Intermittent Vascular Inflow Occlusion Research Articles

Comparison of Perioperative Outcomes between Intermittent Vascular Inflow Occlusion versus Intermittent Selective Hepatic Vascular Exclusion in Liver Resections for Cholangiocarcinoma Treatment

Comparison of Perioperative Outcomes between Intermittent Vascular Inflow Occlusion versus Intermittent Selective Hepatic Vascular Exclusion in Liver Resections for Cholangiocarcinoma Treatment

Comparison of Early Clinical Outcomes between Intermittent Vascular Inflow Occlusion versus Intermittent Selective Hepatic Vascular Exclusion in Hepatic Resections for Cholangiocarcinoma Patients: A Prospective Randomized Controlled Trial Study

Background: There were reported benefits of selective hepatic vascular exclusion (SHVE) in reducing intraoperative blood loss (IBL), intraoperative packed red cell (PRC) transfusion, and perioperative complications over intermittent Pringle maneuver (IPM) in hepatectomies. However, there was lack of data regarding the use of SHVE in comparison with IPM in hepatectomies for cholangiocarcinoma (CCA) patients. Objective: To compare IBL, intraoperative PRC transfusion, total operative time (TOT), and perioperative complications between SHVE and IPM. Materials and Methods: Between October 2018 and September 2019, forty eligible CCA patients participated in the study. They were randomly allocated to the SHVE group (n=20) or the IPM group (n=20). Data regarding patient demographics, tumor characteristics, and the objectives of the study were gathered and analyzed with intention-to-treat principle. Results: The median IBL (range) 923.5 (101 to 4,979) versus 1,109 (413 to 5,305) ml; p=0.2, median intraoperative PRC transfusion (range) 112.5 (0 to 1,745) versus 296 (0 to 1,500) ml; p=0.22, and median TOT (range) 390 minute (220 to 915) versus 320 (240 to 930) minutes; p=0.55 between SHVE and IPM were not significantly different. There was no statistical difference in perioperative complications between SHVE and IPM. Conclusion: Routine use of SHVE during hepatectomies in CCA patients showed no significant difference in outcomes regarding the objectives of the study. Keywords: Selective hepatic vascular exclusion (SHVE), Hepatic vascular exclusion with preservation of caval flow (HVEPV), Hepatic resection, Cholangiocarcinoma, Intraoperative blood loss, Perioperative complications

Hypothermic perfusion with retrograde outflow during right hepatectomy is safe and feasible

In situ hypothermic perfusion during liver resection performed under vascular inflow occlusion decreases hepatic ischemia-reperfusion injury, but technical limitations have restricted its widespread use. In situ hypothermic perfusion with retrograde outflow circumvents these impediments and thus could extend the applicability of in situ hypothermic perfusion. The safety and feasibility of in situ hypothermic perfusion with retrograde outflow were analyzed in selected patients undergoing right (extended) hepatectomy and compared to intermittent vascular inflow occlusion, the gold standard method, in this randomized pilot study. Patients were first screened for parenchymal liver disease (exclusion criteria: steatosis ≥30%, cirrhosis, or cholestasis). Study participants were randomized intraoperatively to undergo in situ hypothermic perfusion with retrograde outflow (n=9) or intermittent vascular inflow occlusion (n=9). The target liver core temperature during in situ hypothermic perfusion with retrograde outflow was 28°C. The primary end point was ischemia-reperfusion injury (expressed by peak postoperative transaminase levels). Secondary outcomes included functional liver regeneration (assessed by hepatobiliary scintigraphy) and clinical outcomes. Peak transaminase levels, total bilirubin, and the international normalized ratio were similar between both groups, although a trend toward more rapid normalization of bilirubin levels was noted for the in situ hypothermic perfusion with retrograde outflow group. Functional liver regeneration as evaluated by hepatobiliary scintigraphy was improved on postoperative day 3 fafter in situ hypothermic perfusion with retrograde outflow but not after intermittent vascular inflow occlusion. Furthermore, in situ hypothermic perfusion with retrograde outflow (requiring continuous ischemia) was comparable to intermittent vascular inflow occlusion for all clinical outcomes, including postoperative complications and hospital stay. The use of in situ hypothermic perfusion with retrograde outflow appears to be safe and feasible in selected patients with healthy liver parenchyma and may benefit early functional liver regeneration. Future applications of in situ hypothermic perfusion with retrograde outflow include patients with damaged liver parenchyma who would require major hepatic resection with a prolonged vascular inflow occlusion duration.

Hepatic cytoprotective effect of ischemic and anesthetic preconditioning before liver resection when using intermittent vascular inflow occlusion: A randomized clinical trial

Ischemic preconditioning (IPC) and anesthetic preconditioning (APC) have been reported to attenuate ischemia-reperfusion (IR) injury after liver resection under continuous inflow occlusion. This study evaluates whether these strategies enhance hepatic protection of remnant liver against IR after liver resection with intermittent clamping (INT). A total of 106 patients without underlying liver disease and submitted to liver resection using INT were randomized into 3 groups: IPC (10 minutes of inflow occlusion followed by 10 minutes of reperfusion before liver transection), APC (sevoflurane administration for 20 minutes before liver transection), and INT (no preconditioning). Patients were also stratified according to the extent of the hepatectomy. Cytoprotection was evaluated by comparing hepatocyte and endothelial dysfunction markers, apoptosis, histologic lesions, and postoperative outcome. No differences were observed in preoperative chemotherapy and steatosis, total warm ischemia time, operative time, or blood loss. Kinetics of transaminases (aspartate aminotransferase, P = .137; alanine aminotransferase, P = .616), bilirubin (P = .980), and hyaluronic acid increase (P = .514) revealed no differences. Significant apoptosis was present in 40% of patients, mild-to-moderate leukocyte infiltration and steatosis in 45% and 55%, respectively, and mild sinusoidal congestion in 65%, with a similar distribution in the 3 groups. When patients were stratified by major versus minor resections, no differences were observed in any of the variables studied. Postoperative clinical outcomes were also similar. These results suggest that these protocols of IPC and APC used in this study do not provide better cytoprotection from IR when INT is used.

Randomized clinical trial of ischaemic preconditioning in major liver resection with intermittent Pringle manoeuvre

Vascular inflow occlusion is effective in avoiding excessive blood loss during hepatic parenchymal transection but may cause ischaemic damage to the remnant liver. Intermittent portal triad clamping (IPTC) is superior to continuous hepatic pedicle clamping as it avoids severe ischaemia-reperfusion (IR) injury in the liver remnant. Ischaemic preconditioning (IPC) before continuous Pringle manoeuvre may protect against IR during major liver resection. This RCT assessed the impact of IPC in major liver resection with intermittent vascular inflow occlusion. Patients undergoing major liver resection with intermittent vascular inflow occlusion were randomized, during surgery, to receive IPC (10 min inflow occlusion followed by 10 min reperfusion) or no IPC (control group). Data analysis was on an intention-to-treat basis. The primary endpoint was serum alanine aminotransferase (ALT) level on the day after surgery. Eighty four patients were enrolled and randomized to IPC (n = 41) and no IPC (n = 43). The groups were comparable in terms of demographic data, preoperative American Society of Anesthesiologists grade and extent of liver resection. Intraoperative morbidity and postoperative outcomes were also similar. ALT levels on the day after operation were not decreased by IPC (mean(s.d.) 537·6(358·5) versus 525·0(400·6) units/ml in IPC and control group respectively; P = 0·881). Liver biochemistry tests in the week after operation showed the same pattern in both groups. IPC did not reduce liver damage in patients undergoing major liver resection with IPTC. NCT00908245 (http://www.clinicaltrials.gov).

Management of hepatobiliary and pancreatic disorders at the Academic Medical Center Amsterdam, Netherlands

Academic Medical Center opened in 1980 and replaced the old pavilion hospitals with separated departments inside Amsterdam. Since that time the concept of a multidisciplinary approach for patients with gastrointestinal disorders, and in particular hepatobiliary and pancreatic diseases, has been developed. This approach started with a strong interest in the non-surgical treatment of HPB diseases by the endoscopic route and stenting developed by Drs Kee S Huibregtse and Guido Tytgat 1,2. The former chairman of the Department of Surgery, Dr Niels van der Heyde, added the expertise of the surgical approach. His main interest was the surgical treatment and effect of radiotherapy for proximal bile duct tumours (Klatskin tumours) 3,4. Drs Huug Obertop (chairman of the Department of Surgery) and Dirk Gouma were appointed in 1993. Together with Dr Thomas van Gulik (head of Experimental Surgery), and Dr Olivier Busch, they lead the ‘surgical’ programme of HPB disorders. The AMC is a tertiary referral center for HPB diseases in the Netherlands as well as providing a general service for the local community. An important binding factor in the clinical programme as a referral centre is the twice-weekly multidisciplinary HPB meeting. The referral and multidisciplinary management of 250 patients with bile duct injuries after laparoscopic cholecystectomy during the past years emphasises this function 5,6. Gallstone formation and the surgical and non-surgical management of symptomatic gallstone disease have also been studied extensively by the departments of Surgery and Gastroenterology 7,8,9. During the past decade several aspects of the management of HPB malignancies have been studied, again by cooperation of different departments. The value of diagnostic laparoscopy and other diagnostic modalities such as endosonography, ultrasound and spiral CT-scan, preoperative biliary drainage and perioperative feeding are analysed in different studies 10,11,12,13,14. The role of systemic inflammation and cytokine release in obstructive jaundice and biliary drainage have been analysed in detail 15,16. The non-operative approach of (benign and malignant) HPB diseases is strongly stimulated by the gastroenterologists and the new team of radiologists (Dr Han Lameris, chairman) 2,5,8,17. The results of the pylorus-preserving pancreatoduodenectomy and aspects of centralisation are studied in data from the AMC and the whole of the Netherlands 18. Together with the Department of Pathology (Drs Fiebo ten Kate and Johan Offerhaus) the prognostic role of diagnostic markers in bile duct and pancreatic carcinoma has been investigated 19,20. Effects of chemoradiotherapy in pancreatic carcinoma and radiotherapy in proximal bile duct tumours are studied in collaboration with the Department of Medical Oncology and Radiotherapy (Drs Gonzalez and Van Tienhoven). Finally within the liver programme, the current studies include the ischaemia-reperfusion phenomenon after liver resection, the effect of extrahepatic cholestasis on liver regeneration, continuous or intermittent vascular inflow occlusion during resection and a new bioartificial liver (BAL) 23,24,25,26. The development of adenoviral gene therapy was initiated recently in a new multidisciplinary research programme. The multidisciplinary approach to patient care has improved the quality of care, as has the combination of clinical and fundamental research by the different members of our HPB team (Figure 1). Figure 1. Standing (from left, to right): Dr Erik AJ Rauws (gastroenterologist), Dr Olivier RC Busch (surgeon), Dr Otto M van Delden (radiologist), Dr Daniel C Aronson (pediatric surgeon), Prof G Johan A Offerhaus (pathologist), Prof Thomas M van Gulik (surgeon), ...

Hepatic resection using intermittent vascular inflow occlusion and low central venous pressure anesthesia improves morbidity and mortality

Hepatic resection results in significant morbidity and mortality primarily related to intraoperative blood loss. Intermittent vascular inflow occlusion (VO) and low central venous pressure (CVP) during hepatectomy have been used to reduced blood loss. To determine the benefit of VO and low CVP, we reviewed the outcomes of 168 consecutive patients who underwent liver resection. The results of 78 patients who had undergone hepatic resection between 1993 and 1998 with the use of VO and low CVP (post-VO/CVP) were compared to the previous 90 patients who had undergone hepatectomy without VO and low CVP (pre-VO/CVP) between 1979 and 1992. Hepatectomies were performed for metastatic disease (65%), hepatoma (20%), and benign tumors (15%). Resections included 18 trisegmentectomies, 67 lobectomies, and 83 segmental resections. Patients in both groups were similar with regard to extent of resection. Post-VO/CVP patients had significantly lower median estimated blood loss (725 ml vs. 2300 ml, P <0.001), less postoperative morbidity (10.3% vs. 22.2%, P = 0.038), lower in-hospital mortality (2.6% vs. 10%, P = 0.050), fewer days in the intensive care unit (1.6 ± 0.1 days vs. 5.6 ± 1.2 days, P = 0.003), and shorter overall length of stay (8.0 ± 0.5 days vs. 15.0 ± 1.6 days, P <0.001) than pre-VO/CVP patients. These data suggest that VO and low CVP during liver resection may improve patient outcomes.

Prolonged continuous or intermittent vascular inflow occlusion during hemihepatectomy in pigs.

To assess ischemia and reperfusion (I/R) injury in a hemihepatectomy model in pigs after prolonged continuous or intermittent vascular inflow occlusion in the liver. Massive intraoperative blood loss during liver resections can be prevented by temporary vascular inflow occlusion, consequently leading to ischemia and reperfusion injury in the remnant liver. Previously, in a pig liver resection model in which only limited I/R injury was induced during brief (90 min) vascular inflow occlusion, the authors demonstrated reduced I/R injury after continuous (CNT) occlusion, compared to intermittent (INT). This liver resection study on pigs was undertaken to assess I/R injury after prolonged (120 min) CNT or INT occlusion. In pigs (37.0 +/- 1.5 kg), liver ischemia during 2 hours was CNT (n = 6) or INT (n = 6) (eight subsequent periods of 12 min ischemia and 3 min recirculation), followed by 6 hours of reperfusion. A left hemihepatectomy (45.5% +/- 1.4%) was performed within the first 12 minutes of ischemia. No hepatic pedicle clamping or liver resection was performed in control experiments (n = 6). Microvascular damage was assessed by hyaluronic acid (HA) uptake capacity of the liver (parameter of early sinusoidal endothelial cell damage) and restoration of intrahepatic tissue pO2 during reperfusion. Hepatocellular damage was tested by plasma concentrations of aspartate aminotransferase (AST), alanine aminotransferase, and lactate dehydrogenase (LDH). Hyaluronic acid uptake after 6 hours of reperfusion, compared to preischemic uptake, was unaltered in the control group, but was significantly reduced in both resection groups. However, more HA was taken up after INT occlusion, compared to CNT (60.4% +/- 5.6% and 39.5% +/- 3.7%, respectively; ANOVA: p = 0.001). Intrahepatic tissue pO2 distribution after 6 hours of reperfusion more closely returned to preischemic configuration in the INT group than in the CNT group, indicating reduced microcirculatory disturbances after INT occlusion. Release of AST and LDH after 6 hours of reperfusion was significantly increased in both CNT and INT groups. Lower AST levels, however, were found after INT occlusion than after CNT occlusion (267.0 +/- 74.7 U/l and 603.3 +/- 132.4 U/l, respectively; p = 0.06). Intermittent hepatic vascular inflow occlusion during prolonged liver ischemia in pigs resulted in less microcirculatory and hepatocellular injury, compared to continuous occlusion. Intermittent clamping is preferable when prolonged periods of vascular inflow occlusion are applied during liver resections.

Prolonged continuous or intermittent vascular inflow occlusion during hemihepatectomy in the pig

Prolonged continuous or intermittent vascular inflow occlusion during hemihepatectomy in the pig

Intrahepatic Tissue pO2 during Continuous or Intermittent Vascular Inflow Occlusion in a Pig Liver Resection Model

Background: Temporary vascular inflow occlusion of the liver (clamping of the hepatic pedicle) can prevent massive blood loss during liver resections. In this study, intrahepatic tissue pO₂ was assessed as parameter of microcirculatory disturbances induced by ischemia and reperfusion (I/R) in the liver following continuous (Cnt) or intermittent (Int) clamping in a hemihepatectomy model in the pig. Methods: Pigs (20–34 kg) were divided into 2 groups: I/R without hemihepatectomy (–HH; n = 10) and I/R with hemihepatectomy (+HH; n = 8). Ischemia during 90 min was Cnt or Int (6 sequential periods of 12 min of ischemia and 3 min of reperfusion), followed by 120 min of reperfusion. Intrahepatic pO₂ histograms (polarographic pO₂ needle electrode) were constructed before ischemia, at the end of 90 min of ischemia and after 120 min of reperfusion, along with assessment of plasma AST, ALT and LDH. Bile production was monitored continuously. Results: Cumulative frequency distribution curves (CFDC) after 120 min of reperfusion in the Cnt–HH group were not different from preischemic CFDC (means ± SEM), whereas in the Int–HH group a left shift occurred indicating more hypo(non)perfused liver areas (pO₂ < 10 mm Hg: 2.6 ± 1.2 and 41.0 ± 17.5% in Cnt–HH and Int–HH; p < 0.01). In the Cnt+HH group, a left shift in the CFDC occurred. In the Int+HH group, a left and a right shift occurred simultaneously, indicating both hypo(non)- and hyperperfused (shunting) liver areas (pO₂ < 10 mm Hg: 4.0 ± 2.7 and 9.6 ± 8.5%, n.s., and pO₂ > 60 mm Hg: 2.0 ± 2.0 and 17.3 ± 6.4%, p = 0.015, in Cnt+HH and Int+HH). Plasma AST, ALT and LDH levels were not increased after 120 min of reperfusion, except for AST in Cnt+HH and Int+HH (from 54.6 ± 14.0 to 270.4 ± 42.8 U/l, p < 0.01, and from 47.8 ± 9.4 to 176.5 ± 55.9 U/l, n.s.). Bile production (percentage of mean preischemic value) during 120 min of reperfusion was significantly reduced in the Int–HH group, as compared to the Cnt–HH group (57.0 and 117.0% after 120 min of reperfusion, p = 0.002). In Cnt+HH and Int+HH, bile production was significantly reduced (33.3 ± 20.0%, p = 0.05, and 38.5 ± 7.9%, p = 0.007); however it was not different between the two groups. Conclusions: (1) Intrahepatic tissue pO₂ as indicator of microvascular perfusion is a parameter of early I/R injury; (2) continuous vascular inflow occlusion resulted in less microcirculatory disturbances, when compared to intermittent occlusion.