Postoperative Protein Catabolism Clinical Trial
Official title:
THE PROTEIN SPARING EFFECT OF PERIOPERATIVE NUTRITION: How Important is the Patient's Catabolic State Before Surgery and do we Need Glucose?
Loss of muscle protein and mass are the main causes of fatigue after bowel surgery which may
result in a longer hospital stay and a higher rate of complications. This problem is
especially important for patients after surgery for bowel cancer because cancer itself
causes a waste of muscle protein. Anesthesiologists can decrease these negative effects of
surgery by choosing the type of pain treatment (analgesia) and by giving nutrition (sugar
and protein). Our group recently observed that optimal pain relief with epidural catheters
(these are placed in the so called epidural space, which lies between the spine and the skin
of the back) in combination with a low calorie protein diet intravenously (through the vein)
maintains the body's protein stores after bowel surgery.
The goal of our new research program is to find out whether this protein saving effect
depends on how protein depleted the patient is before surgery. In other words we would like
to answer the question: do cancer patients who show protein wasting before the operation
benefit more from feeding than patients who show no signs of protein wasting? A second goal
of this program is to find out if we need to use sugar as part of the diet or whether the
infusion of protein alone is sufficient. Just giving protein would make feeding not only
easier but also would avoid the increase in the patient's own blood sugar during and after
the operation, which typically occurs when sugar is given intravenously during that period.
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
catabolic state.
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
| Status | Clinical Trial | Phase | |
|---|---|---|---|
| Completed |
NCT00614133 -
Effect of Intravenous Nutrition and Epidural Analgesia on Protein Loss After Surgery
|
N/A |