Plegisol

PLEGISOL- potassium chloride, sodium chloride, calcium chloride and magnesium chloride injection, solution
Hospira, Inc.

CARDIOPLEGIC SOLUTION FOR CARDIAC PERFUSION

NOT FOR INTRAVENOUS INJECTION

Flexible Plastic Container

R_x Only

DESCRIPTION

Plegisol (Cardioplegic Solution) is a sterile, nonpyrogenic, essentially isotonic, formulation of electrolytes in water for injection. It is a “core solution” intended for use only after addition of sodium bicarbonate to adjust pH prior to administration. After buffering with sodium bicarbonate it is suitable for cardiac instillation (usually with hypothermia) to induce arrest during open heart surgery. Other agents may be added to the solution prior to instillation (See INSTRUCTIONS FOR USE).

Each 100 mL of solution contains calcium chloride, dihydrate 17.6 mg, magnesium chloride, hexahydrate 325.3 mg, potassium chloride 119.3 mg and sodium chloride 643 mg in water for injection. May contain HCl or NaOH for pH adjustment. Electrolyte content per liter (not including ions for pH adjustment): Calcium (Ca⁺⁺) 2.4 mEq; magnesium (Mg⁺⁺) 32 mEq; potassium (K⁺) 16 mEq; sodium (Na⁺) 110 mEq; chloride (Cl‾) 160 mEq. Osmolar concentration, 304 mOsmol/liter (calc.); pH 3.8 (3.5 to 3.9) prior to sodium bicarbonate addition.

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 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 stored under refrigeration and be used within 24 hours.

The buffered admixture contains the following electrolytes (per liter): Ca⁺⁺ 2.4 mEq, Mg⁺⁺ 32 mEq, K⁺ 16 mEq, Na⁺ 120 mEq, Cl‾ 160 mEq and bicarbonate (HCO₃ ‾) 10 mEq; osmolar concentration, 324 mOsmol/liter (calc.); pH 7.8 (approx.). If other agents are added, these values may be altered.

The solution contains no bacteriostat, or antimicrobial agent and is intended only for use (after adjusting pH with sodium bicarbonate) in a single operative procedure. When smaller amounts are required, the unused portion should be discarded.

Plegisol with added sodium bicarbonate used as a coronary artery infusate induces cardiac arrest, combats ischemic ionic disturbances, buffers ischemic acidosis and protects energy sources for functional recovery after ischemia.

Calcium Chloride, USP is chemically designated calcium chloride, dihydrate (CaCl₂ • 2 H₂ O), white fragments or granules freely soluble in water.

Magnesium Chloride, USP is chemically designated magnesium chloride, hexahydrate (MgCl₂ • 6 H₂ O), deliquescent flakes or crystals very soluble in water.

Potassium Chloride, USP is chemically designated KCl, a white granular powder freely soluble in water.

Sodium Chloride, USP is chemically designated NaCl, a white crystalline powder freely soluble in water.

Water for Injection, USP is chemically designated H₂ O.

The flexible plastic container is fabricated from a specially formulated polyvinyl chloride. Water can permeate from inside the container into the overwrap but not in amounts sufficient to affect the solution significantly. Solutions in contact with the plastic container may leach out certain chemical components from the plastic in very small amounts; however, biological testing was supportive of the safety of the plastic container materials. Exposure to temperatures above 25°C/77°F during transport and storage will lead to minor losses in moisture content. Higher temperatures lead to greater losses. It is unlikely that these minor losses will lead to clinically significant changes within the expiration period.

CLINICAL PHARMACOLOGY

Plegisol 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 (HCO₃ ‾) 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.

INDICATIONS AND USAGE

Plegisol (Cardioplegic Solution) when suitably buffered in combination with ischemia and hypothermia is used to induce cardiac arrest during open heart surgery.

CONTRAINDICATIONS

Plegisol must not be administered without the addition of 8.4% Sodium Bicarbonate Injection, USP, Hospira List 4900.

NOT FOR INTRAVENOUS INJECTION.

This solution is only for instillation into cardiac vasculature after buffering with sodium bicarbonate.

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.

PRECAUTIONS

Myocardial temperature should be monitored during surgery to maintain hypothermia.

Continuous electrocardiogram monitoring is essential to detect changes in myocardial activity during the procedure.

Appropriate equipment to defibrillate the heart following cardioplegia should be readily available.

Inotropic support drugs should be available during postoperative recovery.

Do not administer unless solution is clear and container is undamaged. Discard unused portion.

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 Plegisol. It is also not known whether this solution can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. Plegisol should be given to a pregnant woman only if clearly needed.