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The use of combined antegrade-retrograde infusion of blood cardioplegic solution in pediatric patients undergoing heart operations
Cardiopulmonary Bypass, Myocardial Management, and Support Techniques
The use of combined antegrade-retrograde infusion of blood cardioplegic solution in pediatric patients undergoing heart operations The benefits of combined antegrade-retrograde infusion of blood cardioplegic solution are becoming well known in adult coronary and valvular heart operations. Many of these advantages relate directly to the pediatric patient. They include prompt arrest and even distribution, particularly with aortic insufficiency or open aortic root, avoiding or limiting ostial cannulation, allowing uninterrupted surgical procedures, and flushing air/debris from the coronary arteries. We therefore report on the first 123 pediatric patients at the University of California, Los Angeles, to receive myocardial protection with antegrade (aortic) infusion in conjunction with retrograde (coronary sinus) infusion of blood cardioplegic solution. We employed a retroplegia catheter with a self-inflating and deflating occlusion balloon on the tip of a pressure-monitored infusion cannula that remains in the coronary sinus during the operation. Induction blood cardioplegic solution, 30 ml/kg in equally divided doses, is administered in the coronary sinus first antegrade at an aortic pressure less than 80 mm Hg, followed by retrograde infusion at less than 40 mm Hg. Maintenance cardioplegic solution (15 ml/kg) is administered every 20 minutes through one or both of the infusion cannulas, depending on the surgical procedure. Patients' ages ranged from 1 week to 16. years with a mean of 4.6 years. The following procedures were included in descending order: Fontan 20, atrioventricular valve repair/replacement (and complete atrioventricular canal) 16, aortic root/Keene/Ross 16, Rastelli 13, aortic valve repair/replacement 13, ventricular septal defect (and double-outlet right ventricle) 13, tetralogy of FaDot 10, coronary artery reimplantation/fistula repair 6, truncus arteriosus 4, arterial switch 3, bidirectional Glenn 2, sinus venosus 2, and aortopulmonary window, Senning, Stansel, interrupted aortic arch, and Ebstein's, 1 each. Aortic crossclamp times ranged from 6 to 219 minutes with a mean of 87 minutes. Myocardial oxygen consumption data for a series of six patients indicated the supplemental benefit for retrograde infusion of cardioplegic solution along with antegrade infusion, particularly in hypertrophied myocardium. Three deaths occurred (2.4% 30-day mortality), in the following patients: the first with truncus arteriosus and interrupted aortic arch, the second with complete atrioventricular canal and pulmonary hypertension, and the third with truncal valve regurgitation and replacement There were no complica-
Davis C. Drinkwater, Jr, MSc, MD, Christine K. Cushen, BS, CCP, Hillel Laks, MD, and Gerald D. Buckberg, MD, Los Angeles, Calif.
From the Department of Cardiothoracic Surgery, University of California, Los Angeles, Los Angeles, Calif. Delivered in part at the annual meeting of The American Association for Thoracic Surgery, Washington, D.C., May 1991. 12/1/36841
Received for publication May 22, 1991. Accepted for publication Jan. 20, 1992. Address for reprints: Davis C. Drinkwater, Jr., MD, Cardiothoracic Surgery, UCLA Medical Center, B2-375, Los Angeles, CA 90024.
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tions related to the retroplegia catheter. From this initial positive experience, we conclude that (1) combined antegrade-retrograde infusion of blood cardioplegic solution can be safely used in an expanding number of pediatric heart operations in aU age groups, and (2) combined antegraderetrograde infusion of blood cardioplegic solution may provide additional myocardial protection, with exceUent surgical outcome, in complex congenital heart repairs. (J THORAC CARDIOVASC SURG 1992;104:1349-55)
hrough our laboratory and early clinical experience, 1,2 as well as that of others.l- 4 the benefits of antegrade-retrograde infusion of cardioplegic solution in adult patients undergoing cardiac operations are becoming established. A small pilot group of nine pediatric patients with heart disease was included in our initial report with favorable results. On the basis of these findings, a clinical trial of this technique was undertaken in an expanded group of pediatric patients.
Methods Patient population. From November 1988 through January 1991, 123 pediatric patients have undergone combined antegrade-retrograde infusion of cardioplegic solution as the method of myocardial protection during their heart operations. This group included 78 male (63%) and 45 female patients (37%) whose ages ranged from 1week to 16 years (mean 4.5 years) and whose weights, correspondingly, ranged from 3.6 to 72.7 kg (mean 17.3 kg). This group included patients whose complexity of anatomy and anticipated aortic crossclamp times were believed by the surgeon to require maximal myocardial preservation. Also included were patients whose ventricles were impaired preoperatively because of volume or pressure overload, as well as hypoxemia and ischemia. Patients' diagnoses are listed in Table I. Operative technique. Cardiopulmonary bypass (CPB) was established by aortic cannulation with dual venous caval cannulas, in the majority of patients (85%), or a single venous cannula in a lesser number (15%). For patients weighing less than 5 kg, the extracorporeal circuit consisting of a plate membrane oxygenator was primed with 500 ml Plasma-Lyte, 350 ml packed red blood cells, and 100 to 150 ml25% albumin to attain a bypass hematocrit level of 18% to 24%. For patients weighing 5 to 20 kg, 1200 ml of the same prime is used without red blood cells, depending on the initial hematocrit level. Larger children (> 20 kg) require an adult-size oxygenator and priming volumes of 1500 to 1750 ml of crystalloid solution. Cannulas. The retroplegia cannula, modified for pediatric use (Research Medical Inc., Salt Lake City, Utah), has a selfinflating and deflating coronary sinus occlusion balloon and distal pressure monitoring port. It may be introduced in one of two ways at the time of operation. For patients with bicaval cannulation and right atriotomy, the retrograde cannula was directly introduced into the coronary sinus without the malleable stylet; for larger patients (> 15 to 20 kg) with a single venous cannula, it was introduced over the stylet through a pursestring suture in the atrial wall. The latter is a similar "closed" technique used and reported in our initial study with adult patients! (Fig. 1). The self-inflating/deflating balloon allows the retrograde
Table I. Operative procedure and outcome Procedure
Fontan Aortic valverepair/replacement (6/7) VSD closure Tetralogyof Fallot AV canal Rastelli Konno/aortic root/Ross (4/4/1) Subaorticmembrane/myectomy (6/1) Mitral valverepair/replacement (5/1) Coronary reimplantation/fistula (3/3) Truncus arteriosus Conduit replacement Arterial switch Glenn shunt Sinus venosus ASD DORV Aortopulmonary window Ebstein'sanomaly Senning Interrupted aortic arch Stansel-Damus-Kaye
Total
No.
Hospital mortality
20 13 12 10 10 10 9 7
6 6 4 3 3 2 2 I I I I I I 123
3 (2.4%)
VSD, Ventricular septal defect; AV, atrioventricular; ASD, atrial septal defect; DORV, double-outlet right ventricle.
cannula to be left untouched in the coronary sinus during the greater part of the operation. A medium or large Mayo balloon catheter may also be used satisfactorily in a similar manner in the open but not in the transatrial technique. The salient points of transatrial coronary sinus intubation with the retroplegia cannula with malleable stylet are the following: (1) To avoid retroplegia cannula dislodgment, the retroplegia cannula is placed after the venous cannula is satisfactorily in position. (2) Very little, if any, force is required nor resistance met when properly introducing this catheter. (3) Placement is always confirmed by palpation before complete bypass initiation. Whichever cannula is used, accurate infusion pressure monitoring is essential, and the presence of a left superior vena cava draining into the coronary sinus must be ruled out with either ligation or snaring during infusion of retroplegic solution. Cardioplegia. The blood cardioplegic solution is varied slightly depending on the phase of myocardial protection and is divided equally between antegrade aortic and retrograde coronary sinus routes whenever possible in the presence of a competent aortic valve. If there is severe aortic insufficiency, induction and maintenance cardioplegic solution may be administered via
Volume 104 Number 5 November 1992
Combined antegrade-retrograde infusion ofsolution
I 35 I
B
Fig. 1. The two basic techniques of passing the retrograde catheter are illustrated: either directly into the coronary sinus through a concomitant right atriotomy (A) or through a pursestring suture in the right atrium over the malleable stylet (B).
Table II. Composition of blood cardioplegic solution Induction/maintenance pH Ca++
K+ Osmolarity Hematocrit level
7.5-7.6 0.8 mrnol/L 8-20 mEq/L 380-400 mOsm 80% CPB Hct
Table III. Cardioplegic solution delivery protocol
Induction Maintenance Reperfusion (warm)
Antegrade
Retrograde
«80mmHg)
«40mm Hg)
15 ml/kg 10 ml/kg 7.5 ml/kg
15 ml/kg 10 ml/kg 7.5 ml/kg
Modified warm induction/reperfusion Ca++
Neonate Older child Aspartate Glutamate
0.8 mrnol/L
0.5 mmol/L 13 mmol 13 mmol
the retroplegia device after inducing ventricular fibrillation. For regular induction a high-potassium (20 mEqjL) arresting solution is used. In all neonatal patients and in those with preoperative myocardial stress from pressure or volume overload, from hypoxemia and ischemia, or from all of these, modified (glutamate [13 mmoljL] and aspartate additives) warm-induction (37° C) cardioplegic solution is administered for 2 minutes to avoid hypothermic contracture and to replace depleted energy substrates (Table 11). Thirty-three (27%) ofthe patients in this report received modified warm-induction solution. For routinemaintenance cardioplegia a low-potassium (8 mEqjL) solution is used every 20 minutes in either or both antegrade and retro-
grade fashion. Finally, a modified warm reperfusate is administered before removal of the aortic crossclamp in all patients. Administration of cardioplegic solution. The amounts and pressure of the infusion stages are demonstrated in Table III. Induction cardioplegic solution is always administered by the antegrade route first, and doses of cardioplegic solution are never given simultaneously by both routes. For infants weighing less than 5 kg, cardioplegic solution is administered by hand infusion rather than by the perfusion circuit directly as in the larger patient. Strict attention to the infusion pressure of both cannulas will avoid overdistention injuries, particularly with the retroplegia catheter in the distal coronary sinus or in a wedged position within a lesser cardiac vein. If pressures are elevated at anticipated normal flows, by withdrawing the retroplegia catheter a few millimeters, the pressure will generally fall to a satisfactory range of less than 40 to 50 mm Hg. Conversely, if the retroplegia pressure is less than 20 mm Hg at appropriate flows, the cannula is probably in the right atrium or very proximal coronary sinus and therefore requires advancement or replace-
The Journal of Thoracic and Cardiovascular Surgery
I 3 5 2 Drinkwater et at.
r'>:
Pressure
mm Hg
,,'-----------
80 40
I I
I
O..IL.--------
Fig. 2. Overall setup and infusion pressures for antegrade (aortic [dotted lineD and retrograde (coronary sinus [solid lineD combined technique of infusion of cardioplegic solution. During the retroplegic infusion, the aortic vent is opened for the effluent. The retroplegia catheter in this case has been passed through a pursestring suture in the right atrial wall into the coronary sinus over the malleable stylet. ment. Similarly, too Iowa pressure in the aortic root during antegrade infusion indicates either valvular insufficiency or an open aortic vent (Fig. 2). CPB. Deep (18° to 20° C) or moderate (26° to 28° C) hypothermia was employed depending on the anatomy and surgical procedure. In an effort to avoid possible neurologic sequelae, long periods of circulatory arrest with deep hypothermia are limited by the use of low-flow hypothermic technique. This is combined with intermittent short periods of circulatory arrest «5 to I 0 minutes), such as we commonly employ in the neonatal arterial switch procedure. Low-flow hypothermic technique is also employed in patients with prominent noncoronary collateral arteries, to help reduce cardioplegia washout and myocardial rewarming effect. Systemic hypothermia in the entire group of patients ranged from IS ° to 30° C, with a mean of 22° C. Topical myocardial hypothermia with cold saline provides further protection from ischemia during aortic crossclamping. Myocardial oxygen uptake studies. Finally, myocardial oxygen uptake was measured in a consecutive series of six pa-
tients at the completion of antegrade infusion of cardioplegic solution and 30 seconds after the subsequent initiation of retrograde infusion. In this specific group of patients, a complete (30 ml/kg) dose of cardioplegic solution was administered entirely by antegrade technique, during the end of which simultaneous oxygen saturations obtained in the aortic root and coronary sinus were used to calculate a "baseline" oxygen extraction by the myocardium. These same measurements and calculations were then made during an immediate subsequent retrograde infusion at the same flow rate and were compared with the baseline. The formula used to calculate myocardial oxygen extraction was oxygen concentration in ml/rnin = Sao, - SV02 X flow rate X Hgb X 1.34 X 10 where Sao- is percent arterial oxygen saturation, SV02 is venous oxygen saturation, and Hgb is hemoglobin.
Results One hundred twenty-three patients with the aid of antegrade-retrograde infusion of cardioplegic solution,
Volume 104 Number 5 November 1992
underwent multiple and diverse heart procedures to correct or palliate a variety of congenital heart anomalies (see Table I). The retroplegia cannula was passed directly into the coronary sinus through a concomitant right atriotomy in the majority (85%) of patients. The remaining 15%were larger patients (more than 10 to 15 kg) who did not require a right atriotomy for venting or shunt closure and therefore had a transatrial "closed" introduction. There were no complications from the retrograde cannula insertion or cardioplegic solution administration. In particular, as in our adult experience, the use of a retroplegia catheter did not result in any prolonged (> 12 hours) heart block. Three patients did have persistent complete heart block felt because of their anatomy and the procedures performed. This was the case in two patients who had undergone a Konno procedure and the third a repair of corrected transposition. ePB times ranged from 10 to 477 minutes with a mean of 127 minutes for this group of patients, and the aortic crossclamp times ranged from 6 to 219 minutes with a mean of 87 minutes. For comparison, we examined the bypass parameters of a separate consecutive group of 25 pediatric patients who received antegrade infusion of cardioplegic solution only, during this same time period, and were operated on by the same surgical team. For this group, whose weights ranged from 2.4 to 15 kg (mean 6 kg), ePB time was a mean of 85 minutes (33 to 154 minutes), and the aortic crossclamp time was a mean of 48 minutes (16 to 99 minutes). In the group of six patients who underwent oxygen utilization studies (Table IV), there were significant differences between antegrade and combined antegrade-retrograde infusion phases. Comparing the end of a completeinduction antegrade cardioplegic solution infusion dose of 30 ml/kg and the early additional phase of retrograde infusion of cardioplegic solution, the differences in myocardial oxygen uptake are demonstrated in Fig. 3. The differentials were largest in hearts more hypertrophied from both volume and pressure overload anomalies. The amounts of cardioplegic solution administered are equal to those given by antegrade technique alone. Both the open and "closed" retroplegia cannulation techniques used exactly similar cardioplegic solution administration, achievingearly and complete cardiac arrest in 122 of 123 patients. One patient, a 4.5-month-old infant with severe truncal valve regurgitation, status "after truncus arteriosus repair," underwent homograft valve replacement but died of acute cardiac failure in the early postoperative period. This occurred early in our experience, before the finalmodifications of the retroplegia cannula, which provides a more occlusive balloon in the coronary sinus as well as a convenient in-line pressure-monitoring port.
Combined antegrade-retrograde infusion of solution
13 5 3
Table IV. Myocardial oxygen uptake differentials (N= 6) Antegrade-complete Diagnosis
ASD ASD
MV02 (mllmin)
o
o
VSD-large VSD-moderate Fontan (SV) Tetralogy of Fallot
32.2 16.2
Mean
10.7
o 1
Retrograde-initial MV02 (mllmin} 16.1 16.3 193.0 96.5 64.3 80.4 77.7*
MVO], Myocardial oxygen consumption; ASD, atrial septal defect; VSD, ventricular septal defect; SV, single ventricle.
*p < 0.05.
Operative mortality. There were three surgical deaths in the series (including the patient who underwent a truncal valve replacement), for a 2.4% overall 30-day mortality rate. A second patient with complete atrioventricular canal and severe pulmonary hypertension died after a week of postoperative extracorporeal membrane oxygenator support. The third patient, a 2.5-month-old infant with truncus arteriosus and interrupted aortic arch, died 2 weeks postoperatively of respiratory complications. Discussion
This report demonstrates the ease and safety of using combined antegrade-retrograde infusion of cardioplegic solution in pediatric patients with complex cardiac diseases. CPB and aortic crossclamp times of this group are approximately twice that of a contemporaneous series of patients who received antegrade infusion of cardioplegic solution alone, and in general reflect a greater degree of surgical complexity. The low mortality rate in this group of patients with variant and complex anatomy suggests that this method provides at least as effective myocardial protection as the routine antegrade cardioplegia technique. Indeed, those patients whose anticipated surgical times were lengthy or whose preoperative condition was unstable were in fact selected to receive this combined cardioplegia technique whenever possible. Recognizing that while this trial was not part of a controlled, randomized study, we nonetheless are able to draw some conclusions about the use of this method of infusion of cardioplegic solution. There were no complications from the use of retroplegia cannula in either the open or closed technique. Our previous experience in adult cardiac patients reinforced the importance of closely monitoring infusion pressure to avoid complications of barotrauma or perforation of the cardiac veins (or both barotrauma and perforation). Pressures were monitored closely in both cannulas during
13 54
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Drinkwater et al.
N=6
100
80 c
E
<,
60
E (\J
0
>
40
~
20
0 *1'<.05
..........
ANTEGRADE Complete (30mVkg)
RETROGRADE (@ 30 seconds)
Fig. 3. The mean oxygen uptake (MV02) is demonstrated at the time of complete-induction antegrade cardioplegic solution dose and the early phase (30 seconds)of retrograde infusion of cardioplegic solution. The differentials are greatest with hypertrophiedventricles (see Table IV) and may indicate improvedperfusion of the subendocardium by the retrograde technique under these conditions. the antegrade and retrograde infusion of cardioplegic solution and were found to be accurate indications of catheter location or of the need for possible repositioning. During the transition from antegrade to retrograde infusion of cardioplegic solution, the cardioplegic flow should be completely interrupted to avoid any pressure buildup in line. The gradual increase of volume and pressure administration in each system is warranted to prevent both barotrauma and dislodgment of the catheter from the coronary sinus. Two types of retrograde cannula were used during the study period during which modifications from the adultsize catheter were made. Both catheters, the Mayo balloon-tipped and the retroplegia catheter, have similar functional characteristics. The cardioplegic regimen was identical for both, and therefore both experiences can be combined. The one significant difference between the two cannulas is the ability of the retroplegia catheter to be passed transatrially (without atriotomy) into the coronary sinus. This technique has been restricted to patients weighing more than 15 to 20 kg because of size constraints. The majority of patients, however, requiring a vent or concomitant closure of an atrial or ventricular septal defect underwent direct cannulation of the coronary sinus through an existing atrial incision. This would also preclude the use of direct atrial technique retrograde cardioplegia as used by some groups in adult surgery.' Surgical procedures that may benefit from antegraderetrograde infusion of cardioplegic solution include (1)
aortic valve and root operations to provide protection in the face of insufficiency and to avoid or limit coronary ostial cannulation; (2) left-sided valve repairs or replacements, avoiding interruption to adequately deair for antegrade infusion of cardioplegic solution; (3) repair of coronary artery anomalies and fistulas to provide even distribution; and finally, (4) procedures in which continuous (warm) cardioplegia is used. The latter is a technique used in a growing number of adults and in some select pediatric patients with cardiac disease. Caveats for the use of continuous warm cardioplegia in pediatric patients may be (1) the presence of significant noncoronary collateral arteries that, at high flows, may compromise myocardial protection and visualization and (2) the ability for the renal function of smaller infants to handle the additional potassium load. Nevertheless, the technique and setup of this combined method of infusion of cardioplegic solution do allow for the option of continuous warm cardioplegia, which may play an increasing role in cardiac operations in all age groups. The finding of an oxygen uptake differential between the complete-induction antegrade and initial (30-second) retrograde dose provides further evidence that the two techniques may have differing preferential flow distribution, thus complementing one another. Previous laboratory work supports the observation that the subendocardium may be better perfused by retrograde infusion of cardioplegic solution, thus accounting for the differentials observed in this group of patients." It should be noted that
Volume 104 Number 5 November 1992
with the levels of significant hypothermia used in our patients, ongoing myocardial metabolism would not account for these differences in myocardial oxygen extraction in the 5 to 10 seconds between ending antegrade and initiating retrograde infusion of cardioplegic solution. An additional observation is that the greater differentials appear related to the degree of myocardial hypertrophy from the underlying anomaly. By inference, therefore, the combined antegrade-retrograde technique may be even more useful in those hearts that show the effects and changes of greater volume and pressure overload. In summary, this is a report of a clinical experience with combined antegrade-retrograde cardioplegia technique as the method of myocardial preservation in a group of pediatric patients with complex congenital heart disease. The low mortality and no morbidity attest to the safety and ease of the procedure in these patients. Its effectiveness warrants an expanding role in complex pediatric cardiac operations. We gratefullyacknowledge the contributionsof Ms. Arlene Arabe in helping to compilethe data that form the basisfor the clinical results reported herein.
Combined antegrade-retrograde infusion ofsolution
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REFERENCES 1. Drinkwater DC, Laks H, Buckberg GD. A new simplified
method of optimizing cardioplegic delivery without right heart isolation. J THORAC CARDIOVASC SURG 1990; 100:56-63. 2. Buckberg GD, Drinkwater DC, Laks H. A new technique for delivering antegradejretrograde blood cardioplegia without right heart isolation. Eur J Cardiothorac Surg 1990;4:163-8. 3. Menasche P, Subayi JB, Piwnica A. Retrograde coronary sinus cardioplegia for aortic valve operations: a clinical report on 500 patients. Ann Thorac Surg 1990;49:556-64. 4. Mori F, Ivey T, Tabayashi K, Thomas R, Misbach G. Regional myocardial protection by retrograde coronary sinus infusion of cardioplegic solution. Circulation 1986; 74(Pt 2):111-6. 5. Fabiani JN, Deloche A, Swanson J, Carpentier A. Retrograde cardioplegia through the right atrium. Ann Thorac Surg 1986;41:101-2. 6. Partington MT, Acar C, Buckberg GD, Julia T, Kofsky ER, Bugyi H. Studiesof retrograde cardioplegiacapillary bloodflowdistributionto myocardiumsuppliedbyopenand occluded arteries. J THORAC CARDIOVASC SURG 1989; 97:605-12.
The use of combined antegrade-retrograde infusion of blood cardioplegic solution in pediatric patients undergoing heart operations The benefits of combined antegrade-retrograde infusion of blood cardioplegic solution are becoming well known in adult coronary and valvular heart operations. Many of these advantages relate directly to the pediatric patient. They include prompt arrest and even distribution, particularly with aortic insufficiency or open aortic root, avoiding or limiting ostial cannulation, allowing uninterrupted surgical procedures, and flushing air/debris from the coronary arteries. We therefore report on the first 123 pediatric patients at the University of California, Los Angeles, to receive myocardial protection with antegrade (aortic) infusion in conjunction with retrograde (coronary sinus) infusion of blood cardioplegic solution. We employed a retroplegia catheter with a self-inflating and deflating occlusion balloon on the tip of a pressure-monitored infusion cannula that remains in the coronary sinus during the operation. Induction blood cardioplegic solution, 30 ml/kg in equally divided doses, is administered in the coronary sinus first antegrade at an aortic pressure less than 80 mm Hg, followed by retrograde infusion at less than 40 mm Hg. Maintenance cardioplegic solution (15 ml/kg) is administered every 20 minutes through one or both of the infusion cannulas, depending on the surgical procedure. Patients' ages ranged from 1 week to 16. years with a mean of 4.6 years. The following procedures were included in descending order: Fontan 20, atrioventricular valve repair/replacement (and complete atrioventricular canal) 16, aortic root/Keene/Ross 16, Rastelli 13, aortic valve repair/replacement 13, ventricular septal defect (and double-outlet right ventricle) 13, tetralogy of FaDot 10, coronary artery reimplantation/fistula repair 6, truncus arteriosus 4, arterial switch 3, bidirectional Glenn 2, sinus venosus 2, and aortopulmonary window, Senning, Stansel, interrupted aortic arch, and Ebstein's, 1 each. Aortic crossclamp times ranged from 6 to 219 minutes with a mean of 87 minutes. Myocardial oxygen consumption data for a series of six patients indicated the supplemental benefit for retrograde infusion of cardioplegic solution along with antegrade infusion, particularly in hypertrophied myocardium. Three deaths occurred (2.4% 30-day mortality), in the following patients: the first with truncus arteriosus and interrupted aortic arch, the second with complete atrioventricular canal and pulmonary hypertension, and the third with truncal valve regurgitation and replacement There were no complica-
Davis C. Drinkwater, Jr, MSc, MD, Christine K. Cushen, BS, CCP, Hillel Laks, MD, and Gerald D. Buckberg, MD, Los Angeles, Calif.
From the Department of Cardiothoracic Surgery, University of California, Los Angeles, Los Angeles, Calif. Delivered in part at the annual meeting of The American Association for Thoracic Surgery, Washington, D.C., May 1991. 12/1/36841
Received for publication May 22, 1991. Accepted for publication Jan. 20, 1992. Address for reprints: Davis C. Drinkwater, Jr., MD, Cardiothoracic Surgery, UCLA Medical Center, B2-375, Los Angeles, CA 90024.
1349
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Drinkwater et al.
tions related to the retroplegia catheter. From this initial positive experience, we conclude that (1) combined antegrade-retrograde infusion of blood cardioplegic solution can be safely used in an expanding number of pediatric heart operations in aU age groups, and (2) combined antegraderetrograde infusion of blood cardioplegic solution may provide additional myocardial protection, with exceUent surgical outcome, in complex congenital heart repairs. (J THORAC CARDIOVASC SURG 1992;104:1349-55)
hrough our laboratory and early clinical experience, 1,2 as well as that of others.l- 4 the benefits of antegrade-retrograde infusion of cardioplegic solution in adult patients undergoing cardiac operations are becoming established. A small pilot group of nine pediatric patients with heart disease was included in our initial report with favorable results. On the basis of these findings, a clinical trial of this technique was undertaken in an expanded group of pediatric patients.
Methods Patient population. From November 1988 through January 1991, 123 pediatric patients have undergone combined antegrade-retrograde infusion of cardioplegic solution as the method of myocardial protection during their heart operations. This group included 78 male (63%) and 45 female patients (37%) whose ages ranged from 1week to 16 years (mean 4.5 years) and whose weights, correspondingly, ranged from 3.6 to 72.7 kg (mean 17.3 kg). This group included patients whose complexity of anatomy and anticipated aortic crossclamp times were believed by the surgeon to require maximal myocardial preservation. Also included were patients whose ventricles were impaired preoperatively because of volume or pressure overload, as well as hypoxemia and ischemia. Patients' diagnoses are listed in Table I. Operative technique. Cardiopulmonary bypass (CPB) was established by aortic cannulation with dual venous caval cannulas, in the majority of patients (85%), or a single venous cannula in a lesser number (15%). For patients weighing less than 5 kg, the extracorporeal circuit consisting of a plate membrane oxygenator was primed with 500 ml Plasma-Lyte, 350 ml packed red blood cells, and 100 to 150 ml25% albumin to attain a bypass hematocrit level of 18% to 24%. For patients weighing 5 to 20 kg, 1200 ml of the same prime is used without red blood cells, depending on the initial hematocrit level. Larger children (> 20 kg) require an adult-size oxygenator and priming volumes of 1500 to 1750 ml of crystalloid solution. Cannulas. The retroplegia cannula, modified for pediatric use (Research Medical Inc., Salt Lake City, Utah), has a selfinflating and deflating coronary sinus occlusion balloon and distal pressure monitoring port. It may be introduced in one of two ways at the time of operation. For patients with bicaval cannulation and right atriotomy, the retrograde cannula was directly introduced into the coronary sinus without the malleable stylet; for larger patients (> 15 to 20 kg) with a single venous cannula, it was introduced over the stylet through a pursestring suture in the atrial wall. The latter is a similar "closed" technique used and reported in our initial study with adult patients! (Fig. 1). The self-inflating/deflating balloon allows the retrograde
Table I. Operative procedure and outcome Procedure
Fontan Aortic valverepair/replacement (6/7) VSD closure Tetralogyof Fallot AV canal Rastelli Konno/aortic root/Ross (4/4/1) Subaorticmembrane/myectomy (6/1) Mitral valverepair/replacement (5/1) Coronary reimplantation/fistula (3/3) Truncus arteriosus Conduit replacement Arterial switch Glenn shunt Sinus venosus ASD DORV Aortopulmonary window Ebstein'sanomaly Senning Interrupted aortic arch Stansel-Damus-Kaye
Total
No.
Hospital mortality
20 13 12 10 10 10 9 7
6 6 4 3 3 2 2 I I I I I I 123
3 (2.4%)
VSD, Ventricular septal defect; AV, atrioventricular; ASD, atrial septal defect; DORV, double-outlet right ventricle.
cannula to be left untouched in the coronary sinus during the greater part of the operation. A medium or large Mayo balloon catheter may also be used satisfactorily in a similar manner in the open but not in the transatrial technique. The salient points of transatrial coronary sinus intubation with the retroplegia cannula with malleable stylet are the following: (1) To avoid retroplegia cannula dislodgment, the retroplegia cannula is placed after the venous cannula is satisfactorily in position. (2) Very little, if any, force is required nor resistance met when properly introducing this catheter. (3) Placement is always confirmed by palpation before complete bypass initiation. Whichever cannula is used, accurate infusion pressure monitoring is essential, and the presence of a left superior vena cava draining into the coronary sinus must be ruled out with either ligation or snaring during infusion of retroplegic solution. Cardioplegia. The blood cardioplegic solution is varied slightly depending on the phase of myocardial protection and is divided equally between antegrade aortic and retrograde coronary sinus routes whenever possible in the presence of a competent aortic valve. If there is severe aortic insufficiency, induction and maintenance cardioplegic solution may be administered via
Volume 104 Number 5 November 1992
Combined antegrade-retrograde infusion ofsolution
I 35 I
B
Fig. 1. The two basic techniques of passing the retrograde catheter are illustrated: either directly into the coronary sinus through a concomitant right atriotomy (A) or through a pursestring suture in the right atrium over the malleable stylet (B).
Table II. Composition of blood cardioplegic solution Induction/maintenance pH Ca++
K+ Osmolarity Hematocrit level
7.5-7.6 0.8 mrnol/L 8-20 mEq/L 380-400 mOsm 80% CPB Hct
Table III. Cardioplegic solution delivery protocol
Induction Maintenance Reperfusion (warm)
Antegrade
Retrograde
«80mmHg)
«40mm Hg)
15 ml/kg 10 ml/kg 7.5 ml/kg
15 ml/kg 10 ml/kg 7.5 ml/kg
Modified warm induction/reperfusion Ca++
Neonate Older child Aspartate Glutamate
0.8 mrnol/L
0.5 mmol/L 13 mmol 13 mmol
the retroplegia device after inducing ventricular fibrillation. For regular induction a high-potassium (20 mEqjL) arresting solution is used. In all neonatal patients and in those with preoperative myocardial stress from pressure or volume overload, from hypoxemia and ischemia, or from all of these, modified (glutamate [13 mmoljL] and aspartate additives) warm-induction (37° C) cardioplegic solution is administered for 2 minutes to avoid hypothermic contracture and to replace depleted energy substrates (Table 11). Thirty-three (27%) ofthe patients in this report received modified warm-induction solution. For routinemaintenance cardioplegia a low-potassium (8 mEqjL) solution is used every 20 minutes in either or both antegrade and retro-
grade fashion. Finally, a modified warm reperfusate is administered before removal of the aortic crossclamp in all patients. Administration of cardioplegic solution. The amounts and pressure of the infusion stages are demonstrated in Table III. Induction cardioplegic solution is always administered by the antegrade route first, and doses of cardioplegic solution are never given simultaneously by both routes. For infants weighing less than 5 kg, cardioplegic solution is administered by hand infusion rather than by the perfusion circuit directly as in the larger patient. Strict attention to the infusion pressure of both cannulas will avoid overdistention injuries, particularly with the retroplegia catheter in the distal coronary sinus or in a wedged position within a lesser cardiac vein. If pressures are elevated at anticipated normal flows, by withdrawing the retroplegia catheter a few millimeters, the pressure will generally fall to a satisfactory range of less than 40 to 50 mm Hg. Conversely, if the retroplegia pressure is less than 20 mm Hg at appropriate flows, the cannula is probably in the right atrium or very proximal coronary sinus and therefore requires advancement or replace-
The Journal of Thoracic and Cardiovascular Surgery
I 3 5 2 Drinkwater et at.
r'>:
Pressure
mm Hg
,,'-----------
80 40
I I
I
O..IL.--------
Fig. 2. Overall setup and infusion pressures for antegrade (aortic [dotted lineD and retrograde (coronary sinus [solid lineD combined technique of infusion of cardioplegic solution. During the retroplegic infusion, the aortic vent is opened for the effluent. The retroplegia catheter in this case has been passed through a pursestring suture in the right atrial wall into the coronary sinus over the malleable stylet. ment. Similarly, too Iowa pressure in the aortic root during antegrade infusion indicates either valvular insufficiency or an open aortic vent (Fig. 2). CPB. Deep (18° to 20° C) or moderate (26° to 28° C) hypothermia was employed depending on the anatomy and surgical procedure. In an effort to avoid possible neurologic sequelae, long periods of circulatory arrest with deep hypothermia are limited by the use of low-flow hypothermic technique. This is combined with intermittent short periods of circulatory arrest «5 to I 0 minutes), such as we commonly employ in the neonatal arterial switch procedure. Low-flow hypothermic technique is also employed in patients with prominent noncoronary collateral arteries, to help reduce cardioplegia washout and myocardial rewarming effect. Systemic hypothermia in the entire group of patients ranged from IS ° to 30° C, with a mean of 22° C. Topical myocardial hypothermia with cold saline provides further protection from ischemia during aortic crossclamping. Myocardial oxygen uptake studies. Finally, myocardial oxygen uptake was measured in a consecutive series of six pa-
tients at the completion of antegrade infusion of cardioplegic solution and 30 seconds after the subsequent initiation of retrograde infusion. In this specific group of patients, a complete (30 ml/kg) dose of cardioplegic solution was administered entirely by antegrade technique, during the end of which simultaneous oxygen saturations obtained in the aortic root and coronary sinus were used to calculate a "baseline" oxygen extraction by the myocardium. These same measurements and calculations were then made during an immediate subsequent retrograde infusion at the same flow rate and were compared with the baseline. The formula used to calculate myocardial oxygen extraction was oxygen concentration in ml/rnin = Sao, - SV02 X flow rate X Hgb X 1.34 X 10 where Sao- is percent arterial oxygen saturation, SV02 is venous oxygen saturation, and Hgb is hemoglobin.
Results One hundred twenty-three patients with the aid of antegrade-retrograde infusion of cardioplegic solution,
Volume 104 Number 5 November 1992
underwent multiple and diverse heart procedures to correct or palliate a variety of congenital heart anomalies (see Table I). The retroplegia cannula was passed directly into the coronary sinus through a concomitant right atriotomy in the majority (85%) of patients. The remaining 15%were larger patients (more than 10 to 15 kg) who did not require a right atriotomy for venting or shunt closure and therefore had a transatrial "closed" introduction. There were no complications from the retrograde cannula insertion or cardioplegic solution administration. In particular, as in our adult experience, the use of a retroplegia catheter did not result in any prolonged (> 12 hours) heart block. Three patients did have persistent complete heart block felt because of their anatomy and the procedures performed. This was the case in two patients who had undergone a Konno procedure and the third a repair of corrected transposition. ePB times ranged from 10 to 477 minutes with a mean of 127 minutes for this group of patients, and the aortic crossclamp times ranged from 6 to 219 minutes with a mean of 87 minutes. For comparison, we examined the bypass parameters of a separate consecutive group of 25 pediatric patients who received antegrade infusion of cardioplegic solution only, during this same time period, and were operated on by the same surgical team. For this group, whose weights ranged from 2.4 to 15 kg (mean 6 kg), ePB time was a mean of 85 minutes (33 to 154 minutes), and the aortic crossclamp time was a mean of 48 minutes (16 to 99 minutes). In the group of six patients who underwent oxygen utilization studies (Table IV), there were significant differences between antegrade and combined antegrade-retrograde infusion phases. Comparing the end of a completeinduction antegrade cardioplegic solution infusion dose of 30 ml/kg and the early additional phase of retrograde infusion of cardioplegic solution, the differences in myocardial oxygen uptake are demonstrated in Fig. 3. The differentials were largest in hearts more hypertrophied from both volume and pressure overload anomalies. The amounts of cardioplegic solution administered are equal to those given by antegrade technique alone. Both the open and "closed" retroplegia cannulation techniques used exactly similar cardioplegic solution administration, achievingearly and complete cardiac arrest in 122 of 123 patients. One patient, a 4.5-month-old infant with severe truncal valve regurgitation, status "after truncus arteriosus repair," underwent homograft valve replacement but died of acute cardiac failure in the early postoperative period. This occurred early in our experience, before the finalmodifications of the retroplegia cannula, which provides a more occlusive balloon in the coronary sinus as well as a convenient in-line pressure-monitoring port.
Combined antegrade-retrograde infusion of solution
13 5 3
Table IV. Myocardial oxygen uptake differentials (N= 6) Antegrade-complete Diagnosis
ASD ASD
MV02 (mllmin)
o
o
VSD-large VSD-moderate Fontan (SV) Tetralogy of Fallot
32.2 16.2
Mean
10.7
o 1
Retrograde-initial MV02 (mllmin} 16.1 16.3 193.0 96.5 64.3 80.4 77.7*
MVO], Myocardial oxygen consumption; ASD, atrial septal defect; VSD, ventricular septal defect; SV, single ventricle.
*p < 0.05.
Operative mortality. There were three surgical deaths in the series (including the patient who underwent a truncal valve replacement), for a 2.4% overall 30-day mortality rate. A second patient with complete atrioventricular canal and severe pulmonary hypertension died after a week of postoperative extracorporeal membrane oxygenator support. The third patient, a 2.5-month-old infant with truncus arteriosus and interrupted aortic arch, died 2 weeks postoperatively of respiratory complications. Discussion
This report demonstrates the ease and safety of using combined antegrade-retrograde infusion of cardioplegic solution in pediatric patients with complex cardiac diseases. CPB and aortic crossclamp times of this group are approximately twice that of a contemporaneous series of patients who received antegrade infusion of cardioplegic solution alone, and in general reflect a greater degree of surgical complexity. The low mortality rate in this group of patients with variant and complex anatomy suggests that this method provides at least as effective myocardial protection as the routine antegrade cardioplegia technique. Indeed, those patients whose anticipated surgical times were lengthy or whose preoperative condition was unstable were in fact selected to receive this combined cardioplegia technique whenever possible. Recognizing that while this trial was not part of a controlled, randomized study, we nonetheless are able to draw some conclusions about the use of this method of infusion of cardioplegic solution. There were no complications from the use of retroplegia cannula in either the open or closed technique. Our previous experience in adult cardiac patients reinforced the importance of closely monitoring infusion pressure to avoid complications of barotrauma or perforation of the cardiac veins (or both barotrauma and perforation). Pressures were monitored closely in both cannulas during
13 54
The Journal of Thoracic and Cardiovascular Surgery
Drinkwater et al.
N=6
100
80 c
E
<,
60
E (\J
0
>
40
~
20
0 *1'<.05
..........
ANTEGRADE Complete (30mVkg)
RETROGRADE (@ 30 seconds)
Fig. 3. The mean oxygen uptake (MV02) is demonstrated at the time of complete-induction antegrade cardioplegic solution dose and the early phase (30 seconds)of retrograde infusion of cardioplegic solution. The differentials are greatest with hypertrophiedventricles (see Table IV) and may indicate improvedperfusion of the subendocardium by the retrograde technique under these conditions. the antegrade and retrograde infusion of cardioplegic solution and were found to be accurate indications of catheter location or of the need for possible repositioning. During the transition from antegrade to retrograde infusion of cardioplegic solution, the cardioplegic flow should be completely interrupted to avoid any pressure buildup in line. The gradual increase of volume and pressure administration in each system is warranted to prevent both barotrauma and dislodgment of the catheter from the coronary sinus. Two types of retrograde cannula were used during the study period during which modifications from the adultsize catheter were made. Both catheters, the Mayo balloon-tipped and the retroplegia catheter, have similar functional characteristics. The cardioplegic regimen was identical for both, and therefore both experiences can be combined. The one significant difference between the two cannulas is the ability of the retroplegia catheter to be passed transatrially (without atriotomy) into the coronary sinus. This technique has been restricted to patients weighing more than 15 to 20 kg because of size constraints. The majority of patients, however, requiring a vent or concomitant closure of an atrial or ventricular septal defect underwent direct cannulation of the coronary sinus through an existing atrial incision. This would also preclude the use of direct atrial technique retrograde cardioplegia as used by some groups in adult surgery.' Surgical procedures that may benefit from antegraderetrograde infusion of cardioplegic solution include (1)
aortic valve and root operations to provide protection in the face of insufficiency and to avoid or limit coronary ostial cannulation; (2) left-sided valve repairs or replacements, avoiding interruption to adequately deair for antegrade infusion of cardioplegic solution; (3) repair of coronary artery anomalies and fistulas to provide even distribution; and finally, (4) procedures in which continuous (warm) cardioplegia is used. The latter is a technique used in a growing number of adults and in some select pediatric patients with cardiac disease. Caveats for the use of continuous warm cardioplegia in pediatric patients may be (1) the presence of significant noncoronary collateral arteries that, at high flows, may compromise myocardial protection and visualization and (2) the ability for the renal function of smaller infants to handle the additional potassium load. Nevertheless, the technique and setup of this combined method of infusion of cardioplegic solution do allow for the option of continuous warm cardioplegia, which may play an increasing role in cardiac operations in all age groups. The finding of an oxygen uptake differential between the complete-induction antegrade and initial (30-second) retrograde dose provides further evidence that the two techniques may have differing preferential flow distribution, thus complementing one another. Previous laboratory work supports the observation that the subendocardium may be better perfused by retrograde infusion of cardioplegic solution, thus accounting for the differentials observed in this group of patients." It should be noted that
Volume 104 Number 5 November 1992
with the levels of significant hypothermia used in our patients, ongoing myocardial metabolism would not account for these differences in myocardial oxygen extraction in the 5 to 10 seconds between ending antegrade and initiating retrograde infusion of cardioplegic solution. An additional observation is that the greater differentials appear related to the degree of myocardial hypertrophy from the underlying anomaly. By inference, therefore, the combined antegrade-retrograde technique may be even more useful in those hearts that show the effects and changes of greater volume and pressure overload. In summary, this is a report of a clinical experience with combined antegrade-retrograde cardioplegia technique as the method of myocardial preservation in a group of pediatric patients with complex congenital heart disease. The low mortality and no morbidity attest to the safety and ease of the procedure in these patients. Its effectiveness warrants an expanding role in complex pediatric cardiac operations. We gratefullyacknowledge the contributionsof Ms. Arlene Arabe in helping to compilethe data that form the basisfor the clinical results reported herein.
Combined antegrade-retrograde infusion ofsolution
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REFERENCES 1. Drinkwater DC, Laks H, Buckberg GD. A new simplified
method of optimizing cardioplegic delivery without right heart isolation. J THORAC CARDIOVASC SURG 1990; 100:56-63. 2. Buckberg GD, Drinkwater DC, Laks H. A new technique for delivering antegradejretrograde blood cardioplegia without right heart isolation. Eur J Cardiothorac Surg 1990;4:163-8. 3. Menasche P, Subayi JB, Piwnica A. Retrograde coronary sinus cardioplegia for aortic valve operations: a clinical report on 500 patients. Ann Thorac Surg 1990;49:556-64. 4. Mori F, Ivey T, Tabayashi K, Thomas R, Misbach G. Regional myocardial protection by retrograde coronary sinus infusion of cardioplegic solution. Circulation 1986; 74(Pt 2):111-6. 5. Fabiani JN, Deloche A, Swanson J, Carpentier A. Retrograde cardioplegia through the right atrium. Ann Thorac Surg 1986;41:101-2. 6. Partington MT, Acar C, Buckberg GD, Julia T, Kofsky ER, Bugyi H. Studiesof retrograde cardioplegiacapillary bloodflowdistributionto myocardiumsuppliedbyopenand occluded arteries. J THORAC CARDIOVASC SURG 1989; 97:605-12.