Increased liver weights in severely burned children: comparison of ultrasound and autopsy measurements.

Hepatomegaly is a common finding at autopsy in severely burned children surviving less than 6 months. This study validates a reliable ultrasound method which can be used to identify changes in liver size in severely burned children during acute hospitalization. Thirty-eight children, age 0.5-17 years with burns covering over 40% of their total surface area were studied at autopsy. Liver weight was measured at autopsy and compared to predicted liver weight for age and height. Eighteen had liver size measured by ultrasound within 10 days of death while five had ultrasound liver measures after death just prior to autopsy. All burned children who survived 7 days or more (n = 33) had liver weights at autopsy that were greater than predicted for age and height while all 23 livers measured by ultrasound were greater than predicted. Autopsy weights correlated well with weights estimated by ultrasound, R = 0.824. At autopsy, those who survived 7 days or more had enlarged livers ranging from 142 to 406% of their predicted normal age and height. Common histologic findings include large and small-droplet fat deposits, and cholestasis. The degree of these histologic abnormalities correlated with the increase in liver weight, R = 0.652. Ultrasound is a valid, noninvasive method for measuring liver weight changes in severely burned children during acute hospitalization. Ninety-five percent of the severely burned children from this institute had significant hepatomegaly identified at autopsy.

Gene expression profiles of giant hairy naevi.

BACKGROUND: Congenital neomelanocytic naevi appear in nearly 1% of newborns. Giant hairy naevi (GHN) are uncommon lesions covering large areas of the body. They are of concern because they have the potential to transform into malignant melanomas. AIMS: To describe gene expression profiles of GHN and nearby normal skin from patients with GHN and normal control skin (from patients with cleft lip/palate). METHODS: Tissues from three patients with GHN and two normal controls were studied for differences in gene expression profiles. Total RNA was isolated from normal skin near the hairy naevus, GHN, and skin from normal controls. The RNA samples were subjected to probe labelling, hybridisation to chips, and image acquisition according to the standard Affymetrix protocol. RESULTS: There were 227 genes affected across all samples, as determined by DNA microarray analysis. There was increased expression of 22 genes in GHN compared with nearby normal skin. Decreased expression was noted in 73 genes. In addition, there was increased expression of 36 genes in normal skin near GHN compared with normal control skin, and decreased expression of five genes. Categories of genes affected were those encoding structural proteins, proteins related to developmental processes, cell death associated proteins, transcription factors, growth factors, stress response modulators, and collagen associated proteins. Changes in mRNA expression were checked by reverse transcription polymerase chain reaction. CONCLUSIONS: Genetic profiles of GHN may provide insight into their pathogenesis, including their potential for malignant transformation. Such information may be useful in improving the understanding and management of these lesions.

Nutritional intervention high in vitamins, protein, amino acids, and omega3 fatty acids improves protein metabolism during the hypermetabolic state after thermal injury.

HYPOTHESIS: Characteristic of the hypermetabolic response to a thermal injury is the massive protein catabolism and compromised structure and function of essential organs. Nutrition has been suggested to affect protein metabolism and clinical outcome after a severe injury but published studies show controversial data. The purpose of this study was to determine the effect of enriched nutritional support during the postburn hypermetabolic state on protein metabolism in serum, liver, muscle, and skin. SETTING: Laboratory. INTERVENTION: Twenty-two rats were given burns covering 60% of their total body surface area and randomized to receive either standard rat chow (control) or a diet high in vitamins, protein, amino acids, and omega3 fatty acids. MAIN OUTCOME MEASURES: Five weeks after injury, body weight, serum, muscle, and hepatic protein content, insulin-like growth factor I concentration, and wound healing (reepithelization) were determined. RESULTS: Rats receiving the enriched diet showed a gradual improvement in body weight 1, 2, 3, 4, and 5 weeks postburn compared with controls (P< .001). Diet-fed rats demonstrated higher protein and insulin-like growth factor 1 content in serum, muscle, and liver 5 weeks after trauma (P< .001). Serum protein, albumin, and transferrin levels were significantly increased in rats receiving the diet compared with control rats (P< .001). Reepithelization was accelerated in rats receiving the enriched diet 4 (diet-fed, mean +/- SD, 23% +/- 1% vs controls, 17% +/- 1%; P< .001) and 5 (diet-fed, 24% +/- 1% vs controls, 18% +/- 1%; P< .001) weeks postburn compared with control rats. CONCLUSIONS: Nutritional intervention high in protein, vitamins, amino acids, and omega3 fatty acids improves protein net balance during the hypermetabolic response to thermal injury. Compromised organ function and structure and clinical outcome during the hypermetabolic response may be improved.

IGF-I/BP-3 administration preserves hepatic homeostasis after thermal injury which is associated with increases in no and hepatic NF-kappa B.

After a severe trauma, such as a cutaneous thermal injury, an increase in hepatocyte apoptosis has been associated with hepatocyte damage and impairment in hepatic function. Insulinlike growth factor-I (IGF-I) exerts antiapoptotic effects in several organs, thus improving organ homeostasis. The purpose of the present study was to determine whether IGF-I in combination with its principle binding protein-3 (BP-3) attenuates liver damage after a burn and whether this attenuation is through signals of the apoptotic-proliferative axis of hepatocytes. Sprague-Dawley rats (56 males) received a 60% total body surface area third-degree scald burn and were randomly divided to receive either rhlGF-I/BP3 (10 mg/kg/day s.c.) or saline (control). Serum aspartate transaminase (AST) and nitric oxide (NO), and hepatocyte proliferation and apoptosis, were measured on postburn days 1, 2, 5, and 7. Hepatic interleukin-1 beta (IL-1 beta) and tumor necrosis factor-alpha (TNF-alpha) mRNA and hepatic nuclear-factor kappa B (NF-kappa B) were determined at 1 and 2 days postburn. IGF-I/BP-3 decreased serum AST and increased serum NO at 1, 2, and 5 days after burn when compared with controls (P < 0.05). IGF-I/BP-3 increased hepatocyte proliferation on the first day after burn and decreased hepatocyte apoptosis at day 7 postburn when compared with controls (P < 0.05). IGF-I/BP-3 decreased hepatic IL-1 beta and TNF-alpha mRNA 1 day after burn (P < 0.05). IGF-I/BP-3 further increased hepatic NF-kappa B concentration 1 and 2 days postburn when compared with controls (P < 0.05). Recombinant hIGF-I in combination with its principle binding protein conserves hepatic homeostasis, which is associated with a transient increase in hepatocyte proliferation and decrease in hepatocyte apoptosis possibly through NO and hepatic NF-kappa B.

Serum TGF-beta in thermally injured rats.

A severe thermal injury is commonly associated with immune suppression and increased susceptibility to sepsis, frequently leading to multiple organ failure. Transforming growth factor-beta (TGF-beta) is a potent immunosuppressive cytokine involved in complications associated with major trauma. Interleukin- 4 (IL-4) is thought to synergize the immunosuppressive activity of TGF-beta by promoting naive lymphocytes to differentiate and generate TGF-beta secreting cells. This study examines the alterations in serum levels of TGF-beta and IL-4 after a thermal injury. Male Sprague-Dawley rats (300-400 g) were anesthetized and received a 50% total body surface area full-thickness scald burn followed by fluid resuscitation and analgesia. Control rats were given the same treatment, but were immersed in water at room temperature. Rats were sacrificed from 1 h to 8 days after injury. Blood samples were collected aseptically from the inferior caval vein. Serum levels of TGF-beta and IL-4 were measured by enzyme linked immunosorbent assay. Rats in the control and thermal injury groups showed similar increases in serum TGF-beta 1 h after injury. A progressive increase in serum TGF-beta was observed in burned animals compared to control animals starting on day 3 and continued through day 8 (P < 0.01). Serum IL-4 levels in control and thermally injured animals remained undetectable (< 15.6 pg/mL) throughout the experiment. Thermal injury induces a significant increase in serum TGF-beta, which may contribute to post-burn immunosuppression with an increased susceptibility to sepsis.

Liposomal IGF-1 gene transfer modulates pro- and anti-inflammatory cytokine mRNA expression in the burn wound.

The use of systemic IGF-1 has been shown to attenuate the postburn hypermetabolic response and improve burn wound healing. Local IGF-1 gene therapy, however, promotes re-epithelialization in the burn wound without the side-effects associated with systemic delivery. We tested the hypothesis that these beneficial effects are due to changes in local cytokine production. Adult male Sprague-Dawley rats received a 40% total body surface area full-thickness scald burn and randomly received a subcutaneous injection at the burn wound margin of saline or cationic liposomes containing a IGF-1 cDNA construct. Animals were killed at 1, 4, 7 and 10 days after burn trauma. Skin biopsies at the wound border were harvested for total RNA extraction. Cytokine mRNA expression was determined using a multi-probe RNase protection assay. Data are presented as means +/- s.e.m. Statistical analysis used the unpaired t-test or Mann-Whitney test where appropriate. Significance was accepted at P < 0.05. Treatment of the burn wound with liposomal IGF-1-cDNA transfer decreased IL-1beta mRNA levels on day 10 after burn trauma from five-fold burn-induced increases compared with sham-treated rats, to near the control values present in unburned skin samples. Similarly, there was an eight-fold increase in TNF-alpha mRNA expression on postburn day 10 that was abrogated by IGF-1 gene therapy. Local IGF-1 gene transfer attenuates the mRNA expression of the inflammatory cytokines IL-1beta and TNF-alpha in the burn wound. This change may improve burn wound healing by decreasing prolonged local inflammation.

Surfactant phosphatidylcholine in thermally injured pigs.

OBJECTIVE: To investigate the effect of a thermal injury on pulmonary surfactant phosphatidylcholine kinetics. DESIGN: Random, controlled study. SETTING: University research laboratory. SUBJECTS: Yorkshire swine (n = 8) with and without a 40% total body surface area burn. INTERVENTIONS: A new isotope tracer methodology was used to quantify surfactant phosphatidylcholine kinetics. Four days after burn, [1,2-13C2]acetate and [U-(13)C16]palmitate were infused continuously for 8 hrs to quantify surfactant phosphatidylcholine synthesis, secretion, recycling, and irreversible loss. MEASUREMENTS AND MAIN RESULTS: The total surfactant phosphatidylcholine pool size was reduced from the control value of 2.65 +/- 0.05 to 1.61 +/- 0.08 micromol/g wet lung in burned animals (p <.05), as was the proportional contribution of palmitate to lung surfactant phosphatidylcholine composition. This reduction was associated with a significant decrease in lung dynamic compliance from the control value of 66 +/- 6 to 55 +/- 6 mL/cm H2O for burned pigs (p <.05). The most prominent response of lung phosphatidylcholine kinetics was a decrease in the total lung phosphatidylcholine synthesis from a control value of 12.7 +/- 1.2 to 5.5 +/- 0.3 nmol phosphatidylcholine-bound palmitate x hr(-1) x g of wet lung(-1) in burned animals (p<.05). CONCLUSIONS: Pulmonary phosphatidylcholine content and palmitate composition decrease after burn injury because of a decrease in the rate of phosphatidylcholine synthesis. These responses likely contribute to impaired lung compliance.

The effect of short-term growth hormone treatment on growth and energy expenditure in burned children.

Delays in growth are commonly observed in children who have sustained a severe cutaneous burn. The reasons for this growth delay are not completely known, but in adults, plasma growth hormone (GH) levels have been shown to decrease after thermal injury. If this is also the case in severely burned children, the low GH levels may contribute to their chronic growth delay. We propose that treatment with rhGH may prevent this burn-induced growth delay. Height velocities were measured for up to 2 years after injury in 38 burned children (age 7+/-1 years) with a 64+/-2% total burn surface area (TBSA) burn and a 59+/-3% third-degree burn who received 0.2 mg/kg/day rhGH during hospitalization. These height velocities were compared to 41 burned children (age 8+/-1 years) with a 64+/-3% TBSA burn and a 60+/-3% TBSA third-degree burn who were treated similarly but did not receive rhGH. Height velocities and height percentiles were compared to standard height velocity and percentile nomograms of unburned children. To determine the effect of rhGH on energy requirements, resting energy expenditures (REE) were measured by indirect calorimetry and compared to values calculated from the Harris-Benedict equation. All data are presented as mean+/-S.E.M. No differences in average height percentile could be shown between those receiving GH and controls at admission and 6 months after burn. There was, however, a significant difference (P<0.05) in height velocity during the first 2 years after burn between GH (47th+/-6 percentile) and controls (32nd+/-5 percentile). For rhGH-treated children, the REE was elevated by 34+/-4% versus 35+/-5% for controls. Recombinant human GH, given during acute hospitalization, maintained growth in severely burned children who would otherwise experience a significant growth delay. Treatment with rhGH did not atttenuate their elevated REE.

Effect of varying burn sizes and ambient temperature on the hypermetabolic rate in thermally injured rats.

BACKGROUND: Small animals with scald covering 50% of their total body surface area (TBSA) have been used to study the hypermetabolic burn response. In the 50% TBSA burn rat model, the area of normal skin that is available for animal instrumentation is restricted and the mortality rate has been high. The purpose of this study was to determine whether a smaller burn size can induce a similar hypermetabolic response with mortality rates lower than those of the 50% TBSA model. METHODS: Rats were randomly divided into four groups to receive a 0% (sham nonburned), 30%, 40%, or 50% TBSA third-degree scald burn. The hypermetabolic response was determined by measuring changes in body weight and oxygen consumption at ambient temperatures of 21, 26, and 31 degrees C for each burn size. Weight measurements were made daily while oxygen consumption was measured 7, 11, and 14 days after thermal injury. RESULTS: All thermally injured rats lost body weight; however, there were no significant differences between the 30, 40, and 50% TBSA burn groups. Burn induced a hypermetabolic response as indicated by an increase in oxygen consumption from 130 to 200% that of sham nonburned rats. No significant difference in oxygen consumption could be shown over the study period between the three burn sizes at different ambient temperatures. Mortality was 0% in the sham and 30% group, 10% for the 40% group, and 50% for the 50% TBSA burn group. CONCLUSIONS: From our study we conclude that a burn size covering 30% of the TBSA induces the same hypermetabolic response as a 50% TBSA burn.

Cell proliferation, apoptosis, NF-kappaB expression, enzyme, protein, and weight changes in livers of burned rats.

Thermal injury has been shown to alter gut epithelium and heart myocyte homeostasis by inducing programmed cell death. The effect of thermal injury on hepatocyte apoptosis and proliferation, however, has not been established. The purpose of this study was to determine whether a large thermal injury increases liver cell apoptosis and proliferation and whether these changes were associated with alterations in hepatic nuclear factor kappaB (NF-kappaB) expression and changes in liver enzymes and amount of protein. Sprague-Dawley rats received a 40% total body surface area scald burn or sham burn. Rats were killed and livers were harvested at 1, 2, 5, and 7 days after burn. Liver cell apoptosis was determined by terminal deoxyuridine nick end labeling (TUNEL) assay and cell proliferation by immunohistochemistry for proliferating cell nuclear antigen. Hepatic NF-kappaB expression was determined by Western blot, and total hepatic protein content was determined by protein assay. Protein concentration decreased after burn compared with sham controls (P < 0.05). Liver cell apoptosis, proliferation, and NF-kappaB expression in hepatocytes increased in burned rats compared with controls (P < 0.05). It was concluded that thermal injury induces hepatic cell apoptosis and proliferation associated with an increase in hepatic NF-kappaB expression and a decrease in hepatic protein concentration.

Chest radiographic appearances in severely burned adults. A comparison of early radiographic and extravascular lung thermal volume changes.

Chest radiographs (CXRs) have previously been used as a diagnostic tool to detect changes in lung water. In this study CXR changes in severely burned adults, in the absence of an inhalation injury, preceded detectable increases in extravascular lung thermal volume (ELTV) by 3 to 5 days. The hypothesis that early CXR density changes in burned patients have an infectious cause, not related to changes in ELTV, was tested. Blood cultures, CXRs, and ELTV were evaluated during the first 15 days after injury in severely burned adults who had no identified inhalation injury. Chest radiographs were scored daily on a 1 to 5 scale, with 1 = normal, 2 = peribronchial cuffing, 3 = mild interstitial infiltrates, 4 = severe interstitial infiltrates, and 5 = alveolar infiltrates. In all patients, except those who were septic, increases in their CXR density scores correlated well with increases in ELTV. The ELTV/CXR score ratios for septic burn patients on days 1 to 6 postburn was 1.7 +/- 0.2 compared with 4.2 +/- 0.4, (means +/- SEM) for nonseptic (P < .001), whereas the ELTV/CXR score ratios for septic and nonseptic patients, 7 to 15 days postburn, were 3.8 +/- 0.4 and 3.4 +/- 0.5, respectively. We suggest that before any measurable change in ELTV early increases in CXR density scores in burned patients without a concomitant inhalation injury are caused by intraalveolar pneumonitis or hyaline membrane atelectasis and not increased ELTV.

Possibilities of non-viral gene transfer to improve cutaneous wound healing.

Enhancement of dermal and epidermal regeneration represents a crucial goal for the treatment of acute, e.g. burn and trauma wounds, and chronic wounds, e.g. diabetic, autoimmune, arterial and venous wounds. Studies defining molecular mechanisms of the complex cascade of wound healing have shown that growth factors represent a new therapeutic strategy. The clinical application of growth factors in the form of proteins has been shown to be of little benefit. Therefore new delivery systems and therapeutic strategies needed to be developed to improve dermal and epidermal regeneration, one of which is gene therapy. For successful gene delivery the selection of an appropriate vector has been shown to be paramount. Because Retroviruses, Adenoviruses and Adeno-Associated Viruses can cause immunologic reactions and mutations, non-viral delivery systems for gene therapy, such as liposomal gene transfer appear advantageous over viral gene therapy. This review discusses the success, potential and limitations of non-viral gene transfer to improve regeneration of dermal and epidermal structures.

Biobrane improves wound healing in burned children without increased risk of infection.

A synthetic bilaminar membrane used as a skin substitute (Biobrane) has been shown to decrease pain and hospitalization in superficial second-degree burns. Despite these benefits, it has not been utilized universally, particularly in young children, due to a perceived increase in related infections. We propose that when this synthetic membrane is applied to superficial scald burns <25% of the total body surface area (TBSA), decreased healing times are expected without increased risk of infection. Between 1994-1999, 89 children treated within 48 h after receiving superficial partial thickness scald burns covering 5-25% TBSA with no indication of infection were seen at our hospital. Forty-one were assigned randomly to receive treatment with the skin substitute Biobrane and 48 to receive conservative treatment with topical antimicrobials and dressing changes. Comparisons of treatment were made between groups for length of hospitalization, wound healing times, and infectious complications. Children treated with Biobrane or topical antimicrobials were similar in age, race, sex, %TBSA burned, and location of burn. Those receiving Biobrane had shorter hospitalizations and healing times, which was significant for both infants and toddlers and older children. Treatment groups were not different in the use of systemic antibiotics or readmissions for infectious complications. Biobrane was removed in 5.9% of cases for non-adherence. The application of Biobrane within 48 h of superficial burns provides for shorter hospitalizations and faster healing times in children of all ages without increased risk of infection.

Glucose effects on lung surfactant kinetics in conscious pigs.

The primary goal of this study was to investigate the effects of glucose infusion on surfactant phosphatidylcholine (PC) metabolic kinetics in the lungs. A new stable isotope tracer model was used in which [1,2-(13)C(2)]acetate and uniformly labeled [U-(13)C(16)]palmitate were infused in 12 normal overnight-fasted pigs to quantify lung surfactant kinetics with or without glucose infusion (24 mg. kg(-1). min(-1)). With glucose infusion, the rate of surfactant PC incorporation from de novo synthesized palmitate increased from the control value of 2.1 +/- 0.2 to 15.5 +/- 1.9 nmol PC-bound palmitate. h(-1). g wet lung(-1) (P < 0.05), whereas the incorporation rate from plasma preformed palmitate decreased from the control value of 20.9 +/- 1.9 to 11.6 +/- 1.1 nmol palmitate. h(-1). g wet lung(-1) (P < 0.05). The palmitate composition in lamellar body surfactant PC increased from the control value of 61.7 +/- 2.1% to 75.9 +/- 0.6% (P < 0.05). The surfactant PC secretion rate decreased from the control value of 239.0 +/- 26.1 to 81.9 +/- 5.3 nmol PC-bound palmitate. h(-1). g wet lung(-1) (P < 0.05). We conclude that, whereas surfactant secretion was inhibited by glucose infusion, neither total surfactant PC synthesis nor the surfactant PC pool size was significantly affected due to an increased reliance on de novo synthesized fatty acids.

Early fluid resuscitation improves outcomes in severely burned children.

BACKGROUND: Recent evidence suggests that timely fluid resuscitation can significantly reduce multiorgan failure and mortality in thermally injured children. In this study, children who received fluid resuscitation within 2 h of a thermal injury were compared with children in which fluid resuscitation was delayed by 2-12 h. We hypothesized that fluid resuscitation given within 2 h of a thermal injury attenuates renal failure, cardiac arrest, cardiac arrest deaths, incidence of sepsis, and overall mortality. METHODS: A retrospective chart review was made on 133 children admitted to our institute from 1982 to 1999 with scald or flame burns covering more than 50% of their body surface area. Comparisons between early (< 2 h of injury) or delayed (> or = 2 h of injury) fluid resuscitation were made in children experiencing renal failure, sepsis, non-survivors with cardiac arrest requiring pulmonary and advanced life support, and overall mortality. Comparisons were made using the chi2-test with Yates' continuity correction and joint binomial confidence intervals using the Bonferroni correction. RESULTS: The incidence of sepsis, renal failure, non-survivors with cardiac arrest, and overall mortality was significantly higher in burned children receiving fluid resuscitation that was delayed by 2 h or more compared with those receiving fluid resuscitation within 2 h of thermal injury (P < 0.001). CONCLUSIONS: Data suggest that fluid resuscitation, given within 2 h of a thermal injury, may be one of the most important steps in the prevention of multi-organ failure and mortality.

Recombinant human growth hormone treatment in pediatric burn patients and its role during the hepatic acute phase response.

OBJECTIVE: Recombinant human growth hormone (rHGH) has been shown to increase mortality in adult trauma patients; however, little has been reported on its side effects in children. The acute phase response has been suggested to be a contributing factor to trauma mortality. Therefore, the purpose of this study was to examine the effects of exogenous rHGH on the acute phase response in pediatric bum patients. DESIGN: Prospective, randomized, double-blind study. SETTING: Shriners Hospital for Children. PATIENTS: Thermally injured pediatric patients, ranging in age from 0.1 to 16 yrs. INTERVENTIONS: Twenty-eight thermally injured children received either 0.2 mg/kg/day of rHGH or saline (placebo) within 3 days of admission and for at least 25 days. MEASUREMENTS AND MAIN RESULTS: Measurements were patient demographics, incidence of sepsis, inhalation injury, mortality, serum constitutive proteins, acute phase proteins, proinflammatory cytokines and insulin-like growth factor-I (IGF-I), insulin-like growth factor binding protein (IGFBP)-1, and IGFBP-3. No differences could be demonstrated in age, gender, burn size, incidence in sepsis (20% vs. 26%), inhalation injury (46% vs. 27%), or mortality (8% vs. 7%) between those receiving rHGH or placebo. Serum IGF-I and IGFBP-3 increased with rHGH treatment, whereas serum IGFBP-1 decreased compared with placebo (p < .05). Burned children treated with rHGH required significantly less albumin substitution to maintain normal levels compared with placebo (p < .05). Those receiving rHGH demonstrated a decrease in serum C-reactive protein and serum amyloid-A and an increase in serum retinol-binding protein compared with placebo (p < .05). rHGH decreased serum tumor necrosis factor-alpha and interleukin (IL)-1beta, whereas no changes were found for serum IL-1alpha, IL-6, and IL-10 compared with placebo (p < .05). Free fatty acids were elevated in burned children who received rHGH (p < .05). CONCLUSION: Data indicate that rHGH does not increase mortality. rHGH decreased acute phase proteins, tumor necrosis factor-alpha, and IL-1beta, which is associated with increases in constitutive hepatic proteins and IGF-I.

Ibuprofen modulates tissue perfusion in partial-thickness burns.

INTRODUCTION: The anti-inflammatory and anticoagulant effects of ibuprofen and heparin may enhance skin perfusion in cutaneous scald burns. To test this hypothesis, skin perfusion and edema formation in scald burned rabbit ears were measured. METHOD: Eighteen rabbits (3.5-4.5 kg) received partial-thickness scald burns to one ear and then were given normal saline, n = 6, 20 mg/kg ibuprofen, n = 6, or 700 IU/kg heparin, n = 6. Skin perfusion, blood flow and edema formation in the burned ear were measured with laser Doppler, ultrasound flowmeter and skin calipers, respectively. Statistical analysis was performed using repeated measures ANOVA with post hoc Scheffe's test for comparison between groups. RESULTS: Blood flow to the scald burned ear increased 10-15 times that of baseline with tissue perfusion increasing by 70% within 0.5 h compared to pre-burn. Ibuprofen maintained the elevated tissue perfusion for 5 h while the heparin and saline groups showed decreases to 95 and 35% of pre-burn values, respectively. The heparin and ibuprofen groups demonstrated significant increases in ear perfusion at 4 and 5 h postburn. Ibuprofen also showed a significant difference within the first hour postburn, p<0.01. Wet to dry weight ratios in burned ear tissue were greater in rabbits receiving saline or heparin compared to ibuprofen at 3.6+/-0.2 and 2.9+/-0.3 vs. 2.1+/-0.1, respectively (p<0.001). CONCLUSION: Ibuprofen increases tissue perfusion and reduces edema formation in scald burned rabbit ears.

Early release of third-degree eyelid burns prevents eye injury.

Burns to the eyelids occur in more than 20 percent of flame injuries and can lead to ocular damage and even blindness. Burn wound contracture can cause ectropion of the eyelid, resulting in exposure keratitis, corneal ulcers, and conjunctivitis. At our hospital, early eyelid release and grafting has made a significant difference in the long-term outcomes of third-degree eyelid burns; however, the question of just how early eyelid release and grafting should take place is an unresolved issue. Fifty-seven children with third-degree eyelid burns were reviewed; 17 had eyelid release within 7 days of receiving eyelid burns and 40 had a delay in eyelid release of more than 7 days after injury. Analysis was by chi-square with the Yates continuity correction or Fisher's exact test when appropriate. Corneal ulcers developed in 2 of 17 of the early eyelid release of third-degree burns, compared with 25 of 40 delayed releases (p = 0.001), exposure keratitis in 3 of 17 early releases, and 30 of 40 in delayed release (p = 0.000); conjunctivitis was identified in 1 of 17 early releases and 14 of 40 delayed eyelid releases (p = 0.025). Release of eyelid burns within 7 days of injury can prevent the development of exposure keratitis, progressive conjunctivitis, corneal ulceration, and the need for corneal surgery. We suggest that early release and grafting should be the treatment of choice for children and young adults with third-degree burns to the eyelids.

Hepatocyte growth factor modulates the hepatic acute-phase response in thermally injured rats.

OBJECTIVE: Hepatocyte growth factor (HGF) has been shown to modulate the acute-phase response in vitro. The specific in vivo role of HGF in this multifactorial response, however, remains unknown. This study examines the effects of exogenous HGF on the acute-phase response in thermally injured rats. DESIGN: Prospective, randomized, laboratory study. SETTINGS: Shriners Hospital for Children and University of Texas Medical Branch laboratories. SUBJECTS: Fifty-six male Sprague-Dawley rats (weight range, 300-325 g). INTERVENTION: Animals received a 60% total body surface area third-degree scald burn and were randomly divided to receive either 400 microg/kg/day i.v. HGF or saline (control). MEASUREMENTS AND MAIN RESULTS: Serum acute-phase proteins, cytokines, and insulin-like growth factor (IGF)-I concentrations, as well as liver weight, protein and triglyceride content, IGF-I concentrations, and cytokine gene expression were measured 1, 2, 5, or 7 days after burn. Serum albumin was increased on days 2, 5, and 7 after burn, and transferrin was increased on day 7 after burn in HGF-treated rats compared with controls (p<.05). HGF increased alpha2-macroglobulin concentrations on postburn days 2, 5, and 7 compared with controls (p<.05). Serum interleukin-6 and tumor necrosis factor-alpha were significantly higher within 2 days of burn in rats treated with HGF (p<.05). HGF increased the hepatic gene expression of tumor necrosis factor-alpha compared with controls (p<.05). Serum IGF-I decreased in rats receiving HGF 1, 2, and 5 days after burn, whereas liver IGF-I concentrations were higher on days 1 and 7 after burn compared with controls (p<.05). Hepatic protein concentrations were higher in the HGF group compared with controls on postburn days 1, 2, and 7, with a concomitant increase in total liver weight (p<.05). HGF exerted a strong mitogenic effect on hepatocytes 1 and 2 days after thermal injury compared with controls (p<.05). CONCLUSIONS: These findings suggest that HGF modulates the acute-phase response in vivo after burn and causes changes in liver morphology.

Long-term outcomes of burned children after in-hospital cardiac arrest.

OBJECTIVE: Cardiopulmonary resuscitation (CPR) in severely burned patients experiencing cardiac arrest (CA) has been considered by some as futile. The objective of this article is to report predisposing factors and the outcomes of burned children experiencing in-hospital CA at our institution. DESIGN: The records of 595 children admitted from 1985 to 1998 with burns covering >35% of their total body surface area were reviewed. Thirty-four children receiving CPR after in-hospital CA were studied for predisposing factors and long-term outcomes. SETTING AND PATIENTS: Shriners Burns Hospital. Burned children of both genders, 0.5-19 yrs of age, who experienced in-hospital CA and received CPR. INTERVENTION: Standard burn care and CPR. MEASUREMENTS AND MAIN RESULTS: Predisposing factors of CA, mortality, and long-term outcomes were measured. The incidence of CA in burned children with burns on >35% total body surface area was 5.7%. No significant difference in age or burn size could be shown between long-term CA survivors (n = 17) and nonsurvivors (n = 17). CPR was successful (defined as survival for at least 1 day after CA) in 22 of 34 children (65%), with 17 of the 22 survivors (77%) experiencing long-term survival, currently from 2-14 yrs. Significant predisposing factors of CA were sepsis, identified in 53% of the nonsurvivors vs. 12% of the survivors (p<.05), and delayed fluid resuscitation (>2 hrs after burn injury), identified in 82% of the nonsurvivors vs. 6% of the survivors (p<.001). There was only one morbid long-term survivor. This survivor was diagnosed as having anoxic brain injury with persistent neurologic deficiencies. CONCLUSION: In this study, 50% of the burned children experiencing CA are long-term survivors. We suggest that all burned children with CA should be afforded cardiopulmonary resuscitation.