Preoperative Immunonutrition and Cardiac Patients
Condition: Cardiac Function
Study type: Interventional
Phase: Phase 2/Phase 3

Summary: 
      With the progress of cardiac surgery, the indication of cardiac valve replacement has been
      extended to include severely ill patients, even those with cardiac cachexia caused by
      long-standing mitral valve disease. Since patients with advanced cardiac functional
      disability are prone to fall into a low cardiac output state after valve replacement, Those
      severely ill, cachectic patients may be susceptible to postoperative acute renal failure.
      Preoperative malnutrition because of poor oral intake significantly increases the risk of
      adverse events after surgery and leads to increased length of stay.

      Major operation itself possibly cause the dysfunction of the host homeostasis, defense
      mechanisms and inflammatory response, which would increase the rate of postoperative
      complications and prolong hospital stay. Recently, many researchers argued that
      immunonutritional formulas supplemented with biologically active nutrients were more
      effective than standard nutrition intervention in improving inflammation, promoting the wound
      healing and shortening the length of hospital stay (LOS) after operation.
    

Detailed description: 
      Eligibility and type of the study: This randomized clinical trial will be conducted at Assiut
      University Hospital from March 2018 until March 2019 after approval from the Institutional
      Ethics Committee and after obtaining written informed consents from all cardiac patients
      undergoing mitral valve replacement surgery.

      Randomization and sample size :

      Sample size calculation Sample size calculation was carried out using G*Power 3 software. A
      calculated sample of 88 patients (44 cases and 44 controls) will be needed to detect an
      effect size of 0.3 reduction in pro-BNP Level, with an error probability of 0.05 and 90%
      power on a two-tailed test.

      Patients:

      Patients will be assigned into two equal groups of 44 patients each:

      Group 1: patients will take preoperative immunonutrition in the form of intravenous glutamine
      (Dipeptiven-Fersenius Kabi) 0.4 g/kg/day (once daily) for 5 days before surgery in addition
      to a conventional diet.

      Group 2: patients will continue conventional diet. Conventional median sternotomy will be
      performed in all patients. Arterial line will be inserted. Anesthesia will be induced with
      midazolam 0.05mg\kg, propofol 1-1.5mg\kg and fentanyl 2μg\kg. Anesthesia will be maintained
      with isoflurane, fentanyl infusion1-2μ\kg\hr and Cis-atracurium infusion 2μ\kg\min before
      cardiopulmonary bypass (CBP) and with propofol and fentanyl on CBP, according the
      anaesthetist criteria. Anticoagulation will be achieved with heparin 3-4 mg\kg to maintain an
      activated clotting time over 450s .Reversal of heparin will be with protamine.
      Cardiopulmonary bypass will be achieved with a roller pump and a membrane oxygenator. After
      the aortic clamp will be applied, asolution of 1000-1500 cc of hematic cardioplegia will be
      administrated. Then 400-500 cc of solution will be administrated every 30min until the end of
      the procedure. Mean arterial pressure should be above 60 mmHg for the duration of CBP.

      Data collection:

      Cardiac function:

        -  Preoperative and postoperative echocardiography.

        -  Inotropic score every 2hours in first 6 hours then every 6 hours for the rest of 48
           hours postoperatively.

        -  Serum proBNP (Brain natruritic peptide) preoperatively and post operative first and
           forth days.

      Kidney function:

        -  Urine output in the postoperative first and second days.

        -  Serum urea and creatinine in postoperative first and second days.

        -  Serum NGAL (Neutrophil gelatinase-associated lipocalin) preoperatively and postoperative
           first and forth days.

      Hemodynamics:

      - MAP, HR every 2hours in first 6 hours then every 6 hours for the rest of 48 hours
      postoperatively.

      Hours of mechanical ventilation. Hospital and ICU stay. Any postoperative complications will
      be recorded and treated.

      Sampling:

      Venous blood sample will be obtained by direct venipuncture and collected into serum
      separator tubes. Samples will be centrifuged within 20 minutes from withdrawal and stored for
      amixture of 12 hours at 2-8 ゜C before the separation of serum. Serum will be stored frozen at
      -40 ゜C. Pro-BNP serum concentrations will be determined using an automated method.

      Statistical analysis :

      Data will be performed using a standard SPSS software package version 21 (SPSS Inc., Chicago,
      Illinois, USA).Descriptive values will be expressed as mean ± SD, number or percentages. The
      Student t-test will be used for comparison between means of variables and normally
      distributed data. P will be considered significant if (p≤ 0.05).

      Ethical Consideration:

        -  The randomized clinical trial will be approved by local ethics committee of faculty of
           medicine, Assiut University, Egypt after obtaining written informed consent from
           patients.

        -  There is no risk affecting the patients participating in this study.

        -  Every patient can leave the study and will receive the same care.

        -  Any data taken from all patient will be made confidential and available only to persons
           conducting the study.

        -  Any patient can stop participation in the study at any time without any loss of service.
    

Intervention name(s): IV Immunonutrition; Conventional Diet
Intervention type(s): Dietary Supplement; Dietary Supplement
Intervention description(s): patients will receive preoperative immunonutrition in the form of glutamine) Dipeptiven-Fresenius Kabi) given by intravenous infusion 0.4g/kg/day for 3 days before surgery.; patients will continue preoperative oral conventional diet.
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary purpose: Prevention
Keywords: Immunonutrition; Cardiac Patient; Mitral Valve Replacement