Immunonutrition in Cardiac Surgery
|ClinicalTrials.gov Identifier: NCT00247793|
Recruitment Status : Completed
First Posted : November 2, 2005
Last Update Posted : November 2, 2005
|First Submitted Date ICMJE||November 1, 2005|
|First Posted Date ICMJE||November 2, 2005|
|Last Update Posted Date||November 2, 2005|
|Study Start Date ICMJE||July 1996|
|Primary Completion Date||Not Provided|
|Current Primary Outcome Measures ICMJE
|Original Primary Outcome Measures ICMJE||Same as current|
|Change History||No Changes Posted|
|Current Secondary Outcome Measures ICMJE
|Original Secondary Outcome Measures ICMJE||Same as current|
|Current Other Outcome Measures ICMJE||Not Provided|
|Original Other Outcome Measures ICMJE||Not Provided|
|Brief Title ICMJE||Immunonutrition in Cardiac Surgery|
|Official Title ICMJE||The Effect of Pre- and Postoperative Supplemental Enteral Nutrition in High-Risk Patients Undergoing Elective Cardiac Surgery. A Prospective Double Blind Study.|
Effect of two preoperative oral immune-enhancing nutritional supplements in patients at high risk of infection after cardiac surgery: a randomized placebo-controlled study.
Introduction: In our first study we showed that the use of a preoperative oral immune-enhancing nutritional supplement (OIENS) resulted in an improved patients’ host-defence with a reduction in postoperative infectious morbidity in ‘high-risk’ cardiac surgery patients. The use of the OIENS resulted also in less postoperative organ dysfunction. Experimental studies have shown that additional glycine results in less ischemia-reperfusion damage and that glycine has anti-inflammatory properties.
Objective: The use of an OIENS in the preoperative period in patients at high risk of infection after elective cardiac surgery with the use of cardiopulmonary bypass (CPB) results in a reduction in infections as in our first study. The addition of 9.6 gram glycine per sachet OIENS results in a further reduction in postoperative dysfunction.
Design: A prospective randomized placebo controlled study with two oral immune enhancing nutritional formula’s and an isocaloric control formula. Patients: Seventy-four consecutive patients undergoing cardiac surgery with the use of an CPB who met one or more of the following inclusion criteria: Age 70 years or older, mitral valve replacement or cardiac ejection fraction less then 40%. Exclusion criteria were age < 18 years, proven malignancy, use of corticosteroids, severe renal and liver failure. Definition of a protocol violation was the intake of less then 5 L or more then 10 L of the nutritional supplement in the preoperative period.
Intervention: Patients were split up in three groups by concealed randomisation. One group received the arginine, omega3-PUFAs and nucleotides enriched formula (OIENS). Another group received the OIENS further enriched with glycine (OIENS+glyc). The control group received an isocaloric nutritional supplement without the enrichments.
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
|Study Type ICMJE||Interventional|
|Study Phase||Not Applicable|
|Study Design ICMJE||Allocation: Randomized
Intervention Model: Parallel Assignment
Primary Purpose: Treatment
|Intervention ICMJE||Drug: Oral Impact (preoperative enteral nutritional supplement)|
|Study Arms||Not Provided|
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
|Recruitment Status ICMJE||Completed|
|Enrollment ICMJE||Not Provided|
|Original Enrollment ICMJE||Not Provided|
|Study Completion Date||December 1998|
|Primary Completion Date||Not Provided|
|Eligibility Criteria ICMJE||
Patients undergoing cardiac surgery with the use of cardiopulmonary bypass, who met one of the following criteria
|Ages||21 Years and older (Adult, Senior)|
|Accepts Healthy Volunteers||No|
|Contacts ICMJE||Contact information is only displayed when the study is recruiting subjects|
|Listed Location Countries ICMJE||Netherlands|
|Removed Location Countries|
|NCT Number ICMJE||NCT00247793|
|Other Study ID Numbers ICMJE||96.17.066
|Has Data Monitoring Committee||Not Provided|
|U.S. FDA-regulated Product||Not Provided|
|IPD Sharing Statement||Not Provided|
|Responsible Party||Not Provided|
|Study Sponsor ICMJE||Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)|
|Collaborators ICMJE||Not Provided|
|PRS Account||Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)|
|Verification Date||November 2005|
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP