The Influence of Hypercapnia (↑CO 2 ) on Neonatal Brain Injury: How High is Too High? Jeffrey R. Kaiser, MD, MA Section

1. Center for Translational Neuroscience Seminar Series Tuesday, September 16, 2008, 12 noon Rayford Auditorium, Biomed II Bldg. The Influence of Hypercapnia (↑CO2) on Neonatal Brain Injury: How High is Too High? Jeffrey R. Kaiser, MD, MA Section of Neonatology Depts. of Pediatrics and Obstetrics & Gynecology UAMS

2. Annually, 5,000 extremely low birth weight (9 ounces-2 lbs, 3 ounces) infants born in the US survive with severe brain bleeds (intraventricular hemorrhage); this devastating complication is associated with mental retardation and cerebral palsy, 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 costs underscore the need for developing strategies that may limit severe bleeding in the brain. The overall goal of our research is to evaluate disturbances of brain blood flow in order to predict which of infants are at highest risk and to develop better intensive care techniques that will limit severe brain injury. Neonatologists around the world practice a ventilatory strategy called permissive hypercapnia, where CO2 levels are permitted to be quite high in order to lessen ventilator-induced lung injury. Despite 3 randomized trials that reported no pulmonary benefit, and one study that demonstrated significantly worse neurological outcomes, this practice continues. We have retrospectively shown that elevated CO2 is associated with developing severe intraventricular hemorrhage. Further, we were the first to show in ventilated premature infants that increasing hypercapnia is associated with progressively impaired cerebral autoregulation. This is important because infants with impaired cerebral autoregulation develop worse brain injury in the early neonatal period than those with intact autoregulation. We are currently evaluating in a randomized controlled trial whether permissive hypercapnia is in fact associated with worse brain injury. We hypothesize that ventilation strategies that promote normal CO2 levels will normalize brain blood flow and lead to less bleeding in the brain.