LIVER TRANSPLANTATION 19:174-183, 2013
ORIGINAL ARTICLE
Importance of the Temporary Portocaval Shunt During Adult Living Donor Liver Transplantation s,1 Constantino Fondevila,1 David Calatayud,1 Joana Ferrer,1 Santiago Sanchez-Cab u 2 Jose Fuster,1 and Juan Carlos Garcı´a-Valdecasas1 Pilar Taura, 1 Hepatobiliary Surgery and Liver Transplantation Unit and 2Anesthesiology Unit, Hospital Clı´nic of Barcelona, Barcelona, Spain
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 ¼ 0.3, P < 0.001) was found, and so was a correlation between the native liver portal pressure and PVF after reperfusion (R2 ¼ 0.21, P ¼ 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. V 2012 AASLD. C
Received April 17, 2012; accepted September 28, 2012.
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.1 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 [graftto-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.2-5
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%,6 and up to 38% of these morbidities are Clavien-Dindo classification stage I or II.7 Recent studies by Iida et al.8 and Belghiti et al.9 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
Abbreviations: aLDLT, adult living donor liver transplantation; ALT, alanine aminotransferase; GBWR, graft-to-body weight ratio; HVPG, hepatic venous pressure gradient; PP, portal pressure; PPG, portal pressure gradient; PVF, portal vein flow; SFSS, smallfor-size syndrome; rPVF: portal vein flow relative to graft weight. Address reprint requests to Juan Carlos Garcı´a-Valdecasas, M.D., Ph.D., Hepatobiliary Surgery and Liver Transplantation Unit, Hospital Clinic of Barcelona, Villarroel 170, Barcelona, Spain 08036. Telephone: þ34932275718; FAX: þ34932275589; E-mail:
[email protected] DOI 10.1002/lt.23558 View this article online at wileyonlinelibrary.com. LIVER TRANSPLANTATION.DOI 10.1002/lt. Published on behalf of the American Association for the Study of Liver Diseases
C 2012 American Association for the Study of Liver Diseases. V
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of the left lobe in adults has been limited because of its frequent association with SFSS.10 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.11 After the native liver hepatectomy, the hyperdynamic state is temporarily maintained,12 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.14 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.15 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.16-19 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.13 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.
TABLE 1. Demographic Characteristics of Recipients of Living Donor Liver Transplantation Characteristic Age (years)* Sex: male/female (n/n) Patient weight (kg)* Native liver weight (g)* Graft weight (g)* GBWR (%)* Origin of liver disease Hepatitis C virus infection Alcoholic cirrhosis Hepatitis B virus infection Hepatitis B virus and hepatitis C virus infection Cryptogenic cirrhosis Nonalcoholic steatohepatitis Primary biliary cirrhosis Autoimmune hepatitis Child-Turcotte-Pugh score A B C Model for End-Stage Liver Disease score* Hospital stay (days)* Mean follow-up (months)
Value 54.7 6 9.2 32/13 70.6 6 14.9 1119.6 6 224.6 710.7 6 126.6 1.04 6 0.2 30 9 1 1 1 1 1 1 11 21 13 13.5 6 4.1 32.4 6 18.9 44.0
*The data are presented as means and standard deviations.
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.
PATIENTS AND METHODS The aLDLT program and all the clinical protocols derived from it were approved by the hospital’s ethics committee at the start of the program. Forty-five consecutive patients undergoing right lobe aLDLT from 2003 to 2011 were analyzed. No patient was excluded, and these patients represent the full series of aLDLT procedures performed at our center during that period. The data were collected prospectively and were analyzed retrospectively. Table 1 shows the demographic characteristics as well as the indications for transplantation.
Donor Surgery The surgical procedure for the donor was previously published.20 Briefly, it consisted of a right hepatectomy (liver segments V-VIII) with preservation of the
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middle hepatic vein, which remained in the donor. After an ultrasonographic and cholangiographic study, the elements of the hepatic hilum were identified, and the right hepatic vein was isolated. Liver parenchymal transection with a Cavitron ultrasonic surgical aspirator (Tyco Healthcare, Mansfield, MA) and TissueLink (TissueLink Medical, Inc., Dover, NH) was performed. Great care was taken to identify the branches of the middle hepatic vein with a diameter of more than the 5 mm. All were revascularized in the recipient with cryopreserved grafts of the iliac artery to achieve the best possible venous drainage. Once the graft was extracted, it was perfused with Celsior solution through the portal vein.
Recipient Surgery Hepatectomy The surgical operation for the recipient consisted of 2 well-differentiated stages: hepatectomy of the native liver and graft implantation. Before the hepatectomy, a 16-G venous catheter with a length of 30 cm (Certofix Mono S 330, Braun) was placed into the mesenteric vein, and the tip was advanced into the portal vein. This catheter was used to measure PP during the operation. Hepatectomy was performed as previously published21 with systematic preservation of the inferior vena cava as well as a temporary terminolateral portocaval shunt, which was routinely sectioned before graft implantation.
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TABLE 2. Variables Analyzed for the Hemodynamic Monitoring Protocol Preoperative Monitoring Cardiopulmonary Hemodynamics Pulmonary artery pressure Pulmonary capillary wedge pressure Right atrial pressure Cardiac output Median arterial pressure Heart rate Cardiac index Stroke volume Systemic vascular resistance Systemic vascular resistance index Pulmonary vascular resistance Pulmonary vascular resistance index
Hemodynamic Monitoring Hemodynamic monitoring of liver transplant recipients was undertaken only for those receiving living donor grafts at our center. No complications were experienced by the recipients as a result of their compliance with the protocol. The protocol consisted of 2 differentiated stages. First, the recipient’s hemodynamic measurements were taken by the hepatic hemodynamics laboratory22 24 hours before the surgical operation, on the third day after transplantation, and in the third month. The aim of these evaluations was to provide extensive knowledge
Wedged hepatic venous pressure Free hepatic venous pressure HVPG
Perioperative Monitoring Time of Measurement Onset of the intervention After portocaval shunt After portal reperfusion After arterial reperfusion After splenic artery ligation End of the operation
Implantation The implantation began with a wide (4-cm) end-to-lateral anastomosis between the right hepatic vein of the graft and the recipient’s vena cava. If it was necessary, anastomosis of the accessory veins was performed independently of the vena cava. This was followed by sectioning of the portocaval shunt and the performance of an anastomosis between the portal vein of the recipient and the right portal vein of the graft. The portocaval shunt was left in no patients after graft implantation, and none of the patients required ligation of preexisting spontaneous portocaval shunts. Finally, the hepatic artery anastomosis and the bile duct anastomosis were completed.
Hepatic Hemodynamics
Variable Portal vein pressure PVF Hepatic artery flow Cardiac output Median arterial pressure Central venous pressure Vascular resistance
Postoperative Monitoring Wedged hepatic venous pressure Free hepatic venous pressure HVPG
of the hemodynamic status of the recipient before surgery and to ascertain the normalization of the patient’s portal hypertension after liver transplantation. Second, an intraoperative hemodynamic assessment was performed. Hemodynamic measurements were taken in 5 well-defined phases: at the baseline, during the anhepatic phase, after portal reperfusion, after hepatic artery reperfusion, and at the end of the operation. All collected hemodynamic parameters are shown in Table 2. Systemic hemodynamic parameters were continuously monitored with invasive methods (an arterial line and a pulmonary catheter).23 After the vascular anastomoses were completed, hemodynamic measurements were taken for all patients after an arbitrarily defined 5-minute period.
Flow Measurements Flow rate measurements were made with the method for determining the transit time flow, with 8-mm to
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TABLE 3. Criteria for SFSS Small-for-Size Dysfunction Dysfunction* of a small graft (GBWR < 0.8%) during the first postoperative week after the exclusion of other causes†
Small-for-Size Nonfunction ‡
Failure of a small graft (GBWR < 0.8%) during the first postoperative week after the exclusion of other causes†
*Dysfunction is defined as the presence of 2 of the following criteria on 3 consecutive days: bilirubin level > 100 lmol/L, international normalized ratio > 2, and grade 3 or 4 encephalopathy. † The exclusion criteria include technical criteria (eg, arterial or portal occlusion, outflow congestion, or bile leak), immunological criteria (eg, rejection), and infections (eg, cholangitis or sepsis). ‡ Failure is defined as retransplantation or death. NOTE: This table was adapted with permission from American Journal of Transplantation.1 Copyright 2005, John Wiley & Sons, Inc.
12-mm probes used for the portal vein and 3-mm to 5-mm probes used for the hepatic artery; they were monitored with the VeriQ 1001 system (Medi-Stim ASA, Oslo, Norway). The purpose was to achieve a PVF less than 2000 mL/minute at the time of reperfusion and (as long as the weight of the graft was known) a relative PVF less than 300 mL/minute/100 g of liver tissue. An arterial flow less than 100 mL/minute was arbitrarily considered insufficient. Splenic artery ligation was performed in 13 patients for excessive PVF (n ¼ 4), inadequate arterial flow (n ¼ 3), or a combination of the two (n ¼ 6).
Pressure Measurements HVPG was measured preoperatively and postoperatively on the third day and in the third month at the hemodynamics laboratory.22 It was defined as the hepatic wedged pressure (equivalent to PP) minus the hepatic free pressure (equivalent to the central venous pressure). PP was measured continuously with a Philips IntelliVue MP70 anesthesia monitor (Philips MedizinSys€ blingen, Germany) through a portal vein tems, Bo catheter placed at the beginning of the intervention. The normal range for directly measured PP values was considered to be 7 to 12 mm Hg.24 PPG was defined as the PP directly measured during the surgical intervention minus the central venous pressure.
Liver Function Analytical determinations of the liver function [aspartate aminotransferase, alanine aminotransferase (ALT), alkaline phosphatase, gamma-glutamyltransferase, total bilirubin, and prothrombin index] were made in the immediate postoperative period on days 1, 2, 3, 5, 7, and 10 and later in the first and third months after surgery. Patients remained in the intensive care unit under continuous observation during the first few days. For the purposes of this study, a follow-up period of 3 months after transplantation was taken into consideration.
The diagnosis of SFSS used the clinical and analytical criteria described by Dahm et al.1 (Table 3).
Statistical Study The statistical differences between groups were analyzed with the Student t test for numerical variables and with Pearson’s v2 test for categorical variables. The statistical correlations between continuous variables were analyzed with the Pearson correlation test. All the results are expressed as means and standard deviations unless otherwise specified. A measurement was considered statistically significant if P was
