Controlling intraoperative hemorrhage during burn surgery: A prospective, randomized trial comparing NuStat® hemostatic dressing to the historic standard of care.

INTRODUCTION: One of the primary intraoperative challenges during burn surgery is to adequately excise the burn while avoiding massive hemorrhage. This has become increasingly important, as we see more burn patients that are older and with more medical comorbidities. While adequate excision down to healthy tissues for deep burns is essential for skin graft to take, it also leads to active bleeding that can be a challenge to control. Good hemostasis is imperative as a hematoma is the most common cause of graft loss. Several new products have become available to help control intraoperative hemorrhage. A new hemostatic dressing, NuStat®, is available and approved by FDA in United States. METHODS: A single institution prospective randomized control trial was completed at Regional Burn Center of the University of South Alabama comparing NuStat® with the institutional historic standard of care. Twenty such patients were included in our study. A cost analysis was also completed as part of the study retrospectively. RESULTS: For dressings used to treat the burn site, blood loss on the side treated with NuStat® was on average less (27g/100cm2) than the side treated with our historic standard of care (31g/100cm2), though it was not statistically significant (p=0.81). Similarly, on the donor site, blood loss on the side treated with NuStat® was on average less (14g/100cm2) than the side treated with our historic standard of care (15g/100cm2), but it was also not statistically significant (p=0.92). Average total blood loss from both excision and donor sites was also less with NuStat® (10g/100cm2) compared to the historic standard of care (12g/100cm2), but it was also not significant (p=0.77). There was no difference in the number of cycles required to achieve hemostasis for either the burn (1.15 NuStat® vs. 1.1 for historic standard of care, p=0.70) or the donor site (1 vs. 1, p=1.0). When comparing the cost of NuStat® versus the historic standard of care, the actual costs incurred for the wounds was less for the portion treated with NuStat® ($148.43) when compared to the historic standard of care ($186.45) (p<0.001). CONCLUSIONS: Based on these findings, NuStat® hemostatic action should be comparable to the historic standard of care, and these newer hemostatic agents evaluated further in burn surgery and bleeding during other procedures such as trauma surgery.

Cost-benefit analysis of outcomes from the use of fibrin sealant for fixation of skin grafts in small-size burns compared to staples as historical controls: a retrospective review.

INTRODUCTION: Historically, split-thickness skin grafts have been fixed onto the recipient site by suture and/or staples. Fibrin sealants have become available for the fixation in the past 10 years. Fibrin sealants have been shown to be at least as effective as staples, and recent reports show them to cause less pain. However, the product is much more expensive than traditional suture and/or staple fixation. The cost-benefit ratio of sealant has not yet been proven. METHODS: A review of charts for 202 consecutive patients was undertaken for patients with burns that were less than 10% total body surface area (TBSA) that underwent excision and grafting using fibrin sealant at the regional burn center. A historical control comprising 48 consecutive patients with burns that were less than 10% TBSA that underwent excision and grafting using staples as the only means of fixation was used for comparison. Demographics (such as age, weight, and sex), personal history of tobacco use, previous diagnosis of diabetes, type and depth of burn, TBSA, area of grafting, graft and donor locations, mesh type, rate of hematomas, rate of graft loss, rate of complete closure at 1 month, and time to discharge after surgery were recorded for each patient in both cohorts. The data were compared and statistical analysis performed for graft loss complications and number of days until the patient could be discharged home with outpatient wound care. RESULTS: Use of fibrin sealants has resulted in statistically significant lower rates of loss of graft at our institution. Additionally, a decrease in the number of days until discharge to outpatient wound care of nearly 2 days produced a lower cost of care in patients with less than 10% TBSA undergoing excision and grafting. CONCLUSIONS: The use of fibrin sealants allows for fewer graft loss complications and earlier discharge in patients who have burns that are less than 10% TBSA. This decrease in hospital days results in savings, although this difference is not statistically significant.

Contractile protein expression is upregulated by reactive oxygen species in aorta of Goto-Kakizaki rat.

Although it is known that blood vessels undergo remodeling in type 2 diabetes (T2D), the signaling pathways that underlie the structural and functional changes seen in diabetic arteries remain unclear. Our objective was to determine whether the remodeling in type 2 diabetic Goto-Kakizaki (GK) rats is evoked by elevated reactive oxygen species (ROS). Our results show that aortas from GK rats produced greater force (P < 0.05) in response to stimulation with KCl and U46619 than aortas from Wistar rats. Associated with these changes, aortic expression of contractile proteins (measured as an index of remodeling) and the microRNA (miR-145), which act to upregulate transcription of contractile protein genes, was twofold higher (P < 0.05) in GK than Wistar (age-matched control) rats, and there was a corresponding increase in ROS and decrease in nitric oxide signaling. Oral administration of the antioxidant Tempol (1 mmol/l) to Wistar and GK rats reduced (P < 0.05) myocardin and calponin expression. Tempol (1 mmol/l) decreased expression of miR-145 in Wistar and GK rat aorta. To elucidate the mechanism through which ROS increases miR-145, we measured their levels in freshly isolated aorta and cultured aortic smooth muscle cells incubated for 12 h in the presence of H2O2 (300 µmol/l). H2O2 increased expression of miR-145, and there were corresponding nuclear increases in myocardin, a miR-145 target protein. Intriguingly, H2O2-induced expression of miR-145 was decreased by U0126 (10 µmol/l), a MEK1/2 inhibitor, and myocardin was decreased by anti-miR-145 (50 nmol/l) and U0126 (10 µmol/l). Our novel findings demonstrate that ROS evokes vascular wall remodeling and dysfunction by enhancing expression of contractile proteins in T2D.

Low-impact trauma causing acute compartment syndrome of the lower extremities.

Compartment syndrome usually occurs in the muscles of an extremity as a consequence of trauma or reperfusion. However, it can also occur from minor injuries with resulting hematoma.We reviewed the charts of 5 individuals who presented to the emergency department after minimal or no known trauma and were ultimately diagnosed with acute compartment syndrome. None sustained fractures, and 2 had documented muscle tears. All patients were found to have hematomas in the affected compartment at the time of surgery. Low-impact trauma can cause acute compartment syndrome in the lower extremities. These cases could be the result of muscle hemorrhage and subsequent hematoma formation, rather than muscle swelling itself. Anticoagulation therapy can increase the risk of hemorrhage.

Observations on the microcirculation of the human burn wound using orthogonal polarization spectral imaging.

Orthogonal polarization spectral imaging (OPS) utilizes the illumination of the tissue with polarized light within the haemoglobin spectrum. We report here on OPS for the assessment of the skin microcirculation non-invasively through the surface of the human burn wound. This allows inspection of individual capillaries of the cutaneous microcirculation and flow through these vessels in real time. Two distinct microcirculatory patterns were seen. Superficial burns had small visible dermal capillaries studied throughout the field of view. The flow of individual erythrocytes through these capillaries was clearly visible in real-time. Conversely, deep burns showed large thrombosed vessel coursing in a criss-cross fashion. There was marked difference between the mean optical densities for normal skin and superficial burns (65.8+/-15.6 and 64+/-14.6, respectively) and deep burns (131.2+/-31.1). These findings indicate that OPS may have utility in the assessment of cutaneous microcirculation in burns.

Expression of human beta defensin 2 in thermal injury.

Sepsis is a common and serious complication of major burn injury and accounts for over 54% of deaths in burn patients. Burns are associated with high levels of circulating pro-inflammatory cytokines and immunosuppression, promoting systemic inflammatory response syndrome (SIRS) and sepsis, for which no effective treatment is currently available. Defensins, a family of cationic, naturally occurring, antimicrobial peptides are important components of the innate immune system, playing a major role in the body's defence by inhibiting activities of bacteria, fungi and enveloped viruses. These natural antimicrobials also chemoattract immature dendritic cells, some types of T and B-lymphocytes, neutrophils and macrophages, and act as an adjuvant, enhancing adaptive immunity. Our prior studies suggested a decreased expression of human beta defensin 2 (HBD2) in burn wounds. Here we have identified HBD2 protein in skin samples of partial and full thickness burns and in normal skin using fluorescence deconvolution microscopy. Images showed that in normal skin the majority of HBD2 is located in the Malpighian layer and, in smaller amounts, in the more superficial layers, a pattern that is absent in burned skin in which the epidermis is destroyed or damaged. However, surviving dermal and subcutaneous layers revealed the presence of HBD2 in a number of other cell types and structures, such as hair follicles and sweat gland acini, but not in vascular endothelium and fat cells. The results of these studies further contribute to an understanding of the role of antimicrobial peptides in the pathophysiology of burn injury, associated immunosuppression and sepsis and the possibility of using these other sites of HBD2 deposition for upregulation of antimicrobial synthesis in the treatment of burns.

Use of Joshi External Stabilizing System in postburn contractures of the hand and wrist: a 20-year experience.

Postburn contractures of the hand and wrist can range from a minor cosmetic problem to a crippling condition. The contractures, initially limited to the skin, extend to all the soft-tissue structures over time, often necessitating capsulotomies and tendon lengthening, although they still may not be amenable to total correction. The Joshi External Stabilizing System (JESS) is a versatile, lightweight external fixator consisting of K wires, distractors, and connecting rods (both hinged and nonhinged) along with various link joints. JESS is a dynamic system that allows the lengthening of the contracted tissues via slow distraction, causing minimal surgical insult. This is a retrospective review of 218 cases of postburn contractures of the hand treated with JESS during the last 20 years. Deformities varied from finger contractures to metacarpophalangeal joint and wrist contractures. All cases were of long duration at the time of presentation with the original injury being 4 months to 20 years old. All were assessed for the degree of function and deformity. The patients' activities of daily living were recorded and x-rays taken to evaluate joint configuration. The patients underwent a conservative surgical release followed by application of the appropriate JESS frame for the correction of the residual deformity. After 6 weeks, the frame was removed and hand therapy continued. An analysis is provided of the outcome. The technique produces functional hands with minimal surgical insult.

Effects of cytokines and heat shock on defensin levels of cultured keratinocytes.

Burns have been associated with high levels of circulating pro-inflammatory cytokines which promote systemic inflammatory response syndrome (SIRS), immunosuppression and sepsis for which no effective treatment is currently available. Defensins, a family of cationic naturally occurring antimicrobial peptides, are considered important components of the innate immune system and enhance adaptive immunity. This study examines the effects of pro-inflammatory cytokines, interleukin-1beta (IL-1beta), gamma-interferon (IFNgamma) and tumor necrosis factor-alpha (TNFalpha) on human beta-defensin-2 (HBD-2) levels in cultured keratinocytes. We also examined the effects of heat shock at 42 degrees C. The results demonstrate that only TNFalpha shows significant induction of HBD-2 but this induction was not sustained in the long-term. In addition, endogenous levels of defensin were significantly reduced by exposure to heat shock. The keratinocytes also responded to IL-1beta by becoming hypertrophic. These results indicate that stress-related, pro-inflammatory cytokines can induce keratinocytes to synthesize HBD-2, while heat shock appears to reduce its production. These experiments give us further insight into the role of natural antimicrobial peptides under conditions of stress.