Moderate Hypothermia to Treat Perinatal Asphyxial Encephalopathy

Division of Clinical Sciences and Medical Research Council Clinical Sciences Centre, Hammersmith Hospital, Imperial College London, London, United Kingdom.
New England Journal of Medicine (Impact Factor: 55.87). 10/2009; 361(14):1349-58. DOI: 10.1056/NEJMoa0900854
Source: PubMed


Whether hypothermic therapy improves neurodevelopmental outcomes in newborn infants with asphyxial encephalopathy is uncertain.
We performed a randomized trial of infants who were less than 6 hours of age and had a gestational age of at least 36 weeks and perinatal asphyxial encephalopathy. We compared intensive care plus cooling of the body to 33.5 degrees C for 72 hours and intensive care alone. The primary outcome was death or severe disability at 18 months of age. Prespecified secondary outcomes included 12 neurologic outcomes and 14 other adverse outcomes.
Of 325 infants enrolled, 163 underwent intensive care with cooling, and 162 underwent intensive care alone. In the cooled group, 42 infants died and 32 survived but had severe neurodevelopmental disability, whereas in the noncooled group, 44 infants died and 42 had severe disability (relative risk for either outcome, 0.86; 95% confidence interval [CI], 0.68 to 1.07; P=0.17). Infants in the cooled group had an increased rate of survival without neurologic abnormality (relative risk, 1.57; 95% CI, 1.16 to 2.12; P=0.003). Among survivors, cooling resulted in reduced risks of cerebral palsy (relative risk, 0.67; 95% CI, 0.47 to 0.96; P=0.03) and improved scores on the Mental Developmental Index and Psychomotor Developmental Index of the Bayley Scales of Infant Development II (P=0.03 for each) and the Gross Motor Function Classification System (P=0.01). Improvements in other neurologic outcomes in the cooled group were not significant. Adverse events were mostly minor and not associated with cooling.
Induction of moderate hypothermia for 72 hours in infants who had perinatal asphyxia did not significantly reduce the combined rate of death or severe disability but resulted in improved neurologic outcomes in survivors. (Current Controlled Trials number, ISRCTN89547571.)

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    • "Mild encephalopathy may have a normal outcome, 20-40% of neonates with moderate encephalopathy can have an abnormal outcome and severe encephalopathy generally leads to neurological disability or death (Gray et al., 1993) in the majority of neonates. The results of several international trials has shown that early induced hypothermia is beneficial in HIE, improving survival and reducing neurological disability (Azzopardi et al., 2009). The treatment involves cooling the infant to a body temperature of between 32-34°C for 72hours without interruption. "
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    ABSTRACT: This work presents a novel automated system to classify the severity of hypoxic-ischemic encephalopathy (HIE) in neonates using EEG. A cross disciplinary method is applied that uses the sequences of short-term features of EEG to grade an hour long recording. Novel post-processing techniques are proposed based on majority voting and probabilistic methods. The proposed system is validated with one-hour-long EEG recordings from 54 full term neonates. An overall accuracy of 87% is achieved. The developed grading system has improved both the accuracy and the confidence/quality of the produced decision. With a new label 'unknown' assigned to the recordings with lower confidence levels an accuracy of 96% is attained. The statistical long-term model based features extracted from the sequences of short-term features has improved the overall accuracy of grading the HIE injury in neonatal EEG. The proposed automated HIE grading system can provide significant assistance to healthcare professionals in assessing the severity of HIE. This represents a practical and user friendly implementation which acts as a decision support system in the clinical environment. Its integration with other EEG analysis algorithms may improve neonatal neurocritical care. Copyright © 2015 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.
    Clinical neurophysiology: official journal of the International Federation of Clinical Neurophysiology 06/2015; DOI:10.1016/j.clinph.2015.05.024 · 3.10 Impact Factor
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    • "Seetha Shankaran then led the first wholebody cooling (WBC) trial (NICHD) using a cooling blanket, with a target oesophageal temperature of 33.5 C [10]. Later, the TOBY trial led by Denis Azzopardi also applied WBC [11], which since 2007 has become the preferred cooling method. There is no evidence that either method is better. "
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    ABSTRACT: Three ongoing challenges have arisen after the introduction of therapeutic hypothermia (TH) as standard of care for term newborns with moderate or severe perinatal asphyxia: (i) to ensure that the correct group of infants are cooled; (ii) to optimize the delivery of TH and intensive care in relation to the severity of the encephalopathy; (iii) to systematically follow up the long-term efficacy of TH using comparable outcome data between centers and countries. This review addresses the entry criteria for TH, and discusses potential issues regarding patient selection, and management of TH: cooling mild, moderate, and very severe perinatal asphyxia, cooling longer or deeper, and/or starting with a greater delay. This includes cooling of patients outside of standard trial entry criteria, such as after postnatal collapse, premature infants, those with infection, and infants with metabolic, chromosomal or surgical diagnoses in addition to perinatal asphyxia. Copyright © 2015. Published by Elsevier Ltd.
    Seminars in Fetal and Neonatal Medicine 02/2015; 20(2). DOI:10.1016/j.siny.2015.01.002 · 3.03 Impact Factor
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    • "In the cooled group, 11% of patients were discharged on gavage feeds versus 7% of controls (significance not reported but calculated í µí±ƒ > 0.05) and 7% of patients were discharged with a gastric tube (GT) versus 17% of controls (significance not reported but calculated í µí±ƒ > 0.05) [3]. Finally, the TOBY trial for WBTH reported only one case of NEC in a cooled patient and no cases of NEC in the control group (<1% versus 0%, no significance) [1]. To our knowledge, there are no published clinical trials evaluating the effects of therapeutic hypothermia for GI ischemia and reperfusion injury following HIE in humans, but several animal studies suggest a benefit. "
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    ABSTRACT: Objective. This retrospective cohort study evaluated the effects of whole body therapeutic hypothermia (WBTH) on gastrointestinal (GI) morbidity and feeding tolerance in infants with moderate-to-severe hypoxic ischemic encephalopathy (HIE). Study Design. Infants ≥ 35 weeks gestational age and ≥1800 grams birth weight with moderate-to-severe HIE treated from 2000 to 2012 were compared. 68 patients had documented strictly defined criteria for WBTH: 32 historical control patients did not receive WBTH (non-WBTH) and 36 cohort patients received WBTH. Result. More of the non-WBTH group infants never initiated enteral feeds (28% versus 6%; P = 0.02), never reached full enteral feeds (38% versus 6%, P = 0.002), and never reached full oral feeds (56% versus 19%, P = 0.002). Survival analyses demonstrated that the WBTH group reached full enteral feeds (median time: 11 versus 9 days; P = 0.02) and full oral feeds (median time: 19 versus 10 days; P = 0.01) sooner. The non-WBTH group had higher combined outcomes of death and gastric tube placement (47% versus 11%; P = 0.001) and death and gavage feeds at discharge (44% versus 11%; P = 0.005). Conclusion. WBTH may have beneficial effects on GI morbidity and feeding tolerance for infants with moderate-to-severe HIE.
    International Journal of Pediatrics 08/2014; 2014:643689. DOI:10.1155/2014/643689
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