Physiological Disturbances Associated With Neonatal Intraventricular Hemorrhage (PhysDis)

Annually, almost 5,000 extremely low birth weight (9 ounces to about 2 lbs) infants born in the US survive with severe bleeding in the brain (intraventricular hemorrhage); this devastating complication of prematurity is associated with many problems, including mental retardation, cerebral palsy, and learning disabilities, that result in profound individual and familial consequences. In addition, lifetime care costs for these severely affected infants born in a single year exceed $3 billion. The huge individual and societal costs underscore the need for developing care strategies that may limit severe bleeding in the brain of these tiny infants. The overall goal of our research is to evaluate disturbances of brain blood flow in these tiny infants in order to predict which of them are at highest risk and to develop better intensive care techniques that will limit severe brain injury. Since most of these infants require ventilators (respirators) to survive, we will investigate how 2 different methods of ventilation affect brain injury. We believe that a new method of ventilation, allowing normal carbon dioxide levels, will normalize brain blood flow and lead to less bleeding in the brain. We will also examine how treatment for low blood pressure in these infants may be associated with brain injury. We believe that most very premature infants with low blood pressure actually do worse if they are treated. We think that by allowing the infants to normalize blood pressure on their own will allow them to stabilize blood flow to the brain leading to less intraventricular hemorrhage. In 10 premature infants with severe brain bleeding, we have developed a simple technique to identify intraventricular hemorrhage before it happens. Apparently, the heart rate of infants who eventually develop severe intraventricular hemorrhage is less variable than infants who do not develop this. We plan to test this method in a large group of infants, to be able to predict which infants are at highest risk of developing intraventricular hemorrhage and who could most benefit from interventions that would reduce disturbances of brain blood flow.

hypercapnia, normocapnia, chronic lung disease, periventricular leukomalacia, intraventricular hemorrhage, hypotension, cerebral autoregulation, heart rate variability, autonomic nervous system, detrended fluctuation analysis

Hypercapnic ventilation. The goal will be to maintain transcutaneous CO2 55 mm Hg (50-60 mm Hg) during the first week of life, or until extubation. A written, laminated hypercapnic ventilator algorithm will be placed at the bedside.

Normocapnic ventilation. The goal will be to maintain transcutaenous CO2 40 mm Hg (35-45 mm Hg) during the first week of life, or until extubation. A written, laminated normocapnic ventilator algorithm will be placed at the bedside.

The effect of hypercapnia vs. normocapnia on the development of Grade II-IV intraventricular hemorrhage/periventricular leukomalacia (severe brain injury) and/or death

During first 2 weeks of life (intraventricular hemorrhage and/or death), initial hospitalization for periventricular leukomalacia

The effect of hypercapnia vs. normocapnia on the development of chronic lung disease (requirement of supplemental oxygen at 36 weeks corrected gestational age)

Inclusion Criteria: ventilated ELBW (401-1000 grams) infants 23 to 30 weeks' gestation umbilical arterial catheter placed during newborn resuscitation Exclusion Criteria: presence of complex congenital anomalies or chromosomal abnormality presence of central nervous system malformation infants with hydrops fetalis infants in extremis infants with early (<3 hour of age) intraventricular hemorrhage

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