DDAVP Effect by TEG6 in Cardiac Surgery

Official title

Desmopressin Effect on Platelet Function Assessment by Thromboelastography (TEG 6) in Cardiac Surgery

Overview

Cardiopulmonary bypass (CPB) is a process that uses a pump that temporarily takes over the function of the heart and lungs during cardiac surgery to maintain blood circulation and oxygenation. Using CPB during cardiac surgery can result in complications with blood clotting. Blood clotting is achieved when molecules in the blood, called platelets, are able to form together with the help of other clotting factors to form a clot. A drug called desmopressin (DDAVP) is used to help blood clot properly by increasing the amount of clotting factors in the blood. Several studies have shown that desmopressin has the ability to reduce the amount of blood transfusions needed for cardiac surgery patients in the postoperative period. At LHSC desmopressin is frequently requested by Cardiac Surgeons and Anesthesiologists to stop bleeding and promote blood clotting where required. A test called TEG6s platelet mapping is a blood test used to help manage the use of blood products by being able to provide information on platelet function and blood clotting activity. At the moment, there is a lack of information regarding the use of TEG6s platelet mapping to analyze the effect of desmopressin on blood clotting in cardiac surgery patients after CPB. The purpose of this study is to investigate the dose-related effects of desmopressin on platelet function in patients undergoing cardiac surgery with CPB. By using TEG6s platelet mapping, this study aims to observe dynamic changes in platelet function following desmopressin administration at various time points in the perioperative and postoperative periods.

Detailed description

Cardiopulmonary bypass (CPB) during cardiac surgery is frequently complicated by disturbances in coagulation parameters and platelet function. Desmopressin (DDAVP) has been utilized to enhance platelet adhesion and aggregation by increasing plasma levels of von Willebrand factor (vWF) and factor VIII that plays a crucial role in blood clotting. Several studies demonstrated a positive effect of DDAVP in hemostasis (particularly in patients with qualitative platelet dysfunction), reduced blood transfusion and bleeding in the post operative period.

Viscoelastic testing, specifically TEG (Thromboelastography) platelet mapping and TEG6s and have been shown to be helpful in managing the use of blood products, fresh frozen plasma (FFP), platelets and fibrinogen, in coagulopathic patient post cardiopulmonary bypass. Desmopressin is given at a dose 0.3 micrograms/kg intravenously over 15 to 30 minutes as a standard dose in cardiac surgery, up to 20 mcg which is the United States Food and Drug Administration (US FDA) recommended dose for Hemophilia treatment and the most commonly cited dose used in cardiac surgery after cardiopulmonary bypass. The TEG6s platelet mapping shows baseline platelet function and receptor-specific platelet function and inhibition. This assessment is based on four different assays including Koalin, Activator F, ADP (Adenosine Diphosphate), AA (Arachidonic Acid). At the current time there is limited literature looking at the qualitative effect of desmopressin on platelet function using TEG6s platelet mapping analysis. The purpose of this study is to investigate the dose-related effects of desmopressin on platelet function in patients undergoing cardiac surgery. By using TEG6s platelet mapping we aim to observe dynamic changes in platelet function following desmopressin administration at various time points in perioperative and postoperative periods.

Informed, written consent will be obtained prior to the start of surgery.

Participants that are enrolled in this study will have their surgery proceed according to plan and will be placed under general anesthesia using standard of care practices. Cardiopulmonary bypass will be implemented in accordance with standard of care practices. Desmopressin will be given to participants at a dose of 0.3mcg/kg, up to 20 mcg after protamine reversal at the end of cardiopulmonary bypass.

Platelet function will be assessed by TEG platelet mapping at the following points:

1. T1 TEG6s: after arterial line insertion before skin incision. 2. T2 TEG6s: after protamine (baseline function after CPB) 3. T3 TEG6s: 30 minutes after desmopressin 4. T4 TEG6s: 6 hours after (intensive care unit) ICU admission 5. T5 TEG6s: 24hours after ICU admission

This will involve drawing 4 ml of blood from patients at each of the above time points (5 blood draws total), in a dark green-top (Sodium Heparin) Vacutainer® tube by the Cardiac Anesthesiologist who will be also running the test on the TEG Machine. The study team will also collect information such as participant age, biological sex, height, weight, medications, medical history, surgical details, results of preoperative and postoperative blood work, and details of their postoperative recovery.

Interventions

• Drug Desmopressin after protamine reversal
  Desmopressin will be given to participants at a dose of 0.3mcg/kg after protamine reversal at the end of cardiopulmonary bypass (CPB). Platelet function will be assessed by TEG (Thromboelastography) platelet mapping at the following points: 1. T1 TEG6s: after arterial line insertion before skin incision. 2. T2 TEG6s: after protamine (baseline function after CPB) 3. T3 TEG6s: 30 minutes after desmopressin 4. T4 TEG6s: 6 hours after (intensive care unit) ICU admission 5. T5 TEG6s: 24hours after

Primary outcome measures

• Change in platelet function due to desmopressin administration after cardiopulmonary bypass [Time frame: After arterial line insertion - 24 hours after admission to the intensive care unit]

Secondary outcome measures (2)

• Impact of desmopressin on transfusion products required [Time frame: After arterial line insertion - 24 hours after admission to the intensive care unit]
• Impact of desmopressin on chest drainage [Time frame: After arterial line insertion - 24 hours after admission to the intensive care unit]

Eligibility criteria

Inclusion criteria

• Age 18 years and above
• Undergoing elective cardiac surgery with cardiopulmonary bypass
• Able to provide informed consent

Exclusion criteria

• Hyponatremia
• Allergy to desmopressin or its components
• History of coronary artery disease with thrombosis
• Recent history of thromboembolic events (Stroke/TIA/DVTs)
• Severe Renal Impairment Creatinine Clearance<30 ml/min
• Inability to communicate in the English language

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Observational model

Cohort

Study locations

Center list to be confirmed — check the primary protocol.

Publications

• Mongan PD, Hosking MP. The role of desmopressin acetate in patients undergoing coronary artery bypass surgery. A controlled clinical trial with thromboelastographic risk stratification. Anesthesiology. 1992 Jul;77(1):38-46. doi: 10.1097/00000542-199207000-00007. PMID 1610009
• Ozkisacik E, Islamoglu F, Posacioglu H, Yagdi T, Basarir S, Omay SB, Ozbaran M, Buket S. Desmopressin usage in elective cardiac surgery. J Cardiovasc Surg (Torino). 2001 Dec;42(6):741-7. PMID 11698939
• Jahangirifard A, Mirtajani SB, Madadi F. Effect of Desmopressin on Bleeding After Heart Surgeries: A Narrative Review. Anesth Pain Med. 2023 Mar 10;13(2):e133894. doi: 10.5812/aapm-133894. eCollection 2023 Apr. PMID 37645010
• 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. PMID 24263581
• Despotis GJ, Levine V, Saleem R, Spitznagel E, Joist JH. Use of point-of-care test in identification of patients who can benefit from desmopressin during cardiac surgery: a randomised controlled trial. Lancet. 1999 Jul 10;354(9173):106-10. doi: 10.1016/S0140-6736(98)12494-7. PMID 10408485
• Agarwal S, Abdelmotieleb M. Viscoelastic testing in cardiac surgery. Transfusion. 2020 Oct;60 Suppl 6:S52-S60. doi: 10.1111/trf.16075. Epub 2020 Sep 21. PMID 32955756
• Meco M, Montisci A, Giustiniano E, Greco M, Pappalardo F, Mammana L, Panisi P, Roscitano C, Cirri S, Donatelli F, Albano G. Viscoelastic Blood Tests Use in Adult Cardiac Surgery: Meta-Analysis, Meta-Regression, and Trial Sequential Analysis. J Cardiothorac Vasc Anesth. 2020 Jan;34(1):119-127. doi: 10.1053/j.jvca.2019.06.030. Epub 2019 Jun 28. PMID 31445833
• Li C, Zhao Q, Yang K, Jiang L, Yu J. Thromboelastography or rotational thromboelastometry for bleeding management in adults undergoing cardiac surgery: a systematic review with meta-analysis and trial sequential analysis. J Thorac Dis. 2019 Apr;11(4):1170-1181. doi: 10.21037/jtd.2019.04.39. PMID 31179059

Identifiers

NCT: NCT07179991 · DDAVP TEG6

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗