The 1999 clinical research award. Cultured skin substitutes combined with Integra Artificial Skin to replace native skin autograft and allograft for the closure of excised full-thickness burns

Prompt and permanent closure of excised full-thickness burns remains a critical factor in a patient's recovery from massive burn injuries. Hypothetically, Integra Artificial Skin (Integra) may replace the need for allografts for immediate wound coverage, and cultured skin substitutes (CSS) that contain stratified epithelium may replace the need for autografts for definitive wound closure. To test this hypothesis, 3 patients with full-thickness burns of greater than 60% of their total body surface areas had their eschar excised within 14 days of admission. Integra was applied, and a skin biopsy was collected from each patient for the preparation of CSS. At 3 weeks or more after the application of the Integra and the collection of skin biopsies, the outer silastic cover of the Integra was removed and CSS were grafted. The CSS were irrigated with nutrients and antimicrobials for 6 days and then dressed with antimicrobial ointment and cotton gauze. Treated wounds were traced on days 14 and 28 after the grafting of CSS for determination of engraftment and wound closure, respectively. Cost analysis was not performed. Engraftment on postoperative day (POD) 14 was 98%+/-1% (mean +/- standard error of the mean), the ratio of closed:donor areas on POD 28 was 52.3+/-5.2, and no treated sites required regrafting. The histology of the closed wounds showed stable epithelium that covered a layer of newly formed fibrovascular tissue above the reticulated structure of the degrading Integra. The clinical outcomes of the closed wounds after POD 28 demonstrated smooth, pliable, and hypopigmented skin. Two patients who had received CSS grafts over Integra on their backs were positioned supine on air beds from POD 8 or POD 9 with minimal graft loss because of mechanical loading. One patient with a full-thickness burn of 88% of the total body surface area was covered definitively at 55 days postburn. These results demonstrate that the combination of CSS and Integra can accomplish functionally stable and cosmetically acceptable wound closure in patients with extensive full-thickness burns. This combination of alternatives to the conventional grafting of split-thickness skin permits the substitution of cadaveric allograft with Integra and the substitution of donor autograft with CSS. This approach to the closure of excised full-thickness burns is expected to reduce greatly the time to definitive closure of burn wounds and to reduce the morbidity associated with the harvesting of donor sites for split-thickness skin autografts.     

A comparison of total body water analyses: bioelectric impedance analysis versus the tritiated water method.

Bioelectric impedance analysis (BIA) is used to measure the body composition and total body water of normal subjects. The purpose of this study was to determine if the hydration of patients with burns could be assessed by BIA. Assessments of total body water as determined by BIA and the tritiated water method were prospectively compared. The 2 analyses were performed 48 hours after admission for 5 patients with acute burns to determine the correlation of the 2 methods. The patients had a mean age of 36.4+/-14.7 years (range, 20-56 years), a mean burn size of 39.4%+/-15.9% of the body surface area (range, 23%-65%), and a mean full-thickness burn size of 27.7% of the body surface area. The total body water was measured on admission and again at 48 hours postburn. There is an excellent relationship between BIA and tritiated-water-method determinations of the total body water of patients with severe burns (r = 0.958). This correlation suggests that BIA provides an accurate measure of total body water, and so it is a reliable means of monitoring fluid resuscitation in patients with burns.     

The 2002 Clinical Research Award. An evaluation of the safety of early vs delayed enteral support and effects on clinical,nutritional, and endocrine outcomes after severe burns

Early enteral support is believed to improve gastrointestinal, immunological, nutritional, and metabolic responses to critical injury; however, this premise is in need of further substantiation by definitive data. The purpose of this prospective study was to examine the effectiveness and safety of early enteral feeding in pediatric patients who had burns in excess of 25% total body surface area. Seventy-seven patients with a mean percent total body surface area burn of 52.5 +/- 2.3 (range 26-91), percent full thickness injury of 44.7 +/- 2.8 (range 0-90), and age ranging from 3.1 to 18.4 (mean 9.3 +/- 0.5) were randomized to two groups: early (feeding within 24 hours of injury) vs control (feeding delayed at least 48 hours postburn). Nutrient intake was measured daily, indirect calorimetry was performed biweekly, and blood and urine samples were obtained for the assay of cortisol, glucagon, insulin, gastrin, epinephrine, norepinephrine, dopamine, triiodothyronine, tetraiodothyronine, albumin, transferrin, prealbumin, retinol-binding protein, glucose, nitrogen balance, and 3-methylhistidine throughout the study period. Three protocol violations occurred, and two patients were transferred to another hospital; these patients were excluded from the study. No patient in either group experienced tube feeding aspiration. No differences were evident in infection, diarrhea, hospital length of stay, or mortality outcomes. A higher incidence of reportable adverse events coincided with early feeding (22 vs 8%), but this was not statistically significant. The delayed feeding group demonstrated a significant caloric deficit during postburn week (PBW) 1 (P <.0001) and PBW2 (P =.0022). Serum insulin (P =.0004) and triiodothyronine (P =.0162) were higher in the early fed group during PBW1. A decrease in 3-methylhistidine output (suggesting a decrease in protein breakdown) was also evident during PBW1 (P =.0138). No other significant trends in study outcome variables were noted. In conclusion, provision of enteral nutrients shortly after burn injury reduces caloric deficits and may stimulate insulin secretion and protein retention during the early phase postburn. These data, however, do not necessarily reaffirm the safety of early enteral feeding, nor do they associate earlier feeding with a direct improvement in endocrine status or a reduction in morbidity, mortality, hypermetabolism, or hospital stay. Future studies are needed to establish precise feeding implementation times that maximize clinical benefit while minimizing morbidity in the critically injured burn patient.     

Use of Integra artificial skin is associated with decreased length of stay for severely injured adult burn survivors

Mortality and length of stay (LOS) of survivors was examined retrospectively in 270 adults with acute burns > or =20% of body surface area to determine the effect of Integra Dermal Regeneration Template treatment on outcome. No difference in mortality was found between patients who received Integra (30%; n = 43) and patients who did not (30%; n = 227). Surviving Integra patients (n = 30) stayed longer, but they were more extensively injured than survivors who did not receive Integra (n = 158), and therefore longer hospitalizations were expected. In a subgroup analysis, mean LOS of Integra patients with two or more mortality risk factors (age > 60 years, burn size >40% body surface area, or inhalation injury; n = 15) was 63 days compared with 107 days in patients with two or more risk factors (n = 29) who did not receive Integra ( =.014). Integra use in severely injured burned adults was associated with a marked decrease in LOS.     

Severe multiple extensive postburn contractures: a simultaneous approach with total scar tissue excision and resurfacing with dermal regeneration template.

Deep partial or full-thickness burns if untreated, neglected, or managed conservatively can develop dysfunctional scar contractures with severe deformities and significant reduction in patient's activities of daily life. These burn sequelae can require multistage procedures to restore anatomy and function. These include single scar release, use of skin grafts, skin expansion, regional or free musculocutaneous or fasciocutaneous flaps to achieve adequate functional improvement. The use of dermal regeneration template (Integra), initially used in primary burns reconstruction, has been already described and compared in single scar contracture-releasing procedures, but to our knowledge, it has not been used in the simultaneous releasing of multiple severe extensive postburn contractures. A simultaneous approach with total scar tissue excision and resurfacing with Integra may reduce the number of operations and the prolonged time period of treatment required by conventional procedures of multistage scar contracture release. A 7-year-old girl, who developed severe postburn scar contractures involving the right upper limb, right axilla, neck, and face after healing of a deep 16% total body surface area burn injury, was treated with this approach. Restoration of anatomy and function, with significant improvement in the range of movement of the involved regions, was achieved in a relatively short period of time (15 weeks) with limited donor-site morbidity and preservation of donor areas for possible future procedures. Total scar tissue excision and resurfacing with Integra should be considered as a valid option in case of simultaneous management of severe multiple extensive scar contractures.     

Molecular or pharmacologic inhibition of the CD14 signaling pathway protects against burn-related myocardial inflammation and dysfunction

Signaling through toll-like receptor 4 (TLR4) plays an obligate role in burn-related myocardial dysfunction. We hypothesized that signaling through CD14, a cellular receptor for endotoxin that lacks a transmembrane domain but is coupled to TLR4, also plays a role in postburn myocardial inflammation and dysfunction. Burn covering 40% total body surface area (or sham burn for controls) was produced in wild-type (WT) and CD14 knockout (KO) as well as vehicle-treated and geldanamycin-treated WT mice (1 microg/g body weight) to inhibit CD14 signaling. Groups included (1) WT shams, (2) CD14 KO sham, (3) WT burns, (4) CD14 KO burns, (5) vehicle-treated WT shams, (6) geldanamycin-treated WT shams, (7) vehicle-treated WT burns, and (8) geldanamycin-treated WT burns. Twenty-four hours after burn, cardiac function (Langendorff) and cardiomyocyte secretion of inflammatory cytokines TNF-alpha, IL-1 beta, and IL-6 (in pg/mL; 5 x 10(4) myocytes) were studied in all groups. Relative to sham WT controls, burn trauma in increased cardiac myocyte secretion of inflammatory cytokines (TNF-alpha, IL-1 beta, and IL-6 rose from 59 +/- 10 to 171 +/- 8; 6 +/- 0.2 to 78 +/- 1; and 88 +/- 3 to 170 +/- 12 pg/mL, respectively; P < 0.05) and produced robust cardiac contractile dysfunction (left ventricular pressure and +dP/dt fell from 105 +/- 4 to 73 +/- 5 mmHg and 2,400 +/- 73 to 1,803 +/- 90 mmHg/s; P < 0.05). Inability to signal through the CD14/TLR4 pathway (induced by CD14/KO or inhibition of CD14 expression by administration of geldanamycin) attenuated TNF-alpha, IL-1 beta, and IL-6 production in response to burn injury and improved postburn myocardial contractile function. Our data suggest that signaling through the CD14 pathway plays an obligate role in cardiac inflammation/dysfunction which occurs after major burn injury.     

Effect of sequential early burn wound excision and closure on postburn oxygen consumption

OBJECTIVE: To determine the effect of early excision and closure of burns on postburn hypermetabolism, measured as oxygen consumption (VO2). METHODS: Twelve patients with deep burns of 30% to 50% of total body surface underwent sequential excisions and wound coverage, beginning 1 to 3 days after burn. The majority of the deep burn was removed by day 7, but with the addition of a donor site area of 20% to 25% of total body surface. RESULTS: No decrease in VO2 was noted in relation to the percent removal of burn tissue. In addition, a transient further increase in VO2 was noted early after excision, especially with surgical procedures performed after 5 days. This response could not be attributed to wound manipulation-induced bacteremias. CONCLUSION: We conclude that early surgical excision and closure of burns in excess of 30% to 50% of total body surface do not decrease postburn hypermetabolism in proportion to the area closed. It is possible that remaining open wounds in the form of donor sites and nonexcised burn are sufficient to perpetuate the hypermetabolic process, once established.     

特重度烧伤患者细胞免疫功能障碍与预后的相关性研究

目的 探讨特重度烧伤患者细胞免疫功能指标变化与临床预后的关系及其意义.方法 26例总体表面积≥70%的特重度烧伤患者按临床预后分为存活组(12例)和死亡组(14例);11例同期献血者作为健康对照组.采集患者伤后1、3、7和14 d外周静脉血,用流式细胞仪定量分析CD14+单核细胞表面人白细胞DR抗原(HLA-DR)表达量,用噻唑蓝(MTT)比色法测定外周血T淋巴细胞增殖反应活性,用酶联免疫吸附法(ELISA)测定白细胞介素-2(IL-2)分泌水平.结果 与存活组比较,死亡组在伤后14 d T淋巴细胞增殖反应活性(0.739±0.299比0.320±0.237)和IL-2分泌水平[(11.02±2.50)ng/L比(8.21±2.63)ng/L3]均显著下降(P<0.01和P<0.05);伤后1～14 d,死亡组CD14+单核细胞表面HLA-DR表达量持续下降,而存活组则有所回升,伤后14 d时两组比较差异有统计学意义(P<0.01).结论 特重度烧伤患者细胞免疫功能处于持续抑制状态,动态监测CD14+单核细胞表面HLA-DR表达量、T淋巴细胞增殖反应活性和IL-2分泌水平,对于判断患者预后可能有重要临床参考价值.     

Assessment of cardiovascular regulation after burns by nonlinear analysis of the electrocardiogram

Critical illness and hypovolemia are associated with loss of complexity of the R-to-R interval (RRI) of the electrocardiogram, whereas recovery is characterized by restoration thereof. Our goal was to investigate the dynamics of RRI complexity in burn patients. We hypothesized that the postburn period is associated with a state of low RRI complexity, and that successful resuscitation restores it. Electrocardiogram was acquired from 13 patients (age 55 +/- 5 years, total body surface area burned 36 +/- 6%, 11 +/- 5% full thickness) at 8, 12, 24, and 36 hours during postburn resuscitation. RRI complexity was quantified by approximate entropy (ApEn) and sample entropy (SampEn) that measure RRI signal irregularity, as well as by symbol distribution entropy and bit-per-word entropy that assess symbol sequences within the RRI signal. Data (in arbitrary units) are means +/- SEM. All patients survived resuscitation. Changes in heart rate and blood pressure were not significant. ApEn at 8 hours was abnormally low at 0.89 +/- 0.06. ApEn progressively increased after burn to 1.22 +/- 0.04 at 36 hours. SampEn showed similar significant changes. Symbol distribution entropy and bit-per-word entropy increased with resuscitation from 3.63 +/- 0.22 and 0.61 +/- 0.04 respectively at 8 hours postburn to 4.25 +/- 0.11 and 0.71 +/- 0.02 at 24 hours postburn. RRI complexity was abnormally low during the early postburn period, possibly reflecting physiologic deterioration. Resuscitation was associated with a progressive improvement in complexity as measured by ApEn and SampEn and complementary changes in other measures. Assessment of complexity may provide new insight into the cardiovascular response to burns.     

Effect of ibuprofen on the postburn hypermetabolic response: a case report

Severely burned patients exhibit a postburn hypermetabolic response which, with the most severe burns, can double the patient's metabolic rate. We report on a 54-year-old man who was on long-term ibuprofen administration for treatment of arthritis before sustaining a 38% total body surface area burn. This patient failed to demonstrate the normal hypermetabolic response. The possibility that the ibuprofen administration prevented the hypermetabolic response is discussed.     

Effect of blood transfusion on outcome after major burn injury: a multicenter study

OBJECTIVE: To delineate blood transfusion practices and outcomes in patients with major burn injury. CONTEXT: Patients with major burn injury frequently require multiple blood transfusions; however, the effect of blood transfusion after major burn injury has had limited study. DESIGN: Multicenter retrospective cohort analysis. SETTING: Regional burn centers throughout the United States and Canada. PATIENT POPULATION: Patients admitted to a participating burn center from January 1 through December 31, 2002, with acute burn injuries of >or=20% total body surface area. OUTCOMES MEASURED: Outcome measurements included mortality, number of infections, length of stay, units of blood transfused in and out of the operating room, number of operations, and anticoagulant use. RESULTS: A total of 21 burn centers contributed data on 666 patients; 79% of patients survived and received a mean of 14 units of packed red blood cells during their hospitalization. Mortality was related to patient age, total body surface area burn, inhalation injury, number of units of blood transfused outside the operating room, and total number of transfusions. The number of infections per patient increased with each unit of blood transfused (odds ratio, 1.13; p<.001). Patients on anticoagulation during hospitalization received more blood than patients not on anticoagulation (16.3+/-1.5 vs. 12.3+/-1.5, p<.001). CONCLUSIONS: The number of transfusions received was associated with mortality and infectious episodes in patients with major burns even after factoring for indices of burn severity. The utilization of blood products in the treatment of major burn injury should be reserved for patients with a demonstrated physiologic need.     

Early burn center transfer shortens the length of hospitalization and reduces complications in children with serious burn injuries.

Prompt transfer of the child with acute burns can be difficult from distant or inaccessible locations, and it is believed that the outcomes of children with serious burns whose transfer to a specialized burn care facility is delayed may be compromised. A 4-year experience with 16 consecutive children with serious burns (> or =20% of the body surface area) whose transfer to a burn care facility was delayed for 5 or more days was reviewed to document the difficulties that can follow such delays. These 16 children had an average age of 8.6+/-1.6 years and an average wound size of 57.6%+/-5.8% of the body surface area, and they arrived a mean of 16.3+/-3.4 days after the injury (range, 5 to 44 days). These children had undergone an average of 1 operation, excluding escharotomies, at referring facilities. Only 4 (25%) of the children had no infectious focus at transfer, and at admission resistant bacteria were recovered from 9 (56%) of the children and fungal organisms were found in 10 (63%). Compared with a concurrently managed matched control group of patients admitted to the burn center within 24 hours of injury, the delayed-transfer group had statistically significantly more bacteremia, renal dysfunction, wound sepsis, and central venous catheter days. It was also more expensive to manage these children; the delayed-transfer group required statistically significantly longer to achieve 95% wound closure, and they had greater total lengths of hospital stay and more rehabilitation days. The early transfer of children with serious burns to a specialized burn center may truncate hospitalization and thereby reduce costs.     

Evaluating the psychosocial adjustment of 2- and 3-year-old pediatric burn survivors

Very little information has been published about 2- and 3-year-old children who have experienced major burns. This study used a standardized instrument to measure the behavioral adjustment of these young burn survivors, and the results were compared with those of a nonclinical normative sample. Thirty-three pediatric burn survivors with 50%+/-28% total body surface area burns were evaluated 1.2+/-0.7 years postburn. Parental observations were assessed with the use of the Child Behavior Checklist for 2- and 3-Year-Olds, a 99-item standardized checklist designed to identify behavior problems. Forty of the questions are specific to 2- and 3-year-olds, and the scores of male and female children are not differentiated. The raw scores of the children with burns were statistically compared with the reported normative sample for this version of the Child Behavior Checklist. Pediatric burn survivors in this sample exhibited significantly more internalizing behaviors than the children in the normative group. Parents reported children who had been burned to be more depressed and to have more somatic complaints and sleep problems. Determining the relationship of behavior problems to posttrauma sequelae and preburn environmental factors would assist with the establishment of appropriate psychosocial interventions.     

The Effects of Epidermal Debridement of Partial-thickness Burns on Infection and Reepithelialization in Swine

OBJECTIVE: Early postburn debridement of burn blisters is controversial. This study was conducted to compare rates of infection and reepithelialization in debrided vs nondebrided second-degree burns in swine. METHODS: This was a prospective, blinded, controlled, experimental trial using isoflurane-anesthetized swine. Standardized partial-thickness burns were inflicted by applying an aluminum bar preheated to 80 degrees C to the backs and flanks of two young pigs for 20 seconds. In half of the burns the necrotic epidermis was manually debrided. All burns were randomly treated with octylcyanoacrylate spray (OCA) or dry gauze (C). Full-thickness biopsies were taken at 7, 10, and 14 days for blinded histopathologic evaluation. The primary outcomes were the proportions of infected burns at days 7 and 10 and the proportion of completely reepithelialized burns at day 14. Burns were considered infected in the presence of intradermal neutrophils containing bacteria (intraobserver agreement, K = 1.00). A secondary outcome was the proportion of burns with the presence of scar tissue (abnormal collagen under polarized light; intraobserver correlation, K = 0.93). Chi-square tests were used for group comparisons. This study had 90% power to detect a 40-percentage-point difference in infection rates (alpha = 0.05). RESULTS: A total of 126 biopsies from 42 burns were available for review. Infection rates were higher in the debrided burns both at day 7 (55% vs 4.5%, p < 0.001) and at day 10 (65% vs 9%, p < 0.001) after injury. The proportion of nondebrided burns that were completely reepithelialized was higher at days 10 (68% vs 0%, p < 0.001) and 14 (100% vs 65%, p = 0.003). The presence of scar tissue was more common in debrided burns (75% vs 4.5%, p < 0.001). Burns treated with OCA had fewer infections than controls (4% vs 55%, p < 0.001). Fewer OCA-treated debrided burns were reepithelialized at 14 days than those that were not debrided (30% vs 100%, p = 0.001). CONCLUSIONS: Under the current study conditions, early postburn epidermal debridement of second-degree burns resulted in more infections and slower reepithelialization rates in swine. The effects of early postburn epidermal debridement in humans should be explored.     

严重烧伤早期肠黏膜组织热休克蛋白70的表达规律

目的探讨大鼠烧伤后早期肠黏膜组织热休克蛋白70(HSP70)的表达变化规律及其意义。方法采用大鼠烫伤模型,通过逆转录-聚合酶链反应(RT-PCR)、蛋白质免疫印迹(Westernblot)及免疫组化等方法,检测伤后3、6、12、24和48h不同时间点肠黏膜组织内HSP70及热休克因子1(HSF1)的表达分布情况。结果烫伤后3h肠黏膜组织内HSP70mRNA及蛋白表达均显著增加,分别在伤后6h和12h达高峰,伤后48h仍高于正常对照组(P均<0.01);伤后3h大鼠肠黏膜组织HSF1出现一过性降低,伤后6h其表达显著高于正常对照组,并呈逐渐增加的趋势直至持续到伤后48h(P均<0.01)。结论严重烧伤早期肠黏膜组织HSP70及HSF1表达均显著增加,提示严重烧伤早期即可引起肠黏膜组织细胞的应激反应,可能与细胞的自我保护机制启动有关。     

Cholesterol and interleukin-6 concentrations relate to outcomes in burn-injured patients

The goal of this study was to determine the relationship among lipid concentrations, cytokine concentrations, and clinical outcomes of burn patients. Twenty-eight patients admitted within 24 hours of burn injury, segregated based on burn size, had blood samples drawn 24 and 48 hours after burn injury and then weekly for 3 weeks. Measurements included total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglyceride, interleukin (IL)-6, soluble IL-2 receptor, and soluble necrosis factor p55 and p75 receptors. Infection, length of stay (LOS), and survival were monitored. Cholesterol and lipoprotein concentrations decreased by at least 40% in patients with burns >20% total body surface area and inversely correlated with IL-6. Lower cholesterol and higher IL-6 values correlated with higher infection rates and longer LOS. IL-6 was the strongest predictor for LOS. In conclusion, outcomes after burn injury are related to low cholesterol and elevated IL-6 levels.     

Marked increase in plasma interleukin-6 in burn patients.

We measured the levels of interleukin-6 in plasma samples from 18 consecutive burn patients, including three lethal cases, during the early postburn period. In survivors burn injury caused initial increases in interleukin-6 levels that peaked at 6 hours after burn; this was significantly higher than interleukin-6 levels in normal controls (718 +/- 216 vs 70 +/- 4 pg/ml; p < 0.01). The increment in nonsurvivors was even more prominent (11,554 +/- 4,407 pg/ml; p < 0.01). The peak interleukin-6 levels at 6 hours correlated with total burn surface area (r = 0.65, p < 0.025), and tended to be higher in patients with inhalation injury. These data provide evidence that burn injury causes rapid release of interleukin-6 according to the severity of the injury. We also measured acute-phase reactants including fibrinogen, alpha 1-antitrypsin, C1 inhibitor, and alpha 2-plasmin inhibitor. After initial declines, these four proteins increased rapidly in survivors. In addition, the peak interleukin-6 levels correlated well with the increases in fibrinogen (p < 0.025), alpha 1-antitrypsin (p < 0.01), C1 inhibitor (p < 0.01), and alpha 2-plasmin inhibitor (p < 0.0001). In contrast, despite the marked increase in interleukin-6, the levels of acute phase proteins in nonsurvivors remained low. Based on these observations, we suggest that interleukin-6 is released as an alarm signal and has a role for the wound healing in burn patients, and that the levels of interleukin-6 after injury is an indicator of the severity of burn.     

Prevalence of postburn depression following burn injury

We examined the prevalence of depression after burn injury in 139 adults treated at a major burn center. Interviews were held from one to eight years following the burn. Our subsample, taken from 882 patients treated over a six-year period, comprised all patients with 30% total body surface area burns and a random sample of those with burns of lesser severity. We considered 17 possible predictors of depression (including the severity and placement of the burn and the patient's age, educational background, medical history, employment status, income level, and emotional and psychiatric history). We found that it is the person, rather than the injury, that best predicts postburn depression. The factor most strongly linked with depression was a past history of emotional disturbance. However, after being burned, a significant number of even previously well-adjusted patients show clinical postburn depression.     

The burn unit experience at Grady Memorial Hospital: 844 cases.

Between February 20, 1987 and July 13, 1990, 844 patients were admitted to the Grady Memorial Hospital Burn Unit. Mean age was 25.5 years, mean burn size 16.5% total body surface area, mean survivor hospital length of stay 15.9 days, and an overall survival 90.5%. Seventy-three percent were male. One half of the burns were less than 10% total body surface area. Almost half (48.5%) of the patients had flame burns, which accounted for 88.8% of the 80 deaths. The peak burn incidence occurred in infants and children as a result of scalds. If those with toxic epidermal necrolysis (n = 5), those without skin injury (n = 13), and those who were allowed to die (n = 16) are excluded, survival was 92.2%. Survival in 62 patients with inhalation injury (55.23%) was significantly less than that in 474 patients without inhalation injury (98.10%) (p less than 0.0001). The three variables--age, burn size, and inhalation injury--each influenced survival significantly but appeared to be dependent on each other; all three tended to increase or decrease together. Logistic regression equations to predict survival were developed.     

WEB2170, a specific platelet-activating factor antagonist, attenuates neutrophil priming by human serum after clinical burn injury: the 1991 Moyer Award.

Primed neutrophils may contribute to endothelial and end-organ damage after burn injury because of increased endothelial adherence and enhanced toxic oxygen metabolite generation in response to a "second insult" such as bacterial sepsis. The purposes of this study were to determine: (1) whether serum from patients with thermal injury causes priming of the neutrophil NADPH:O2 oxidoreductase, (2) whether time after burn (early vs late) influences neutrophil priming, and (3) whether priming could be attenuated by a specific platelet-activating factor antagonist, WEB2170. Normal human neutrophils were incubated with 10% sera that was obtained from healthy adult controls (normal human sera) and with 10% sera from patients with greater than 30% total body surface area burns, which was collected early (early postburn sera) (i.e., between 12 and 48 hours after burn) or late (late postburn sera) (5 to 15 days, after burn). Priming of the neutrophil oxidase was tested for by measurement of the generation of superoxide anion after a stimulus of 10(-6) mol/L formyl-methionine-leucine-phenylalanine (fMLP). In separate experiments, neutrophils were pretreated with WEB2170 before serum incubation and fMLP stimulation to block any priming that may be mediated by platelet-activating factor. All sera caused an increased rate of superoxide anion production in response to fMLP and thus "primed" the neutrophil NADPH:O2 oxidoreductase. Greater priming occurred after incubation with late postburn sera than with other sera. WEB2170 completely inhibited priming by normal human sera and early postburn sera and partially inhibited priming by late postburn sera.(ABSTRACT TRUNCATED AT 250 WORDS)