What is the role of hypothermia therapy in the treatment of hypoxic-ischemic encephalopathy (HIE)?

Updated: Jul 18, 2018
  • Author: Santina A Zanelli, MD; Chief Editor: Dharmendra J Nimavat, MD, FAAP  more...
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The clinical efficacy of therapeutic hypothermia in neonates with moderate-to-severe hypoxic-ischemic encephalopathy (HIE) has been evaluated in multiple randomized controlled trials. [27, 28, 86, 87, 88, 89, 90, 91] for a total of greater than 1500 infants enrolled. Inclusion criteria varied slightly between studies and are summarized as follows:

  • Near-term infants born at 36 weeks' gestation or more with birth weight of 1800-2000 g or more, younger than 6 hours at admission. Some trials have enrolled infants as young as 35 weeks' gestation (Eicher and ICE trial)

  • Evidence of acute event around the time of birth – Apgar score of 5 or less at 10 minutes after birth (In the study by Shankaran et al, this needed to be in conjunction with either evidence of acute perinatal event or need for assisted ventilation for at least 10 min. [28] ), severe acidosis, defined as pH level of less than 7 or base deficit of 16 mmol/L or less (cord blood or any blood gas obtained within 1 h of birth), continued need for resuscitation at 10 minutes after birth

  • Evidence of moderate to severe encephalopathy at birth – Clinically determined (at least 2 of the following: lethargy, stupor, or coma; abnormal tone or posture; abnormal reflexes [suck, grasp, Moro, gag, stretch reflexes]; decreased or absent spontaneous activity; autonomic dysfunction [including bradycardia, abnormal pupils, apneas]; and clinical evidence of seizures), moderately or severely abnormal amplitude-integrated electroencephalography (aEEG) background or seizures (CoolCap, TOBY and Neo-Neuro, Neonatal Network trial)

All of these studies have shown benefits, and 9 independent meta-analyses have confirmed a consistent and robust beneficial effect of therapeutic hypothermia for moderate-to-severe encephalopathy with a number needed to treat between 5 and 9.

The 2013 cochrane review included 11 randomized controlled trials and 1505 infants and found that therapeutic hypothermia resulted in the following:

  • A decrease in the combined outcomes of mortality/major neurodevelopmental disability at 18 months (8 studies, 1344 infants): relative risk [RR] 0.75 (0.68-0.83); number needed to benefit (NNTB) 7 (5-10)

  • A reduction in mortality (11 studies, 1468 infants): RR 0.75 (0.64-0.88); NNTB 11 (8-25)

  • A reduction in neurodevelopmental disability in survivors (8 studies, 917 infants): RR 0.77 (0.63-0.94); NNTB 8 (5-14)

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