THE PROTEIN SPARING EFFECT OF PERIOPERATIVE NUTRITION: How Important is the Patient's Catabolic State Before Surgery and do we Need Glucose?
1. Goals The overall goal of perioperative nutrition support is to abolish protein wasting
and to promote anabolic processes by directing amino acids into protein synthesis
rather than oxidation. Protein repletion and enhancement of anabolism appear to be
particularly important in cancer patients who enter major abdominal surgery in a
2. Objectives The objectives of this research program are
- to examine whether the anabolic effects of hypocaloric nutrition depend on the
degree of catabolism before the operation and thus identify patients who benefit
the most from perioperative nutrition support (study I)
- to investigate whether excluding glucose from hypocaloric nutrition, i.e. infusing
an isonitrogenous amount of amino acids without glucose avoids hyperglycemia and,
thus, accentuates the patient's anabolic response to feeding (study II).
In order to confirm the validity of our assumptions we will perform two consecutive studies
in two distinct patient populations. For the assessment of the patients' catabolic state and
obtaining insight into the biochemical mechanisms, whereby the effects of nutrition are
mediated, stable isotope tracer kinetics will be applied. Using primed continuous infusions
of L-[1-13C]leucine and [6,6-2H2]glucose we will quantitate the whole body dynamics of
protein and glucose metabolism, i.e. protein breakdown, amino acid oxidation, protein
synthesis, glucose production and glucose uptake before and after surgery. A positive
protein balance (difference between protein synthesis and protein breakdown) will be used as
an indicator of anabolism. Anabolic processes at the organ level (liver, muscle), i.e.
fractional synthesis rates of the acute phase proteins albumin and fibrinogen and muscle
protein synthesis will be determined using L-[2H5]phenylalanine infusions. Skeletal muscle
protein catabolism will be characterized by measuring the mRNA expression of ubiquitin and
two of its key ligases in muscle (MAFbx/atrogen-1 and MuRF-1).
Allocation: Non-Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Single Blind (Subject), Primary Purpose: Treatment
two days after surgery
Thomas Schricker, MD PhD
Department of Anaesthesia, McGill University Health Centre
Canada: Canadian Institutes of Health Research