Perfusion Policies 101: Custodial Cardioplegia

Editor’s Note:

Renee is a colleague I work with quite often. She is an amazing perfusionist as well as administrator, mom, and just a decent all around human being. She has a pretty scathing wit- so beware.

She offered to share a policy on the administration of CUSTODIAL THK Cardioplegia. This is a collaborative effort as I have added some other valuable background information- garnered from other articles on this topic 🙂

So I welcome you to read it and share it. It is well written, and hopefully we shall add Renee to our editorial staff.

Enjoy 🙂

Perfusion Policies 101: Custodial Cardioplegia

Renee Toth, BS, CCP

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Myocardial protection and preservation is a primary goal for open-heart surgery patients. To ensure that the patient’s heart is protected during ischemic arrest, the Perfusionist is responsible for the delivery of the cardioplegia solution. Custodiol HTK (Histidine-Trytophan-Ketoglutarate) is a crystalloid cardioplegia, an understanding of its function and delivery is essential.

Discussion:

Cardioplegia solution is the means by which the ischemic myocardium is protected from cell death. This is achieved by reducing myocardial metabolism through a reduction in cardiac work load and by the use of hypothermia.

Chemically, the high potassium concentration present in most cardioplegia solutions decreases the membrane resting potential of cardiac cells.
Interestingly Custodiol uses two other cations, Na+ and Ca++, to arrest the heart.
By removing extracellular Na+ from perfusate the heart will not beat because the action potential is dependent upon extracellular Na ions.
However the removal of Na+ does not alter the resting membrane potential of the cell.
Likewise removal of extracellular Ca++ results in a decreased contractile force, and eventual arrest in diastole.
Custodial HTK (Histidine-Tryptophan-Ketoglutarate) is an example of a low [K+] low [Na+] solution.

Chemistry and Pharmacology

As a crystalloid cardioplegia solution, Custodiol HTK solution is considered an intracellular solution, i.e., electrolyte concentrations similar to an intracellular concentration, containing low concentrations of the electrolytes sodium, calcium, potassium and magnesium.

CustodiolHTK Solution also contains a high concentration of an amino acid buffering agent, histidine/histidine hydrochloride, the amino acid tryptophan a-ketoglutarate, and the osmotic agent mannitol.

The histindine/histidine hydrochloride buffering system provides normal osmolarity and enhances the solution’s buffering capacity during the ischemic-induced acidosis. With the exception of mannitol, all constituents are normally found in the body.

Custodiol HTK Solution is devoid of colloid and has a viscosity of 1.8 cP, which is similar to the viscosity of water (1.0020 cP). The osmolality of CustodiolHTK Solution is 310 mosmol/kg.

The pH of CustodiolHTK Solution is 7.02 – 7.2 at 25°C.

The low sodium content makes it possible to use a high concentration of biological buffer systems, namely histidine and histidine HCL which confer a buffering capacity superior to that of blood.

The histidine/histidine hydrochloride buffering system provides osmolarity and enhances the solution’s buffering capacity during ischemia-induced acidosis. Histidine is also an effective membrane protectant, and improves the provision of ATP.

CustodiolHTK Solution contains the amino acid tryptophan to protect cell membranes. a-ketoglutarate helps to stabilize cell membranes and is a substrate for anaerobic metabolism; it is an intermediary in the Krebs cycle and a precursor of nicotinamide adenine dinucleotide offering improved production of ATP during reperfusion and inhibiting the production of lactate through glycolysis.

Mannitol maintains physiological or slightly increased osmolality and thereby counteracts the colloidal osmotic pressure of intracellular protein to reduce cellular edema. Mannitol may also act as a free-radical scavenger.

The efficacy of the low sodium and low calcium concept of CustodiolHTK Solution, buffered with Histidine, has been demonstrated in a number of studies.

The advantages of CustodiolHTK Solution to improve clinical outcomes are, in part, based on the buffer effect of histidine/histidine hydrochloride which may enhance the efficiency of anaerobic glycolysis. Also, the addition of mannitol has been shown to decrease cellular edema.

Delivery Technique

Custodial HTK will be delivered at 3-4⁰ Celsius, 20 ml/kg to a maximum of 2 liters for the initial dose; subsequent doses are delivered at 3-4⁰ Celsius, 10ml/kg to a maximum of 1 liter. The delivery pressure for Custodial is different from blood based cardioplegia due to its low viscosity, which is similar to sterile water. The pressure drop with custodiol for the long plegia needle is only 25 mmhg and for the “push/pull” plegia catheter it is only 15 mmhg.

Initially Custodiol will be delivered at a line pressure of approximately 125 mmhg with the long plegia needle or approximately 115 mmhg with the push pull until an electrical arrest of the heart. The line pressure will then be reduced to approximately 75 mmhg with the Long plegia needle or approximately 65 mmhg with the push pull.

The nature of Custodial allows for extended ischemic periods. The perfusionist will notify the Surgeon at 90 minutes after the initial dose. An additional dose of 10ml/kg should be given before 120 minutes of myocardial ischemia has passed.

Important Considerations

Due to the electrolyte properties of Custodiol HTK, systemic Na+ levels will drop precipitously, Ph may also drop and also the crystalloid load from the Custodial will need to be removed.

Add a Hemoconcentrator into your ECC

Therefore, to correct these imbalances, continuous hemoconcentration and ZBUF (Zero-Balance UltraFiltration) will need to be performed on all patients receiving Custodiol. After removing the crystalloid load, ZBUF will need to be performed using at least, 1 liter of 0.9% NaCl with 50ml of Sodium Bicarbonate added to it.

This will help to correct the sodium level and bring it within the normal range of 135-145 mmol/L as well as correcting the slight acidosis occasionally seen with Custodiol HTK. When sending blood gases you must check the Sodium levels.

Background Information

Depolarizing Solutions

Most cardioplegia solutions can be classified as either depolarizing or hyperpolarizing solutions. The most common method of myocardial protection during cardiac surgery is depolarized diastolic arrest with a hyperkalemic infusion. During administration, myocardial cells depolarize, allowing sodium channels to open and sodium to flow into the cell like a normal action potential. But, because of the elevated extracellular potassium concentration, sodium channels are locked in an inactive state, preventing the cells from repolarizing and keeping them in an unexcitable state.

Depolarizing solutions have been used since the 1970s and are currently considered to be the gold standard of myocardial protection. These solutions tend to contain between 10-25 mEq/L of potassium which, when administered via an aortic root injection, raises cell membrane potential to approximately -50 mV from a resting membrane potential of -90 mV. Diastolic arrest occurs at – 50 mV because fast sodium channels, which have a threshold potential between -65 to -70 mV, are inactivated at this potential. The Nernst potential for sodium-calcium exchangers is also -50 mV, meaning at a diastolic arrest of -50 mV, no net movement of calcium or sodium ions should occur across the cell membrane.

Hyperpolarizing Solutions

Hyperpolarizing solutions are used as an alternative to hyperkalemic solutions and work by making the membrane potential more negative than resting potential. This is achieved by using solutions with no calcium and low sodium to induce an arrest. They also add procaine, a sodium-channel blocker, to prevent action potential propagation

Transmembrane ion gradients are maintained closer to normal physiologic levels by utilizing a hyperpolarizing arrest as opposed to hyperkalemic depolarized arrest. This approach has the theoretical benefit of reducing the severity of ionic imbalance during the ischemic period. Additionally, few ion channels and pumps are active and the metabolic demand of the myocardium is greatly reduced. The potential for influxes and overload of sodium and calcium during hyperpolarized arrest is reduced because at hyperpolarized membrane potentials, sodium and calcium channels are closed.

These channels have threshold potentials near -40 mV, which is close to predicted membrane potentials of cells exposed to depolarizing cardioplegia solutions. Rising intracellular calcium is a concern because it is associated with irreversible muscle contracture and myocyte necrosis. Additionally, placing cells in a prolonged depolarized state increases the consumption of high-energy phosphate stores when compared to hyperpolarizing solutions. Based on these concerns, some surgical teams prefer the use of hyperpolarizing solutions.

While cardioplegia solutions can be grouped into two general groups, additional differences exist in the additives used in each solution. Each additive used serves a specific purpose: ion channel blockers, buffer pH, and so on. A general understanding of some common cardioplegia additives is beneficial when choosing which solution to use. While formulations and techniques vary, the goals of each solution are the same: to lower cell metabolism, to achieve electrical and mechanical quiescence, and to reduce the impact of prolonged ischemia.

Cardioplegia consists of three major components: an arresting agent, hypothermia, and additional protective agents in the form of additives. Formulations vary between solutions and surgical preference. Some common additive agents are outlined below

Adenosine is used in depolarizing agents to enhance cardiac arrest. When compared to hyperkalemic solutions alone, a combination of adenosine and hyperkalemia reduces the time to induce cardiac arrest. This is thought to be associated with transient hyperpolarization caused by adenosine prior to the hyperkalemic-induced depolarization. Electrical arrest of the SA node conduction prior to mechanical quiescence produces a more rapid global arrest.

During hyperkalemic depolarized arrest, high extracellular potassium causes fast sodium-channels to be inactivated. Over time a sodium window current can allow calcium to enter the cell, leading to intracellular calcium accumulation and eventual cellular damage. Keeping sodium-channels in an inactivated state keeps the cell membrane depolarized, reducing sodium window currents, and preventing intracellular calcium buildup. Sodium-channel blockers, such as lidocaine or procaine, have been added to some cardioplegia solutions

. Sodium-channel blockers cause the cell membrane to become slightly polarized in comparison to depolarizing solutions without these agents. Hyperkalemic solutions containing sodium-channel blockers, such as del Nido cardioplegia, are classified as modified depolarizing solutions.

Custodiol HTK hyperpolarizes the heart to induce cardiac arrest. Hyperpolarizing solutions prevents calcium overload because few channels or ion pumps are active at hyperpolarized membrane potentials. Additionally, energy consumption is low and the metabolic demand of cardiac myocytes is minimal at these highly negative potentials.

One of the attractive qualities of HTK is its claim to offer adequate myocardial protection for a 3-hour period with a single dose, allowing the surgeon to complete complex repairs without the need to stop or slow down for additional doses. HTK is classified as an intracellular solution because it contains low sodium and calcium concentrations. When administered, it causes extracellular sodium washout, hyperpolarizes the cell membrane, and induces diastolic arrest.

The major advantage of HTK over conventional cardioplegia solutions is its immense buffering capacity because of the high content of histidine. Histidine is an amino acid which acts as the body’s main intracellular buffer and promotes conditions optimal for hypothermic glycolysis to occur.

References and Citations:

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