Rescuers of Body and Brain

by Zan Hale

When a hospitalized child stops breathing or their heart stops, Critical Care Medicine specialists respond to save the child’s life. At Children’s Hospital of Philadelphia, they’ve gotten extraordinarily good at it; fewer than 2% of children who “code” in the hospital and require resuscitation die. But for Critical Care physicians Todd Kilbaugh, MD, and Robert Sutton, MD, MSCE, keeping a child alive is just the beginning.

“Survival is not enough,” Kilbaugh says. “These kids need to thrive. We consider ourselves rescuers of the brain, not just the body.”

That mission is behind the launch of the Resuscitation Science Center, co-directed by Kilbaugh and Sutton. The center builds on CHOP’s long history of breakthroughs in caring for the sickest children.

Innovation on a skateboard

Joey Romano, now 16, is a healthy, skateboarding testament to that philosophy. Ten years ago, a bad case of the H1N1 flu landed him in CHOP’s Pediatric Intensive Care Unit (PICU), where he was put on a ventilator because his lungs were barely functioning. It wasn’t enough. He went into cardiac arrest and coded.

“We were in the hallway, watching Dr. Bobby [Sutton] lead the team doing CPR,” his mother, Betsy, remembers. “He stopped, and we thought Joey had died. But Dr. Bobby had saved him.”

Sutton and Kilbaugh determined Joey needed extracorporeal membrane oxygenation (ECMO), a lung-heart support system typically used with cardiac patients to oxygenate and pump their blood until they’re strong enough to do so themselves. Joey was among the first children at CHOP put on a new form of ECMO so his lungs could recover. He was on ECMO for 13 days.

Joey’s full recovery took about a year. Now, he’s a high school junior with good grades and a part-time job.

“I’m so grateful we had Dr. Todd and Dr. Bobby on Joey’s team,” Betsy says. “Thank God we live where we live — so close to CHOP.”

Sharing advances, fueled by philanthropy

Through the Resuscitation Science Center, innovations generated and tested in the lab can quickly move to clinical trials. Once confirmed, they become the protocol at CHOP and, eventually, nationwide.

For example, CHOP has long been the national leader in improving cardiopulmonary resuscitation (CPR) in children. Sutton led a multi-institution clinical trial that moved pediatric CPR from a one-size-fits-all model to one that considers the child’s blood pressure. This approach is outlined in the updated 2020 American Heart Association resuscitation guidelines, and Sutton and his team are now developing the curriculum for national training.

Those efforts recently received a $1 million boost from the Ferrier, Nicoletti and Peruto families, who made their commitment to honor their mother, the late philanthropist Beatrice F. Nicoletti. The gift supports a strategic partnership between CHOP’s Center for Pediatric Resuscitation and the American Heart Association.

“We are incredibly grateful for the generous funding from the Ferrier, Nicoletti and Peruto families and our continued partnership with the American Heart Association,” says Vinay Nadkarni, MD, co-founder of the Center for Pediatric Resuscitation, with which Sutton and Kilbaugh are also affiliated. “Their support will allow us to discover the next-generation interventions for pediatric cardiac arrest and share our knowledge widely to help children and families who need these services the most.”

Precise and personal

For his part, Sutton’s ongoing research is testing how to personalize the amount of heart-stimulating medication to give during CPR, how to better time chest compressions and how to determine the optimal rate and pressure to force air into the lungs.

One problem: A child needing CPR may have a pulse detectable only with an invasive catheter. To help address this, Sutton is partnering with biomedical engineers at Villanova University to develop methods to use pulse oximetry data — the oxygen monitor used on nearly all patients — to monitor CPR quality. By using machine learning analytics, otherwise “unknowable” information can be detected in high-fidelity waveforms collected at speeds of up to 250 data points per second. With further development, these algorithms can be brought to the bedside to improve CPR dramatically.

The same analytics can also be used to determine if the child’s heart is starting to beat under CPR. “It can tell you if the heart is coming back, even the tiniest bit,” Sutton says. “It’s more helpful for the child if you can synchronize chest compressions at the time when their own heart is trying to push blood out. When we get this to the bedside, we can save a ton of lives.”

Brain power

To improve outcomes beyond saving lives, it’s critical that oxygenated blood reaches the brain to minimize or prevent neurological problems.

Kilbaugh and his collaborators have created a prototype device that can monitor blood flow and metabolism in the brain in real time, noninvasively and within seconds. The neurometabolic optical monitor (NOM) is a small disk placed on a child’s forehead that beams near-infrared light into the head. The light reaches red blood cells in the brain, then bounces back to the NOM, which calculates blood flow and oxygenation.

While clinicians could use the NOM during CPR and surgery, it could also be used to monitor any critically ill child — including during ECMO.

Currently, a child’s weight determines the rate of blood flow for the ECMO machine, which is monitored 24/7 by a respiratory therapist who makes any needed adjustments. A NOM, though, could “talk” to the ECMO machine, which would automatically make adjustments depending on the oxygenation of blood in the child’s brain — a much more precise way to optimize brain health.

“It’s like science fiction,” Kilbaught says. “It’s the ultimate in personalized care.”

Critical care makes advances possible

Critical Care Medicine also plays an essential role in improving treatments for illnesses and diseases across the hospital. Sometimes, when a treatment is new, there can be unexpected and severe side effects. Again, Critical Care specialists are on the front lines, figuring out how to counteract those effects so the new treatment can do its work.

Emily Whitehead, the first child treated with then-experimental CAR T-cell therapy for relapsed leukemia, is one example. She experienced a life-threatening inflammatory response to CAR T-cell therapy, a treatment that uses a patient’s own modified immune system cells to attack their cancer. It was Critical Care specialists, along with her oncologists, who helped her through so the CAR T-cells could kill off her cancer. Nine years later, she’s still in remission, and more than 375 other children with relapsed leukemia treated at CHOP have a future because of the special collaboration between Critical Care and Oncology.

“The program may not have accelerated like it did if the ICU had not rescued those kids early on,” Kilbaugh says. “Critical Care helps aggressive, next-generation programs throughout CHOP push the limits.”

What ‘no other hospital is doing’

In a more perfect world, fewer sick kids would need the PICU or require resuscitation.

The Resuscitation Science Center is working toward that end, too. Along with the devices in progress, Kilbaugh — whose research is supported by the Mary Jane Raymond Fund, the Ryan Family Fund and the Chappell-Culpeper Family Foundation — is investigating medications that reduce brain injury after a child has had a period of inadequate blood supply to the brain. Additionally, in collaboration with the Department of Defense, he is developing therapeutics to treat traumatic brain injury. Sutton is working to figure out how to identify inpatients whose health is just beginning to deteriorate so interventions can be started earlier to reverse the trend.

Critical Care specialists are also an important presence on the hospital’s medical and surgical units. Twice a day, a Critical Care physician, nurse and respiratory therapist visit the sicker patients and consult with staff caring for them. The aim of this approach is to provide advice on care to keep children out of the ICU, or if a child does need stepped-up care, to transfer them to the ICU before their situation becomes urgent.

“Our goal is to eliminate codes outside the ICU,” Sutton says. While the group has work to do, they are on pace for a 50% reduction in emergency transfers to the ICU in 2021 compared to last year.

Reflecting on the breadth of the team’s work, Kilbaugh adds, “We have a pipeline that goes from lab to concept to patient to trial. We’re extremely excited to do the work no other hospital in the country is doing for pediatric patients.”