Prophylactic intubation and continuous positive airway pressure in the management of inhalation injury in burn victims

Burn mortality statistics are influenced by age and degree of total surface body burn. The addition of an inhalation injury to a cutaneous burn results in a significant increase in mortality rate. Nine hundred fourteen patients with acute thermal injury were screened for positive history of burn in a closed space, facial or oropharyngeal burn, singed nasal vibrisae, carbonacious sputum, and clinical signs of upper airway involvement. On admission, 84 patients (9.2%) had more than one of the previously mentioned factors. They were prophylactically intubated and placed on optimum level of continuous positive airway pressure (CPAP) and intermittent mandatory ventilation (IMV). The mortality rate among patients without inhalation injury was 7.1%, while 54.7% of patients with inhalation injury died. Comparison of burn patients with inhalation injury to those without pulmonary involvement at the same age group and with the same percentage of burn showed significantly higher mortality rate in patients with inhalation injury. The main cause of death in the first 72 h postburn (stage 1) in patients without inhalation injury was peripheral shock (10.1%) and in patients with inhalation injury was peripheral shock (15.2%) and cardiac failure (10.8%). No pulmonary related death occurred in this stage. In 3-10 days postburn period (stage 2), burn wound sepsis (10.1%) and cardiac failure (11.8%) were the major causes of death in patients with inhalation injury. In patients with inhalation injury, pulmonary sepsis (26%) was the major cause of death in this stage. Major causes of death after 10 days postburn (stage 3) in patients without inhalation injury were pulmonary sepsis (20%) and burn wound sepsis (22%). In patients with inhalation injury, burn wound sepsis (21.7%) was the main cause of death. These data suggest that prophylactic intubation and CPAP therapy in burn patients with suspected inhalation injury prevent pulmonary related death in early stage of burn. Irrespective of presence of inhalation injury, sepsis originating from the wound or respiratory tract is the main cause of death in the late stage of burn.     

The control of burn wound sepsis

This presentation reviews the course of burn wound sepsis in a group of 621 acute patients treated at the Shriners Burns Institute, Cincinnati Unit, between 1970 and 1976. During this period of time, the overall mortality rate fell from 14% in 1970 to 3 and 5%, respectively, in 1975 and 1976. Staphylococcus aureus was the most commonly recovered organism from the burn wound, colonizing 85% of the burn patients. Beta hemolytic streptococcus represented a potential threat despite the fact that it was recovered from only 5 to 10% of the patients.Pseudomonas aeruginosa showed a decrease in colonization during the period of this study, from 50% of the wounds in 1970 to 21% in 1976.Candida albicans was the fungal organism most commonly recovered from the burn wound and from the blood stream. Fifteen deaths occurred in this group as a result of invasive infection, one fromS. aureus, five fromP. aeruginosa, two fromKlebsiella-Enterobacter, and one fromEscherichia coli, as well as six fungal deaths, five fromCandida albicans and one from mucormycosis. Therapeutic measures used to control burn wound sepsis consisted of prevention of contamination from exogenous sources, control of burn wound pathogens, early recognition of invasive burn wound sepsis, aggressive management of the burn wound, and optimal nutritional support. During this period the extent of burn associated with a survival of 50% has risen from 50% in 1970 to 80% in 1976. This improvement in survival is directly related to progressive improvement in local and systemic measures available for the control of infection.     

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.     

Pharmacokinetics and burn eschar penetration of intravenous ciprofloxacin in patients with major thermal injuries

Adequate penetration of antibiotics into burn tissue and maintenance of effective serum levels are essential for the treatment of patients sustaining major thermal injuries. The pharmacokinetics and burn eschar penetration of intravenous ciprofloxacin were determined in 12 critically ill patients with burn injuries. Mean age for the 12 patients was 45 +/- 17 (range 25-82 years), total body surface area burned (TBSAB) = 38 +/- 15% and Acute Physiology and Chronic Health Evaluation (APACHE) II score = 8 +/- 6. Patients received recommended doses of ciprofloxacin, 400 mg q12h iv, for three doses beginning 72 h post-burn. Serum concentrations were measured at t = 0, 0.25, 0.5, 0.75, 1.0, 1.25, 1.5, 2.0, 4.0 and 12.0 h after the first and third doses. Burn eschar biopsies were obtained after the third ciprofloxacin dose. Three of these 12 patients (25%) manifested later signs of clinical sepsis (TBSAB = 61 +/- 6% and APACHE II score = 11 +/- 3) and underwent a second infusion of three doses of intravenous ciprofloxacin, blood sampling and eschar biopsy. Serum and eschar concentrations were determined by high performance liquid chromatography. Serum ciprofloxacin concentrations were comparable to those of normal volunteers (C(max) = 4.0 +/- 1 mg/L and AUC = 11.4 +/- 2 mg.h/L) during the immediate post-burn period after dose 1 (C(max1) = 4.8 +/- 3 mg/L and AUC(0-12) = 12.5 +/- 7 mg. h/L) and dose 3 (C(max3) = 4.9 +/- 2 mg/L and AUC(24-36) = 17.5 +/- 11 mg.h/L). Mean burn eschar concentration during the 72 h post-burn was significantly lower than that found during clinical sepsis (18 +/- 17 compared with 41.3 +/- 54 microg/g; P < 0.05 by t test). Similar serum concentrations were achieved in patients with clinical sepsis (C(max1) = 4.2 +/- 0.2 mg/L and AUC(0-12) = 15.0 +/- 3 mg. h/L; C(max3) = 5.0 +/- 1 mg/L and AUC(24-36) = 22.8 +/- 9 mg.h/L). A positive correlation between burn eschar concentrations and C(max) (r = 0.71, r(2) = 0.51, P = 0.01) was found by linear regression analysis. A C(max)/MIC ratio > 10 (MIC = 0.5 mg/L) and an AUC/MIC ratio > 100 SIT(-1).h (serum inhibitory titre) (MIC = 0.125 mg/L) were achieved. High burn eschar concentrations and serum levels, similar to those found in normal volunteers, can be achieved after intravenous ciprofloxacin infusion in critically ill burns patients.     

Positive fungal cultures in burn patients: a multicenter review.

Fungal infections are increasingly common in burn patients. We performed this study to determine the incidence and outcomes of fungal cultures in acutely burned patients. Members of the American Burn Association's Multicenter Trials Group were asked to review patients admitted during 2002-2003 who developed one or more cultures positive for fungal organisms. Data on demographics, site(s), species and number of cultures, and presence of risk factors for fungal infections were collected. Patients were categorized as untreated (including prophylactic topical antifungals therapy), nonsystemic treatment (nonprophylactic topical antifungal therapy, surgery, removal of foreign bodies), or systemic treatment (enteral or parenteral therapy). Fifteen institutions reviewed 6918 patients, of whom 435 (6.3%) had positive fungal cultures. These patients had mean age of 33.2 +/- 23.6 years, burn size of 34.8 +/- 22.7%TBSA, and 38% had inhalation injuries. Organisms included Candida species (371 patients; 85%), yeast non-Candida (93 patients, 21%), Aspergillus (60 patients, 14%), other mold (39 patients, 9.0%), and others (6 patients, 1.4%). Systemically treated patients were older, had larger burns, more inhalation injuries, more risk factors, a higher incidence of multiple positive cultures, and significantly increased mortality (21.2%), compared with nonsystemic (mortality 5.0%) or untreated patients (mortality 7.8%). In multivariate analysis, increasing age and burn size, number of culture sites, and cultures positive for Aspergillus or other mold correlated with mortality. Positive fungal cultures occur frequently in patients with large burns. The low mortality for untreated patients suggests that appropriate clinical judgment was used in most treatment decisions. Nonetheless, indications for treatment of fungal isolates in burn patients remain unclear, and should be developed.     

Management of severe toxic epidermal necrolysis in children

Toxic epidermal necrolysis (TEN) is a severe form of erythema multiforme that results in extensive epidermal sloughing; the condition is associated with a mortality of up to 70%. From 1991 to 1998, 10 children with severe toxic epidermal necrolysis were referred to a regional pediatric burn facility. Wounds were managed with strategy involving prevention of wound desiccation and superinfection, including the frequent use of biologic wound coverings. Children unable to guard their airway because of extensive oropharyngeal involvement were prophylactically intubated. Enteral nutrition was stressed. Steroids were not used and antibiotics were administered to managed specific foci of infection only. The 2 boys and 8 girls had an average age of 7.2+/-1.8 years (range 6 months to 15 years) and sloughed surface area of 76+/-6% of the body surface (range 50 to 95%). Antibiotics (3 children), anticonvulsants (3 children), nonsteroidals (2 children), and viral syndrome or unknown agents (2 children) were felt to have triggered the syndrome. Six children (60%) required intubation for an average of 9.7+/-1.8 days (range 2 to 14 days). Buccal mucosal involvement occurred in 9 (90%) and ocular involvement in 9 (90%). Although infectious complications were common (2 pneumonias, 2 urinary infections, 1 bacteremia, 2 central line infections, and 2 candidemias), all children survived after lengths of stay in the burn unit averaging 19+/-3 (range 6 to 40) days. The most common long-term morbidity was keratitis sicca (2 children, 20%), finger nail deformities (3 children, 30%), and variegated skin pigment changes (5 children, 50%). Although having both a cutaneous and visceral wound that predispose them to infectious complications, most children with TEN will survive if managed with a strategy emphasizing biologic wound closure, intensive nutritional support, and early detection and treatment of septic foci. Burn units have the resource set required to manage severe TEN and early referral of such children may have a favorable impact on survival.     

Ornithine alpha-ketoglutarate improves wound healing in severe burn patients: a prospective randomized double-blind trial versus isonitrogenous controls

OBJECTIVE: To compare the effectiveness on wound healing time in severe burn patients of ornithine alpha-ketoglutarate supplementation of enteral feeding vs. an isonitrogenous control. Previous clinical and experimental studies suggest a beneficial effect of enterally administered ornithine alpha-ketoglutarate supplementation on protein metabolism in burn patients, but few data deal with clinical outcome. DESIGN: Prospective double-blind randomized trial. SETTING: Burn treatment center of an army hospital. PATIENTS: Forty-seven severe burn patients with total burned body surface areas of 25% to 95% and presence of full thickness burn who were prescribed early exclusive enteral nutrition. Either ornithine alpha-ketoglutarate or isonitrogenous control (soy protein mixture, Protil-1) were administered twice a day as a bolus (2 x 10 g) at 9 am and 9 pm for 3 wks. The patients were evaluated for wound healing time (primary end point), antibiotic use, tolerance, duration of enteral nutrition, and nutritional status. INTERVENTIONS: Serial blood samples were collected in each patient for determination of serum transthyretin and plasma phenylalanine, and urine sampling was performed for determination of 3-methylhistidine excretion at day 4 and day 21 after burn injury. MEASUREMENTS AND MAIN RESULTS: Wound healing times in patients receiving ornithine alpha-ketoglutarate or Protil-1 were 60 +/- 7 and 90 +/- 12 days, respectively (p < .05) for similar grafted surfaces. Based on increased serum transthyretin concentrations, both groups showed an improvement of nutritional status at day 21 after burn. Taking a cut-off value of 110 unit burn standard for severity of injury, plasma phenylalanine concentrations, and urinary 3-methylhistidine/creatinine ratio were significantly reduced (p < .05) in the less severe burn patients (<110 unit burn standard) supplemented with ornithine alpha-ketoglutarate. CONCLUSIONS: Ornithine alpha-ketoglutarate supplementation of enteral feeding significantly shortens wound healing time in severe burn patients. In addition, ornithine alpha-ketoglutarate administration was safe and well tolerated and decreased protein hypercatabolism in the less severe burn patients.     

Increased survival after massive thermal injuries in adults: preliminary report using artificial skin

Survival of major burn injuries has improved markedly from an expected survival of 10% to 20% in both children and adults to an expected survival of 60% in children with burns greater than 70% BSA. Increased survival for adults after similar burn injuries has been less dramatic than in children because of the profound influences of advancing age and the coexistent processes of aging upon survival after a major injury. Consecutive admissions of patients with massive burn injuries (greater than or equal to 70% BSA) to the Massachusetts General Hospital Adult Burn Unit from 1974 to 1986 were analyzed statistically using univariate and multiple logistic regression analysis to identify factors associated with survival and to identify patient characteristics associated with increases in expected survival. Survival of adults with massive burn injuries has improved markedly, from 24% of adults admitted to the Adult Burn Center in 1974-75 to 48% of adults admitted in 1984-86. An increased likelihood of survival was shown to be associated with the use of artificial skin. Improved survival rates in these massive burn injuries were attributed to multiple factors including wound management of prompt eschar excision and immediate wound closure.     

Venous thrombosis incidence in burn patients: preliminary results of a prospective study

There are few prospective data on the incidence of deep venous thrombosis (DVT) in burn patients. In an on-going prospective study, hospitalized burn patients 18 years or older with an expected hospital length of stay more than 72 hours were imaged with baseline venous duplex ultrasound of all extremities within the first 48 hours after admission and weekly until discharge. Patient demographics and clinical risk factors for DVT were assessed. At the time of submission, 40 patients met screening criteria, and 30 were enrolled. Ultrasound diagnosed seven patients with 11 acute DVT for an incidence of 23%. One pulmonary embolism was documented. DVT patients had a mean age of 49 +/- 23 years with an average TBSA burn of 15 +/- 4% compared with those without thrombosis with a mean age of 44 +/- 17 years (P = NS) and TBSA burn of 18 +/- 25% (P = NS). There were no statistically significant differences for DVT patients in terms of age, number of central line days, hospital length of stay, or TBSA burned. Given the preliminary findings of this small study, we believe that all hospitalized burn patients are at risk for DVT. On-going investigation will be helpful in defining level of risk and improved prevention strategies for thromboembolic complications in burn patients.     

Autologous scalp skin grafting to treat toxic epidermal necrolysis in a patient with a large skin injury: A case report

BACKGROUNDToxic epidermal necrolysis (TEN) is often associated with skin wounds affecting large areas. Healing of this type of wound is difficult because of pressure, infection and other factors. It can increase the length of hospital stay and result in wound sepsis and even death.CASE SUMMARYA 49-year-old woman developed a skin lesion covering 80% of the total body surface area after using a kind of Chinese medicinal ointment on a burn wound on her back; she developed life-threatening wound sepsis and septic shock. Methicillin-resistant Staphylococcus aureus, carbapenem-resistant Acinetobacter baumannii, carbapenem-resistant Pseudomonas aeruginosa and other bacteria were cultured from wound tissue, deep venous catheter and blood samples. Imipenem cilastatin sodium, tigecycline and teicoplanin were used for anti-infection therapy. Finally, the patient was transferred to the burn department because of severe wound sepsis. In the burn intensive care unit, pain-free dressing changes and autologous scalp skin grafting were performed to heal the wound in addition to reasonable and effective antibacterial treatment according to microbial susceptibility test results. After three operations within 2 wk, the wound healed and sepsis resolved.CONCLUSIONTEN patients with large areas of skin injury may develop wound infection and life-threatening wound sepsis. Autologous scalp skin grafting may be beneficial for rapid wound healing and reducing the risk of sepsis in TEN patients, and it leaves no scar at the donor site.     

Blockade ofthe negative co-stimulatory molecules PD-1 and CTLA-4 improves survival in primary and secondary fungal sepsis

Introduction

Fungal sepsis is an increasingly common problem in intensive care unit patients.Mortality from fungal sepsis remains high despite antimicrobial therapy that is highly active against most fungal pathogens, a finding consistent with defective host immunity that is present in many patients with disseminated fungemia.One recently recognized immunologic defect that occurs in patients with sepsis is T cell "exhaustion" due to increased expression of programmed cell death -1 (PD-1).This study tested the ability of anti-PD-1 and anti-programmed cell death ligand -1 (anti-PD-L1) antagonistic antibodies to improve survival and reverse sepsis-induced immunosuppression in two mouse models of fungal sepsis.

Methods

Fungal sepsis was induced in mice using two different models of infection, that is, primary fungal sepsis and secondary fungal sepsis occurring after sub-lethal cecal ligation and puncture (CLP).Anti-PD-1 and anti-PD-L1 were administered 24 to 48 h after fungal infection and effects on survival, interferon gamma production, and MHC II expression were examined.

Results

Anti-PD-1 and anti-PD-L1 antibodies were highly effective at improving survival in primary and secondary fungal sepsis.Both antibodies reversed sepsis-induced suppression of interferon gamma and increased expression of MHC II on antigen presenting cells.Blockade of cytotoxic T-lymphocyte antigen-4 (CTLA-4), a second negative co-stimulatory molecule that is up-regulated in sepsis and acts like PD-1 to suppress T cell function, also improved survival in fungal sepsis.

Conclusions

Immuno-adjuvant therapy with anti-PD-1, anti-PD-L1 and anti-CTLA-4 antibodies reverse sepsis-induced immunosuppression and improve survival in fungal sepsis.The present results are consistent with previous studies showing that blockade of PD-1 and CTLA-4 improves survival in bacterial sepsis.Thus, immuno-adjuvant therapy represents a novel approach to sepsis and may have broad applicability in the disorder.Given the relative safety of anti-PD-1 antibody in cancer clinical trials to date, therapy with anti-PD-1 in patients with life-threatening sepsis who have demonstrable immunosuppression should be strongly considered.     

Comparison of mortality associated with sepsis in the burn, trauma, and general intensive care unit patient: a systematic review of the literature

The purpose of this systematic review of the literature was to determine the association of sepsis with mortality in the severely injured adult patient by means of a comparative analysis of sepsis in burn and trauma injury with other critically ill populations. The MEDLINE (PubMed), Cochrane Library, and ProQuest databases were searched. The following keywords and MeSH headings were used: "sepsis," septicemia," "septic shock," "epidemiology," "burns," "thermal injury," "trauma," "wounds and injuries," "critical care," "intensive care," "outcomes," and "mortality." Included studies were clinical studies of adult burn, trauma, and critically ill patients that reported survival data for sepsis. Thirty-eight articles were reviewed (9 burn, 11 trauma, 18 general critical care). The age of burn (<45 years) and trauma (34-49 years) groups was lower than the general critical care (57-64 years) population. Sepsis prevalence varied with trauma-injured patients experiencing fewer episodes (2.4%-16.9%) contrasted with burn patients (8%-42.5%) and critical care patients (19%-38%). Survival differed with trauma patients experiencing a lower rate of mortality associated with sepsis (7%-36.9%) compared with the burn (28%-65%) and critical care (21%-53%) groups. This study is the first to compare sepsis outcomes in three distinct patient populations: burn, trauma, and general critical care. Trauma patients tend to have relatively low sepsis-associated mortality; burn patients and the older critical care population have higher prevalence of sepsis with worse outcomes. Great variability of criteria to identify septic patients among studies compromises population comparisons.     

Early clinical experience with high-frequency oscillatory ventilation for ARDS in adult burn patients

Lung protective ventilation strategies are recommended in acute respiratory distress syndrome to avoid ventilator associated lung injury, a recently characterized complication of mechanical ventilation. High-frequency oscillatory ventilation (HFOV) is an unconventional ventilation strategy which may achieve this goal. We reviewed our experience with HFOV in six severely burned patients with acute respiratory distress syndrome. The mean age (+/- SD) of the patients was 34 +/- 13 years, and the mean TBSA burn was 52 +/- 10%, with a mean full-thickness injury of 49 +/- 12%. HFOV was initiated as "rescue therapy" in three patients with oxygenation failure (mean PaO2/FIO2 ratio of 71 +/- 8 and mean oxygenation index [OI] of 42 +/- 3) that was unresponsive to conventional ventilation (mean FIO2, 1.0 +/- 0; mean positive end expiratory pressure, 14.8 +/- 2.8 cm H2O; and mean inhaled nitric oxide, 20 +/- 0 ppm). In the other three cases, HFOV was initiated "prophylactically" as a lung protective ventilation strategy in an attempt to prevent further respiratory deterioration. All six patients showed a rapid and substantial improvement in oxygenation after initiation of HFOV, with significant improvements in the PaO2/FIO2 and OI by 12 hours (P = 0.02). In four patients HFOV was also used during anesthesia and surgery, where a total of 10 procedures involving a mean excision and closure of 15 +/- 7% TBSA burns was performed. Five of the six patients died, but none died because of oxygenation failure. In three patients death resulted from sepsis and multiple organ dysfunction syndrome; their mean PaO2/FIO2 was 107 +/- 31 and their mean OI was 30 +/- 11 immediately before death. Two patients with multiple organ dysfunction syndrome died after withdrawal of life support; their mean PaO2/FIO2 and OI were 178 +/- 31 and 18 +/- 2 respectively, at the time of this decision. Although HFOV had no impact on mortality, it played a useful role in the supportive management of burn patients with severe oxygenation failure unresponsive to conventional ventilation. Importantly, HFOV allowed surgery to proceed in patients who may have otherwise been too unstable to go to the operating room. As far as we are aware, this is the first report of the use of intraoperative HFOV in burn patients.     

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.     

The anticatabolic and wound healing effects of the testosterone analog oxandrolone after severe burn injury

PURPOSE: Severe burn injury leads to marked catabolism and decreased lean mass, which can impair healing. Anabolic agents can attenuate net catabolism. Our purpose was to determine whether the testosterone analog, oxandrolone, given during the acute post burn period decreased the degree of nitrogen loss and loss of body weight while also increasing the healing rate of a skin donor site. MATERIALS AND METHODS: Patients with burns between 40% and 70% of body surface were studied. A randomized double-blinded placebo-controlled study design was used. Patients were given oxandrolone 20 mg/day (n = 11) or a placebo 20 mg/day (n = 9) beginning between days 2 and 3 post burn. Net nitrogen balance and the healing time of a standardized donor site were measured. Patients were monitored until transferred to a burn rehabilitation facility, an average time period of 33 +/- 9 days. RESULTS: Mean burn size was 49 +/- 8% for placebo and 53 +/- 9% of total body surface for the oxandrolone group. Smoke inhalation was present in approximately 50% of patients in both groups. All patients survived the burn injury. Net weight loss was 8 +/- 3.1 kg in the placebo group compared with 3 +/- 1.9 kg in the oxandrolone group, a statistically significant decrease. Net daily nitrogen loss over a 3-week period (days 7 to 28) was 13 +/- 4 g in placebo treated compared with 4 +/- 1.9 g for the oxandrolone group, a statistically significant decrease. The healing time of a standardized donor site, decreased from the placebo group value of 13 +/- 3 days to 9 +/- 2 days for oxandrolone treated patients, a significant improvement. No major liver dysfunction, or other complication attributable to an anabolic steroid was seen in either group. CONCLUSION: We found the anabolic agent, oxandrolone, significantly decreased weight loss and net nitrogen loss and increased donor site wound healing compared with placebo controls. We noted no complications with the use of oxandrolone.     

大面积烧伤合并创面脓毒症40例临床分析

目的:总结烧伤合并创面脓毒症的临床特点和防治措施。方法:回顾性分析我科2007年1月至2012年12月收治的烧伤合并创面脓毒症40例的临床资料。结果:治愈32例,死亡8例。结论:烧伤早期休克渡过不平稳及创面早期处理不当易致创面脓毒症,预防强调积极有效的液体复苏、早期肠道营养、加强代谢与免疫调理、尽早封闭创面及加强多器官功能保护与支持,治疗强调以创面处理为核心的综合治疗策略,尽早手术覆盖封闭深度创面是救治成功的关键。     

Longitudinal assessment of Integra in primary burn management: a randomized pediatric clinical trial

BACKGROUND: Early excision with autograft-allograft closure is standard in severe burn management. Cadaver skin is associated with risks such as antigenicity, infection, and limited availability and shelf life. Previous studies have shown that Integra is safe to use in burns of <20% total body surface area. However, the suitability of its use in large burns (>50% total body surface area), its effects on postburn hypermetabolism, and the long-term cosmetic and functional results have not yet been evaluated. MATERIALS AND METHODS: Twenty children with an average burn size of 73 +/- 15% total body surface area (71 +/- 15% full-thickness burn) were randomized to be treated with either Integra or with autograft-allograft technique. Outcome measures such as length of hospital stay, mortality, incidence of infection and sepsis, acute phase protein levels, and muscle fractional synthetic rate were compared between and within groups during the acute stay (admission to discharge). Outcome measures such as resting energy expenditure, body composition data (measured by dual-energy radiograph absorptiometry), cardiac function indexes, and number of reconstructive procedures were compared during acute hospital stay and at long-term follow-up (up to 2 yrs postinjury). Scar evaluation was performed at long-term follow-up. RESULTS: There were no significant differences between Integra and controls in burn size (70 +/- 5% vs. 74 +/- 4% total body surface area), mortality (40% vs. 30%), and length of stay (41 +/- 4 vs. 39 +/- 4 days). In the short term, resting energy expenditure significantly decreased (p < .01), and serum levels of constitutive proteins significantly increased (p < .03) in the Integra group compared with controls. Long-term follow-up revealed a significant increase in bone mineral content and density (24 months postburn, p < .05), as well as improved scarring in terms of height, thickness, vascularity, and pigmentation (12 months and 18-24 months, p < .01) in the Integra group. CONCLUSION: Integra can be used for immediate wound coverage in children with severe burns without the associated risks of cadaver skin.     

Lipid peroxidation inhibition by raxofelast improves angiogenesis and wound healing in experimental burn wounds

We investigated the effects of raxofelast, a lipid peroxidation inhibitor, in an experimental model of burn wounds. C57BL/6 male mice of 25-30 g were immersed in 80 degrees C water for 10 seconds to achieve a partial-thickness scald burn. Animals received intraperitoneally either raxofelast (20 mg/kg/day for 14 days in 100 microL) or its vehicle alone (100 microL/day for 14 days). On day 14, burn areas were used for measuring conjugated dienes, reduced glutathione levels, histological damage, neoangiogenesis by immunohistochemistry and expression (Western blot) of the specific endothelial marker CD31 as well as quantification of microvessel density, VEGF wound content, endothelial and inducible nitric oxide synthase (eNOS and iNOS) expression and wound nitrite content. Raxofelast decreased tissue conjugated dienes (vehicle 6.1 +/- 1.4 DeltaABS/mg protein; raxofelast 3.7 +/- 0.8 DeltaABS/mg protein), prevented tissue glutathione consumption (vehicle 3.2 +/- 0.9 micromol/g protein; raxofelast 6.7 +/- 1.8 mumol/g protein), increased epithelial proliferation, extracellular matrix maturation, and augmented neoangiogenesis as suggested by the marked increase in microvessel density and by the robust expression of the specific endothelial marker CD31 (vehicle 9.4 +/- 1.1 integrated intensity; raxofelast 14.8 +/- 1.8 integrated intensity). Furthermore, raxofelast enhanced VEGF wound content (vehicle 1.4 +/- 0.4 pg/mg protein; raxofelast 2.4 +/- 0.6 pg/mg protein), caused a marked expression of eNOS (vehicle 16.1 +/- 3 integrated intensity; raxofelast 26.2 +/- 4 integrated intensity) and iNOS (vehicle 9.1 +/- 1.8 integrated intensity; raxofelast 16.2 +/- 3.5 integrated intensity) and increased wound nitrite content. Lipid peroxidation inhibition by raxofelast may be an effective therapeutic approach to improve clinical outcomes after thermal injury.     

Use of 5% sulfamylon (mafenide) solution after excision and grafting of burns

In previous reports, 5% sulfamylon solution has been utilized on unexcised burns and granulation tissue. We prospectively evaluated 67 burn patients to determine graft take and the incidence of side effects with use of sulfamylon solution dressings after excision and grafting. Of patients excised and grafted, the mean graft take for a total of 100 procedures was 86%. Rash occurred in 18% of patients and sulfamylon was discontinued with no sequelae. Twenty-five percent had at least one positive fungal wound culture, yet only 3% required treatment for candidemia. Those patients who developed a rash and fungal colonization had a significantly larger percent burn and were treated with sulfamylon for a longer period of time. Pain intensity was rated on a Visual Analog Scale with a mean score of 2.4; in no case was the pain considered severe enough by the patient to terminate treatment. Acidosis was present in 3% of patients but felt to be unrelated to the sulfamylon treatment. As an antimicrobial agent, 5% sulfamylon solution is a viable alternative for fresh autografts with excellent graft take and acceptable side effects.     

Fournier's gangrene: management at a regional burn center.

Fournier's gangrene (FG) describes necrotizing infections of the perineum in both sexes. Controversies in treatment of FG include the roles of orchiectomy, urinary and/or fecal diversion, and hyperbaric oxygen (HBO). Because burn centers often treat these patients, we reviewed our experience with FG during a 14-year period. With Institutional Review Board approval, we reviewed our TRACS/ABA database for patients treated for FG during 1992 to 2005. Data was recorded on demographics, preexisting medical conditions, treatment, and outcomes. Thirty patients (20 men) were identified. Mean age was 54.3 +/- 14.1 years. Predisposing conditions included diabetes in 16 patients (53%), and morbid obesity and immunosuppression in 6 each. Twenty-two patients were transferred from outside hospitals, 12 after initial surgery. Sixteen patients presented with shock (blood pressure <90/60 mm Hg). Patients underwent a mean of 4.1 surgical procedures. Ten infections penetrated the deep fascia of the perineum or abdominal wall. Suprapubic cystostomy was performed in three patients, colostomy in seven, orchiectomy in one. HBO was not used. Hospitalization averaged 25.3 +/- 15.6 days. Mean charges ($1000) were $131.5 +/- 108.3. Definitive wound closure was obtained before discharge with suture repair and/or skin grafting in 18 of 25 survivors (72%). Five patients died (17%). In logistic regression analysis, the presence of shock on admission and female gender (mortality 40%) were significantly associated with mortality. FG remains a devastating infection, which occurs primarily in compromised patients. In this series, aggressive burn center care produced outcomes equivalent to those published in other series with or without use of HBO. Colostomy and urinary diversion can be used very selectively in these patients; orchiectomy is rarely required.