Trial Information

Hypocaloric Isonitrogenous Nutrition and Epidural Analgesia: a Novel Strategy to Induce Anabolism After Surgery

The major objective of the nutritional management of surgical patients is to accelerate
wound healing and increase resistance to infection while preventing wastage of functional
and structural proteins. Parenteral nutrition represents a useful strategy to achieve this
goal, particularly in patients undergoing major abdominal procedures with temporary
intolerance to oral feeding. At present administration of large, hypercaloric amounts of
glucose together with amino acids is the only nutritional modality to establish a positive
protein balance (anabolism) after surgery. The fact that hyperalimentation requires central
venous cannulation, causes hyperglycemia and is associated with increased morbidity is an
impediment to its routine use. Attempts to induce anabolism by diminishing the glucose load
to iso- or hypocaloric quantities failed because of

- failure to control for type and quality of perioperative analgesia

- inadequate assessment of the patient`s catabolic status prior to surgery with
subsequent

- lack of individualization of energy and substrate supply.

We recently demonstrated that segmental pain relief by epidural analgesia facilitates
oxidative glucose utilization thereby decreasing the amount of glucose necessary to
attenuate protein losses after surgery. Hypocaloric glucose and epidural analgesia prevented
the postoperative increase in protein oxidation, but only if preoperative fasting was
avoided, i.e. the glucose infusion was started 24 hours before surgery. We also showed that
patients with epidural analgesia could be rendered anabolic by short term administration of
glucose and amino acids. Based on our findings of anti-catabolic and anabolic effects of
epidural analgesia in the presence of energy and substrate supply we now propose that
epidural analgesia and hypocaloric parenteral nutrition initiated 24 hours before colorectal
surgery will produce a more positive postoperative protein balance including a greater
muscle protein synthesis than when initiated with skin incision.

In order to test the validity of this assumption, patients scheduled for elective colorectal
cancer surgery will be randomly assigned to an "early" or "late" feeding protocol. "Early"
nutrition will start 24 hours prior to surgery, "late" nutrition will commence with surgical
skin incision. Nutrition will be adjusted to provide 50% of the patient`s actual energy
expenditure as glucose and 20% as amino acids. The stable isotope tracer L-[1-13C]leucine
will be applied to assess whole body protein breakdown, amino acid oxidation and protein
synthesis. A positive protein balance (difference between protein synthesis and protein
breakdown) will be used as an indicator of anabolism. Because whole body protein kinetics
provide no insight into metabolic processes at organ level (muscle, liver), the fractional
synthesis rates of albumin, fibrinogen and muscle protein will also be determined after
surgery.

The demonstration of anabolic effects of epidural analgesia and nutrition with less than
half the commonly used energy would have a valuable practical application. If the nutrient
load can be decreased, use can be made of peripheral veins and hyperglycemia can be avoided,
thus making nutritional therapy more efficacious, safer and available to more patients.