Pharmacokinetics of Ampicillin in Neonates With Moderate to Severe Hypoxic-Ischemic Encephalopathy Undergoing Controlled Hypothermia

Hypoxic-ischemic encephalopathy (HIE) affects approximately 1 to 2 per 1000 live births and remains a cause of significant morbidity and mortality in the neonatal period. In response to an anoxic insult, perfusion to vital organs is preserved; however, when this injury is profound concomitant injury to nonvital organs is observed. Controlled hypothermia (CH) has been accepted as a neuroprotective therapeutic modality for neonates with moderate to severe HIE because of its role in attenuating secondary brain injury. Neonates exhibit varying degrees of multiorgan dysfunction after a hypoxic-ischemic insult, although the added beneficial and potential adverse effects that CH has in these babies have not been completely delineated or understood.

CH has been shown to alter normal physiologic functioning of several organ systems. Specific physiologic changes as a consequence of CH have been demonstrated in both animal and human models. The observed reduction in cardiac output and reflexive increase in systemic vascular resistance in response to CH alter renal perfusion and subsequently reduce glomerular filtration . Drugs that are renally cleared may develop a prolonged half-life in this setting. Finally, drug metabolism may further be affected by altered hepatic blood flow and temperature-dependent effects on hepatic enzyme activity . Collectively, the potential effects of CH on drug metabolism and clearance are significant warranting further investigation. The investigator aims to evaluate the combined effects of hypoxia and hypothermia on ampicillin clearance and excretion