Reparative Cardiac Surgery in Infants and Small Children Five Years Experience with Profound Hypothermia and Circulatory Arrest HARVEY W. BENDER, JR., M.D., R. DARRYL FISHER, M.D., WILLIAM E. WALKER, M.D., THOMAS P. GRAHAM, M.D.
A five year experience of profound hypothermia and circulatory arrest in the operative management of severe congenital heart disease in 128 infants and children weighing 10 kg or less is reviewed. Hospital mortality was 13% for the entire series-8% in the last two years. Mortality varied with t4e defect present rather than with the age at operation, and appeared to decline over the five years. There was no morbidity associated particularly with this technique, and no evidence of permanent neurologic nor intellectual impairment. Total arrest time averaged 55 minutes, was related significantly to the defect being repaired, but was not related to hospital mortality. The results support the idea of definitive early cardiac repair for severely symptomatic infants and young children, rather than surgical palliation. The hypothermic arrest technique is attractive silce it allows optimal operating conditions, thus permitting an accurate repair and the consequent improvement in surgical results. S EVERELY SYMPTOMATIC INFANTS and young chil-
dren with congenital heart disease continue to pose a serious challenge for cardiologist and surgeon alike. Despite advances in diagnostic skills, surgical techniques, anesthesia, and perfusion technology, there is still a lack of uniformity in the management of these small patients. At the end of the first decade of open heart surgery, it was clear that in many congenital defects the standard methods were not well suited to optimal repair, contributing thereby to a high operative and postoperative mortality.3 4 9 Because of the high risk of repair in these infants, palliative procedures such as systemic-pulmonary artery shunts for severe cyanosis and pulmonary artery banding for severe heart failure due to left to right shunting at the ventricular level became the conventional mode of therapy. 13.16.23 While this represented a temporary improvement in survival, the risk of multiple operative procedures, endocarditis, and Presented at the Annual Meeting of the American Surgical Association, Hot Springs, Virginia, April 26-28, 1979. Reprint requests: Harvey W. Bender, Jr., M.D., Department of Cardiac and Thoracic Surgery, Vanderbilt University School of Medicine, Nashville, Tennessee 37232.
From the Department of Cardiac and Thoracic Surgery and Department of Pediatrics, Vanderbilt University School of Medicine, Nashville, Tennessee
paradoxical embolism was still high. In the late 1960's profound hypothermia and circulatory arrest were introduced as ap alternative to standard cardiopulmonary bypass for the definitive management of infants with complicated congenital heart disease.2"10"13 In the succeeding years there appeared an increasing number of reports urging earlier complete repair in infants and small children using this technique with decreasing morbidity and mortality.7"18'20 Over the past seven years we have used the hypothermic arrest technique to facilitate operative management. Our early results with this technique have been reported previously.6 This report details our experience with 128 procedures over the five year period 1974-1978. The results have convinced us that this method allows accurate cardiac repair at an early age without undue mortality or morbidity, thereby obviating the need for palliative surgery in most infants, and permitting the children to develop free of the physiological disadvantages of their heart disease. Technique
All patients weighing 10 kg or less requiring open cardiac repair are considered candidates. The age range in this series was 12 hours to 3h years, with 35 (27%) being less than two months of age, and 102 (80o) being less than one year of age. Cardiac failure is controlled preoperatively, if possible, and time allowed for the patient to recover from catheterization in most instances. Balloon septostomy is performed where indicated to improve mixing, and prostaglandin E-1 infusion used to maintain ductal patency when necessary.
00034932,79/1000/0437 $00.85 C J. B. Lippincott Company
437
Ann. Surg.
BENDER AND OTHERS
438
HYPOTHERMIA CIRCULATORY C.M. AGE: 2
mos.
FIG. 1. Typical graph of
WT.: 4.9 KG SENNING PROCEDURE
nasopharyngeal temperature during time in the operating room of a two
40XX
XXX w
35
XX
XXxxx
XXXXXXXXX)
X x X
a:
X x
X
301_
X
KXXXX
X
z w
X X
w
X X
X
25_
X X
I
201-
X
XX
X X XXXXXXX
w
15 PREPARATION
5'-I Iv'
ICE IIOPENINGICOOL I a
I
*
ARREST -
WARM
3 2 TIME IN OPERATING ROOM (HOURS)
ECG monitoring is begun on arrival in the operating and anesthesia induced by inhalation of halothane, nitrous oxide, and oxygen. When the patient is still, an intravenous line is started, he is paralyzed, and the trachea intubated. Arterial and central venous lines are inserted, and a small catheter placed in the bladder. Temperature probes are situated in the nasopharynx, esophagus, and rectum, although we generally consider the nasopharyngeal temperature to be most representative. The patient is surrounded by plastic bags filled with ice, protecting the ears, extremities, and genitals from the cold. Low molecular weight dextran, 10 cc/kg body weight, is,given intravenously, and occasionally atropine if bradycardia occurs. When the temperature reaches 300 the ice is removed, the patient is prepped and draped in the usual manner, and sternotomy performed. Heparin 100 units/kg is given, the ascending aorta and right atrium cannulated, and cardiopulmonary bypass instituted. Fresh blood is added to the pump prime to give an estimated hematocrit of 30%o on bypass, and the resultant prime buffered with sodium bicarbonate before bypass is begun. The patient is cooled to 180 using the pump heat exchanger, and during this time a patent ductus can be ligated, previous shunts controlled, and other preliminary dissection carried out as necessary. Intermittent ventilation is maintained until the patent ductus or shunt is occluded. Blood room,
gases are
October 1979
ARREST
-
7/17/78
*
OFF -CLOSING 4
_
month old child undergoing the Senning procedure for transposition of the great arteries. The ordinate is temperature, degrees Centigrade, the abscissa number of hours since arrival in the operating room. "Preparation" refers to anesthesia induction and insertion of monitoring catheters etc.; "ice" is the period of surface cooling; "opening" indicates the time of prepping, draping, sternotomy, and insertion of cannulae; "cool" is time spent on core cooling with cardiopulmonary bypass; "arrest" is the time of actual cardiac repair with circulatory standstill; "warm" is rewarming on the pump; and "off-closing" is weaning from bypass, removing the cannulae, and closing the chest.
rechecked before the institution of circula-
tory arrest, and further buffering carried out as necessary. The aorta is cross-clamped, blood drained
into the reservoir, the aortic line disconnected, and the venous cannula removed. The repair is performed with blood circulating in the pump oxygenator, at a temperature 100 warmer than the patient, to prevent the formation of bubbles and microaggregates. When the repair is complete, the aortic line is reattached, the drained volume returned to the patient, air vented from all cardiac chambers, and the cross-clamp removed. After replacing the right atrial cannula, cardiopulmonary bypass is restarted, anl the patient warmed to 37°. Care is taken to keep the perfusate temperature no more than 100 warmer than the patient, and no higher than 410. In patients undergoing repair of transposition of the great arteries, the venous cannula is returned to what is now the pulmonary venous atrium, and left heart bypass used for rewarming.
After satisfactory separation from bypass, the lines are removed and protamine 3 mg/kg given slowly. Fresh frozen plasma is given in a volume dependent on the child's size, unless the procedure has been unusually brief, and the wound is dry. Meticulous hemostasis is pursued, and the chest closed with drainage in the usual fashion. Figure 1 shows the typical time-course of naso-
HYPOTHERMIC ARREST
Vol. 190 * No. 4
TABLE 1. Profound Hypothermia and Circulatory Arrest (Vanderbilt University 1974-1978)
Number
Transposition of great arteries simple complex Ventricular septal defect Total anomalous pulmonary venous connection Tetralogy/DORV/pulmonary atresia Atrioventncularis communis Miscellaneous Total
TABLE 3. Hospital Mortality by Year of Operation
Hospital Mortality (Per Cent)
30
439
11 29
7 9 0
17 15 12 14 128
18 13 25 43 13
pharyngeal temperature during the patient's stay in the operating room. Surface cooling, core cooling, and rewarming each generally last between 15 and 25 minutes depending on the size and configuration of the child. No attempt is made to keep the child warm during preparation and induction of anesthesia. After bypass is terminated the temperature may drift downwards again, but this is usually not a problem. The child lies on a warming blanket, and the operating room may be warmed rapidly if the chest must remain open unusually long or if inadvertent hypothermia threatens. Postoperative care centers on careful attention to respiratory support and the maintenance of clear airways and expanded lungs, adequate blood volume replacement, and a low threshold for beginning inotropic or chronotropic support of the heart. Like any other infant, these children are susceptible to the metabolic derangements of the newborn, and a careful watch is kept for incipient hypoglycemia or hypocalcemia. The child is extubated as quickly as is appropriate, begins feeding shortly thereafter, and generally returns to his preoperative environment as soon as possible. Results The numbers of the various anomalies repaired, and their respective hospital mortalities, for the 128 patients are shown in Table 1. Overall mortality was 13%. The miscellaneous group is detailed in Table 2, with only persistent truncus arteriosus and aortic stenosis being represented by more than one patient.
Year
Number
Mortality (Per Cent)
1974 1975 1976 1977 1978 Total
11 12 16 41 48 128
27 25 25 7 8 13
As shown in Table 3, hospital mortality declined significantly during the five years of the study as the numbers of patients increased. The mortality was 26% in 39 patients repaired during the first three years, and 8% in 89 patients repaired during the last two years.
Mortality according to age at the time of operation is shown in Table 4. The overall mortality of 14% in the first year of life was evenly distributed, including 35 patients (27% of the series) repaired in the first two months of life. Twenty-six patients (20% of the series) underwent surgery after the first year of life, and in them the hospital mortality was 8%. Hypothermic arrest time averaged 55 minutes for the entire group, with a range of 22-105 minutes. Arrest time varied significantly according to the anomaly present, and the averages for each anomaly are shown in Table 5. Arrest times averaged 41 minutes for patients with ventricular septal defect and the group with miscellaneous lesions, slightly more for those with "tetralogy type" defects or total anomalous pulmonary venous connection, and just over 70 minutes for those with transposition of the great arteries or atrioventricularis communis. Hospital mortality was not associated with a long arrest period, as shown in Figure 2. In fact the mortality was 10% in 31 patients arrested over 65 minutes, compared to 16% in 97 patients arrested for shorter periods. Table 6 outlines our experience with repair of transposition of the great arteries-the one lesion for which there has been a major revision of operative technique during the period of the study. 'The 11 children having the Senning operation during 1978 underwent repair at an earlier age than those having the Mustard repair in previous years, and without hospital mortality. TABLE 4. Hospital Mortality by Age at Operation
TABLE 2. Miscellaneous Lesions
Mortality
Persistent truncus arteriosus Aortic stenosis Tricuspid atresia Venous obstruction postmustard Aortopulmonary window TGA/TAPVR/AVC VSD/interrupted arch
5 4 1 1 I 1 1
Age
Number
(Per Cent)
0-2 months 3-6 months 7-12 months Over 1 year Total
35 31 36 26 128
14 13 14 8 13
Ann. Surg. * October 1979
BENDER AND OTHERS
440
TABLE 5. Arrest Times According to Malformation
Defect
Arrest Time
Transposition VSD Tetralogy AVC TAPVR Miscellaneous Total (Range
71 ± 2 min
41±2min 46 ± 5 min 72 ± 5 min 52 ± 2 min 41 ± 4 min 55 ± 3 min 22-105 min)
Arrest times are shown as mean
+
standard error of the estimate.
Morbidity was low in this group of patients. Cardiac function was good following satisfactory repair, and the children separated from cardiopulmonary bypass without undue difficulty. Pulmonary function was generally as would be predicted, with some children requiring prolonged ventilation following preoperative pulmonary vascular congestion, but the maj ority of patients were extub4te&1 satisfactorily within 24 hours. Hepatic and gastrointestinal function was preserved and these children normally took feedings within 48 hours of surgery. Occasional oliguria and azotemia were seen, particularly in sick neonates, and particularly with total anomalous pulmonary venous
return, but this never persisted as an isolated problem when the child was doing well otherwise. Postoperative bleeding and coagulopathy were not a serious problem. Five patients (4%) were returned to the operating room because of bleeding. It is our impression that the actual volume of blood lost in the postoperative period has declined during the five years of this experience, and attribute this to decreased heparin usage, increased protamine dosage, and careful attention to hemostasis intraoperatively. Temporary seizure activity in the days immediately following surgery was prominent early in the series but may have been due to unrecognized hypoglycemia or hypocalcemia. Over the past few years it has been very rare. In no patient did the seizures persist, and no patient is on long-term anticonvulsant therapy. No other neurologic complication was recognized with the exception of one child at the upper ends of the scales of weight and age, who had a long arrest time followed by a long period of unconsciousness and a very slow recovery over a period of several weeks. He now shows normal developmental parameters fifteen months postoperatively. While no specific psychological testing has been applied to this series, we are unaware of any
HYPOTHERMIA CIRCULATORY ARREST -
1974
-
1978 128 PATIENTS
4
DEATHS QSURV IVORS
Cr)
z
w
20-
2
aLL
0 w
m
1o-
z
I
41II
I-T
20
17, I
III
I
16 I
I T%F
22 21 16 _ 1--u a1--l 80 70 60 50 ARREST TIME (MINUTES) 1-. Ia
&%A-k
30
40
90
ivi lf%f%~ lvu
FIG. 2. Numbers of patients surviving and dying according to arrest time. Arrest times are rounded to the nearest multiple of 10 minutes. Figures within the clear boxes indicate numbers of survivors, and figures above the shaded boxes indicate numbers of deaths.
441
HYPOTHERMIC ARREST
Vol. 190 * No. 4
TABLE 6. Transposition of the Great Arteries
Technique
Year
Number
Mustard Senning
1974-1977 1978
30 11
Average age and arrest time are shown as mean
Average Age 12 6 +
+ +
I months 1 months
Median Age
Arrest Time
Hospital Mortality (Per Cent)
10 months 5 months
73 + 2 min 65 + 3 min
10 0
standard error of the estimate.
developmental abnormality as reported by parent, general pediatrician, or cardiologist. Discussion It is difficult if not impossible to compare the results of various surgical techniques in neonates and young children with congenital heart disease because of patient selection and possible failure to review the entire hospital population of a given disease. We believe, however, that these results support the contention of others18'20'22 who now advocate definitive repair of congenital cardiac anomalies at an early age rather than temporizing palliative procedures. Reparative surgery is normally mandatory for neonates with total anomalous pulmonary venous connection, but there are still those who advocate palliation for many other defects. Clearly some patients with these anomalies can survive to be several years of age with or without surgical palliation, but we believe reports of good results of surgery in older children with these defects may represent a selected population of whom some have died in infancy without being exposed to the benefits of surgical treatment. The major benefit of the hypothermic arrest technique is that it allows accurate repair in a bloodless, motionless operative field unencumbered by venous cannulae, especially valuable in the very small heart. This is particularly applicable to the transatrial repair of the transposition complexes, atrioventricularis communis, ventricular septal defect, and total anomalous pulmonary venous connection. Good results of the technique are predicated on an accurate preoperative diagnosis and an unhurried, careful repair of the heart, protecting the myocardium, and avoiding damage to essential structures such as valves and conduction tissue. Our philosophy is that if the diagnosis is correct, and the operation carried out carefully enough, the patient should do well regardless of age. The risk of cerebral damage during hypothermic arrest is clearly worrisome, and is at the present time the only potential drawback of the technique. The recent report of Wright et al.24 suggests that the risk of intellectual impairment may be real, but other
authors21'22 have described a normal spectrum of intelligence on careful follow-up of their patients. We have not noted any developmental abnormality, either mental or physical, in our patients, with the single exception of the child described above, who appears to be recovering completely. There have also been reports of isolated instances of neurologic rather than intellectual impairment using the hypothermic arrest technique, but we have not seen choreoathetoid movements, discoordination, nor prolonged seizure activity in this series. It will be important for all groups using the technique to review their own long-term results, as it is possible that minor variations in operative management may explain the apparently disparate results of neuropsychiatric follow-up. Even if there is some risk of reduction in cerebral function following hypothermic arrest, the balance may still favor the method because of increased survival, especially in particularly challenging defects in neonates. The improvement in hospital survival over the period of the study suggests that experience does indeed increase survival, but even initially there was no undue mortality nor morbidity when the severity of the defect is considered. This improvement is partially explained by the inclusion of more patients with less serious defects, such as a one year old child with uncomplicated ventricular septal defect, as confidence in the technique was gained. Early in the study period such an infant might have been handled with conventional perfusion methods. Increased familiarity with the technique has in fact encouraged us to repair more serious defects in infancy, and allowed the increased use of such techniques as transatrial repair of ventricular septal defect, which may be difficult in very small children with standard methods of perfusion. Clearly prognosis depends on the anatomic situation present in the child regardless of whether hypothermic arrest or conventional perfusion is used. For instance, in "tetralogy type" defects the chance of survival depends on the characteristics of the outflow tract and pulmonary arteries. Patients with severe valvular defects and complicated supravalvular de-
442
BENDER AND OTHERS
fects, such as persistent truncus arteriosus, will still have an increased mortality, and those with "uncorrectable" lesions such as the hypoplastic left heart syndromes will still have a bad prognosis, regardless of perfusion technique. We believe, however, that when allowance is made for the gravity of the procedures undertaken, the results obtainable with the hypothermic arrest technique will compare favorably with the current results attained using standard cardiopulmonary bypass in neonates.'9 There are some lesions for which the hypothermic arrest technique is not particularly helpful, an example being isolated obstruction of the left ventricular outflow tract. The hypertrophied left ventricle may well be at increased risk during surface cooling, and these hearts are more liable to show dysrhythmias. A more prudent technique for these infants is low flow and hypothermia to 22-25°. If excessive venous return is a problem, a short period of arrest may be undertaken without removal of the cannulae. Infants with severely symptomatic transposition of the great arteries, either simple or complex, persistent truncus arteriosus, atrioventricularis communis, as well as some other less common lesions, can be added to the group8""l 22 meriting early definitive operation because of the improvement in the quality of the repair brought about by the use of hypothermic arrest, and the consequent reduction in the chance of operative error. The successful renaissance of the Senning operation14"16 in particular attests to improvements in operative technology, and many children with various transposition complexes can undergo satisfactory repair shortly after birth. We have had no hospital mortality in our patients having the Senning operation including five undergoing operation in the first two months of life. It now appears that the trend towards the early, definitive repair of complicated congenital heart defects has physiologic merit. It has been our experience, as stated above, that these operations are facilitated by the use of profound hypothermia and circulatory arrest allowing anatomic repair with low morbidity and mortality. If, in the future, the clinical courses of these children remain free of hemodynamic and developmental complications, the early, complete repair of congenital cardiac malformations using this technique appears to be justified, thereby avoiding the metabolic and developmental derangements produced by prolonged cardiac decompensation. References 1. Aoyagi, M., Flasterskin, A. H., Barnette, J., et al.: Cerebral Effects of Profound Hypothermia (18°C) and Circulatory Arrest. Circulation, 49,50(suppl 2):60, 1974. 2. Barrett-Boyes, B. G., Simpson, M. J. and Neutze, J. M.:
3. 4.
5.
6.
7. 8. 9.
10. 11.
12. 13.
14. 15. 16.
17. 18. 19. 20. 21.
22.
23. 24.
Ann. Surg. * October 1979
Intracardiac Surgery in Neonates and Infants Using Deep Hypothermia with Surface Cooling and Limited Cardiopulmonary Flow. Circulation, 43-44(suppl 1):25, 1971. Bernhard, W. F., Litwin, S. B., Williams, W. W., et al.: Recent Results of Cardiovascular Surgery in Infants in the First Year of Life. Am. J. Surg., 123:451, 1972. Breckenridge, I. M., Oelert, H., Graham, G. R., et al.: Openheart Surgery in the First Year of Life. J. Thorac. Cardiovasc. Surg., 65:58, 1973. Brunberg, J. A., Reilly, E. L. and Doty, D. B.: Central Nervous System Consequences in Infants of Cardiac Surgery Using Deep Hypothermia and Circulatory Arrest. Circulation, 49,50(suppl 2):60, 1974. Caldwell, III, T. B., Blunk, J. N. and Escobar, A.: Experience with Deep Hypothermia and Elective Circulatory Arrest for Cardiac Surgery in Infants. South. Med. J., 70: 681, 1977. Castaneda, A. R., Lamberti, J., Sade, R. M., et al.: Openheart Surgery During the First Three Months of Life. J. Thorac. Cardiovasc. Surg., 68:719, 1974. Castaneda, A. R., Freed, M. D., Williams, R. G. and Norwood, W. I.: Repair of Tetralogy of Fallot in Infancy. J. Thorac. Cardiovasc. Surg., 74:372, 1977. Hallman, G. L. and Cooley, D. A.: Cardiovascular Surgery in Newborn Infants: Results in 1,050 Patients Less Than One Year Old. Ann. Surg., 173:1007, 1971. Hikasa, Y., Shirotani, H. and Satomura, K.: Open-heart Surgery in Infants with the Aid of Hypothermic Anesthesia. Arch. Jap. Chir., 36:495, 1967. Katz, N. M., Kirklin, J. W. and Pacifico, A. D.: Concepts and Practices in Surgery for Total Anomalous Pulmonary Venous Connection. Ann. Thorac. Surg., 25:479, 1978. Mahle, S., Nicoloff, D. M., Knight, L. and Moller, J. H.: Pulmonary Artery Banding: Long-term Results in 63 Patients. Ann. Thorac. Surg., 27:216, 1979. Muraoka, R., Hikasa, Y., Shirotani, H., et al.: Open-heart Surgery in Infants Under Two Years of Age Using Deep Hypothermia with Surface Cooling and Partial Cardiopulmonary Bypass. J. Cardiovasc. Surg., 15:231, 1974. Parenzan, L., Locatelli, G., Alfieri, O., et al.: The Senning Operation for Transposition of the Great Arteries. J. Thorac. Cardiovasc. Surg., 76:305, 1978. Paton, B. C., Stewart, J. R., Nora, J. J., et al.: Pulmonary Artery Banding for Ventricular Septal Defect with Pulmonary Hypertension. Arch. Surg., 112:1454, 1977. Quaegebeur, J. M., Rohmer, J., Brom, A. G. and Tinkelenberg, J.: Revival of the Senning Operation in the Treatment of Transposition of the Great Arteries. Thorax, 32: 517, 1977. Rittenhouse, E. A., Mohri, H., Dillard, D. H. and Merendino, K. A.: Deep Hypothermia in Cardiovascular Surgery. Ann. Thorac. Surg., 17:63, 1974. Sade, R. M., Williams, R. G. and Castaneda, A. R.: Corrective Surgery for Congenital Cardiovascular Defects in Early Infancy. Am. Heart J., 90:656, 1975. Shuichiro, S. and Starr, A.: Cardiopulmonary Bypass in Infants Under Four Months of Age. J. Thorac. Cardiovasc. Surg., 73:894, 1977. Smith, D. L., Wilson, J. M. and Ebert, P. A.: Cardiac Surgery in Infants Up to One Year Old. Cardiovasc. Med. 3:925, 1978. Steven, J. G., Stone, E. F., Dillard, D. H. and Morgan, B. C.: Intellectual Development of Children Subjected to Prolonged Circulatory Arrest During Hypothermic Open Heart Surgery in Infancy. Circulation, 49,50(suppl 2):54, 1974. Wagner, H. R. and Subramanian, S.: Deep Hypothermia in Infant Cardiac Surgery. Pediatrics, 61:479, 1978. Wood, W. C., McCue, C. M. and Lower, R. R.: BlalockTaussig Shunts in the Infant. Ann. Thorac. Surg., 16: 454, 1973. Wright, J. S., Hicks, R. G. and Newman, D. C.: Deep Hypothermic Arrest: Observations on Later Development in Children. J. Thorac. Cardiovasc. Surg., 77:466, 1979.
A five year experience of profound hypothermia and circulatory arrest in the operative management of severe congenital heart disease in 128 infants and children weighing 10 kg or less is reviewed. Hospital mortality was 13% for the entire series-8% in the last two years. Mortality varied with t4e defect present rather than with the age at operation, and appeared to decline over the five years. There was no morbidity associated particularly with this technique, and no evidence of permanent neurologic nor intellectual impairment. Total arrest time averaged 55 minutes, was related significantly to the defect being repaired, but was not related to hospital mortality. The results support the idea of definitive early cardiac repair for severely symptomatic infants and young children, rather than surgical palliation. The hypothermic arrest technique is attractive silce it allows optimal operating conditions, thus permitting an accurate repair and the consequent improvement in surgical results. S EVERELY SYMPTOMATIC INFANTS and young chil-
dren with congenital heart disease continue to pose a serious challenge for cardiologist and surgeon alike. Despite advances in diagnostic skills, surgical techniques, anesthesia, and perfusion technology, there is still a lack of uniformity in the management of these small patients. At the end of the first decade of open heart surgery, it was clear that in many congenital defects the standard methods were not well suited to optimal repair, contributing thereby to a high operative and postoperative mortality.3 4 9 Because of the high risk of repair in these infants, palliative procedures such as systemic-pulmonary artery shunts for severe cyanosis and pulmonary artery banding for severe heart failure due to left to right shunting at the ventricular level became the conventional mode of therapy. 13.16.23 While this represented a temporary improvement in survival, the risk of multiple operative procedures, endocarditis, and Presented at the Annual Meeting of the American Surgical Association, Hot Springs, Virginia, April 26-28, 1979. Reprint requests: Harvey W. Bender, Jr., M.D., Department of Cardiac and Thoracic Surgery, Vanderbilt University School of Medicine, Nashville, Tennessee 37232.
From the Department of Cardiac and Thoracic Surgery and Department of Pediatrics, Vanderbilt University School of Medicine, Nashville, Tennessee
paradoxical embolism was still high. In the late 1960's profound hypothermia and circulatory arrest were introduced as ap alternative to standard cardiopulmonary bypass for the definitive management of infants with complicated congenital heart disease.2"10"13 In the succeeding years there appeared an increasing number of reports urging earlier complete repair in infants and small children using this technique with decreasing morbidity and mortality.7"18'20 Over the past seven years we have used the hypothermic arrest technique to facilitate operative management. Our early results with this technique have been reported previously.6 This report details our experience with 128 procedures over the five year period 1974-1978. The results have convinced us that this method allows accurate cardiac repair at an early age without undue mortality or morbidity, thereby obviating the need for palliative surgery in most infants, and permitting the children to develop free of the physiological disadvantages of their heart disease. Technique
All patients weighing 10 kg or less requiring open cardiac repair are considered candidates. The age range in this series was 12 hours to 3h years, with 35 (27%) being less than two months of age, and 102 (80o) being less than one year of age. Cardiac failure is controlled preoperatively, if possible, and time allowed for the patient to recover from catheterization in most instances. Balloon septostomy is performed where indicated to improve mixing, and prostaglandin E-1 infusion used to maintain ductal patency when necessary.
00034932,79/1000/0437 $00.85 C J. B. Lippincott Company
437
Ann. Surg.
BENDER AND OTHERS
438
HYPOTHERMIA CIRCULATORY C.M. AGE: 2
mos.
FIG. 1. Typical graph of
WT.: 4.9 KG SENNING PROCEDURE
nasopharyngeal temperature during time in the operating room of a two
40XX
XXX w
35
XX
XXxxx
XXXXXXXXX)
X x X
a:
X x
X
301_
X
KXXXX
X
z w
X X
w
X X
X
25_
X X
I
201-
X
XX
X X XXXXXXX
w
15 PREPARATION
5'-I Iv'
ICE IIOPENINGICOOL I a
I
*
ARREST -
WARM
3 2 TIME IN OPERATING ROOM (HOURS)
ECG monitoring is begun on arrival in the operating and anesthesia induced by inhalation of halothane, nitrous oxide, and oxygen. When the patient is still, an intravenous line is started, he is paralyzed, and the trachea intubated. Arterial and central venous lines are inserted, and a small catheter placed in the bladder. Temperature probes are situated in the nasopharynx, esophagus, and rectum, although we generally consider the nasopharyngeal temperature to be most representative. The patient is surrounded by plastic bags filled with ice, protecting the ears, extremities, and genitals from the cold. Low molecular weight dextran, 10 cc/kg body weight, is,given intravenously, and occasionally atropine if bradycardia occurs. When the temperature reaches 300 the ice is removed, the patient is prepped and draped in the usual manner, and sternotomy performed. Heparin 100 units/kg is given, the ascending aorta and right atrium cannulated, and cardiopulmonary bypass instituted. Fresh blood is added to the pump prime to give an estimated hematocrit of 30%o on bypass, and the resultant prime buffered with sodium bicarbonate before bypass is begun. The patient is cooled to 180 using the pump heat exchanger, and during this time a patent ductus can be ligated, previous shunts controlled, and other preliminary dissection carried out as necessary. Intermittent ventilation is maintained until the patent ductus or shunt is occluded. Blood room,
gases are
October 1979
ARREST
-
7/17/78
*
OFF -CLOSING 4
_
month old child undergoing the Senning procedure for transposition of the great arteries. The ordinate is temperature, degrees Centigrade, the abscissa number of hours since arrival in the operating room. "Preparation" refers to anesthesia induction and insertion of monitoring catheters etc.; "ice" is the period of surface cooling; "opening" indicates the time of prepping, draping, sternotomy, and insertion of cannulae; "cool" is time spent on core cooling with cardiopulmonary bypass; "arrest" is the time of actual cardiac repair with circulatory standstill; "warm" is rewarming on the pump; and "off-closing" is weaning from bypass, removing the cannulae, and closing the chest.
rechecked before the institution of circula-
tory arrest, and further buffering carried out as necessary. The aorta is cross-clamped, blood drained
into the reservoir, the aortic line disconnected, and the venous cannula removed. The repair is performed with blood circulating in the pump oxygenator, at a temperature 100 warmer than the patient, to prevent the formation of bubbles and microaggregates. When the repair is complete, the aortic line is reattached, the drained volume returned to the patient, air vented from all cardiac chambers, and the cross-clamp removed. After replacing the right atrial cannula, cardiopulmonary bypass is restarted, anl the patient warmed to 37°. Care is taken to keep the perfusate temperature no more than 100 warmer than the patient, and no higher than 410. In patients undergoing repair of transposition of the great arteries, the venous cannula is returned to what is now the pulmonary venous atrium, and left heart bypass used for rewarming.
After satisfactory separation from bypass, the lines are removed and protamine 3 mg/kg given slowly. Fresh frozen plasma is given in a volume dependent on the child's size, unless the procedure has been unusually brief, and the wound is dry. Meticulous hemostasis is pursued, and the chest closed with drainage in the usual fashion. Figure 1 shows the typical time-course of naso-
HYPOTHERMIC ARREST
Vol. 190 * No. 4
TABLE 1. Profound Hypothermia and Circulatory Arrest (Vanderbilt University 1974-1978)
Number
Transposition of great arteries simple complex Ventricular septal defect Total anomalous pulmonary venous connection Tetralogy/DORV/pulmonary atresia Atrioventncularis communis Miscellaneous Total
TABLE 3. Hospital Mortality by Year of Operation
Hospital Mortality (Per Cent)
30
439
11 29
7 9 0
17 15 12 14 128
18 13 25 43 13
pharyngeal temperature during the patient's stay in the operating room. Surface cooling, core cooling, and rewarming each generally last between 15 and 25 minutes depending on the size and configuration of the child. No attempt is made to keep the child warm during preparation and induction of anesthesia. After bypass is terminated the temperature may drift downwards again, but this is usually not a problem. The child lies on a warming blanket, and the operating room may be warmed rapidly if the chest must remain open unusually long or if inadvertent hypothermia threatens. Postoperative care centers on careful attention to respiratory support and the maintenance of clear airways and expanded lungs, adequate blood volume replacement, and a low threshold for beginning inotropic or chronotropic support of the heart. Like any other infant, these children are susceptible to the metabolic derangements of the newborn, and a careful watch is kept for incipient hypoglycemia or hypocalcemia. The child is extubated as quickly as is appropriate, begins feeding shortly thereafter, and generally returns to his preoperative environment as soon as possible. Results The numbers of the various anomalies repaired, and their respective hospital mortalities, for the 128 patients are shown in Table 1. Overall mortality was 13%. The miscellaneous group is detailed in Table 2, with only persistent truncus arteriosus and aortic stenosis being represented by more than one patient.
Year
Number
Mortality (Per Cent)
1974 1975 1976 1977 1978 Total
11 12 16 41 48 128
27 25 25 7 8 13
As shown in Table 3, hospital mortality declined significantly during the five years of the study as the numbers of patients increased. The mortality was 26% in 39 patients repaired during the first three years, and 8% in 89 patients repaired during the last two years.
Mortality according to age at the time of operation is shown in Table 4. The overall mortality of 14% in the first year of life was evenly distributed, including 35 patients (27% of the series) repaired in the first two months of life. Twenty-six patients (20% of the series) underwent surgery after the first year of life, and in them the hospital mortality was 8%. Hypothermic arrest time averaged 55 minutes for the entire group, with a range of 22-105 minutes. Arrest time varied significantly according to the anomaly present, and the averages for each anomaly are shown in Table 5. Arrest times averaged 41 minutes for patients with ventricular septal defect and the group with miscellaneous lesions, slightly more for those with "tetralogy type" defects or total anomalous pulmonary venous connection, and just over 70 minutes for those with transposition of the great arteries or atrioventricularis communis. Hospital mortality was not associated with a long arrest period, as shown in Figure 2. In fact the mortality was 10% in 31 patients arrested over 65 minutes, compared to 16% in 97 patients arrested for shorter periods. Table 6 outlines our experience with repair of transposition of the great arteries-the one lesion for which there has been a major revision of operative technique during the period of the study. 'The 11 children having the Senning operation during 1978 underwent repair at an earlier age than those having the Mustard repair in previous years, and without hospital mortality. TABLE 4. Hospital Mortality by Age at Operation
TABLE 2. Miscellaneous Lesions
Mortality
Persistent truncus arteriosus Aortic stenosis Tricuspid atresia Venous obstruction postmustard Aortopulmonary window TGA/TAPVR/AVC VSD/interrupted arch
5 4 1 1 I 1 1
Age
Number
(Per Cent)
0-2 months 3-6 months 7-12 months Over 1 year Total
35 31 36 26 128
14 13 14 8 13
Ann. Surg. * October 1979
BENDER AND OTHERS
440
TABLE 5. Arrest Times According to Malformation
Defect
Arrest Time
Transposition VSD Tetralogy AVC TAPVR Miscellaneous Total (Range
71 ± 2 min
41±2min 46 ± 5 min 72 ± 5 min 52 ± 2 min 41 ± 4 min 55 ± 3 min 22-105 min)
Arrest times are shown as mean
+
standard error of the estimate.
Morbidity was low in this group of patients. Cardiac function was good following satisfactory repair, and the children separated from cardiopulmonary bypass without undue difficulty. Pulmonary function was generally as would be predicted, with some children requiring prolonged ventilation following preoperative pulmonary vascular congestion, but the maj ority of patients were extub4te&1 satisfactorily within 24 hours. Hepatic and gastrointestinal function was preserved and these children normally took feedings within 48 hours of surgery. Occasional oliguria and azotemia were seen, particularly in sick neonates, and particularly with total anomalous pulmonary venous
return, but this never persisted as an isolated problem when the child was doing well otherwise. Postoperative bleeding and coagulopathy were not a serious problem. Five patients (4%) were returned to the operating room because of bleeding. It is our impression that the actual volume of blood lost in the postoperative period has declined during the five years of this experience, and attribute this to decreased heparin usage, increased protamine dosage, and careful attention to hemostasis intraoperatively. Temporary seizure activity in the days immediately following surgery was prominent early in the series but may have been due to unrecognized hypoglycemia or hypocalcemia. Over the past few years it has been very rare. In no patient did the seizures persist, and no patient is on long-term anticonvulsant therapy. No other neurologic complication was recognized with the exception of one child at the upper ends of the scales of weight and age, who had a long arrest time followed by a long period of unconsciousness and a very slow recovery over a period of several weeks. He now shows normal developmental parameters fifteen months postoperatively. While no specific psychological testing has been applied to this series, we are unaware of any
HYPOTHERMIA CIRCULATORY ARREST -
1974
-
1978 128 PATIENTS
4
DEATHS QSURV IVORS
Cr)
z
w
20-
2
aLL
0 w
m
1o-
z
I
41II
I-T
20
17, I
III
I
16 I
I T%F
22 21 16 _ 1--u a1--l 80 70 60 50 ARREST TIME (MINUTES) 1-. Ia
&%A-k
30
40
90
ivi lf%f%~ lvu
FIG. 2. Numbers of patients surviving and dying according to arrest time. Arrest times are rounded to the nearest multiple of 10 minutes. Figures within the clear boxes indicate numbers of survivors, and figures above the shaded boxes indicate numbers of deaths.
441
HYPOTHERMIC ARREST
Vol. 190 * No. 4
TABLE 6. Transposition of the Great Arteries
Technique
Year
Number
Mustard Senning
1974-1977 1978
30 11
Average age and arrest time are shown as mean
Average Age 12 6 +
+ +
I months 1 months
Median Age
Arrest Time
Hospital Mortality (Per Cent)
10 months 5 months
73 + 2 min 65 + 3 min
10 0
standard error of the estimate.
developmental abnormality as reported by parent, general pediatrician, or cardiologist. Discussion It is difficult if not impossible to compare the results of various surgical techniques in neonates and young children with congenital heart disease because of patient selection and possible failure to review the entire hospital population of a given disease. We believe, however, that these results support the contention of others18'20'22 who now advocate definitive repair of congenital cardiac anomalies at an early age rather than temporizing palliative procedures. Reparative surgery is normally mandatory for neonates with total anomalous pulmonary venous connection, but there are still those who advocate palliation for many other defects. Clearly some patients with these anomalies can survive to be several years of age with or without surgical palliation, but we believe reports of good results of surgery in older children with these defects may represent a selected population of whom some have died in infancy without being exposed to the benefits of surgical treatment. The major benefit of the hypothermic arrest technique is that it allows accurate repair in a bloodless, motionless operative field unencumbered by venous cannulae, especially valuable in the very small heart. This is particularly applicable to the transatrial repair of the transposition complexes, atrioventricularis communis, ventricular septal defect, and total anomalous pulmonary venous connection. Good results of the technique are predicated on an accurate preoperative diagnosis and an unhurried, careful repair of the heart, protecting the myocardium, and avoiding damage to essential structures such as valves and conduction tissue. Our philosophy is that if the diagnosis is correct, and the operation carried out carefully enough, the patient should do well regardless of age. The risk of cerebral damage during hypothermic arrest is clearly worrisome, and is at the present time the only potential drawback of the technique. The recent report of Wright et al.24 suggests that the risk of intellectual impairment may be real, but other
authors21'22 have described a normal spectrum of intelligence on careful follow-up of their patients. We have not noted any developmental abnormality, either mental or physical, in our patients, with the single exception of the child described above, who appears to be recovering completely. There have also been reports of isolated instances of neurologic rather than intellectual impairment using the hypothermic arrest technique, but we have not seen choreoathetoid movements, discoordination, nor prolonged seizure activity in this series. It will be important for all groups using the technique to review their own long-term results, as it is possible that minor variations in operative management may explain the apparently disparate results of neuropsychiatric follow-up. Even if there is some risk of reduction in cerebral function following hypothermic arrest, the balance may still favor the method because of increased survival, especially in particularly challenging defects in neonates. The improvement in hospital survival over the period of the study suggests that experience does indeed increase survival, but even initially there was no undue mortality nor morbidity when the severity of the defect is considered. This improvement is partially explained by the inclusion of more patients with less serious defects, such as a one year old child with uncomplicated ventricular septal defect, as confidence in the technique was gained. Early in the study period such an infant might have been handled with conventional perfusion methods. Increased familiarity with the technique has in fact encouraged us to repair more serious defects in infancy, and allowed the increased use of such techniques as transatrial repair of ventricular septal defect, which may be difficult in very small children with standard methods of perfusion. Clearly prognosis depends on the anatomic situation present in the child regardless of whether hypothermic arrest or conventional perfusion is used. For instance, in "tetralogy type" defects the chance of survival depends on the characteristics of the outflow tract and pulmonary arteries. Patients with severe valvular defects and complicated supravalvular de-
442
BENDER AND OTHERS
fects, such as persistent truncus arteriosus, will still have an increased mortality, and those with "uncorrectable" lesions such as the hypoplastic left heart syndromes will still have a bad prognosis, regardless of perfusion technique. We believe, however, that when allowance is made for the gravity of the procedures undertaken, the results obtainable with the hypothermic arrest technique will compare favorably with the current results attained using standard cardiopulmonary bypass in neonates.'9 There are some lesions for which the hypothermic arrest technique is not particularly helpful, an example being isolated obstruction of the left ventricular outflow tract. The hypertrophied left ventricle may well be at increased risk during surface cooling, and these hearts are more liable to show dysrhythmias. A more prudent technique for these infants is low flow and hypothermia to 22-25°. If excessive venous return is a problem, a short period of arrest may be undertaken without removal of the cannulae. Infants with severely symptomatic transposition of the great arteries, either simple or complex, persistent truncus arteriosus, atrioventricularis communis, as well as some other less common lesions, can be added to the group8""l 22 meriting early definitive operation because of the improvement in the quality of the repair brought about by the use of hypothermic arrest, and the consequent reduction in the chance of operative error. The successful renaissance of the Senning operation14"16 in particular attests to improvements in operative technology, and many children with various transposition complexes can undergo satisfactory repair shortly after birth. We have had no hospital mortality in our patients having the Senning operation including five undergoing operation in the first two months of life. It now appears that the trend towards the early, definitive repair of complicated congenital heart defects has physiologic merit. It has been our experience, as stated above, that these operations are facilitated by the use of profound hypothermia and circulatory arrest allowing anatomic repair with low morbidity and mortality. If, in the future, the clinical courses of these children remain free of hemodynamic and developmental complications, the early, complete repair of congenital cardiac malformations using this technique appears to be justified, thereby avoiding the metabolic and developmental derangements produced by prolonged cardiac decompensation. References 1. Aoyagi, M., Flasterskin, A. H., Barnette, J., et al.: Cerebral Effects of Profound Hypothermia (18°C) and Circulatory Arrest. Circulation, 49,50(suppl 2):60, 1974. 2. Barrett-Boyes, B. G., Simpson, M. J. and Neutze, J. M.:
3. 4.
5.
6.
7. 8. 9.
10. 11.
12. 13.
14. 15. 16.
17. 18. 19. 20. 21.
22.
23. 24.
Ann. Surg. * October 1979
Intracardiac Surgery in Neonates and Infants Using Deep Hypothermia with Surface Cooling and Limited Cardiopulmonary Flow. Circulation, 43-44(suppl 1):25, 1971. Bernhard, W. F., Litwin, S. B., Williams, W. W., et al.: Recent Results of Cardiovascular Surgery in Infants in the First Year of Life. Am. J. Surg., 123:451, 1972. Breckenridge, I. M., Oelert, H., Graham, G. R., et al.: Openheart Surgery in the First Year of Life. J. Thorac. Cardiovasc. Surg., 65:58, 1973. Brunberg, J. A., Reilly, E. L. and Doty, D. B.: Central Nervous System Consequences in Infants of Cardiac Surgery Using Deep Hypothermia and Circulatory Arrest. Circulation, 49,50(suppl 2):60, 1974. Caldwell, III, T. B., Blunk, J. N. and Escobar, A.: Experience with Deep Hypothermia and Elective Circulatory Arrest for Cardiac Surgery in Infants. South. Med. J., 70: 681, 1977. Castaneda, A. R., Lamberti, J., Sade, R. M., et al.: Openheart Surgery During the First Three Months of Life. J. Thorac. Cardiovasc. Surg., 68:719, 1974. Castaneda, A. R., Freed, M. D., Williams, R. G. and Norwood, W. I.: Repair of Tetralogy of Fallot in Infancy. J. Thorac. Cardiovasc. Surg., 74:372, 1977. Hallman, G. L. and Cooley, D. A.: Cardiovascular Surgery in Newborn Infants: Results in 1,050 Patients Less Than One Year Old. Ann. Surg., 173:1007, 1971. Hikasa, Y., Shirotani, H. and Satomura, K.: Open-heart Surgery in Infants with the Aid of Hypothermic Anesthesia. Arch. Jap. Chir., 36:495, 1967. Katz, N. M., Kirklin, J. W. and Pacifico, A. D.: Concepts and Practices in Surgery for Total Anomalous Pulmonary Venous Connection. Ann. Thorac. Surg., 25:479, 1978. Mahle, S., Nicoloff, D. M., Knight, L. and Moller, J. H.: Pulmonary Artery Banding: Long-term Results in 63 Patients. Ann. Thorac. Surg., 27:216, 1979. Muraoka, R., Hikasa, Y., Shirotani, H., et al.: Open-heart Surgery in Infants Under Two Years of Age Using Deep Hypothermia with Surface Cooling and Partial Cardiopulmonary Bypass. J. Cardiovasc. Surg., 15:231, 1974. Parenzan, L., Locatelli, G., Alfieri, O., et al.: The Senning Operation for Transposition of the Great Arteries. J. Thorac. Cardiovasc. Surg., 76:305, 1978. Paton, B. C., Stewart, J. R., Nora, J. J., et al.: Pulmonary Artery Banding for Ventricular Septal Defect with Pulmonary Hypertension. Arch. Surg., 112:1454, 1977. Quaegebeur, J. M., Rohmer, J., Brom, A. G. and Tinkelenberg, J.: Revival of the Senning Operation in the Treatment of Transposition of the Great Arteries. Thorax, 32: 517, 1977. Rittenhouse, E. A., Mohri, H., Dillard, D. H. and Merendino, K. A.: Deep Hypothermia in Cardiovascular Surgery. Ann. Thorac. Surg., 17:63, 1974. Sade, R. M., Williams, R. G. and Castaneda, A. R.: Corrective Surgery for Congenital Cardiovascular Defects in Early Infancy. Am. Heart J., 90:656, 1975. Shuichiro, S. and Starr, A.: Cardiopulmonary Bypass in Infants Under Four Months of Age. J. Thorac. Cardiovasc. Surg., 73:894, 1977. Smith, D. L., Wilson, J. M. and Ebert, P. A.: Cardiac Surgery in Infants Up to One Year Old. Cardiovasc. Med. 3:925, 1978. Steven, J. G., Stone, E. F., Dillard, D. H. and Morgan, B. C.: Intellectual Development of Children Subjected to Prolonged Circulatory Arrest During Hypothermic Open Heart Surgery in Infancy. Circulation, 49,50(suppl 2):54, 1974. Wagner, H. R. and Subramanian, S.: Deep Hypothermia in Infant Cardiac Surgery. Pediatrics, 61:479, 1978. Wood, W. C., McCue, C. M. and Lower, R. R.: BlalockTaussig Shunts in the Infant. Ann. Thorac. Surg., 16: 454, 1973. Wright, J. S., Hicks, R. G. and Newman, D. C.: Deep Hypothermic Arrest: Observations on Later Development in Children. J. Thorac. Cardiovasc. Surg., 77:466, 1979.
