effectiveness of Desmopressin Acetate After Cardiac Surgery Supplemented With Point-of-Care Hemostatic Testing: A Propensity-Score-Matched Analysis. J Cardiothorac Vasc Anesth. 2017 Jun;31(3):883-895. doi: 10.1053/j.jvca.2016.11.022. Epub 2016 Nov 17.
• Background Dias JD, Sauaia A, Achneck HE, Hartmann J, Moore EE. Thromboelastography-guided therapy improves patient blood management and certain clinical outcomes in elective cardiac and liver surgery and emergency resuscitation: A systematic review and analysis. J Thromb Haemost. 2019 Jun;17(6):984-994. doi: 10.1111/jth.14447. Epub 2019 May 13.
• Background Fleming NW, Burke TA. Infusion rate and hemodynamics with desmopressin. J Cardiothorac Anesth. 1989 Dec;3(6):813-5. doi: 10.1016/s0888-6296(89)96804-x. No abstract available.
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• Background 16. Spyridakis, E., Pentilas, N., Retzios, G., Pappa, E., & Kalakonas, S. (2017). The use of desmopressin (DDAVP) as haemostatic agent in patients undergoing coronary artery bypass grafting (CABG) surgery. Journal of Cardiothoracic and Vascular Anesthesia, 31, S69.https://doi.org/10.1053/j.jvca.2017.02.153
• Background Marquez J, Koehler S, Strelec SR, Benckart DH, Spero JA, Cottington EM, Torpey DJ Jr. Repeated dose administration of desmopressin acetate in uncomplicated cardiac surgery: a prospective, blinded, randomized study. J Cardiothorac Vasc Anesth. 1992 Dec;6(6):674-6. doi: 10.1016/1053-0770(92)90049-d.
• Background Salmenpera M, Kuitunen A, Hynynen M, Heinonen J. Hemodynamic responses to desmopressin acetate after CABG: a double-blind trial. J Cardiothorac Vasc Anesth. 1991 Apr;5(2):146-9. doi: 10.1016/1053-0770(91)90328-q.
• Background Oliver WC Jr, Santrach PJ, Danielson GK, Nuttall GA, Schroeder DR, Ereth MH. Desmopressin does not reduce bleeding and transfusion requirements in congenital heart operations. Ann Thorac Surg. 2000 Dec;70(6):1923-30. doi: 10.1016/s0003-4975(00)02176-7.
• Background Reich DL, Hammerschlag BC, Rand JH, Weiss-Bloom L, Perucho H, Galla J, Thys DM. Desmopressin acetate is a mild vasodilator that does not reduce blood loss in uncomplicated cardiac surgical procedures. J Cardiothorac Vasc Anesth. 1991 Apr;5(2):142-5. doi: 10.1016/1053-0770(91)90327-p.
• Background Brown MR, Swygert TH, Whitten CW, Hebeler R. Desmopressin acetate following cardiopulmonary bypass: evaluation of coagulation parameters. J Cardiothorac Anesth. 1989 Dec;3(6):726-9. doi: 10.1016/s0888-6296(89)94790-x.
• Background Dilthey G, Dietrich W, Spannagl M, Richter JA. Influence of desmopressin acetate on homologous blood requirements in cardiac surgical patients pretreated with aspirin. J Cardiothorac Vasc Anesth. 1993 Aug;7(4):425-30. doi: 10.1016/1053-0770(93)90164-g.
• Background Hackmann T, Naiman SC. Con: desmopressin is not of value in the treatment of post-cardiopulmonary bypass bleeding. J Cardiothorac Vasc Anesth. 1991 Jun;5(3):290-3. doi: 10.1016/1053-0770(91)90291-z.
• Background Shiffrin JS, Glass DD. Pro: desmopressin is of value in the treatment of post-cardiopulmonary bypass bleeding. J Cardiothorac Vasc Anesth. 1991 Jun;5(3):285-9. doi: 10.1016/1053-0770(91)90290-a. No abstract available.
• Background Casselman FPA, Lance MD, Ahmed A, Ascari A, Blanco-Morillo J, Bolliger D, Eid M, Erdoes G, Haumann RG, Jeppsson A, van der Merwe HJ, Ortmann E, Petricevic M, Weltert LP, Milojevic M; EACTS/EACTAIC/EBCP Scientific Document Group. 2024 EACTS/EACTAIC Guidelines on patient blood management in adult cardiac surgery in collaboration with EBCP. Interdiscip Cardiovasc Thorac Surg. 2025 May 6;40(5):ivae170. doi: 10.1093/icvts/ivae170. No abstract available.
• Background Wademan BH, Galvin SD. Desmopressin for reducing postoperative blood loss and transfusion requirements following cardiac surgery in adults. Interact Cardiovasc Thorac Surg. 2014 Mar;18(3):360-70. doi: 10.1093/icvts/ivt491. Epub 2013 Nov 21.
• Background Desborough MJ, Oakland K, Brierley C, Bennett S, Doree C, Trivella M, Hopewell S, Stanworth SJ, Estcourt LJ. Desmopressin use for minimising perioperative blood transfusion. Cochrane Database Syst Rev. 2017 Jul 10;7(7):CD001884. doi: 10.1002/14651858.CD001884.pub3.
• Background PROVE Network Investigators for the Clinical Trial Network of the European Society of Anaesthesiology; Hemmes SN, Gama de Abreu M, Pelosi P, Schultz MJ. High versus low positive end-expiratory pressure during general anaesthesia for open abdominal surgery (PROVHILO trial): a multicentre randomised controlled trial. Lancet. 2014 Aug 9;384(9942):495-503. doi: 10.1016/S0140-6736(14)60416-5. Epub 2014 Jun 2.
• Background Smilowitz NR, Gupta N, Ramakrishna H, Guo Y, Berger JS, Bangalore S. Perioperative Major Adverse Cardiovascular and Cerebrovascular Events Associated With Noncardiac Surgery. JAMA Cardiol. 2017 Feb 1;2(2):181-187. doi: 10.1001/jamacardio.2016.4792.
• Background Thiele RH, Raphael J. A 2014 Update on Coagulation Management for Cardiopulmonary Bypass. Semin Cardiothorac Vasc Anesth. 2014 Jun;18(2):177-89. doi: 10.1177/1089253214534782.
• Background Newcomb AE, Dignan R, McElduff P, Pearse EJ, Bannon P. Bleeding After Cardiac Surgery Is Associated With an Increase in the Total Cost of the Hospital Stay. Ann Thorac Surg. 2020 Apr;109(4):1069-1078. doi: 10.1016/j.athoracsur.2019.11.019. Epub 2020 Jan 2.

Drugs

Indications

No indication recorded.