Effects of the intermittent Pringle manoeuvre on hepatic gene expression and ultrastructure in a randomized clinical study. Acute reactant cytokines and neutrophil adhesion after warm ischemia in cirrhotic and noncirrhotic human livers. Prospective evaluation of Pringle maneuver in hepatectomy for liver tumors by a randomized study. Effects of Pringle manoeuvre and ischaemic preconditioning on haemodynamic stability in patients undergoing elective hepatectomy: a randomized trial. Randomized clinical trial of liver resection with and without hepatic pedicle clamping.
The intermittent Pringle manoeuvre during hepatectomy results in a better clinical outcome when the accumulated ischaemia time is less than 120 min. The aim of this study was to investigate hepatic gene expression related to microcirculatory modulation and ultrastructural changes in patients having the intermittent Pringle manoeuvre.
                Forty patients who underwent hepatectomy for liver tumours were randomly assigned to liver transection with intermittent Pringle manoeuvre (Pringle group, n = 20) or without the manoeuvre (control group, n = 20). The clinical data and hepatic expression of endothelin (ET) 1 and endothelial nitric oxide synthase (eNOS) combined with liver ultrastructure were compared.
                The Pringle manoeuvre resulted in less blood loss (8.9 versus 12.4 ml/cm(2); P = 0.034), a shorter transection time (2.7 versus 4.1 min/cm(2); P = 0.015) and a lower serum bilirubin level on postoperative day 2 (26 versus 35 microm/l; P = 0.04). The hepatic messenger RNA content of ET-1 decreased by 38 per cent of the basal level in the Pringle group, whereas it increased by 28 per cent in the control group (P = 0.026). More patients in the control group showed swelling of mitochondria in hepatocytes and disruption of sinusoidal lining cells (12 of 20 patients versus three of 20 in the Pringle group; P = 0.008).
                The intermittent Pringle manoeuvre results in less disturbance of the hepatic microcirculation and better preservation of liver sinusoids after hepatectomy. Animal studies suggest that acute phase reactant cytokines and polymorphonuclear leukocytes (PMN) may play a critical role in ischemia-reperfusion injury. To evaluate whether similar mechanisms are operative in human liver, six cirrhotic and nine noncirrhotic patients undergoing right hepatectomy were randomized for utilization of hepatic vascular exclusion (HVE) as a model of ischemia-reperfusion injury. Portal and systemic levels of acute reactant cytokines (interleukin 6 [IL-6], interleukin 1 [IL-1], tumor necrosis factor alpha [TNF-alpha]) and neutrophil adhesion in serial liver biopsy specimens were studied. Correlations among mediators, leukocyte adhesion, and markers of liver injury were also evaluated. Hepatic vascular exclusion resulted in substantial and reproducible changes in portal and arterial IL-6 levels in both cirrhotic and noncirrhotic patients. Portal and systemic cytokine levels were comparable in most instances, whereas levels were usually higher in cirrhotic patients than in noncirrhotic patients. Negative correlations were found between IL-6 levels at the time of reperfusion and later TNF-alpha levels. IL-6 levels correlated negatively with numerous markers of hepatocellular injury and the number of postoperative complications. Hepatic vascular exclusion increased neutrophils adhesion after reperfusion in cirrhotic patients but not in noncirrhotic patients. In cirrhotic patients, the degree of leukocyte adhesion after reperfusion correlated with several postoperative markers of liver injury. This study in humans shows that acute reactant cytokines are released during liver ischemia and, interestingly, that IL-6 levels strongly correlate with clinical and laboratory measures of injury. Further studies to evaluate possible causal relationship with hepatic injury are warranted, with emphasis on the role of IL-6 and PMN adhesion. To evaluate whether vascular inflow occlusion by the Pringle maneuver during hepatectomy can be safe and effective in reducing blood loss.
                Hepatectomy can be performed with a low mortality rate, but massive hemorrhage during surgery remains a potentially lethal problem. The Pringle maneuver is traditionally used during hepatectomy to reduce blood loss, but there is a potential harmful effect on the metabolic function of hepatocytes. There has been no prospective randomized study to determine whether the Pringle maneuver can decrease blood loss during hepatectomy, improve outcome, or affect the metabolism of hepatocytes.
                From July 1995 to February 1997, we studied 100 consecutive patients who underwent hepatectomy for liver tumors. The patients were randomly assigned to liver transection under intermittent Pringle maneuver of 20 minutes and a 5-minute clamp-free interval (n = 50), or liver transection without the Pringle maneuver (n = 50). The surface area of liver transection was measured and blood loss during transection per square centimeter of transection area was calculated. Routine liver biochemistry, arterial ketone body ratio (AKBR), and the indocyanine green (ICG) clearance test were done.
                The two groups were comparable in terms of preoperative liver function and in the proportion of patients having major hepatectomy. The Pringle maneuver resulted in less blood loss per square centimeter of transection area (12 mL/cm2 vs. 22 mL/cm2, p = 0.0001), a shorter transection time per square centimeter of transection area (2 min/cm2 vs. 2.8 min/cm2, p = 0.016), a significantly higher AKBR in the first 2 hours after hepatectomy, lower serum bilirubin levels in the early postoperative period, and, in cirrhotic patients, higher serum transferrin levels on postoperative days 1 and 8. The complication rate, the hospital mortality rate, and the ICG retention at 15 minutes on postoperative day 8 were equal for the two groups.
                Performing the Pringle maneuver during liver transection resulted in less blood loss and better preservation of liver function in the early postoperative period. This is probably because there was less hemodynamic disturbance induced by the bleeding. The Pringle manoeuvre and ischaemic preconditioning are applied to prevent blood loss and ischaemia-reperfusion injury, respectively, during liver surgery. In this prospective clinical trial we report on the intraoperative haemodynamic effects of the Pringle manoeuvre alone or in combination with ischaemic preconditioning.
                Patients (n=68) were assigned randomly to three groups: (i) resection with the Pringle manoeuvre; (ii) with ischaemic preconditioning before the Pringle manoeuvre for resection; (iii) without pedicle clamping.
                Following the Pringle manoeuvre the mean arterial pressure increased transiently, but significantly decreased after unclamping as a result of peripheral vasodilation. Ischaemic preconditioning improved cardiovascular stability by lowering the need for catecholamines after liver reperfusion without affecting the blood sparing benefits of the Pringle manoeuvre. In addition, ischaemic preconditioning protected against reperfusion-induced tissue injury.
                Ischaemic preconditioning provides both better intraoperative haemodynamic stability and anti-ischaemic effects thereby allowing us to take full advantage of blood loss reduction by the Pringle manoeuvre. The purpose of this study was to compare the perioperative outcome of liver resection with and without intermittent hepatic pedicle clamping.
                Between June 2002 and June 2004, 126 consecutive patients with resectable liver tumours were randomized to undergo resection with (63 patients) or without (63 patients) intermittent hepatic pedicle clamping.
                The transection time was significantly higher in the group without hepatic pedicle clamping. The blood loss per cm(2) was similar in the two groups: 2.7 ml/cm(2) in the group with versus 3.2 ml/cm(2) in group without hepatic pedicle clamping (P = 0.425). In the subset of patients with an abnormal liver, there were no differences in blood loss per transection surface: 3.1 ml/cm(2) in the group with versus 2.9 ml/cm(2) in the group without clamping (P = 0.829). The rate of blood transfusions was not higher in the non-clamping group. No differences were observed in the postoperative liver enzyme serum levels, the in-hospital mortality (one patient in each group) or the number of complications.
                This study showed clearly that liver resection without hepatic pedicle clamping is safe, even in patients with a diseased liver.
                Copyright (c) 2006 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd.
Intermittent vascular occlusion seems safe in liver resection. However, it does not seem to decrease morbidity. More randomised trials seem to be needed.