Michael J. Mosier

Early acute kidney injury predicts progressive renal dysfunction and higher mortality in severely burned adults

The incidence and prognosis of acute kidney injury (AKI) developing during acute resuscitation have not been well characterized in burn patients. The recently developed Risk, Injury, Failure, Loss, and End-stage (RIFLE) classification provides a stringent stratification of AKI severity and can allow for the study of AKI after burn injury. We hypothesized that AKI frequently develops early during resuscitation and is associated with poor outcomes in severely burned patients. We conducted a retrospective review of patients enrolled in the prospective observational multicenter study “Inflammation and the Host Response to Injury.” A RIFLE score was calculated for all patients at 24 hours and throughout hospitalization. Univariate and multivariate analyses were performed to distinguish the impact of early AKI on progressive renal dysfunction, need for renal replacement therapy, and hospital mortality. A total of 221 adult burn patients were included, with a mean TBSA burn of 42%. Crystalloid resuscitation averaged 5.2 ml/kg/%TBSA, with urine output of 1.0 ± 0.6 ml/kg/hr at 24 hours. Sixty-two patients met criteria for AKI at 24 hours: 23 patients (10%) classified as risk, 32 patients (15%) as injury, and 7 (3%) as failure. After adjusting for age, TBSA, inhalation injury, and nonrenal Acute Physiology and Chronic Health Evaluation II ≥20, early AKI was associated with an adjusted odds ratio 2.9 for death (95% CI 1.1-7.5, P = .03). In this cohort of severely burned patients, 28% of patients developed AKI during acute resuscitation. AKI was not always transient, with 29% developing progressive renal deterioration by RIFLE criteria. Early AKI was associated with early multiple organ dysfunction and higher mortality risk. Better understanding of how early AKI develops and which patients are at risk for progressive renal dysfunction may lead to improved outcomes.

Early Enteral Nutrition in Burns: Compliance With Guidelines and Associated Outcomes in a Multicenter Study

Early nutritional support is an essential component of burn care to prevent ileus, stress ulceration, and the effects of hypermetabolism. The American Burn Association practice guidelines state that enteral feedings should be initiated as soon as practical. The authors sought to evaluate compliance with early enteral nutrition (EN) guidelines, associated complications, and hospitalization outcomes in a prospective multicenter observational study. They conducted a retrospective review of mechanically ventilated burn patients enrolled in the prospective observational multicenter study “Inflammation and the Host Response to Injury.” Timing of initiation of tube feedings was recorded, with early EN defined as being started within 24 hours of admission. Univariate and multivariate analyses were performed to distinguish barriers to initiation of EN and the impact of early feeding on development of multiple organ dysfunction syndrome, infectious complications, days on mechanical ventilation, intensive care unit (ICU) length of stay, and survival. A total of 153 patients met study inclusion criteria. The cohort comprised 73% men, with a mean age of 41 ± 15 years and a mean %TBSA burn of 46 ± 18%. One hundred twenty-three patients (80%) began EN in the first 24 hours and 145 (95%) by 48 hours. Age, sex, inhalation injury, and full-thickness burn size were similar between those fed by 24 hours vs after 24 hours, except for higher mean Acute Physiology and Chronic Health Evaluation II scores (26 vs 23, P = .03) and smaller total burn size (44 vs 54% TBSA burn, P = .01) in those fed early. There was no significant difference in rates of hyperglycemia, abdominal compartment syndrome, or gastrointestinal bleeding between groups. Patients fed early had shorter ICU length of stay (adjusted hazard ratio 0.57, P = 0.03, 95% confidence interval 0.35–0.94) and reduced wound infection risk (adjusted odds ratio 0.28, P = 0.01, 95% confidence interval 0.10–0.76). The investigators have found early EN to be safe, with no increase in complications and a lower rate of wound infections and shorter ICU length of stay. Across institutions, there has been high compliance with early EN as part of the standard operating procedure in this prospective multicenter observational trial. The investigators advocate that initiation of EN by 24 hours be used as a formal recommendation in nutrition guidelines for severe burns, and that nutrition guidelines be actively disseminated to individual burn centers to permit a change in practice.

Predictive value of bronchoscopy in assessing the severity of inhalation injury.

Inhalation injury is associated with severe pulmonary complications as inhaled products of combustion cause lung inflammation and loss of natural defenses. A bronchoscopic grading for inhalation injury has been proposed but has not yet been validated in burn patients. In this study, the authors evaluated whether bronchoscopic grading of injury clinically correlated with indices of gas exchange over the first 72 hours or predicted differences in hospitalization outcomes. They conducted a single-center retrospective review of all mechanically ventilated adults with suspected inhalation injury and thermal injury over an 18-month period. All recorded bronchoscopy examinations were reviewed and categorized injury according to the published abbreviated injury score (AIS 0: no injury, 1: mild, 2: moderate, 3: severe, and 4: massive injury). They also compared changes in oxygenation, airway pressures, chest radiograph findings, fluid administration, and early development of pneumonia and organ failure, by severity of inhalation injury according to the AIS. Thirty-two adult patients met inclusion criteria over the study period. This cohort was 69% male with a mean age of 44.5 ± 14 years and a mean % TBSA burn of 33.9 ± 17%. Of these 32 patients, 11 patients (34%) were classified as grade 0, 9 patients (28%) were classified as grade 1, 7 patients (22%) were classified as grade 2, and 5 patients (16%) were classified as grade 3. Measured carboxyhemoglobin levels increased significantly with higher AIS grade. Oxygenation indices were worse as grade worsened by 24, 48, and 72 hours. The incidence of acute respiratory distress syndrome increased by grade of injury: 0, 22, 57, and 80%, respectively, at 24 hours (P < .01), and remained statistically different at 48 and 72 hours. After adjustment for age, % TBSA burn, and full-thickness component, severe inhalation injury (grades 2 and 3) was associated with an increased risk of acute respiratory distress syndrome at 24 and 72 hours, as well as ventilator days >21 days, and a trend toward multiple organ dysfunction syndrome and mortality. Better understanding of the relationship between inhalation injury and lung physiologic sequelae is a burn research priority. The bronchoscopic grading of inhalation injury moderately correlates with early indices of impaired gas exchange in this cohort and may be a promising tool for staging lower airway injury. Prospective studies should definitively answer whether AIS bronchoscopy staging predicts hospitalization outcomes in inhalation injury.

Inhalation injury severity and systemic immune perturbations in burned adults.

Objective:We aimed to determine whether the severity of inhalation injury evokes an immune response measurable at the systemic level and to further characterize the balance of systemic pro- and anti-inflammation early after burn and inhalation injury. Background:Previously, we reported that the pulmonary inflammatory response is enhanced with worse grades of inhalation injury and that those who die of injuries have a blunted pulmonary immune profile compared with survivors. Methods:From August 2007 to June 2011, bronchoscopy was performed on 80 patients admitted to the burn intensive care unit when smoke inhalation was suspected. Of these, inhalation injury was graded into 1 of 5 categories (0, 1, 2, 3, and 4), with grade 0 being the absence of visible injury and grade 4 corresponding to massive injury. Plasma was collected at the time of bronchoscopy and analyzed for 28 immunomodulating proteins via multiplex bead array or enzyme-linked immunosorbent assay. Results:The concentrations of several plasma immune mediators were increased with worse inhalation injury severity, even after adjusting for age and % total body surface area (TBSA) burn. These included interleukin (IL)-1RA (P = 0.002), IL-6 (P = 0.002), IL-8 (P = 0.026), granulocyte colony-stimulating factor (P = 0.002), and monocyte chemotactic protein 1 (P = 0.007). Differences in plasma immune mediator concentrations in surviving and deceased patients were also identified. Briefly, plasma concentrations of IL-1RA, IL-6, IL-8, IL-15, eotaxin, and monocyte chemotactic protein 1 were higher in deceased patients than in survivors (P < 0.05 for all), whereas IL-4 and IL-7 were lower (P < 0.05). After adjusting for the effects of age, % TBSA burn, and inhalation injury grade, plasma IL-1RA remained significantly associated with mortality (odds ratio, 3.12; 95% confidence interval, 1.03–9.44). Plasma IL-1RA also correlated with % TBSA burn, inhalation injury grade, fluid resuscitation, Baux score, revised Baux score, Denver score, and the Sequential Organ Failure Assessment score. Conclusions:The severity of smoke inhalation injury has systemically reaching effects, which argue in favor of treating inhalation injury in a graded manner. In addition, several plasma immune mediators measured early after injury were associated with mortality. Of these, IL-1RA seemed to have the strongest correlation with injury severity and outcomes measures, which may explain the blunted pulmonary immune response we previously found in nonsurvivors.

Synopsis of the 2013 annual report of the national burn repository.

Most burn centers maintain some record or registry of the patients they treat. These registries typically include information on the clinical characteristics of the patients and their injuries, the care and treatment they received, and the clinical outcome. These records document the burn center’s work and experience. They can be used to estimate the resources—supplies, personnel, space—required to provide care. They can be reviewed by the clinicians working there to discern imperfections in their systems of providing care and to identify opportunities to improve the structure, processes, and outcomes of those systems. They may also, in part, describe the characteristics of burn injury in the community served by the burn center. More than 40 years ago, burn clinicians envisioned the creation of a larger database of burn-injured patients. Such a database would be composed of data from several individual facility registries. It could provide a much broader view of burn injury and burn care in a larger geopolitical region than a single community. It could serve as the basis for burn research, burn prevention, public health, health planning, and advocacy at a regional, state, and even national level. This database then would benefit victims of burn injury, providers of burn care, state and national policy makers, and the public. Such a database was started at the University of Michigan in the early 1970s. It included a handful of burn centers. Over the years, that database was transferred to other entities, and in 2001, the American Burn Association (ABA) assumed responsibility for it, almost three decades after it was begun. By then, it had become national in scope and was known as the National Burn Repository (NBR). An NBR Committee was formed by the ABA, and it began preparing annual summaries of the database in 2006. These reports summarized cases treated by contributing centers during a 10-year period. They were made available not only to members of the ABA but also to the public. Two of these reports were summarized for publication in this Journal,1,2 the most recent of which was a summary of the 2007 annual report published in 2008. As the result of efforts of both the NBR Committee and the Burn Registry Committee of the ABA to improve the quality of the data in the NBR in the intervening years, the annual NBR report prepared in 2013 was based on data that were of a much higher quality than those that existed before. The purpose of this current article is to summarize and review highlights from that 2013 NBR Report.

Microbial contamination in burn patients undergoing urgent intubation as part of their early airway management.

Inhalation injuries occur in approximately one third of all major burns and account for a significant number of deaths in burn patients each year. Previous studies have examined ventilator-associated pneumonia in patients with inhalation injury, but no study to date has evaluated the incidence of bacterial contamination of the airways on admission in patients with inhalation injuries. Because pulmonary complications have been found to cause or directly contribute to mortality in as high as 77% of patients, with combined inhalation injury and thermal injury, early detection of community-acquired pneumonia may significantly alter treatment outcomes. The authors conducted a retrospective review of all burn patients with early intubation and inhalation injury admitted between January 1, 2004 and December 31, 2006 who underwent bronchoscopy with bronchoalveolar lavage (BAL) within 24 hours of admission. Seventy-four consecutive patients fulfilled the inclusion criteria. Age, sex, percentage of total body surface area (%TBSA), presence of alcohol, site of intubation, grade of injury, and BAL results were examined. Analysis revealed a patient population that was 67.6% male, with a 42.0 ± 17.1-year-old mean age, 27.0 ± 24.7 %TBSA average burn, 1.6 ± 1.2 inhalation grade, 17.8 ± 24.4 ventilator days requirement, 27.3 ± 31.4 days of length of stay, and 21.6% mortality. BAL results were grouped into four categories: 1) No growth, 2) Normal flora, 3) <100,000 colony-forming units (cfu), and 4) >100,000 cfu. By this criteria, 13 patients (17.6%) had no growth, 22 (29.7%) had normal flora, 27 (36.5%) had <100,000 cfu, and 12 (16.2%) had >100,000 cfu on the initial BAL. Therefore, 53% grew pathogenic organisms and 16% had >100,000 cfu on BAL with initial bronchoscopy. The predominant organisms were gram-positive cocci, with Streptococcus viridans found in 15 patients (20%), Staphylococcus aureus in eight (11%), and Streptococcus pneumonia in four (6%). Analysis of the patients with the highest bacterial loads revealed that they were 75% female and had a trend toward an increased ventilator requirement and longer length of stay. Patients with combined thermal and inhalation injury requiring urgent intubation have a high incidence of bacterial bronchial contamination. Inhalation injury creates a damaged tracheobronchial mucosa and early intubation provides a portal for bacterial contamination. Further studies with a larger patient population and randomization to treatment and nontreatment of the BAL culture results may show statistically significant differences in ventilator days, length of stay, and mortality.

A 15-Year Review of Pediatric Toxic Epidermal Necrolysis

Owing to the rare, yet serious nature of toxic epidermal necrolysis (TEN) and Stevens–Johnson syndrome (SJS), the authors would like to describe our experience with 41 pediatric patients to contribute to the current clinical understanding of the disease. From records at a single institution, 41 patients ⩽18 years of age with a diagnosis of SJS or TEN were retrospectively identified. Data were obtained from the hospital’s medical record, and a variety of variables were collected, including causative agent, percentage of total body surface area (%TBSA) slough, ocular involvement, medical treatment, operative procedures, time to wound closure, ventilator days, intensive care unit length of stay, and associated hospital mortality. Of the pediatric TEN patients included, the mean epidermal sloughing was 39.7 ± 26% TBSA. The presumptive inciting agent was a medication in 90% of cases. Mycoplasma pneumoniae was implicated in two cases (5%). The average time between onset of symptoms and burn intensive care unit admission was 3.6 ± 2.0 days. Acutely, 73% of patients exhibited ocular involvement, 90% needed supplemental enteral nutritional support, and 51% required mechanical ventilation. On average, subjects spent 19.9 ± 13.9 days in the intensive care unit. While acute mortality was 0%, 100% of patients still experienced long-term complications and 30% required follow-up procedures. When compared to current literature, the outcomes of our patients were similar to that of pediatric TEN at other institutions. While acute mortality is typically better within the pediatric population, patients still experience a significant level of morbidity and have serious long-term sequelae.

Predicting acute kidney injury among burn patients in the 21st century: a classification and regression tree analysis.

Historically, acute kidney injury (AKI) carried a deadly prognosis in the burn population. The aim of this study is to provide a modern description of AKI in the burn population and to develop a prediction tool for identifying patients at risk for late AKI. A large multi-institutional database, the Glue Grants Trauma-Related Database, was used to characterize AKI in a cohort of critically ill burn patients. The authors defined AKI according to the RIFLE criteria and categorized AKI as early, late, or progressive. They then used Classification and Regression Tree (CART) analysis to create a decision tree with data obtained from the first 48 hours of admission to predict which subset of patients would develop late AKI. The accuracy of this decision tree was tested in a separate, single-institution cohort of burn patients who met the same criteria for entry into the Glue Grant study. Of the 220 total patients analyzed from the Glue Grant cohort, 49 (22.2%) developed early AKI, 39 (17.7%) developed late AKI, and 16 (7.2%) developed progressive AKI. The group with progressive AKI was statistically older, with more comorbidities and with the worst survival when compared with those with early or late AKI. Using CART analysis, a decision tree was developed with an overall accuracy of 80% for the development of late AKI for the Glue Grant dataset. The authors then tested this decision tree on a smaller dataset from our own institution to validate this tool and found it to be 73% accurate. AKI is common in severe burns with notable differences between early, late, and progressive AKI. In addition, CART analysis provided a predictive model for early identification of patients at highest risk for developing late AKI with proven clinical accuracy.

Use of therapeutic plasma exchange in the burn unit: a review of the literature.

Burn centers routinely treat a complex mix of patients with soft tissue injuries, including burn injuries, necrotizing soft tissue infections, and dermatologic conditions such as toxic epidermal necrolysis (TEN). In each of these conditions, fluid resuscitation, surgical interventions, and advances in critical care have improved survival significantly; however, there remains a subset of patients who do not respond to conventional means. It is because of these patients that we continue to seek means to “rescue” patients who are failing to respond to conventional care. Therapeutic plasma exchange (TPE) is an uncommon and underutilized treatment modality that has been used as a form of treatment “rescue.” We provide a review of the literature describing the use of TPE in TEN, burn shock, and sepsis. Our review of the literature over the past 30 years demonstrates persistent clinical benefits and reduced morbidity and mortality with use of TPE in TEN, burn shock, and sepsis. Many studies demonstrate significant improvement in morbidity and mortality with TPE in patients suffering from these conditions. However, future well-designed studies of the role of TPE in conditions commonly encountered in burn units are indicated. Improved awareness of TPE may lead to increased use of this uncommonly utilized modality and allow for potential future collaboration in a prospective, randomized, controlled trial with a larger number of subjects.

Pediatric toxic epidermal necrolysis: using SCORTEN and predictive models to predict morbidity when a focus on mortality is not enough.

Toxic epidermal necrolysis (TEN) and Stevens–Johnson Syndrome (SJS) are rare yet severe exfoliative skin disorders. The authors examined the efficacy of predictive models for their use as prognostic indicators in pediatric SJS or TEN. Over a 15-year period, 41 patients ⩽18 years of age were identified and reviewed. Predictive models compared retrospectively to the observed mortality in the population included: SCORTEN (Score of Toxic Epidermal Necrolysis), Pediatric Index of Mortality 2, Pediatric Risk of Mortality III-24, and Abbreviated Burn Severity Index. Correlation coefficients and 95% confidence intervals were calculated for the following: acute hospital length of stay, days until wound closure, days of mechanical ventilation, number of infectious complications, and number of acute operative procedures. When calculated within the first 24 hours of admission, the four models predicted low rates of mortality, approaching our 0% observed mortality, and also demonstrated a significant correlation between higher scores and the five chosen indicators of morbidity (P < .05). SCORTEN on day 3 of admission was statistically significant (P < .05) only when predicting the number of infectious complications and days of mechanical ventilation and was therefore felt to be less predictive than use of SCORTEN on admission. When calculated within the first day of admission of pediatric SJS or TEN patients, SCORTEN, Abbreviated Burn Severity Index, Pediatric Index of Mortality 2, and Pediatric Risk of Mortality III all significantly predict acute morbidity. This is the first time scoring systems have been assessed for their ability to predict mortality and morbidity in pediatric SJS or TEN despite its widely recognized, severe acute course of disease.