Our primary objective is to evaluate the effect of perioperative enteral and parenteral nutrition on amino acid profile and cardiomyocytes functioning in the cardiac surgical patient. Our secondary objective is to study the effect of the (par)…
ID
Source
Brief title
Condition
- Coronary artery disorders
- Cardiac therapeutic procedures
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The main study outcomes are concentrations of amino acids and cardiomyocytes
functioning.
The amino acid profile will be studied in blood plasma and cardiac tissue
(sample 1) by: determining the concentration of all amino acids, asymmetric
dimethyl arginine (ADMA) and its region isomer symmetric dimethylarginine
(SDMA). In cardiac tissue, also the activity of dimethylarginine
dimethylaminohydrolase (DDAH, an enzyme which degrades ADMA) will be measured.
Cardiomyocytes functioning as presented by histology (sample 2): evaluation of
the orientation and size of cardiomyocytes, the endocard, the interstitial,
replaced and/or perivascular fibrosis, the intramyocardial vessels, glycogen
stacking, hibernation of cardiomyocytes, cytosolic glycogen, iron, amyloid,
CD45 (lymphocytes), CD68 (macrophages), myeloperoxidase (MPO) (neutrophil
granulocytes), C3d, carboxymethyl lysine (CML), myofibril density, expanded
sarcoplasmatic reticulum as marker of cellular damage, amount of mitochondria,
and thickness of the basal membrane of capillaries.
We expect the concentration of several amino acids to be reduced in the
cardio-surgical patient and that our nutrition will normalize these
concentrations with a subsequent improvement in cardiomyocytes functioning
shown by histology. Because of the arginine in the nutrition, we expect an
increase in the arginine/ADMA ratio (as an indicator of nitric oxide (NO)
production).
Secondary outcome
The secondary study outcomes are cardiac perfusion and cardiac fatty acid and
glucose metabolism. Cardiac perfusion will be measured with 99mTc-SPECT,
cardiac fatty acid metabolism with 123IBMIPP-SPECT and cardiac glucose
metabolism with 18FFDG-PET.
We expect the (par)enteral nutrition to increase glucose metabolism (reflected
by an increased uptake of 18FFDG by the myocardium), because the utilization of
glucose as energy source by the myocardium increases under the anaerobic
conditions of coronary atherosclerosis and surgery. We expect the arginine in
the (par)enteral nutrition to improve the arginine/ADMA ratio and to
concomitantly increase NO production and thereby improve cardiac perfusion
(reflected by an increased uptake of 99mTc by the myocardium). Because the
myocardium main energy source under aerobic conditions are fatty acids, we
expect the increased NO production to reduce hypoxic conditions resulting in an
increased fatty acid metabolism (reflected by an increased uptake of 123IBMIPP
by the myocardium).
Another parameter is nutritional status. Nutritional status will be determined
by measured of fat free mass by BIS. We expect that the (par)enteral nutrition
to improve nutritional status reflected by an increase in fat free mass.
Other parameters are diastolic functioning by measuring diastolic pressure,
cardiac function by measuring plasma levels of Troponin T, CK-MB, NT-proBNP,
Copeptin (CT-proAVP), MR-proANP, MR-proADM, CT-proET-1, BrahmsX1 and BrahmsX2,
switch in metabolic regulation with microRNA, and clinical parameters like ICU
stay, hospital length of stay, organ failure, infections, and bleeding.
Because we expect our nutrition to normalize amino acid concentrations and to
improve cardiomyocytes functioning at histological level and cardiac perfusion
and metabolism, we hypothesize an improvement in blood parameters of cardiac
function and a switch in metabolic regulation. The novo-cardiac parameter,
BrahmsX1 and BrahmsX2, has only been studied in animal experiments and will be
studied in this human study of cardio-surgical patients. In addition, because
of the improvement in cardiac functioning we expect reductions in ICU and
hospital stay, organ failure, infections and bleeding. As a result patients
receiving our nutrition return to duties earlier.
Finally, the concentrations of ADMA and SDMA will be measured in an aortic
sample because of the following. Intracellular concentrations of ADMA are more
relevant than those in plasma, since generation, degradation and inhibition of
NOS occur inside the endothelial cells. Therefore we are interested in the
relation of ADMA in plasma and intracellular ADMA in peripheral blood
mononuclear cells (PBMC) with intracellular ADMA in vascular tissue. The
intracellular concentrations of ADMA in PBMC should, better than concentrations
found in plasma, reflect the concentrations in the vascular wall.
Background summary
Malnutrition is very common in patients undergoing cardiac surgery as well as
other types of surgery. For example, in a population of cardiac and abdominal
surgical patients, respectively 9.1% and 44% was malnourished. Malnutrition can
change myocardial substrate utilization which can induce adverse effects on
myocardial metabolism. Interestingly, malnutrition is an underlying risk factor
for the perioperative cardiac complications seen in patients undergoing
non-cardiac surgery. Therefore, by optimizing nutritional status of (cardiac)
surgical patients, cardiac metabolism and function might be improved. This can
be done by administration of enteral or parenteral feeding.
Study objective
Our primary objective is to evaluate the effect of perioperative enteral and
parenteral nutrition on amino acid profile and cardiomyocytes functioning in
the cardiac surgical patient.
Our secondary objective is to study the effect of the (par)enteral nutrition on
cardiac perfusion, and fatty acid and glucose metabolism.
We hypothesize there is a disturbed amino acids profile in the cardiac surgical
patient and that our perioperative nutrition will normalize this profile with a
subsequent improvement in cardiomyocytes functioning shown by histology, and in
cardiac perfusion and metabolism which able patients to return to duties
earlier.
Study design
A randomized controlled intervention study.
Intervention
Enteral group:
Four days before hospital admission, patients in the enteral group will take
250 ml of Multipower Super Charger (Shimano, Nunspeet, The Netherlands) each
day consisting of amino acids (PeptoPro, DSM, Delft, The Netherlands) and
carbohydrates. When admitted to the hospital, patients in the enteral group
will receive a solution containing amino acids (PeptoPro, DSM, Delft, The
Netherlands), carbohydrates (Fantomalt, Danone, Wageningen, The Netherlands),
and vitamins and minerals (Phlexy-Vits, SHS International Ltd., Liverpool,
United Kingdom) which will be prepared at the AMC. This solution will be
prepared for each patient by the *speciaal keuken (afd. ADMF)* of the AMC twice
a day. The enteral nutrition will be given by a post-pyloric feeding tube. It
will be given three days before CABG and during CABG. The enteral nutrition
will also be given the day after CABG unless the patient needs optimal
(hypercaloric or hyperprotein) nutrition. An amount of 1000 ml (two times 500
ml) of the enteral feeding will be given during the day and will contain 80.5 g
amino acids (12.618 g N), 95 g carbohydrates, 1.5 g fats, and 7 g vitamins and
minerals which in total provide 745 kcal.
Parenteral group:
The patients in the parenteral group will receive 1250 ml of an amino acid
infusion of Nutriflex Lipid peri (B.Braun, Oss, The Netherlands). The
parenteral nutrition will be given three days before CABG and during CABG. The
parenteral nutrition will also be given the day after CABG unless the patient
needs optimal (hypercaloric or hyperprotein) nutrition. The parenteral
nutrition will be given by a peripheral and/or central line (PICC). An amount
of 1250 ml of Nutriflex Lipid peri (840 mOsm/L) will be given in 24 hours and
contains 40 g amino acids (5.7 nitrogen/L), 80 g glucose, 50 g lipids, and
electrolytes which provides 955 kcal. In addition, just before the
administration of the parenteral nutrition to the patient is started, vitamins
(Cernevit, Baxter, Utrecht, The Netherlands) and trace elements (Nutritrace,
B.Braun, Oss, The Netherlands) will be added to the solution.
Study burden and risks
In total patients in the enteral will be asked to visit the hospital 3 times
(1st: blood sampling, 99mTc-SPECT, 123IBMIPP-SPECT, 18FFDG-PET, and BIS; 2nd:
blood sampling (6x), CABG, myocardial tissue (2x) and aortic tissue (1x); 3rd:
blood sampling, 99mTc-SPECT, 123IBMIPP-SPECT, 18FFDG-PET, and BIS). In
addition, these patients will be asked to take 250 ml of Multipower Super
Charger each day four days before hospital admission. At admission, a
post-pyloric tube will be placed in order to administer the enteral nutrition
before (3 days), during and after (1 day) surgery.
The patients in the parenteral and control group will be asked to give to visit
the hospital 2 times (1st: blood sampling (6x), 99mTc-SPECT, 123IBMIPP-SPECT,
18FFDG-PET, BIS, CABG, myocardial tissue (2x) and aortic tissue (1x); 2nd:
blood sampling, 99mTc-SPECT, 123IBMIPP-SPECT, 18FFDG-PET, and BIS). At
admission, a peripheral and/or central line will be placed in order to
administer in the parenteral nutrition before (3 days), during and after (1
day) surgery. The control group will receive a saline solution.
Postbus 22700
1100 DE Amsterdam
NL
Postbus 22700
1100 DE Amsterdam
NL
Listed location countries
Age
Inclusion criteria
- Patients undergoing off-pump CABG operation
- Aged 18 till 81 years
- Having obtained his/her informed consent
Exclusion criteria
- Combined valve and coronary artery procedures
- Absent informed consent
- Aged younger than 18 and older than 80 years
- Diabetes mellitus type I
- Pregnancy
- Renal insufficiency defined as creatinine > 95 µmol/L for women and > 110 µmol/L for men
- Liver insufficiency defined as alanine aminotransferase > 34 U/I for women and > 45 U/I for men
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
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Other (possibly less up-to-date) registrations in this register
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2009-017812-33-NL |
| CCMO | NL28231.018.09 |
| OMON | NL-OMON20597 |