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Updated: Jun 2, 2026
A Piglet Model of Neonatal Hypoxic-Ischemic Encephalopathy
Published on: May 16, 2015
Does phenobarbital improve the effectiveness of therapeutic hypothermia in infants with hypoxic-ischemic
S Sarkar1, J D Barks, J R Bapuraj
1Division 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
Insights
Phenobarbital (PB) given before therapeutic hypothermia did not improve outcomes for infants with hypoxic-ischemic encephalopathy (HIE). This treatment was associated with increased neonatal death and brain injury, warranting further investigation into long-term effects.
Area of Science:
- Neonatal Neurology
- Pediatric Critical Care
- Neuroprotection Strategies
Background:
- Hypoxic-ischemic encephalopathy (HIE) is a serious condition in newborns.
- Therapeutic hypothermia is a standard treatment for HIE.
- The potential benefit of adjunctive phenobarbital (PB) before cooling is unclear.
Purpose of the Study:
- To investigate if phenobarbital (PB) administered before therapeutic hypothermia enhances neuroprotection in infants with HIE.
- To compare outcomes between infants receiving PB before hypothermia and those who did not.
Main Methods:
- Retrospective review of 68 infants (gestation ≥36 weeks) with moderate/severe HIE treated with hypothermia.
- Comparison of a composite outcome (neonatal death or abnormal brain MRI) between infants who received prophylactic PB and those who did not.
- Logistic regression analysis to identify predictors of the primary outcome.
Main Results:
- The PB group (n=36) had a higher composite outcome rate (78%) compared to the No PB group (n=32, 44%; P=0.006).
- Multivariate analysis revealed PB administration before hypothermia (OR 9.5) and placental abruption were independently associated with worse outcomes.
- Groups were similar in initial asphyxia severity and clinical factors.
Conclusions:
- Phenobarbital (PB) treatment initiated before therapeutic hypothermia did not improve the composite outcome of neonatal death or abnormal post-hypothermia brain MRI in HIE infants.
- The findings suggest a potential detrimental effect of prophylactic PB in this context.
- Long-term outcomes require further evaluation.
Objective:
To determine whether phenobarbital (PB) given before therapeutic hypothermia to infants with hypoxic-ischemic encephalopathy (HIE) augments the neuroprotective efficacy of hypothermia.
Study Design:
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.
Result:
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.
Conclusion:
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.
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