Trial Information

The Effect of Pre- and Postoperative Supplemental Enteral Nutrition in High-Risk Patients Undergoing Elective Cardiac Surgery. A Prospective Double Blind Study.

Objective To study the effect of two preoperative immune enhancing nutritional supplements
compared with a control nutritional supplement in 'high risk' risk cardiac surgery patients

Introduction: Elderly patients and patients with a poor ventricular function undergoing
cardiac operations with hypothermic cardiopulmonary bypass (CPB), have an increased
postoperative morbidity and mortality. Host defence may be diminished due to nutritional
deficiencies, hypoperfusion, anaesthesia and operative trauma. Immune function is
additionally depressed by the use of CPB and hypothermia. It has been suggested that
L-arginine can improve postoperative outcome in cardiac surgery patients, glycine may have a
role in protecting tissues against insults such as ischemia-reperfusion and hypoxia, and
omega-3 polyunsaturated fatty acids (omega3-PUFA's) can limit the postoperative generalised
inflammatory response.

Experimental studies have shown that the use of nutritional supplements containing
L-arginine, omega3-PUFA's or nucleotides, boost immune responsiveness after surgery or
trauma. L-arginine is a semi-essential amino acid and precursor of nitrous oxide (NO), the
most important endothelial vasodilator. In experimental studies, L-arginine improved wound
healing, restored postoperative depressed macrophage function and lymphocyte responsiveness
and augmented resistance to infections. Arginine protected against ischemia-reperfusion
injury by increasing oxygen delivery upon reflow, thereby improving cardiac function. The
intake of additional omega3-PUFA's alters cell membrane phospholipid content and
prostaglandin synthesis. This might be an important factor in limiting the generalised
inflammatory response and subsequent immunosuppression and capillary leakage following major
surgery. Purines and pyrimidines are essential nutrients for rapidly dividing cells. The
administration of nucleotides in the form of yeast-RNA has improved the host immune response
to an infectious challenge. In experimental studies glycine has been proven cytoprotective
in stomach, kidney, liver and cardiovascular system. The metabolic response to oral glycine
is that it facilitates the uptake op glucose from the circulation.

The immunonutrients, arginine, omega3-PUFA’s and yeast-RNA, have been combined into a single
oral immune enhancing nutritional supplement (OIENS). In cancer surgery, trauma and
critically ill patients ‘post event’ nutrition with this immune enhancing formula has
improved immunocompetence, reduced infections and shortened length of stay in the hospital
(LOSH). The onset of the effect of postoperative immune enhancing nutrition starts after 3
days and seems to be dose dependent. For this reason, it can be hypothesised that it may be
beneficial to commence an oral immune enhancing nutritional supplement (OIENS) before
surgery. A recent published clinical trail showed that the OIENS with these three
immunonutrients in high risk cardiac surgery patients improves preoperative clinical
relevant immunological parameters, reduced postoperative infectious morbidity and attenuated
postoperative organ dysfunction. Recently, the three immunonutrients have been combined with
glycine into a new single OIENS. Aim of the present study in ‘high risk’ cardiac surgery
patients was to determine whether the intake of the new OIENS for minimally five days
improves preoperative host defence and subsequently reduces postoperative infections and
organ dysfunction.

Study design: A prospective randomized placebo-controlled three armed double blind study

Setting: Departments of cardiopulmonary surgery, anesthesiology and intensive care of the
Academic Medical Center, Amsterdam, The Netherlands

Patients: Eligible patients will be included in the study after obtaining written informed
consent Inclusion criteria: Patients who met one or more of the inclusion criteria: aged 70
years or more, undergoing cardiac surgery with the use of CPB, or patients with a poor left
ventricular function (Ejection fraction < 0.40) or patients undergoing a mitral valve
replacement.

Exclusion criteria: Age < 21 years, pregnancy, insulin dependent diabetes mellitus, hepatic
cirrhosis, known malignancy, the use of chemotherapy, NSAIDs (excluding acetyl salic acid)
or corticosteroids, schizophrenia, severe renal insufficiency (creatinine clearance < 25
mL/h), patients with an organ transplantation in the past

Randomization: 74 patients will be randomized by closed envelop method

Intervention: All patients will receive one of the three enteral nutritional supplements. A
formula enriched with arginine, omega-3 PUFA's and nucleotides or the enriched formula
further enriched with additional glycine or a control formula. Patients that needs
postoperative enteral nutritional support will receive the same formula as preoperative.
Patients that need no postoperative enteral nutrition nasogastric tube feeding will not
receive the nutritional supplement

Endpoints: Patient compliance, infections, postperfusion phenomena, post-operative organ
function (need of postoperative support e.g. inotropic, vasopressor support, fluids,
myocardial infarction, ventilation parameters, renal function) time of recovery, mortality