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Preoperative Glucose Infusion: a Novel Strategy to Improve Liver Function After Liver Resection

The recruitment status of this study is unknown because the information has not been verified recently.
Verified February 2012 by McGill University Health Center.
Recruitment status was  Recruiting
Sponsor:
Information provided by (Responsible Party):
Ralph Lattermann, McGill University Health Center
ClinicalTrials.gov Identifier:
NCT00623662
First received: February 15, 2008
Last updated: February 7, 2012
Last verified: February 2012
  Purpose

The goal of the study is to determine whether intravenous glucose administration before liver resection preserves hepatic glycogen resulting in improved hepatic metabolic function after the operation.

We further investigate whether the benefit of avoiding preoperative fasting is more pronounced in patients undergoing more extensive liver resection.


Condition Intervention
Hepatic Insufficiency
Liver Failure
Other: Preoperative glucose infusion
Other: Preoperative normal saline infusion

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: Metabolic Preconditioning Using Intravenous Dextrose: a Novel Strategy to Improve Hepatic Function After Liver Resection

Resource links provided by NLM:


Further study details as provided by McGill University Health Center:

Primary Outcome Measures:
  • Rate of albumin synthesis [ Time Frame: One day before and one day after surgery ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Transthyretin synthesis, fibrinogen synthesis, whole body glucose and protein kinetics [ Time Frame: One day before and one day after surgery ] [ Designated as safety issue: No ]

Estimated Enrollment: 50
Study Start Date: February 2008
Estimated Study Completion Date: March 2012
Estimated Primary Completion Date: March 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 1
Glucose infusion.
Other: Preoperative glucose infusion
Glucose infusion from 15:00 on the day before the operation until beginning of surgery.
Placebo Comparator: 2
Normal saline infusion.
Other: Preoperative normal saline infusion
Normal saline infusion from 15:00 on the day before surgery until beginning of the operation.

Detailed Description:

Background. With a reported incidence of up to 70%, liver failure is the most frequent complication necessitating intensive care and prolonging hospital stay. Animal studies suggest that the glycogen content of the liver is a key regulator of liver function and that glycogen depletion, a mandatory consequence of preoperative fasting, is associated with poor clinical outcome.

The results of a pilot study demonstrate that metabolic preconditioning, i.e. the avoidance of preoperative fasting by intravenous administration of dextrose preserves hepatic glycogen and prevents hepatic dysfunction after liver resection. Liver function in this protocol was assessed by a score originally proposed by Schindl including serum concentrations of total bilirubin and lactate, prothrombin time and degree of encephalopathy. Due to alterations induced by anesthesia and surgery, e.g. blood loss necessitating transfusion, hypothermia, inflammatory responses and use of drugs with impact on hepatobiliary metabolism, liver function scores do not necessarily reflect functional integrity and metabolic capacity of the liver. In contrast, measuring the production of proteins that are exclusively synthetized by hepatocytes such as albumin allows a more specific and quantitative assessment of hepatic performance under perioperative conditions.

Hypothesis. We propose a randomized double-blinded study to test the hypothesis that, in patients scheduled for resection of liver cancer, metabolic preconditioning with intravenous dextrose preserves hepatic glycogen resulting in improved hepatic metabolic function postoperatively. We further hypothesize that the benefit of avoiding preoperative fasting is more pronounced in patients undergoing more extensive liver resection. Hepatic synthetic capacity will be assessed by measuring albumin synthesis using a stable isotope tracer technique.

Research plan. In order to test the validity of our assumptions, we will perform studies in patients scheduled for minor (study I; one or two liver segments, n=30) or major (study II; three or more liver segments, n=20) liver resection. In a double blinded fashion patients will be randomly assigned to receive either intravenous dextrose at 2 mg/kg/min or saline from 15:00 on the day before the operation until surgical skin incision. Metabolic processes at the organ level (liver, muscle), i.e. fractional synthesis rates of albumin, hepatic acute phase proteins (transthyretin (=prealbumin), fibrinogen, total plasma proteins) and muscle protein will be determined one day before and one day after the operation using primed-continuous infusions of L-[2H5]phenylalanine. Stable isotopes (L-[1-13C]leucine, [6,6-2H2]glucose) will be applied to assess dynamic changes in whole body protein and glucose metabolism before and after surgery, i.e. protein breakdown, amino acid oxidation, protein synthesis, glucose production and glucose uptake.

Significance. The demonstration that the preconditioning with dextrose preserves metabolic performance of the liver would have important implications for the clinical management of surgical patients with liver cancer. If preoperative dextrose administration attenuates hepatic dysfunction after liver resection, it will provide these patients with a readily available, safe and inexpensive therapy.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • American Society of Anesthesiologists class ≤3
  • liver resection (one or more liver segments) for primary or secondary malignancy
  • ability to give informed consent

Exclusion Criteria:

  • signs of severe malnutrition or obesity: body mass index (BMI) <20 or >30 kg.m-2, more than 10% involuntary body weight loss over the preceding six months, serum albumin <35 g.L-1
  • chronic viral liver disease
  • diabetes mellitus
  • significant cardiorespiratory, renal and neurological disease
  • musculoskeletal or neuromuscular disease
  • severe anemia (hemoglobin <10 g.dL-1)
  • history of severe sciatica or back surgery or other conditions which contraindicate the use of an epidural catheter
  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: NCT00623662

Contacts
Contact: Ralph Lattermann, MD PhD 514-934-1934 ext 35802 ralph.lattermann@muhc.mcgill.ca
Contact: Thomas Schricker, MD PhD 514-934-1934 ext 36057 thomas.schricker@mcgill.ca

Locations
Canada, Quebec
Royal Victoria Hospital, McGill University Health Centre Recruiting
Montreal, Quebec, Canada, H3A 1A1
Contact: Ralph Lattermann, MD PhD    514-934-1934 ext 35802    ralph.lattermann@muhc.mcgill.ca   
Contact: Thomas Schricker, MD PhD    514-934-1934 ext 36057    thomas.schricker@mcgill.ca   
Principal Investigator: Ralph Lattermann, MD PhD         
Sub-Investigator: Thomas Schricker, MD PhD         
Sub-Investigator: George Carvalho, MD MSc         
Sub-Investigator: Peter Metrakos, MD         
Sub-Investigator: Linda Wykes, PhD         
Sub-Investigator: Mazen Hassanain, MD         
Sponsors and Collaborators
McGill University Health Center
Investigators
Principal Investigator: Ralph Lattermann, MD PhD Department of Anaesthesia, McGill University Health Centre
  More Information

No publications provided

Responsible Party: Ralph Lattermann, Assistant Professor, McGill University Health Center
ClinicalTrials.gov Identifier: NCT00623662     History of Changes
Other Study ID Numbers: GEN-07-075, CIHR 183635
Study First Received: February 15, 2008
Last Updated: February 7, 2012
Health Authority: Canada: Canadian Institutes of Health Research

Keywords provided by McGill University Health Center:
Glucose infusion
Liver function
Liver resection
Albumin synthesis
Stable isotopes

Additional relevant MeSH terms:
Hepatic Insufficiency
Liver Failure
Digestive System Diseases
Liver Diseases

ClinicalTrials.gov processed this record on November 20, 2014