Adding Lidocaine to Custodiol Mixture

Not Applicable

Not yet recruiting

• Conditions: CAD; Arrhythmia Ventricular
• Interventions: Drug: Custodiol Solution; Drug: Lidocaine Hydrochloride

• Registration Number: NCT07205757
• Lead Sponsor: Fayoum University Hospital

Brief Summary

The Bretschneider solution, also known as Custodiol, has been widely used in open-heart surgery requiring cardiopulmonary bypass (CPB) since its introduction in 1970. Custodiol is widely favored by cardiac surgeons, being administered as a single dose, and is supposed to offer myocardial protection for up to three hours, permitting an uninterrupted surgical time, especially for intricate procedures The literature continues to debate the superiority of custodial and other cardioplegic solutions, such as the Del Nido and St. Thomas solutions, regarding both short-term and long-term outcomes. Clinical trials and daily practice showed that the use of custodial cardioplegic solution is associated with increased incidences of ventricular arrhythmias, and subsequently, the use of a defibrillator after Aortic Cross Clamp (ACC) removal at the end of CPB when compared to other types of cardioplegia solutions .One of the reasons for this difference mentioned in the literature is the lidocaine contained in other types of cardioplegic solutions. Lidocaine acts as a membrane stabilizer by blocking rapid sodium channels in the heart, thus preventing arrhythmias, in addition to its ability to inhibit calcium influx, which is the primary cause of ischemic-reperfusion injury.

Based on these data, the investigators hypothesize that the increased incidence of Ventricular arrhythmias with the use of Custodiol compared to other solutions, such as St Thomas and Del Nido, may be attributed to the absence of lidocaine. Although Custodiol contains tryptophan as a membrane-stabilizing component, it may be beneficial to add lidocaine to the Custodiol mixture to decrease the incidence of VF after cross-clamp removal in adult patients undergoing elective CABG.

Detailed 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.

Study Timeline

• Status Verified: 2025-09
• Study First Submitted: 2025-09-18
• Study First Submitted QC: 2025-09-25
• Last Update Submitted: 2025-09-25
• Study Start: 2025-10-01
• Study First Posted: 2025-10-03
• Last Update Posted: 2025-10-03
• Primary Completion: 2026-04-30
• Study Completion: 2026-06-01

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 70

Inclusion Criteria

• patients scheduled for elective Coronary artery bypass grafting surgery

Exclusion Criteria

• Emergency or Redo surgery.
• Baseline rhythm other than sinus rhythm
• Any degree of heart block, bundle branch block or hemiblock
• Known allergy to lidocaine.
• Chronic kidney disease.
• Hepatic impairment.
• Severe psychiatric illness.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Custodiol group	Custodiol Solution	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
Lidocaine and Custodiol group	Lidocaine Hydrochloride	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.
Lidocaine and Custodiol group	Custodiol Solution	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.

Primary Outcome Measures

Name	Time	Method
incidence of ventricular fibrillation (VF)	Perioperative	incidence of VF occurring after Aorta cross-clamp (ACC) removal

Secondary Outcome Measures

Name	Time	Method
Troponin I (µg/L)	At immediate postoperatively, 12 and 24 hours postoperative	Troponin I to assess myocardial protection between the two cardioplegia solutions used.
Number of defibrillator shocks	Perioperative	shocks required to terminate ventricular arrhythmia after ACC removal
Total volume of cardioplegia solution (in ml).	Perioperative	cardioplegia volume given to the patient
Total cross-clamp time	from cross clamp until removal of aorta cross clamp up to 6 hours	in minutes
total CPB time	from starting CPB until weaning from bypass is completed up to 6 hours	in minutes
Number of grafts	at the end of surgery up to 6 hours	anastomosis coronary grafts
Time taken to cardiac arrest after cardioplegia infusion	from the start of cardioplegia administration until asystole up to one hour	time to asystole
Left ventricular ejection fraction assessed both preoperative and after 24 hours postoperatively.	assessed both preoperative and after 24 hours postoperatively.	echo assessment
Preoperative EURO II score	assessed preoperatively at the start of patient enrollment	EURO II score
Inotropic support.	assessed after patient is transferred to intensive care up to 6 hours from start of surgery	the need for inotropes on transfer to intensive care
Total time of inotropes or vasopressor requirement in hours	assessed after patient is weaned from inotropes up to one month	the need for inotropes in intensive care
Mortality rate	assessed up to one month postoperatively	Mortality rate
CK-MB (U/L) .	at immediate postoperatively, 12 and 24 hours after surgery	CK-MB (U/L) .
Serum lactate level	at immediate postoperatively, 12 and 24 hours after surgery.	Serum lactate level
Incidence of postoperative Myocardial infarction	assessed from icu admission until discharge up to one month	Incidence of postoperative Myocardial infarction
Incidence of postoperative Atrial fibrillations	assessed from icu admission until ICU discharge up to one month	Incidence of postoperative Atrial fibrillations
Time for weaning from mechanical ventilation	assessed from icu admission until ventilator weaning up to one month	from mechanical ventilation (in hours).
ICU length of stay	assessed from icu admission until ICU discharge up to one month	in hours
hospital length of stay (in days)	assessed from icu admission until home discharge up to one month	in days

Trial Locations

Locations (1)

Fayoum University Hospital; 🇪🇬 Al Fayyum, Egypt