| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Ann Thorac Surg 1996;61:783-787
© 1996 The Society of Thoracic Surgeons
Departments of Surgery and Pediatrics, Loma Linda University Medical Center, Loma Linda, California
 |
Abstract |
|---|
 TopFootnotes Abstract IntroductionPatients and MethodsResultsCommentReferences |
|---|
Methods. We prospectively studied the neurodevelopmental outcome in 38 infants undergoing cardiac transplantation using DHCA before the age of 4 months (mean age, 37.0 days). Neurodevelopmental outcome in the 22 boys and 16 girls was tested up to 2.5 years after transplantation using the Bayley scales of infant development. Bayley scores were compared with the rate of core cooling and the length of DHCA in all patients. Deep hypothermic circulatory arrest was accomplished using an asanguineous prime resulting in hematocrits of 5% +/- 5% and ionized Ca2+, 0.4 +/- 0.1 mmol/L. No surface precooling was used, but the head was packed in ice. Mean core cooling time was 14.0 +/- 3.5 minutes, resulting in rectal temperatures of 18° +/- 2.5°C. Duration of DHCA ranged from 42 to 70 minutes (mean duration, 56.0 +/- 6.6 minutes).
Results. Postoperatively, the mean Bayley psychomotor development index was 91 (range, 50 to 130) and mental developmental index was 88 (range, 50 to 130). No relationship was found between either the rate of cooling or the duration of DHCA and the Bayley scores (r = 0.227 and r = 0.322, respectively).
Conclusions. These data suggest that neither the rate of cooling nor DHCA times between 42 and 70 minutes using profoundly low ematocrits and low ionized calcium levels has any measurable effect on neurologic outcome up to 2.5 years postoperatively. It is possible that adverse neurologic outcomes from DHCA reflect particular methods of achieving DHCA.
|
Introduction |
|---|
|
TopFootnotesAbstractIntroductionPatients and MethodsResultsCommentReferences |
|---|
The use of deep hypothermic circulatory arrest (DHCA) during cardiac operations in infants is common but controversial. Cardiac transplantation that requires aortic arch reconstruction and many intracardiac repairs in infants is facilitated by a bloodless field. The safety of hypothermic arrest depends on the resultant decrease in metabolism and therefore oxygen consumption, especially in the central nervous system at low temperatures. Also, hypothermia protects against ischemic damage by preserving high intracellular pH and high-energy phosphates [1, 2]. However, the limiting factor during low-flow states and circulatory arrest is protection of the brain from injury, because this organ is sensitive to ischemic or hypoxic injury [3]. The neurologic effects that follow DHCA remain controversial [4–10]. Moreover, because the techniques of DHCA have never been standardized, it is difficult to ascertain what part of DHCA procedures is injurious. Indeed, it is believed that some portion of neuropsychologic disability in infants with congenital heart lesions requiring cardiac surgical intervention early in life results from the support techniques used to protect vital organs such as the brain perioperatively [10]. Finally, unless the microcirculation is protected, any efforts to protect the end organ (ie, the brain) will ultimately fail when circulation is reestablished.
For editorial comment, see page 779.
The purpose of this prospective study was to ascertain if correlation exists between core cooling rates or length of DHCA and neurodevelopmental outcome after infant cardiac transplantation. This group of recipients was selected because the operative technique was uniform, the heart was ``normal'' after transplantation, and serial studies could be performed on a local ``captive'' patient group with extensive and 100% follow-up.
|
Patients and Methods |
|---|
|
TopFootnotesAbstractIntroductionPatients and MethodsResultsCommentReferences |
|---|
Surgical Methodology
Anesthesia management was standardized. Premedication consisted of oral administration of atropine sulfate, 20 µg/kg. Induction was achieved with intravenous administration of fentanyl, 40 µg/kg, and pancuronium bromide, 0.2 mg/kg, followed by endotracheal intubation and mechanical ventilation. Because systemic perfusion was ductal dependent, infants were hypoventilated to maintain partial carbon dioxide tension higher than 45 mm Hg, and ventilation was accomplished with room air. Arterial and venous lines were placed for monitoring mean arterial pressure, pH, blood gases, and hematocrit. No surface precooling was used, but the head was packed in ice beginning at the time of preparation and continued during core cooling on cardiopulmonary bypass (CPB) and circulatory arrest.
The conduct of bypass has been described previously [11]. Briefly, the patient was heparinized with 400 IU/kg of heparin sodium at the time the head was packed in ice. The bypass circuit was primed with 700 mL of Normosol R to which was added 100 mL of 25% albumin and 25 mEq of NaHCO3. Methylprednisolone sodium succinate, 25 mg/kg, was administered before bypass and again at the initiation of rewarming. Specifically, no red cells or mannitol was used in the priming circuit. Arterial cannulation was through the patent ductus arteriosus, which was snared to direct flow to the aorta. A single cannula in the right atrium provided venous drainage. The CPB circuit used a membrane oxygenator (model 308; Terumo, Tokyo, Japan) and a nonpulsatile pump that delivered blood at a minimum rate of 25 mL•kg-1• min-1 and a maximum rate of 150 mL•kg-1•min-1. The pH management was done according to the alpha-stat principles [12].
The patient was placed on CPB and core cooled to a rectal temperature of 18° +/- 2.5°C. Arterial inflow perfusate temperature was not allowed to go lower than 15°C. Length of cooling or rate of cooling varied by individual patient or surgeons preference but was as rapid as possible. Deep hypothermic circulatory arrest commenced after the patient's blood was drained and circulation stopped. Cardiac transplantation was then performed; details have been described elsewhere [11]. Hematocrits on CPB were 5% +/- 5%, and ionized calcium levels were 0.4 +/- 0.1 mmol/L during cooling and at initial rewarming. After transplantation, the heart and great vessels were deaired before resumption of CPB and rewarming. Ice packs around the head were removed. Rewarming was begun at low flow (25 mL•kg-1•min-1) and low arterial pressure (10 to 20 mm Hg), with flows gradually increased over a 10-minute period. Washed, irradiated packed red blood cells and fresh frozen plasma were added gradually to the bypass circuit over a 30-minute period to elevate the hematocrit to 25%. Calcium gluconate (to normalize ionized calcium levels) was added to the circuit only after 30-minutes of reperfusion. Maximum arterial inflow temperature during rewarming was 10°C higher than rectal temperature. Rewarming and reperfusion were continued for 1 hour. The patient was then weaned from CPB and decannulated, and the chest was closed in standard fashion after the administration of protamine sulfate.
Neurologic and Developmental Methodology
A pediatric neurologist evaluated each patient before and after operation. Neurodevelopmental outcome in the 22 boys and 16 girls was serially tested by a pediatric occupational therapist for up to 30 months after cardiac transplantation (at 12, 18, and 30 months of age) using the Bayley scales of infant development [13]. This test is composed of two parts: a mental development index (MDI) and a psychomotor development index (PDI). The standardized mean for both the MDI and PDI is 100 with two standard deviations of 68 to 132. All patients were at least 1 year of age at test time, and the oldest was 30 months of age. Bayley scores (MDI and PDI, respectively) were compared with the rate of core cooling and the length of DHCA to determine the effect of cooling and DHCA on mental and psychomotor development. The patients were also observed for other neurologic deficits like seizures and choreoathetosis.
Statistical evaluation was done using linear regression analysis.
|
Results |
|---|
|
TopFootnotesAbstractIntroductionPatients and MethodsResultsCommentReferences |
|---|
Mean core cooling was achieved in 14.0 +/- 3.5 minutes (range, 9 to 24 minutes) (Fig 1
). This resulted in average rectal and esophageal temperatures of 18° +/- 2.5°C (range, 16° to 23°C) and 16° +/- 2.0°C (range, 14° to 18°C), respectively.
|
). Likewise, there was no correlation between duration of DHCA and neurodevelopmental outcome (r = 0.322 and r = 0.120 for PDI and MDI, respectively) (Fig 3). The distribution of Bayley scores is shown in Figure 4. No patient had choreoathetosis, and no patient was on a regimen of antiseizure medication.
|
|
|
|
Comment |
|---|
|
TopFootnotesAbstractIntroductionPatients and MethodsResultsCommentReferences |
|---|
Considerable controversy surrounds the use of DHCA; many authors [4–6] have provided laboratory or clinical evidence that DHCA causes cerebral damage and thus produces neurologic sequelae postoperatively. Although there is general agreement that the period of DHCA should be less than 60 minutes, the techniques of DHCA have never been standardized, and the safe arrest period for any given temperature is uncertain [7]. Griepp and Griepp [15] have identified some general perioperative risk factors associated with a less favorable cerebral outcome after DHCA including prolonged duration of DHCA (usually >60 minutes), advanced patient age, rapid cooling, hyperglycemia either before DHCA or during reperfusion, preoperative cyanosis or lack of adequate hemodilution, evidence of increased oxygen extraction before DHCA or during reperfusion, and delayed reappearance of the electroencephalogram or marked electroencephalographic abnormality.
Recently, Newburger and associates [16] compared the perioperative neurologic effects of hypothermia and support consisting chiefly of DHCA versus mainly low-flow CPB in 171 infants undergoing repair of D-transposition with or without ventricular septal defect before the age of 3 months. They reported a higher incidence of perioperative (first 48 hours) epileptiform activity on continuous electroencephalographic monitoring and clinical seizures in the DHCA group. Perhaps more importantly, they found no significant difference on the electroencephalogram obtained 1 week postoperatively or on the neurologic examination at the time of hospital discharge between the two groups. It is noteworthy that certain differences exist between their method of DHCA and ours. First, they used a sanguineous prime with resulting bypass hematocrits of 25% versus our asanguineous prime. Second, they used much longer cooling times prior to arrest.
These differences demonstrate that there is no standardized way of performing DHCA; hence it is difficult, if not impossible, to implicate DHCA in an adverse outcome unless all of its parts are examined. The areas where DHCA techniques vary among our study and other studies include the use of surface versus core cooling, the rate of cooling, the type of CPB perfusate or prime (sanguineous versus asanguineous), the duration of DHCA, and the method of rewarming and reperfusion.
Institutional preference usually determines the mode of cooling used. Surface cooling may result in fewer metabolic abnormalities [17] and more uniform cooling of organs [18], but studies [19] have shown no significant differences in body metabolism between this method and core cooling. In this study, we did not use surface cooling. Core cooling was rapidly achieved within an average of 14.0 minutes, and we did not find an association between this and the Bayley scores, ie, no adverse neurologic sequelae. This result contradicts that of Bellinger and co-workers [10], who found a significant association between core-cooling periods of less than 20 minutes and slower development in 28 children who underwent corrective cardiac operation in early infancy. We think that their use of surface cooling prior to core cooling on CPB may have been responsible for such a finding, as problems in maintaining adequate tissue perfusion can occur with surface cooling [20].
Indeed, Kern and colleagues [21] found that differences in cooling techniques used during CPB may alter the efficiency of brain cooling and thus cerebral protection during DHCA. In comparing the effect of rapid versus gradual core cooling on jugular venous oxygen saturation, they found a significant difference between arterial oxygen saturation and jugular venous oxygen saturation between the two groups at the point of complete cooling. Specifically, the measured jugular versus oxygen saturation and the difference between arterial oxygen saturation and jugular venous oxygen saturation were 98.0% +/- 0.9% and 0.3% +/- 0.5%, respectively, in the rapid-cooling group versus 86.2% +/- 12% and 10.8% +/- 12.2%, respectively, in the gradually cooled group (p < 0.01). Their data suggest that adequate brain cooling (cerebral protection) was not achieved by gradual cooling, as the brain remained metabolically active and at the time of circulatory arrest, was still extracting large amounts of the oxygen supplied during CPB.
Although some studies [4–6] have found an association between duration of DHCA and postoperative adverse neurologic outcome, others [7–10] including this study have not done so. Interestingly, some of the patients with the longest DHCA times in our study had the best Bayley scores (see Fig 3
).
We believe that the use of asanguineous CPB perfusate (resulting in a hematocrit of about 5% and an ionized calcium level of 0.4 mmol/L on bypass) is more advantageous than solutions with higher hematocrits (20% to 22%) as used in some institutions and in most clinical and experimental reports on the adverse effects of DHCA. Our reasons are as follows: First, at the low temperatures required for DHCA, the oxygen dissociation curve is shifted to the left; excess hemoglobin binds tightly to oxygen, which is not released to tissues [22]. Thus, almost all oxygen delivery is from oxygen dissolved in the perfusate, thereby making red cells superfluous during hypothermia. Second, at low temperatures, red blood cells tend to form a rouleau, which can lodge in the microvasculature. In fact, red cells lose their ability to deform at low temperatures, an ability that is critical to pass through the microcirculation. One may imagine that if inflexible red cells are clumped in the microvasculature, reperfusion will not occur. In an analogous situation involving the hematocrit of blood cardioplegic solutions, our group [23] found profound atrioventricular node conduction disturbances with a cold blood cardioplegia hematocrit of 20%, all of which disappeared when the hematocrit of the cardioplegia was lowered to 12%. Last, the low calcium content of the perfusate may decrease the incidence of the no-reflow phenomenon, which is thought to be the result of ischemia-induced vasoconstriction mediated by the influx of calcium into vascular smooth muscle [24]. This vasoconstrictive effect will involve not only the cerebral vasculature but also the coronary vessels.
We [25] have previously shown that use of an asanguineous, low-calcium CPB perfusate and a calcium-channel blocker influences the successful resuscitation and reanimation of severely ischemic warm hearts used for transplantation. It is possible that such perfusate modification would have a similar beneficial effect on the brain, which is equally susceptible to ischemia during DHCA. Indeed, others [26] have shown that neuronal cell membrane damage from the calcium paradox phenomenon can be prevented by the use of calcium-channel blockers or calcium-free perfusate. Although the exact role of calcium in the brain during perfusion and reperfusion after DHCA awaits further investigation, the foregoing discussion suggests that there is far more to DHCA than the mere cessation of blood flow and that what we now view as uncontrollable outcomes of ischemia are, in fact, easily preventable or at least modifiable.
Nevertheless, we recognize that our study has certain limitations including the small population and the lack of a control group with similar characteristics who were treated using a different DHCA technique. Also, because multiple factors can contribute to the neurologic development of infants with serious congenital heart diseases and because as many as 45% of patients with hypoplastic left heart syndrome sustain hypoxic brain injury or intracranial hemorrhage [27], it is difficult to delineate the exact effect of DHCA on neurologic outcome irrespective of the method employed. This awaits further studies.
In summary, our data from 38 infants undergoing DHCA for cardiac transplantation suggest that neither the rate of core cooling, the length of cooling, nor DHCA times between 42 and 70 minutes using profoundly low hematocrits and low ionized calcium levels has any measurable effect on neurologic outcome up to 3 years postoperatively. It is possible that the adverse neurologic outcomes reported to be associated with DHCA reflect the particular methods of achieving DHCA, although our data do not provide conclusive information on this. To determine the ideal technique for DHCA will require prospective studies that specifically address surface versus core cooling, rate of cooling, sanguineous versus asanguineous CPB perfusate, length of DHCA, reperfusion methods, and their effects on postoperative neurodevelopment. We believe that insight into the beneficial and adverse effects of DHCA will be forthcoming only when all of the parts of CPB as delineated here are examined. In short, the part that circulatory standstill plays in producing neurologic injury (if any occurs) is unclear.
|
Footnotes |
|---|
|
TopFootnotesAbstractIntroductionPatients and MethodsResultsCommentReferences |
|---|
Address reprint requests to Dr Gundry, Division of Cardiothoracic Surgery, Department of Surgery, Loma Linda University Medical Center, 11234 Anderson St, Loma Linda, CA 92354.
|
References |
|---|
|
TopFootnotesAbstractIntroductionPatients and MethodsResultsCommentReferences |
|---|
Related Articles
This article has been cited by other articles:
|
|
 |
|
  A. A. Kon, L. Ackerson, and B. Lo How Pediatricians Counsel Parents When No "Best-Choice" Management Exists: Lessons to Be Learned From Hypoplastic Left Heart Syndrome Arch Pediatr Adolesc Med, May 1, 2004; 158(5): 436 - 441. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W. C. Oliver Jr, F. M. Beynen, G. A. Nuttall, D. R. Schroeder, M. H. Ereth, J. A. Dearani, and F. J. Puga Blood loss in infants and children for open heart operations: albumin 5% versus fresh-frozen plasma in the prime Ann. Thorac. Surg., May 1, 2003; 75(5): 1506 - 1512. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. M. Forbess, K. J. Visconti, C. Hancock-Friesen, R. C. Howe, D. C. Bellinger, and R. A. Jonas Neurodevelopmental Outcome After Congenital Heart Surgery: Results From an Institutional Registry Circulation, September 24, 2002; 106(12_suppl_1): I-95 - I-102. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. M. Forbess, K. J. Visconti, D. C. Bellinger, R. J. Howe, and R. A. Jonas Neurodevelopmental outcomes after biventricular repair of congenital heart defects J. Thorac. Cardiovasc. Surg., April 1, 2002; 123(4): 631 - 639. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Sakamoto, D. Zurakowski, L. F. Duebener, S.'i. Hatsuoka, H. G.W. Lidov, G. L. Holmes, U. A. Stock, P. C. Laussen, and R. A. Jonas Combination of alpha-stat strategy and hemodilution exacerbates neurologic injury in a survival piglet model with deep hypothermic circulatory arrest Ann. Thorac. Surg., January 1, 2002; 73(1): 180 - 189. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. J. Cook, U. S. Boston, T. A. Orszulak, and J. M. Slater Carbon dioxide management and the cerebral response to hemodilution during hypothermic cardiopulmonary bypass in dogs Ann. Thorac. Surg., October 1, 2001; 72(4): 1331 - 1335. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. M. Forbess, K. J. Visconti, D. C. Bellinger, and R. A. Jonas Neurodevelopmental Outcomes in Children After the Fontan Operation Circulation, September 18, 2001; 104(90001): I-127 - 132. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Suominen, R. Palo, H. Sairanen, K.T. Olkkola, and J. Rasanen Perioperative determinants and outcome of cardiopulmonary arrest in children after heart surgery Eur. J. Cardiothorac. Surg., February 1, 2001; 19(2): 127 - 134. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Wernovsky, K. M. Stiles, K. Gauvreau, T. L. Gentles, A. J. duPlessis, D. C. Bellinger, A. Z. Walsh, J. Burnett, R. A. Jonas, J. E. Mayer Jr, et al. Cognitive Development After the Fontan Operation Circulation, August 22, 2000; 102(8): 883 - 889. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. K. Kirklin Pediatric cardiac transplantation Ann. Thorac. Surg., May 1, 2000; 69(5): 1627 - 1628. [Full Text] [PDF]
|
|
|
|
 |
|
 H. Sungurtekin, D. J. Cook, T. A. Orszulak, R. C. Daly, and C. J. Mullany Cerebral Response to Hemodilution During Hypothermic Cardiopulmonary Bypass in Adults Anesth. Analg., November 1, 1999; 89(5): 1078 - 1078. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. J Elliott Recent advances in paediatric cardiopulmonary bypass Perfusion, July 1, 1999; 14(4): 237 - 246. [PDF]
|
|
|
|
|
|
D. L. Reich, S. Uysal, M. Sliwinski, M. A. Ergin, R. A. Kahn, S. N. Konstadt, J. McCullough, M. R. Hibbard, W. A. Gordon, and R. B. Griepp NEUROPSYCHOLOGIC OUTCOME AFTER DEEP HYPOTHERMIC CIRCULATORY ARREST IN ADULTS J. Thorac. Cardiovasc. Surg., January 1, 1999; 117(1): 156 - 163. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. H. Hovels-Gurich, M.-C. Seghaye, S. Dabritz, B. J. Messmer, and G. von Bernuth COGNITIVE AND MOTOR DEVELOPMENT IN PRESCHOOL AND SCHOOL-AGED CHILDREN AFTER NEONATAL ARTERIAL SWITCH OPERATION J. Thorac. Cardiovasc. Surg., October 1, 1997; 114(4): 578 - 585. [Abstract] [Full Text]
|
|
|
|
|
|
P. J. del Nido Myocardial Protection and Cardiopulmonary Bypass in Neonates and Infants Ann. Thorac. Surg., September 1, 1997; 64(3): 878 - 879. [Full Text]
|
|
|
|
|
|
R. A. Jonas Deep Hypothermic Circulatory Arrest: A Need for Caution Ann. Thorac. Surg., March 1, 1996; 61(3): 779 - 780. [Full Text]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| ANN THORAC SURG | ASIAN CARDIOVASC THORAC ANN | EUR J CARDIOTHORAC SURG |
| J THORAC CARDIOVASC SURG | ICVTS | ALL CTSNet JOURNALS |
