Continuing Education Activity

The current gold standard of cardiac surgical myocardial protection is the administration of cardioplegia. The optimal temperature of the cardioplegia solution is a topic of debate. Early cardioplegic methods used cold crystalloid solutions to induce and maintain cardiac arrest during heart surgery. Although hypothermia has the advantage of decreasing myocardial oxygen demand, it has been criticized for impairing the homeostatic processes of the myocardium. Normothermic or warm-blood cardioplegia provides a metabolically balanced milieu for the myocardium and helps in the resuscitation of energy-depleted myocardium. This activity reviews the indications, contraindications, outlines the role of warm blood cardioplegia, and highlights the role of the interprofessional team in evaluating and treating patients undergoing cardiopulmonary bypass.

Objectives:

• Identify the indications for warm blood cardioplegia.
• Describe the preparation and technique in regards to warm blood cardioplegia.
• Review the potential complications with warm blood cardioplegia.
• Outline interprofessional team strategies for improving care coordination and communication to understand warm blood cardioplegia and improve outcomes.

Introduction

The current gold standard of cardiac surgical myocardial protection is the administration of cardioplegia. Administration of potassium-rich cardioplegia solution leads to elective reversible diastolic cardiac arrest and results in decreased myocardial metabolic demand. It provides intraoperative myocardial protection by matching myocardial oxygen demand during intraoperative periods of decreased oxygen supply. The goal of cardioplegia is to provide a motionless (non-beating) operative field along with the protection of myocardial function. Early cardioplegic methods used cold crystalloid solutions to induce and maintain cardiac arrest during heart surgery. Since the 1950s, cold crystalloid cardioplegia (CCC) was the cornerstone of cardiac surgical practice.[1][2] 

In the 1970s, blood was introduced as a medium of cardioplegia delivery because of its increased oxygen-carrying capacity, innate buffering capacity (from histidine), and superior osmotic properties.[3] The majority of cardiac surgeons in the United States use blood cardioplegia (72%). No standard federal guidelines exist for the composition of cardioplegia solution. The optimal temperature of cardioplegia has been a matter of debate. Although hypothermia has the advantage of decreasing myocardial oxygen demand, it has been criticized for impairing the homeostatic processes of the myocardium.[4] Normothermic or warm blood cardioplegia (WBC) provides a metabolically balanced milieu for the myocardium and helps in the resuscitation of energy-depleted myocardium.[5] Lichtenstein et al. were the first to report the use of warm heart surgery when they administered continuous warm cardioplegia for a patient requiring a cross-clamp time of over 6 hours.[6]

Anatomy and Physiology

The right and left coronary arteries originate from the aortic root and supply the myocardium. Coronary blood is predominantly drained to the right side of the heart through the coronary sinus. The coronary sinus lies in the left atrioventricular groove on the posterior aspect of the heart and drains directly into the right atrium. The WBC is usually delivered in an antegrade manner through the aortic sinus (or directly through individual coronary ostia). It can also be delivered in a retrograde fashion through the coronary sinus (after right atriotomy) via a retrograde cannula placed in the coronary sinus through the right atrial appendage. Delivery of the WBC can be intermittent or continuous depending on a number of factors like nature and type of the surgery, surgeon's preference, and technical considerations.

Indications

The optimal temperature of the cardioplegia solution is a topic of debate. Even though WBC has been in use for the past three decades, there is controversy regarding the superiority of WBC over cold crystalloid cardioplegia. The WBC has been shown to improve metabolic recovery of the myocardium. The warm blood cardioplegia induction using normothermic blood cardioplegia solution followed by cold cardioplegia could theoretically provide a period of resuscitation in patients at high risk for ischemia. With this technique, the WBC-induced initial electromechanical arrest decreases the cardiac energy demands, and normothermic cellular reaction favors repayment of oxygen debt, restoration of ATP, restabilization of ionic balance, and the divergence of oxygen to reparative metabolic processes.[7]

Potential advantages of warm blood cardioplegia include:

• Improve myocardial restoration and repair
• Improve oxygen delivery and dissociation
• Decrease intracellular swelling
• Decrease red blood cells (RBC) deformation and rouleaux formation
• Decrease impairment of ATP dependent cellular processes
• Improve membrane stabilization

Contraindications

The warm heart trial[8] was a large randomized controlled trial (RCT) that showed decreased all-cause mortality and decreased incidence of low-output state with warm blood cardioplegia. A meta-analysis of 41 RCTs published in 2010[9] compared warm blood cardioplegia and cold crystalloid cardioplegia. The risk of in-hospital death and the incidence of myocardial infarction were similar in both groups. Another meta-analysis of 12 RCTs compared cold crystalloid cardioplegia with cold blood cardioplegia.[10] It concluded that there were no significant differences in the risk of arrhythmia, 30-day mortality, stroke, or acquired atrial fibrillation between the two groups. Cold blood cardioplegia, however, resulted in significantly lower perioperative myocardial infarction.

Potential disadvantages of warm blood cardioplegia include:

• Maldistribution of cardioplegic solution 
• Impaired visualization of the distal coronary anastomosis
• Increased requirement of alpha agonists due to vasodilation
• Warm heart surgeries are technically challenging
• Increased incidence of neurological injury/perioperative strokes
• More frequent dosing required when employing the intermittent WBC technique
• Aggravation of ischemia-reperfusion injury with intermittent perfusion of WBC
• Inadequate myocardial protection, especially in procedures requiring long periods of aortic cross-clamping

Complications

One of the most dreaded complications of warm blood cardioplegia is perioperative strokes and neurological injury. A large RCT from Emory university was prematurely stopped due to unexpected high rates of perioperative strokes (3.1% versus 1.0%) and neurological events (4.5% versus 1.4%).[11] Warm or tepid heart surgery often leads to vasodilation on cardiopulmonary bypass. This can lead to decreased perfusion pressure requiring increased use of alpha agonists. Another drawback of the WBC technique is inadequate surgical visualization, especially during distal coronary anastomosis. 

Clinical Significance

Warm-blood cardioplegia was introduced in 1977 by Buckberg et.al.[12] The premise behind the WBC technique was to decrease the reperfusion injury that occurred after aortic cross-clamp removal. The WBC is usually delivered as a terminal cardioplegia dose given a few minutes before the aortic cross-clamp removal.[13] In 1983 the concept of WBC induction was introduced with the hope of resuscitating a chronically ischemic and energy-depleted heart.[7][14][15][16] Subsequently, multidose warm cardioplegia has been used throughout the cross-clamp duration and the period of myocardial ischemia. Warm-blood cardioplegia is prepared by mixing potassium-rich substrates with the patient's own blood. Cold cardioplegia is typically delivered at 4-degree Celcius, while the WBC is delivered at 34–35°Celcius. Some studies have shown that the WBC technique may be less detrimental to the heart and improve postoperative outcomes. The WBC is given either antegrade down the aortic root or retrograde via the coronary sinus.

Retrograde warm blood cardioplegia is particularly beneficial in the setting of normothermic cardioplegia.[17] Even though cold crystalloid cardioplegia (CCC) is associated with good clinical outcomes in cardiac surgery, this standard technique can lead to ischemia and delay the recovery of postoperative myocardial metabolism and function. With electromechanical arrest alone, one could reduce the oxygen demand of the heart by nearly 90%.[18] Lowering the myocardial temperature has little effect on lowering the metabolic demand of a non-beating heart.

Hypothermia can have many harmful effects at the cellular level. These include impaired enzymatic activity, cell membrane instability, impaired glucose utilization, impaired adenosine triphosphate (ATP) generation and utilization, impaired tissue oxygen uptake, and impaired osmotic homeostasis. Proponents of warm blood cardioplegia believe that the use of blood as a cardioplegia solution component is physiologic and provides better buffering, tonicity, and rheology compared to the crystalloids. Also, blood can carry and deliver oxygen more efficiently than crystalloids. Finally, it is believed that the antioxidant effects of blood can help lower ischemic injury and limit the reperfusion injury once the aortic cross-clamp is removed.

Established strategies of intraoperative myocardial protection include:

• Chemically induced cardiac arrest in diastole, most often by hyperkalemic solution administered through antegrade or retrograde techniques
• Hypothermia to decrease myocardial oxygen demand with the optimal temperature between 12 degrees C and 28 degrees C
• Minimizing myocardial edema by monitoring the pressure of cardioplegia infusion and administering a moderately hyperosmolar solution
• Buffering the ischemia-induced acidosis using THAM (tromethamine solution), bicarbonate, histidine-imidazole, or blood buffers
• Avoiding hyperoxia to minimize reperfusion injury
• Avoiding extreme swings in intracellular calcium
• Avoiding hyperglycemia and hyperthermia

The warm blood cardioplegia technique is a promising strategy in the ever-expanding field of myocardial protection. Continous WBC provides variable protection against ischemia by eliminating hypothermic myocardial ischemia and reperfusion injury. Disadvantages include inadequate visualization, increased cardioplegic requirements, and increased risks of neurological complications. Other consequences of normothermic cardiopulmonary bypass using the WBC technique include complement activation, increased use of pressor agents to counteract vasodilation, and increased fluid requirements. Current evidence does not suggest unequivocal adoption of the WBC technique. The WBC technique does appear to offer some benefit in acutely ischemic hearts; however, routine use of continuous warm blood cardioplegia cannot be recommended at this time. 

Enhancing Healthcare Team Outcomes

Careful communication between perioperative stakeholders (surgeon, perfusionist, anesthesiologist, nurse, and scrub technician) is critical during any cardiac surgical procedure. Institution-wide policy involving pharmacists should be implemented regarding the preparation of cardioplegia solutions. The WBC is technically demanding and is often associated with vasodilation, requiring pressors to maintain mean arterial pressure. Close interprofessional communication between the anesthesiologist and perfusionist should be maintained to prevent hypoperfusion and end-organ damage. This type of interprofessional teamwork and open information sharing will drive improved patient outcomes from all cardiac procedures, including warm blood cardioplegia. [Level 5]