Cardioplegia solutions have been considered as a corner stone for myocardial protection during cardiac surgery with cardiopulmonary bypass and cardiac arrest, it limits the metabolic activity and increases the capacity of the myocardium to withstand prolonged ischemic time, and thus it has a direct impact on surgical outcomes. (1, 2) Long acting cardioplegic solutions with a single dose strategy are beneficial as they allow surgery without interruptions, reducing cross clamp time and provide more cardiac protection. (3) Custodiol (histidine- tryptophan- ketoglutarate) solution has been described in the 1970s by Bretschneider (4), and used as an alternative to hyperkalemic crystalloid solutions especially during complex cardiac surgeries, also used for organ preservation during transplant surgery. (5, 6) In the 1990s Pedro del Nido and his team introduced a new cardioplegic solution (del Nido cardioplegia) for pediatric cardiac surgeries. (7) But recently, many studies postulated its use for adults. (8) The base solution for the traditional del Nido cardioplegia is Plasma-Lyte A which is a calcium free solution and electrolyte composition similar to the extracellular fluid. (7) However Plasma-Lyte A is unavailable in many countries, this precludes its use. Some authors have advocated lactated Ringer's as a base solution instead of Plasma-Lyte A for preparing del Nido cardioplegia, now known as modified del Nido cardioplegia. (9) Custodiol and modified del Nido cardioplegia can be used in a single dose fashion with proper myocardial protection and minimal surgical interruptions. However, the literature also does not confirm the superiority of one over another. (1) Also, limited number of clinical trials compared both cardioplegic solutions directly. So, in this study we aimed to assess the efficacy of both Custodiol and modified del Nido cardioplegia in myocardial protection and clinical outcomes among adult patients undergoing cardiac surgery.

Patients will be divided into two groups with 1:1 allocation, randomized by computer generated random numbers that will be placed in separate opaque envelopes opened by study investigators at OR. MDN group (will receive modified Del Nido cardioplegia solution) and C group (will receive Custodiol cardioplegia). Participants and data collectors will be blinded with the group allocation till the end of the study.

Inclusion criteria: patients ≥ 18 years old, scheduled for elective valve replacement surgery or coronary artery bypass grafting surgery.

All patients will be preoperatively examined and investigated by complete blood count, coagulation profile, liver and kidney functions and electrolytes. Electrocardiography, chest x ray and echocardiography will be routinely done. Coronary angiography and carotid arterial duplex will be requested on demand.

Patient will be premedicated by intramuscular injection of 10mg morphine at morning of the operation. Before induction of anesthesia, a five-lead electrocardiography system will be applied to monitor heart rate, rhythm, and ST segments (leads II and V5). A pulse oximeter probe will be attached, and a peripheral venous cannula will be placed. For measurement of arterial pressure and blood sampling, a 20 G cannula will be inserted into either right or left radial artery under local anesthesia. After pre-oxygenation, general anesthesia will be induced by midazolam 2-5 mg, fentanyl (10μg/kg), propofol (3-4mg/Kg), followed by atracurium (0.5 mg/kg).

Trachea will be intubated; patients will be mechanically ventilated with oxygen in air so as to achieve normocarbia. This will be confirmed by radial arterial blood gas analysis and capnogram. An esophageal temperature probe and a urinary catheter will also be placed. For drug infusion, a triple-lumen central venous catheter will be inserted via the right internal jugular vein. Anesthesia will be maintained by inhaled Isoflurane 0.4 to 1% and atracurium infusion at a rate of 0.5 mg/kg/h for continued muscle relaxation. During extracorporeal circulation, patients will receive propofol infusion at a rate of 50-100 µ/kg/min. in addition to atracurium infusion.

Before initiation of cardiopulmonary bypass (CPB), the patients will receive intravenous heparin (300-500 units/kg body weight) to achieve an activated clotting time >480s. CPB will be instituted via an ascending aortic cannula and a two-stage right atrial cannula. Before, during (pump blood flow: 2.4l/min/m2), and after CPB, mean arterial pressure will be adjusted to exceed 60mmHg.

Surgery will be done via median sternotomy; CBP will be established via arterial cannula in the ascending aorta and venous drainage obtained via two-stage cannula in the right atrium or bicaval cannulation.

Myocardial protection:

Cardioplegic solution will be administered via antegrade technique through the aortic root or the coronary ostia accordingly. Patients will receive either Custodiol cardioplegia or modified Del Nido cardioplegia according to their allocation.

Ready Custodiol cardioplegia solution will be administered in a single dose of 25ml.kg-1 over 6-8 minutes with 4-8 oC temperature and 150-200 mmHg infusion pressure. Custodiol is a ready sterile cardioplegia composed of; sodium chloride 15 mmol/L, potassium chloride 9 mmol/L, magnesium chloride 4 mmol/L, calcium chloride 0.015 mmol/L, histidine 180 mmol/L, tryptophan 2 mmol/L, ketoglutarate 1 mmol/L and mannitol 30 mmol/L with pH 7.4-7.45 at 4°C and osmolality 310 mosmol/Kg.

Modified Del Nido cardioplegia will be prepared at OR, and lactated Ringer's solution will be used as a crystalloid base, with crystalloid: blood ratio of 4:1 and will be given with a dose of 20 ml/kg (with a maximum dose of 1000 ml) at 4 oC temperature and 200-300 mmHg administration pressure and if necessary additional dose will be given after 90 minutes of the initial dose. The composition of modified Del Nido cardioplegia will be as follows: lactated Ringer's solution 1000ml, 13 ml sodium bicarbonate (1 mEq/ ml), 16.3 ml of mannitol 20%, 4 ml magnesium 50%, 6.5 ml of lidocaine 2% and 13ml of potassium chloride (2 mEq/L).

Inclusion Criteria:

• patients ≥ 18 years old, scheduled for elective valve replacement surgery or coronary artery bypass grafting surgery.

Exclusion Criteria:

• Emergency surgery.
• Chronic kidney disease.
• Hepatic impairment.
• Re-do surgery.
• Severe psychiatric illness.