What year was therapeutic hypothermia introduced in practice for neonatal hypoxic ischemic encephalopathy (HIE)?

Introduction of Therapeutic Hypothermia for Neonatal Hypoxic Ischemic Encephalopathy

Therapeutic hypothermia was introduced as standard care for neonatal hypoxic ischemic encephalopathy (HIE) in high-income countries following successful clinical trials in the early 2000s, with widespread clinical implementation occurring after 2005. 1, 2

Historical Development of Therapeutic Hypothermia for HIE

• Early pilot trials of moderate systemic hypothermia (33°C) for neonatal HIE began reporting efficacy outcomes around 2005, demonstrating promising results in reducing adverse neurological outcomes 3
• By 2008-2010, sufficient evidence had accumulated from multiple randomized controlled trials to support the implementation of therapeutic hypothermia as standard care in high-income countries 2
• A 2012 meta-analysis of seven trials including 1,214 newborns firmly established the evidence base for therapeutic hypothermia in treating moderate to severe HIE 4

Current Standard of Care

• Therapeutic hypothermia is now considered standard care in high-income countries for the treatment of moderate or severe HIE in term and near-term infants 1, 2, 5
• Treatment protocols typically include:
  • Initiation of cooling within 6 hours of birth 2
  • Strict temperature control to 33-34°C 1, 2
  • Duration of cooling for 72 hours 1, 2
  • Rewarming over at least 4 hours 1, 2

Efficacy of Therapeutic Hypothermia

• Therapeutic hypothermia reduces the risk of death or major neurodevelopmental disability by approximately 22-33% in infants with moderate-to-severe HIE 2
• For every 5-7 infants treated with therapeutic hypothermia, one fewer infant will die or have significant neurodevelopmental disability 2
• In moderate HIE, therapeutic hypothermia reduces the risk of death or major neurodevelopmental disability by approximately 33% 2, 4
• In severe HIE, the reduction is approximately 17% 2, 4

Implementation Requirements

• Cooling should only be conducted in neonatal care facilities with capabilities for multidisciplinary care 1, 2
• Required resources include intravenous therapy, respiratory support, pulse oximetry, antibiotics, anticonvulsants, and pathology testing 1, 2
• Implementation without proper protocols and monitoring may lead to harm, including risk of extreme hypothermia 2, 6

Ongoing Research and Future Directions

• Current research is exploring combination therapies to enhance the neuroprotective effects of hypothermia, such as erythropoietin plus hypothermia 7
• There is an increasing trend to use therapeutic hypothermia even in infants with mild HIE, though evidence for this practice remains limited 6
• Further research is needed on optimal rewarming rates after hypothermia 2

Cautions and Considerations

• Despite the benefits of therapeutic hypothermia, a significant proportion of treated infants still experience adverse outcomes 5
• Potential adverse effects include extreme hypothermia, bradycardia, hypoglycemia, sepsis, skin necrosis, pulmonary hypertension, and systemic hypotension 6
• The rate of death or disability following hypothermia therapy has been reduced substantially, but research continues to evaluate whether mortality or disability can be reduced further following combination therapy 5