Preload responsiveness is associated with increased interleukin-6 and lower organ yield from brain-dead donors

Solid organ transplantation is currently the only definitive treatment option available for patients with end-stage organ failure. In the United States, approximately 100,000 candidates were on the transplant waiting list for various organs in 2008 (1). However, there were only 5,000 brain-dead organ donors, who donated approximately >14,000 organs for transplantation, an average of only 2.8 organs per donor (1). This large disparity between the transplant waiting-list candidates and the limited number of available organs poses a significant public health crisis. Although there are many reasons why not all organs are transplanted, such as donor age, comorbidities, and inflammation (2), hemodynamic instability in brain-dead organ donors is an important cause (3, 4). Hemodynamic instability in potential organ donors is caused by several factors, such as autonomic dysfunction, hypovolemia, cardiac dysfunction, release of vasoactive inflammatory molecules, and secondary adrenal insufficiency (5), and may result in ischemia and reperfusion injury leading to organ dysfunction and loss (6). Hemodynamic instability can lead to increased inflammation and cardiac ischemia, which in turn can result in further hemodynamic instability, producing a vicious cycle (7–9). Therefore, optimal donor resuscitation may salvage many borderline organs and is critical to improve the number and quality of organs for transplantation (10). However, little is known about organ donor resuscitation practices because many donors are not invasively monitored. Although resuscitation with fluids, vasopressors, and inotropes is the only practical and effective management strategy available to optimize donor hemodynamics, traditional tools for assessing preload and preload (fluid) responsiveness (i.e., increase in cardiac output following fluid infusion) using central venous pressure and pulmonary artery occlusion pressure are notoriously inaccurate (11, 12). Recently, less invasive, functional hemodynamic variables, such as pulse pressure variation (PPV), derived from the arterial waveform analysis, have been found to be more sensitive and specific in assessing preload responsiveness (13). In this observational pilot study in brain-dead organ donors, we use PPV to assess donor preload responsiveness and test two hypotheses: 1) donor preload responsiveness is associated with increased inflammatory response; and 2) donor preload responsiveness is associated with lower number of organs procured and transplanted. Although preload responsiveness is a normal state, it also exists in hypovolemia, and we hypothesized that in resuscitation of organ donors, the presence of preload responsiveness would be a marker of underresuscitation. We have previously shown that inflammation in the donor, as measured by circulating interleukin (IL)-6 concentration, is associated with decreased organ yield and reduced hospital-free survival in recipients of organs from donors with increased IL-6 (2).