Description

After Ethical Review Board of Fayoum University Hospital (FUH) approval and clinicaltrials.gov registration, all patients scheduled for isolated on-pump Coronary Artery Bypass Grafting (CABG) surgery in FUH starting from August 2025 will be enrolled in the study by signing a written informed consent until the sample size is fulfilled. This randomized double-blinded clinical trial will be reported following the tenets of the Declaration of Helsinki and the Consolidated Standards of Reporting Trials (CONSORT) 2025-updated statement.

Patients will be randomized into two equal groups (1:1 allocation) using a computer-generated random number that will be enclosed in a sealed opaque envelope opened by an anesthesiologist, who is responsible for preparing the cardioplegia solution outside the OR and will not be involved in patient management or data collection.

According to each envelope, the Study solution will be either standard Custodiol cardioplegia solution (manufactured by Dr. Franz Köhler Chemie GmbH, Bensheim, Germany), punctured at the injection port with a 10-cc syringe for blinding (Group C), or the modified solution prepared by adding 6.5 ml of 2% lidocaine (Lidocaine HCL -Sunny Pharmaceutical) to each 1 L bag of Custodiol (Group L), using a 10-cc syringe. According to the patient's weight, one or two 1-L solutions will be prepared (calculated at 20 ml/kg, with a maximum of 2 L), kept at 5-8°C, and handed to the cardiothoracic anesthesia team when ordered. Patients, cardiothoracic surgeons, anesthesiologists, and data collectors will be blinded to group allocation until the end of the study.

All patients will be preoperatively examined and investigated by complete blood count, coagulation profile, liver and kidney functions, and electrolytes. A chest x-ray, Electrocardiography (ECG), echocardiography, Carotid arterial duplex, and Coronary angiography will be routinely ordered. Patients will receive an intramuscular injection of 10 mg morphine on the morning of the operation Upon arrival at OR, Standard monitoring will be applied, involving a 5-lead ECG and pulse oximetry. Blood pressure will be monitored through a 20-G cannula inserted into either the right or left radial artery under local anesthesia. Atracurium (0.5 mg/kg), midazolam (2-5 mg), fentanyl (2-5 μg/kg), and propofol (1-2 mg/kg) will be used to induce general anesthesia following pre-oxygenation.

After tracheal intubation, patients will be mechanically ventilated with an Oxygen and air mixture, maintaining normocapnia confirmed by capnogram and arterial blood gas analysis. A urinary catheter, an esophageal temperature probe, and a right internal jugular triple-lumen central venous catheter will be inserted. Inhalational isoflurane (0.4 to 1 %) and atracurium infusion at 0.5 mg/kg/h will be used to maintain anesthesia and muscle relaxation. A 50-100 µg/kg/min propofol infusion will replace isoflurane inhalation during extracorporeal circulation.

To achieve an active clotting time of greater than 480 seconds, patients will receive intravenous heparin (300-500 units/kg body weight) prior to the initiation of cardiopulmonary bypass (CPB). An ascending aortic cannula and a two-stage right atrial cannula will be used to implement CPB. Before, during, and following CPB, mean arterial pressure will be adjusted to be higher than 60 mmHg (pump blood flow: 2.4 l/min/m2).

Myocardial protection:

The antegrade approach will be utilized to deliver the cardioplegic solution through the coronary ostia or the aortic root, as appropriate. The cardioplegic solution will be either the classic Custodiol or the modified Custodiol according to the group allocation of each patient.

A ready-blinded cardioplegia solution will be administered as a single dose of 20 mL/kg over 6-8 minutes at a temperature of 5-8 °C. An additional half dose of the same solution will be prepared and infused if the procedure exceeds 180 minutes after the initial dose is completed.

Mean arterial blood pressure will be maintained at 50-70 mmhg during the bypass period.

By completing distal anastomosis and before the ACC removal, all patients will be rewarmed to a core temperature of 36°C and have an arterial blood gas analysis that should have a normal PH (7.35-7.45), a normal potassium level (3.5 - 5.5) mg/dl, and a hemoglobin level above 10 g/dl, any abnormal value should be corrected before ACC removal. A 1.5 mg/kg lidocaine and 1 gram of Magnesium sulfate will be administered on the cardiopulmonary bypass machine just before the ACC release.

After cross clamp removal, internal paddles will be used to defibrillate any ventricular fibrillation VF with 10 joule of energy.

If VF is resistant after three 10 j shocks, a 150 mg of Amiodarone will be administered and subsequent defibrillator shocks with escalating energy level 10, 20, and 30 joules will be used.

Proximal venous graft anastomoses will be carried out after applying a partial aortic cross clamp. Then, the patient will be gradually weaned from cardiopulmonary bypass after rewarming to normal core temperature and applying any needed inotropic or vasopressor support to maintain optimal cardiac output.

Protamine sulfate will be administered after achieving hemodynamic stability to reverse the actions of heparin. The patient will be transferred to the postoperative cardiac surgery intensive care unit after completing hemostasis, drains, epicardial pacing wires, and wound closure.

Sample size calculation:

the sample size was calculated based on a previous study from Kammerer et.al, the incidence of ventricular fibrillation after ACC removal with Custodiol was 45.45 % and the incidence with conventional cardioplegic solution was 9.6 %. the investigators hypothesize that the addition of lidocaine to Custodiol will decrease the incidence of VF after ACC removal to a percentage similar to the conventional cardioplegic solution.

To account for this proportion difference, a minimal sample size of 31 patients in each group is needed to get a power level of 0.90 and an alpha level of 0.05. The calculated sample size will be increased to 35 in each group to allow for dropouts up to 10%. IBM SPSS software version 31 was used to estimate the required sample size.

Statistical Analysis Statistical analysis will be performed using IBM SPSS software version 31. Descriptive statistics will be used to summarize participant demographics and clinical characteristics. Continuous variables will be reported as means ± standard deviations or medians with interquartile ranges, depending on normality of data assessed using the Shapiro-Wilk test. Categorical variables will be presented as frequencies and percentages. Independent t-tests or Mann-Whitney U tests will be applied to compare continuous variables between the two groups, while chi-square or Fisher's exact tests will be used for categorical variables as appropriate. Survival analysis with Kaplan Meier plot will be used for comparison of time to event variables. P-value less than 0.05 will be considered statistically significant.