Research Spotlight - Cool Kids Trial
In the past, it had been thought that children had better outcomes than adults following traumatic brain injury. In fact, younger children (those less than four years of age) actually have worse outcomes. In addition, trauma is the leading cause of death and disability in children; more than all other causes combined. Problems that develop with motor, behavior, learning, memory and other higher-level functions are common even in children with only ?moderate? or ?mild? concussion injuries. Unfortunately, the reason(s) for the difference between children and adults and between children of different ages remain unclear. With the publication of the Guidelines for the Acute Medical Management following Severe Traumatic Brain Injury in Infants, Children, and Adolescents
in 2003 , we have become much more aware of the need for further research in pediatric traumatic brain injury.
Many experimental, pre-clinical studies have shown that the use of hypothermia, or cooling of the core body and brain temperature has been helpful in lessening the damage following a brain injury. Recently, a trial in newborns with hypoxic ischemic brain injury found that hypothermia significantly improved the outcomes in children who were cooled . In one of our first studies, a pilot Phase II safety and performance trial, we showed that not only was hypothermia safe in children following severe traumatic brain injury but may potentially improve outcome .
An article was recently published in the New England Journal of Medicine about hypothermia in children with traumatic brain injury . This multi-center trial assigned 225 children to receive either cooling (temperature of 32.5ºC) or normal care (temperature of 37ºC). The authors started cooling between 1.6 and 19.7 hours, kept the children cool for an average less than 1 day, and re-warmed them on average over a period of less than 1 day. Cooling was achieved by use of a hypothermia blanket only. There were deaths in 21% of the hypothermia group and in 12% of the normothermia group, but this was not different statistically. Of concern, there was a significant difference in blood pressure between groups, with the hypothermia group experiencing lower blood pressures during the time they were re-warmed. The authors reported that this particular
protocol did not improve outcome in children and then concluded that further research was necessary to determine if earlier initiation and longer cooling would be efficacious.
Presently, the Cool Kids Trial (CKT) investigators are conducting a clinical trial to determine if hypothermia improves neurological outcomes after traumatic brain injury in children. There are substantial differences between this recent trial and the CKT. In the CKT, children who are made cool will be started earlier (within 6 hours), receive 2 days of cooling (32-33ºC) and then be more slowly re-warmed over at least 2-3 days. In the CKT protocol, both intravenous and surface cooling will be used and children will begin to receive cooling within 6 hours of injury. Unlike the previous trial, the Guidelines for the Management of Severe Traumatic Brain Injury in Infants, Children, and Adolescents
 will be followed and avoiding low blood pressures is a top priority within those guidelines. The children will be followed for up to 12 months after their injuries and they will have detailed neuropsychological testing at various times throughout their recovery. Overall, this clinical trial will involve 12 pediatric trauma centers and plans to enroll 340 children over 5 years. We believe that this trial will determine if carefully applied hypothermia through a rigorous protocol can improve the neurological outcomes of children after traumatic brain injury.
- 1. Adelson PD, Bratton, SL, Carney, NA et al. Guidelines for the acute management of severe traumatic brain injury in infants, children and adolescents. Pediatr Crit Care Med. 4 (3): S2-75, 2003
- 2. Shankaran S, Laptook AR, Ehrenkranz RA, et al. Whole-body hypothermia for neonates with hypoxic-ischemic encephalopathy. N Med. 353: 1574-1584, 2005
- 3. Adelson PD, Rageb, J, Muizelaar JP, Johnson D, Kanev P, Brockmeyer, D, Beers S, Brown, SD, Cassidy L, Chang Y, Levin H. Phase II Clinical trial of moderate hypothermia following severe traumatic brain injury. Neurosurgery. 56 (4): 740-754, 2005
- 4. Hutchison JS, Ward, RE, Lacroix J, Hebert PC, Barnes MA, Bohn DJ, Dirks PB, Doucette S, Fergusson D, Gottesman R, Joffe AR, Kirpalani HM, Meyer PG, Morris KP, Moher D, Sing, RN, Skippen PW, for the Hypothermia Pediatric Head Injury Investigators and the Canadian Critical Care Trials Group. Hypothermia therapy after traumatic brain injury in children. N Engl J Med. 358: 2447-2456, 2008