Bioscaffold developed with decellularized human amniotic membrane seeded with mesenchymal stromal cells: assessment of efficacy and safety profiles in a second-degree burn preclinical model.

Therapies to deep burn injuries remain a global challenge. Human amniotic membrane (hAM) is a biomaterial that has been increasingly explored by the field of regenerative medicine. A decellularized hAM (DhAM) can be used as scaffold for mesenchymal stromal cells (MSCs) to grow without the loss of their stemness potential, allowing its application as cell therapy for wound healing. In this work, we associated DhAM with adipose-derived MSCs (DhAM + AD-MSCs), as a therapy strategy for second-degree burns in a preclinical model. Animals with induced second-degree burns were divided into four groups: control, which consists of a non-adherent gauze; a synthetic commercial dressing as the positive control (Control+); DhAM; and DhAM plus rat AD-MSCs (DhAM + AD-MSCs), followed by detailed and long term analysis (5 weeks). The macroscopical analysis showed the healing improvement in the wound area after the DhAM + AD-MSC treatment. Histological analysis also showed no alteration in the animal organs and a regular epithelial progression in comparison to the control. This observation was also confirmed by the analysis of suprabasal layers in the neoepidermis with CK10, showing a stratified and differentiated epithelium, when compared to Control and Control+. A strong CD73 (ecto-5'-nucleotidase) labeling was observed in the first 2 weeks postburn in dermis and epidermis. The expression in dermis was stronger in the second week in the middle of the wound, when comparing the Control+ with DhAM + AD-MSCs (p= 0.0238). In the epidermis the expression of CD73 was increased in all regions when compared to the control. This data suggests the involvement of this protein on wound healing. A low CD11b labeling was observed in DhAM + AD-MSCs treatment group mainly in the last treatment week, in comparison to Control and Control+ (p< 0.0001), which indicates a reduction in the inflammatory process. MSCs through CD73 can release high concentrations of adenosine, an immunosuppressive molecule, suggesting that this could be the mechanism by which the inflammation was better modulated in the DhAM + AD-MSCs group. The results obtained with this preclinical model confirm the effectiveness and safety of this low-cost and highly available dressing for future clinical application as a therapy for burn treatments.

Investigation and assessment of neutrophil dysfunction early after severe burn injury.

BACKGROUND: Extensive burn injury results in a complex immune response that is associated with mortality and prognosis. Studies on acquired immune and the development of sepsis in burn patients have been reported. However, one of the main cells in innate immune, neutrophil dysfunction in the burn shock stage has not been thoroughly characterized. METHODS: Neutrophil chemotaxis, expression of neutrophil surface markers (P2X1 receptor, [P2RX1]), degranulation (myeloperoxidase [MPO], heparin-binding protein [HBP], matrix metalloproteinase-9 [MMP-9] and neutrophil elastase [NE]), oxidative burst capacity, neutrophil extracellular trap (NET) generation, phagocytosis and apoptosis were measured in 18 patients with major burns (≥30% total body surface area [TBSA]) within 48 h after burn injury. In addition, circulating neutrophils and vascular permeability in mice model with 30% TBSA third-degree burns were also observed and investigated. RESULTS: Neutrophil functions were reduced considerably in burn shock stage, which was characterized by decreased chemotaxis, phagocytosis and abnormal bactericidal function. Increased release of heparin-binding protein (HBP) and the expression of P2RX1 on the neutrophil surface are related to fluid leakage and decreased chemotaxis during burn shock stage, respectively. The combination of HBP concentration in plasma and P2RX1 expression on neutrophils gives a better prediction of neutrophil dysfunction in burn-injured patients. CONCLUSION: Neutrophil dysfunction plays a key role in the development of burn injury. Targeting the restoration of neutrophil function may be a feasible therapeutic intervention to help reduce fluid loss during shock and the severity of subsequent infection.

Risk Assessment of Deep Venous Thrombosis and Its Influencing Factors in Burn Patients.

The objective of this study is to explore the relevant risk factors of deep venous thrombosis (DVT) in burn patients. A retrospective analysis was conducted for the medical records of 845 hospitalized burn patients from September 2012 to August 2017. Caprini thrombosis risk assessment scale (CTRAS) was employed for evaluating the risks of DVT. Based upon whether or not DVT occurred, they were divided into non-DVT group (n = 830) and DVT group (n = 15). Among 360 (42.7%) patients with high-risk Caprini scores, only 30 patients received color Doppler examination of lower limb veins, and 15 patients were diagnosed as DVT with a diagnostic rate of 1.8%. Caprini scores of non-DVT and DVT groups were 4.30 ± 2.71 and 9.87 ± 1.46 points, respectively. There was statistically significant difference (P < .05). As revealed by stepwise Logistic regression analysis, age, lower limb burn, wound infection, femoral vein catheterization, and long bedriddening time (>40 days) were independent risk factors for DVT. Burn patients are particularly prone to develop DVT. Age, wound infection, femoral vein catheterization, and long bedriddening time (>40 days) are risk factors. Aggressive preventive measures of DVT should be implemented.

ASSESSMENT OF THE LIPID PEROXIDE OXIDATION PROCESSES AND ANTIOXIDANT PROTECTION IN THE TREATMENT OF RATS THERMAL BURNING BY DOXICYCLINE AS A SYNTHETIC INHIBITOR OF MATRIX METALLOPROTEINASES IN EXPERIMENT.

Aim - to assess the effects of doxycycline on the state of lipid peroxidation processes and the activity of the antioxidant system. The study was performed on 144 rats of the WAG population weighing 200-250 g (6 rats in each group). Animals with thermal burns were injected with the test drug doxycycline, as well as reference drugs - thiotriazolin and methyluracil orally in starch suspensionafter thermal exposure and daily during the entire experiment period (28 days). Animals were removed from the experiment in accordance with the rules of bioethics on the 7th, 14th, 21st and 28th day. As a result of the research, the most intense influence of doxycycline on the processes of lipid peroxidation in the blood serum of rats was found - a decrease in DC activity by the end of the experiment (regardless of dose) and TBA-AP starting from the 14th day of observation reaching the value of intact rats (at a dose of 30 mg/kg). At the same time, an increase in the activity of enzymes of the antioxidant system was noted - the level of catalase from the 14th day (significantly higher than the control group regardless of dose) and the level of ceruloplasmin (from the second week of observation the indicator reached intact values ​​at a dose of 30 mg/kg). Reference drugs were inferior to doxycycline in their effectiveness. The data obtained may indicate the possibility of reducing the healing time of a thermal burn due to the suppression of excessive free radical oxidation activity and activation of antioxidant protection.

Energy Expenditure and Protein Requirements Following Burn Injury.

Severe burn injuries have long been known to have a profound effect on metabolic equilibrium that can persist after resolution of the cutaneous injuries. Following burn injury, metabolism is a dynamic state resulting in the need for frequent interval reassessment over the course of the care continuum. The acute phase of injury transitions to chronic alterations in macronutrient utilization characterized by futile energy cycling and disproportionate catabolism of skeletal muscle. Protein supplementation appears to be preferentially distributed to the burn wound rather than the skeletal muscle pool. Accurate assessment of caloric and protein requirements is extremely difficult in these patients but is an essential step in efforts to attenuate functional impairment. Indirect calorimetry should be utilized to determine caloric requirements, but trophic feeding strategies are preferred in the initial resuscitative phase to prevent overfeeding while maintaining enteric and immune function. Controversy persists regarding optimal protein targets, and weight-based estimates remain the norm. Exogenous protein and caloric provision performed in isolation is insufficient to optimize outcomes and should be incorporated within a multidisciplinary approach to include muscle loading and pharmaceutical adjuncts.

Predictive energy equations are inaccurate for determining energy expenditure in adult burn injury: a retrospective observational study.

BACKGROUND: Severe burn injuries are associated with hypermetabolism. This study aimed to compare the measured energy expenditure (mEE) with predicted energy requirements (pERs), and to correlate energy expenditure (EE) with clinical parameters in adults with severe burn injury. METHODS: Data were retrospectively analysed on 29 burn patients (median (interquartile range) age: 46 (28-61) years, % total body surface area burn: 37% (18-46%)) admitted to an intensive care unit. Indirect calorimetry was performed on 1-4 occasions per patient to measure EE. mEE was compared with pER calculated using four prediction equations. Bland-Altman and correlation analyses were performed. RESULTS: Mean ± SD mEE was 9752 ± 2089 kJ/day (143 ± 32% of predicted basal metabolic rate). Bland-Altman analysis demonstrated clinically important overestimation for three of the four prediction equations and wide 95% limits of agreement for all equations. Overestimation of EE was more marked early post-burn. mEE correlated with day post-burn (r = 0.42, P = 0.004) and number of operations prior to first EE measurement (r = 0.34, P = 0.016), but not with % total body surface area (r = 0.02, P = 0.9). CONCLUSIONS: Patients with severe burn injury exhibit hypermetabolism. The observed poor agreement between pER and mEE at an individual level indicates the value of indirect calorimetry in determining EE in burn injury.

Assessment of the impact of oxandrolone on outcomes in burn injured patients.

The purpose of this study is to use a retrospective cohort of burn patients to evaluate the contribution of oxandrolone on burn care outcomes. Longitudinal clinical data is used to analyze outcomes from a new perspective. Our random-effects longitudinal regression analysis model used temporal clinical data to evaluate oxandrolone's impact on outcomes (oxandrolone/non-oxandrolone n=50/11, median length of stay [LOS]=42.2/39.3, mean weight (kg)=192.2/207.6, mean initial prealbumin (mg/dL) 10.1/7.5). The resultant predictive models (p<0.001) described how certain factors influence clinically significant outcomes via a robust data analysis method. LOS was predicted and extended by a greater magnitude of 3rd-degree versus 2nd-degree burns (1.01 versus 0.85 additional days for each %TBSA, p<0.001). Weight was decreased by LOS (145.2g lost per day, p<0.001). Oxandrolone improved prealbumin (3.503mg/dL increase, p<0.001) but instead did not influence patient weight (p>0.05) nor LOS (5.27days shortening, p=0.361). Prealbumin over time was also influenced by initial value (0.293mg/dL, p=0.003), LOS (0.072mg/dL increase per additional day, p<0.001), and the presence of inhalation injury (2.652mg/dL decrease if present, p=0.009). Oxandrolone appears to benefit anabolic protein production. It is difficult to isolate the role of oxandrolone on major outcomes due to the concomitant influence of other variables.

Reliability of resting energy expenditure in major burns: Comparison between measured and predictive equations.

BACKGROUND & AIMS: Poor outcomes can result from inadequate energy intake. We aimed to investigate the reliability of resting energy expenditure (REE) measured by indirect calorimetry (IC) with REE calculated using predictive equations for nutritional support in patients with major burns. METHODS: REE was measured using IC and compared with predictive equations in 215 adult severe burns patients from Jan 2011 to Jun 2015. Agreement between IC and predictive equations was assessed using Bland-Altman methods. RESULTS: All predictive equations, including newly developed Hangang equation, were compared with REE measured using IC. The mean measured REE was 1712 kcal/d. Bland-Altman analysis showed that 1.2 times HBE, Thumb 25, and Ireton-Jones equations had higher accuracy and reliability. The concordance correlation coefficient was higher (0.49) in the Ireton-Jones equation, and root mean square error (RMSE) was lowest (471.5) in the Thumb 25 equation. The proportion of patients with predicted REE within ±10% of measured REE was highest with Thumb 25 (52.5%). In the validation set, the Hangang equation showed the highest Lin's concordance correlation coefficient (0.67) and the lowest RMSE (311.4). Other equations for burns patients had higher mean bias and overestimated REE when compared with IC results. CONCLUSIONS: This study suggests that Thumb 25 can be used as an alternative method for estimating energy requirements of patients with major burns when IC is not available or applicable. However, for these patients with significant variation in metabolism over time, an alternative equation is the new Hangang equation.

Population Pharmacokinetic Study of Amoxicillin-Treated Burn Patients Hospitalized at a Swiss Tertiary-Care Center.

The objective of this study was to investigate the population pharmacokinetics (PK) of amoxicillin in ICU burn patients and the optimal dosage regimens. This was a prospective study involving 21 consecutive burn patients receiving amoxicillin. PK data were analyzed using nonlinear mixed-effects modeling. Monte-Carlo simulations assessed the influence of various amoxicillin dosage regimens with identified covariates on the probability to achieve a target (PTA) value of time during which free amoxicillin concentrations in plasma exceeded the MIC (fT>MIC). A two-compartment model best described the data. Creatinine clearance (CLCR) and body weight (BW) influenced amoxicillin CL and central volume of distribution (V1), respectively. The median CLCR (Cockcroft-Gault formula) was high (128 ml/min), with 25% of patients having CLCRs of >150 ml/min. The CL, V1, and half-life (t1/2) values at steady state for a patient with a CLCR of 110 ml/min and BW of 70 kg were 13.6 liters/h, 9.7 liters, and 0.8 h, respectively. Simulations showed that a target fT>MIC of ≥50% was achieved (PTA > 90%) with standard amoxicillin dosage regimens (1 to 2 g every 6 to 8 h [q6-8h]) when the MIC was low (<1 mg/liter). However, increased dosages of up to 2 g/4 h were necessary in patients with augmented CLRs or higher MICs. Prolonging amoxicillin infusion from 30 min to 2 h had a favorable effect on target attainment. In conclusion, this population analysis shows an increased amoxicillin CL and substantial CL PK variability in burn patients compared to literature data with nonburn patients. Situations of augmented CLCR and/or high bacterial MIC target values may require dosage increases and longer infusion durations. (This study has been registered at ClinicalTrials.gov under identifier NCT01965340.).

Graphical Calculation of Estimated Energy Expenditure in Burn Patients.

BACKGROUND: Historically, estimated energy expenditure (EEE) has been related to the percent of body surface area burned. Subsequent evaluations of these estimates have indicated that the earlier formulas may overestimate the amount of caloric support necessary for burn-injured patients. Ireton-Jones et al derived 2 equations for determining the EEE required to support burn patients, 1 for ventilator-dependent patients and 1 for spontaneously breathing patients. Evidence has proved their reliability, but they remain challenging to apply in a clinical setting given the difficult and cumbersome mathematics involved. This study aims to introduce a graphical calculation of EEE in burn patients that can be easily used in the clinical setting. METHODS: The multivariant linear regression analysis from Ireton-Jones et al yielded equations that were rearranged into the form of a simple linear equation of the type y = mx + b. By choosing an energy expenditure and the age of the subject, the weight was calculated. The endpoints were then calculated, and a graph was mapped by means of Adobe FrameMaker. RESULTS: A graphical representation of Ireton-Jones et al's equations was obtained by plotting the weight (kg) on the y axis, the age (years) on the x axis, and a series of parallel lines representing the EEE in burn patients. The EEE has been displayed graphically on a grid to allow rapid determination of the EEE needed for a given patient of a designated weight and age. Two graphs were plotted: 1 for ventilator-dependent patients and 1 for spontaneously breathing patients. Correction factors for sex, the presence of additional trauma, and obesity are indicated on the graphical calculators. CONCLUSIONS: We propose a graphical tool to calculate caloric requirements in a fast, easy, and portable manner.

In Vivo Assessment of Engineered Skin Cell Delivery with Multimodal Optical Microscopy.

The healing process is often significantly impaired under conditions of chronic or large area wounds, which are often treated clinically using autologous split-thickness skin grafts. However, in many cases, harvesting of donor tissue presents a serious problem such as in the case of very large area burns. In response to this, engineered biomaterials have emerged that attempt to mimic the natural skin environment or deliver a suitable therapy to assist in the healing process. In this study, a custom-built multimodal optical microscope capable of noninvasive structural and functional imaging is used to investigate both the engineered tissue microenvironment and the in vivo wound healing process. Investigation of various engineered scaffolds show the strong relationship among the microenvironment of the scaffold, the organization of the cells within the scaffold, and the delivery pattern of these cells onto the healing wound. Through noninvasive tracking of these processes and parameters, multimodal optical microscopy provides an important tool in the assessment of engineered scaffolds both in vitro and in vivo.

Histopathological assessment of OASIS Ultra on critical-sized wound healing: a pilot study.

BACKGROUND: Dermatopathologists assess wounds secondary to trauma, infection, or oncologic resection that can be challenging to reconstruct. OASIS Ultra, an extracellular matrix, has been described for use in chronic and burn wounds. The aim of this pilot study is to assess wound healing in post-traumatic and infective wounds treated with OASIS using histological markers of repair. MATERIALS AND METHODS: Adults with traumatic, infective or iatrogenic wound defects with size precluding primary closure were eligible. Half the wound was randomly assigned to receive OASIS plus standard therapy; the other half received standard of care (SOC) therapy. During dressing changes, standardized-scale photographs were taken and biopsies obtained. Histologic sections were reviewed for degree of acute inflammation and extent of tissue repair. Neutrophils, edema, hemorrhage, necrosis, fibroblasts, collagen density and neovascularization were semi-quantitatively assessed. RESULTS: Forty-four skin biopsies from 7 patients with 10 acute wounds met eligibility criteria. Histologically, OASIS samples demonstrated improved acute inflammation scores compared to SOC. No patients experienced OASIS-related complications. OASIS-treated wound halves trended toward more wound contraction and improved tissue repair. CONCLUSION: Our scoring system aids histopathological wound assessment. Treatment of critical-sized, post-traumatic, acute wounds with OASIS resulted in decreased inflammation, and potentially more advanced wound healing, compared to SOC.

Intravenous Antibiotic and Antifungal Agent Pharmacokinetic-Pharmacodynamic Dosing in Adults with Severe Burn Injury.

PURPOSE: Despite advances in the care of patients with severe burn injury, infection-related morbidity and mortality remain high and can potentially be reduced with antimicrobial dosing optimized for the infecting pathogen. However, anti-infective dose selection is difficult because of the highly abnormal physiologic features of burn patients, which can greatly affect the pharmacokinetic (PK) disposition of these agents. We review published PK data from burn patients and offer evidence-based dosing recommendations for antimicrobial agents in burn-injured patients. METHODS: Because most infections occur at least 48 hours after initial burn injury and anti-infective therapy often lasts ≥10 days, we reviewed published data informing PK-pharmacodynamic (PD) dosing of anti-infectives administered during the second, hypermetabolic stage of burn injury, in those with >20% total body surface area burns, and in those with normal or augmented renal clearance (estimated creatinine clearance ≥130 mL/min). Analyses were performed using 10,000-patient Monte Carlo simulations, which uses PK variability observed in burn patients and MIC data to determine the probability of reaching predefined PK-PD targets. The probability of target attainment, defined as the likelihood that an anti-infective dosing regimen would achieve a specific PK-PD target at the single highest susceptible MIC, and the cumulative fraction of response, defined as the population probability of target attainment given a specific dose and a distribution of MICs, were calculated for each recommended anti-infective dosing regimen. FINDINGS: Evidence-based doses were derived for burn-injured patients for 15 antibiotics and 2 antifungal agents. Published data were unavailable or insufficient for several agents important to the care of burn patients, including newer antifungal and antipseudomonal agents. Furthermore, available data suggest that antimicrobial PK properties in burned patients is highly variable. We recommend that, where possible, therapeutic drug monitoring be performed to optimize PK-PD parameter achievement in individual patients. IMPLICATIONS: Given the high variability in PK disposition observed in burn patients, doses recommended in the package insert may not achieve PK-PD parameters associated with optimal infectious outcomes. Our study is limited by the necessity for fixed assumptions in depicting this highly variable patient population. New rapid-turnaround analytical technology is needed to expand the menu of antimicrobial agents for which therapeutic drug monitoring is available to guide dose modification within a clinically actionable time frame.

Establishment and assessment of new formulas for energy consumption estimation in adult burn patients.

OBJECTIVE: An accurate knowledge of energy consumption in burn patients is a prerequisite for rational nutrition therapy. This study sought to create a formula that accounts for the metabolic characteristics of adult burn patients to accurately estimate energy consumption of patients with different areas and extents of burn and at different times after injury. METHODS: Resting energy expenditure (REE) data on 66 burn patients, with total body surface area (TBSA) of burns ranging from 4% to 96%, were evaluated at different times after injury. REE values were determined in patients using indirect calorimetry at days 1, 2, 3, 7, 14, 21, and 28 after injury. We then constructed a mathematical model of REE changes post-burn. Next, established two new formulas (one non-linear and the other linear) for energy consumption estimation using model-based analytical solution and regression analysis. The new formulas were compared with measured REE and commonly used formulas including those of Carlson, Xie, Curreri, and Milner to determine accuracy and reliability. RESULTS: Comparative analysis showed that the new formulas offered significantly higher accuracy and reliability than the Milner formula, which is considered the most accurate of commonly used burn energy consumption estimate formulas. The accuracy of the new nonlinear formula (94.29%) and that of the linear formula (91.43%) were significantly higher than that of Milner formula (72.86%) when compared to measured REE (χ2  =  11.706, P  =  0.001; χ2  =  8.230, P  =  0.004, respectively). The reliabilities of the new estimation formulas were both 100% and that of Milner formula was 74.24% (χ2  =  19.513, P  =  0.000). CONCLUSION: The new formulas constructed in this study provide reliable simulation of the impact of the degree of burn and post-burn days on energy consumption and offer notably higher accuracy and reliability than other formulas. These formulas will help determine nutritional needs of burn patients. TRIAL REGISTRATION: The study was registered on Chinese Clinical Trial Registry as ChiCTR-TRC-13003806.

Assessment of biochemical markers in the early post-burn period for predicting acute kidney injury and mortality in patients with major burn injury: comparison of serum creatinine, serum cystatin-C, plasma and urine neutrophil gelatinase-associated lipocalin.

INTRODUCTION: The reported mortality rates range from 28% to 100% in burn patients who develop acute kidney injury (AKI) and from 50% to 100% among such patients treated with renal replacement therapy. Recently, the serum cystatin C and plasma and urine neutrophil gelatinase-associated lipocalin (NGAL) levels have been introduced as early biomarkers for AKI; the levels of these biomarkers are known to increase 24 to 48 hours before the serum creatinine levels increase. In this study, we aimed to estimate the diagnostic utility of the cystatin C and plasma and urine NGAL levels in the early post-burn period as biomarkers for predicting AKI and mortality in patients with major burn injuries. METHODS: From May 2011 to July 2012, 90 consecutive patients with a burn wound area comprising ≥ 20% of the total body surface area (TBSA) were enrolled in this study. Whole blood and urine samples were obtained for measuring the serum creatinine, serum cystatin C, and urine and plasma NGAL levels at 0, 3, 6, 12, 24, and 48 hours after admission. Receiver operating characteristic curve, area under the curve, and multivariate logistic regression analyses were performed to assess the predictive values of these biomarkers for AKI and mortality. RESULTS: In the multivariate logistic regression analysis, all variables, including age, percentage TBSA burned, sex, inhalation injury, and serum creatinine levels, serum cystatin C levels, and plasma and urine NGAL levels were independently associated with AKI development. Moreover, age, sex, percentage TBSA burned, and plasma and urine NGAL levels were independently associated with mortality. However, inhalation injury and the serum creatinine and cystatin C levels were not independently associated with mortality. CONCLUSIONS: Massively burned patients who maintained high plasma and urine NGAL levels until 12 hours after admission were at the risk of developing early AKI and early mortality with burn shock. However, the plasma and urine NGAL levels in the early post-burn period failed to predict late AKI and non-burn shock mortality in this study. Nevertheless, the plasma and urine NGAL levels were independently associated with AKI development and mortality within 48 hours after admission.

[Energy expenditure prediction equations in burn patients; bibliographic review]. / Estimación del gasto energético en el paciente quemado mediante la utilización de ecuaciones predictivas; revisión bibliográfica.

INTRODUCTION: The estimation of the caloric requirements of the burn patient is based on the measurement of his resting energy expenditure (REE) via indirect calorimetry, which is not available in all Burn Units, or its estimation by means of predictive equations. GOALS: we analyze the history and state of art of the use of REE predictive equations in burn patients, and determine their validity. METHODS: bibliographic review of the studies and reviews written in English and Spanish between 1989 and 2013. RESULTS: More than 190 equations have been designed to estimate energy expenditure. These equations can be imprecise because they are based on measurements with a heterogeneous methodology and in heterogeneous groups. We describe the different parameters that are used in the different equations (stress and activity factors, total burn surface area, post-burn day, lean body mass), the influence of age in the calculation of the caloric requirements, and the most commonly used equations nowadays. We also describe the articles that evaluate the accuracy of the predictive equations when compared to REE indirect calorimetry measurements. CONCLUSIONS: Predictive equations are not precise in general in the burn patient. Until more accurate predictive equations are developed, we recommend calculation of the nutritional requirements in burn patients based on the energy expenditure measurement via indirect calorimetry.

Introducción: La valoración de las necesidades calóricas del paciente quemado se ha basado en la medición del gasto energético en reposo (GER) mediante calorimetría indirecta, no siempre disponible en las unidades de quemados, o en su estimación mediante el uso de ecuaciones predictivas. Objetivos: analizar la historia y estado del arte del uso de las ecuaciones predictivas de GER en el paciente quemado crítico, y determinar su validez. Métodos: revisión bibliográfica de estudios y revisiones en español y en inglés entre 1989 y 2013. Resultados: Se han diseñado más de 190 ecuaciones para estimar el gasto energético que pueden ser imprecisas por estar basadas en mediciones con metodología heterogénea y en grupos heterogéneos. Describimos los distintos parámetros que aplican las distintas fórmulas predictivas (factores de estrés y de actividad, superficie corporal quemada, tiempo desde la lesión, masa corporal magra), la influencia de la edad en el cálculo de las necesidades calóricas y las fórmulas más utilizadas en el momento actual. También describimos los artículos que evalúan exactitud de las fórmulas cuando se comparan con mediciones mediante calorimetría indirecta. Conclusiones: Las ecuaciones predictivas son poco precisas en general en el paciente quemado. Hasta que se desarrollen ecuaciones predictivas más precisas, recomendamos calcular los requerimientos nutricionales de los pacientes quemados basándose en la medición del gasto energético por calorimetría indirecta.

Influence of inhalation injury on energy expenditure in severely burned children.

OBJECTIVE: Determine the effect of inhalation injury on burn-induced hypermetabolism in children. DESIGN: Prospective study comparing hypermetabolism (i.e., resting energy expenditure and oxygen consumption) in burned children with and without inhalation injury during acute hospitalization. SETTING: Single pediatric burn center. PATIENTS: Eighty-six children (1-18 years) with ≥40% total body surface area burns were stratified to two groups: no inhalation injury and inhalation injury. INTERVENTIONS: None. MAIN MEASUREMENTS AND RESULTS: Inhalation injury was diagnosed based on bronchoscopic evaluation. At admission, PaO2:FiO2 ratios (an index of respiratory distress) were significantly higher in patients with no inhalation injury than in patients with inhalation injury. No differences were detected in resting energy expenditure or percent of the predicted basal metabolic rate between groups. Additionally, oxygen consumption did not significantly differ between groups. CONCLUSIONS: Inhalation injury does not augment the burn-induced hypermetabolic stress response in children, as reflected by resting energy expenditure and oxygen consumption.

Population pharmacokinetic analysis of piperacillin in burn patients.

Piperacillin in combination with tazobactam, a ß-lactamase inhibitor, is a commonly used intravenous antibiotic for the empirical treatment of infection in intensive care patients, including burn patients. The purpose of this study was to develop a population pharmacokinetic (PK) model for piperacillin in burn patients and to predict the probability of target attainment (PTA) using MICs and concentrations simulated from the PK model. Fifty burn patients treated with piperacillin-tazobactam were enrolled. Piperacillin-tazobactam was administered via infusion for approximately 30 min at a dose of 4.5 g (4 g piperacillin and 0.5 g tazobactam) every 8 h. Blood samples were collected just prior to and at 1, 2, 3, 4, and 6 h after the end of the infusion at steady state. The population PK model of piperacillin was developed using NONMEM. A two-compartment first-order elimination PK model was finally chosen. The covariates included were creatinine clearance (CLCR), day after burn injury (DAI), and sepsis. The final PK parameters were clearance (liters/h) (equal to 16.6 × [CLCR/132] + DAI × [-0.0874]), central volume (liters) (equal to 25.3 + 14.8 × sepsis [0 for the absence or 1 for the presence of sepsis]), peripheral volume (liters) (equal to 16.1), and intercompartmental clearance (liters/h) (equal to 0.636). The clearance and volume of piperacillin were higher than those reported in patients without burns, and the terminal half-life and PTA decreased with the increased CLCR. Our PK model suggests that higher daily doses or longer durations of infusion of piperacillin should be considered, especially for burn patients with a CLCR of ≥ 160 ml/min.

Animal models in burn research.

Burn injury is a severe form of trauma affecting more than 2 million people in North America each year. Burn trauma is not a single pathophysiological event but a devastating injury that causes structural and functional deficits in numerous organ systems. Due to its complexity and the involvement of multiple organs, in vitro experiments cannot capture this complexity nor address the pathophysiology. In the past two decades, a number of burn animal models have been developed to replicate the various aspects of burn injury, to elucidate the pathophysiology, and to explore potential treatment interventions. Understanding the advantages and limitations of these animal models is essential for the design and development of treatments that are clinically relevant to humans. This review aims to highlight the common animal models of burn injury in order to provide investigators with a better understanding of the benefits and limitations of these models for translational applications. While many animal models of burn exist, we limit our discussion to the skin healing of mouse, rat, and pig. Additionally, we briefly explain hypermetabolic characteristics of burn injury and the animal model utilized to study this phenomena. Finally, we discuss the economic costs associated with each of these models in order to guide decisions of choosing the appropriate animal model for burn research.

Toxicity assessment of nanosilver wound dressing in Wistar rat.

Antibiotic resistance to microorganisms is one of the major problems faced in the field of wound care in burns patients. Silver nanoparticles have come up as potent antimicrobial agent and are being evaluated in diverse medical applications ranging from silver based dressings to silver coated medical devices. We aimed in present study to test the release of nanosilver from nanosilver wound dressing and compare the dermal and systemic toxicity of nanosilver dressings in a repeated dose (21 days) model. Under general anesthesia, a limited standard 2nd degree burns were provided on the back of each rat in all treatment, negative control (simple dressing) and 5% silver nitrate groups, each contained 5 male wistar rats. According to the analysis made by atomic absorption spectrometry, the wound dressings released 0.599 ± 0.083 ppm of nanosilver during first 24 hrs of study. Daily observations were recoded and wounds were covered with new dressings each 24 hrs. Burn healing was observed in nanosilver wound dressing group in shorter time periods than the control groups. In toxicity assessment, this dressing didn't cause any hematological and histopathological abnormalities in treatment group but biochemical studies showed significant rise of plasma transaminase (ALT) at the endpoint (21 days) of the study (P=0.027). Portal mononuclear lymphoid and polymorphonuclear leukocyte infiltrations in three to four adjacent foci were recognized around the central hepatic vein in treatment group. Mild hepatotoxic effects of nanosilver wound dressing in wistar rat emphasize the necessity of more studies on toxicity potentials of low dose nanosilver by dermal applications.