- Top of page
- PATIENTS AND METHODS
Adult living donor liver transplantation (aLDLT) is associated with surgical risks for the donor and with the possibility of small-for-size syndrome (SFSS) for the recipient, with both events being of great importance. An excessively small liver graft entails a relative increase in the portal blood flow during reperfusion, and this factor predisposes the recipient to an increased risk of SFSS in the postoperative period, although other causes related to recipient, graft, and technical factors have also been reported. A hemodynamic monitoring protocol was used for 45 consecutive aLDLT recipients. After various hemodynamic parameters before reperfusion were analyzed, a significant correlation between the temporary portocaval shunt flow during the anhepatic phase and the portal vein flow (PVF) after reperfusion of the graft (R2 = 0.3, P < 0.001) was found, and so was a correlation between the native liver portal pressure and PVF after reperfusion (R2 = 0.21, P = 0.007). The identification of patients at risk for excessive portal hyperflow will allow its modulation before reperfusion. This could favor the use of smaller grafts and ultimately lead to a reduction in donor complications because it would allow more limited hepatectomies to be performed. Liver Transpl 19:174–183, 2013. © 2012 AASLD.
Like all types of partial graft transplantation, adult living donor liver transplantation (aLDLT) includes the risk of developing so-called small-for-size syndrome (SFSS), which is characterized by a progressive impairment of the synthesizing capacity of the liver and progressive liver failure. This possibility is inversely proportional to the graft size. An excessively small graft is incapable of meeting the metabolic demands of the recipient; thus, it is important in a clinical setting to ensure the correct relationship between the patient's weight and the graft size [graft-to-body weight ratio (GBWR)] as well as the hemodynamic condition of the recipient. Nowadays, the consensus is that grafts are small for size when the GBWR is less than 0.8% or the standard liver volume is less than 35%. Furthermore, a number of studies have shown that these grafts are related to poor survival rates.
The safety of the donor is undoubtedly one of the most important and controversial aspects of aLDLT. The morbidity rate associated with donation of the right liver lobe has been estimated to be 27% to 67%, and up to 38% of these morbidities are Clavien-Dindo classification stage I or II. Recent studies by Iida et al. and Belghiti et al. have confirmed that the most important factor in the appearance of complications is the magnitude of the hepatectomy (44.2% of overall complications in right lobe donors vs. 18.8% in left lobe donors, P < 0.05). The possibility of reducing the surgical risk in the donor necessarily involves reducing the size of this surgical operation.
It is obvious that if the left liver (representing 35% of the total volume) could guarantee the viability of the patient despite its small size, this would considerably reduce the size of the operation and thus the objective risk for the donor. However, to date, the use of the left lobe in adults has been limited because of its frequent association with SFSS.
On the other hand, the recipient of a liver transplant is generally a patient with advanced cirrhosis. The presence of portal hypertension in these patients is characterized by a hyperdynamic state with high cardiac output and reduced peripheral vascular resistance. After the native liver hepatectomy, the hyperdynamic state is temporarily maintained, so a high portal vein flow (PVF) persists. The combination of these 2 factors—a partial (small) graft and a high PVF—may lead to a situation of excessively high flow with respect to a reduced vascular bed and thus increase the risk of SFSS.[4, 13]
From a physiopathological point of view, these facts are of prime importance, and so transplant groups working in Asia have attempted to control the excess flow after reperfusion. These groups have been able to demonstrate that the portal pressure (PP), an indirect indicator of the flow, is a survival factor to the extent that at present, they suggest that it should be approximately 15 mm Hg at the end of the operation. Furthermore, a Hong Kong group has established that as long as PP is within this range, the graft size can be considerably reduced to a GBWR of 0.6%, and this makes it possible to use the left lobe of the donor with the same level of safety.
On the other hand, different authors have suggested that measuring only PP may not be adequate because a low PP does not necessarily mean an appropriate PVF. Instead, the portal pressure gradient (PPG) or the hepatic venous pressure gradient (HVPG) in addition to PVF may be better for evaluating graft compliance to hemodynamic stress, and this has been confirmed in both clinical and experimental studies.
Our group has shown in different experimental works that several factors must be taken into consideration. In the first place, when we are dealing with a partial graft, there is a need for a relative increase in the PVF rate, and this is known to be related to survival.[18, 20] However, if this flow is excessive, it might immediately damage the vascular endothelium and, depending on the degree, might lead to the development of SFSS. Two important conclusions can be derived from these experimental results: PVF at the time of reperfusion is of paramount importance, and it would be most interesting to know this information actually before reperfusion in order to be able to prevent excessive portal blood flow and subsequent endothelial injury.
From the beginning of our aLDLT program, we have systematically performed hemodynamic monitoring of our patients during the surgical procedure. Our purpose has been to control all factors that can place the graft in the most favorable situation at the time of reperfusion (appropriate PVF and artery flow). This surgical protocol includes the systematic performance of a portocaval shunt during the anhepatic phase. Recently, the possibility of modifying these conditions through what is called graft inflow modulation has given greater importance to hemodynamic monitoring during the transplant procedure.
The purposes of this study were to analyze hemodynamic parameters during liver transplantation with a living donor graft and to validate their usefulness for deciding what measures to take to improve posttransplant outcomes. In this sense, the hemodynamic information obtained with a portocaval shunt during the anhepatic phase of the procedure may be of great interest.
- Top of page
- PATIENTS AND METHODS
aLDLT has 2 major controversial issues. On the donor side, there is an objective surgical risk, which is in direct relationship to the magnitude of the operation. Right hepatectomy in itself involves morbidity and mortality rates that are considerably higher than those associated with left hepatectomy. On the recipient side, the appearance of SFSS is one of the most feared complications with a partial graft. Although the relatively small size of the graft is the major factor, other factors, such as a prolonged ischemia time, the presence of steatosis (which can be avoided in living donor liver transplantation), and the poor clinical condition of the recipient, may also play an important role in certain clinical situations.[19, 25]
The physiopathology of SFSS is complex; however, it is known that one of the most important factors is excessive flow at the moment of reperfusion, which results in damage to the sinusoidal vascular endothelium and ischemia of the hepatocyte cells (which, if it is severe enough, leads to functional failure of the graft). Thus, it is important to know the hemodynamic situation before reperfusion.
A pretransplant hemodynamic evaluation and hemodynamic monitoring during the procedure may facilitate important information not only about the degree of portal hypertension but also about the vascular status of the splanchnic area. This type of information may be of paramount importance if we are to avoid excessive portal blood flow after reperfusion.
Although the hemodynamic situation may be suggested by the overall clinical situation (including measurements such as the cardiac index and the peripheral vascular resistance index), to date there is no reliable factor (either preoperative or perioperative) that can be used to precisely identify the splanchnic hemodynamic situation and allow an adequate surgical approach, especially when a partial graft is being used. Current clinical experience is limited to altering the hemodynamic conditions once the graft is reperfused. The data in this study establish a direct relationship between the flow in the portocaval shunt and the flow during reperfusion of the partial graft, and they suggest for the first time that performing this temporary portocaval shunt during the anhepatic phase enables us to know the conditions before reperfusion, and determine whether they will be favorable or not (an appropriate PVF), and thus alter them to prevent any injury to the vascular endothelium (which appears, as we have shown previously, immediately after reperfusion). The experimental model shows that guaranteeing the recovery of the graft requires a relative increase in PVF. However, if this is excessive, it may be detrimental. Our group has been able to demonstrate in an experimental model of SFSS in pigs that this increase should be 2 to 3 times the initial PVF rate measured in the donor. Other groups have also confirmed this in clinical practice. Although it is still a matter of debate, the relative PVF considered to be the most suitable is approximately 250 to 300 mL/minute/100 g of liver tissue with a maximum value of 360 mL/minute/100 g of liver tissue.
To date, groups with greater experience have given considerable importance to the PP at the end of the operation. Early in their experience, they showed that a pressure greater than 20 mm Hg at the end of the operation was related to lower survival. Recently, these same authors demonstrated that a PP of 15 mm Hg was also associated with improved survival. They recommended achieving these values via splenectomy. This study is important because it establishes that when PP is within this range (<15 mm Hg), the size of the graft can be considerably reduced to a GBWR of approximately 0.6%.
This opens up the possibility of systematically using smaller grafts. Some groups have shown that the use of left grafts in adults may be safe despite portal hyperperfusion and a lack of graft inflow modulation; however, the lack of good systematic results in the literature means that most groups (including those in Asian countries) have relied on right lobes in order to guarantee adequate outcomes. The Fukuoka group recently showed that right living donor liver transplantation and left lobe living donor liver transplantation had comparable outcomes as long as the graft volume/standard liver volume ratio was greater than 35%. Despite their good results, the authors recognized that they had been using some type of graft inflow modulation (splenic artery ligation, splenectomy, or a permanent hemiportocaval shunt) and that criteria for performing such graft inflow modulation are lacking. In the United States, some other authors recently published their experience with the use of left lobes in adults, and they altered the flow by performing a partial portocaval shunt. Unfortunately, they also relied on PP, and the portal blood flow was measured in only 4 patients. Furthermore, the need for late occlusion and reoperation of the shunt due to the appearance of encephalopathy caused by excessive shunting or insufficient PVF has been described for this type of patient.
The common factor for all these groups (apart from their modifications relying on PP) is the fact that readings were taken once the graft had been reperfused, that is, when the endothelial damage may already have occurred. Our group and others believe that a normal or almost normal PP does not necessarily mean a suitable PVF; for this reason, we believe that it would be better to monitor PVF along with PP or PPG, preferably before reperfusion, in order to be able to modify it if that is necessary.
A recent clinical study by Sainz-Barriga et al. showed that the PP and flow rate do not always have a significant correlation, and the PP does not adequately reflect the hemodynamic situation in the graft. These authors described specific cases in which there was excessive PVF with a normal PP. They also pointed out that up to 25% of patients with an excessive PP (>20 mm Hg) had low PVF rates (<90 mL/minute/100 g). In conclusion, as these authors suggested previously, we think that both measurements, on which all modifications should be based, should be taken into account.
PP and especially PPG can undoubtedly be used to measure the compliance of the graft. However, a reduction in the compliance could be due to 2 factors: excessive incoming blood flow or inadequate venous drainage. Even though all groups are seeking the best possible drainage, this may be relative and sometimes even insufficient. This further stresses the importance of knowing the PVF rate during the anhepatic phase because this reading is made in the absence of any resistance. On the basis of the relationship found in this study, this information should be used to determine that there is no problem with the outflow drainage. The objective is to maintain, together with a normal or nearly normal PP or PPG, a flow similar (if it is satisfactory) to that obtained during the anhepatic phase in the absence of any type of modulation. In our experience, PVF not only is maintained but also tends to increase after reperfusion and, at the same time, reduce PP. The hemodynamic study on the third postoperative day allowed us to evaluate this trend to normality (7.5 mm Hg), which was later confirmed at 3 months.
In summary, hemodynamic monitoring during liver transplantation with a partial graft is necessary. In this context, we believe that a portocaval shunt should be performed systematically during the anhepatic phase. Knowledge of the PVF rate during this phase enables a precise determination of the conditions at the moment of reperfusion and thus allows any type of hemodynamic alteration to be made before reperfusion to ensure that the graft is in the most favorable situation. Moreover, this measured information enables us to ensure the best possible outflow drainage.