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).