Beyond the Clinical Trials: Off-Protocol Therapeutic Hypothermia.

Mild therapeutic hypothermia has been extensively studied and validated as an effective and safe treatment for term and near-term infants with moderate and severe hypoxic encephalopathy meeting narrow inclusion criteria. Unanswered questions remain about whether cooling treatment can be optimized to improve outcomes even further, and whether it is reasonable to offer treatment to infants excluded from the foundational studies. Consideration of "off-protocol" cooling practices requires methodical review of available evidence and analysis using both a clinical and a research ethical framework.