Warm Blood Cardioplegia

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, and outlines the role of warm blood cardioplegia and highlights the role of the interprofessional team in evaluating and treating patients undergoing cardiopulmonary bypass.


  • 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.


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 1950's 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;[3] innate buffering capacity (from histidine); and superior osmotic properties. 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

Right and left coronary artery originates from the aortic root and supplies the myocardium. Coronary blood is predominantly drained to the right side of the heart through the coronary sinus. 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.


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


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 was 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


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 may 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 a delay in 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 of 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 the 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 solution. The WBC is technically demanding and is often associated with vasodilation, requiring pressors to maintain mean arterial pressure. Close communication between the anesthesiologist and perfusionist should be maintained to prevent hypoperfusion and end-organ damage. 

Article Details

Article Author

Andaleeb Ahmed

Article Editor:

Sohail Mahboobi


1/29/2021 3:16:00 PM



BIGELOW WG,LINDSAY WK,GREENWOOD WF, Hypothermia; its possible role in cardiac surgery: an investigation of factors governing survival in dogs at low body temperatures. Annals of surgery. 1950 Nov;     [PubMed PMID: 14771796]


MELROSE DG,DREYER B,BENTALL HH,BAKER JB, Elective cardiac arrest. Lancet (London, England). 1955 Jul 2;     [PubMed PMID: 14382605]


Follette DM,Mulder DG,Maloney JV,Buckberg GD, Advantages of blood cardioplegia over continuous coronary perfusion or intermittent ischemia. Experimental and clinical study. The Journal of thoracic and cardiovascular surgery. 1978 Nov;     [PubMed PMID: 703365]


Fremes SE,Weisel RD,Mickle DA,Ivanov J,Madonik MM,Seawright SJ,Houle S,McLaughlin PR,Baird RJ, Myocardial metabolism and ventricular function following cold potassium cardioplegia. The Journal of thoracic and cardiovascular surgery. 1985 Apr     [PubMed PMID: 3872382]


Rosenkranz ER,Vinten-Johansen J,Buckberg GD,Okamoto F,Edwards H,Bugyi H, Benefits of normothermic induction of blood cardioplegia in energy-depleted hearts, with maintenance of arrest by multidose cold blood cardioplegic infusions. The Journal of thoracic and cardiovascular surgery. 1982 Nov;     [PubMed PMID: 7132406]


Lichtenstein SV,el Dalati H,Panos A,Slutsky AS, Long cross-clamp time with warm heart surgery. Lancet (London, England). 1989 Jun 24;     [PubMed PMID: 2567442]


Rosenkranz ER,Buckberg GD,Laks H,Mulder DG, Warm induction of cardioplegia with glutamate-enriched blood in coronary patients with cardiogenic shock who are dependent on inotropic drugs and intra-aortic balloon support. The Journal of thoracic and cardiovascular surgery. 1983 Oct;     [PubMed PMID: 6621080]


Randomised trial of normothermic versus hypothermic coronary bypass surgery. The Warm Heart Investigators. Lancet (London, England). 1994 Mar 5;     [PubMed PMID: 7906327]


Fan Y,Zhang AM,Xiao YB,Weng YG,Hetzer R, Warm versus cold cardioplegia for heart surgery: a meta-analysis. European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery. 2010 Apr;     [PubMed PMID: 19850490]


Zeng J,He W,Qu Z,Tang Y,Zhou Q,Zhang B, Cold blood versus crystalloid cardioplegia for myocardial protection in adult cardiac surgery: a meta-analysis of randomized controlled studies. Journal of cardiothoracic and vascular anesthesia. 2014 Jun;     [PubMed PMID: 24721161]


Martin TD,Craver JM,Gott JP,Weintraub WS,Ramsay J,Mora CT,Guyton RA, Prospective, randomized trial of retrograde warm blood cardioplegia: myocardial benefit and neurologic threat. The Annals of thoracic surgery. 1994 Feb;     [PubMed PMID: 8311588]


Cooper N,Brazier JR,McConnell DH,Buckberg GD, Studies of the effects of hypothermia on regional myocardial blood flow and metabolism during cardiopulmonary bypass. IV. Topical atrial hypothermia in normothermic beating hearts. The Journal of thoracic and cardiovascular surgery. 1977 Feb;     [PubMed PMID: 834058]


Lazar HL,Buckberg GD,Manganaro AJ,Foglia RP,Becker H,Mulder DG,Maloney JV Jr, Reversal of ischemic damage with secondary blood cardioplegia. The Journal of thoracic and cardiovascular surgery. 1979 Nov;     [PubMed PMID: 491722]


Borger MA,Wei KS,Weisel RD,Ikonomidis JS,Rao V,Cohen G,Shirai T,Omran AS,Siu SC,Rakowski H, Myocardial perfusion during warm antegrade and retrograde cardioplegia: a contrast echo study. The Annals of thoracic surgery. 1999 Sep;     [PubMed PMID: 10509991]


Ikonomidis JS,Yau TM,Weisel RD,Hayashida N,Fu X,Komeda M,Ivanov J,Carson S,Mohabeer MK,Tumiati L, Optimal flow rates for retrograde warm cardioplegia. The Journal of thoracic and cardiovascular surgery. 1994 Feb;     [PubMed PMID: 8302071]


Yau TM,Weisel RD,Mickle DA,Komeda M,Ivanov J,Carson S,Mohabeer MK,Tumiati LC, Alternative techniques of cardioplegia. Circulation. 1992 Nov;     [PubMed PMID: 1424027]


Hayashida N,Ikonomidis JS,Weisel RD,Shirai T,Ivanov J,Carson S,Mohabeer MK,Tumiati LC,Mickle DA, Adequate distribution of warm cardioplegic solution. The Journal of thoracic and cardiovascular surgery. 1995 Sep;     [PubMed PMID: 7564449]


Buckberg GD,Brazier JR,Nelson RL,Goldstein SM,McConnell DH,Cooper N, Studies of the effects of hypothermia on regional myocardial blood flow and metabolism during cardiopulmonary bypass. I. The adequately perfused beating, fibrillating, and arrested heart. The Journal of thoracic and cardiovascular surgery. 1977 Jan;     [PubMed PMID: 831012]