The optimal degree of hemodilution during profoundly hypothermic cardiopulmonary bypass (CPB) remain controversial, and widely disparate hemodilution protocols have evolved at centers undertaking infant cardiac surgery. Higher hematocrit (hct) exposes patients to the risks of microvascular occlusion, while lower hct may critically limit oxygen delivery to the brain and other organs. Preliminary data suggest 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. In a single-center, prospective, randomized trial, hemodilution to a hct of 30 percent vs. 20 percent will be compared with respect to neurodevelopmental outcome and early postoperative course in a homogeneous population of infants with d-transposition of the great arteries undergoing the arterial switch operation.
Specific Aim 1 will test the hypothesis that hemodilution to a hct of 30 percent, compared to 20 percent, will be associated with superior central nervous system protection. Our primary outcome variable will be developmental outcome at age 1 year, assessed with the 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 on MRI.
Specific Aim 2 will test the hypothesis that hemodilution to a hct of 30 percent, compared to 20 percent, will be associated with better early postoperative cardiovascular status. Our primary outcome measure will be the minimum cardiac index over the first postoperative 24 hours. 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 variable 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.
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