Best Practice Guideline article Therapeutic hypothermia for neonatal hypoxic ischaemic encephalopathy Aniko Roka a , Denis Azzopardi a,b, ⁎ a The Neonatal Unit, Queen Charlottes and Chelsea Hospital, London, UK b Institute of Clinical Sciences, Imperial College London, UK abstract article info Keywords: Induced hypothermia Hypoxia-ischaemia brain Encephalopathy Intensive care There is now a strong evidence base supporting therapeutic hypothermia for infants with moderate or severe neonatal hypoxic ischaemic encephalopathy. Experimental and clinical data indicate that induced hypothermia reduces cerebral hypoxic ischaemic injury and randomized clinical trials in newborns with hypoxic ischaemic encephalopathy confirm improved neurological outcomes and survival at 18 months of age with therapeutic hypothermia. Studies are on-going to confirm whether these benefits are maintained in later childhood. Efforts are now focused on optimal implementation of therapeutic hypothermia in clinical practice: training in the assessment of severity of encephalopathy; initiation and maintenance of hypothermia before admission to a cooling facility; care of the infant during cooling; and appropriate investigation and follow-up are crucial for optimizing neurological outcomes. The establishment of registries of infants with hypoxic ischaemic encephalopathy and audit are important for guiding clinical practice. © 2010 Elsevier Ireland Ltd. All rights reserved. Contents 1. Clinical evidence supporting therapeutic hypothermia in newborns . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 362 2. Mechanism of action of therapeutic hypothermia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 363 3. Clinical application of therapeutic hypothermia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 363 4. Which infants should be considered for treatment with cooling? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 364 5. Therapeutic hypothermia in infants born outside treatment centres . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 364 6. Therapeutic hypothermia in cooling centres . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 364 7. Assessment of prognosis following therapeutic hypothermia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 366 8. Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 366 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 366 There have been intensive efforts over several years to improve the dismal outcome that follows moderate or severe neonatal hypoxic ischaemic encephalopathy. Though several experimental therapies for hypoxic ischaemic encephalopathy seemed promising none proved consistently successful in clinical studies, and therapeutic options for infants with hypoxic ischaemic encephalopathy were limited to supportive care [1–3]. However, over the past two decades, experimental and clinical evidence have accumulated showing that a3–4 °C reduction of body temperature maintained for at least 72 h in newborns with hypoxic ischaemic encephalopathy may reduce cerebral injury and improve neurological outcomes. In newborns, therapeutic hypothermia was first described as a method of reanimation by immersion in cold water [4,5]. Later, experimental studies in adult models of hypoxic ischaemic injury suggested that brief periods of post insult hypothermia offered neuroprotection. These results led to a series of studies in newborn animal models which showed repeatedly that moderate hypothermia significantly reduced cerebral injury following hypoxic ischaemia. (For an account of the evolution of hypothermic neural rescue therapy see http://en.wikipedia.org/wiki/Hypothermia_therapy_for_neonata- l_encephalopathy). These investigators went on to perform a series of clinical studies first to confirm the safety of prolonged moderate hypothermia in asphyxiated newborns and then to determine therapeutic effect by carrying out randomized controlled trials that together with other studies now form the evidence base for the clinical use of therapeutic hypothermia for neonatal hypoxic ischaemic encephalopathy. Early Human Development 86 (2010) 361–367 ⁎ Corresponding author. The Neonatal Unit, Queen Charlottes and Chelsea Hospital, London, UK. E-mail address: d.azzopardi@imperial.ac.uk (D. Azzopardi). 0378-3782/$ – see front matter © 2010 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.earlhumdev.2010.05.013 Contents lists available at ScienceDirect Early Human Development journal homepage: www.elsevier.com/locate/earlhumdev