Brain Death as a Novel Preclinical Human Model for the Advancement of Medicine
1University of Alabama at Birmingham, Birmingham, AL, 2University of Alabama at Birmingham Hospital, Birmingham, AL, 3Legacy of Hope, Birmingham, AL
Meeting: 2022 American Transplant Congress
Abstract number: 1789
Keywords: Hemodynamics
Topic: Clinical Science » Organ Inclusive » 68 - Deceased Donor Management and Intervention Research
Session Information
Session Name: Deceased Donor Management and Intervention Research
Session Type: Poster Abstract
Date: Tuesday, June 7, 2022
Session Time: 7:00pm-8:00pm
Presentation Time: 7:00pm-8:00pm
Location: Hynes Halls C & D
*Purpose: For interventions that lack US Food and Drug Administration approval, testing is limited and relies on preclinical animal models to determine safety and efficacy. Brain dead organ donors may better replicate human physiology, though hemodynamic instability associated with brain death poses a potential barrier to testing invasive interventions. Herein we describe the hemodynamic findings of the first major non-procurement, surgical intervention in a decedent model.
*Methods: The decedent was declared brain dead and transferred to the local organ procurement organization. Family authorization was obtained. Brain death physiology was managed with intravenous corticosteroids, vasopressors, levothyroxine, and fluids. Bilateral native nephrectomies and renal xenograft transplants were performed. Procedure-associated heparin, diuretics, antibiotics, and immunosuppressive therapy were provided. Hemodynamics were monitored from enrollment to somatic death, and descriptive statistics were calculated.
*Results: The 57-year-old male decedent was enrolled on day 5 of brain death. Preoperatively, the descendent was mildly bradycardic (mean heart rate (HR) 58 (standard deviation (SD) 1) bpm) and normotensive (average mean arterial pressure (MAP) 89 (SD 15) mmHg) on phenylephrine (0.3-1 mcg/kg/min) and vasopressin (0.001-0.008 units/min; Figure 1A). Intraoperative hemodynamic monitoring demonstrated HR and MAP stability with phenylephrine (0.1-1 mcg/kg/min), dopamine (2.5-5 mcg/kg/min), and ephedrine (10 mg x 3 doses). Reperfusion of neither xenograft resulted in hemodynamic collapse (Figure 1B). Postoperatively, the decedent was intermittently tachycardic (HR 92 (SD 8) bpm) and normo- to hypertensive (MAP 107 (SD 17) mmHg) but required increasing vasopressor support with phenylephrine (0.2-3 mcg/kg/min), dopamine (4-25 mcg/kg/min), and norepinephrine (0.03-0.2 mcg/kg/min). On postoperative day 3 (day 8 of brain death), cardiopulmonary support ceased, and the decedent progressed to somatic death.
*Conclusions: We describe a preclinical American Society of Anesthesiologists class VI human model for research. Using standard of care management for brain dead organ donors and relatively low vasopressor support, hemodynamic stability was maintained pre-, intra- and postoperatively. These findings have promising implications not only for xenotransplantation but for the preclinical evaluation of novel devices or procedures.
To cite this abstract in AMA style:
Killian C, Orandi B, Anderson D, Kumar V, Stegner K, Budd N, Macedon S, Shunk A, Porrett P, Locke J. Brain Death as a Novel Preclinical Human Model for the Advancement of Medicine [abstract]. Am J Transplant. 2022; 22 (suppl 3). https://atcmeetingabstracts.com/abstract/brain-death-as-a-novel-preclinical-human-model-for-the-advancement-of-medicine/. Accessed September 7, 2024.« Back to 2022 American Transplant Congress