Topical ibuprofen decreases early postburn edema

We determined the effect of topically applied ibuprofen on formation of second-degree burn edema and prostanoid production, a possible causative factor. Six adult sheep were given second-degree burns on both flanks with water at 80 degrees C while they were under general anesthesia. Lymph (QL), draining the flank areas, was used to monitor edema formation and prostanoid production. A 5% ibuprofen cream was applied at 2 and 5 hours after the burn and full-thickness biopsy specimens of burned hide were obtained at 8 hours for determination of water content. The QL increased sixfold in nontreated and 2.5 times in treated burn tissue. The lymph/plasma (L/P) protein ratio increased from 0.4 to 0.58 in both sides. Lymph TxB2 was increased from baseline of 200 pg/ml to 500 +/- 100 and 310 +/- 90 pg/ml in untreated and treated sides, respectively. Lymph 6-keto-PGF1 alpha increased from a baseline of 50 +/- 10 to 150 +/- 40 and 90 +/- 80 pg/ml in untreated and treated sides. The difference between PG content of lymph in treated and untreated sides was significant. Plasma prostanoids, except for a transient early rise, remained at preburn baseline. Lymph ibuprofen content on the treated side rose to 1.9 +/- 0.8 mcg/ml with no detectable plasma level. Water content of hide increased from a control value of 74 +/- 2% to 84 +/- 2% in untreated burn, while the value in the treated side was 76 +/- 4%, a significant difference between the two sides. We conclude that topically applied ibuprofen decreases both local edema and prostanoid production in burn tissue without altering systemic production.     

Topical therapy for control of bacteria in the burn wound

The concept of burn wound sepsis and the demonstration of the avascular nature of the burn wound paved the way for the development of effective antibacterial therapy of the burn wound. Many agents have been tried, but the most effective are those with a broad spectrum of antibacterial activity, lack of developing resistance, low toxicity, and active penetration of the wound. The resultant lowering of mortality and improvement in patient care have dramatically altered the prognosis of burn injury. The primary drugs in use today, their advantages and limitations, and the pathophysiology of the burn wound and burn wound sepsis are presented.

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Résumé Le traitement de l'infection des brûlures est basé sur la compréhension des mécanismes de l'infection et la démonstration de l'absence de vascularisation des tissus brûlés. De nombreux médicaments ont été essayés. Les plus efficaces sont ceux qui ont une activité antibactérienne à large spectre, qui ne permettent pas le développement d'une résistance, qui ont une toxicité faible et qui pénètrent activement dans les tissus brûlés. Ils réduisent la mortalité, ils facilitent les soins aux malades, ils améliorent considérablement le pronostic des brûlures. Les avantages et les limites des principaux médicaments utilisés à l'heure actuelle, la physiopathologie de la brûlure et de son infection sont discutés.

     

Topical oxygen and burn wound healing: a review

Oxygen is essential for the epithelialization and contraction of the burn wound as well as for the collagen maturation and synthesis. Inspiration of pure oxygen or employing hyperbaric oxygen might delay wound healing due to an intensive vasoconstriction. The accumulated data suggest a beneficial effect of topical oxygen on the wound healing process of burns.     

Topical flurbiprofen decreases burn wound-induced hypermetabolism and systemic lipid peroxidation

We studied the effect of the topical application of the nonsteroidal anti-inflammatory agent, flurbiprofen, on postburn hypermetabolism and systemic lipid peroxidation. Twelve sheep with a 15% total body surface third-degree burn were monitored over a 4-day postburn period. In six sheep, a single application of a 5% flurbiprofen cream was placed on the burn wound on day 3. Data were compared to both burned and nonburned controls (n = 6). All animals were killed on day 4. Oxygen consumption was increased at day 3 by 28% +/- 10% over the preburn value in all animals. Flurbiprofen significantly attenuated the increase in oxygen consumption, returning the value essentially to baseline by 12 hours after application. Lung and liver peroxidation, as measured by malondialdehyde, was significantly increased in the burned, nontreated sheep at day 4 from a control value of 45 +/- 9 and 110 +/- 12 to 60 +/- 6 and 310 +/- 71 nmol/gm tissue, respectively. In flurbiprofen-treated animals, values were 42 +/- 8 and 160 +/- 18 nmol/gm at day 4, significantly attenuated from burn alone. Protein-rich burn lymph flow remained fourfold increased in both groups, indicating a persistent increase in burn tissue vascular permeability, not modified by flurbiprofen. Burn wound biopsies revealed bacterial contents of less than 10(4) organisms/gram tissue in all animals. We conclude that topical flurbiprofen significantly decreases burn wound-induced systemic hypermetabolism and oxidant-induced lipid peroxidation seen at 3 days after burn injury, but does not attenuate the remaining local burn-wound vascular permeability.     

Topical chlorhexidine diphosphanilate (WP-973) in burn wound sepsis

We studied the diphosphanilate salt of chlorhexidine (WP-973), as a 2% cream, for therapeutic activity in two rat models of fatal burn wound infection. Control treatments were infection and placebo cream; infection only; infection and 1% sulfadiazine silver; and burning only. Activity against Pseudomonas aeruginosa or Proteus mirabilis was tested in surface-inoculated rats with 20% scalds. Treatments were initiated 24 hours or four hours, respectively, after inoculation. Pseudomonas-infected rats were treated once a day for ten days. Proteus-infected rats were treated once a day for five days. In these experimental models, chlorhexidine diphosphanilate was equal to silver sulfadiazine, an established topical chemotherapeutic agent. In vitro activity was examined using bacteremia isolates from 65 burned patients. Using agar diffusion trench plates, chlorhexidine diphosphanilate was active against all strains. No evidence of cross-resistance between sulfonamide and chlorhexidine diphosphanilate or its components was observed.     

Topical antimicrobial testing of burn wound microorganisms: evaluation of a new technique

A new system of determining susceptibility of burn wound microorganisms to topical antimicrobial therapy was studied. The new method, TOPITEST, employs a methacrylate vehicle impregnated with various antimicrobial agents and an agar overlay. Test plates can be inoculated by a direct swab culture of the wound or with micro-organisms isolated by other methods. This new technique was compared to an agar well diffusion (AWD) method using commercially compounded antimicrobials and biopsy-recovered organisms. The new test method provided comparable results to the more established AWD test when using biopsy-recovered organisms. Using the swab culture technique, however, TOPITEST had a high rate of failure to recover sufficient organisms from the burn wound for testing. The new, more standardized test provided results earlier than the AWD test, but may prove to be less cost effective.     

Topical p38 MAPK inhibition reduces bacterial growth in an in vivo burn wound model

BACKGROUND: Although the inflammatory response is a prerequisite for wound healing, excessive activation of the innate immune system can induce epithelial cell damage and apoptosis, which may further compromise dermal integrity. In a noninfectious burn wound model, we previously demonstrated that topical inhibition of p38 MAPK, an important inflammatory signaling pathway, attenuated epithelial cell damage and apoptosis. We now question whether attenuating local inflammation would weaken bacterial wound resistance and compromise host defense. METHODS: Rats received 30% total body surface area burn, and the wound was treated with topical application of a p38 MAPK inhibitor or vehicle. At 24 hours after injury, burn wounds were inoculated with Pseudomonas aeruginosa. At 48 hours postinjury, animals were sacrificed, and the burn wound was analyzed. RESULTS: Inoculating burn wounds induced significant bacterial growth. Dermal inflammatory changes were markedly accentuated in the inoculated animals. Topical p38 MAPK inhibition reduced the proinflammatory cytokine expression in the burn wounds and neutrophil sequestration with or without bacterial inoculation. Interestingly, the bacterial wound growth was significantly attenuated in animals treated with topical p38 MAPK inhibitor. CONCLUSIONS: Topical p38 MAPK inhibition attenuated wound inflammation without interfering with bacterial host defense. Attenuation of excessive burn wound inflammatory signaling may prevent secondary damage of the dermal barrier and reduce the growth of opportunistic pathogens.     

Pathophysiology of the burn wound

The pathophysiology of the burn wound is characterized by an inflammatory reaction leading to rapid oedema formation, due to increased microvascular permeability, vasodilation and increased extravascular osmotic activity. These reactions are due to the direct heat effect on the microvasculature and to chemical mediators of inflammation. The earliest stage of vasodilatation and increased venous permeability is commonly due to histamine release. Damage to the cell membranes partly caused by oxygen-free radicals released from polymorphonuclear leucocytes would activate the enzymes catalyzing the hydrolysis of prostaglandin precursor (arachidonic acid) with rapid formation of prostaglandin as the result. Prostaglandins inhibit the release of norepinephrine and may thus be of importance in modulating the adrenergic nervous system which is activated in response to thermal injury. The morphological interpretations of the changes in the functional ultrastructure of the bloodlymph barrier following thermal injury seem to be an increase in the numbers of vacuoles and many open endothelial intercellular junctions. Furthermore changes of the interstitial tissue after burn trauma are of great importance. The continuous loss of fluid from the blood circulation within the thermally damaged tissue causes increased haematocrit levels and a rapid fall in plasma volume, with decreased cardiac output and hypoperfusion on the cellular level. If the fluids are not adequately restored burn shock develops. Furthermore, the burn wound provides a vast area of entry of surface infection with a high risk of septic shock. Four main principles are of utmost importance in the current management of patients with severe thermal injury, namely early wound closure, prevention of septic complications, adequate nutrition and control of the external environment.     

Management of the burn wound

Thermal injury sets off a chain of pathophysiologic events that evolve into the problems encountered in management of the burn wound. This article reviews those events and presents a method of caring for wounds sustained from thermal injury.     

Closing the burn wound.

With recent advances in supportive therapy and surgical care, closure of the burn wound now can be accomplished earlier and more effectively than previously. Only by keeping the patient in a state of positive nitrogen balance, immunologically competent, and in equilibrium with the bacteria colonizing the burn wound can early wound closure be carried out with a minimal number of postburn complications.     

Granulocyte colony-stimulating factor: release is not impaired after burn wound infection

BACKGROUND: The production of granulocyte colony-stimulating factor (G-CSF), the lineage specific essential regulator of neutrophil progenitor cell proliferation and differentiation, has been thought to be impaired in the setting of burn infection. The ability to directly measure murine G-CSF allows the further delineation of the G-CSF response in a clinically relevant model of thermal injury and infection. METHODS: We used a commercially available solid phase enzyme-linked immunoabsorbent assay to quantify G-CSF production after burn wound infection in mice. Bone marrow cells, splenic cells, and serum were obtained from BDF1 mice on day 3 after a 15% total body surface area full-thickness scald burn with or without Pseudomonas aeruginosa burn wound infection. G-CSF production of bone marrow cells or splenic cells and the serum level of G-CSF were measured. A clonogenic assay of bone marrow and spleen granulocyte-macrophage progenitor cells as well as blood leukocyte counts were also performed. RESULTS: After burn sepsis, we noted that G-CSF production of the bone marrow and spleen was significantly increased; the numbers of progenitor cells in bone marrow and spleen were markedly enhanced; serum values of G-CSF were 14 times greater than control values; serum colony-stimulating activity was greater than in control mice; and total blood leukocyte counts were significantly depressed. CONCLUSION: These findings support the notion that granulocytopoietic failure after burn sepsis is not significantly related to defective endogenous G-CSF synthesis. More likely, hyporesponsiveness of granulocyte progenitor cells to G-CSF, changes in the relative balance of granulocyte versus monocyte progenitors within the granulocyte-macrophage progenitor cell compartment, and enhanced release of monocyte lineage specific growth factors are the critical elements responsible for burn infection-induced hematopoietic failure.     

烧伤创面与糖尿病溃疡创面的比较

目的比较烧伤创面与糖尿病溃疡创面的差异，初步分析糖尿病患者溃疡创面难愈的机制。方法分别切取非糖尿病烧伤患者的足部创面（对照组）和糖尿病患者的足部溃疡创面（试验组）组织，行组织块培养。用酶联免疫吸附测定（ELISA）法、反转录-PCR法分别检测创面组织释放的成纤维细胞生长因子2（FGF2）、血管内皮生长因子（VEGF）蛋白质及其mRNA水平；免疫组织化学法检测创面微血管密度（MVD）的变化。人脐静脉内皮细胞分别在含5mmol／L葡萄糖的培养液（正常培养液组）、含30mmol／L葡萄糖的培养液（高糖组）、含30mmol／L甘露醇的培养液（甘露醇组）中培养7d，以ELISA法测定VEGF蛋白质水平。结果对照组患者FGF2、VEGF蛋白质水平分别为（59±3）ng／ml、（56±7）pg／ml，试验组2种蛋白质水平分别为（89±6）ng／ml、（108±5）pg／ml，组间比较差异均有统计学意义（P〈0．05或P〈0．01），mRNA比较结果与蛋白质相似；2组的MVD水平，差异亦有统计学意义（P〈0．05）。体外细胞培养时当培养液含FGF2，高糖组与正常培养液组的VEGF蛋白质水平相近（P〉0．05）；移去FGF2后2、5d，正常培养液组该指标明显高于高糖组（P〈0．05或P〈0．01）。结论糖尿病患者溃疡创面难愈与血管化受到抑制以及调控血管生长的因子低表达密切相关。     

Primary excision of the burn wound

Early excision of burn eschar and wound closure significantly improves survival following major burn injury. Immediate primary excision performed by burn-experienced surgeons in dedicated burn care facilities can reduce further morbidity and mortality, length of hospital stay and medical costs. Burn care at the millennium is evolving rapidly into a subcategory of trauma surgery, with burn patients increasingly being viewed as victims of major trauma who benefit most from immediate and definitive surgical correction of their injuries.