Summer is the Deadliest Season for Brain Injury and Dr. Gaylan Rockswold is Working to Change What Happens Next

Memorial Day weekend has come and gone, and with that has come a familiar shift at Hennepin Healthcare's emergency department.

Motorcycles hit the road. People take risks they wouldn't take in February. And when things go wrong, some of those people arrive at Hennepin in a coma, their brains swollen and bleeding, with families in waiting rooms who haven't yet absorbed what is happening.

Gaylan Rockswold, MD, PhD, has seen it more times than he can count.

"When people start doing crazy things, that's when it happens," said Rockswold, a neurosurgeon and principal investigator at Hennepin Healthcare Research Institute (HHRI). "The summer months, Memorial Day weekend, classic. Fall can be busy too. It's seasonal, but not always predictable."

Rockswold has spent more than 40 years trying to do something about brain injury care. He is the lead investigator of a landmark NIH-funded clinical trial testing whether a pressurized oxygen treatment can change outcomes for patients with severe traumatic brain injury (TBI), a diagnosis that has stumped the medical community for decades. The trial is called HOBIT, short for Hyperbaric Oxygen Brain Injury Treatment, and after more than 40 years of groundwork, it may be closer to an answer than the field has ever been.

A Stubborn Problem

Most people have experienced some form of traumatic brain injury or know someone who has. A fall, a car accident, a collision on the field. Most of those injuries are recoverable. Severe TBI is something else entirely.

Severe TBI accounts for roughly 10% of all brain injuries, but it carries a mortality rate of 30% or higher. Of those who survive, only about 30% make what physicians consider a good recovery. It is the leading cause of death and severe disability in young adults. Nearly 69,000 Americans die from TBI-related injuries every year.

What makes it so hard to treat comes down to what happens inside the brain in the hours right after an injury.

The brain makes up only about 2% of body weight, but it uses roughly 20% of the body's oxygen supply. It runs at full demand around the clock, not like a muscle but more like a system that never gets to rest. When a severe injury disrupts blood flow and oxygen delivery, that system starts to fail fast.

Without oxygen, the brain's cells shift into an inefficient backup mode, producing lactic acid and triggering a chain of damage that can lead to widespread cell death. The mitochondria, the tiny structures inside cells that generate energy, essentially stop working. And once that process starts, there has been very little medicine can do to stop it.

"Outcomes have flatlined for basically my whole career," Rockswold said. "We can take care of their lungs. We can take blood clots out. But we don't have anything to give to the patient that will actually make a difference."

That is the problem he has spent his career trying to solve.

Where Oxygen Comes In

The treatment at the center of the HOBIT Trial is called hyperbaric oxygen therapy, or HBO. The idea is that if the brain is starved of oxygen after an injury, delivering a concentrated, pressurized dose of it might be enough to interrupt the damage and give the brain a fighting chance.

Normally, oxygen travels through the bloodstream attached to red blood cells, and there is a limit to how much they can carry. Inside a pressurized chamber, oxygen gets forced directly into plasma, the liquid part of the blood, which means significantly more of it reaches the brain.

Rockswold experienced HBO treatment himself after losing hearing in one ear due to sudden inflammation. "I experienced it firsthand," he said. "So, I know what these patients go through."

In severely injured patients, the results have been striking. Brain tissue oxygen levels that typically sit between 25 and 30 mmHg in an ICU have been measured above 400 mmHg in patients receiving HBO treatment. Research by Rockswold and his team has shown that oxygen consumption in the brain stays elevated for at least six hours after a session ends, a sign that the mitochondria are coming back online.

"What HBO does is rejuvenate those mitochondria," Rockswold said. "It helps reverse the cascade that results in cell death. That's the foundation this whole trial is built on."

Inside the Trial

The HOBIT Trial spans 12 Level I trauma centers across the country. Hennepin Healthcare is the only Minnesota site and has enrolled approximately 42% of all participants, more than any other site in the trial by a wide margin.

The trial tests six different HBO treatment approaches at varying pressures. Several are combined with normobaric hyperoxia, which is 100% oxygen delivered at normal atmospheric pressure for three hours after each HBO session. Rockswold's earlier research found that the mitochondria are most active in the hours right after HBO treatment, so the follow-on oxygen gives them more to work with. A standard-care control arm and a normobaric-only arm round out the design.

Getting a patient enrolled is not simple. From the moment of injury, the clock is running. Patients who don't require surgery have a six-hour window to receive their first treatment. Those who need surgery have up to 14 hours. In that time, the team has to stabilize the patient in the emergency department, get them to the ICU, potentially take them through surgery and back, get consent from a family member, and then transport them to the HBO suite.

"It requires everybody really, really working and moving," Rockswold said. "It's a scramble. But the more you do it, the better you get at it."

Once in the chamber, patients receive two treatments per day for five days. Each session runs at least 90 minutes. Because these patients are in a coma, the pressurization has to happen slowly and carefully. A small incision is made in the eardrum beforehand to help equalize pressure and avoid a spike in intracranial pressure. A full care team accompanies every patient inside, and the chamber itself is equipped like a small ICU.

"One of the things we've shown is that you can treat severe TBI patients with multiple injuries safely in a chamber," Rockswold said. "It has been scrutinized thoroughly, and it has been safe."

Waiting for the Answer

The trial has enrolled approximately 160 of its 200-patient goal. COVID-19 hit the study hard, slowing a recruitment process that was already demanding. Additional NIH funding has helped the team push through.
With the end in sight, the results are still blinded. Rockswold and his clinical team do not know how the treatment arms are performing. Only the trial's statisticians have that information.

"Sometimes you wish you could take a little peek," Rockswold said. "But the unblinded statisticians are absolutely firm, which is totally appropriate."

Success would mean identifying one or two treatment arms that clearly outperform the others and showing a greater than 50% probability that a larger phase 3 trial would succeed. Only about 20% of large clinical trials in this space have historically proven effective, so clearing that bar would be a significant step forward.

What keeps Rockswold going after more than four decades is not complicated.

"A young person is laying there, comatose, with a severe brain injury, and you can give them supportive care, but there's nothing specific," he said. "To provide a treatment that's going to improve functional outcome for many of these young patients, if this is successful, it's huge."

For the patients who will arrive at Hennepin's emergency department this summer, Rockswold is still doing what he has always done: working, waiting and fighting for a treatment that could change everything.