Actin polymerization contributes to neutrophil chemotactic dysfunction following thermal injury.

The agent(s) and mechanism(s) responsible for suppression of neutrophil chemotaxis in association with major thermal injury have not been identified. We have proposed that the reduced random motility characterizing patients' cells may contribute to their generalized chemotactic dysfunction. Here we report that actin polymerization may be responsible for the loss of neutrophil motility associated with major thermal injury. Using a fluorescent ligand specific for polymerized or filamentous actin (NBD-phallacidin) in conjunction with flow cytometry, we have discovered that peripheral blood and exudate neutrophils from patients with major thermal injury contain increased levels of actin in a stably polymerized form. Because cyclic polymerization and depolymerization of actin is essential to cell motility, we suggest that actin polymerization may contribute in a major way to the attenuation of neutrophil random and chemotactic functions induced by major thermal injury.

Serum copper and ceruloplasmin levels and urinary copper excretion in thermal injury.

Conflicting reports regarding copper status in thermal injury patients have been published. We determined serial serum-copper and serum-ceruloplasmin levels and 24-h urinary excretion of copper in 23 patients with second- and third-degree thermal burns. Throughout hospitalization, mean serum-copper concentration was significantly depressed; lowest levels were found in patients with greater than 40% total body surface area burns. Serum ceruloplasmin was also depressed, an unexpected finding because this protein is a positive acute-phase reactant poststress. Mean urinary excretion of copper was elevated, reaching 2.5 times the upper limit of normal 2 wk postburn. Depressed serum-copper levels paralleled the serum-ceruloplasmin levels rather than the increased urinary-copper losses. Further studies are required to determine the mechanism(s) of this altered copper metabolism and whether physiological or biochemical evidence of copper deficiency accompanies the observed hypocupremia.

Creatine kinase as a prognostic indicator in electrical injury.

Serial serum creatine kinase (CK) and creatine kinase myocardial band isoenzyme (CK-MB) levels were obtained from 116 of 125 electrical burn patients admitted from 1976 through 1986. We divided patients into three groups (peak CK within 2 days after admission) as follows: group 1, CK less than 400 U/L; group 2, CK = 400 to 2500 U/L; group 3, CK greater than 2500 U/L. Clinical myocardial infarction (MI) was determined by ischemic ECG changes, LDH isoenzyme patterns, and clinical course. Skin grafts occurred in 2 of 24 patients from group 1, in 15 of 31 from group 2, and in 37 of 61 from group 3. Hospital stay (mean +/- SEM) was 4.6 +/- 1.3 days for group 1, 20.2 +/- 5.4 for group 2, and 37.7 +/- 3.6 for group 3. Group 1 patients required no amputations; group 2 had 1 limb and 5 digit amputations; group 3 had 22 limb and 16 digit amputations. Only three clinical MIs were found (all in group 3), although 1 of 31 patients from group 2 and 32 of 61 from group 3 had CK-MB greater than 4%. Highly elevated CK and CK-MB are associated with longer hospitalization, and a greater risk of skin grafting or amputation, than with levels less than 400 U/L. Clinical MI is rare and cannot be diagnosed by elevated CK-MB alone.

Serum and urinary silver levels in thermal injury patients.

Although silver sulfadiazine has been used extensively as an effective topical antimicrobial agent in thermal injury patients, little is known about the cutaneous absorption of the silver moiety in these patients. Therefore, we longitudinally evaluated both serum silver concentration and 24-hour urinary excretion of silver in 23 patients with second- and third-degree thermal burns. Mean serum silver concentrations were modestly elevated throughout the patients' hospital course. Urinary excretion of silver was markedly elevated, especially in those patients with more severe burns. Indeed, in patients who had burns covering more than 60% of the total body surface area mean peak silver excretion was 1100 micrograms/24 hr (normal, less than 1 micrograms/24 hr). Thus, silver ion is absorbed across the burn wound in thermal injury patients treated with silver sulfadiazine. The 24-hour urinary excretion of silver appears to be a very sensitive indicator of cutaneous absorption in these patients. Possible implications of this cutaneous silver absorption warrant further evaluation.

Ecthyma gangrenosum: survival with individualized antibiotic therapy.

Five burn patients with ecthyma gangrenosum were treated with gentamicin sulfate in an individualized aminoglycoside regimen. Dosages greater than the currently recommended 3 to 5 mg/kg/day were necessary and ranged from 15 to 30 mg/kg/day. These increased dosages cannot be used routinely but only as serum level data indicate the need. Four of the five patients survived their course of ecthyma gangrenosum. The single fatality received a much smaller dosage of gentamicin as compared with the other four patients. No ototoxic or nephrotoxic reactions were noted in any of the patients.

Thermal injury effects on drug disposition: a prospective study with piperacillin.

The disposition of piperacillin was prospectively evaluated in nine severely burned patients who had normal renal and hepatic function. Wide interpatient variations were demonstrated in the drug's distribution volume, half-life, and clearance, with mean (+/- SD) values of 55.0 (+/- 44.2) liters, 3.6 (+/- 5.2) hours, and 14.9 (+/- 6.3) liters/hour, respectively. Piperacillin clearance was best explained by patient factors other than age, renal function, and the percentage of body surface area burns. Piperacillin disposition was related to the patients' serum albumin, total bilirubin, blood urea nitrogen, and the amount of urea nitrogen excreted daily in urine. Altered piperacillin disposition thus appeared to occur secondary to changes in the patients' physiologic and metabolic state caused by injury-related stress and fluid therapy. The patient's physiologic and metabolic response to injury, along with age and renal function, should be considered when instituting treatment with piperacillin or other agents cleared from the body in a similar manner.

Scalping injuries: new technique for stabilization of flaps to the skull.

Extensive scalping injuries offer a unique challenge for tissue coverage because of the wide expanse of bone and lack of deep soft tissue or significant perforating vessels. For smaller injuries, pedicle flaps offer ideal coverage. Larger defects can be covered by omental flaps. Coverage with a free muscle flap followed by split-thickness skin grafting offers optimal long-term coverage. Two new techniques are introduced. The wire-button technique offers stabilization, and the halo frame provides good support and protection for a new free-flap graft and may increase the success rate of flaps in patients with scalping injuries.

Burns and wound management.

The evaluation and treatment of head and neck burns remains a challenge to the burn surgeon, because of the long-term emotional and psychologic effects of even the most minor change in facial appearance. Fortunately, the results currently achieved are orders of magnitude better than previously available, but they still remain far below the perfect outcome desired by both the physician and the burn victim.

Burns from hot oil and grease: a public health hazard.

We examined the incidence, etiology, and morbidity of burns due to hot oil and grease. Over a 10-year period from 1976 to 1985, of 1818 patients hospitalized for burns, 85 (4.7%) injuries were due to hot grease or oil. The mean age was 20 years; 34% of patients were less than 8 years old. The mean total body surface areas of second- and third-degree burns was 11.5% (range 0.5% to 40%), and the average length of hospital stay was 19.6 days. Fifty-eight percent of patients required split-thickness skin grafting (n = 49), three required intubation, and one required tracheostomy. Seventy-eight percent of oil burns occurred in the home. The most common circumstances consisted of children who grabbed the handle or electric cord of a frying pan and pulled the hot oil down onto themselves. (Nineteen of the 29 children were less than 8 years old (66%).) Burns due to cooking oil and grease are associated with considerable morbidity. The high boiling point, high viscosity, and potential combustibility of oil increase the potential soft-tissue damage when compared with typical scald injuries from hot water. The dangers of children pulling on the appliance, the dangers of transporting hot oil, the importance of supervision while children are cooking, and the importance of knowledge of the management of grease fires is stressed. Public education is needed to underline the potential seriousness of these burns.

Gasoline burns: the preventable cause of thermal injury.

Gasoline related burns are a significant cause of thermal injuries each year in the United States. In this retrospective review of 1858 admissions to our Regional Burn Center from 1979 to 1988, 270 (14.5%) were persons with gasoline-related injuries. Natural gas and other distillates were excluded. Most victims were male (228 of 270); mean age was 27 years; mean burn size was 25% total body surface area. There were 299 skin grafts performed on 172 patients, and there were 16 deaths. The mean length of stay decreased from 38 to 17 days (p less than 0.001) between the first and second 5-year time periods, even though there was no significant change in age or mean burn size. The majority (59%) of gasoline-related burns were the result of inappropriate or unsupervised use of gasoline. The general public is largely unaware of the dangers of gasoline, and further education in this area is needed.

Paraquat poisoning in a burn patient.

Paraquat is a bipyridyl compound widely used as a contact herbicide. Since its introduction in 1962, hundreds of deaths have occurred, usually after suicidal or accidental ingestion. Death after dermal absorption of paraquat is uncommon, but has occurred after either contact with undiluted paraquat, disruption of skin integrity, or prolonged exposure. It is the purpose of this case report to describe a patient who had fatal dermal paraquat absorption after a crop-dusting accident in which he sustained 37% TBSA burns. After 9.5 hours of cutaneous exposure, a paraquat level of 0.169 mg/ml was obtained at 20 hours, the standard lethal dose at 16 hours being 0.16 mg/ml. In light of the apparently irreversible pathophysiology of paraquat poisoning with plasma levels as low as 3 mg/L, prevention and early intervention are the best treatments. Our patient may have survived an otherwise routine thermal injury had his wounds been aggressively irrigated in the field.

Pulmonary failure in geriatric patients with burns: the need for a diagnosis-related group modifier.

One hundred eleven patients with burns who were age 60 years or older were treated from January 1984 through December 1992. Twenty-nine patients had pulmonary failure defined as 7 or more days of ventilatory support from the day of burn. The mortality rate for these patients was 41%; only four were discharged to home. The mortality rate for patients without pulmonary failure was 11%. Billing information was analyzed for 102 of the 111 patients. Charges for patients without pulmonary failure were two to three times greater than reimbursement. Charges for patients with pulmonary failure were 4 to 14 times greater than reimbursement. Reimbursement for elderly patients with burns is inadequate. Altering the Diagnosis-Related Group (DRG) definition of extensive burn to reflect the severity of injury in the geriatric population is one step toward reimbursement reform. Patients who require 7 or more days of ventilatory support after burn injury should be reimbursed under a separate DRG category or should have a DRG modifier.

Mechanisms of loss of human neutrophil chemotaxis following thermal injury.

The increased susceptibility to infection of patients with thermal injury is related to loss of host defense, which is reflected, in part, by the temporal loss of chemotactic function of leukocytic phagocytes. Our studies of patient neutrophils to define the mechanism of this phenomenon involved evaluation of both random and chemotactic migratory functions of patient neutrophils, measurement of receptors for chemotactic ligands, and measurement of receptors mediating substrate adherence of the cells. Measurements of migratory functions were made using the under-agarose technique and measurements of receptor expression were accomplished by flow cytometry using fluorescein-labeled ligand or receptor-specific antibody. We conclude that loss of chemotaxis in response to C5a/C5adesArg is the results of down-regulation of receptors for C5a and of reduced motility, and that loss of chemotaxis in response to the tripeptide FMLP is the result of reduced motility alone. Measurements of changes in the expression of "adherence" (iC3b) receptors revealed that up-regulation occurs early and can be sustained for weeks after injury. These results are taken to suggest that either hyper- or hypo-adherence could explain the loss of random migratory function observed for patient cells. Evidence of auto-oxidative alteration of cytoskeletal elements, to produce loss of random migratory function, also is reviewed. Considering the evidence for activation of the complement cascade after thermal injury C5a and C5adesArg are likely primary factors in effecting the down-regulation of C5a receptors, stimulation of secretion to mobilize iC3b receptors, and stimulation of respiration to auto-oxidize cell components. Such evidence of injury-mediated complement activation included data derived from application of a novel immunoassay for iC3b.

Halo immobilization in the treatment of burns to the head, face, and neck.

The care of burns to the head, face, and neck remains a challenge to the clinician. From 1978 to 1986, halo traction was used as an immobilizing device and as a protective frame for 31 patients with burns to the head (n = 8), face (n = 24), and neck (n = 28). The patients ranged in age from 8 months to 80 years (mean = 16 years) and had second- and third-degree burns covering a total body surface area of 8% to 75% (mean = 28%). The halo was used for an average of eight days (range one to 19 days) and served to immobilize and protect areas of fresh skin grafts, as well as to elevate and protect scalp donor sites (n = 10). Traction was initially used in patients who were confused and uncooperative, and in patients whose burns involved the neck to provide extension for prophylaxis against contractures. Treatment side effects included intermittent headache and backache, the latter occurring especially in the patients subjected to hyperextension. Eight patients (26%) complained of discomfort, which was reduced with adequate analgesia, sedation, and emotional support. The halo had to be removed from one patient after one day because of a loose pin, and in another patient after eight days because of the development of cellulitis at a pin site. Halo immobilization was used successfully to minimize graft loss in 30 of 31 patients.

Initial dosage regimens of gentamicin in patients with burns.

For 95 patients with burns the gentamicin dosage regimen necessary to achieve optimal serum concentrations was determined. Individual elimination rates and distribution volumes for gentamicin were determined and correlated with renal function parameters and age. In patients with burns who had normal serum creatinine levels (less than 1.5 mg/dl), gentamicin clearance and thus dosage regimens can be stratified by age. Gentamicin's clearance decreased inversely with age. Initial dosage guidelines were calculated for different age groups of patients with normal levels of serum creatinine. The guidelines were developed to assist the clinician in attaining therapeutic concentrations with initial doses of gentamicin. Therapeutic serum concentrations were reached in most patients with burns dosed by these guidelines. Serum gentamicin concentrations should always be monitored during therapy, and dosages should be adjusted to ensure optimal concentrations during the course of therapy.

Thermal injury, the inflammatory process, and wound dressing reduce human neutrophil chemotaxis to four attractants.

The purpose of this study was to assess the influence of thermal injury and the inflammatory process on chemotactic responses of neutrophils to four attractants (N-formyl-methionyl-leucyl-phenylalanine, the complement fragment C5a, interleukin-8, and leukotriene B4) under agarose, expression of Mac-1 (CD11b/CD18) adherence receptors on the cell surface, and polymerization of actin in the cell cytoplasm. Circulating neutrophils were isolated from peripheral blood, and exudate neutrophils from fluid collecting under two different wound dressings applied to abrasion sites of healthy subjects and to skin graft donor sites of patients with burns. Burn injury reduced the chemotactic responses of circulating neutrophils to all four attractants, suggesting a "global" defect in chemotactic function. Patient-exudate neutrophils collected under Tegaderm exhibited further decrements in all chemotactic responses, and patient-exudate neutrophils collected under Biobrane were nonmotile. The exudate neutrophils collected under Biobrane expressed high levels of Mac-1 receptors and irreversibly polymerized actin, which may contribute to the nonmotility of these exudate cells.

Inaccuracy of nitrogen balance determinations in thermal injury with calculated total urinary nitrogen.

Many burn centers use nitrogen balance studies to estimate the adequacy of nutritional support. Nitrogen loss includes the sum of urinary urea nitrogen, nonurea urinary nitrogen, and losses from skin, wound, and stool. Urinary urea nitrogen is often used to calculate total urinary nitrogen by multiplying the urinary urea nitrogen by a factor of 1.25 to account for nonurea urinary nitrogen. This formula is appropriate when applied to a nonstressed individual who has fasted overnight but is not appropriate for patients who have undergone surgery or experienced trauma. We have undertaken this study to assess the predictability of this formula in patients with thermal injuries. Twenty-seven patients with major thermal injuries had random 24-hour urine collections, which were analyzed for both urinary urea nitrogen and total urinary nitrogen. In these patients with burns we found that urinary urea nitrogen represented approximately 65% of the directly measured total urinary nitrogen rather than 80% as assumed by the formula. This increase in the nonurea nitrogen loss is greater than that found after surgery or trauma. Individual measurements may underestimate losses by 20% to 60%. Directly measured total urinary nitrogen should replace calculated total urinary nitrogen as the index of urine nitrogen losses for nitrogen balance studies in patients with burns.

Accelerated healing and reduced need for grafting in pediatric patients with burns treated with arginine-glycine-aspartic acid peptide matrix. RGD Study Group.

Arginine-glycine-aspartic acid (RGD) peptide matrix is designed to promote dermal healing by providing a molecular scaffold that facilitates cell ingrowth and establishment of normal tissue architecture. This study investigated the effectiveness and safety of RGD peptide matrix in the treatment of partial-thickness scald burns in pediatric patients. Either topical RGD peptide matrix or control treatment with silver sulfadiazine was applied to matched burn sites daily for up to 21 days. With RGD peptide matrix application under synthetic occlusive dressing, the incidence of healing was nearly threefold higher, average time to healing 2.5 days shorter (regression estimation), extent burn closure at all treated sites 37% greater, and number of needed grafting procedures fourfold lower compared with control treatment. All these differences were statistically significant. RGD peptide matrix was well tolerated. RGD peptide matrix promoted and accelerated healing in this study and thus may be able to reduce morbidity and treatment costs of partial-thickness burns in pediatric patients.

The influence of serum albumin and alpha 1-acid glycoprotein on vancomycin protein binding in patients with burn injuries.

Ten patients with burn injuries (mean total body surface area burn = 29% +/- 16) were studied at various points in the course of their burn therapy. Alpha 1-Acid glycoprotein, albumin, and vancomycin concentrations were determined with either a trough or peak vancomycin quantitative determination. Alpha 1-Acid glycoprotein concentrations ranged from 125 to 333 mg/dl and albumin concentrations ranged from 1.7 to 4.2 gm/dl. Vancomycin protein binding, as determined by ultrafiltration, averaged 29% +/- 6%. There was a strong (r = 0.92) relationship between percent protein-bound vancomycin and albumin. There was a poor statistical relationship between percent protein-bound vancomycin and alpha 1-acid glycoprotein (r = 0.28). Alpha 1-Acid glycoprotein appeared to have virtually no effect on the protein-binding characteristics of vancomycin over the range of concentrations studied.

A biopsy of the use of the Baxter formula to resuscitate burns or do we do it like Charlie did it?

The Baxter formula is commonly used to calculate fluid requirements. Baxter reported that 12% of patients would require more than 4.3 mL/kg per percentage of total body surface area (%TBSA). We anecdotally observed that we frequently exceeded the predictions of the formula, and we wondered if this was unique to our practice. We studied our last 11 burn-related resuscitations and collected fluid resuscitation data from US burn centers. Twenty-eight centers were queried, and 6 centers shared data. We were therefore able to study the resuscitation data of 50 adult patients. For 29 patients (58%), 4.3 mL/kg/%TBSA was exceeded compared with the 12% reported by Baxter. These findings suggest that in actual practice, fluid volumes administered are larger than the Baxter formula predicts. This survey does not explain why. Possible reasons for the larger fluid volumes are as follows: (1) the sample is not representative; (2) the formula is used improperly; (3) burns have changed and require more fluids; (4) burn care has changed.