Correspondence
Developmental and Neurologic Status of Children after Heart Surgery
N Engl J Med 1995; 333:391-392August 10, 1995
- Article
To the Editor:
With respect to the study by Bellinger et al. (March 2 issue),1 in the large majority of newborns with transposition of the great arteries, in the absence of aortic-arch obstruction the arterial-switch operation can be performed with cardiopulmonary bypass and physiologic flow rates (minimum, 150 ml per kilogram of body weight per minute). Indeed, this has been the practice at my institution for the past 10 years in over 300 neonatal arterial-switch operations. Neither low-flow cardiopulmonary bypass nor circulatory arrest is required, except during closure of the atrial septal defect (about two minutes). In view of the subnormal neurodevelopmental scores in both treatment groups in the study by Bellinger et al., one can only speculate that patients who underwent surgery under conditions of full-flow cardiopulmonary bypass would have fared better.
1 ReferencesT.R. Karl, M.S., M.D.
Melbourne Royal Children's Hospital, Parkville 3052, Victoria, Australia1
Bellinger DC ,Jonas RA ,Rappaport LA , et al. Developmental and neurologic status of children after heart surgery with hypothermic circulatory arrest or low-flow cardiopulmonary bypass. N Engl J Med 1995;332:549-555
Full Text | Web of Science | Medline
To the Editor:
Since it is the consensus that brain damage in infants after open-heart surgery is primarily due to hypoperfusion, hypoxia, or ischemia, it is not surprising that Bellinger et al. found that the developmental and neurologic status of children one year after undergoing heart surgery with hypothermic circulatory arrest was less favorable than that of those who underwent heart surgery with low-flow bypass. However, all the infants had some period of circulatory arrest during surgery,1 and the performance on developmental testing was “considerably below average” in both treatment groups. We are concerned that other perioperative and intraoperative procedures may have contributed to this outcome. Glucose was not administered unless the blood level fell below 50 mg per deciliter (2.8 mmol per liter), a value only slightly higher than that accepted as hypoglycemic — 40 mg per deciliter (2.2 mmol per liter) — in the full-term newborn infant. During ischemia only glucose can subserve the synthesis of ATP for brain function and structural integrity. In contrast to the situation in the adult brain, in which it is well known that hyperglycemia potentiates hypoxic or ischemic brain damage, an increasing number of reports suggest that intraischemic hyperglycemia may be beneficial in the immature brain. Pretreatment with glucose increased the survival of infant mice in an atmosphere of pure nitrogen gas (survival rate, 82 percent, vs. 5 percent in controls) and prolonged the gasping of the isolated head.2 In the neonatal rat model of hypoxia or ischemia, doubling the blood glucose level reduced the volume of cerebral infarction by 50 percent,3 whereas a glucose level of 630 to 720 mg per deciliter (35 to 40 mmol per liter) protected the brain completely from ischemic damage.4
4 ReferencesJean Holowach Thurston, M.D.
Richard E. Hauhart, M.S.
Washington University School of Medicine, St. Louis, MO 631101
Newburger JW ,Jonas RA ,Wernovsky G , et al. A comparison of the perioperative neurologic effects of hypothermic circulatory arrest versus low-flow cardiopulmonary bypass in infant heart surgery. N Engl J Med 1993;329:1057-1064
Full Text | Web of Science | Medline2
Holowach-Thurston J ,Hauhart RE ,Jones EM . Anoxia in mice: reduced glucose in brain with normal or elevated glucose in plasma and increased survival after glucose treatment. Pediatr Res 1974;8:238-243
Web of Science | Medline3
Tuor UI ,Simone CS ,Arellano R ,Tanswell K ,Post M . Glucocorticoid prevention of neonatal hypoxic-ischemic damage: role of hyperglycemia and antioxidant enzymes. Brain Res 1993;604:165-172
CrossRef | Web of Science | Medline4
Reeves I ,Mujsce D ,Vannucci R . Extreme hyperglycemia (HG) protects the perinatal brain from hypoxic-ischemic (H-I) brain damage. Pediatr Res 1992;31:Suppl:352A-352A abstract.
Author/Editor Response
The authors reply:
To the Editor: We agree with Dr. Karl that a flow rate of 150 ml per kilogram of body weight per minute (which is equivalent to a cardiac index of approximately 2.5 liters per minute per square meter of body-surface area in the average neonate) is physiologic at normothermia, but we question whether such a flow rate is physiologic at a core temperature of 18°C or less. Numerous studies of cerebral blood flow and metabolic rate in animals and small children demonstrate that the cerebral metabolic rate at these temperatures is only 10 to 20 percent of that at 37°C and that even low-flow bypass at the rates used in our study provides ample cerebral perfusion, as judged by cerebral oxygen consumption and the metabolic rate. Furthermore, cardiopulmonary bypass itself is not a physiologic state and has multiple deleterious effects.1 Using full normothermic bypass flows at hypothermic temperatures, which are known to disable the normal vascular autoregulatory mechanisms of the brain, could well produce larger numbers of particulate and gaseous microemboli, as well as induce excess inflammatory mediators.
We share the concern of Dr. Thurston and Mr. Hauhart about the possible contribution of other factors, particularly glucose levels, to outcome. Analyses to address these issues are under way and suggest that lower, but not hypoglycemic, levels of blood glucose may be associated with perioperative indicators of neurologic damage. In addition, higher glucose levels are associated with less damage and might be protective, as suggested by Dr. Thurston and Mr. Hauhart and by experimental studies in immature animals.
1 ReferencesDavid C. Bellinger, Ph.D.
Richard A. Jonas, M.D.
Paul R. Hickey, M.D.
Children's Hospital, Boston, MA 02115- Citing Articles (1)
Citing Articles
1
Frank L. Hanley. (2005) Religion, politics…deep hypothermic circulatory arrest. The Journal of Thoracic and Cardiovascular Surgery 130:5, 1236.e1-1236.e8
CrossRef
