title: Does phenobarbital improve the effectiveness of therapeutic hypothermia in infants with hypoxic-ischemic encephalopathy?
abstract: OBJECTIVE
  To determine whether phenobarbital (PB) given before therapeutic hypothermia to infants with hypoxic-ischemic encephalopathy (HIE) augments the neuroprotective efficacy of hypothermia.
  
  
  METHODS
  Records of 68 asphyxiated infants of 36 weeks' gestation, who received hypothermia for moderate or severe HIE were reviewed. Some of these infants received PB prophylactically or for clinical seizures. All surviving infants had later brain magnetic resonance imaging (MRI). The composite primary outcome of neonatal death related to HIE with worsening multiorgan dysfunction despite maximal treatment, and the presence of post-hypothermia brain MRI abnormalities consistent with hypoxic-ischemic brain injury, were compared between the infants who received PB before initiation of hypothermia (PB group, n=36) and the infants who did not receive PB before or during hypothermia (No PB group, n=32). Forward logistic regression analysis determined which of the pre-hypothermia clinical and laboratory variables predict the primary outcome.
  
  
  RESULTS
  The two groups were similar for severity of asphyxia as assessed by Apgar scores, initial blood pH and base deficit, early neurologic examination, and presence of an intrapartum sentinel event. The composite primary outcome was more frequent in infants from the PB group (PB 78% versus No PB 44%, P=0.006, odds ratio 4.5, 95% confidence interval 1.6 to 12.8). Multivariate analysis identified only the PB receipt before initiation of hypothermia (P=0.002, odds ratio 9.5, 95% confidence interval 2.3 to 39.5), and placental abruption to be independently associated with a worse primary outcome.
  
  
  CONCLUSIONS
  PB treatment before cooling did not improve the composite outcome of neonatal death or the presence of an abnormal post-hypothermia brain MRI, but the long-term outcomes have not yet been evaluated.
authors.affiliation: Division of Neonatal-Perinatal Medicine, Department of Pediatrics, University of Michigan Health System, CS Mott Children's Hospital, Ann Arbor, MI, USA. subratas@med.umich.edu
authors.forename: S
authors.initials: S
authors.lastname: Sarkar
authors.forename: J D
authors.initials: JD
authors.lastname: Barks
authors.forename: J R
authors.initials: JR
authors.lastname: Bapuraj
authors.forename: I
authors.initials: I
authors.lastname: Bhagat
authors.forename: R E
authors.initials: RE
authors.lastname: Dechert
authors.forename: R E
authors.initials: RE
authors.lastname: Schumacher
authors.forename: S M
authors.initials: SM
authors.lastname: Donn
mesh_terms: D001238:Asphyxia Neonatorum / Q000150:complications / Q000628:therapy*; D001921:Brain / Q000473:pathology*; D003131:Combined Modality Therapy; D005260:Female; D006801:Humans; D007036:Hypothermia, Induced / Q000379:methods*; D020925:Hypoxia-Ischemia, Brain / Q000209:etiology / Q000401:mortality / Q000628:therapy*; D007226:Infant Mortality; D007231:Infant, Newborn; D016015:Logistic Models; D008279:Magnetic Resonance Imaging; D008297:Male; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D010634:Phenobarbital / Q000627:therapeutic use*; D012189:Retrospective Studies
chemical_list: D018696:Neuroprotective Agents; D010634:Phenobarbital