Putting traumatic brain injury on ice
By Gabrielle Gray

In the seconds before Derek Smith was struck by the van, he was a typical kid enjoying the freedom of lunch break on an unseasonably fine November afternoon.

Like a lot of teenagers, the Grade 10 student at Lisgar Collegiate in Ottawa was not very interested in school and very interested in the multitude of things that capture the imaginations of most 15-year-old boys: hanging out with friends, video games, music, girls — loosely in that order. 

In a bid to get him to improve his grades, Derek's parents had offered the bright but unmotivated teen a deal. If he was able to maintain a decent grade point average, he could attend a much-begged for ski instructor school during the upcoming Christmas holidays. The dangled carrot had been a success, and Derek had an improved report card and a ticket to ski school. He had also unwittingly discovered a talent for computers and math. 

On the afternoon of the accident, Derek and a few friends had decided to while away their lunch hour down at the Rideau Canal, nearby their high school. It was when crossing the busy Queen Elizabeth Driveway to get back to school that Derek became a statistic.

According to Health Canada, head injury is the number one killer and disabler of Canadians under the age of 40. Car crashes account for over half of all traumatic brain injuries. Every five minutes, someone is injured. Every seven hours, someone dies. Males are twice as likely as females to suffer head trauma, and the 15- to 19-year-old age category is most at risk. The long-term effects are staggering: 22 per cent of people with catastrophic injuries never leave their homes; 92 per cent of men and 100 per cent of women who sustain a brain injury can never hold down a full-time job.

Derek's mother, Heather Smith, was at her mother-in-law's house when she got the call from her husband telling her Derek had been involved in an accident and was on his way to the Children's Hospital of Eastern Ontario. Smith had been in the middle of helping her mother-in-law sort through paperwork. Just three months earlier, Derek's grandfather had been killed in a horrific car crash. The two women had been about to leave for an appointment with their lawyer when the phone rang.

Smith recalls what raced through her mind during the drive to the hospital.

"There's this sense of disbelief and fear. You don't know what you're going to face. In my mind, the picture I was hoping for was that I would arrive at the hospital, and there would be my son, sitting on a gurney with a rueful smile on his face. But of course, there are lots of other fears too dark to face."

Miraculously, Derek had survived, but just barely. When the Smiths arrived at CHEO, they were initially not allowed to see Derek, told only by doctors that it had been a very bad accident, "The implication was obvious," says Smith. "It was touch-and-go."

Derek had suffered a severe brain injury. He was unconscious and required a mechanical ventilator to help him breath. His Glasgow Coma Score  — a 13-point score that measures a person's level of consciousness (three being brain death, 15 being full consciousness) — was around eight. A CAT scan came back showing abnormal brain activity.

Derek's family and friends began to pour into the hospital waiting room, sitting side by side with parents' whose children were in for day surgery. "There we were sitting in the day room with all these strangers around, while doctors came in and told us the most terrifying news that a parent can ever hear," says Smith.

It was in this tiny, windowless waiting room that Smith first met Dr. James Hutchison. The doctor on duty in the intensive care unit (ICU) had sent Hutchison because he thought the pediatric intensive care specialist might be particularly interested in Derek's case. Hutchison had just received ethics approval to begin a clinical trial studying the effect of mild hypothermia on children with traumatic brain injury.

"Jamie talked a bit about the study, and why they were doing it," says Smith. "And my husband and I sat there with no opportunity to review the literature, no idea about how promising this looked or didn't look. I felt terrified of making the wrong decision."

Derek's parents had to give their consent within eight hours of his accident, or he could not be included in the study. The reason for the haste was, according to the guidelines of Hutchison's trial, mild hypothermia needs to be induced as soon as possible after a child's head injury (no more than eight hours) in order for the treatment to be effective.

Having to make a quick decision about the clinical trial only added one more layer of complexity to what Smith was already going through.

"It put me on the spot right away. But was that more difficult than sitting there and waiting to see my child? Than hanging on to him for a month wondering if he'd live or die, or what he would be like for the rest of his life? I don't know. I turned into a super-efficient person, and I looked at this decision and I realized that it was one that had to be made quickly. I wanted my child to have every advantage possible. And really, I mean, we were talking about hypothermia. I'm not an uneducated person. I had heard lots about hypothermia lowering temperature to reduce the brain's need for oxygen. I didn't see how it could be harmful."

Derek shortly became the very first patient enrolled in the Hypothermia Pediatric Head Injury Trial, or HyP-HIT.

After receiving consent, doctors promptly placed a cooling blanket under Derek, packed garbage bags full of ice on top of him, and put another cooling blanket over the ice packs. They inserted a temperature probe in his throat to monitor his body temperature, making sure he reached and maintained a temperature of 32 to 33 C. They also gave him a neuromuscular blocker to prevent shivering. When the bags of ice started to melt, the ICU nurse who never left his side replaced them. Derek stayed in this state of hibernation for 24 hours. Then, doctors slowly warmed him back to life and a normal body temperature of around 37 C.

Hypothermia history

The idea of hypothermia as a possible treatment for traumatic brain injury is nothing new — it's a theory that's been kicking around since the 1930s and '40s. Many doctors who conduct research in the area of head injury believe the potential benefit of hypothermia is a question that finally needs to be answered. 

With a severe head injury, there is irreparable damage caused to the brain at the moment of impact. However, immediately after the head trauma, white blood cells begin to trespass across the blood brain barrier, inflaming the brain and further destroying brain cells. This is especially devastating to children, because their brains are still developing. The theory behind hypothermia is that by cooling a person's body temperature immediately after a traumatic brain injury, this secondary brain damage can be slowed.

Previous studies

Clinical trials have shown that in rat populations with traumatic brain injuries, hypothermia has reduced the permeability of the blood brain barrier, the bruising and swelling of the brain, and neural cell death and injury; while it has improved neurological behaviour scores. In recent years, there have been a number of human clinical trials studying the connection between hypothermia and traumatic brain injury outcomes (Marion, et al., NEJM, 1997; Jiang, et al., J Neurosurgery, 2000; Clifton, et al., NEJM, 2001). Two of the trials showed promising results, while one showed no benefit and, in fact, indicated hypothermia may be harmful to patients over 45 years of age. However, all these trials looked only at adult populations, and none of them come even close to the size, scope and standardization of HyP-HIT. 

HyP-HIT

Hutchison first become interested in traumatic head injury when a university friend, who was on the national ski team, was severely disabled by a head injury. 

"He was a fantastic skier, and now he's still in a wheelchair, still dependent for care."

During his residency, Hutchison was dismayed by the number of children who came in with severe brain injuries, and he became committed to finding new and better treatments.

In 1998, Hutchison decided it was time to study the effectiveness of hypothermia treatment for children with traumatic brain injury. The ultimate goal of Hutchison's clinical trial is to determine the effect of mild (32-33 C), short-term (24-hour period) hypothermia on the neurological outcome of children who have suffered serious head trauma, compared with similarly-injured children who do not receive hypothermia treatment. The method of cooling is exactly that experienced by Derek.

Dr. Sally Kuehn was the first pediatric neuropsychologist Hutchison brought on board. She was instrumental in helping to design the post-head trauma testing measures for the children involved in the trial. Kuehn says children with traumatic brain injury need a more comprehensive set of tests than adults. "Children are much more variable than adults, because they're on a developmental continuum. So they change rapidly. And in order to compare across ages, and determine whether a treatment has been effective, you need to have fairly sensitive measures."

While the children are administered various cognitive function, intelligence, memory and attention tests at one, three, six and 12 months post-head trauma, the most important is the Pediatric Cerebral Performance Category (PCPC) measure. All the children are assessed at six months post-head injury using the PCPC, a six-point scale measuring a child's cognitive function (one being normal, six being death). A score of one, two or three is considered a successful PCPC score by the study. When the trial is complete, the test results of both the hypothermic and normothermic groups will be compared and contrasted to determine if hypothermia treatment improves a child's PCPC score, or cognitive outcome.

HyP-HIT is now in its fourth year, and Hutchison hopes it will be complete by 2004. It is a massive collaborative effort that will eventually involve over a $1.5 million in funding, 225 patients, 19 hospitals, four countries and one central randomization system. Each new hospital involved in the trial undergoes a run-in phase to make sure they have all the randomizing, cooling, warming and testing procedures down pat. 

So far, there are 100 patients enrolled in the study, with an average of five new patients recruited per month.

An interim progress report on HyP-HIT is due out this summer, when Hutchison and his colleagues will decide whether the results are promising enough to continue the trial to completion.

Roxanne Ward is the study coordinator for HyP-HIT. She says the trial is important because all the children, in both the experimental and control groups, receive superior primary and follow-up care. However, the registered nurse says it is sometimes hard to reconcile the excitement over enrolling a new patient (and being one step closer to completion), with the fact a family has just suffered an immense tragedy, possibly one in which other family members have been killed.

"I know the study's not responsible for the injuries that the child has incurred. I have to look at it that the more patients we recruit, the sooner the study will be complete. Then, we will be able to publish results and perhaps change care for those kids all over the country and in other parts of the world. So that's how I kind of justify my elation."

Hutchison is likewise pretty thrilled to be doing what he does.

"Research is very, very exiting, and it's fantastic to have the opportunity to do it. I hope that part of what we do here is train people, instill them with that excitement about doing research and actually discovering new therapies that work and make an improvement in the health of patients that we treat."

Derek today

The bottom line is that while the beneficial effect of hypothermia treatment on traumatic head injury in children remains to be proven, no one's arguing it's a miracle cure.

For Derek, the progress is slow.

He is almost completely recovered physically, but the neurological healing has come more haltingly.

"What I have now is a boy who has no social life, no friends left in his life," says Smith, "That's a huge challenge. He spends all of his time, at 18 going on 19, with his dad and with me. So, here we are three and a half years later, and I'm still trying to prioritize what's important in this boy's life, and find ways of making things happen for him."

It's not yet clear whether Derek will ever be able to have a job.

When asked what's the most positive thing to come out of Derek's accident, his mom replies, "That we all survived it. My marriage is intact, my family is intact. And those are huge accomplishments. We're stronger, our priorities are clearer to us. I have no difficulty saying, no, I'm not going on that board, or I can't do that right now."

Derek and his mom went together to see the movie i am sam, about a mentally disabled father who fights for custody of his daughter.

"He came out of that saying, 'Well, I could be in that situation one day,' " says Smith. "Derek is an amazing young man, absolutely terrified about his future."