To compare hemodilution to a hematocrit of 35 percent versus a hematocrit of 25 percent during hypothermic cardiopulmonary bypass in infants with d-transposition of the great arteries.

BACKGROUND: The optimal degree of hemodilution during profoundly hypothermic cardiopulmonary bypass (CPB) remains controversial, and widely disparate hemodilution protocols have evolved at centers undertaking infant cardiac surgery. Hematocrit (hct), a measurement of the volume of red cells, is of interest in cardiopulmonary bypass. Higher hematocrit exposes patients to the risks of microvascular occlusion, while lower hct may critically limit oxygen delivery to the brain and other organs. Preliminary data suggests that a higher hct provides superior brain and myocardial protection, but no randomized trials of outcome after use of higher vs. lower hct have been reported.

DESIGN NARRATIVE: In the single-center, prospective, randomized trial, hemodilution to a hct of 35 percent vs. 25 percent will be compared with respect to neurodevelopmental outcome and early postoperative course in a homogeneous population of infants with congenital heart disease. Specific Aim 1 will test the hypothesis that hemodilution to a hct of 35 percent, compared to 25 percent, will be associated with superior central nervous system protection. The primary outcome variable will be developmental outcome at age 1 year, assessed using a Bayley Scales of Infant Development. Secondary outcome variables include 1) tissue release of S-100 protein as a measure of cerebral cellular injury; 2) cerebral hemodynamics and oxygenation, determined by near infrared spectroscopy (NIRS); 3) intrinsic cerebral vasoregulation, measured by NIRS and transcranial Doppler; and 4) at age 1 year, neurologic examination, the MacArthur inventory, and structural and volumetric findings of magnetic resonance imaging (MRI).

Specific Aim 2 will test the hypothesis that hemodilution to a hct of 35 percent, compared to 25 percent, will be associated with better early postoperative cardiovascular status. The primary outcome measure will be serum lactate 1 hour after the surgery. Secondary outcome measures will include 1) the duration of postoperative endotracheal intubation, ICU stay, and hospital stay; 2) serum lactate levels; 3) the PaO2/FiO2 ratio; 4) levels of circulating pro-inflammatory cytokines; and 5) the percent change in total body water, estimated by bioelectrical impedance. The structure of the study will allow assessment of whether 1-year outcomes can be predicted by perioperative variables other than the hct strategies and, through the use of novel techniques such as NIRS and volumetric MRI, may provide insight into mechanisms by which hct and other perioperative variables affect the brain. The inferences reached in this study population should be broadly generalized to infants with other forms of congenital heart disease undergoing early repair and thus should have substantial impact on clinical practice.

Ages Eligible for Study:  up to  1 Year,  Genders Eligible for Study:  Both

Criteria