Medical Student Research Fellowship for Summer 2010

Mentor: Philip E. Greilich, MD
Department: Department of Anesthesiology, Division of Cardiothoracic Anesthesia
Room number: HQ3.320B
Mail Code: 8894
Phone number: 58018
E-mail: Philip.Greilich@utsouthwestern.edu
Project title: Management of Excessive Bleeding following Cardiopulmonary Bypass: A Pilot Feasibility Study
Human subjects IRB approved project number (where applicable): 082006-043
Animal subjects IRB approved project number (where applicable): N/A
Project Type: Patient-based research
Brief Description of Project:
The treatment of excessive bleeding after cardiac surgery is a growing problem. The risk of mortality exceeds 20%-30% when massive transfusion is required. A large-scale interventional study seems warranted but is hampered by questions of our ability to (a) define excessive bleeding, (b) identify patients at high risk for this problem, (c) develop a protocol that will be reliably adhered to, and (d) define appropriate outcome measures. We, therefore, designed a feasibility study in patients that fail conventional (transfusion) therapy. Our hypotheses were: 1) surgical complexity can be used to identify patients at risk for excessive bleeding following CPB; 2) patients who fail conventional therapy have an increased risk of massive transfusion; and 3) compliance with a standardized blood management protocol prior to randomization is achievable.
Patients scheduled for cardiac surgery requiring CPB who were at risk for excessive bleeding based on pre-operative characteristics were screened and enrolled, if appropriate. A standardized, multi-disciplinary blood management protocol was designed to manage excessive bleeding following CPB. Sixteen tasks (treatments, Hemostasis Score, point-of-care labs, blood loss measurements and transfusion of blood products) were assessed for compliance. Excessive bleeding was defined as frequent packing in the pericardium, bleeding >600mL/hr in the operating room, >300mLs in 1 hour or 150mLs/hr over 2 consecutive hours in the ICU. Conventional replacement therapy was considered a "failure" if excessive bleeding persisted despite replacement therapy consisting of transfusion with 2U single-donor aphereis platelets, 6U FFP and 10U cryoprecipitate. Blood loss and transfusion were measure during the intraoperative and first twenty-four (24) hours postoperative period.
The primary measurements were: 1) number of patients enrolled per conventional treatment failure; 2) compliance with the 16 essential tasks in the blood management protocol; 3) units of packed red blood cells (PRBC) and total blood products transfused; and 4) bleeding rate before and after conventional and rescue therapy.
Role of the Student:

The enrollment phase of this project is complete. The role of the student will be to assist with the data management, statistical analysis (SPSS) and preparation of publications for this project. This will include preparation of key Figures and Tables. Proficiency in MS Word/Excel and Endnote is required. This training can be provided, if needed.

Students will work hard and will have an opportunity to be exposed to the cardiac surgery team. I will assign authorship based on the quality and quantity of work done contributed to the project.

Project Grant Support:

2006-2010 "Management of Excessive Bleeding following Cardiopulmonary Bypass: A Multicenter Pilot Feasibility Study" Principle Investigator: Philip E. Greilich, MD. Unrestricted Grant from NovoNordisk Corporation, $132, 000 (Direct $84,952.14).

Previous Research Activities or Publications with Medical Students:
1) Jonathan Boyd, BS (2008-09) - Medical Student at UT Southwestern- Dallas
Jonathan worked as a research assistant in my lab before his 4th year of medical school to gain experience in clinical research with the roles described above.

(Manuscript) John A, Yeh C, Boyd J, Greilich PE, Treatment of Refractory Hypotension with Vasopressin in a Patient Receiving High-Dose Clozapine. Journal of Cardiothoracic and Vascular Anesthesia. Accepted

(Manuscript) Greilich PE, Leonard D, Boyd J, Brilakis E, Jessen ME. Epsilon-aminocaproic acid, but not aprotinin increases cardiac enzyme levels following CABG surgery. In Preparation

(Manuscript) Wyrick CC, Adesanya A, Greilich PE, Boyd J, Sarode R. Body mass index does not influence platelet responsiveness to clopidogrel in patients undergoing percutaneous neurovascular procedures. In Preparation

(Abstract) Wyrick CC, Greilich PE, Boyd J, Adesanya A, Sarode R. Body mass index does not influence platelet responsiveness to clopidogrel in patients undergoing percutaneous neurovascular procedures. In Preparation

(Poster Presentation) Refractory Hypotension with Vasopressin in a Patient Receiving High-Dose Clozapine. Presented at the International Anesthesia Research Society Meeting. March 14th -17th, 2009, San Diego, CA.

(Poster Presentation) High-dose epsilion-aminocaproic acid increases cardiac enzyme levels in patients following CABG surgery. Presented at the 9th UT Southwestern Cardiovascular Research Symposium, October 26-27, 2009, Dallas, TX.

(Poster Presentation) Designing an interventional trial in cardiac surgery patients with excessive bleeding after conventional blood transfusion therapy: A feasibility study. Presented at the 15th Society of Cardiovascular Anesthesiologists Update on Cardiopulmonary Bypass, March 21-26, 2010, Whistler, BC Canada.

2) Neeraj Satyanarayana, BS (2007-08) Medical Student at UT San Antonio
Neeraj worked as a research assistant in my lab for the year prior to starting at UTSA. He worked on a number of projects with the roles described above.

(Manuscript) Greilich PE, Jessen ME, Satyanarayana N, Whitten CW, Nuttall G, Beckham JM, Wall MH. Effect of epsilon-aminocaproic acid and aprotinin on fibrinolysis and blood loss in patients undergoing primary, isolated coronary artery bypasses grafting: A Placebo-controlled non-inferiority trial. Anesthesia and Analgesia 2009;109:15-24.

(Abstract) May T, Douning LK, Satyanarayana N, Sarode R, Gaza J, Davis M, Jenevein E, Buck B, Jessen M, Greilich PE. Cost: benefit analysis of thromboelastography in cardiac surgery. Transfusion 2007;47 (11):A123.

(Abstract) Greilich PE, Taneja R, Satyanarayana N, Whitten CW, Sarode R. Thrombin generation is attenuated with aprotinin, but not with epsilon-aminocaproic acid, in patients undergoing cardiopulmonary bypass surgery. Anesth Analg 2008;106 (SCA suppl):A80.

(Abstract) Greilich PE, Satyanarayana N, Brilakis E, Leonard D, Jessen ME. Epsilon-aminocaproic acid, but not aprotinin increases cardiac enzyme levels following CABG surgery. Anesthesiology 2008;109:A1620.

(Poster Presentation) Cost: Benefit Analysis of Thromboelastography in Cardiac Surgery: A Process Improvement Approach. Presented at the 7th UT Southwestern Cardiovascular Symposium, October 22-23, 2007, Dallas, TX

(Poster Presentation) Epsilon-aminocaproic acid, but not aprotinin increases myocardial ischemic injury in patients undergoing primary coronary artery bypass surgery. Presented at the 13th Annual Society of Cardiovascular Anesthesiologists Update on Cardiopulmonary Bypass, March 9-14, 2008, Whistler, BC, Canada.

(Poster Presentation) Thrombin generation is attenuated with aprotinin, but not with epsilon-aminocaproic acid in patients undergoing cardiopulmonary bypass surgery Presented at the 30th Annual Meeting of the Society of Cardiovascular Anesthesiologists, June 18-20, 2008, Vancouver, BC, Canada.

(Poster Discussion) Epsilon-aminocaproic acid, but not aprotinin increases cardiac enzyme levels following CABG surgery. Presented at American Society of Anesthesiology Meeting, October 18-22, 2008, Orlando, FL.

3) Chad Brouse, MS (2001-2004) Biomedical Engineering student who returned to his home in Nebraska to attend medical school. Chad worked as a research assistant in my lab for several years and was involved in a number of projects with the roles described above.

(Manuscript) Greilich PE, Brouse C, Beckham J, Estrera A, Carr ME: Reductions in platelet contractile force correlates with duration of cardiopulmonary bypass and blood loss in patients undergoing cardiac surgery. Thrombosis Research 2002;105:523-529.

(Manuscript) Nguyen KT, Su1 SH, Sheng1 A, Wawro D, Schwade ND, Brouse CF, Greilich PE, Tang L, Eberhart RC. In vitro hemocompatibility studies of drug-loaded poly (L-lactic acid) fibers. Biomaterials 2003;24:5191-5201.

(Manuscript) Greilich PE, Brouse CF, Whitten CW, Chi L, DiMaio JM, Jessen ME. Antifibrinolytic Therapy During Cardiopulmonary Bypass Reduces Proinflammatory Cytokine Levels: A Randomized, Double-Blind, Placebo-Controlled Study of -Aminocaproic Acid and Aprotinin. Journal Thoracic and Cardiovascular Surgery 2003;1498-1503.

(Manuscript) Greilich PE, Brouse CF, Rinder CS, Smith BR, Jessen ME. Antifibrinolytic therapy during cardiopulmonary bypass reduces leukocyte-platelet adhesion. Anesthesiology 2004;100:225-233.

(Manuscript) Greilich PE, Brouse CF, Rinder HR, Jessen ME, Rinder CS, Eberhart RC, Whitten CW, Smith BR. Monocyte activation in on-pump versus off-pump coronary artery bypass surgery. J Cardiothorac Vasc Anesth 2008;22:361-368.