Preoperative Immunonutrition and Cardiac Patients

Implication of Preoperative Immunonutrition Upon Cardiac Patients Undergoing Mitral Valve Replacement Surgery

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.

Study Overview

• Status: Completed
• Conditions: Cardiac Function
• Intervention / Treatment: Dietary supplement: IV Immunonutrition; Dietary supplement: Conventional Diet

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.

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• Egypt
  • Assiut, Egypt, 71515
    • Assiut University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Both sex
• Age: 18-60 years.
• Valvular heart disease .
• ASA II,III
• Non-diabetic.
• Elective surgery.

Exclusion Criteria:

• Pre-existing renal disease(creatinine3.5mg/dl or dialysis)
• Diabetic.
• Off pump surgery.
• Long CBP time >120 min .
• Previous cardiac surgery.
• Hepatic failure or established cirrhosis.
• Emergency surgery

Study Plan

How is the study designed?

Design Details

• Primary Purpose: PREVENTION
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: TRIPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Group I; 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.	Dietary supplement: IV Immunonutrition; 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.
ACTIVE_COMPARATOR: Group II; Patients will continue preoperative oral conventional diet.	Dietary supplement: Conventional Diet; patients will continue preoperative oral conventional diet.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cardiac Fuction	Serum proBNP (Brain natruritic peptide)	4 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Inotropic score	Dopamine dose (mcg/kg/min) + Dobutamine dose (mcg/kg/min) + 100 x Epinephrine dose (mcg/kg/min) min 20 and max 60 The lower the inotropic score the better cardiac function and lower morbidity	4 days
Kidney Function	Serum NGAL (Neutrophil gelatinase-associated lipocalin)	4 days
urine output	urine volume per day	2 days
Hemodynamics	mean arterial blood pressure	2 days
Postoperative Hospital Data	Hospital and ICU stay	4 days
Postoperative complications	any postoperative complications	4 days

Collaborators and Investigators

• Sponsor: Assiut University
• Investigators: Study Director: Khaled M Morsy, MD, Assistant prof of anesthesia and intensive care

Study record dates

Study Major Dates

• Study Start (ACTUAL): August 1, 2018
• Primary Completion (ACTUAL): March 31, 2022
• Study Completion (ACTUAL): March 31, 2022

Study Registration Dates

• First Submitted: February 16, 2018
• First Submitted That Met QC Criteria: February 22, 2018
• First Posted (ACTUAL): February 26, 2018

Study Record Updates

• Last Update Posted (ACTUAL): August 16, 2022
• Last Update Submitted That Met QC Criteria: August 12, 2022
• Last Verified: August 1, 2022

More Information

Terms related to this study

• Keywords: Immunonutrition; Mitral Valve Replacement; Cardiac Patient
• Other Study ID Numbers: Immunonutrition

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No