Preoperative Glucose Infusion: a Novel Strategy to Improve Liver Function After Liver Resection
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|ClinicalTrials.gov Identifier: NCT00623662|
Recruitment Status : Unknown
Verified March 2016 by Ralph Lattermann, McGill University Health Center.
Recruitment status was: Recruiting
First Posted : February 26, 2008
Last Update Posted : March 28, 2016
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 or disease||Intervention/treatment|
|Hepatic Insufficiency Liver Failure||Other: Preoperative glucose infusion Other: Preoperative normal saline infusion|
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.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||50 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
|Official Title:||Metabolic Preconditioning Using Intravenous Dextrose: a Novel Strategy to Improve Hepatic Function After Liver Resection|
|Study Start Date :||February 2008|
|Estimated Primary Completion Date :||March 2017|
|Estimated Study Completion Date :||March 2017|
Active Comparator: 1
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.
- Rate of albumin synthesis [ Time Frame: One day before and one day after surgery ]
- Transthyretin synthesis, fibrinogen synthesis, whole body glucose and protein kinetics [ Time Frame: One day before and one day after surgery ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00623662
|Contact: Ralph Lattermann, MD PhD||514-934-1934 ext firstname.lastname@example.org|
|Contact: Thomas Schricker, MD PhD||514-934-1934 ext email@example.com|
|Royal Victoria Hospital, McGill University Health Centre||Recruiting|
|Montreal, Quebec, Canada, H3A 1A1|
|Contact: Ralph Lattermann, MD PhD 514-934-1934 ext 35802 firstname.lastname@example.org|
|Contact: Thomas Schricker, MD PhD 514-934-1934 ext 36057 email@example.com|
|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|