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Transportation of immunosuppressive substances produced at the site of burn injury into the systemic circulation: the role of lymphatics.

Serum of patients with severe burns has the ability to suppress mitogen-induced lymphocyte proliferation. Edema fluid collected from the site of injury during resuscitation and at the time of fascial excision has also been shown to suppress this response. An animal model was designed to identify the onset time of the formation of suppressive factors, their potential site(s) of origin, and their route of entry into the systemic circulation. Femoral artery, saphenous vein, and lateral saphenous lymphatic vessels were cannulated in an anesthetized dog. Baseline samples were collected, the hind paw was subjected to scald injury, and samples were collected serially for up to 6 hours after burn injury. Tissue fluid beneath the scald injury was harvested at the end of the experiments. In the absence of significant serologic evidence for inhibition, lymph and tissue fluid exhibited early and prolonged suppression of mitogen-induced lymphocyte proliferation. We concluded that edema fluid capable of cell-mediated immune suppression forms early after thermal injury and that lymph generated from the site of burn injury is immunosuppressive.

Animals↗

A descriptive summary of New Jersey's 1985 burn population.

Data obtained from the New Jersey State Department of Health on the 1985 hospitalized patients with burns and data collected from the National Burn Victim Foundation's standard burn reporting form were analyzed to gather information about the epidemiology of burns. Children (0 to 4 years of age) continue to be the largest percentage of the 0- to 18-year-old age group who sustain burn injuries, and 67% of those injuries are sustained by children under the age of 5. Males accounted for 69% of the total burn population; 58% of admissions were white; 69% of patients were admitted for partial-thickness burns, and 31% were admitted for full-thickness burns; the largest primary payer was third-party payers; and 92% of patients with burns were discharged to home or self-care. Data were also analyzed by examination of selected age groups to determine individual needs of specific groups. An analysis of burn injuries reported to the National Burn Victim Foundation confirmed previous reports that the home is the most likely place for a burn injury to occur and that flame and scald injuries predominate; scald injuries comprise 50% of all sustained burns. Gasoline vapors accounted for 54% of burn injuries caused by flames. The data supported efforts to develop programs that address the needs of the urban child, the 17- to 19-year-old age groups, and the elderly. The information that was collected served to redefine objectives for burn prevention programs.

Accidents, Home↗

Management of the pediatric patient with burns.

Two million people in the United States receive medical treatment each year for burn injuries. One hundred thousand of these patients are hospitalized, and 7800 die as a direct result of their injuries. Of the patients that are hospitalized 30% to 40% are under 15 years of age. Sixty-seven percent are male. The average age of children with burns is 32 months. Flame burns account for approximately 13% of accidents, scalds account for 85%, and electrical and chemical burns account for approximately 2%. The majority of scald injuries are small. Sixteen percent of burn injuries are not accidental, and approximately half of these are a result of documentable, inflicted abuse.

Biological Dressings↗

Burn-induced alterations in vasoactive function of the peripheral cutaneous microcirculation.

Alterations in the cutaneous vasomotion function caused by scald burns to a large area on the flank were observed and quantified in a dorsal skin flap window with a hamster model. Subsequent to chronic implantation of the window chamber to provide direct microscopic observation of blood flow for an entire thickness of skin, control measurements of vasoactivity in a defined network of arterioles were taken by means of a digital video image splitter over a period of several days. A 100 degrees C, 5-second water scald was then effected over 17% to 55% of the total body surface area, and the vasoactivity was remeasured in the targeted set of sites at serial time intervals for 2 to 4 days. Data were acquired directly into a computer and analyzed for both the magnitude and time pattern of diameter fluctuations during 3-minute observation periods. Average and standard deviations of diameters were computed, and the Prony power spectral analysis method was applied to identify the presence and strength of fluctuation frequencies. In general, vasomotion was suppressed for several hours subsequent to the burn, and the activity was dominated by much slower contractions than control. No direction of vessel diameter changes prevailed uniformly throughout the peripheral microcirculation. Large alternate constrictions and dilations were also observed for some arteriolar and venular components, but others exhibited no significant change at all. The incidence and magnitude of peripheral microvascular response was proportional to the size of the injured area.

Anesthesia, Inhalation↗

Burn injury enhances alveolar macrophage endotoxin sensitivity.

Systemic activation of inflammatory cascades has been implicated in the pathogenesis of the multiple organ dysfunction syndrome. To begin to determine whether dysregulation of macrophage cytokine expression after burn plays a role in organ failure, we examined tumor necrosis factor alpha bioactivity of liver and lung macrophages under two conditions: (1) at 1, 3, 5, and 7 days after 40% scald burn, and (2) after sequential insult consisting of 40% scald burn followed by in vitro incubation with endotoxin. Burn alone did not significantly alter alveolar macrophage or Kupffer cell tumor necrosis factor alpha bioactivity at any of the timepoints examined. Sequential insult did not result in significant changes in Kupffer cell tumor necrosis factor alpha, but tumor necrosis factor alpha was increased 11.1 times in alveolar macrophages harvested on postburn day 3. Therefore macrophage cytokine responses to thermal injury are apparently both tissue-specific and time-dependent.

Animals↗

A comparison of two different 2400 mOsm solutions for resuscitation of major burns.

The reduction of burn edema is a common goal in the resuscitation of patients with thermal injury. Initial infusion of a 2400 mOsm hypertonic 7.5% NaCl 6% dextran (HSD) has been shown to reduce volume needs, but elevated serum sodium levels limit the dose that can be safely used. This study tested the hypothesis that a 2400 mOsm solution of NaCl, amino acids, glucose, and 6% dextran (Isosal-D) would reduce similar volume requirements while maintaining normal plasma sodium levels. Hemodynamics, plasma sodium, fluid balance, and tissue water content were measured after an initial baseline period and during resuscitation of a large scald injury in 21 anesthetized sheep. Resuscitation was begun 30 minutes after the scald with infusion of 10 ml/kg of either lactated Ringer's (LR), Isosal-D, or HSD and was continued with LR to restore and maintain baseline oxygen delivery throughout the 8-hour period. Oxygen delivery, cardiac output, and mean arterial pressure were rapidly reestablished by all three solutions, although a persistent tachycardia was noted with Isosal-D. Net fluid requirements of both HSD (35 +/- 13 ml/kg) and Isosal-D (72 +/- 13 ml/kg) were significantly lower than in the LR group (203 +/- 39 ml/kg). Mean serum sodium increased 11 mEq with HSD to a peak after 4 hours of 152 +/- 5 mEq, whereas with LR sodium fell 7 mEq to 132 +/- 4. Isosal-treated animals had minimal change in serum sodium. HSD significantly decreased tissue water content in colon, liver, pancreas, and nonburned skin compared with LR, whereas Isosal-D reduced edema only in the colon. It is concluded that in this protocol Isosal-D was not as effective as HSD at reducing volume needs and edema and had unexpected chronotropic effects.

Animals↗

Extracorporeal membrane oxygenation in the treatment of respiratory failure in pediatric patients with burns.

Extracorporeal membrane oxygenation (ECMO) as a treatment for pulmonary failure from postshock respiratory distress in burned children recently has been shown to salvage patients who were thought to have more than a 90% chance of dying. We describe five burned children in whom severe respiratory failure--not responsive to medical management and maximal ventilatory support--developed, and who underwent ECMO treatment. Three (60%) cases involved flame burns, with significant inhalation injury as diagnosed after a bronchoscopy; mean age was 3 years (2 to 4 years), with a mean total body surface area (TBSA) burn of 32% (15% to 53%), mean third-degree burns of 25% (5% to 53%). Two (40%) cases involved scald burns; mean age was 6 years (7 months to 11 years), with a mean TBSA burn of 56.5% (43% to 70%), mean third-degree burns of 40% (10.5% to 70%). Outcome was poor for those burned children who received ECMO therapy after prolonged ventilatory support for smoke inhalation injury. Children who experience perfusion/reperfusion shock injury to the lungs as a result of delayed resuscitation of scald burns may have an improved chance of survival with short courses of ECMO regardless of the burn size.

Burns↗

Endogenous production of heparin-binding EGF-like growth factor during murine partial-thickness burn wound healing.

Heparin-binding EGF-like growth factor (HB-EGF), a potent epithelial cell mitogen, has been identified in human burn blister fluid and excised human burn wounds. Topical application of HB-EGF to murine partial-thickness scald burns accelerated reepithelialization, increased keratinocyte proliferation, and enhanced production of endogenous transforming growth factor-alpha in the healing wounds. The goal of the present study was to examine the production of endogenous HB-EGF and transforming growth factor-alpha (TGF-alpha) in a murine partial-thickness scald burn model. Keratinocyte proliferation was assessed by 5-bromo-deoxyuridine incorporation, and tissue sections were examined by in situ hybridization for HB-EGF mRNA expression and by immunohistochemistry for HB-EGF and TGF-alpha production. HB-EGF mRNA expression and production of HB-EGF and TGF-alpha proteins by both marginal surface keratinocytes and hair follicle epithelial cells reached a maximum by postburn day five and decreased thereafter. This corresponded to the peak period of keratinocyte proliferation. We conclude that HB-EGF and TGF-alpha act in conjunction to stimulate wound healing following thermal injury.

Animals↗

A survey of risk factors for burns in the elderly and prevention strategies.

Elderly burn patients suffer from greater morbidity and mortality than younger patients with similar burn extents. The purpose of this study was to identify risk factors for burn injuries in the elderly to develop an effective preventive program. A cross-sectional survey was conducted among 20 elderly (> or =65 years of age) burn survivors on the circumstances surrounding their burn injury and on burn prevention. A control group of 20 nonburned elderly completed a similar survey only on burn prevention. The majority of burned subjects believed that their injury was preventable (85%). The home was the commonest location for burn injury (70%), and scalds (50%) and flame burns (25%) were the most common etiologies. Most subjects felt that a burn prevention program would be useful (95%) and television, news, and posters were the preferred sources of prevention information. Compared with the burn group, the control group had more risk factors for burn injury. However, the control group also took more active preventive measures. Burn prevention campaigns for elderly should focus on reducing flame and scald burns that occur in the home, preferably using television, news, and poster media.

Aged↗

Burn sepsis: bacterial interference with Pseudomonas aeruginosa.

The pathogenicity of several strains of Pseudomonas aeruginosa for burned rats (3 degrees scald burns, 20% body surface) following topical application of the bacteria to the burn within 1 hour after burning was established. Following this, it was demonstrated that purposeful infection of such 3 degrees scald burns of rats by a strain of Ps. aeruginosa of low virulence (JB-77) protects the rats from the lethal effect of subsequent (48-hour) topical contamination of the burn by a highly virulent strain of Ps. aeruginosa (VA-134) (p less than 0.001). This finding was confirmed in a similar experiment beginning with germfree rats. When the challenge with the highly virulent Ps. aeruginosa strain was 24 hours (rather than 48 hours) after the burning and topical contamination of the burn with the low virulence strain of Ps. aeruginosa, there was little protection (p N.S.). When burned rats were given the low virulence strain of Ps. aeruginosa by gavage right after burning, there was not protection to subsequent (48 hours) challenge by topical application of the highly virulent strain of Ps. aeruginosa to the burn (11/12 vs 12/12 dying). Our finding that purposeful infection of a 3 degrees burn of rats (conventional and also germfree) by a strain of Ps. aeruginosa of low virulence protects from the lethal effect of subsequent (48-hour) topical contamination of the burn by a highly virulent strain of Ps. aeruginosa is due, we believe, to direct bacterial interference between the two strains of pseudomonas.

Animals↗

Cooling the burn wound to maintain microcirculation.

To evaluate the effect which cooling of burn wounds has upon dermal microvascular circulation, standard 10% BSA dorsal guinea-pig scald burns were created. In treated animals, the dorsal burned region was immersed in a circulating ice-water bath (0-3 degrees C) for 30 minutes at various time intervals postburn (10,20,30, and 60 minutes after scald). India-ink perfusion was used to determine the level of dermal vessel patency at 2, 4, 8, 24, 72, and 96 hours after burning. By 96 hours, significant differences could be seen in animals cooled 10, 20, or 30 minutes after burning. Those not treated until 60 minutes after burning had dermal perfusion essentially the same as control animals. 133Xe dermal washout studies were performed at 8 and 24 hours and corroborated these findings. Grossly, burn wounds cooled by 30 minutes after burn had markedly better healing than control animals and animals cooled 60 minutes after burning. We believe these data support the early use of cold water treatment of partial-thickness burn wounds, as demonstrated in this experimental study.

Animals↗

The beneficial effect of early excision on clinical response and thymic activity after burn injury.

Catabolic response and immunodepression were studied in guinea pigs with scald burns that were excised on day 1 postburn and those that were scald burned but unexcised. Weight gain returned to normal by day 6 in the excised group but remained depressed in burned but unexcised animals whose wounds were untreated, or in unexcised animals whose wounds were treated by topical silver sulfadiazine. Thymic DNA synthesis returned to normal by day 6 in the excised group but remained depressed in the unexcised group. Plasma and thymic-free cortisol returned to normal by day 6 in the excised group but remained markedly elevated in the burned, unexcised animals. These studies indicate early excision and early wound closure reduce the catabolic response and immunodepression of guinea pigs following burn injury.

Anesthetics↗

The Cool Kids Coalition.

The Cool Kids Coalition was initiated as a community response to more than 214 hospitalizations of children under the age of five for burns over a 6-year period in one township in Long Island, NY. The coalition was started by public health nurses in partnership with the local chapter of the National Safe Kids Campaign. Goals included: 1. parent education regarding scald burn prevention; 2. development of innovative interventions for those at risk; and 3, development of innovative community approaches to scald prevention. Coalition members had diverse backgrounds and the coalition integrated non-traditional partners in injury control. The coalition doubled in size due to overwhelming community interest, growing within a few months from an initial group of 15 to a well-represented group of 30. Innovative programs were implemented that reached more than 3,000 parents, both in the community and home. Teaching was conducted with parents in the target population in Head Start centers, homeless shelters, the home, libraries, child care centers, a shelter for teen parents, etc. Member agencies incorporated the booklet and materials into their individual programs. The development of the Cool Kids Coalition illustrates the power of nursing in community health.

Burns↗

Walker-related burns in infants and toddlers.

During one year, four (6.5%) of the 61 children who were hospitalized for burns at a children's hospital sustained their injuries in a walker. Records from a total of nine children hospitalized with walker burns were compared to those from other hospitalized burned children. Patients who were burned while in a walker had a greater body surface area burned (11.6%) than those with burns from abuse (1.7%), neglect (2.5%), or other accidents (6.2%). A higher percentage of males were burned, and the burn patterns differed among all four groups. Seven of the nine walker burns resulted from scalds, with three scalds from hot grease. Walker-related burn patients required more physical or occupational therapy and a longer mean hospital stay. Social histories of infants with walker and other accidental burns differed from those associated with abuse or neglect. Walkers expose infants to unnecessary hazards, including potentially serious burns; their use should be discouraged.

Accidents, Home↗

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.

Anti-Infective Agents, Local↗

Feasibility of biolistic gene therapy in burns.

Skin is an especially attractive target for genetic manipulation because it is readily accessible and easily monitored for both the presence and the expression of inserted genes. This study was designed to assess the feasibility of particle mediated gene transfer to burned skin and to compare the transfection efficiency, anatomic distribution, and duration of transgene expression achievable in normal versus burned skin. Two days following scald injury of varying depths in 60 degrees C water (10 s: superficial partial; 20 s: deep partial; 40 s: full thickness) reporter gene (beta-galactosidase) constructs were delivered using a gene gun at various helium pressures (200-600 psi) to normal and burned skin. A time course study was performed to examine the kinetics of transgene expression. Animals received a superficial partial thickness burn and were sacrificed 12 h, 1, 3, 5, 7, 14, or 21 days after gene transfer. India Ink injection and immunohistochemistry were used to assess the depth of the scald injury. Transfection efficiency was measured in skin homogenates 24 h after gene transfer by morphometric and chemoluminescent assays. We found that the extent of tissue damage was directly related to the duration of heat source exposure. Reporter gene activity was significantly higher in superficial partial thickness burns compared to normal controls and gradually declined with increasing tissue injury. No activity was seen in the full thickness burn group. Beta-galactosidase activity reached a maximum level 12 h after gene transfer in both normal and superficial partial thickness burned skin with no levels seen after 5 days post-transfection. These findings indicate that particle-mediated gene transfer in thermally injured skin is feasible and may provide a means of introducing biologic agents into injured tissue capable of enhancing bacterial clearance and improving wound healing.

Animals↗

Burn-induced impairment of cardiac contractile function is due to gut-derived factors transported in mesenteric lymph.

Neither the source nor the cause of burn-induced myocardial dysfunction is known. Because scald burns have been shown to cause cardiac contractile dysfunction, the purpose of this study was to test the hypothesis that gut-derived myocardial depressant factors were responsible for burn-induced cardiac contractile dysfunction. Male rats were subjected to laparotomy with or without mesenteric lymph duct ligation (LDL). After LDL or sham-LDL, the rats were randomized to receive sham or scald burn (43% TBSA full thickness) after which they were resuscitated for 24 h with 4 mL/kg/%burn of Ringers lactate solution, and then killed, and the hearts removed. Cardiac function was assessed by measuring the left ventricular pressure (LVP) and maximal rate of LVP rise and fall (+/-dP/dt) in response to increases either in 1) preload, 2) coronary flow rate, or 3) perfusate calcium. At 24 h after burn or sham burn and before killing, the mean arterial pressure of the burn group was less than the burn + LDL or the sham burn groups (P < 0.05). Pre-burn LDL significantly prevented burn-induced depression in LVP and +/-dP/dt (P < 0.05). In addition, the hearts harvested from the burn group showed a significant impairment in contraction and relaxation when preload, coronary flow, or perfusate calcium was increased compared with the burn + LDL and sham groups (P < 0.05). Burn-induced cardiac dysfunction, manifested by impaired contraction and relaxation, is prevented by pre-burn lymph duct ligation. These results indicate that gut-derived myocardial depressant factors transported in mesenteric lymph contribute to burn-induced impairment of cardiac contractile function, because burn-induced cardiac dysfunction can be totally abrogated by pre-burn mesenteric lymph duct ligation.

Animals↗

The potential role of Staphylococcal enterotoxin B in rats with postburn Staphylococcus aureus sepsis.

Staphylococcal enterotoxin B (SEB) is an important member of the superantigen family, which exerts a number of pathological effects in the human, as well as susceptible animals. The present study was conducted to observe the time course and tissue distribution of SEB in postburn Staphylococcus aureus infection; meanwhile, the relationship between SEB and multiple organ dysfunction was also studied. Eighty-six male Wistar rats were randomly divided into four groups as follows: normal control group (n = 10); scald control group (n = 10); postburn sepsis group (n = 50) in which rats inflicted with 20% total body surface area (TBSA) III degrees scald followed by SEB-producing S. aureus challenge were further divided into 0.5-, 2-, 6-, 12-, and 24-h subgroups, with 10 rats in each subgroup; and SEB monoclonal antibody (MAb) treatment group (n = 16) in which a dose of 4 mg/kg SEB MAb was given intravenously just before S. aureus challenge, and the rats were further divided into 2- and 6-h subgroups. It was found that after thermal injury combined with S. aureus infection, SEB was widely distributed to the liver, kidneys, lungs, and heart, exacerbating the pathophysiology of multiple organ dysfunction induced by postburn sepsis. At the same time, the gene and protein expressions of tumor necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma) were also markedly upregulated in various tissues. Early treatment with SEB-specific MAb-MAb2D(1)-could markedly decrease SEB levels in plasma as well as in various tissues, and could significantly reduce the 6-h mortality rate (17.64% [3/17] vs. 55.6% [20/36], P = 0.02). These data suggested that neutralization of SEB is effective in ameliorating S. aureus sepsis and subsequent multiple organ damage, which might be attributed to its inhibitory effect on inflammatory mediator formation.

Animals↗