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            Advances in Burn Care

David. N. Herndon, M.D., Chief of Staff and Director of Research
Galveston SHC

  
   Recent changes and new therapies have been incorporated into burn care worldwide through the efforts of clinical and basic research. This article will summarize some of the important advances in treating burned children that were made possible through the support of the Shriners Hospitals for Children.

   It is often difficult to determine what specific discoveries change health delivery in burns.  The areas of advancement in burn care that have improved outcome are myriad and include acute care, burn wound treatment, control of the hypermetabolic responses, and control of life threatening infections.  The mortality and length of hospital stay of burned children have been greatly reduced over the last 25 years.  In the 1960's, the likelihood of survival was only 50% for pediatric burns covering 35-44% of the TBSA (total body surface area), and few patients with burn sizes above 45% TBSA survived.  The average length of stay for the acutely burned child was 103 days.  Today, the LB₅₀ (lethal burn size for 50% of the patients) for children exceeds 95% TBSA, and the average length of hospital stay for most serious burn injuries can be expected to be only 0.5 days per percent of TBSA that is burned.  This is truly a remarkable achievement and is striking testimony to the concentrated effort in personnel and resources that have been directed toward severely burned children.  The Shriners Hospitals for Children have contributed in a major way to this remarkable achievement by their very sound and sustained investment of substantial resources toward this endeavor at all four centers.  Specific aspects of burn care that have dramatically improved in burn hospitals include: treatment to improve acute care, such as resuscitation, early excision and grafting, the control of infections and improving the immune system, improvements in provision of metabolic and nutritional requirements, and the evolution of effective skin banks, infection control, and alternative wound-closure materials and strategies.

      Most importantly however, not only have the length of stay and survival rates improved over the last 25 years, it is also a remarkable achievement that severely burned patients have tremendously improved long-term outcomes.  Over the last decade major advances enabled burn patients to be effectively rehabilitated and reintegrated as productive members into society.  These patients have skills and developmental improvements that are truly outstanding leading to effective, productive, and thoughtful members of society and also making this world a better place.

   In the following we would like to point out specific achievements that have been done in the aforementioned areas, early excision and would treatment, improvement in acute care, resuscitation, controlling infections, understanding hypermetabolic response and lastly improvement in wound care.  The acute care of the burn patients encompasses adequate outpatient treatment as well as emergent treatment of the patient once the child is admitted into one of the four burn hospitals. 

Early Excision and Wound Treatment

   Although as early as 1947 researchers (1) had recognized that prompt eschar removal and immediate wound closure could improve outcome in burn injuries, application of this approach to large burns had not been practical before the 1970’s because of an associated high rate of infection, bleeding complications and wound failure. Many burn units adopted the excision technique (2), which was a single tangential slice that was intended to remove the superficial layer of second-degree injuries. The application of this tangential excision method to superficial injuries by most surgeons had been frustrated by the excessive blood losses that accompanied its use in large burns and those burns with full-thickness depths. The development of effective topical antimicrobials and systemic antibiotics in the 1960’s, combined with hypotensive anesthetic techniques and other blood-conservation measures, allowed prospective, but non-randomized, clinical trials to be conducted. In these studies (3), improvements in survival and length of hospital stay were seen and as a result of these encouraging outcomes this surgical approach was promoted.

   The exact contribution to the outcome of prompt eschar excision and immediate wound closure in large burns has largely remained unknown because prospective randomized clinical trials have not been conducted. A few prospective studies have been performed (4,5), which demonstrated that prompt excision improves hospital stay (6) and survival (7). These studies originated from Shriners Hospitals for Children and opened a new horizon for the treatment of severely burned children. Not only has survival improved, several centers have reported improvements in long-term function and cosmetics, leading to a decreased need for reconstructive procedures. Further developments have allowed safer operations and minimized blood losses (8). These advancements have allowed this method to be effectively used in burns of all sizes and make this approach the standard method of treating burn injuries (9,10). These standards leading to improved acute and long-term outcomes have been generated by the science and the research conducted at the centers of the Shriners Hospitals for Children.

   Because a clear clinical need for a skin-replacement material was evident by 1981, a bilayer artificial skin for permanent wound closure was developed, and preliminary clinical results of its use were reported (11,12). This material has been studied in an 11-center clinical trial comparing the artificial dermis to conventional grafting techniques after the early excision of the burns in patients with major thermal injuries (13). This artificial skin provided a permanent wound cover that was at least as satisfactory as currently available skin-grafting techniques. The take of the “thin” epidermal grafts on the artificial skin was 80% successful, and at the completion of the study less hypertrophic scarring was seen with artificial dermis. Furthermore, patients preferred the artificial skin to conventional grafting methods. Continued experience with this artificial skin has been extremely favorable, and a potential survival benefit has been associated with its use in massive burns (14).

Results from research over the last 10 to 15 years are now the standard of care and opened new directions for how patients undergoing early excision and grafting can be adequately covered. New approaches that will potentially be new standards of care in the near future include liposomal gene transfer (15) the use of artificial skin substrates, such as dermal matrices with epidermal components (16), amniotic wound coverage devices (17), dermal component matrices (18), as well as new areas involving stem cells (19). Several new studies are emerging from the four Shriners Burn Hospitals determining the efficacy and role of stem cells in severely burned patients and it appears that stem cells have a tremendous potential for the treatment of severely burned children. Despite the potential of stem cells the use is limited because of ethical concerns. However, ethical concerns can be avoided by using adult stem cells. Several groups at the Shriners Hospitals for Children are studying the efficacy and the potency of using adult stem cells to enhance regeneration of skin, liver, kidney, heart, pancreas or gut. Currently many studies funded by the Shriners are investigating the role of adult stem cells and the importance of adult stem cells is clearly shown in recent publications.

Gene therapy is another emerging technique to alter dermal and epidermal regeneration and to improve wound healing. The research performed at Shriners Hospitals for Children is using this cutting edge technique that may be a standard therapeutic approach in 10 to 20 years. Non viral constructs have been shown to effectively change the cells into a productive and active cell that releases growth factors and other signaling factors to improve dermal and epidermal regeneration (20). Another study demonstrated that this approach has even more potential and relevance as liposomal gene constructs transfect dermal stem cells increasing the therapeutic possibilities (21). This futuristic technology has evolved from cell cultures to small animal models and now to large animal models. Currently new research demonstrated that this technique is possible in large animal models, which is the last step before possible clinical trials. Therefore gene therapy may be not only a new approach to affect wound healing, but also other organs that are in need of a survival treatment.

That the future has arrived is clearly shown in a skin-substitute originating from the Shriners Hospital in Cincinnati in conjunction with the Shriners in Boston. A dermal substitute was developed at Shriners in Boston (Integra) which then has been used by the Cincinnati group to construct an artificial skin which is called Cultured Skin Substitute (CSS). CSS is the patients own skin (epithelium) in combination with a dermal substitute (Integra) represents a full skin substitue including dermis as well as epidermis. This newly functional skin is a major advancement in coverage of large burns in which we are in urgent need (22). This technique will open new developments and new approaches for an artificial skin, which will reduce the amount of donor sites taken from the patient and improve cosmetics associated with an improved quality of life in severely burned patients.

Fluid Resuscitation

   Another major improvement based on research conducted via support from the Shriners Hospital was major improvement and adjustment of resuscitation therapy. In the early 1960’s, formulas for fluid resuscitation for adults were already established. There was, however, a major controversy concerning the use of colloids as a part of the fluid resuscitation regimen (23). Studies led to the development of a resuscitation formula that was based upon body surface area and body weight (24), which proved to be more appropriate for the care of pediatric patients (25,26). This formula is now used around the world and has made a substantial contribution to survival of thermally injured pediatric patients, decreasing mortality from renal failure from 100% before 1984 to 56% after 1984 (27). Studies have further shown that patients with smoke inhalation injury require 2 cc per kg per percent TBSA burn more fluid than equivalent size burns without smoke inhalation injury.

Investigations have shown that after thermal injury there was a massive systemic vasoconstriction that occurred independent of sympathetic nervous system activity (28). These studies implicated antidiuretic hormones and the renin angiotensin systems as probable vectors of this response (29). The changes discovered from these investigations bear an important relationship to bacterial translocation (the passage of bacteria from the intestine into the circulation) after thermal injury, which may contribute to the development of multiorgan failure (30).

Recent studies from all four centers indicated that early initiation of resuscitation within 2 to 4 hours improves survival, organ function and morbidity as well as long-term outcomes of severely burned patients (31).

Despite advances made over the last decade, it is becoming more evident that each patient varies in their need of resuscitation. The formulas constructed do not really reflect the need of the patient. New formulas derived from several laboratories as well as clinical centers from the four Shrine centers show that patients should be intensively monitored, in terms of the cardiovascular system, the urinary system as well as the pulmonary system. Studies originating from the Shriners Hospitals looking at new catheter devices demonstrated the need of online, non-invasive monitoring of cardiopulmonary functions and its tremendous potential to individually direct fluid resuscitation (32). Other groups go one step further (33). The investigators used a closed-loop system to adjust resuscitation rates in conjunction with the non-invasive cardiovascular and pulmonary systems, resulting in the improvement of initial resuscitation and treatment of the severely burned child (33). This research is supported by the Shriners Burns Hospitals for Children centers and will be a major milestone in future patient care to improve the acute outcome of severely burned children.

Infection Control

   Infections in severely burned children are one of the main causes of mortality. A recent study originating from one of the centers at Shriners delineated that 30 to 50% of the burned children died due to infections or sepsis (34). Due to research originating from the Shriners Hospitals for Children studies showed that early excision and grafting not only leads to improved scarring and cosmetics, it also leads to decreased incidences of infections and sepsis (35). Removal of the burn scar dramatically decreases colonization of bacteria and fungi that can be detrimental and can lead to a systemic infection or sepsis. Studies conducted at the Shrine demonstrated that antimicrobial anti-fungal soaks play a major role to prevent tissue infection, systemic infection or sepsis. Soaks that are currently being used are effective by decreasing bacterial and fungal colonization of the burns originated from basic science and clinical studies conducted at Shriners Hospitals. Mafenide acetate, silver sulfadiazine and 0.5% Dakins solution are current topical treatments and have shown to greatly improve graft take and prevent infections. (36)

The finding of a high incidence of gram-negative sepsis in thermally injured patients without an obvious source of bacteria led to the development of the hypothesis that the source was from the gastrointestinal tract. The concept that the burn wound became infected as a result of organisms from the gut entering into the circulation was proposed. To test this hypothesis, the gastrointestinal tract of a group of dogs was infected with Pseudomonas labeled with a fluorescein tag. Bacteria crossing the mucosal barrier in burned animals were identified from fluorescence tags in the plasma. Later, this tagged material was found in the burn wound itself (37).

Recently, the importance of bacterial translocation has been recognized after cutaneous thermal injury, endotoxin administration, or an inhalation injury (30,38). Bacterial translocation associated with reduced blood flow was prevented by the use of vasodilators (39). These changes may be clinically important since a reduction in blood flow to abdominal organs is associated with the release of myocardial depressants (40-42). This could also explain the increase in mortality seen in patients with combined thermal and inhalation injury, since these two insults in combination produce a greater increase in abdominal vascular resistance than either insult alone. The need to prevent “under resuscitation” of burned patients has been well recognized (43-45). Most recently, a drug that inhibits the formation of one of the vasoconstrictive mediators (a thromboxane synthetase inhibitor), which was previously shown to be released by burn injury (46), has been shown to reverse the bacterial translocation of a thermal injury (47) and to reverse the myocardial depression that occurs with the administration of endotoxin (48). Preliminary data also indicate that compounds with anti thromboxane activities may also be effective in preventing the mesenteric vasoconstriction and myocardial depression observed with inhalation injury (48,49).

An important aim of current research in all Shriners centers is to improve the immune system. Burn patients are severely immunocompromised and are unable to fight off infections and bacteria. Research from the Shrine centers is not only focused on the treatment of infections but also the prevention and improvement of the host to defend infections. At all four centers several grant applications are looking at new ways to improve the immune system. New pathways, receptors, cell populations, drugs and new interventions are currently being investigated to change the immune compromised patient into an immune competent patient to improve survival. One of the examples of ongoing research are studies determining the effects of propranolol, a β1/β2, non-selective receptors antagonist, and its effect on the immune system. Preliminary data show that propranolol is able to reverse immune incompetent macrophages and monocytes into functional cells increasing bacterial clearance. This indicates that we have possibly a new treatment to reverse the devastating immune compromised state of severely burned children.

Another approach that originated from research performed at Shriners Hospitals is the interaction between the inflammatory response and the immune system, so that the severe burn causes a traumatic upregulation of the inflammatory response in the immune system. Recent studies (49-50) showed that a dramatic upregulation of many cytokines and inflammatory markers, hormones, stress hormones and stress markers persist over a prolonged period of time leading the alteration of the immune system but also in the body’s metabolic response. Therefore the immune system and the inflammatory response play a major role as mediators in the post-burn response and the alteration is thought to improve the outcome of severely burned children.

Metabolism and Nutrition

   Fundamental questions regarding the metabolic demands of the thermally injured patient have been evaluated, and several practical answers have emerged. The metabolic and nutritional questions include 1) How many calories do thermally injured patients require? 2) How many carbohydrate (glucose) calories should these injured patients be given to avoid starvation and to promote protein synthesis? 3) How many protein calories should these patients be given in order to achieve net protein synthesis? 4) What treatments should be given to reduce diabetic-like symptoms such as insulin resistance?

While the body of a burn victim undergoes many changes, the rampant acceleration of metabolism places an increased load on the heart, liver, kidneys, lungs and other vital organs that provide normal body stability. Massively burned children have two to three fold elevations in both heart rate and catecholamine levels, resulting in the body digesting peripheral muscles in order to support the voracious need for building materials necessary to heal wounds (51). Part of this high metabolic rate is useful as it helps the body provide building materials for the wound-healing process. There are, however, some adverse effects where the elevated metabolic rate may complicate respiratory problems. In addition, not all of the increased energy mobilized peripherally goes to wound healing. Burn patients show muscle wasting and become centrally fat as the liver is apparently unable to process the large amount of peripheral fuel presented to it. In many cases the metabolism in non-injured areas is so high that wound healing becomes retarded.

In light of the above events, choosing the proper level and source of energy is one of the most critical requirements to the patient recovering from a severe burn. Large amounts of carbohydrates and fat must be converted to energy to satisfy the requirements needed to nourish the traumatized body and fuel the rapid growth of new cells. An insufficient diet, therefore, can be extremely detrimental to the burn patient. On the other hand, excess calories can also be harmful. One major cause of mortality in burn patients is respiratory failure. Decreased respiratory and peripheral muscle mass reduces the ability to breathe and exercise. Excessive carbohydrate administration may increase CO2 production and further complicate the respiratory status. Determining the optimal caloric intake therefore requires giving sufficient but not excess calories, which has been an intense area of research funded by the Shriners.

Carbohydrate metabolism has been found to be greatly altered in these patients, and burn centers have pursued studies to consider how best to compensate for these changes (52,53). One of the more dramatic alterations is that glucose uptake rates and gluconeogenesis are greatly increased after burn injury. Despite these increased rates, researchers have demonstrated a practical limit in the glucose infusion rate (5 mg/kg/min) beyond which the excess glucose is not oxidized for energy but simply becomes stored as fat (53). The excess fat is stored in the liver and results in fatty livers, which elevate the diaphragm and compromise breathing. At glucose infusion rates above 5 mg/kg/min, the respiratory quotient exceeds unity and causes excess CO2 production and increases minute alveolar ventilation requirements. The combination of diaphragmatic elevation and increases in CO2 makes the respiratory failure frequently seen in these patients more severe.

Malnutrition and burn injuries have been associated with infection and death. Burn physicians in various cities began continuous feeding of milk to reduce the incidence of gastric and duodenal ulcers (54,55). As a result, stress ulcers rarely occurred in milk-fed patients. It was further shown that milk could prevent weight loss in children who were recovering from severe burns. This led to the practice of milk feeding up to one hour before any surgical procedure. Accurate formulas for the precise amount of calories required to maintain weight in burned children of different ages have continued to develop (56-59). The use of supplemental parenteral hyperalimentation, however, was shown not only unnecessary but also detrimental (60, 61). Early enteral and continuous feeding has now decreased mortality in burned children and is now accepted practice in burn units around the world. Because giving fat rather than carbohydrate can exacerbate fatty liver, in recent years there has been a shift away from providing high fat formulations such as milk toward high carbohydrate formulations.

Marked changes in organ and whole-body protein metabolism often accompany a severe thermal injury. Much of the knowledge about the nature of whole-body protein metabolism after trauma has been obtained from nitrogen-balance studies. These studies uncovered changes in total body nitrogen content without revealing the pathways in which these changes occurred. Many studies using stable isotopes and steady-state kinetic models have greatly contributed to understanding these changes in whole-body protein metabolism, and these studies have suggested how best to compensate for these changes in total body nitrogen content (62). Unlike most research, these experiments do not use laboratory animals or in vitro studies but are performed on patients. This is research made possible through the use of nonradioactive isotopic tracers (stable isotopes) which are naturally occurring atoms that possess an extra neutron that distinguish them from their more abundant natural form. By collecting expired air, blood, or tissue samples containing these stable isotopes, research scientists can track the transformation of amino acids into protein used to build muscle tissue.

Researchers have also studied protein metabolism in which tissues, such as muscle, are constantly being built up and broken down into basic components or amino acids. After thermal injury, protein breakdown exceeds synthesis, causing a net release of amino acids (63). When elevated in the serum, these amino acids are converted in the liver to glucose, a process known as gluconeogenesis, and then broken down to smaller compounds in peripheral tissues by anaerobic or aerobic metabolism. When the energy-producing process is anaerobic, the smaller sugars are converted into lactate and pyruvate; and this appears to be the process in thermally injured patients (64,65). The elevation of these substances can be detrimental to the patient. In addition to the acidosis created, other compensatory changes occur involving the utilization of glutamine, which is an essential fuel for the cells that line the gastrointestinal tract and of the immune system. Depletion of this amino acid causes the starvation of these cells, allowing toxic materials and bacteria from the gut to enter the systemic circulation. A potential therapy to combat this is being tested is the administration of compounds that stimulates the incorporation of amino acids into protein. Exogenously administered treatments such as oxandrolone and human recombinant growth hormone reverse the net protein breakdown produced by thermal injury and stimulates the use of amino acids for muscle synthesis (66,67). This not only redirects metabolism away from gluconeogenesis but also causes an increased incorporation of amino acids into healing wounds. An increase in rate of donor site healing and a decrease in length of hospital stay have been shown when growth hormone and other anabolic agents are used to treat burn children. Patients with 60% burn wounds had a decrease in length of hospital stay from 46 to 32 days (68).

After a thermal injury there is also a reorganization of protein synthesis. Several enzymes and proteins involved in the body’s defense system, such as blood coagulation factors, proteolytic enzyme inhibitors, and enzymes involved in the destruction of bacteria are increased at the same time other proteins such as albumin are reduced. A reduction in albumin can be detrimental since this plasma protein plays an important role in prevention of edema. Investigators are now beginning to identify the genetic and proteomic mechanisms responsible for these changes and have identified several factors that play a role in the regulation of these genes and proteins.

Researchers have demonstrated a very high level of the hormone epinephrine (adrenaline) in thermally injured patients (69,70). This hormone can increase metabolism by stimulating the -adrenergic receptors. Propranolol, a drug that is a competitive antagonist of -adrenergic receptors, has been shown to lower heart rates in burned children, decrease the amount of oxygen needed to keep the heart pumping and reduce the anxiety caused by burn released epinephrine without impairing the ability of the patient to respond to stresses (71,72). Fat is metabolized 2.5 times the normal rate in thermally injured patients, a process that is apparently the result of elevated catecholamines and -adrenergic stimulation since it has been shown to be blocked by propranolol (73,74). This fat is deposited in the liver, causing fatty liver. It has been speculated that this resulting fatty liver in turn causes insulin resistance in burned children, and they display many symptoms similar to diabetic patients. Shriners researchers have shown that reducing fatty liver in burned children with treatments such as propranolol and fenofibrate also improves insulin sensitivity. In summary, optimizing the nutritional and hormonal milieu is a critical area of improving burn care that is undergoing important advances.

One of the recent contributions from Shriners Hospitals research is that the hypermetabolic response also leads to effects on a cellular level. Hypermetabolism is associated with cell deaths (apoptosis), skeletal muscle, fat, liver, kidney, lung, heart and gut. These detrimental cellular events are also associated with dysfunction of the cellular organelles such as the mitochondria or the endoplasmic reticulum. These new studies clearly delineate that a burn injury is not limited to the skin. A burn is associated with the dysfunction of almost every cell in the body and various organs leading to alterations, again not only in cellular functions but also in cellular signaling pathways. Alterations and new treatments of these pathways may restore cellular function and productivity which leads to an improved energy metabolism, cell survival, morbidity, mortality not only during acute hospitalization but also long-term. Burn patients used to lose 40-50% lean body mass which was almost equivalent to a death sentence. Due to several new approaches to alter hypermetabolic response using early excision and grafting, adequate nutrition, growth factors, adequate ventilation, adequate fluid resuscitation, air beds and warm environment have decreased the loss of lean body mass, muscle, fat as well as bone to 5 to 8%. This is a dramatic change and improvement given the fact that losing 5 to 8% lean body mass is associated with a dramatic increase in survival. In summary, the hypermetabolic response to burn injury plays a major role and is a major determinant in a burn patient’s survival. Research originating from Shriners Hospitals for Children at all four centers advanced knowledge how to attenuate this hypermetabolic response, how to reverse this hypermetabolic response and improve patient outcome as well as quality of life. The less lean body mass a patient loses the better their strength, endurance, rehabilitation and reintegration.

Inhalation Injury

   Inhalation injury studies often follow two main pathways, one relating to parenchymal injury and the other to damage of the airway of the tracheobronchial tree (75-77). Inhalation injury was found to be associated with a marked increase in a transvascular fluid flux across the lungs (78). This fluid flux occurred as the result of changes in both microvascular pressure and permeability to protein (78, 79). Later studies revealed that lung edema formation was associated with polymorphonuclear cells (80). These cells induced their injury to the lungs as the result of the release of proteolytic enzymes (81) and free oxygen radicals (80). It was determined that the amount of fluid resuscitation required after smoke inhalation was greater than that required for a burn alone and that appropriate fluid resuscitation would reduce, rather than enhance, transvascular fluid flux (82, 83). These studies have resulted in an enhancement of fluid resuscitation in patients with concomitant thermal and inhalation injury. Techniques for measuring extravascular lung water by the thermal dilution technique have been applied to patients to evaluate the extent of their pulmonary edema (84).

Hyperemia (excessive amounts of blood) of the tracheobronchial tree after an inhalation injury is a characteristic used for the diagnosis of an inhalation injury (85). Investigators have shown that hyperemia is associated with a 10-fold increase in bronchial blood flow (86-90) and an increase in the permeability of the tracheobronchial areas involved. Reducing the hyperemia has been shown to reduce the pulmonary edema seen after smoke inhalation (88,91). Treating animals with capsaicin, a compound that depletes sensory nerves of their neuropeptides, markedly reduced both the elevation in bronchial blood flow and transvascular fluid flux commonly associated with an inhalation injury.

There are several concomitant changes in the systemic circulation related to an inhalation injury. The heart muscle is depressed, there is an increase in the vasomotor tone of the gut, and systemic microvascular permeability is elevated. Initial investigations have shown that the blockade of a potent arachidonic acid derivative, thromboxane A2, could markedly reduce these changes (92). With inhalation injuries presently accounting for the majority of the deaths in thermally injured patients (93,94), research and clinical advances in these areas have become the new horizons for improved patient outcomes.

The association of the airway damage with the pulmonary changes noted with inhalation injury has changed just how patients with an inhalation injury are treated. It was first reasoned that the placement of an endotracheal tube into a patient with existing damage to the airway would only aggravate the injury. Therefore, endotracheal tubes were not used in patients with bronchoscopic evidence of inhalation injury and the placement of tubes was avoided, even for anesthetic procedures. Endotracheal tubes are now used only if there is a marked reduction in arterial oxygen, an increase in carbon dioxide, or evidence of severe respiratory distress. The practice of avoiding endotracheal intubation has resulted in a decline in the number of ventilator days and a reduction in morbidity (unpublished data).

Scar development, rehabilitation, and psychological adjustment

   One of the major issues of burn victims once they survive the acute phase is formation of hypertrophic scar. Current research performed at several centers investigates how the development of hypertrophic scar can be attenuated and can be altered. The questions being pursued are: is hypertrophic scar genetically predisposed, is it a proteomic predisposition or is it simply a surgical technique? These answers are extremely relevant because hypertrophic scarring requires reoccurring operations for burn patients. The debilitating looks of hypertrophic scars limit the reintegration and rehabilitation of burn patients and diminishes the patients self perception. These research endeavors funded by Shriners Hospitals for Children are not only relevant for our burn patients but also for other surgical patients that develop hypertrophic scars or Keloids. Major steps will be achieved in this area over the next decade. One of the main achievements that have taken place is the institution of pressure garment to attenuate hypertrophic scar development.

Pressure garments, which are used to reduce scarring, were developed 20 years ago. Traditionally, elastic bandages were placed on the legs of the burn patients to improve venous return and decrease bruising or blood blister formation. These bandages were also applied to splints to reduce and prevent contractures. Therapists observed that burn patients rarely developed hypertrophic scars when these pressure garments were applied (95,96). Unsightly scars could be prevented if the pressure garments were continuously worn and if hypertrophic scars had already formed, they could be reversed if the pressure garments were applied. Investigators studying scar formation found that collagen fiber deposition in non-hypertrophic scars were parallel, whereas those of the hypertrophic scar formed predominantly nodular or whorl-like patterns (96-99). With the application of pressure, these diffuse, disorganized fibers became parallel. The relationship of the whorl-like fibers was found to depend on the quantity of proteoglycan that make up the scar tissue. In hypertrophic scars, this material is more abundant. Several researchers concluded that the pressure application reduced the scar by limiting the blood supply to the wound. It has now been determined that the macrophages of patients with keloids and hypertrophic scars produce elevated levels of the cytokines interleukin 6,  interferon, and tumor necrosis factor (100,101).

The frequency of inadequate decompression and its complications have been studied and it was concluded that compartment pressures should be followed in burn patients since pressures may increase over time and pulses are not predictive of ischemia. Failure to decompress extremities with elevated pressures may lead to significant, but preventable, complications (102). Models of burn treatment strongly emphasize the integration of basic science, clinical research, and clinical treatment that share information in a continuous feedback loop. It is customary for each clinical innovation to be based on empirical data and to be evaluated for effectiveness through scientific study.

Aspects in burn victims have emerged in the last 5-7 years that the quality of life of burned victims, which was decreased in the past, needs to be improved. Improvements made are due to the attenuation of the hypermetabolic response, increased patient’s physical function and performance, and well-being. One of these programs is a 12 week exercise training regime and has been shown to improve body composition, such as lean mass, strength, and muscle content, but also decrease the need for reconstructive surgery due to improved scarring, as well as, improve life quality, and the reintegration and the rehabilitation of the burned patient (103-106). We therefore have not only decreased mortality and hypermetabolism in burned patients acutely, but we have also achieved the rehabilitation and reintegration of patients in a much improved manner. This has resulted from research performed at Shriners Hospitals for Children.

Additionally, through research grants from Shriners Hospitals for Children, a database has also been developed to follow patients longitudinally on specific measures of physical and psychosocial recovery. Four hundred patients have been entered into a database, which includes longitudinal assessments of cardiopulmonary functions, physical growth and maturation, bone density, measures of functional capability, including range of motion and activities of daily living, scar formation, reconstructive needs, and several measures of the psychosocial adjustment of the child/patient and parent(s).

One important finding from these data is that the long-term successful psychosocial adjustment of burned children largely depends on the enduring qualities of the families in which they live (107-109). Based on these data, a treatment program has been developed that centers on strengthening the welfare of the family/patient unit. We emphasize the importance of having at least one parent/guardian available. Studies consistently indicate that, regardless of burn size, the majority of the children eventually function satisfactorily as socially integrated, behaviorally well-adjusted individuals with positive self-regard; only about 20-30 percent of each sample has moderate behavior problems. These outcomes have been consistent even for survivors of the most massive injuries, many of who have now grown into young adults with careers and families of their own. In terms of physical impairment, the children, even those with the most severe injuries, are remarkably independent in their capabilities (110,111).

In summary, due to the incredible amount of support by the Shriners Hospitals for Children, research markedly decreased morbidity and mortality, not only during acute hospitalization but also long-term, by increasing quality of life, rehabilitation and reintegration of the burned child.

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References Cited

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101. McCauley, R.L., Chopra, V., Li, Y.Y., Herndon, D.N., Robson, M.C. Altered cytokine production in black patients with keloids. Journal of Clinical Immunology 12:300-308, 1992.

102. Brown, R.L., Greenhalgh, D.G., Kagan, R.J., Warden, G.D. The adequacy of limb escharotomies-fasciotomies after referral to a major burn center. Journal of Trauma 37(6): 916-920, 1994.

103. Suman OE, Spies RJ, Celis MM, Mlcak RP, Herndon DN. Effects of a 12-wk resistance exercise program on skeletal muscle strength in children with burn injuries. J Appl Physiol 91:1168-1175, 2001.

104. Suman OE, Mlcak RP and Herndon DN. Effects of exercise training on pulmonary function in children with thermal injury. J Burn Care Rehab. 23:288-293, 2002.

105. Celis MM, Suman OE, Huang TT, Yen P and Herndon DN. Effect of a supervised exercise and physiotherapy program on surgical interventions in children with thermal injury. J. Burn Care Rehab. 24(1): 57-61, 2003.

106. Suman OE, Thomas SJ, Wilkins JP, Mlcak RP, Herndon DN. Effect of exogenous growth hormone and exercise on lean mass and muscle function in children with burns. J Appl Physiol. 94: 2273-2281, 2003.

107. Blakeney, P., Herndon, D.N., Desai, M., Beard, S., Wales-Seale, P. Long-term psychosocial adjustment following burn injury. Journal of Burn Care & Rehabilitation 19(6): 661-665, 1998.

108. Blakeney, P., Portman, S., Rutan, R. Familial values as factors influencing long-term psychological adjustment of children after severe burn injury. Journal of Burn Care & Rehabilitation 11(5): 472-475, 1990.

109. Meyer, W., III, Blakeney, P., Moore, P., Murphy, L., Robson, M. and Herndon, D.N. Parental well being and behavioral adjustment of pediatric burn survivors. Journal of Burn Care & Rehabilitation 15: 62-68, 1994.

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111. LeDoux, J., Meyer, W., III, Blakeney, P., Herndon, D. Positive self-regard as a coping mechanism for pediatric burn survivors. Journal of Burn Care & Rehabilitation 17: 472-476, 1996.

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