Early serum (1→3)-ß-D-glucan levels in patients with burn injury.

Serum (1→3)-ß-D-glucan (BG) is increasingly used as diagnostic marker for invasive fungal infections. Exposure to gauze may lead to false-positive BG assays. The role of BG is unclear in thermally injured patients who frequently require extensive gauze coverage; therefore, we prospectively evaluated BG levels in burn-injured patients. Serum BG levels were measured in 18 burn patients immediately before application of the first dressing and 12 h after. Patients were stratified by extent of total body surface area (TBSA) requiring gauze coverage: <20%, 20-39%, 40-60% and >60%. BG levels were obtained from patients with non-burn trauma as controls. BG results were positive (>80 pg ml⁻¹) in 9/18 (50%) patients at baseline and in 8/18 (44%) 12 h after application of the first dressing. BG levels were positive in 1/5 (20%) of patients with <20% TBSA requiring gauze and in 10/13 (77%) with ≥ 20% (P < 0.05). None of the control patients had positive BG at any time point and none of the patients had candidemia at baseline. Mean serum BG levels decreased (19.44 pg ml⁻¹) after gauze placement. False-positive serum BG elevations are common in this patient population. Positivity correlates with extent of TBSA injured, but is not impacted by the gauze itself.

Epidemiology of bloodstream infections in burn-injured patients: a review of the national burn repository.

Bloodstream infections (BSIs) are a major cause of morbidity and mortality in thermally injured patients. However, these infections have not been well defined in this patient population. Therefore, the authors performed a retrospective case-control study to characterize the epidemiology, microbiology, and outcomes of burn-associated BSIs. A retrospective review of all patients in the National Burn Repository (NBR) between the years 1981 and 2007 was performed. All cases that had infection listed under complications were included in this study. For each case, two randomly selected patients from the same time period served as controls. Patient demographic data, extent of %TBSA, and type of infection were extracted. Primary end point was mortality. Secondary endpoints were hospital length of stay (LOS), intensive care unit LOS, total ventilator days, and hospital charges. Further analysis of the data involved case-matching patients by TBSA deciles, adjustment for the effects of TBSA and other potential confounders, and a sensitivity analysis of the effects of including or excluding sites that might have failed to consistently capture BSI information. A total of 11,793 patients (3931 cases and 7862 control) were included in the study. Of cultures revealing a Gram-positive organism, Staphylococcus aureus (32%) was the most common. From samples where isolation of a Gram-negative species occurred, Pseudomonas aeruginosa (35%) was more prominent. Infected patients were older (40.9 vs 32.8, P < .05) and had higher %TBSA (22.2 vs 7.9, P < .05). BSI was associated with significantly higher mortality (21.9% vs 3.09%), hospital LOS (47.4 vs 8.8 days) intensive care unit LOS (30.8 vs 2.6 days), ventilator days (29.2 vs 1.4 days), and hospital charge ($339,909.91 vs $33,272.43); P < .001 for all values. On evaluation of case-matched controls, mortality was higher for patients with BSI only <50% TBSA strata. Conclusions were unaffected by adjustment for TBSA and other possible confounders and was not influenced by possible failure of some sites to consistently capture BSI information. Development of BSI in hospitalized burn patients is associated with significant increases in morbidity, mortality, and resource utilization.

Critical review of burn depth assessment techniques: part II. Review of laser doppler technology.

The judgment of which wounds are expected to heal within 21 days is one of the most difficult and important tasks of the burn surgeon. The quoted accuracy of 64 to 76% by senior burn surgeons underscores the importance of an adjunct technology to help make this determination. A plethora of techniques have been developed in the last 70 years. Laser Doppler imaging (LDI) is one of the most recent and widely studied of these techniques. The technology provides an estimate of perfusion through the burn wound, the assumption being that a lower perfusion correlates with a deeper wound and, therefore, a longer time to heal. Although some reports suggest accuracy between 96 and 100% and that it does this 2 days ahead of clinical judgment, others have questioned its applicability to clinical practice. This article, the second of a two-part series, has two objectives: 1) a review of the Doppler principle and how the LDI uses it to estimate perfusion; and 2) a critical assessment of the burn literature on the LDI. Part I provides a historical perspective of the different technologies used through the last 70 years to assist in the determination of burn depth. Laser Doppler has brought technology closer to provide a reliable adjuvant to the clinical prediction of healing, yet, caution is warranted. A clear understanding of the limitations of LDI is needed to put the current research in perspective to find the right clinical application for LDI.

Apoptosis is differentially regulated by burn severity and dermal location.

BACKGROUND: The cellular processes that contribute to cell death in burns are poorly understood. This study evaluated the distribution and extent of apoptosis in an established rat model of acute dermal burn injury. MATERIALS AND METHODS: A branding iron (100 degrees C) was applied to the depilated dorsum of seven rats, creating burn contact times of 1-8, 10, 12, and 14 s. Biopsies were collected and immunohistochemistry performed for apoptosis and cell injury/necrosis by detection of terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) and high-mobility group box 1 (HMGB1), respectively. The slides were scored by evaluating staining in superficial, middle, and deep dermal fields. Within these, basal keratinocytes of the epidermis, mesenchymal cells, adnexal epithelia, and vasculature wall cells were morphometrically analyzed for stain detection of selected markers. RESULTS: TUNEL staining had an inverse relationship with contact time in most fields except in deep dermal mesenchymal cells where it was increased. HMGB1 nuclear staining was significantly decreased with progressive contact time consistent with transition to cell injury/necrosis. CONCLUSIONS: This study is the first to demonstrate that apoptosis rate is dependent on dermal location, cell type, and severity of thermal injury. Furthermore, this work suggests that for most dermal locations increased thermal injury corresponds with decreased apoptosis and increased cell injury/necrosis. Together, these findings indicate that many parameters can regulate apoptosis in burn wounds, and these results will be critical to understanding burn pathogenesis and assessing future therapies.

Pharmacologic modification to resuscitation fluid after thermal injury--is drotrecogin alfa the answer to arrest burn depth progression?

HYPOTHESIS: The addition of drotrecogin alfa (DA), an anti-inflammatory useful in septic shock, to standard burn shock resuscitation fluids will protect burned, injured skin from further injury. METHODS: Anesthetized animals were subjected to a standardized burn pattern by applying a branding iron to 10 different locations on the back of the rat for 1 seconds to 14 seconds, creating a range of burn depths and severities. DESIGN: Animal burn shock and resuscitation model. PARTICIPANTS: Thirty-one male adult Sprague-Dawley rats. INTERVENTIONS: Control animals were resuscitated with lactated Ringer's solution (LRS) at 2 mL/kg/percent total body surface area/24 h; experimental animals received LRS plus DA 24 microg/kg/h (LRS + DA). OUTCOME MEASURES: Perfusion to each burned area was assessed using a laser Doppler imaging technology. Punch biopsies at each burned area were stained with hematoxylin and eosin and assessed for burn depth and for inflammation using previously reported measures. Samples from 14 animals were stained for terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling and caspase-3 (apoptosis markers). RESULTS: Increasing branding iron contact times worsened perfusion, burn depth, and apoptotic ratios. There was no correlation between inflammatory markers and burn contact time. The addition of DA leads to worse perfusion, deeper burns, worse inflammation, and decreased apoptotic ratios. CONCLUSIONS: Laser Doppler imaging is a useful technology to assess burn depth. The addition of DA to traditional resuscitation fluids for burn shock is deleterious to the injured, burned skin. Modifying the traditional burn shock resuscitation fluids, although intellectually attractive, needs to be rigorously studied.

Critical review of burn depth assessment techniques: Part I. Historical review.

The assessment of burn depth, and as such, the estimation of whether a burn wound is expected to heal on its own within 21 days, is one of the most important roles of the burn surgeon. A false-positive assessment and the patient faces needless surgery, a false-negative one and the patient faces increased length of stay, risks contracture, and hypertrophic scar formation. Although many clinical signs can aid in this determination, accurate assessment of burn depth is possible only 64 to 76% of the time, even for experienced burn surgeons. Through the years, a variety of tools have become available, all attempting to improve clinical accuracy. Part 1 of this two-part article reviews the literature supporting the different adjuvants to clinical decision making is, providing a historical perspective that serves as a framework for part 2, a critical assessment of laser Doppler imaging.

Outcomes from burn injury-should decreasing mortality continue to be our compass?

Patient survival continues to be the standard measure of outcomes after burn injury. The current mortality following thermal injury, however, is very low, around 5% to 6%, and has changed little in almost 30 years. This article uses the National Burn Repository to assess the factors that affect mortality and discusses the need for other outcome measures. Although improving survival is a lofty goal and should not be abandoned, aspects such as quality of life and return to baseline activity should be taken into account in the assessment of patient outcome after burn injury.

Use of Integra in the treatment of third degree burns to the penile shaft: a case series with 6-month follow-up.

Third-degree burns to the penile shaft are serious injuries sometimes accompanied by poor healing, hypertrophic scar formation, painful erections, and dyspareunia. At this burn center, three patients with penile shaft burns have been treated successfully with Integra followed by thin, split-thickness skin grafting. Allowing a scar-free foundation for skin grafting to the penile shaft, in combination with early excisions and split-thickness autografting, Integra application facilitated the early return of near-normal skin quality, no contractures, and pain-free erectile function. With innovative management techniques, functional outcomes were obvious throughout the 6-month follow-up period.

Methylene blue in the treatment of vasoplegia following severe burns.

Vasoplegia resulting from severe burns may persist despite adequate fluid resuscitation and treatment with norepinephrine (NE), vasopressin (VP), and steroids. The adenylate cyclase inhibitor methylene blue (MB), currently used in the burn patient to treat methemoglobinemia, has been used to treat vasoplegia after cardiopulmonary bypass. We report the case of MB infusion in two burn patients refractory to NE. The patients had severe burns, 95 and 80% TBSA not responding to conventional treatment. Fluid requirements were estimated according to Parkland formula and then to maintain a urinary output of 30-50 ml/hr. Patient #1, 95% TBSA, was adrenally insufficient and was receiving steroids according to the Annane protocol, as well as VP at 0.2 U/min. His NE requirements were 55 mcg/kg/min. Patient #2, 80% TBSA, was receiving 20 mcg/kg/min of NE. Circulatory failure was defined as inability to maintain mean arterial pressure >70 mm Hg. Hemodynamic and physiologic parameters were measured before and after infusion of a single dose of 2 mg/kg of MB. Both patients showed dramatic improvements in their shock after MB. Patient #1 had an initial reaction within 30 minutes and reached peak effect at 1 hour. His NE requirements decreased to 0.2 mcg/kg/min and VP decreased to 0.04 U/min. Patient #2 showed effects within 15 minutes of the infusion and by 2 hours the NE was stopped. No adverse side effects were noted in either of the two patients. The fact that MB successfully reversed refractory vasoplegia after severe burns suggests a new tool for treating a small subgroup of patients who exhibit persistent vasoplegia from their burn injury. A controlled randomized trial is needed to test its effects on a large number of patients and graft survival.

Improved markers for burn wound perfusion in the severely burned patient: the role for tissue and gastric Pco2.

Improved markers of resuscitation are needed in patients with severe burn injuries. In previous animal and human work, we showed 1) wound hypoperfusion plays a role in burn depth progression, 2) that there are periods of repetitive ischemia and reperfusion which correlate closely to wound hypoperfusion, and 3) that wound and splanchnic bed CO2 measurements are dependent on the adequacy of resuscitation. We and others believe that current markers for resuscitation, urine output (U/O), and mean arterial pressure (MAP), lag behind in reflecting wound perfusion. In this study, we explore whether gastric and tissue tonometry are better in reflecting minute-to-minute changes in wound perfusion in humans. During the 48-hour experimental period, burn wound, gastric, and arterial pH, Pco2, and PaO2 were measured every 6 seconds using a Paratrend 7 monitor in four patients with life threatening burns. Slopes of change were analyzed and a proportion derived relative to pooled data on 5-minute intervals. Serum lactate, U/O, and MAP were recorded. Laser Doppler Imager (LDI) scans were performed on burn areas every 4 hours, allowing real-time determination of burn perfusion. Resuscitation followed current clinical guidelines. All four patients eventually succumbed, one doing so during the observation period. In the remaining three, U/O and MAP goals were met within 2 hours of resuscitation. Our analysis shows cyclic changes in burn wound pH, CO2, and PaO2, gastric CO2, and PaO2, and arterial base deficit (all P < .005). LDI showed cyclic changes in perfusion (P < .0001) which closely mimic the changes in wound pH, gastric CO2, and arterial base deficit. These changes preceded changes in U/O, MAP, and lactate. Although U/O, MAP, and serum lactate reflect changes in burn wound perfusion, they lag behind other markers. Tissue pH and CO2 and gastric CO2 seem to be more timely related to changes in actual burn perfusion.

Repetitive ischemia-reperfusion injury: a plausible mechanism for documented clinical burn-depth progression after thermal injury.

Our previous studies confirmed the phenomenon of burn depth progression despite adequate Parkland formula resuscitation [Kim et al. J Burn Care Rehabil 2001;22960:406-6]. Repetitive ischemia-reperfusion injury (I-R) is a plausible explanation and is suggested by the concomitant swings we have observed in serum base deficit (BD) during resuscitation from burn shock. We chose to explore whether laser Doppler imaging (LDI) evidence of burn depth progression mirrored cycles of I-R (episodic swings in continuously measured BD). Positive findings would support the hypothesis that repetitive episodes of I-R is a factor in burn depth progression despite apparently adequate resuscitation. A total of 14 patients with severe life-threatening burns (median 51% TBSA) underwent continuous BD monitoring using a Paratrend 7 (Malvern PA) during 48 hours of resuscitation. Fluid needs were estimated using the Parkland formula, then were titrated to urine output. The slopes of BD changes were then analyzed. Worsening of BD greater than 0.2 mmol/l/min was noted, and a proportion derived relative to pooled data on 5-minute intervals. In four of the patients, LDI scans were performed on six representative areas sequentially every 4 hours. The analysis of median flux in these LDI images provided real-time determination of burn depth progression. Eight patients eventually died. Only four patients achieved a normal BD within 12 hours of monitoring despite exceeding the Parkland formula estimate and meeting urinary output parameters. Our analysis also showed cyclical peaks and valleys in the BD curve (P < .001), suggesting repetitive I-R insults. All increases in BD preceded changes that could be detected in vital signs or urine output. Finally, LDI confirmed that the burn depths continued to progress despite apparently adequate resuscitation, and also showed that there are similar peaks and valleys in the perfusion of the wounds (P < .0001), which mimic the changes in the BD curve. Responses to fluid resuscitation do not follow a linear pattern in the case of massive burns. These results in repetitive periods of tissue hypoperfusion evidenced by BD alterations and may contribute to progressive deepening of the burn wound.

Seven years' experience with Integra as a reconstructive tool.

The bilayered dermal substitute Integra (Integra Life Sciences Corp., Plainsboro, NJ) was developed and has been widely used as primary coverage for excised acute burns. Our take has been slightly different, finding it most useful in the management of complex soft-tissue loss and threatened extremities as the result of tendon, joint, or bone exposure. Often tasked to fill significant volume loss, we have become adept at stacked multiple-layer applications. Creative use of this material has resulted in unexpected successes with distal limb salvage; the technique takes its place beside adjacent tissue transfer, composite flaps, and vascular pedicle flaps in our burn reconstructive practice. A prospective registry (44 patients) has been kept during the past 7 years that catalogs wounds with complex soft-tissue loss treated with Integra grafts. Many of these patients were at risk of extremity loss because of exposed tendons, joints, or bone. Integra was applied after 1:1 meshing. With profound soft-tissue defects, multiple layers of Integra were serially applied 1 to 2 weeks apart for reconstitution of soft-tissue contours. Local Integra graft infections were managed by silicone unroofing followed by topical sulfamylon liquid dressings. Wounds addressed included fourth-degree burns, necrotizing fasciitis, pit-viper envenomations, and total abdominal wall avulsion in one patient after being run over by a bus. Patients generally were free of pain from their wounds during the maturation phase of the Integra neodermis. Restoration of tissue contour was significantly better when using multiple layers for deep defects. Second and third layers of Integra were successfully applied after an abbreviated first graft maturation period of 7 days. Epithelial autografts on multilayer Integra applications frequently "ghosted"; they would auto-digest to dispersed cells followed subsequently by the reappearance of a confluent epithelial layer. Final grafted skin morphology over palmar and plantar surfaces assumed the type and fingerprint pattern of the original tissues. Infections were readily visible. Early recognition kept them to easily treated circumscribed areas, which did not jeopardize the entire wound. Lengths of stay were long (range, 2-246 days) but not significantly greater than with traditional techniques. The specific reconstructive use of Integra permitted unexpected salvage of several threatened extremities by protecting exposed tendons, bones and joints. Long-term histologic examination revealed unexpected persistence of Integra collagen. Large volume loss wounds benefited from the ability to fill voids with multilayered applications.