Therapeutic Hypothermia for Treatment of Neonatal Encephalopathy

Current Research and Nursing Care

Carmen K. Cederholm, BSN, RN, CCRN; C. Michael Cotten, MD, MHS


NAINR. 2014;14(2):77-81. 

In This Article

Therapeutic Hypothermia

Treatment of NE is aimed at disruption of the cascade of events leading to secondary energy failure and neuronal death.[8] TH is thought to diminish the severity of secondary energy failure by reducing the brain's energy utilization, decreasing free radical production and release of extracellular excitatory neurotransmitters, and normalizing protein synthesis.[9,10] Combined, these effects lead to reduced neuronal apoptosis.[9,10]

Westin first reported the use of TH as treatment for asphyxiated infants in 1959.[4] Infants had improved neurological outcomes after being immersed in cold water to achieve core body temperatures of 23–25 °C for 20 minutes. However, clinical trials in the neonatal setting did not start in earnest until the late 1990s and early 2000s when pilot studies showed TH was safe for infants greater than 36 weeks gestation.[11,12] Then, in 2005, the results of the first multicenter phase III trial showed TH was both safe and effective for the treatment of mild and moderate NE.[12]

Since then, multicenter randomized controlled trials (RCTs) including the U.K.'s Total Body Hypothermia Trial (TOBY), Europe's "" trial of whole body cooling, the National Institute of Child Health and Human Development's (NICHD) trial, and Australia's Infant Cooling Evaluation (ICE) encompassing over 1000 infants have commenced.[13–15] The results from these trials were published in the early to mid 2000s and since then several meta-analyses of these and other studies have been published that help to summarize the outcomes.[16–18] Edwards, et al. (2010) performed a meta-analysis of 10 clinical trials encompassing 1320 infants.[16] Their analysis showed lower rates of mortality, cerebral palsy, hearing and visual impairment, and neurodevelopmental delay in cooled infants. They concluded that the overall effect of TH is significant for preventing the primary outcomes of death and major disability as well as secondary outcomes such as cerebral palsy caused by NE. Shah (2010) reviewed 19 reports of 14 clinical trials of 1440 patients and found significant reductions in the risk of mortality or moderate to severe developmental delay.[18] Tagin, et al. (2011) reviewed 7 trials encompassing 1214 newborns and also found overall reduced risk of death and major disability along with cerebral palsy, developmental delay, and blindness.[19] Though there is some overlap in the studies included in these meta-analyses, they highlight the growing pool of evidence supporting the efficacy of TH.

Since the initial results of the large RCTs were published, subsequent follow-up studies were done on the surviving participants. Researchers were interested in whether TH provided long-lasting neuroprotection. The 18-month to 8-year follow-up results are summarized in Table 1 . In general, TH was shown to reduce the incidence of death and major disability into childhood.[13–15,17,20]

Of particular interest are outcome measures of treatment subjects who are now reaching school age. Shankaran, et al. performed follow-up evaluations on 122 surviving subjects of the NICHD RCT.[20] They evaluated survivors on IQ and motor function, including classifying the level of cerebral palsy if present. At 6–7 years post treatment, they found no statistically significant difference in the rates of the composite outcome of death or IQ below 70 between the hypothermia and control groups. However, reduced mortality continued through age 6–7 years in the hypothermia group. Additionally, survivors had no significant increase risk of negative neurodevelopmental outcomes. These results suggest that TH safely provides long-term neuroprotection.[20]