John P. Heggers

Association of hyperglycemia with increased mortality after severe burn injury.

BACKGROUND Hyperglycemia is commonly associated with the hypermetabolic stress response. However, persistent hyperglycemia may adversely affect wound healing and immunity. The purpose of this study was to assess any relationship between hyperglycemia and clinical outcome after severe burn injury. METHODS Survey of the medical records from January 1996 to July 1999 identified 58 pediatric patients with burns > or = 60% body surface. Patients were categorized as having poor glucose control (n = 33) if > or = 40% of all plasma glucose determinations were > or = 7.8 mmol/L (140 mg/dL) and compared with patients deemed to have adequate glucose control (n = 25) in whom > or = 40% of all glucose values were > or = 7.8 mmol/L. RESULTS Despite similar age, burn size, caloric intake, and frequency of wound infection, patients categorized with poor glucose control had a significantly greater incidence of positive blood cultures (positive blood cultures/length of stay days, 0.42 +/- 0.04 for hyperglycemia patients vs. 0.30 +/- 0.03 for normoglycemia patients; mean +/- SEM, p > or = 0.05). This finding was especially prominent for blood cultures positive for yeast. Hyperglycemia patients had significantly less percentage of skin graft take than did the normoglycemic patients (percent take/operative procedure, 64 +/- 9 for hyperglycemia patients vs. 88 +/- 5 for normoglycemia patients; p < 0.05). Nine patients (27%) with persistent hyperglycemia died compared with only one death (4%) in patients with adequate glucose control (p > or = 0.05). CONCLUSION This association between poor glucose control, bacteremia/fungemia, reduced skin graft take, and subsequent mortality in severely burned children may be related to a hyperglycemia-induced detriment in antimicrobial defense. Although this report fails to establish cause and effect, these findings suggest that aggressive maneuvers to normalize plasma glucose in critically injured patients may be warranted.

The safety and effect of topically applied recombinant basic fibroblast growth factor on the healing of chronic pressure sores.

The first randomized, blinded, placebo-controlled human trials of recombinant basic fibroblast growth factor (bFGF) for pressure sore treatment were performed. Three different concentrations of bFGF in five dosing schedules were tested for safety using hematology, serum chemistries, urinalysis, absorption, antibody formation, and signs of toxicity. Efficacy was evaluated by wound volumes, histology, and photography. No toxicity, significant serum absorption, or antibody formation occurred. In six of eight subgroups, there was a trend toward efficacy with bFGF treatment. When all subgroups were combined, comparison of the slopes of the regression curves of volume decrease over initial pressure sore volume demonstrated a greater healing effect for the bFGF-treated patients (p < 0.05). Histologically, bFGF-treated wound sections demonstrated increased fibroblasts and capillaries. More patients treated with bFGF achieved >70% wound closure (p < 0.05). Blinded observers were able to distinguish differences in visual wound improvement between bFGF and placebo groups. These data suggest that bFGF may be effective in the treatment of chronic wounds.

Biocompatibility of Silicone Implants

The biocompatibility of silicone implants has been a source of long-standing controversy. An attempt to ascertain this biocompatibility with regard to the cellular immune mechanism was undertaken. Silicone gel from a mammary prosthesis was sonicated with Freund adjuvant under aseptic conditions to produce an injectable mixture, and injected subcutaneously in 10 female guinea pigs. Control animals did not receive this initial stimulus. After four weeks each animal received a challenge silicone implant of the same product in a gel form, surgically placed intraperitoneally in the omentum. Four weeks later peritoneal exudate cells were harvested for migration inhibition studies. Site of implantation and regional lymph nodes were processed for histological and electron microscopy.The migration inhibition studies showed that the silicone environment resulted in 45% inhibition of migration of the sensitized cell population. All sites of implantation showed a marked inflammatory response with silicone inclusions in giant cells, surrounded by neutrophils, plasma cells, and lymphocytes. Electron microscopy and x-ray energy spectrograph (XES) analysis revealed cytoplasmic transference of silicone from macrophages to lymphocytes, via a cytoplasmic bridge. There was no comparable response in control animals. Although apparently inert, silicone is capable of eliciting a cellular immune response demonstrated by the migration inhibition technique. This response is comparable to that elicited by purified protein derivative and may indicate that silicone acts as a hapten-like incomplete antigen.

Effects of early excision and aggressive enteral feeding on hypermetabolism, catabolism, and sepsis after severe burn.

BACKGROUND Severe burn induces a systemic hypermetabolic response, which includes increased energy expenditure, protein catabolism, and diminished immunity. We hypothesized that early burn excision and aggressive enteral feeding diminish hypermetabolism. METHODS Forty-six burned children were enrolled into a cohort analytic study. Cohorts were segregated according to time from burn to transfer to our institution for excision, grafting, and nutritional support. No subject had undergone wound excision or continuous nutritional support before transfer. Resting energy expenditure, skeletal muscle protein kinetics, the degree of bacterial colonization from quantitative cultures, and the incidence of burn sepsis were measured as outcome variables. RESULTS Early, aggressive treatment did not decrease energy expenditure; however, it did markedly attenuate muscle protein catabolism when compared with delay in aggressive treatment. Wound colonization and sepsis were diminished in the early treatment group as well. CONCLUSION Early excision and concurrent aggressive feeding attenuate muscle catabolism and improve infectious outcomes after burn.

Recombinant human platelet-derived growth factor-BB for the treatment of chronic pressure ulcers.

A randomized phase I/II double-blind, placebo-controlled study was designed to evaluate 1, 10, and 100 µg/ml (0.01, 0.1, and 1.0 µg/cm2) recombinant human BB homodimeric platelet-derived growth factor (rPDGF-BB) applied topically to chronic pressure ulcers for 28 days. Twenty patients were enrolled and completed the trial. No toxicities were associated with rPDGF-BB treatment. Patients treated with 100 µg/ml of rPDGF-BB had a pronounced healing response compared with placebo-treated patients. By day 29, ulcers treated with 100 µg/ml of rPDGF-BB were smaller in remaining size compared with those of placebo-treated patients when the following specific parameters were measured: percentage of initial depth (14.1 ± 7.4 vs. 34.9 ± 6.7) and percentage of initial volume (6.4 ± 4.0 vs. 21.8 ± 5.6). Histological analyses of biopsies revealed active wound healing processes in all groups with no disruption in the normal healing sequence in rPDGF-BB-treated wounds. The results of this small, descriptive study suggest rPDGF-BB is a potent vulnerary agent for accelerating soft-tissue repair, warranting further study.

The detrimental effect of cigarette smoking on flap survival: an experimental study in the rat.

Cigarette smoking is commonly prohibited after surgery involving flaps. This admonition against smoking has been justified on the theoretical grounds that flap survival could be decreased by the cutaneous vasoconstriction and increased platelet aggregation produced by smoking cigarettes. A smoke chamber was constructed to evaluate directly the effect of intermittent cigarette smoke exposure on the survival of a McFarlane flap on the dorsum of a rat. The O2, CO2 and temperature were monitored in the chamber during smoke exposures and consistently approximated values seen in room air. Average flap survival at 7 days in control rats not exposed to cigarette smoke was 75.2% while flap survival decreased to 40.1% in rats intermittently exposed to cigarette smoke. The difference was statistically significant (p less than 0.01). Changes in carboxyhaemoglobin levels similar to those observed in human smokers were also found in the smoke-exposed rats. These findings support the concept that post-operative cigarette smoking is detrimental to flap survival.

Comparison of Silver Sulfadiazine, Povidone‐Iodine and Physiologic Saline in the Treatment of Chronic Pressure Ulcers

ABSTRACT: The presence of bacteria and local infection is an important factor in the local management of chronic pressure ulcers. For successful closure of the ulcer, the bacterial count should be 105 or less per gram of tissue in the granulating wound. In a prospective randomized study of 45 (eventually 40) hospitalized patients, silver sulfadiazine (Silvadene) cream and povidone‐iodine (Betadine) solution were compared to physiologic saline for effectiveness in preparing pressure ulcers for closure. Quantitative bacteriologic techniques on tissue biopsy specimens were used for objective evaluation. In 100 percent of the ulcers treated with silver sulfadiazine cream (15 patients) the bacterial counts were reduced to 105 or less per gram of tissue within the three‐week test period, compared to 78.6 percent in those treated with saline (14 patients) and 63.6 percent in those treated with povidone‐iodine solution (11 patients). Moreover, the ulcers treated with silver sulfadiazine cream responded more rapidly, with one‐third showing bacterial levels of <105 within three days, and half within a week.

The Effectiveness of Processed Grapefruit-Seed Extract as An Antibacterial Agent: II. Mechanism of Action and In Vitro Toxicity

OBJECTIVES Recent testimonials report grapefruit-seed extract, or GSE (Citricidal) to be effective against more than 800 bacterial and viral strains, 100 strains of fungus, and a large number of single and multicelled parasites. This study investigated GSE for antibacterial activity at varying time intervals and concentration levels and tissue toxicity at varying concentrations in an effort to determine if a concentration existed that was both microbicidal and nontoxic and in what period of time. DESIGN Gram-negative and gram-positive isolates were introduced into graduated dilutions of GSE (twofold concentrations ranging from 1:1, through 1:512) for determination of bacterial activity. In vitro assays with human skin fibroblast cells were also performed at the same dilutions to determine toxicity. RESULTS These tests indicated that from the 1:1 through the 1:128 concentrations, GSE remained toxic as well as bactericidal. However, test results indicated that at the 1:512 dilution, GSE remained bactericidal, but completely nontoxic. CONCLUSIONS The initial data shows GSE to have antimicrobial properties against a wide range of gram-negative and gram-positive organisms at dilutions found to be safe. With the aid of scanning transmission electron microscopy (STEM), the mechanism of GSEs antibacterial activity was revealed. It was evident that GSE disrupts the bacterial membrane and liberates the cytoplasmic contents within 15 minutes after contact even at more dilute concentrations.

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.

Acute effects of tobacco smoking on blood flow in the cutaneous micro-circulation

p6 experimental model has been designed to help study the acute effects of tobacco smoking on the cutaneous micro-circulation. Arterioles in the nude mouse ear are directly visualised by intravital microscopy and the blood flow is quantified. Arteriolar vasoconstriction and decreased blood flow are seen in response to smoking. The implications of post-operative smoking for the patient undergoing flap surgery are discussed.