Expanding Therapeutic Hypothermia Services to Improve Care for Neonates with Neurological Conditions

Therapeutic hypothermia (TH) is established as a treatment for infants with hypoxic ischemic encephalopathy (HIE). It has been available for more than a decade at Children’s Hospital of Philadelphia (CHOP), where 25 to 30 infants are treated annually with whole-body TH.

CHOP continues to be involved with cutting-edge research for infants with HIE, including a clinical trial evaluating the role of erythropoietin together with hypothermia in limiting brain injury (HEAL Study) as well as the role of hypothermia for preterm infants who sustain brain injury (Preemie Hypothermia).

In addition, local quality improvement efforts have led to updating our cooling equipment to blankets that allow families to hold their infants (when stable enough to tolerate) as well as provide more data regarding how precisely temperatures are controlled during the 3 days of therapy. Finally, pilot work is underway to evaluate novel imaging techniques that may offer insights into blood flow changes during hypothermia and be a way to identify brain injury earlier in the treatment course.

Bringing therapeutic hypothermia to more NICUs

While this work is exciting and will hopefully push the state of the field forward, infants still have to transfer to CHOP to be treated with TH. Recognizing the stress this puts on a family to be separated and the potential delay in beginning therapy, which has been shown to be time sensitive, level III NICUs throughout the CHOP Newborn Care Network (CNBCN) are moving to start their own hypothermia programs.

Some, like Pennsylvania Hospital, have a long history of providing TH and have evolved a model of care that is replicable by other NICUs in the CNBCN. Other NICUs have newer cooling programs or are due to open them in the coming year. Planning for this expansion has been underway for a couple of years and comes after a coordinated effort to review existing evidence by both Neonatology and Neurology divisions and align care practices across the network through development of an HIE pathway.

Ensuring consistency of care

A primary objective of the group was to ensure consistent practice as this therapy is rolled out to new centers. There was careful discussion regarding eligibility criteria (including gestational age of 35 weeks and above) and how late to apply the therapy (within 6 hours), after considering newly available data from clinical research. Further, it was important to ensure the same access for these patients to consulting services, when necessary.

Neurology was closely involved with this work and future directions will likely include finding ways to incorporate telemedicine and expanded EEG services in the coming years. For the time being, close follow-up is planned for these infants, and criteria exist to guide decisions for transferring to CHOP for the more complicated patients. This will be aided by the new availability of devices to continue active cooling by our Transport Team.

In the year leading up to the expansion of the cooling program, there was careful discussion about how to ensure adequate neuromonitoring, particularly in units without access to continuous EEG. A workshop was sponsored with an outside consultant to provide a primer on amplitude-integrated EEG (aEEG) use and interpretation, and consensus evolved around use of intermittent full EEG and when to transfer for more intensive monitoring. In time, we look forward to expansion of continuous EEG services where possible. Additionally, the group created a standard approach to the management of neonatal seizures. While not at this time a formal “pathway,” in the coming year, Neurology and Neonatology will partner to create one that includes early stopping of anti-seizure medications to prevent overtreatment and prolonged exposure to these medications and their potential side effects.

Einstein Montgomery Medical Center’s (EMMC) NICU is the most recent unit to begin offering therapeutic hypothermia, and members of their staff were intimately involved with development of the pathway. Since starting their program, they have had the opportunity to provide therapeutic hypothermia to 4 patients. Two received the entirety of their treatment at EMMC and were able to stay close to their families and be discharged from this unit. Two other patients ultimately transferred to CHOP. One transferred due to suspected seizures on the aEEG that required more intensive management. These were identified by staff on-site, medications given, and transfer accomplished before 48 hours of life.

The second case involved a severely impacted infant and transfer was immediate after initiation of cooling locally in order to allow in-person participation of neurologists and advanced EEG/imaging. While both of these cases ended in transfer to CHOP, cooling began earlier and seizure surveillance was sooner than would have been the case prior to expansion of this program. A fifth patient was preterm and less than 35 weeks’ gestation and was transferred to CHOP immediately for access to a research study evaluating hypothermia in preterm infants. Efforts are underway to monitor objective metrics to ensure ongoing high-quality care for this patient population and adjust the hypothermia pathway and approach as needed.