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Effect of Intermittent Pedicle Clamping on Hepatocellular Injury During Liver Surgery

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Maastricht University Medical Center
ClinicalTrials.gov Identifier:
NCT01099475
First received: April 1, 2010
Last updated: October 13, 2014
Last verified: October 2014
  Purpose

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.


Condition Intervention
Hepatocellular Injury
Blood Loss
Procedure: Pringle manoeuvre 15 minutes
Procedure: Pringle manoeuvre 30 minutes

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single Blind (Subject)
Primary Purpose: Basic Science
Official Title: Randomized Controlled Trial on the Effect of Intermittent Pedicle Clamping Using 15 or 30 Minutes Ischemic Intervals During Liver Surgery

Resource links provided by NLM:


Further study details as provided by Maastricht University Medical Center:

Primary Outcome Measures:
  • Hepatocellular Damage Reflected by Liver Fatty-acid Binding Protein (L-FABP) Levels [ Time Frame: L-FABP area under curve from start of surgery up until postoperative day 3 ] [ Designated as safety issue: No ]
    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 [ Time Frame: within 90-days after initial liver surgery ] [ Designated as safety issue: No ]
    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 [ Time Frame: at the end of liver surgery, an average of 225 minutes ] [ Designated as safety issue: No ]
    amount of blood in the suction container (and, if applicable, in the weighted gauzes)

  • Hepatocellular Damage Reflected by Alanine Aminotransferase (ALAT) Levels [ Time Frame: ALAT area under curve from start of surgery up until postoperative day 3 ] [ Designated as safety issue: No ]
    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.


Enrollment: 20
Study Start Date: October 2007
Study Completion Date: April 2011
Primary Completion Date: July 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Pringle manoeuvre 15 minutes
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.
Procedure: Pringle manoeuvre 15 minutes
During parenchymal transection, the hepatoduodenal ligament will be clamped by a rubber band for 2-times 15 minutes with 5 minutes reperfusion
Experimental: Pringle manoeuvre 30 minutes
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.
Procedure: Pringle manoeuvre 30 minutes
During parenchymal transection, the hepatoduodenal ligament will be clamped by a rubber band for 30 minutes with 5 minutes reperfusion

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01099475

Locations
Netherlands
Maastricht University Medical Centre
Maastricht, PO Box 5800, Netherlands, 6202 AZ
Sponsors and Collaborators
Maastricht University Medical Center
Investigators
Principal Investigator: Cornelis HC Dejong, MD, PhD Maastricht University Medical Centre
  More Information

Publications:
Responsible Party: Maastricht University Medical Center
ClinicalTrials.gov Identifier: NCT01099475     History of Changes
Other Study ID Numbers: 06-2-067
Study First Received: April 1, 2010
Results First Received: January 18, 2014
Last Updated: October 13, 2014
Health Authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)

Keywords provided by Maastricht University Medical Center:
liver surgery
pringle manoeuvre
hepatocellular damage
surgical complications
patients requiring liver surgery

ClinicalTrials.gov processed this record on November 25, 2014