A 27-year-old woman, gravida 1 para 0, at 37 weeks gestation comes to the emergency department after spontaneous rupture of membranes with leakage of blood mixed with fluid. Emergency cesarean delivery is performed due to severe fetal bradycardia. On delivery, the neonate is apneic and hypotonic. Resuscitation with endotracheal intubation and assisted ventilation is performed, which improves bradycardia. Apgar scores are

Question

A 27-year-old woman, gravida 1 para 0, at 37 weeks gestation comes to the emergency department after spontaneous rupture of membranes with leakage of blood mixed with fluid.  Emergency cesarean delivery is performed due to severe fetal bradycardia.  On delivery, the neonate is apneic and hypotonic.  Resuscitation with endotracheal intubation and assisted ventilation is performed, which improves bradycardia.  Apgar scores are <5 at 5 and 10 minutes.  Umbilical cord blood analysis shows high anion gap metabolic acidosis.  Controlled hypothermia to maintain body temperature at 33-35 C (91.4-95 F) is begun.  This therapy is most likely to provide benefit via which of the following mechanisms?

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11ec160b_3b02_241c_9249_f7e0748b9381_MD0001_00 This early-term infant has sustained hypoxic-ischemic injury during delivery and is at risk of worsening neonatal encephalopathy (eg, decreased consciousness, impaired respiration, seizures). Hypoxia can lead to neuronal injury through multiple injury cascades, many of which lead to the formation of reactive oxygen species (ROS). ROS can mediate cellular damage of DNA, cell membranes, proteins, and enzymes, leading to widespread neuronal death. Therapeutic hypothermia (maintenance of temperature at 33-35 C [91.4-95 F]) leads to improved neurologic outcomes in a variety of hypoxia-induced injuries (eg, after cardiac arrest, seizures). The formation of ROS after ischemic injury is temperature dependent, so it can be decreased by therapeutic hypothermia. In addition, therapeutic hypothermia decreases cerebral blood flow, oxygen consumption, and glucose metabolism, thereby decreasing the formation of ROS due to both cellular metabolism and reperfusion. Therapeutic hypothermia has other beneficial effects, including lowering intracranial pressure, reducing excitatory neurotransmitters, and decreasing activation of inflammatory and apoptotic pathways (eg, blocks tumor necrosis factor and caspase pathways). (Choice A) Therapeutic hypothermia impairs both platelets and clotting factors, which, rather than being neuroprotective, can lead to an increased risk of bleeding complications (eg, intracranial hemorrhage). (Choice C) In neonates with severe hyperbilirubinemia, unbound, lipid-soluble bilirubin can cross the blood-brain barrier. This neurotoxic bilirubin preferentially deposits in the basal ganglia and brainstem nuclei, leading to permanent neurologic damage. The primary treatment for hyperbilirubinemia converts bilirubin to a more water-soluble form (isomers) that can be excreted. However, this is accomplished through phototherapy rather than therapeutic hypothermia. (Choice D) This patient has anion gap metabolic acidosis due to lactic acidosis caused by tissue hypoxia. Although the liver is responsible primarily for clearing lactate, its rate of clearance does not seem to be significantly impacted by therapeutic hypothermia. Rather, lactic acidosis typically improves after an increase in oxygenation and the restoration of circulation. Educational objective: Neuronal damage after hypoxic-ischemic injury is often related to the formation of reactive oxygen species, which mediate widespread cellular damage. Therapeutic hypothermia decreases the formation of reactive oxygen species by decreasing cellular metabolism and slowing reperfusion. __________ References: Therapeutic hypothermia: critical review of the molecular mechanisms of action. (http://www.ncbi.nlm.nih.gov/pubmed/21331282)

A 27-Year-Old Woman, Gravida 1 Para 0, at 37 Weeks