Pharmacological Approaches in Newborn Infants with Hypoxic Ischemic Encephalopathy

Kim, Heng Mi

Abstract

Despite marked improvements in perinatal practice, neonatal hypoxic-ischemic encephalopathy (HIE) remains one of the major causes of acute mortality and chronic neurologic disability in infants and children. Several new therapeutic approaches aiming at this condition have been used in the last decade, including therapeutic hypothermia and many pharmacological agents. Therapeutic hypothermia remarkably reduces death and neurological impairment, and has therefore rapidly become the standard therapy for full-term newborn infants with moderate-to-severe HIE. However, despite these promising outcomes of therapeutic hypothermia, approximately 50% of the infants treated with hypothermia have an adverse outcome. Therefore, there exists an urgent need for other treatment options. A mechanistically driven approach to HIE has resulted in the development of many drugs that are potent antagonists of specific steps in cascades of molecular reactions in HI injury. This review provides an overview of promising pharmacological approaches of neuroprotection that may be used in clinical practice. Although several drugs have been found to be effective in preclinical evaluations, such antagonists have been ineffective in human trials. Failure has been attributed to many factors such as the complex pathology of HIE in neonates, the inevitable delays in initiation of therapy in clinical practice, and the side effects of the drugs. Moreover, many of these drugs interfere with only one step of the cascades, while multiple biochemical cascades are put in motion simultaneously. Therefore, neuroprotective strategies such as hypothermia have to deal with multiple cascades. Research is now being focused on drugs that may act synergistically or additively with hypothermia, with the hope that combination therapy might augment neuroprotection.