NIDILRR Burn Model Systems Priorities and Galveston Studies
Importance of the Problem
This proposal presents a model system of rehabilitation for
burned children that will conduct studies on behalf of those children
who have large and severe burn injuries.
Many burn survivors are children with severe burn injuries. The National Burn Repository 2016 Report1
registered 205,033 burn center admissions from 1996-2015. Of these, 97%
or 198,369 persons survived. Approximately one-third of the survivors
(33.7%) were under age 20 years; almost 20% were under 5 years old and
14.3% were 5-19.9 years. It is clear that a large number of children
suffer burn injuries and survive to return to their home communities.
Many of these will be recovering from large severe burns. At Shriners
Hospital for Children in Galveston (SHC-G), approximately 17% of our
admissions (60 children) per year can be expected to have burns > 40%
Total Body Surface Area (TBSA); 8.5 % of our admissions (30 per year)
will have suffered burns of over 60% TBSA and almost half of these will
have burns over 80% TBSA. Mortality of children with large burns has
diminished dramatically. Half the children under age 14 who are admitted
to us with burns of TBSA=99% can be expected to survive; half the
children over 14 who are admitted to us with burns of TBSA=88% can be
expected to survive.2
Pediatric injuries present unique challenges at the time of acute
treatment and throughout rehabilitation. Although there are
similarities in treatment of adults with burns, children have special
needs requiring treatment protocols designed for them. Whereas the adult
body and brain are mature and relatively static, the body and brain of a
child are constantly evolving. Skin grafts in children must be placed
with a consideration for the changes that occur during growth and
development, and scar contractures limiting movement are more common.
The child's self-concept and cognitive schema of the world are
rudimentary. There is little known of how a severe burn and intrusive
treatments may impact children cognitively and emotionally; even less is
understood about the varying impact at different developmental stages.
Our research emphasis is on children with large and severe burns
because they present the greatest challenges to the burn care team,
acutely and throughout the years of very expensive recovery, extensive
rehabilitation, and reconstructive procedures. The problems addressed by
research in this proposal threaten the survival of persons with large
and severe burn injuries; for those who do survive, these problems
impede their rehabilitation and badly interfere with their successful
resumption of participatory life in their homes and communities.
A hypermetabolic/catabolic stress response occurs with severe burn injury and lasts for about 1 year post-burn.3,4 This stress response is characterized by a number of events that are life-threatening,5 to
the patient, e.g. tachycardia and cardiac dysfunction, increased
cardiac output, increased resting energy expenditure, increased protein
catabolism and peripheral protein wasting, hyperpyrexia, and increased
lipolysis. The erosion of body mass that occurs with catabolism can lead
to impaired immune function, decreased wound healing, pneumonia,
pressure sores, and eventually death. Children with large burns suffer
arrested vertical growth6. Bone formation is slowed, and bones are weakened7. In no other disease or trauma is the hypermetabolic response as severe as it is following a thermal injury5.
Even when the patient survives, the debilitating effects of
hypermetabolism delay and limit restoration of function for the patient.
Without intervention directed toward mitigating the effects of this
stress response, such debilitated survivors are destined to return to
their communities still struggling with the fatigue and frailty
secondary to this stress response. Survivors of large burns, during the
critical first year post-burn, are reestablishing body competence with
daily painful physical therapy exercises and application of appliances
to assist in their rehabilitation. They must reintegrate into society
and interpersonal relationships with attendant insecurities about their
changed appearances; they are returning to work and/or school; they are
grieving their losses. At a time when they most need strength, their
bodies are in a catabolic state resulting in muscle wasting, bone
weakness, and extreme fatigue.
They must endure their physical rehabilitation and return to
activities such as school or work in spite of their physical exhaustion,
for delaying these activities would further debilitate them physically,
psychologically, and socially. Often, they are experiencing
psychological symptoms of the response to trauma, Post-traumatic Stress
Disorder, concomitantly with the hypermetabolic stress response, and are
additionally plagued by such symptoms as sleep disturbance, irrational
fear, and flashbacks8. Their performance in daily activities
is impaired by stress and fatigue, so, in addition to their other
difficulties, they may now fail to achieve success in school or at work.
During that first year post-burn, survivors of large severe burns
suffer stigmatization, not only because their appearance is different
from non-burned peers, but also because they cannot keep pace with those
peers. Burn survivors must develop new self-concepts to allow for the
changes in their bodies; for survivors of severe burns, the rudimentary
changes to self-image are established during these months when it is
probable that they begin to define their “new selves” as less competent
Because SHC-G receives so many children and adolescents with
massive burn injuries that survive and because we follow these patients
into early adulthood, we have both a need and an opportunity to explore
venues that have the possibility of diminishing their difficulties and
assisting them in recovery and long-term gains to achieve maximal
The vision that has guided our research for 25 years is to
diminish mortality from burn injuries and to improve the quality of life
for survivors of burn injuries; for the last 10 years, our research has
emphasized the importance of finding means to mitigate the effects of
the hypermetabolic/catabolic response to large severe burn injury. We
envision patients with life-threatening severe burns who survive with
shorter hospital stays and less overall debilitation. The survivors in
our vision will be stronger, have greater endurance, and will return to
active, participatory lives suffering less from physical fatigue,
constricted movement, and psychological terror. They will begin the
tasks of relating to the non-burned world and building a new
self-concept with more energy and a more positive attitude. We predict
they will have even better outcomes and at an earlier time post-injury
than expected with current usual care.
The studies we propose directly address this vision:
- We propose a collaborative study of the efficacy of
propranolol administered for 1 year post-burn to moderate the effects of
the hypermetabolic response for patients of all ages; because
propranolol has been suggested as a means of secondary prevention of
post-traumatic stress disorder (PTSD), we include in the collaborative
study a method for studying this effect of propranolol as well. The
target population for this study is survivors of large burns, Total Body
Surface Area burns (TBSA) â?¥ 30%, ages 0-90 years. Although we include
adults in this target group, our center will contribute a large number
of pediatric patients as subjects with a lesser number of adults who can
be recruited from the Blocker Burn Unit at the University of Texas
Medical Branch. Our collaborators would also contribute subjects, thus
increasing the number of adults sufficiently to conduct the study.
- For children ages 7-19 with large burns, TBSA â?¥ 30%, we
propose (2) a study of the efficacy of long-term propranolol in addition
to a 3 month in-house resistance training and aerobic exercise program
previously shown to ameliorate many effects of the
hypermetabolic/catabolic response9,10. As part of the exercise study, we
propose continuing to study the efficacy of a similar program that was
begun during the previous funding cycle for children under the age of 7
with TBSA â?¥ 30%; we also will examine these data for benefits of
adding propranolol to the exercise regime.
- Finally we propose a study of the natural history, treatment
efficacy, and predictors of acute stress disorder (ASD) and
post-traumatic disorder (PTSD) in children (ages 3-18) who have survived
burn injury and who are treated at SHC-G with the expectation that this
study will facilitate early diagnosis and improved treatment of those
conditions that plague a sizeable group of burn survivors.
The first 2 studies are extensions of work initiated in Galveston
in 1997 with the inception of the Burn Model System at SHC-G and
continued through the 2002-2007 funding cycle. As detailed in Section C,
those studies have demonstrated that the anabolic agents growth hormone
and oxandrolone and a resistance and aerobic exercise program,
separately and together, significantly diminished the negative impact of
the early and enduring hypermetabolic state. However, growth hormone
must be given by daily injection and can be dangerous for older
patients. Cost of oxandrolone is prohibitive for most situations.
Propranolol can be administered orally, is much less expensive, and is
safer for patients of elder ages. Pilot studies with propranolol
indicate it to be very promising in mitigating effects of the
hypermetabolic/catabolic response, and some evidence suggests it to be
effective in preventing the development of PTSD. Thus, it seems a
logical choice for study.
The 3 month in-house exercise program for children 7 years and
older, with or without addition of anabolic agents, presented such clear
evidence of efficacy that, by 2004, it was accepted as state of the art
“usual” care for large burns at SHC-G. Unfortunately, such a program
has not been integrated into care in most other burn centers. There are
reasons to believe that the beneficial effects of this exercise program
may be enhanced by the long-term administration of propranolol, and that
is the purpose of proposing it as a site specific study here.
Additionally, we have begun to develop a comparable “play” program
accompanied by music for the children under age 7 that should be studied
in the same way as that for the older children.
The ASD-PTSD study is also an extension of a project begun during
the last funding cycle, and as reported in Section C it is producing
interesting results. Thus, we include it here in the belief that the
findings will facilitate efforts to assist children suffering the
debilitating effects of these disorders.
- American Burn Association Advisory Committee. National Burn Repository 2016 Report,, 2016.
- Pereira CT et al. Age-dependent differences in survival after severe burns. J Am Coll Surg 202(3):536-48, 2006.
- Hart DW, SE Wolf, R Mlcak, DL Chinkes, PI Ramzy, MK Obeng,
RR Wolfe, Herndon DN. Persistence of muscle catabolism after severe
burn. Surgery 128 (2):312-319, 2000.
- Hart DW, Wolf SE, Chinkes DL, Gore DC, Mlcak RP, Beauford,
RB, Obeng MK, Lal S, Gold WF, Wolfe RR, Herndon DN. Determinants of
skeletal muscle catabolism after severe burn. Annals of Surgery 232(4):455-465; 2000.
- Spies M, Muller MJ, Herndon DN. Modulation of the hypermetabolic response after burn. In Total Burn Care(2nd Edition), DN Herndon (Ed.):363-381. WB Saunders, London, 2002.
- Low JFA, Herndon DN, Barrow RE. Growth hormone ameliorates growth delay in burned children: a 3-year follow up study. The Lancet, 354:1789, 1999.
- Klein GL, Herndon DN, Goodman WG, et al. Histomorphometric
and biochemical characterization of bone following acute severe burns
in children. Bone, 17(5):455-60, 1995.
- Saxe G, Stoddard F, Sheridan R. PTSD in children with burns: a longitudinal study. J Burn Care Rehabil 1998; 19(1, part 2): S206.
- Pitman RK, Sanders KM, Zusman RM, Healy AR, Cheema F, Lasko
NB, Cahill L, Orr SP. Pilot study of secondary prevention of
posttraumatic stress disorder with propranolol. Biol. Psychiatry 51:189-142, 2002.
- Zatzick D & Roy-Byrne PP. From bedside to bench: How the
epidemiology of clinical practice can inform the secondary prevention
of PTSD. Psychiatric Services 57(12):1726-1730, 2006.