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Sponsored by: |
McGill University Health Center |
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Information provided by: | McGill University Health Center |
ClinicalTrials.gov Identifier: | NCT00623662 |
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 |
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Hepatic Insufficiency Liver Failure |
Other: Preoperative glucose infusion Other: Preoperative normal saline infusion |
Study Type: | Interventional |
Study Design: | Prevention, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Active Control, Parallel Assignment, Efficacy Study |
Official Title: | Metabolic Preconditioning Using Intravenous Dextrose: a Novel Strategy to Improve Hepatic Function After Liver Resection |
Estimated Enrollment: | 50 |
Study Start Date: | February 2008 |
Estimated Study Completion Date: | March 2011 |
Estimated Primary Completion Date: | March 2011 (Final data collection date for primary outcome measure) |
Arms | Assigned Interventions |
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1: Active Comparator
Glucose infusion.
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Other: Preoperative glucose infusion
Glucose infusion from 15:00 on the day before the operation until beginning of surgery.
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2: Placebo Comparator
Normal saline infusion.
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Other: Preoperative normal saline infusion
Normal saline infusion from 15:00 on the day before surgery until beginning of the operation.
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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.
Ages Eligible for Study: | 18 Years and older |
Genders Eligible for Study: | Both |
Accepts Healthy Volunteers: | No |
Inclusion Criteria:
Exclusion Criteria:
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 |
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 |
Principal Investigator: | Ralph Lattermann, MD PhD | Department of Anaesthesia, McGill University Health Centre |
Responsible Party: | Department of Anaesthesia, McGill University Health Centre ( Ralph Lattermann, MD PhD ) |
Study ID Numbers: | CIHR 183635 |
Study First Received: | February 15, 2008 |
Last Updated: | February 3, 2009 |
ClinicalTrials.gov Identifier: | NCT00623662 History of Changes |
Health Authority: | Canada: Canadian Institutes of Health Research |
Glucose infusion Liver function Liver resection Albumin synthesis Stable isotopes |
Liver Failure Liver Diseases Digestive System Diseases Hepatic Insufficiency |
Liver Failure Liver Diseases Digestive System Diseases Hepatic Insufficiency |