**6. Conclusions**

390 Liver Transplantation – Basic Issues

tachycardia, dysrrythmias, and severe myocardial depression by producing changes in resting membrane potential and threshold potential and an increase in the rate of phase IV depolarization. Therefore the use of VVB has been proposed to decrease the incidence of

Lastly, the release of inflammatory factors from the post-ischemic donor liver graft into the recipient systemic circulation also can trigger a systemic inflammatory chain reaction that can lead to systemic hypotension and multi-organ dysfunction. Therefore, the quality of the donor can be a risk factor for PRS, and postoperative graft function (primary non-function, and graft survival). A donor organ with certain characteristics such as extreme age, adverse past medical history, preexisting liver damage or disease, obesity, hemodynamic instabilities, deceased cardiac donor (DCD), risk of sepsis and malignancies, hypernatremia, and prolonged ICU stay, may be more susceptible to ischemia, and more likely to have higher incidence of primary non-function (PNF), delayed function or subsequent risk for reduction in long-term graft survival. Similarly, several studies have attempted to identify donor risk factors for PRS. Hilmi et al reported warm ischemia time as a risk factor and more recently Paugam-Burtz, et al reported cold ischemia time is also a risk for PRS. In addition to those prior studies, donor age is an important risk factor for PRS. The older donor graft has a lower tolerance for hypoxia, and a greater susceptibility to reperfusion injury, probably due to metabolic changes associated with senescence, age related atherosclerotic changes in vascular structures , or steatotic changes of the parenchyma. The type of preservation solution and the graft flushing techniques have also been shown to

Warm recipient blood flows into the cold organ after revascularization of the portal vein, causing immediate volume shifts, re-oxygenation of the ischemic organ, and outflow of cold preservation solution saturated with vasoactive pro-inflammatory factors. Optimization of volume status in the recipient prior to reperfusion may minimize hemodynamic changes related to volume shifts by maximizing hemodynamic capacity to maintain good perfusion pressure throughout the liver graft, especially the large-for-size graft. TEE coupled with close monitoring of hemodynamic parameters with continuous cardiac output (CO)/SvO2, and standard cardiac monitors are particularly helpful to ensure hemodynamic integrity of the recipient. To obtain sufficient perfusion of the liver graft, especially through the hepatic microcirculation, vasodilating agents such as prostaglandin or calcium channel blockers can be used but with caution since those agents can aggravate hemodynamic instability. To minimize the sudden outflow of preservation solution from the liver graft, flushing the organ prior to reperfusion has been used and currently proposed as the most effective way of preventing hemodynamic instability associated with the inadvertent release of preservation solution. Ingredients of the flush solution as well as rate of infusion, temperature of flush solution, and amount of solution are still under investigation. Gradual and homogeneous perfusion of the organ by machine perfusion immediately prior to implantation may improve graft function by effectively removing the pro-inflammatory factors from the graft microcirculation, may reduce PRS and improve short and long term graft survival, especially in the ECD. Preemptive use of vasopressors may help maintain the

PRS by minimizing small bowel edema/ischemia with varying results.

**5. Strategy for the intraoperative management of PRS** 

**4.3 Donor factors** 

affect the severity of PRS.

After having contributed to the establishment of liver transplantation as a safe and definitive treatment option for patients with end stage liver disease, including those with ESLD complicated by hepatocarcinomas, in the latter half of the 20th century, the next challenge to Transplant Anesthesiologists and Critical Care Specialists in the 21st is to continue to improve the perioperative management of the donor and organ transplant recipient during the most critical period of the liver transplant procedure namely, revascularization, reperfusion and re-oxygenation of the graft. This effort will undoubtedly require multicenter research collaborations, the determination of better and more reliable end-points for PRS and graft function, and the institution and conduct of multicenter clinical trials. Inevitably research will most likely reveal the need for a multi-factorial treatment strategy to preempt or mitigate PRS and the deterioration of graft function, especially of the ECD graft. This effort comprises preconditioning of the donor, preservation and post condition of the recipient transplanted, a process that can be succinctly described as 'organ resuscitation'. Better post-transplant outcomes will decrease the costs involved in retransplantation, and prolonged ICU and hospital stays.
