Hypoxic ischemic encephalopathy (HIE) occurs in ~ 2-4/1000 term infants and is a major cause of neonatal morbidity and mortality. To date, therapeutic hypothermia started within 6 h of birth is the only intervention known to be effective in reducing the morbidity and mortality of HIE. Hypothermia does not totally reverse the injury in many infants and is associated with side effects that may compromise its effectiveness. Low dose morphine is often used to reduce shivering in infants undergoing therapeutic hypothermia, but escalating doses of sedatives/analgesics are often required. Escalating doses of opioids and benzodiazepines causes respiratory depression and can either cause the need for or prolong mechanical ventilation.Agonists to the central a2 - adrenergic receptors are more effective at reducing postoperative shivering than opioid receptor agonists and provide analgesia and sedation without respiratory depression. The most desirable sedative-analgesic agent used in infants with HIE would: (a) have an excellent safety profile, (b) reduce shivering, (c) provide adequate analgesia and sedation, (d) cause minimal respiratory depression, (e) preserve cerebrovascular autoregulation, and (f) confer neuroprotection.