812 - A Historical Journey: The Development and Adoption of Therapeutic Hypothermia in Neonatal Medicine

Publication Number: 812.3785

Monsur Jaiyeola, Allen High School, Allen, TX, United States; Paolo I. Amar, Loyola University Chicago, Dallas, TX, United States; Saul A. LEON, University of Texas Southwestern Medical School, Garland, TX, United States; Suryatej V. Chamarthi, Centennial High school, Frisco, TX, United States; Kikelomo Babata, University of Texas Southwestern Medical School, Dallas, TX, United States; Rachel L.. Leon, University of Texas Southwestern Medical School, Dallas, TX, United States; Lina Chalak, UTSW, Dallas, TX, United States

Background: Hypothermia, the reduction of core body temperature, has been recognized for its therapeutic potential since ancient times. The Egyptians and Greeks employed cooling methods for various medical treatments. In modern times, specific compelling cases of improbable survival in hypothermic conditions have inspired further exploration into the therapeutic effects of hypothermia on the human body.

Objective: To chronicle the historical progression and clinical advancements of hypothermia as a treatment, with a focus on its application to neonatal hypoxic ischemic encephalopathy (HIE).

Design/Methods: Analysis of published literature on the history and clinical use of hypothermia for its therapeutic properties.

Results: Dr. Temple Fay pioneered the modern use of controlled hypothermia in the 1930s, and by the 1950s, it was adopted as a method to reduce metabolic tissue demand and improve outcomes from open heart surgery. Early studies in the 1950s showed promise for the application of therapeutic hypothermia (TH) to specific neonatal populations, but this research was discontinued due to safety concerns. Renewed interest in the 1990s led to pivotal animal studies using TH which demonstrated neuronal protection in piglets following birth asphyxia and prevention of cortical infarction in rats after experimental brain injury. Pilot studies in the late 1990s using a compelling model of HIE in the chronically instrumented ewe laid the groundwork for large-scale clinical trials. These trials established TH as the standard of care for moderate to severe HIE in neonates. The TOBY trial (2005-2011) was particularly influential, demonstrating improved long-term outcomes for those treated with TH. In a meta-analysis including over 1500 infants, the number needed to treat for TH was 7 to prevent one case of death or moderate to severe disability, underscoring the success of TH as an intervention. The COOLPRIME study now addresses the safety and effectiveness of TH in neonates with mild HIE, potentially expanding the application of this therapy.

Conclusion(s): Hypothermia has evolved from an ancient remedy to a critical intervention in neonatology, significantly improving outcomes for newborns with HIE. The COOLPRIME study continues to refine its use, with a focus on a potential therapeutic role in neonates with mild HIE.

Timeline of development and adoption of therapeutic hypothermia in neonatal medicine
Therapeutic hypothermia timeline figure

The development and adoption of therapeutic hypothermia in Neonatal Medicine
Therapeutic Hypothermia timeline table