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Effect of Intermittent Pedicle Clamping on Hepatocellular Injury During Liver Surgery

Primary Purpose

Hepatocellular Injury, Blood Loss

Status
Completed
Phase
Not Applicable
Locations
Netherlands
Study Type
Interventional
Intervention
Pringle manoeuvre 15 minutes
Pringle manoeuvre 30 minutes
Sponsored by
Maastricht University Medical Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional basic science trial for Hepatocellular Injury focused on measuring liver surgery, pringle manoeuvre, hepatocellular damage, surgical complications, patients requiring liver surgery

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • patients > 18 years of age and < 100 years of age
  • primary or secondary liver tumours requiring liver surgery

Exclusion Criteria:

  • pre-existent liver disease (e.g. inflammatory liver disease, cirrhosis, inborn errors of metabolism)
  • cholangiocarcinoma requiring biliary tract reconstruction during surgery
  • steroid hormone medication
  • tumours deemed irresectable during liver surgery
  • laparoscopic liver surgery

Sites / Locations

  • Maastricht University Medical Centre

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Pringle manoeuvre 15 minutes

Pringle manoeuvre 30 minutes

Arm Description

When intermittent pedicle occlusion during parenchymal transection is necessary, 2 cycles of 15 minutes of hepatic inflow occlusion will be applied each followed by 5 minutes of reperfusion. During inflow occlusion, the complete portal triad was clamped using a rubber sling.

When intermittent pedicle occlusion during parenchymal transection is necessary, 1 cycle of 30 minutes of hepatic inflow occlusion will be applied followed by 5 minutes of reperfusion. During inflow occlusion, the complete portal triad was clamped using a rubber sling.

Outcomes

Primary Outcome Measures

Hepatocellular Damage Reflected by Liver Fatty-acid Binding Protein (L-FABP) Levels
At specific time points before, during and after liver surgery, plasma samples will be obtained to analyse the amount of hepatocellular damage reflected by L-FABP) level. These timepoints include: baseline (before operation), just before intermittent pedicle clamping, just before end of 15 or 30 minutes pedicle clamping, end of 5 minutes reperfusion, end of liver surgery, 8 hours after start liver surgery, postoperative day 1, 2 and 3. This continuous variable with repeated measurements was summarized as area under the curve (AUC) from baseline to postoperative day 3 (as described in Matthews JN, Altman DG, Campbell MJ, Royston P. Analysis of serial measurements in medical research. Bmj 1990;300:230-5).

Secondary Outcome Measures

Post-resectional Complications
morbidity and mortality occuring after liver surgery graded according to Clavien-Dindo's grading system. In short, any deviation from the postoperative course without the need for pharmacological, radiological or surgical intervention was classified as Clavien-Dindo grade 1; complications requiring pharmacological treatment were graded as grade 2; complications requiring surgical or radiological intervention not under general anesthesia as grade 3a and under general anesthesia as grade 3b; grade 4 complications were life-threatening complications requiring intensive care unit care because of single organ dysfunction (grade 4a) or multiple organ dysfunction (grade 4b); mortality was classed as grade 5.
Amount of Blood Loss
amount of blood in the suction container (and, if applicable, in the weighted gauzes)
Hepatocellular Damage Reflected by Alanine Aminotransferase (ALAT) Levels
At specific time points before, during and after liver surgery, plasma samples will be obtained to analyse the amount of hepatocellular damage reflected by ALAT level. These timepoints include: baseline (before operation), just before intermittent pedicle clamping, just before end of 15 or 30 minutes pedicle clamping, end of 5 minutes reperfusion, end of liver surgery, 8 hours after start liver surgery, postoperative day 1, 2 and 3.

Full Information

First Posted
April 1, 2010
Last Updated
October 13, 2014
Sponsor
Maastricht University Medical Center
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1. Study Identification

Unique Protocol Identification Number
NCT01099475
Brief Title
Effect of Intermittent Pedicle Clamping on Hepatocellular Injury During Liver Surgery
Official Title
Randomized Controlled Trial on the Effect of Intermittent Pedicle Clamping Using 15 or 30 Minutes Ischemic Intervals During Liver Surgery
Study Type
Interventional

2. Study Status

Record Verification Date
October 2014
Overall Recruitment Status
Completed
Study Start Date
October 2007 (undefined)
Primary Completion Date
July 2009 (Actual)
Study Completion Date
April 2011 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Maastricht University Medical Center

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
In order to prevent excessive blood loss during liver surgery, an intermittent Pringle manoeuvre (IPM) can be applied. This implies a temporary clamping of the portal vein and hepatic artery in the hepatoduodenal ligament in order to occlude hepatic inflow. The optimal duration of the IPM is unknown. This randomized controlled trial aimed to analyse differences in hepatocellular damage after 15 minutes or 30 minutes IPM during liver surgery for primary or secondary liver tumours.
Detailed Description
Surgical procedure Patients were anaesthetized using isoflurane and propofol. They routinely had an epidural catheter, urinary catheter, two peripheral venous catheters and indwelling catheters in a jugular vein and radial artery. Body temperature was maintained using a Bair Hugger system (Arizant Healthcare Inc. Eden Prairie, Minnesota). The surgical procedure was performed using a subcostal bilateral incision and Olivier retractors to improve exposure. After dissection of the teres hepatis ligament, the liver was mobilized. Thereafter, an intra-operative ultrasound was performed to define the position of the tumour in relation to vascular and biliary structures. As IPM was not routinely applied, a patient was randomized for 15 minted IPM (15IPM) or 30 minutes IPM (30IPM) only after the surgeon had decided a complete Pringle manoeuvre would be required. During 15IPM or 30IPM, the complete portal triad was clamped using a rubber sling. The time of inflow occlusion was adapted to the need according to the randomization protocol. Occasionally, the left or right pedicle was ligated after protocolled IPM. Five minutes reperfusion intervals were applied during which transection was stopped and cut surfaces were gently compressed to ensure hemostasis. A Cavitron Ultrasonic Surgical Aspirator (CUSA system 200 macrodissector, Cavitron Surgical Systems, Stamford, Connecticut) and Argon beam coagulation (Force GSU System, Valleylab, Boulder, Colorado) were used for liver transection. A stapler device or clamps were used for transection of the hepatic veins. Central venous pressure was maintained below 5 centimetre of water (cm H2O) during transection to reduce venous back-bleeding. After surgery, the weight of the resection specimen was recorded. Perioperative care was protocolled, as described earlier.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hepatocellular Injury, Blood Loss
Keywords
liver surgery, pringle manoeuvre, hepatocellular damage, surgical complications, patients requiring liver surgery

7. Study Design

Primary Purpose
Basic Science
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
Participant
Allocation
Randomized
Enrollment
20 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Pringle manoeuvre 15 minutes
Arm Type
Experimental
Arm Description
When intermittent pedicle occlusion during parenchymal transection is necessary, 2 cycles of 15 minutes of hepatic inflow occlusion will be applied each followed by 5 minutes of reperfusion. During inflow occlusion, the complete portal triad was clamped using a rubber sling.
Arm Title
Pringle manoeuvre 30 minutes
Arm Type
Experimental
Arm Description
When intermittent pedicle occlusion during parenchymal transection is necessary, 1 cycle of 30 minutes of hepatic inflow occlusion will be applied followed by 5 minutes of reperfusion. During inflow occlusion, the complete portal triad was clamped using a rubber sling.
Intervention Type
Procedure
Intervention Name(s)
Pringle manoeuvre 15 minutes
Intervention Description
During parenchymal transection, the hepatoduodenal ligament will be clamped by a rubber band for 2-times 15 minutes with 5 minutes reperfusion
Intervention Type
Procedure
Intervention Name(s)
Pringle manoeuvre 30 minutes
Intervention Description
During parenchymal transection, the hepatoduodenal ligament will be clamped by a rubber band for 30 minutes with 5 minutes reperfusion
Primary Outcome Measure Information:
Title
Hepatocellular Damage Reflected by Liver Fatty-acid Binding Protein (L-FABP) Levels
Description
At specific time points before, during and after liver surgery, plasma samples will be obtained to analyse the amount of hepatocellular damage reflected by L-FABP) level. These timepoints include: baseline (before operation), just before intermittent pedicle clamping, just before end of 15 or 30 minutes pedicle clamping, end of 5 minutes reperfusion, end of liver surgery, 8 hours after start liver surgery, postoperative day 1, 2 and 3. This continuous variable with repeated measurements was summarized as area under the curve (AUC) from baseline to postoperative day 3 (as described in Matthews JN, Altman DG, Campbell MJ, Royston P. Analysis of serial measurements in medical research. Bmj 1990;300:230-5).
Time Frame
L-FABP area under curve from start of surgery up until postoperative day 3
Secondary Outcome Measure Information:
Title
Post-resectional Complications
Description
morbidity and mortality occuring after liver surgery graded according to Clavien-Dindo's grading system. In short, any deviation from the postoperative course without the need for pharmacological, radiological or surgical intervention was classified as Clavien-Dindo grade 1; complications requiring pharmacological treatment were graded as grade 2; complications requiring surgical or radiological intervention not under general anesthesia as grade 3a and under general anesthesia as grade 3b; grade 4 complications were life-threatening complications requiring intensive care unit care because of single organ dysfunction (grade 4a) or multiple organ dysfunction (grade 4b); mortality was classed as grade 5.
Time Frame
within 90-days after initial liver surgery
Title
Amount of Blood Loss
Description
amount of blood in the suction container (and, if applicable, in the weighted gauzes)
Time Frame
at the end of liver surgery, an average of 225 minutes
Title
Hepatocellular Damage Reflected by Alanine Aminotransferase (ALAT) Levels
Description
At specific time points before, during and after liver surgery, plasma samples will be obtained to analyse the amount of hepatocellular damage reflected by ALAT level. These timepoints include: baseline (before operation), just before intermittent pedicle clamping, just before end of 15 or 30 minutes pedicle clamping, end of 5 minutes reperfusion, end of liver surgery, 8 hours after start liver surgery, postoperative day 1, 2 and 3.
Time Frame
ALAT area under curve from start of surgery up until postoperative day 3

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: patients > 18 years of age and < 100 years of age primary or secondary liver tumours requiring liver surgery Exclusion Criteria: pre-existent liver disease (e.g. inflammatory liver disease, cirrhosis, inborn errors of metabolism) cholangiocarcinoma requiring biliary tract reconstruction during surgery steroid hormone medication tumours deemed irresectable during liver surgery laparoscopic liver surgery
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Cornelis HC Dejong, MD, PhD
Organizational Affiliation
Maastricht University Medical Centre
Official's Role
Principal Investigator
Facility Information:
Facility Name
Maastricht University Medical Centre
City
Maastricht
State/Province
PO Box 5800
ZIP/Postal Code
6202 AZ
Country
Netherlands

12. IPD Sharing Statement

Citations:
PubMed Identifier
21147188
Citation
van den Broek MA, Bloemen JG, Dello SA, van de Poll MC, Olde Damink SW, Dejong CH. Randomized controlled trial analyzing the effect of 15 or 30 min intermittent Pringle maneuver on hepatocellular damage during liver surgery. J Hepatol. 2011 Aug;55(2):337-45. doi: 10.1016/j.jhep.2010.11.024. Epub 2010 Dec 13.
Results Reference
result
PubMed Identifier
22291982
Citation
Dello SA, Reisinger KW, van Dam RM, Bemelmans MH, van Kuppevelt TH, van den Broek MA, Olde Damink SW, Poeze M, Buurman WA, Dejong CH. Total intermittent Pringle maneuver during liver resection can induce intestinal epithelial cell damage and endotoxemia. PLoS One. 2012;7(1):e30539. doi: 10.1371/journal.pone.0030539. Epub 2012 Jan 24.
Results Reference
result

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Effect of Intermittent Pedicle Clamping on Hepatocellular Injury During Liver Surgery

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