The Impact of glutamine suppletion on outcome in patients undergoing high-risk cardiothoracic surgery.

The amino acid glutamine is an important substrate for numerous metabolic and
immunological processes. Glutamine is the major nitrogen transporter in the
body, a significant substrate for the intestinal tract in humans, and is
essential for the normal function and replication of the cells of the immune
system shown both in vitro and in vivo. Glutamine is synthesized in the body in
large quantities and therefore considered nonessential. It is the most abundant
amino acid in the body constituting 60% of the total amino acid and amino
nitrogen pool.
Reduction in free glutamine concentration in plasma is seen in response to a
variety of insults such as trauma, major surgery, infection, acidosis and
fasting. Postoperatively patients in a critical state develop glutamine
deficiency, associated with loss of intestinal integrity and immunological and
anti-oxidant response. Lowered levels of plasma glutamine have been associated
with higher mortality in critical ill patients. The role of glutamine in
restoring reduced glutathione levels and as a fuel for preservation of tissue
metabolism implies that a reduction in the free plasma concentration of
glutamine is associated with cardiac dysfunction inflicted by I/R
(Ischemia/Reperfusion) injury. Studies have shown that infusions with end
products of glutamine improve heart function in patients with heart failure
after cardiac surgery. Also several studies have demonstrated that supplemental
parenteral glutamine administration improves postoperative nitrogen balance,
supports immune function, enhances the rate of protein synthesis, maintains
normal gastrointestinal permeability characteristics and is associated with
reduced hospitalization and mortality.

Aim of the study is to assess the effects of supplemental parenteral
L-alanyl-L-glutamine treatment on infectious, cardiac, cerebral, pulmonary and
gastro-intestinal morbidity during the ICU- (Intensive Care Unit) and hospital
stay in patients after high-risk cardiothoracic surgery. Furthermore, the
effect on length of stay in the ICU-, hospital- and on in-hospital mortality
will be studied.

This is a prospective, single center, double blind, placebo controlled
randomized trial in the LUMC (Leiden University Medical Center) in Leiden, the
Netherlands. A total of 80 patients, 40 in each arm, undergoing high-risk
cardiothoracic surgery will receive a daily support of glutamine or placebo,
starting 1 day preoperatively and lasting for 5 postoperative days.

Patients will be randomized to receive either placebo- or
L-alanyl-L-glutamine-treatment. Treatment will start one day before surgery and
continue five days thereafter. Vital characteristics will be recorded. Blood
samples will be collected according to the schedule provided on page 13 of the
research protocol.

Burden:
- Infusion of study-medication will take place during several daytime hours in
patients already treated intra-venously.
- Bloodsampling: an additional 46 ml will be collected during 72 hours, using
present arterial or venous cannulas.


Risks:
- There are no known negative effects of additional parenteral glutamine
suppletion. A saline solution will be used as placebo.
- Thromboflebitis is a possible risk of venous cannulation and parenteral
treatment.