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

NCT ID: NCT00623662

Last Updated: 2018-04-03

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: NA
• Total Enrollment: 50 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-02-29
• Study Completion Date: 2019-03-31

Brief Summary

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.

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.

Conditions

Hepatic Insufficiency; Liver Failure

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: QUADRUPLE

Study Groups

1

Glucose infusion.

Group Type: ACTIVE_COMPARATOR

Preoperative glucose infusion

Intervention Type: OTHER

Glucose infusion from 15:00 on the day before the operation until beginning of surgery.

2

Normal saline infusion.

Group Type: PLACEBO_COMPARATOR

Preoperative normal saline infusion

Intervention Type: OTHER

Normal saline infusion from 15:00 on the day before surgery until beginning of the operation.

Interventions

Preoperative glucose infusion

Glucose infusion from 15:00 on the day before the operation until beginning of surgery.

Intervention Type: OTHER

Preoperative normal saline infusion

Normal saline infusion from 15:00 on the day before surgery until beginning of the operation.

Intervention Type: OTHER

Eligibility 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

McGill University Health Centre/Research Institute of the McGill University Health Centre

OTHER

Sponsor Role: lead

Responsible Party

Ralph Lattermann

Assistant Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Ralph Lattermann, MD PhD

Role: PRINCIPAL_INVESTIGATOR

Department of Anaesthesia, McGill University Health Centre

Locations

Royal Victoria Hospital, McGill University Health Centre

Montreal, Quebec, Canada

Site Status: RECRUITING

Countries

Canada

Central Contacts

Ralph Lattermann, MD PhD

Role: CONTACT

ralph.lattermann@muhc.mcgill.ca

514-934-1934 ext. 35802

Thomas Schricker, MD PhD

Role: CONTACT

thomas.schricker@mcgill.ca

514-934-1934 ext. 36057

Facility Contacts

Ralph Lattermann, MD PhD

Role: primary

ralph.lattermann@muhc.mcgill.ca

514-934-1934 ext. 35802

Thomas Schricker, MD PhD

Role: backup

thomas.schricker@mcgill.ca

514-934-1934 ext. 36057

Other Identifiers

CIHR 183635

Identifier Type: -

Identifier Source: secondary_id

GEN-07-075

Identifier Type: -

Identifier Source: org_study_id