Hypoglycemic episodes predict length of stay in patients with acute burns.

Hypoglycemic episodes are associated with worse hospital outcomes. All adult patients admitted to our burn center from 2015 to 2019 were retrospectively reviewed. Patient demographics and burn characteristics were recorded. The primary outcome was mortality, and secondary outcomes were total length-of-stay and intensive care unit length-of-stay. All patients experiencing at least one hypoglycemic episode were compared to patients who did not experience hypoglycemia. There were 914 patients with acute burns admitted during the study period, 33 of which (4%) experienced hypoglycemic episodes. Of these, 17 patients (52%) experienced a single hypoglycemic episode, while the remainder experienced multiple hypoglycemic episodes. Patients with one or more hypoglycemic events were matched to non-hypoglycemic controls using propensity matching. Patients that experienced hypoglycemia had significantly less TBSA involvement (5% vs. 13%,median, p < 0.0002), higher prevalence of diabetes (48% vs. 18%, p < 0.0001), higher mortality (18% vs. 7%, p = 0.01), longer total length-of-stay (22 vs. 8 days, median, p < 0.0001), and longer ICU length-of-stay (12 vs. 0 days, median, p < 0.0001). A single hypoglycemic episode was associated with prolonged total (IRR = 1.91, p < 0.0001) and ICU length-of-stay (IRR = 3.86, p < 0.0001). Hypoglycemia was not associated with higher mortality in the survival analysis (p = 0.46).

The Impact of Peer Support Group Programs on Psychosocial Outcomes for Burn Survivors and Caregivers: A Review of the Literature.

Peer support group programs are often recommended for burn survivors as a way to facilitate their psychosocial recovery and reintegration into the community. Such programs provide opportunities for burn patients and their caretakers to access emotional and informational support from healthcare providers and other survivors in inpatient or outpatient settings. Despite their popularity, however, there is little information currently available on the efficacy of these groups. In response, we reviewed the existing literature on peer support group programs and their impacts on psychosocial outcomes for burn survivors and their caregivers. A systematic review of the literature utilizing PubMed, PsycINFO, and Medline databases was conducted for articles published between 1990 and 2018. Twenty-five articles including inpatient, outpatient, integrative peer support groups, and burn camps met our inclusion criteria. All inpatient peer support group program articles (n = 4) reported associations with psychosocial improvements. Integrative peer support group program articles (n = 2) reported associations with social integration and reduction in post-traumatic stress and anxiety. All outpatient peer support group program articles (n = 8) demonstrated associations with psychosocial outcomes involving life satisfaction, acceptance of self, and reduced levels of isolation. Findings were less consistent for burn camps: eight articles suggested improvements in psychological outcomes while three articles reported no significant psychosocial effects. Although these results are encouraging, further study is indicated both to replicate these findings, and to determine the optimal implementation of inpatient and outpatient peer support programs.

Venous Thromboembolism Chemoprophylaxis in Burn Patients: A Literature Review and Single-Institution Experience.

Hospitalized burn patients meet the criteria for Virchow's triad (endothelial damage, hypercoagulability, and stasis), predisposing them to venous thromboembolism (VTE). Although the disease burden of VTE suggests a need for prevention in this population, unreliable reported VTE rates, costly and complicated prophylaxis regimens, and chemoprophylaxis risks have prevented the establishment of a universal protocol. This paper reviews thromboprophylaxis practices both in the literature and at our own institution. A systematic review was conducted according to PRISMA guidelines identifying studies pertaining to VTE chemoprophylaxis in burn patients. Additionally, medical records of patients admitted to an American Burn Association-verified burn center between June 2015 and June 2019 were retrospectively reviewed for demographics, chemoprophylaxis, and presence of VTE defined as either deep vein thrombosis (DVT) or pulmonary embolism (PE). Thirty-eight studies met inclusion criteria. In the 12 studies that reported VTE incidence, rates ranged widely from 0.25% to 47.1%. The two largest retrospective studies (n = 33,637 and 36,638) reported a VTE incidence of 0.61% and 0.8% in populations with unknown or inconsistently recorded chemoprophylaxis. Throughout the literature, prevention protocols were mixed, though a trend toward using dose-adjusted subcutaneous low molecular weight heparin based on serum anti-factor Xa level was noted. At our burn center, 1,068 patients met study criteria. At-risk patients received a simple chemoprophylaxis regimen of 5000U of subcutaneous unfractionated heparin every 8 hours. No routine monitoring tests were performed to limit cost. Nine cases of DVT and two cases of PE were identified with an incidence of 0.84% and 0.19%, respectively, and a total VTE incidence of 1.03%. Only one patient developed heparin-induced thrombocytopenia (HIT). No cases of other heparin-associated complications were observed. VTE incidence rates reported in the literature are wide-ranging and poorly capture the effect of any one chemoprophylaxis regimen in the burn population. Our center uses a single, safe, and cost-effective protocol effecting a low VTE rate comparable to that of large national retrospective studies.

The Impact of No Next of Kin Decision Makers on End-of-Life Care.

For critically ill burn patients without a next of kin, the medical team is tasked with becoming the surrogate decision maker. This poses ethical and legal challenges for burn providers. Despite this frequent problem, there has been no investigation of how the presence of a next of kin affects treatment in burn patients. To evaluate this relationship, a retrospective chart review was performed on a cohort of patients who died during the acute phase of their burn care. Variables collected included age, gender, length of stay, total body surface area, course of treatment, and presence of a next of kin. In total, 67 patients met the inclusion criteria. Of these patients, 14 (21%) did not have a next of kin involved in medical decisions. Patients without a next of kin were significantly younger (P = .02), more likely to be homeless (P < .01), had higher total body surface area burns (P = .008), had shorter length of stay (P < .001), and were five times less likely to receive comfort care (P = .01). Differences in gender and ethnicity were not statistically significant. We report that patients without a next of kin present to participate in medical decisions are transitioned to comfort care less often despite having a higher burden of injury. This disparity in standard of care demonstrates a need for a cultural shift in burn care to prevent the suffering of these marginalized patients. Burn providers should be empowered to reduce suffering when no decision maker is present.

Small Pediatric Burns Can Be Safely Managed on an Outpatient Basis.

American Burn Association (ABA) guidelines recommend that all pediatric burns be transferred to a burn center if their presenting hospital lacks the necessary personnel or equipment for their care. Our institution often treats small burns (<10% TBSA) in pediatric patients in an ambulatory setting with a nondaily dressing. The aim of this study was to determine whether small pediatric burns could be safely managed on an outpatient basis. A retrospective review at a single ABA-verified burn center was conducted, including 742 pediatric patients presenting to the burn evaluation clinic in a 3-year period. Postburn day, age, sex, TBSA, burn etiology, body area burned, burn dressing type, outpatient versus inpatient management, reason(s) for admission, and any operative intervention were collected. Overall, the most common burn etiologies were scald (68%), contact (20%), and flame (5%). In this cohort, 14% (101) of patients were admitted on evaluation to the burn center with a mean TBSA of 9%. The remaining 86% (641) of patients were treated outpatient with a mean TBSA of 3%. Of those who were treated outpatient, 96% (613) successfully completed outpatient care and 4% (28) were subsequently admitted. The patients who were successfully managed in an ambulatory setting had a mean TBSA of 3%, whereas the patients who failed outpatient care had a mean TBSA of 4%. The primary reason for the subsequent admission of these patients was nutrition optimization (61%). The vast majority of small pediatric burns can be effectively treated on an outpatient basis with a nondaily dressing.

The Homelessness Crisis and Burn Injuries: A Cohort Study.

The United States is facing a growing homelessness crisis. We characterize the demographics and outcomes of homeless patients who sustain burn injury and compare them to a cohort of domiciled patients. A retrospective cohort study was performed at the Los Angeles County + University of Southern California Regional Burn Center for consecutive acute burn admissions in adults from June 1, 2015, to December 31, 2018. Patients were categorized as either domiciled or homeless at the time of their injury. Prevalence rates were estimated using data from the regional homeless count. From 881 admissions, 751 (85%) had stable housing and 130 (15%) were homeless. The rate of burn injury requiring hospitalization for homeless adults was estimated at 88 per 100,000 persons. Homeless patients had a significantly larger median burn size (7 vs 5%, P < .05) and a greater rate of flame burns (68 vs 42%, P < .001). For the homeless, rates of assault and self-inflicted injury were 4- (18 vs 4%, P < .001) and 2-fold higher (9 vs 4%, P < .001), respectively. Homeless patients had higher rates of mental illness (32 vs 12%, P < .001) and substance abuse (88 vs 22%, P < .001), and were less likely to follow-up as outpatients (54 vs 87%, P < .001). There was no difference in mortality. Homeless patients had a longer median length of stay (LOS; 11 vs 7 days, P < .001) without significant differences in LOS per percentage TBSA. Homeless individuals should be considered a high-risk population for burn injury. This distinction serves as a call to action for the development of burn prevention strategies.

Stimulant Abuse in Burn Patients Is Associated With an Increased Use of Hospital Resources.

Stimulant (cocaine, methamphetamine, and amphetamine) abuse compromises the peripheral vasculature through endothelial injury. In combination with the physiologic derangements seen in burn injuries, patients abusing stimulants may have additional impairments in wound healing. A retrospective review from July 1, 2015 to July 1, 2018 was performed at an American Burn Association-verified burn center. Patients with positive urine toxicology results for stimulants (ST(+)), and those without (ST(-)), who sustained burn injuries were identified and matched by age and TBSA. The primary outcome was mortality, and secondary outcomes included total length of stay (LOS), and need-for-surgery (grafting). In total, 130 patients ST(+) and 133 ST(-) patients were identified. There were no significant differences in age (40.9 ± 13.5 vs 39.2 ± 23.7 years, P = 0.46), Inhalation Injury (12.3 vs 9.0%, P = 0.39), or nutritional status (prealbumin: 17.3 ± 6.1 vs 17.1 ± 12.7 mg/dl, P = 0.66; albumin: 3.5 ± 0.6 vs 3.6 ± 0.7 g/dl, P = 0.45). There were no differences in mortality (6.1 vs 4.5%, P = 0.55), intensive care unit LOS (9.3 ± 16.5 vs 10.2 ± 20.9 days, P = 0.81), wound infections (15.4 vs 23.9%, P = 0.07), or wound conversion (6.9 vs 3.0%, P = 0.14). ST(+) patients had a significantly longer LOS (15.0 ± 16.9 vs 10.7 ± 17.3 days, P = 0.04), greater tobacco use (56.9 vs 18.0%, P = 0.00001), and greater need for grafting (54.6 vs 33.1%, P = 0.0004). ST(+) patients require more hospital resources-surgical operations and hospital days-than ST(-) patients. The increased need for surgical intervention may partially explain the increase in hospital days, in addition to the observation that ST(+) patients had more complex disposition issues than ST(-) patients.

The State of Burn Care Training During Plastic Surgery Residency.

INTRODUCTION: There is an ongoing shortage of burn specialists, and workforce reports suggest possible hurdles attracting plastic surgeons into burn care. The purpose of this study was to (1) determine the state of burn care in plastic surgery residency and (2) identify what barriers might exist for plastic surgeons pursuing a practice that involves burn care. METHODS: Surveys were distributed to North American plastic surgery program directors and residents, respectively, during the 2018-2019 academic year. RESULTS: Fifty-eight program directors (response, 54%) and 320 plastic surgery residents (response, 30%) participated. Burn care was felt to be an important component in training by most program directors (USA, 88%; Canada, 100%) and residents (USA, 87%; Canada, 99%). The majority of program directors included a burn unit rotation (USA, 88%; Canada, 90%). Rotations for integrated residents averaged 2.5 months and most commonly occurred during second year; independent residents spent 1.2 months on rotation, usually in first year. Three-quarters of American residents were interested in a career that involves burn care in some capacity, primarily burn reconstruction (40%). Factors that would discourage a trainee from practicing burn care in the future included the nature of burn care (60%) and burn operations (45%), the on-call commitment (39%), and a narrow scope of practice (38%). DISCUSSION: This study challenges the belief that plastic surgery trainees are disinterested in burn care. Burn surgery remains an important component of training programs, and we propose several steps to encourage greater interest and participation in the burn surgery workforce.

Combination therapy: Etanercept and intravenous immunoglobulin for the acute treatment of Stevens-Johnson syndrome/toxic epidermal necrolysis.

BACKGROUND: Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) is an autoimmune condition with significant morbidity and mortality. METHODS: A retrospective review was performed at a single institution. All patients admitted to the LAC+USC burn unit from May 1st 2015-January 1st 2018 with a histologic diagnosis of SJS/TEN were reviewed. Patient characteristics and outcomes were recorded. These outcomes were compared to our previously published cohort. RESULTS: Thirteen total consecutive SJS/TEN patients were treated with etanercept. Compared to non-etanercept treated patients, etanercept-treated patients did not experience a significant difference in mortality (15.4% vs. 10%, P=0.58), ICU days (6.9 vs. 15.1, P=0.08), length-of-stay (9.8 vs 16.4, P=0.11), or infections (38.5% vs. 57.5%, P=0.58). The standardized mortality ratio in etanercept-treated patients was 0.44 (95% CI, 0.21, 0.65). In general, etanercept-treated patients had higher SCORTENs (3 vs. 2, P=0.03) and longer delays to presentation (5.2 vs. 2.7 days, P<0.01). CONCLUSIONS: Etanercept can be considered in the treatment of SJS/TEN patients in addition to IVIg, and supportive care in a burn unit.

Donor-site preferences in women during autologous skin grafting.

BACKGROUND: Autologous split-thickness skin grafting has been proven to provide the best cosmetic and functional outcome after cutaneous burn injuries and thus is the standard of care. Clinical observations have shown that female burn patients frequently have greater difficulty choosing a donor site than do male burn patients. However, there is a lack of data characterizing donor-site preferences among women with burns. METHODS: The purpose of this study was to examine donor-site preferences among women using an online survey that included 356 responders between January 4, 2012, and April 4, 2012. RESULTS: This study found that there was a preference for posterior donor sites, with lower back, left buttock, and left posterior thigh being the most preferred sites. The least preferred locations were the right anterior upper arm, any aspect of the forearms, and the chest. Those surveyed and reporting a higher education level or concerns with scarring were least likely to choose anterior locations. Age, concern for color changes, and prior surgery or grafting had no statistically significant effect on donor-site preference. CONCLUSION: Given these strong preferences among female patients, posterior donor sites should be considered and discussed as compared with the current standard of using lateral or anterior thigh donor sites.

Cost-effectiveness comparison between topical silver sulfadiazine and enclosed silver dressing for partial-thickness burn treatment.

The standard treatment of partial-thickness burns includes topical silver products such as silver sulfadiazine (SSD) cream and enclosed dressings including silver-impregnated foam (Mepilex Ag; Molnlycke Health Care, Gothenburg, Sweden) and silver-laden sheets (Aquacel Ag; ConvaTec, Skillman, NJ). The current state of health care is limited by resources, with an emphasis on evidence-based outcomes and cost-effective treatments. This study includes a decision analysis with an incremental cost-utility ratio comparing enclosed silver dressings with SSD in partial-thickness burn patients with TBSA less than 20%. A comprehensive literature review was conducted to identify clinically relevant health states in partial-thickness burn patients. These health states include successful healing, infection, and noninfected delayed healing requiring either surgery or conservative management. The probabilities of these health states were combined with Medicare CPT reimbursement codes (cost) and patient-derived utilities to fit into the decision model. Utilities were obtained using a visual analog scale during patient interviews. Expected cost and quality-adjusted life years (QALYs) were calculated using the roll-back method. The incremental cost-utility ratio for enclosed silver dressing relative to SSD was $40,167.99/QALY. One-way sensitivity analysis of complication rates confirmed robustness of the model. Assuming a maximum willingness to pay $50,000/QALY, the complication rate for SSD must be 22% or higher for enclosed silver dressing to be cost effective. By varying complication rates for SSD and enclosed silver dressings, the two-way sensitivity analysis demonstrated the cost effectiveness of using enclosed silver dressing at the majority of complication rates for both treatment modalities. Enclosed silver dressings are a cost-effective means of treating partial thickness burns.

High frequency percussive ventilation and low FiO(2).

BACKGROUND: High-frequency percussive ventilation (HFPV) is an effective rescue therapy in ventilated patients with acute lung injury. High levels of inspired oxygen (FiO(2)) are toxic to the lungs. The objective of this study was to review a low FiO(2) (0.25)/HFPV protocol as a protective strategy in burn patients receiving mechanical ventilation greater than 10 days. METHODS: A single-center, retrospective study in burn patients between December 2002 and May 2005 at the LAC+USC Burn Center. Demographic and physiologic data were recorded from time of admission to extubation, 4 weeks, or death. RESULTS: 32 subjects were included in this study, 1 patient failed the protocol. 23 of 32 (72%) patients were men and mean age was 46±15 years. Average TBSA burn was 30±20 with 9 of 32 (28%) having >40% TBSA involved. Average burn index was 76±21. 22 of 32 (69%) had inhalation injury and 23 of 32 (72%) had significant comorbidities. Average ventilator parameters included ventilator days 24±12, FiO(2) 0.28±0.03, PaO(2) 107±15 Torr, PaCO(2) 42±4 Torr, and PaO(2)/FiO(2) ratio 395±69. 16 of 32 (50%) patients developed pneumonia and 9 of 32 (28%) died. No patient developed ARDS, barotrauma, or died from respiratory failure. There was no association between inhalation injury and mortality in this group of patients. CONCLUSION: A low FiO(2)/HFPV protocol is a safe and effective way to ventilate critically ill burn patients. Reducing the oxidative stress of high inspired oxygen levels may improve outcome.

Epithelial to mesenchymal transition in human skin wound healing is induced by tumor necrosis factor-alpha through bone morphogenic protein-2.

Epithelial-mesenchymal transition (EMT), characterized by loss of epithelial adhesion and gain of mesenchymal features, is an important mechanism to empower epithelial cells into the motility that occurs during embryonic development and recurs in cancer and fibrosis. Whether and how EMT occurs in wound healing and fibrosis in human skin remains unknown. In this study we found that migrating epithelial cells in wound margins and deep epithelial ridges had gained mesenchymal features such as vimentin and FSP1 expression. In hypertrophic scars, EMT-related genes were elevated along with inflammatory cytokines, indicating a causal relationship. To reconstitute EMT in vitro, normal human skin and primary keratinocytes were exposed to cytokines such as tumor necrosis factor-alpha (TNF-alpha), resulting in expression of vimentin, FSP1, and matrix metalloproteinases. Moreover, TNF-alpha-induced EMT was impaired by antagonists against bone morphogen proteins (BMP) 2/4, suggesting that BMP mediates the TNF-alpha-induced EMT in human skin. Indeed, TNF-alpha could induce BMP-2 and its receptor (BMPR1A) in human skin and primary keratinocytes, and BMP2 could induce EMT features in skin explants and primary keratinocytes. In summary, we uncovered EMT features in both acute and fibrotic cutaneous wound healing of human skin. Moreover, we propose that the mesenchymal induction in wound healing is motivated by TNF-alpha, in part, through induction of BMP.

Matrix metalloproteinase-9 delays wound healing in a murine wound model.

BACKGROUND: Metalloproteinase-9 (MMP-9) is a type IV collagenase found at elevated levels in chronic wounds. As wounds heal, MMP-9 diminishes. In this study, we investigated whether MMP-9 directly contributes to chronic wound pathogenesis. METHODS: Recombinant proMMP-9 was prepared using immortalized keratinocytes transduced by a lentivirus. ProMMP-9 was purified from cell culture media and activated using 4-aminophenylmercuric acetate. Active MMP-9 was then suspended in xanthan gum to a concentration paralleling that found in human chronic wounds. Two parallel 6-mm punch biopsies were made on the backs of C57BL mice. Wounds were treated daily with MMP-9 or vehicle. Wound areas were measured and tissues examined by densitometry, real-time RT-PCR, histology, and immunohistochemistry at days 7, 10, and 12. RESULTS: Exogenous MMP-9, at the level found within chronic wounds, delayed wound healing in this animal model. By 7 days, wounds in the MMP-9-injected group were 12% larger than control wounds (P = .008). By day 12, wounds in the MMP-9-injected group were 25% larger than those of the control group (P = .03). Histologic examination shows that high levels of active MMP-9-impaired epithelial migrating tongues (P = .0008). Moreover, consistent with elevated MMP-9, the collagen IV in the leading edge of the epithelial tongue was diminished. CONCLUSION: MMP-9 appears to directly delay wound healing. Our data suggests that this may occur through interference with re-epithelialization. We propose that MMP-9 interferes with the basement membrane protein structure, which in turn impedes keratinocyte migration, attachment, and the reestablishment of the epidermis.

Alpha1-antichymotrypsin activity correlates with and may modulate matrix metalloproteinase-9 in human acute wounds.

Matrix metalloproteinase-9 (MMP-9) plays a central role in many physiologic processes including acute and the chronic wounds. MMP-9 is not routinely expressed in healthy tissues but is promptly expressed as a proenzyme and converted into active enzyme after tissue injury. The mechanisms involved, including the activators and inhibitors for this enzyme in human tissue remain largely obscure. We recently identified alpha1-antichymotrypsin (alpha1-ACT), an acute phase factor, as a potent inhibitor controlling activation of pro-MMP-9 by human skin. The aim of this study is to establish the clinical relevance of the inhibitor in cutaneous wound healing. Fluids from acute burn blisters and conditioned media from skin explants of burn patients were analyzed. We observed that the presence pro-MMP-9 and its activation correlated with the proximity to and degree of injury. Early after trauma, massive levels of wound alpha1-ACT were associated with an absence of pro-MMP-9 activation. Conversely, the active MMP-9 occurs simultaneously with inactivation of alpha1-ACT. Our results suggest a role for alpha1-ACT as a physiologic inhibitor of MMP-9 activation in human wound healing.

Acute burns.

LEARNING OBJECTIVES: After studying this article, the participant should be able to: 1. Describe the pathophysiology of burn injury. 2. Identify patient criteria for transfer to a burn center. 3. Calculate burn size and resuscitation requirements. 4. Treat inhalation injury in the acute setting. 5. Describe treatment options for burn injuries. 6. Describe preoperative selection, intraoperative procedures, and postoperative protocols for patients who require surgical care for their burn injuries. 7. Understand the survival and functional outcomes of burn injury. SUMMARY: The review article summarizes basic issues in the treatment of acute burn injury as practiced in 2008. The pathophysiology, treatment options, and expected outcomes for an acute burn are described and discussed. Special attention is directed to the nonoperative and surgical management of small to moderate-size burns that might be treated by the practicing plastic surgeon.

Proteolytic activation of matrix metalloproteinase-9 in skin wound healing is inhibited by alpha-1-antichymotrypsin.

An excessive amount of matrix metalloproteinase-9 (MMP-9) has been well documented in inflammatory diseases, including chronic wounds and cancers. Secreted as a zymogen, proMMP-9 can be irreversibly converted to a mature form through cleavage of the N-terminal propeptide domain. Although the converting enzyme for proMMP-9 in human tissues is unknown, we previously found that tumor necrosis factor-alpha (TNF-alpha) promotes activation of proMMP-9 in human skin, and characterized the converting activities as tissue-associated chymotrypsin-like proteinases. On the other hand, the pathophysiologic inhibitor to prevent proMMP-9 maturation also remains elusive. In this regard, we observed the presence of the inhibitory property in burn blister fluid that abrogates the skin extract-mediated activation of proMMP-9. Then we determined that alpha-1-antichymotrypsin (alpha-ACT), an acute-phase factor abundantly present in the blister, effectively inhibited proMMP-9 activation in human and rodent skin. In contrast, the aminophenylmercuric acetate-induced "cysteine switch" and activation of proMMP-9 were not affected by alpha-ACT. TNF-alpha-induced activation of proMMP-9 by the explants of human skin was inhibited by alpha-ACT but not by related alpha-1-antitrypsin. alpha-ACT specifically attenuated maturation of proMMP-9 but not proMMP-2 or proMMP-13. Furthermore, short peptides that mimic the reactive center loop (RCL) of alpha-ACT were sufficient to inhibit the conversion. Mutation analysis demonstrated that a conserved leucine within the RCL was critical for alpha-ACT-exerted inhibition. In chronic wounds, a large amount of mature MMP-9 was associated with fragmentation and inactivation of alpha-ACT. Taken together, these results demonstrate that, to the best of our knowledge, alpha-ACT is a previously unreported pathophysiologic inhibitor that controls proMMP-9 activation in skin tissue.