Calcium Chloride, Magnesium Chloride, Potassium Chloride and Sodium Chloride

INDICATIONS AND USAGE Baxter Cardioplegic Solution when suitably buffered in combination with ischemia and hypothermia is used to induce cardiac arrest during open heart surgery.

DOSAGE AND ADMINISTRATION The following information is suggested as a guide and is subject to variation according to the preference and experience of the surgeon. It is required that 10 mL (840 mg) of 8.4% Sodium Bicarbonate Injection, USP (10 mEq each of sodium and bicarbonate) be added aseptically and thoroughly mixed with each 1000 mL of cardioplegic solution to adjust pH. Use 10 mL of Hospira 1 List 4900, 8.4% Sodium Bicarbonate Injection, USP, to achieve the approximate pH of 7.8 when measured at room temperature. Use of any other Sodium Bicarbonate Injection may not achieve this pH due to the varying pH’s of Sodium Bicarbonate Injections. Due to its inherent instability with other components, sodium bicarbonate must be added just prior to administration. After this addition, the solution must be used within 24 hours. The solution should be cooled to 4°C prior to use. Following institution of cardiopulmonary bypass at perfusate temperatures of 28° to 30°C, and after cross-clamping of the ascending aorta, the buffered solution is administered by rapid infusion into the aortic root. The initial rate of infusion may be 300 mL/m 2 /minute (about 540 mL/min in a 5’ 8”, 70 kg adult with 1.8 square meters of surface area) given for a period of two to four minutes. Concurrent external cooling (regional hypothermia of the pericardium) may be accomplished by instilling a refrigerated (4°C) physiologic solution such as a Normosol® 2 -R (balanced electrolyte replacement solution) or Ringer's Injection, USP into the chest cavity. Should myocardial electromechanical activity persist or recur, the solution may be reinfused at a rate of 300 mL/m 2 /min for a period of two minutes. Reinfusion of the solution may be repeated every 20 to 30 minutes or sooner if myocardial temperature rises above 15° to 20°C or returning cardiac activity is observed. The regional hypothermia solution around the heart also may be replenished continuously or periodically in order to maintain adequate hypothermia. Suction may be used to remove warmed infusates. An implanted thermistor probe may be used to monitor myocardial temperature. The volumes of solution instilled into the aortic root may vary depending on the duration or type of open heart surgical procedure. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit (See PRECAUTIONS ).

WARNINGS This solution should be used only by those trained to perform open heart surgery. This solution is intended only for use during cardiopulmonary bypass when the coronary circulation is isolated from the systemic circulation (See INDICATIONS AND USAGE ). Do not instill the solution into the coronary vasculature unless sodium bicarbonate has been added. If large volumes of cardioplegic solution are infused and allowed to return to the heart lung machine without any venting from the right heart, then plasma magnesium and potassium levels may rise. Development of severe hypotension and metabolic acidosis while on bypass has been reported when large volumes (8 to 10 liters) of solution are instilled and allowed to enter the pump and then the systemic circulation. Right heart venting is therefore recommended. The buffered solution with added sodium bicarbonate should be cooled to 4°C prior to administration and used within 24 hours of mixing.

CONTRAINDICATIONS Baxter Cardioplegic Solution must not be administered without the addition of 8.4% Sodium Bicarbonate Injection, USP, Hospira 1 List 4900. NOT FOR INTRAVENOUS INJECTION. This solution is only for instillation into cardiac vasculature after buffering with sodium bicarbonate.

Drug Interactions Additives may be incompatible. Consult with pharmacist, if available. When introducing additives, use aseptic technique, mix thoroughly and do not store (See INSTRUCTIONS FOR USE ). Pregnancy: Animal reproduction studies have not been conducted with Cardioplegic Solution. It is also not known whether this solution can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. Cardioplegic Solution should be given to a pregnant woman only if clearly needed.

ADVERSE REACTIONS Intraoperative and perioperative potential hazards of open heart surgery include myocardial infarction, electrocardiographic abnormalities, and arrhythmias, including ventricular fibrillation. Spontaneous recovery after cardioplegic cardiac arrest may be delayed or absent when circulation is restored. Defibrillation by electric shock may be required to restore normal cardiac function.

CLINICAL PHARMACOLOGY Cardioplegic Solution with added sodium bicarbonate when cooled and instilled into the coronary artery vasculature, causes prompt arrest of cardiac electromechanical activity, combats intracellular ion losses and buffers ischemic acidosis. When used with hypothermia and ischemia, the action may be characterized as cold ischemic potassium-induced cardioplegia. This is conducive to providing the surgeon with a quiet, relaxed heart and bloodless field of operation. Calcium (Ca ++ ) ion in low concentration is included in the solution to maintain integrity of cell membrane to ensure that there is no likelihood of calcium paradox during reperfusion. Magnesium (Mg ++ ) ion may help stabilize the myocardial membrane by inhibiting a myosin phosphorylase, which protects adenosine triphosphate (ATP) reserves for postischemic activity. The protective effects of magnesium and potassium have been shown to be additive. Potassium (K + ) ion concentration is responsible for prompt cessation of mechanical myocardial contractile activity. The immediacy of the arrest thus preserves energy supplies for postischemic contractile activity in diastole. The chloride (Cl - ) and sodium (Na + ) ions have no specific role in the production of cardiac arrest. Sodium is essential to maintain ionic integrity of myocardial tissue. The chloride ions are present to maintain the electroneutrality of the solution. Added bicarbonate (HCO 3 - ) anion is included as a buffer to render the solution slightly alkaline and compensate for the metabolic acidosis that accompanies ischemia. Extemporaneous alternative buffering to the described formulation of this solution is not recommended.