Demonstration of the safety and effectiveness of the RECELL® System combined with split-thickness meshed autografts for the reduction of donor skin to treat mixed-depth burn injuries.

INTRODUCTION: Split-thickness skin grafts (STSG) are the standard of care (SOC) for burns undergoing autografting but are associated with donor skin site morbidity and limited by the availability of uninjured skin. The RECELL® Autologous Cell Harvesting Device (RECELL® System, or RECELL) was developed for point-of-care preparation and application of a suspension of non-cultured, disaggregated, autologous skin cells, using 1cm2 of the patient's skin to treat up to 80cm2 of excised burn. METHODS: A multi-center, prospective, within-subject controlled, randomized, clinical trial was conducted with 30 subjects to evaluate RECELL in combination with a more widely meshed STSG than a pre-defined SOC meshed STSG (RECELL treatment) for the treatment of mixed-depth burns, including full-thickness. Treatment areas were randomized to receive standard meshed STSG (Control treatment) or RECELL treatment, such that each subject had 1 Control and 1 RECELL treatment area. Effectiveness measures were assessed and included complete wound closure, donor skin use, subject satisfaction, and scarring outcomes out to one year following treatment. RESULTS: At 8 weeks, 85% of the Control-treated wounds were healed compared with 92% of the RECELL-treated wounds, establishing the non-inferiority of RECELL treatment for wound healing. Control-treated and RECELL-treated wounds were similar in mean size; however, mean donor skin use was significantly reduced by 32% with the use of RECELL (p<0.001), establishing the superiority of RECELL treatment for reducing donor skin requirements. Secondary effectiveness and safety outcomes were similar between the treatments. CONCLUSIONS: In combination with widely meshed STSG, RECELL is a safe and effective point-of-care treatment for mixed-depth burns without confluent dermis, achieving short- and long-term healing comparable to standard STSG, while significantly decreasing donor skin use.

A comparison of renal phosphorus regulation in thermally injured and multiple trauma patients receiving specialized nutrition support.

To compare phosphorus intake and renal phosphorus regulation between thermally injured patients and multiple trauma patients, 40 consecutive critically ill patients, 20 with thermal injury and 20 with multiple trauma, who required enteral tube feeding were evaluated. Phosphorus intakes were recorded for 14 days from the initiation of tube feeding which was started 1 to 3 days postinjury. Serum for determination of phosphorus concentrations was collected at days 1, 3, 7, and 14 of the study period. A 24-hour urine collection was obtained during the first and second weeks of nutrition support for urinary phosphorus excretion, fractional excretion of phosphorus, renal threshold phosphate concentration, and phosphorus clearance. Average total daily phosphorus intake during the 14-day study for thermally injured patients and multiple trauma patients was 0.99+/-0.26 mmol/kg/d vs 0.58+/-0.21 mmol/kg/d, respectively, p < .001. Serum phosphorus concentration on the third day of observation was significantly lower in the thermally injured group than those with multiple trauma (1.9+/-0.8 mg/dL vs 3.0+/-0.8 mg/dL, p < or = .01). A trend toward hypophosphatemia in the thermally injured group persisted by the seventh day of feeding (2.7+/-1.2 mg/dL vs 3.3+/-0.6 mg/dL, p < or = .04). Differences in urinary phosphorus excretion was not statistically significant between the thermally injured and multiple trauma groups (271+/-213 mg/d vs 171+/-181 mg/d for week 1, and 320+/-289 mg/d vs 258+/-184 mg/d for week 2, respectively). Urinary phosphorus clearance, fractional excretion of phosphorus, or renal threshold phosphate concentrations were also not significantly different between thermally injured and multiple trauma patients. During nutrition support, serum phosphorus concentrations are lower in thermally injured patients compared with multiple trauma patients despite receiving a significantly greater intake of phosphorus. Renal phosphorus regulation does not significantly contribute to the profound hypophosphatemia observed in thermally injured patients when compared with multiple trauma patients during nutrition support.

Fluconazole pharmacokinetics in burn patients.

The pharmacokinetics of fluconazole in nine adult patients with severe (30 to 95% total body surface area) burns were studied. There was no significant difference in half-life (t1/2), clearance (CL), or volume of distribution (V) over time in five patients on days 3 and 8 of the study (P > 0.05). Combined parameter estimates (means +/- standard deviations) for all nine patients for the two study periods were as follows: t1/2, 24.4 +/- 5.8 h; CL, 0.36 +/- 0.09 ml/min/kg; and V, 0.72 +/- 0.12 liters/kg. These estimates of t1/2 and CL in burn patients were approximately 13% shorter and 30% more rapid, respectively, than the most extreme estimates reported for other populations.

Fournier's gangrene: therapeutic impact of hyperbaric oxygen.

Many controversial issues exist surrounding the disease pathogenesis and optimal management of Fournier's gangrene. In Fournier's original descriptions, the disease arose in healthy subjects without an obvious cause. Most contemporary studies, however, are able to identify definite urologic or colorectal etiologies in a majority of cases. To investigate disease presentation, treatment modalities, and overall mortality, a retrospective analysis of Fournier's gangrene from a single institution is presented. Since 1990, 26 cases of Fournier's gangrene have been diagnosed at the University of Tennessee. An evaluation of intercurrent disease revealed that 38 percent of the patients had diabetes mellitus, 35 percent manifested ethanol abuse, and 12 percent were systemically immunosuppressed. Fifteen patients (58 percent) presented with identifiable etiologies for their disease: 31 percent (8) urethral disease or trauma, 19 percent (5) colorectal disease, and 8 percent (2) penile prostheses. Management in all cases involved prompt surgical debridement with initiation of broad-spectrum antibiotics. Multiple debridements, orchiectomy, urinary diversion, and fecal diversion were performed as clinically indicated. Fourteen patients received hyperbaric oxygen as adjuvant therapy. Statistically significant results were noted with mortality rates of 7 percent in the group receiving hyperbaric oxygen (n = 14) versus 42 percent in the group not receiving hyperbaric oxygen (n = 12). Overall mortality was 23 percent. Controversy still surrounds disease pathogenesis in Fournier's gangrene, particularly in regard to etiology. Our study corroborates current trends in that a clear focus or origin was identified in a majority of the cases. Although a grim prognosis usually accompanies the diagnosis, this study shows significant improvement combining traditional surgical and antibiotic regimens with hyperbaric oxygen therapy.

A multicenter clinical trial of a biosynthetic skin replacement, Dermagraft-TC, compared with cryopreserved human cadaver skin for temporary coverage of excised burn wounds.

This multicenter study compared the use of a biosynthetic human skin substitute with frozen human cadaver allograft for the temporary closure of excised burn wounds. Dermagraft-TC (Advanced Tissue Sciences, Inc.) (DG-TC) consists of a synthetic material onto which human neonatal fibroblasts are cultured. Burn wounds in 66 patients with a mean age of 36 years and a mean burn size of 44% total body surface area (28% total body surface area full-thickness) were surgically excised. Two comparable sites, each approximately 1% total body surface area in size, were randomized to receive either DG-TC or allograft. Both sites were then treated in the same manner. When clinically indicated (> 5 days after application) both skin replacements were removed, and the wound beds were evaluated and prepared for grafting. DG-TC was equivalent or superior to allograft with regard to autograft take at postautograft day 14. DG-TC was also easier to remove, had no epidermal slough, and resulted in less bleeding than did allograft while maintaining an adequate wound bed. Overall satisfaction was better with DG-TC.

Managed health care: therapist responsibilities.

Goals identified by managed health care organizations are to contain costs and to provide services that produce functional outcomes. Burn clients with managed care have experienced a lack of reimbursement for rehabilitation that results in less than functional outcomes. For therapy to receive reimbursement the therapist's responsibilities must begin on day 1 of burn injury. Traditional burn therapist responsibilities must be coupled with interactions to families, managed care, employers, and case managers. Clinical skills must foster the client assuming responsibility for improvement and returning to preinjury activities. Therapists must develop the ability to communicate and present data illustrating the why of therapy as it relates to costs, goals, and time frames. Anticipating and developing rationale for burn rehabilitation can facilitate reimbursement, minimize delay between inpatient/outpatient therapy programs, and ensure that the client obtains functional outcomes. Information to assist the therapist to develop appropriate information for reimbursement of burn rehabilitation is presented.

Propane gas dangers and strategies for prevention of injuries.

Although the overall incidence of thermal injuries continues to decrease, the incidence of certain types of burns is alarmingly high. Approximately 3000 propane fires and explosions are reported yearly. More than 9% of these cases result in bodily injury, and the mortality rate is more than 7% of the injured. Most of the accidents are felt to be the result of a lack of knowledge among the general public in regard to the use of liquid petroleum (LP) gas, which is a low-cost and widely used fuel source. A series of accidents that resulted in several injuries in the midsouth area heightened our awareness of the problems associated with LP-gas storage, transportation, and use. A review of the incidence of use and injury, warning systems, product liability status, and prevention strategies are reported to help educate health care providers and increase public awareness of the problems associated with propane gas.

Quality burn rehabilitation: cost-effective approach.

As funding for health care becomes a national concern, and workman's compensation and private health insurance companies attempt to limit their expenditures in the treatment of the client with burns, it may become the responsibility of the burn specialists to create a cost-effective approach to quality burn rehabilitation. Our outpatient rehabilitation program has taken a cost-effective approach that limits the use of inpatient rehabilitation, emphasizes the burn team guiding the client to a quick functional return to home and work, and concentrates costs for therapy rather than room and board. This cost-effective rehabilitation approach emphasizes an intensive 6-hours-per day, 5-days-per-week outpatient program that begins immediately after discharge. In a 2 1/2-year follow-up of this cost-effective program, the following were identified. (1) A 40% reduction in costs for third-party payers and (2) clients returning to work an average of 4 months after their injury. In the cost-effective rehabilitation approach, 82% of the health care costs are concentrated for therapy. In the traditional inpatient rehabilitation program, room and board costs comprise 57% of the charges. Because it is the responsibility of the burn specialists to educate the health care payers, a program description to implement the cost-effective approach to burn rehabilitation is provided.

A prospective comparison of a new, synthetic donor site dressing versus an impregnated gauze dressing.

Three institutions enrolled 38 patients who required bilateral skin graft donor sites into a safety and efficacy study of a new synthetic donor site dressing. Bilateral donor sites were randomized to receive either a new, synthetic donor site dressing or an impregnated gauze dressing. Wounds were assessed by time to healing, pain, and patient preference. Synthetic dressing wounds were treated 7.9 days compared with 10.2 days for gauze dressing wounds (p < 0.001), and synthetic dressing wounds were more completely epithelialized. Visual analogue pain analysis revealed significantly less donor site pain with synthetic dressing (2.94) versus gauze dressing (4.64) (p < 0.001). Synthetic dressing had fewer treatment-related adverse experiences than gauze dressing (2 vs 7) and was judged by recipients to be superior to gauze dressing in comfort, pain relief, cosmetic appeal, ease of ambulation, and overall acceptance.

Planned ventral hernia. Staged management for acute abdominal wall defects.

OBJECTIVE: Analysis of a staged management scheme for initial and definitive management of acute abdominal wall defects is provided. METHODS: A four-staged scheme for managing acute abdominal wall defects consists of the following stages: stage I--prosthetic insertion; stage II--2 to 3 weeks after prosthetic insertion and wound granulation, the prosthesis is removed; stage III--2 to 3 days later, planned ventral hernia (split thickness skin graft [STSG] or full-thickness skin and subcutaneous fat); stage IV--6 to 12 months later, definitive reconstruction. Cases were evaluated retrospectively for benefits and risks of the techniques employed. RESULTS: Eighty-eight cases (39 visceral edema, 27 abdominal sepsis, 22 abdominal wall resection) were managed during 8.5 years. Prostheses included polypropylene mesh in 45 cases, polyglactin 910 mesh in 27, polytetrafluorethylene in 10, and plastic in 6. Twenty-four patients died from their initial disease. The fistula rates associated with prosthetic management was 9%; no wound-related mortality occurred. Most wounds had split thickness skin graft applied after prosthetic removal. Definitive reconstruction was undertaken in 21 patients in the authors' institution (prosthetic mesh in 12 and modified components separation in 9). Recurrent hernias developed in 33% of mesh reconstructions and 11% of the components separation technique. CONCLUSIONS: The authors concluded that 1) this staged approach was associated with low morbidity and no technique-related mortality; 2) prostheses placed for edema were removed with fascial approximation accomplished in half of those cases; 3) absorbable mesh provided the advantages of reasonable durability, ease of removal, and relatively low cost--it has become the prosthesis of choice; and 4) the modified components separation technique of reconstruction provided good results in patients with moderate sized defects.

Cultured epidermal autografts and allodermis combination for permanent burn wound coverage.

Cultured epidermal autografts (CEA) have been shown to be an effective permanent skin replacement for major burn injuries, but are more sensitive to adverse conditions than split thickness grafts (Clarke et al., 1988). Cuono et al. (1986, 1987) have described the successful use of engrafted allodermis as a wound bed for cultured grafts. We report on a method of preparing allodermis and grafting CEA in five patients with major burns (48-70 per cent TBSA, average 59.6 per cent). The average age was 38.8 years (20-60 years). All full thickness wounds were excised down to fat within 7 days of admission, and covered with meshed split thickness cryopreserved homograft. Over the ensuing 2-3 weeks, the homograft became engrafted. At surgery, the allo-epidermis was removed, leaving the dermal components as a viable bed for the CEA. Keratinocytes derived from a full thickness biopsy were grown to confluence by the method of Rheinwald and Green (1975), and 25 cm2 sheets were stapled to Vaseline gauze backings and applied to freshly excised wounds. Seven to 10 days after surgery, the gauze backings were removed. The average take ranged from 87-100 per cent (average 93.6 per cent). Follow-up for up to 4 years shows supple skin that has been durable, and resistant to trauma and infection.

Pharmacokinetics of systemically administered antibiotics in patients with thermal injury.

Patients who sustain thermal injury may require adjustments of antibiotic dosing because of pharmacokinetic alterations and pathological changes that occur in this patient subset. In general, studies of gentamicin, tobramycin, and amikacin have demonstrated lower elimination half-lives in burn patients than in nonburn patients and healthy volunteers. Other studies have shown a strong correlation between vancomycin clearance and creatinine clearance and the need for higher vancomycin dosages for burn patients than for nonburn patients. Studies of ceftazidime, ticarcillin, enoxacin, and aztreonam have shown increases in the volume of distribution or decreases in the maximum concentration achieved. Total and renal drug clearance of aztreonam was highly correlated with creatinine clearance. With imipenem, the half-life, clearance, and volume of distribution observed in burn patients were not significantly different from those in nonburn patients, although substantial interpatient variability existed. Imipenem clearance was significantly correlated with creatinine clearance. Individualization of antibiotic therapy for burn patients is recommended with use of measured serum concentrations of the antibiotic or creatinine clearance as an estimate of renal function.

Early upper-extremity prosthetic fit in patients with burns.

Patients with upper-extremity amputations necessitated by burn injury have frequently faced delays in prosthetic fit. At the Regional Medical Center, Memphis, Tennessee, seven patients required amputations because of burns. These injuries were electrical in four cases, thermal and crush in one case, thermal in one case, and steam and crush in one case. Five patients had below-elbow amputations, one had a bilateral below-elbow amputation, and one had a bilateral above-elbow amputation. All patients were fitted with prostheses within 30 days of the last definitive surgery on the amputated extremity. All patients continued to wear a prosthesis and no patient exhibited skin breakdown. Patients returned to independence with self care within 2 weeks and to preamputation activities within an average of 2.5 months.

The use of cultured epithelial autograft in a patient with idiopathic pyoderma gangrenosum.

Pyoderma gangrenosum is an ulcerative cutaneous disorder that remains a diagnostic and therapeutic dilemma. Several medical therapies have been tried in treating the disorder. We report a patient with idiopathic pyoderma gangrenosum treated with the application of cultured epithelial autograft.

The management of mid-face fractures with intracranial injury.

Recent advances have radically changed the management of facial fractures. CT scanning, extensive exposure, and rigid plate fixation in the setting of the trauma center have permitted early operation with improved results. A subset of patients with facial fractures will also have intracranial injuries (ICI). We sought to identify parameters associated with an increased risk for ICI. We also sought to examine the safety and limits of early craniofacial repair in patients with intracranial injuries. Of 114 mid-face fractures treated over a 1-year period, 43 (38%) had a concomitant ICI. The majority, 36 (84%), were from motor vehicle accidents (MVA). Frontal sinus and orbitoethmoid fractures were at the highest risk for ICI, although orbitozygomatic fractures caused by MVAs also had a surprisingly high incidence of ICI. Our results show that early craniofacial repair can be performed safely with appropriate general surgical and neurosurgical support.

Beneficial actions of exogenous hyaluronic acid on wound healing.

To determine the effect of exogenous hyaluronic acid (HA) on healing of experimental wounds, responses in the hamster cheek pouch were measured after a hole was cut through the tissue with a biopsy punch. Fluorescence-labeled dextran was administered intravenously as a macromolecular tracer and the microcirculation was observed in vivo with a fluorescence microscope connected to a high-resolution television system. In one group a gelatin sponge soaked in 1.5 ml 16 mg/dl HA in water was applied topically at the time of injury and on postinjury days 1, 3, 5, and 7. The control group received the sponge soaked in the aqueous vehicle. Every 2 days after injury, the microcirculation was observed or histologic specimens were harvested. Wound size decreased almost twice as fast with HA compared with its vehicle (p less than 0.05). Healing was defined as time for total wound closure with at least one microvessel bridging the site of injury and required 16 or more days with vehicle but averaged less than 9 days with HA. Early during healing the repair site was surrounded by widespread extravasation of the fluorescent tracer, an index of inflammation; this area was reduced by two thirds 2 to 4 days after injury with HA compared with its vehicle (p less than 0.05). The density of perfused microvessels was twofold higher with HA 2 to 4 days after injury (p less than 0.05). However, microvessel density was similar in both groups by 6 days after injury and remained similar for at least 45 days after injury, which suggests that HA evoked no unusual angiogenic response. Histologic examination of fixed, stained specimens showed increases in intravascular leukocytes after injury and treatment-related differences in the distribution of intravascular leukocytes in 20 to 40 microns and 40 to 80 microns diameter microvessels 1 to 2 days after injury. Otherwise, leukocyte infiltration during healing was similar in both groups. The mechanism for the beneficial action of HA on healing is unknown. However, several in vitro studies suggest that HA is part of a feedback loop that promotes cell proliferation and migration in actively growing tissues. Alternatively, the role of HA in water homeostasis could favor tissue hydration, which has a well-known beneficial effect on healing.

Comparison of modified amino acids and standard amino acids in parenteral nutrition support of thermally injured patients.

Twenty thermally injured patients who could not tolerate enteral nutrition support were randomized to receive parenteral nutrition (PN) with either modified amino acids (MAA) or standard amino acids (SAA). There was no significant difference between groups for age, sex, weight, percent BSA area burn, percent third-degree burn, or operative procedures. N balance (NB) was measured and serum was harvested for circulating fibronectin (Fn), somatomedin-C/insulin-like growth Factor I (Sm-C), prealbumin (PA), and retinol-binding protein (RBP) analysis on days 1, 4, 7, 14, 21, and 28 of PN. The patient groups received similar doses of PN for a similar number of days. Fn did not change significantly from baseline in either group and there was no significant difference between groups. Sm-C increased significantly from baseline at day 7 in the SAA group and in both groups on day 14, but there was no significant difference between groups. PA and RBP increased significantly from baseline on day 7 in the MAA group and in both groups on days 14, 21, and 28. RBP was significantly higher in the MAA group only on day 21, and there was no significant difference between groups for PA. NB increased significantly from baseline for all study days; however, there was no significant difference between groups. PN in thermally injured patients significantly improves NB and increases visceral protein concentrations. However, there appears to be no difference between PN with MAA or SAA.

Regional variations of laser Doppler blood flow in ischemic skin flaps.

An island skin flap was designed on the left inferior epigastric neurovascular bundle of anesthetized male rats. Blood flow was measured in situ with a laser Doppler flowmeter at 20 discrete points on a grid system (5 points in each quadrant of the flap) before and after surgery, or before vascular occlusion, during reperfusion, and 48 to 72 hours later. Two series of experiments were performed. In the first series, the raised flap was placed in a bath containing heated Ringer's solution and the left pedicle was cross-clamped. After 30 minutes, adenosine at a concentration that produced supramaximal vasodilatation, or its vehicle, was added to the bath. After 1 hour total occlusion time, the vascular clamp was released and adenosine treatment was continued for the first 30 minutes of reperfusion. In the second series, the protocol was similar except that adenosine, or its vehicle, was infused into the ischemic flap by means of the distal stump of the right inferior epigastric artery. After 48 to 72 hours, fluorescein was injected IV. The data showed a significant regional variation in baseline laser Doppler blood flow that was further altered by surgically raising the flap. Whereas proximal axial laser Doppler blood flow was essentially unchanged from the preoperative baseline, distal axial laser Doppler blood flow decreased 10 to 50 percent, and proximal and distal dependent laser Doppler blood flow decreased 50 to 80 percent. Thus no single value accurately reflected total flap perfusion. Necrosis occurred only in the dependent flap regions, which confirmed previous work. In the dependent regions, especially along the incision line, postoperative laser Doppler blood flow was lowest.(ABSTRACT TRUNCATED AT 250 WORDS)

Imipenem pharmacokinetics in patients with burns.

The pharmacokinetics of imipenem were studied in 11 adult patients with severe burns who were receiving a therapeutic regimen of imipenem-cilastatin 500 mg intravenously every 6 hours. Serial blood samples for measuring imipenem and 24-hour urine collections for creatinine clearance (CrCl) were obtained after the initial dose and after multiple dosing. Plasma was assayed for imipenem by use of HPLC. A two-compartment model provided a superior fit to the data compared with a one-compartment model in 9 of the 11 patients. There was no significant difference in any pharmacokinetic parameter between the initial dose and after multiple dosing (p greater than 0.05). Combined mean (+/- SD) parameter estimates for the two dosing periods were as follows: VC, 0.11 +/- 0.06 L/kg; Vss, 0.22 +/- 0.06 L/kg; CL, 12.5 +/- 3.6 L/hr/1.73 m2; t1/2 alpha, 0.18 +/- 0.13 hr; t1/2 beta, 1.12 +/- 0.44 hr. Mean clearance in two patients with creatinine clearance values greater than 150 ml/min/1.73 m2 was 17.7 L/hr/1.73 m2. Mean clearance in two patients with creatinine clearance values less than 50 ml/min/1.73 m2 was 8.5 L/hr/1.73 m2. No pharmacokinetic parameter was significantly different from previously reported parameters in normal volunteers (p greater than 0.05). Creatinine clearance ranged from 17 to 218 ml/min/1.73 m2. Imipenem clearance was significantly related to creatinine clearance (CL = 63 + 0.059 CLCR; r2 = 0.60, p = 0.001). No significant association was found between total body surface area burns and imipenem clearance (p greater than 0.05). Our data suggest imipenem pharmacokinetics in patients with burns are comparable to those in normal volunteers although substantial intersubject variability exists.(ABSTRACT TRUNCATED AT 250 WORDS)