blood cardioplegia - area-c54.it cardioplegia.pdf · 2006 european association for cardio-thoracic...

1 2006 European Association for Cardio-thoracic Surgery

doi:10.1510/mmcts.2004.000745

Blood cardioplegia

Jurgen Martin*, Christoph Benk

University Hospital Freiburg, Department of Cardiovascular Surgery, Hugstetter Strasse 44,D-79106 Freiburg, Germany

We present the technical details of blood cardioplegia as the standard clinical practice inmost centers today. In addition, the contribution refers to the advanced strategies usingblood cardioplegia in specific situations, including warm cardioplegia induction, controlledreperfusion in acute myocardial infarction, and the application of leucocyte filtration.

Keywords: Myocardial protection; Blood cardioplegia; Controlled reperfusion

IntroductionCurrently, blood cardioplegia is the preferred cardio-protective strategy in the United States and in mostWest European countries. The technical details ofblood cardioplegia have evolved as a consequence ofexperimental studies and clinical application, includ-ing multidose cold blood cardioplegia, warm bloodcardioplegic reperfusion, warm induction, antegradeand retrograde delivery, continuous cold blood per-fusion, and intermittent warm blood cardioplegia.

The fact that blood cardioplegia has emerged as thepreferred cardioprotective strategy is based on its ver-satility, because a blood vehicle for cardioplegic deliv-ery blends onconicity, buffering, rheology, and anti-oxidant benefits with its capacity to augment oxygendelivery and ability to resuscitate the heart, preventischemic injury, and limit reperfusion damage.

In detail, the cardioprotective potential of blood car-dioplegia is represented by the synergistic effect of itsdifferent components:

Hyperkalemia: induction and maintenance of car-dioplegic arrest

Hypocalcemia: avoidance of mitochondrial calciumoverload and prevention of irreversible myocyteinjury.

* Corresponding author: Tel.: q49-761-270 2818; fax: q49-761-2702550E-mail: [email protected]

Tris buffer: prevention of tissue acidosis

Hyperosmolarity and hyperglycemia: prevention ofmyocardial edema

Glutamate and aspartate: these amino acidsreplenish key Krebs-cycle depleted during ischemiaby enhancing aerobic metabolism and reparativeprocesses.

In this chapter we describe the so-called standardblood cardioplegia that is based on the intensiveexperimental and clinical investigations of GeraldBuckberg9s research group and has been proven inleading cardiac centers worldwide over the last20 years.

Blood cardioplegia is provided by a mixture of nativeblood and a commercially-available crystalloid solu-tion (Kohler-Chemie, Alsbach-Hahnlein, Germany,www.koehler-chemie.de) at a ratio of 4:1.

Surgical technique

Arterial and venous cannulation is performed accord-ing to the planned surgical procedure. The cannulasare connected to the heart-lung machine. Insertion ofa combined antegrade cardioplegia-vent catheter w1x,cannulation of the coronary sinus w2x, and connectionof the cardioplegia-catheters to a manifold cardiople-gia delivery system and the pressure monitoring linesare performed thereafter.

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J. Martin and C. Benk / Multimedia Manual of Cardiothoracic Surgery / doi:10.1510/mmcts.2004.000745

Video 1. After starting the cardiopulmonary bypass the blood car-dioplegia is mixed by a double headed roller pump using 4 partsarterialized autologous blood from the oxygenator and one part ofcrystalloid cardioplegic solution. Thereafter the admixture is passedthrough a heat exchanger and then infused into the patients heartwith the pressure and flow controlled.

Schematic 1. Delivery system for blood cardioplegia using a doubleheaded roller pump. The different cross section area of the twotubes provides a constant ratio of blood and crystalloid solution of4:1 regardless of different flow rates. A special heat exchanger isrequired to adjust the temperature of the blood cardioplegicsolution.

Cardiopulmonary bypass is commenced and the per-fusionist initiates delivery of blood cardioplegia bymixing oxygenated blood with a crystalloid solution ata ratio of 4:1 using a double-headed roller pump(Schematic 1). The blood cardioplegic solution is guid-ed through a special heat exchanger (i.e. Sidus MMCTSLink 107) before it is applied to the patient9sheart. Careful de-airing of the delivery system and ofthe aortic root is necessary to avoid coronary arteryair embolism.

Cardiopulmonary bypass for routine cardiac surgeryis instituted with linear flow at 2.6 l/min per m2, main-taining perfusion pressure of 6080 mmHg and sys-temic blood temperature at 35 8C.

Application of standard blood cardioplegia

The following phases of myocardial protection can bedifferentiated during routine open heart operations(i.e. coronary artery bypass procedures) according toour institutional protocol:

1. Cold induction. Reduction in extracorporeal circu-lation flow and aortic cross-clamping. Delivery of coldcardioplegic solution (812 8C) antegrade and retro-grade for 2 min each until complete cardioplegicarrest is achieved (flow 200 ml/min, in hypertrophiedhearts increase to 300 ml/min) (Video 1).

2. Reinfusions with cold blood cardioplegia. Duringaortic cross-clamping, multidose cold blood cardio-plegia is applied at intervals of 20 min to maintain car-dioplegic arrest and myocardial hypothermia. Coldblood cardioplegic infusions are routinely deliveredretrograde and simultaneously via vein grafts for 1 min(flow 200 ml/min). Antegrade administration via theaortic root or direct cannulation of the coronary ostiais also applicable in specific situations.3. Warm terminal reperfusion (hot shot). Normo-thermic, substrate-enriched blood cardioplegia isapplied before aortic unclamping. This warm reper-fusate is usually delivered via the coronary sinus andthe vein grafts for 1 min. This is followed by a brief(2030 s) retrograde administration of normothermicblood. Retrograde blood delivery is stopped whenspontaneous electrical and mechanical activity of theheart is visible, and the aortic clamp is released.

This method usually allows discontinuation of bypasswithin 5 min of releasing the aortic clamp.

Advanced strategies using blood cardioplegiain specific situations

Warm cardioplegic induction The concept of warmcardioplegic induction was introduced to activelyresuscitate the ischemically-damaged, energy- andsubstrate-depleted heart by maximizing the kineticsof repair and minimizing O2 demands by maintainingarrest w3x. Therefore, blood cardioplegia is supple-mented with the amino acids glutamate and aspartateto replenish Krebs9 cycle intermediates that aredepleted in compromised hearts. Warm cardioplegicinduction is applied to patients in cardiogenic shock,with severely impaired ejection fraction, or in acutemyocardial infarction.

Normothermic blood cardioplegia (solution for warminduction, Table 1) is administered initially at 250

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Table 1. Composition of blood cardioplegia (Buckberg/Beyersdorf)

Compound Principle Cold Warm Warm Controlled(unit) induction induction terminal reperfusion

reperfusion(hot shot)

Tromethamin Buffer (pH) 7.77.8 7.57.6 7.57.6 7.67.8Citrate-phosphate- Ca-reduction 0.50.6 0.150.25 0.150.25 0.150.20Dextrose (mmol/l)Glucose Osmolarity 340360 380400 380400 350400

(mOsmol/l)KCl Cardioplegic 1820 2025 810 1014

arrest(mmol/l)

Glutamate/aspartate Substrate of 13 mmol/l 13 mmol/l 13 mmol/lKrebs9 cycle each each each

300 ml/min via the aortic root until cardioplegic arrestis achieved. Thereafter, cardioplegic flow is reducedto 150 ml/min (antegrade perfusion pressure 4060 mmHg). Warm cardioplegic perfusion is appliedante- and retrogradely (1 min each). This is followedby cold cardioplegic standard blood cardioplegia.

Controlled reperfusion Controlled reperfusion is astrategy to reduce reperfusion injury after acute cor-onary occlusion. After completion of the final distalanastomosis and release of the aortic clamp, the con-trolled blood cardioplegic solution (Table 1) is given ata flow rate of up to 50 ml/min per graft with a perfu-sion pressure not exceeding 50 mmHg for 20 min intothe grafts only. Cannulation of a side branch of thevein graft makes delivery of the reperfusate possiblewhile the proximal anastomosis is being performed(Schematic 2) w4x. In a multicenter trial, the results ofcontrolled reperfusion were evaluated in 156 consec-utive patients with acute coronary occlusion and com-pared to 1203 patients who underwent PTCA as theprimary therapy w5x. Controlled reperfusion reducedoverall mortality from 8.7% to 3.9%.

Blood cardioplegia leucocyte filtration Myocardialischemia and reperfusion are associated with activa-tion of neutrophils and expression of adhesion mole-cules on the myocardial endothelium surface. In thecase of long cross-clamp time, acute myocardialinfarction, or in heart transplantation, activated leu-cocytes in blood cardioplegia or initial reperfusatemay cause significant myocardial damage. Clinicalstudies have demonstrated the benefit of blood car-dioplegia filtration in patients undergoing emergencycoronary bypass surgery or prolonged crossclamping,in patients with depressed ejection fraction, and inheart transplantation w68x. Experimental studieshave shown that at least 90% of leucocytes must be

removed to attenuate reperfusion injury markedly. Inaddition, leucocyte depletion should be maintainedfor 510 min after the start of initial reperfusion priorto aortic clamp release. Commercially available bloodcardioplegia filters remove more than 90% of the leu-cocytes up to a total volume of 1500 ml of blood car-dioplegia (i.e. Pall BC1B MMCTSLink 108).

Blood cardioplegia in heart transplantation Weuse leucocyte-depleted blood cardioplegia and startwith the first retrograde administration after the heartis removed from the storage solution. The coronarysinus catheter is introduced and secured with a pro-lene pursestring suture using a tourniquet. Initially,cold blood cardioplegia is administered for 3 min. Thesecond application of cold blood cardioplegia (2 min)is performed after 20 min (end of right atrial anasto-mosis). The third application is a warm terminal reper-fusion with leucocyte-depleted and substrate-enriched blood cardioplegia for 45 s. Retrograde per-fusion is continued with normothermic leucocyte-filtrated blood. The aortic clamp is released as the firstcontractions of the transplanted heart become visible.

Other current techniques using bloodcardioplegia

In addition to the classic standard technique ofblood cardioplegia, several modifications haveevolved and are used in different centers.

Continuous warm blood cardioplegia The goal ofthis technique is to prevent any myocardial ischemiaduring aortic cross-clamping by continuous retro-grade delivery of warm blood cardioplegia w9x. How-ever, most surgeons discontinue cardioplegic flow fora few minutes during construction of the distal anas-

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Schematic 2. Delivery of blood cardioplegic solution for controlledreperfusion after cannulation of the vein graft9s side branch permitssimultaneous completion of proximal anastomoses. (Reprinted fromRef. w4x with the permission of Landes Company.)

tomoses leading to unintentional myocardial ische-mia. In addition, cardioplegic overdose is a potentialproblem using this technique.

Intermittent antegrade warm blood cardioplegiaThis concept was first published by Calafiore in 1995and had been developed to eliminate the problem ofblood in the operative field when using continuouswarm blood cardioplegia w10x. Normothermic blood ismixed with a Kq solution using a syringe pump.Repeated doses are delivered after 15 min. Hypo-thermia is completely avoided. The presence of criti-cal coronary stenoses limits the delivery of antegradecardioplegia to ischemic regions of the heart, partic-

ularly when revascularization with the internal mam-mary artery prevents vein graft infusions to the leftanterior descending artery. This inadequate cardio-plegic delivery using only the antegrade route mayinduce warm ischemic injury.

Tepid blood cardioplegia Antegrade tepid bloodcardioplegia was introduced by the Toronto group tocombine the advantages of warm and cold blood car-dioplegia and to minimize the detrimental effects ofblood cardioplegia w11x. Reducing the heart9s temper-ature from 37 8C to 29 8C did not alter myocardialoxygen consumption but did reduce myocardial lac-tate release.

Results

Since its initial description, blood cardioplegia hasbecome the preferred tool to arrest the heart for openheart surgery. This shift from crystalloid-type to bloodcardioplegia occurred because experimental and clin-ical studies demonstrated superior protectionof the arrested myocardium by blood cardioplegiaw1214x.

The efficacy of myocardial protection with a singleaortic crossclamp and blood cardioplegia was evalu-ated in a clinical study including 819 consecutivepatients (stratified for risk profile) and compared withantegrade crystalloid cardioplegia in 2582 patientsw13x. The use of combined antegrade/retrogradeblood cardioplegia resulted in lower postoperativemorbidity by significantly reducing perioperative myo-cardial infarction, wound complications, and length ofstay in patients having reoperations. However, therewas no significant difference in one-year mortalitybetween the two groups.

Kirklin compared the results of primary isolated cor-onary bypass operations in the 19771981 era (crys-talloid cardioplegic solution) with those from 19861988. During the latter era cold blood cardioplegicperfusions and warm reinfusions were used inpatients with longer clamping times w14x (Graph 1).There was a significant drop in 30-day mortality afterintroduction of blood cardioplegia, i.e. after 180 mincross-clamping from 7.3% to 1.7%. These clinicalresults confirm the experimental findings and dem-onstrate that warm, controlled reperfusion provides apowerful tool to limit reperfusion damage and mini-mize the adverse effects of prolonged aortic clamping.

In a multicenter trial patients were randomized toreceive either continuous warm blood cardioplegia orintermittent cold blood cardioplegia w15x. The investi-

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Graph 1. Relation between global myocardial ischemic time (inminutes) and the probability of death within 30 days of operation.The two depictions describe the results with isolated primary cor-onary artery bypass grafting from 1967 to 1981 and from 1986 to1988. In both eras, cold cardioplegia was used, but in the latter eracontrolled aortic root reperfusion was used in patients with longerglobal myocardial ischemic times. The solid lines depict the contin-uous estimate of probability, and the dashed lines enclose the 70%confidence intervals around the estimate. (Reproduced from Ref.w14x with the permission of Elsevier.)

gators found similar myocardial preservation (mortal-ity, postoperative incidence of myocardial infarction,need for intraaortic balloon counterpulsation).

Another randomized study in 1001 patients comparedcontinuous warm blood cardioplegia with intermittentcold crystalloid cardioplegia w16x. The data showed nodifference in the postoperative rates of myocardialinfarction, death or need for intraaortic balloon coun-terpulsation. Of substantial concern was an unex-pected increased rate of perioperative stroke andoverall neurologic events in the warm cardioplegicgroup. Systemic body temperature was actively main-tained )35 8C in the warm blood cardioplegia group.

The CABG patch trial enrolled a high-risk group of885 coronary artery disease patients with an ejectionfraction of -36% w17x. The patients were randomizedwith respect to the use of blood and crystalloid car-dioplegia. Patients receiving crystalloid cardioplegiaversus those receiving blood cardioplegia were foundto have significantly more operative deaths (2% vs.0.3%), postoperative myocardial infarctions (10% vs.2%), shock (13% vs. 7%), and postoperative conduc-tion defects (21.6% vs. 12.4%). Despite this, therewas no significant difference in early or late survival.

Cardiogenic shock is the leading cause of death afteracute myocardial infarction. Modern myocardial pres-ervation strategies using blood cardioplegia havebeen used with promising results for surgical revas-

cularization in acute myocardial infarction w18x.Recent analyses of the New York State Cardiac Sur-gery Registry revealed that there is a significant cor-relation between hospital mortality and time intervalfrom acute myocardial infarction to time of operation.Coronary bypass operation within the first 24 h wasassociated with an in-hospital mortality of 14% intransmural infarction. In contrast, mortality haddecreased to 3% after a time interval of more than7 days w19x. Despite of these good results logistic andeconomic constraints relegate surgical revasculariza-tion to a third option behind thrombolysis and PTCAfor the primary treatment of acute myocardialinfarction.

The SHOCK (should we emergently revascularizeoccluded coronaries for cardiogenic shock) trial foundclear survival benefits for early revascularization byPTCA or CABG over initial medical stabilization bythrombolytic therapy w20x.

Excellent recovery of myocardial contractility afterintermittent warm blood cardioplegia could be dem-onstrated in elective coronary artery bypass patients.The analysis of pressure-volume-loops after cardio-pulmonary bypass revealed no change in end-systolicelastance while the diastolic chamber stiffness wassignificantly increased indicating impaired diastolicfunction w21x.

Discussion

The versatility of blood cardioplegia provides the car-diac surgeon with a tool to actively treat the jeopard-ized myocardium as well as to prevent ischemicdamage. The known benefits of using blood as thevehicle for delivering oxygenated cardioplegia includeoxygen carrying capacity, active resuscitation of myo-cardium, avoidance of reperfusion damage, limitationof hemodilution, provision of onconicity, buffering,rheologic effects, and endogenous oxygen free radicalscavengers. The major prerequisite to provide thesebenefits to the patient is ensuring adequate deliveryof the cardioplegic solutions.

Current standard of myocardial protection using bloodcardioplegia has evolved as a consequence of exper-imental studies and their subsequent clinical appli-cation over the last decades. It combines differentprinciples, such as cold blood cardioplegia, warmblood cardioplegic reperfusion, warm induction, andalternating and simultaneous ante- and retrogradedelivery to compensate for the individual shortcom-ings of each procedure and permit optimum myocar-dial preservation.

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It is essential to understand and use the various tech-niques to obtain the desired protective effect. Somesurgeons who are not familiar with blood cardioplegiacriticize it as cumbersome and overly complicatedcompared to the simpler administration of crystalloidcardioplegia. However, in this case, simplicity andsafety are not synonymous w22x. Cardiac damagefrom inadequate myocardial protection leading to low-output syndrome can prolong hospital stay and cost,and may result in delayed myocardial fibrosis.

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