COOLING THERAPY IN NEONATAL HYPOXIC ISCHEMIC ENCEPHALOPATHY

Abstract

HIE is characterized by clinical and laboratory evidence of acute or sub-acute brain injury due to asphyxia. The primary causes of this condition are systemic hypoxemia and/or reduced cerebral blood flow (CBF). Birth asphyxia causes 23% of all neonatal deaths worldwide. HIE is an important cause of death and neuro-developmental delay worldwide. Treatment for infants with hypoxic-ischemic encephalopathy was limited to supportive care for a long time, but efforts have been made to develop effective therapies. However, through several experimental therapies for hypoxic ischemic encephalopathy seemed promising none proved consistently successful in clinical studies. Over the past two decades, experimental and clinical evidence has accumulated that a 3-4oC reduction of body temperature maintained for at least 72 hours in newborns with hypoxic ischemic encephalopathy may reduce cerebral injury and improve neurological outcomes. Recent clinical trials have demonstrated that prolonged cooling of either the head or the whole body of neonates with HIE is safe and associated with reduced short-term mortality and morbidity at 18 months of age. Neuronal damage and death after asphyxia occurs in different phases and pathways. Initially primary energy failure and oxidative stress are responsible for tissue injury followed by secondary activated long term processes like excite-toxicity, inflammation, and apoptosis. Hypothermia, which decreases the cerebral metabolism and possibly affects on many other ways is the first therapeutic intervention proven being able to improve neurological outcome. Hypothermia that is proven to decrease brain damage following asphyxia has an additional beneficial effect on the hypoxic damage of other organs than brain. It is well known that in addition to brain injury neonatal asphyxia has a profound effect on the function of major organ systems. Pulmonary, cardiovascular, hepatic, renal and gastrointestinal dysfunction may evolve due to hypoxicischemic damage as a result of the temporary lack of oxygen supply. Mild hypothermia is safe with no serious side effects reported. Mild bradycardia, mild hypotension, arrythmias, mild thrombocytopenia and sclerema/edema have been described. Hypothermia is associated with increased mortality in the premature infant. Data in premature and fetal asphyxiated animals are controversial, with some studies showing no effect and others showing improvement. There is currently no evidence that therapeutic hypothermia offers any benefit to infants <36 weeks’ gestational age; the safety and efficacy of cooling in this population are unknown. Clinical trials in late preterm infants are in progress.