Systemic inflammation in the brain‐dead organ donor

Abstract

Brain death itself impairs organ function in the potential donor, thereby limiting the number of suitable organs for transplantation. In addition, graft survival of kidneys obtained from brain-dead (BD) donors is inferior to that of kidneys obtained from living donors. Experimental studies confirm an inferior graft survival for the heart, liver and lungs from BD compared with living donors. The mechanism underlying the deteriorating effect of brain death on the organs has not yet been fully established. We know that brain death triggers massive circulatory, hormonal and metabolic changes. Moreover, the past 10 years have produced evidence that brain death is associated with a systemic inflammatory response. However, it remains uncertain whether the inflammation is induced by brain death itself or by events before and after becoming BD. The purpose of this study is to discuss the risk factors associated with brain death in general and the inflammatory response in the organs in particular. Special attention will be paid to the heart, lung, liver and kidney and evidence will be presented from clinical and experimental studies.

Brain death and its implications for management of the potential organ donor

“…49 Although the up-regulation of blood cytokines is well documented, the question of origin still remains unclear, and the link(s) between brain death and a systemic inflammatory response may be formed from many sources. 59 Possible sources include affected organs as well as immunocompetent cells in the blood or the damaged brain itself. Both the sympathetic storm and the hemodynamic instability following brain death seem to be involved in these processes because they can be attenuated experimentally by a-receptor blockade during brain death avoiding the hypertensive crisis, and by norepinephrine or volume loading after brain death avoiding the subsequent hemodynamic instability.…”

Influence of brain death and associated trauma on solid organ histological characteristics

“…However, many factors associated with BD which occur before it, such as multi-trauma, hemorrhage and hypoxia can trigger different pathophysiological responses in the organs [3][4][5] .…”

Lung Transplantation for Cystic Fibrosis

“…A variety of surgical complications can contribute to or mimic PGD, including venous obstruction, arterial stenosis, malorientation of the graft, phrenic nerve injury, and size mismatch between graft and recipient. Donor factors also contribute to PGD including the inflammatory state (45,49), endocrine failure, and hemodynamic instability associated with brain death (45,49), as well as ventilator-associated injury (35,(23)(24)(25) from ventilator trauma or bacterial overgrowth of the graft. The age of the donor also has a significant effect on the deleterious effect of prolonged ischemic time, a point first demonstrated by Novick and coauthors (44).…”

“…There remains a need to determine which factors are most useful in directing changes in pre-transplant and post-transplant patient management to improve outcome. The consensus of Conference attendees was that without clinical factors clearly predictive of outcomes, a range of biomarkers and additional potential risk factors should be considered for further multicenter investigation (35,37,38,45,46,49,68,71). For example, biomarkers of inflammation (IL-2; IL-6; IL-8; IL-10; TGF-b, etc.)…”