Gabriel Hundeshagen

Satellite cell activation and apoptosis in skeletal muscle from severely burned children

Severe burns result in profound skeletal muscle atrophy that hampers recovery. The activity of skeletal muscle stem cells, satellite cells, acutely following a severe burn is unknown and may contribute to the recovery of lean muscle. Severe burn injury induces skeletal muscle regeneration and myonuclear apoptosis. Satellite cells undergo concurrent apoptosis and activation acutely following a burn, with a net reduction in satellite cell content compared to healthy controls. The activation and apoptosis of satellite cells probably impacts the recovery of lean tissue following a severe burn, contributing to prolonged frailty in burn survivors.

Transpulmonary Thermodilution Versus Transthoracic Echocardiography for Cardiac Output Measurements in Severely Burned Children

Introduction: Severe burns trigger a hyperdynamic state, necessitating accurate measurement of cardiac output (CO) for cardiovascular observation and guiding fluid resuscitation. However, it is unknown whether, in burned children, the increasingly popular transthoracic echocardiography (TTE) method of CO measurement is as accurate as the widely used transpulmonary thermodilution (TPTD) method. Patients and Methods: We retrospectively compared near-simultaneously performed CO measurements in severely burned children using TPTD with the Pulse index Continuous Cardiac Output (PiCCO) system or TTE. Outcomes were compared using t tests, multiple linear regression, and a Bland-Altman plot. Results: Fifty-four children (9 ± 5 years) with 68 ± 18% total body surface area burns were studied. An analysis of 105 data pairs revealed that PiCCO yielded higher CO measurements than TTE (190 ± 39% vs. 150 ± 50% predicted values; P < 0.01). PiCCO- and TTE-derived CO measurements correlated moderately well (R2 = 0.54, P < 0.01). A Bland-Altman plot showed a mean bias of 1.53 L/min with a 95% prediction interval of 4.31 L/min. Conclusions: TTE-derived estimates of CO may underestimate severity of the hyperdynamic state in severely burned children. We propose using the PiCCO system for objective cardiovascular monitoring and to guide goal-directed fluid resuscitation in this population.

Propranolol Reduces Cardiac Index But does not Adversely Affect Peripheral Perfusion in Severely Burned Children.

Purpose: The aim of this study was to quantify the effect of propranolol on hemodynamic parameters assessed using the PiCCO system in burned children. Methods: We analyzed hemodynamic data from patients who were randomized to receive either propranolol (4 mg/kg/day) or placebo (control), which was initiated as a prospective randomized controlled trial. Endpoints were cardiac index (CI), percent predicted heart rate (%HR), mean arterial pressure (MAP), percent predicted stroke volume (%SV), rate pressure product (RPP), cardiac work (CW), systemic vascular resistance index (SVRI), extravascular lung water index (EVLWI), arterial blood gases, events of lactic acidosis, and mortality. Mixed multiple linear regressions were applied, and a 95% level of confidence was assumed. Results: One hundred twenty-one burned children (control: n = 62, propranolol: n = 59) were analyzed. Groups were comparable in demographics, EVLWI, SVRI, %SV, arterial blood gases, Denver 2 postinjury organ failure score, incidence of lactic acidosis, or mortality. Percent predicted HR, MAP, CI, CW, and RPP were significantly reduced in the propranolol-treated group (P <0.01). Conclusions: Propranolol significantly reduces cardiogenic stress by reducing CI and MAP in children with severe burn injury. However, peripheral oxygen delivery was not reduced and events of lactic acidosis as well as organ dysfunction was not higher in propranolol treated patients.

A Prospective, Randomized, Controlled Trial Comparing the Outpatient Treatment of Pediatric and Adult Partial-Thickness Burns with Suprathel or Mepilex Ag

Modern treatment of partial-thickness burns follows the paradigm of less frequent dressing changes to allow for undisturbed reepithelialization of the burn wound. We compared Mepilex Ag (M), a silver-impregnated foam dressing, and Suprathel (S), a DL-lactid acid polymer, in the outpatient treatment of partial-thickness burns in pediatric and adult patients. Patients were enrolled in a randomized, controlled, prospective clinical trial. We monitored time to reepithelialization, wound pain, discomfort during dressing changes, and treatment cost. Objective scar characteristics (elasticity, transepidermal water loss, hydration, and pigmentation) and subjective assessments (Patient and Observer Scar Assessment Scale) were measured at 1 month post burn. Data are presented as mean ± SEM, and significance was accepted at P < 0.05. Sixty-two patients (S n = 32; M n = 30) were enrolled; age, sex, and burn size were comparable between the groups. Time to reepithelialization was not different between the groups (12 days; P = 0.75). Pain ratings were significantly reduced during the first 5 days after burn in the Suprathel group in all patients (P = 0.03) and a pediatric subgroup (P < 0.001). Viscolelasticity of burned skin was elevated compared with unburned skin in the Mepilex Ag group at 1 month post burn. Patients treated with Suprathel reported better overall scar quality (S: 2; M: 4.5; P < 0.001). The cost of treatment per square centimeter for Mepilex Ag was considerably lower than that of Suprathel. Both dressings are feasible and efficacious for the outpatient treatment of minor and selected moderate partial-thickness burns. Reduced pain, especially in a pediatric patient population, may be advantageous, despite increased treatment cost.

Two-year follow-up of outcomes related to scarring and distress in children with severe burns

Abstract Purpose: We assessed the perception of scarring and distress by pediatric burn survivors with burns covering more than one-third of total body surface area (TBSA) for up to 2 years post-burn. Methods: Children with severe burns were admitted to our hospital between 2004 and 2012, and consented to this IRB-approved-study. Subjects completed at least one Scars Problems and/or Distress questionnaire between discharge and 24 months post burn. Outcomes were modeled with generalized estimating equations or using mixed linear models. Significance was accepted at p < 0.01. Results: Responses of 167 children with a mean age of 7 ± 5 years and burns covering an average 54 ± 14% of TBSA were analyzed. Significant improvements over the 2-year period were seen in reduction of pain, itching, sleeping disturbance, tightness, range of motion, and strength (p < 0.01). There was a significantly increased persistent desire to hide the scarred body areas over time (p < 0.01). The perception of mouth scarring, inability to portray accurate facial expressions, and skin coloration did not improve over the follow-up period. Conclusions: According to self-assessment questionnaires, severely burned children exhibit significant improvements in their overall perception of scarring and distress. However, these patients remain self-conscious with respect to their body image even 2 years after burn injury. Implications for Rehabilitation According to self-assessment questionnaires, severely burned children perceive significant improvements in scarring and distress during the first 2 years post burn. Significant improvements were seen in reduction of pain, itching, sleeping disturbances, tightness, range of motion, and strength (p < 0.01). Burn care providers should improve the treatment of burns surrounding the mouth that with result in scarring, and develop strategies to prevent skin discoloration. Careful evaluation of pain and sleeping disorders during the first year post burn are warranted to improve the patient rehabilitation. Overall, significantly more female patients expressed a persistent desire to hide their scarred body areas. The rehabilitation team should provide access to wigs or other aids to pediatric burn survivors to address these needs.

Body Composition Changes in Severely Burned Children during ICU Hospitalization

Objectives: Prolonged hospitalization due to burn injury results in physical inactivity and muscle weakness. However, how these changes are distributed among body parts is unknown. The aim of this study was to evaluate the degree of body composition changes in different anatomical regions during ICU hospitalization. Design: Retrospective chart review. Setting: Children’s burn hospital. Patients: Twenty-four severely burned children admitted to our institution between 2000 and 2015. Interventions: All patients underwent a dual-energy x-ray absorptiometry within 2 weeks after injury and 2 weeks before discharge to determine body composition changes. No subject underwent anabolic intervention. We analyzed changes of bone mineral content, bone mineral density, total fat mass, total mass, and total lean mass of the entire body and specifically analyzed the changes between the upper and lower limbs. Measurements and Main Results: In the 24 patients, age was 10 ± 5 years, total body surface area burned was 59% ± 17%, time between dual-energy x-ray absorptiometries was 34 ± 21 days, and length of stay was 39 ± 24 days. We found a significant (p < 0.001) average loss of 3% of lean mass in the whole body; this loss was significantly greater (p < 0.001) in the upper extremities (17%) than in the lower extremities (7%). We also observed a remodeling of the fat compartments, with a significant whole-body increase in fat mass (p < 0.001) that was greater in the truncal region (p < 0.0001) and in the lower limbs (p < 0.05). Conclusions: ICU hospitalization is associated with greater lean mass loss in the upper limbs of burned children. Mobilization programs should include early mobilization of upper limbs to restore upper extremity function.

The occurrence of single and multiple organ dysfunction in pediatric electrical versus other thermal burns

BACKGROUND Multiple organ failure (MOF) is a major contributor to morbidity and mortality in burned children. While various complications induced by electrical injuries have been described, the incidence and severity of single organ failure (SOF) and MOF associated with this type of injury are unknown. The study was undertaken to compare the incidence and severity of SOF and MOF as well as other complications between electrically and thermally burned children. PATIENTS AND METHODS Between 2001 and 2016, 288 pediatric patients with electrical burns (EB; n = 96) or thermal burns (CTR; n = 192) were analyzed in this study. Demographic data; length of hospitalization; and number and type of operations, amputations, and complications were statistically analyzed. Incidence of SOF and MOF was assessed using the DENVER2 classification in an additive mixed model over time. Compound scores and organ-specific scores for lung, heart, kidney, and liver were analyzed. Serum cytokine expression profiles of both groups were also compared over time. Significance was accepted at p < 0.05. RESULTS Both groups were comparable in age (CTR, 11 ± 5 years, vs EB, 11 ± 5 years), percent total body surface area burned (CTR, 33% ± 25%, vs EB, 32 ± 25%), and length of hospitalization (CTR, 18 ± 26 days, vs EB, 18 ± 21 days). The percentage of high-voltage injury in the EB group was 64%. The incidence of MOF was lower in the EB group (2 of 96 [2.1%]) than the CTR group (20 of 192 [10.4%]; p < 0.05). The incidence of single organ failure was comparable between groups. Incidence of pulmonary failure was comparable in both groups, but incidence of inhalation injury was significantly higher in the CTR group (p < 0.0001). Patients in the EB group had more amputations (p < 0.001), major amputations (p = 0.001), and combined major amputations (p < 0.01). Mortality was comparable between the groups. Serum cytokine expression profiles were also comparable between the groups. CONCLUSIONS In pediatric patients, electrical injury is associated with a lower incidence of MOF than other thermal burns. Early and radical debridement of nonviable tissue is crucial to improve outcomes in the electrical burn patient population. LEVEL OF EVIDENCE Retrospective chart review, level III.

Closed-Loop– and Decision-Assist–Guided Fluid Therapy of Human Hemorrhage

Objectives: We sought to evaluate the efficacy, efficiency, and physiologic consequences of automated, endpoint-directed resuscitation systems and compare them to formula-based bolus resuscitation. Design: Experimental human hemorrhage and resuscitation. Setting: Clinical research laboratory. Subjects: Healthy volunteers. Interventions: Subjects (n = 7) were subjected to hemorrhage and underwent a randomized fluid resuscitation scheme on separate visits 1) formula-based bolus resuscitation; 2) semiautonomous (decision assist) fluid administration; and 3) fully autonomous (closed loop) resuscitation. Hemodynamic variables, volume shifts, fluid balance, and cardiac function were monitored during hemorrhage and resuscitation. Treatment modalities were compared based on resuscitation efficacy and efficiency. Measurements and Main Results: All approaches achieved target blood pressure by 60 minutes. Following hemorrhage, the total amount of infused fluid (bolus resuscitation: 30 mL/kg, decision assist: 5.6 ± 3 mL/kg, closed loop: 4.2 ± 2 mL/kg; p < 0.001), plasma volume, extravascular volume (bolus resuscitation: 17 ± 4 mL/kg, decision assist: 3 ± 1 mL/kg, closed loop: –0.3 ± 0.3 mL/kg; p < 0.001), body weight, and urinary output remained stable under decision assist and closed loop and were significantly increased under bolus resuscitation. Mean arterial pressure initially decreased further under bolus resuscitation (–10 mm Hg; p < 0.001) and was lower under bolus resuscitation than closed loop at 20 minutes (bolus resuscitation: 57 ± 2 mm Hg, closed loop: 69 ± 4 mm Hg; p = 0.036). Colloid osmotic pressure (bolus resuscitation: 19.3 ± 2 mm Hg, decision assist, closed loop: 24 ± 0.4 mm Hg; p < 0.05) and hemoglobin concentration were significantly decreased after bolus fluid administration. Conclusions: We define efficacy of decision-assist and closed-loop resuscitation in human hemorrhage. In comparison with formula-based bolus resuscitation, both semiautonomous and autonomous approaches were more efficient in goal-directed resuscitation of hemorrhage. They provide favorable conditions for the avoidance of over-resuscitation and its adverse clinical sequelae. Decision-assist and closed-loop resuscitation algorithms are promising technological solutions for constrained environments and areas of limited resources.

Cardiorespiratory Capacity and Strength Remain Attenuated in Children with Severe Burn Injuries at Over 3 Years Postburn

Objectives To compare physical capacity and body composition between children with burn injuries at approximately 4 years postburn and healthy, fit children. Study design In this retrospective, case‐control study, we analyzed the strength, aerobic capacity, and body composition of children with severe burn injuries (n = 40) at discharge, after completion of a 6‐ to 12‐week rehabilitative exercise training program, and at 3‐4 years postburn. Values were expressed as a relative percentage of those in age‐ and sex‐matched children for comparison (n = 40 for discharge and postexercise; n = 40 for 3.5 years postburn). Results At discharge, lean body mass was 89% of that in children without burn injuries, and exercise rehabilitation restored this to 94% (P < .01). At 3.5 years postburn, lean body mass (94%), bone mineral content (89%), and bone mineral density (93%; each P ≤ .02) remained reduced, whereas total body fat was increased (148%, P = .01). Cardiorespiratory fitness remained lower in children with burn injuries both after exercise training (75%; P < .0001) and 3.5 years later (87%; P < .001). Peak torque (60%; P < .0001) and average power output (58%; P < .0001) were lower after discharge. Although exercise training improved these, they failed to reach levels achieved in healthy children without burns (83‐84%; P < .0001) but were maintained at 85% and 82%, respectively, 3.5 years later (P < .0001). Conclusions Although the benefits of rehabilitative exercise training on strength and cardiorespiratory capacity are maintained at almost 4 years postburn, they are not restored fully to the levels of healthy children. Although the underlying mechanism of this phenomenon remains elusive, these findings suggest that future development of continuous exercise rehabilitation interventions after discharge may further narrow the gap in relation to healthy adolescents.

Long-term effect of critical illness after severe paediatric burn injury on cardiac function in adolescent survivors: an observational study

Background Sepsis, trauma, and burn injury acutely depress systolic and diastolic cardiac function; data on long-term cardiac sequelae of pediatric critical illness are sparse. This study evaluated long-term systolic and diastolic function, myocardial fibrosis, and exercise tolerance in survivors of severe pediatric burn injury. Methods Subjects at least 5 years after severe burn (post-burn:PB) and age-matched healthy controls (HC) underwent echocardiography to quantify systolic function (ejection fraction[EF%]), diastolic function (E/e′), and myocardial fibrosis (calibrated integrated backscatter) of the left ventricle. Exercise tolerance was quantified by oxygen consumption (VO2) and heart rate at rest and peak exercise. Demographic information, clinical data, and biomarker expression were used to predict long-term cardiac dysfunction and fibrosis. Findings Sixty-five subjects (PB:40;HC:25) were evaluated. At study date, PB subjects were 19±5 years, were at 12±4 years postburn, and had burns over 59±19% of total body surface area, sustained at 8±5 years of age. The PB group had lower EF% (PB:52±9%;HC:61±6%; p=0.004), E/e′ (PB:9.8±2.9;HC: 5.4±0.9;p<0.0001), VO2peak (PB:37.9±12;HC: 46±8.32 ml/min/kg; p=0.029), and peak heart rate (PB:161±26;HC:182±13bpm;p=0.007). The PB group had moderate (28%) or severe (15%) systolic dysfunction, moderate (50%) or severe diastolic dysfunction (21%), and myocardial fibrosis (18%). Biomarkers and clinical parameters predicted myocardial fibrosis, systolic dysfunction, and diastolic dysfunction. Interpretation Severe pediatric burn injury may have lasting impact on cardiac function into young adulthood and is associated with myocardial fibrosis and reduced exercise tolerance. Given the strong predictive value of systolic and diastolic dysfunction, these patients might be at increased risk for early heart failure, associated morbidity, and mortality. Funding Conflicts of Interest and Sources of Funding: The authors do not have any conflicts of interest to declare. This work was supported by NIH (P50 GM060338, R01 GM056687, R01 HD049471, R01 GM112936, R01-GM56687 and T32 GM008256), NIDILRR (H133A120091, 90DP00430100), Shriners Hospitals for Children (84080, 79141, 79135, 71009, 80100, 71008, 87300 and 71000), FAER (MRTG CON14876), and the Department of Defense (W81XWH-14-2-0162 and W81XWH1420162). It was also made possible with the support of UTMB’s Institute for Translational Sciences, supported in part by a Clinical and Translational Science Award (UL1TR000071) from the National Center for Advancing Translational Sciences (NIH).