An alteration of the gut-liver axis drives pulmonary inflammation after intoxication and burn injury in mice

Approximately half of all adult burn patients are intoxicated at the time of their injury and have worse clinical outcomes than those without prior alcohol exposure. This study tested the hypothesis that intoxication alters the gut-liver axis, leading to increased pulmonary inflammation mediated by burn-induced IL-6 in the liver. C57BL/6 mice were given 1.2 g/kg ethanol 30 min prior to a 15% total body surface area burn. To restore gut barrier function, the specific myosin light chain kinase inhibitor membrane-permeant inhibitor of kinase (PIK), which we have demonstrated to reduce bacterial translocation from the gut, was administered 30 min after injury. Limiting bacterial translocation with PIK attenuated hepatic damage as measured by a 47% reduction in serum alanine aminotransferase ( P < 0.05), as well as a 33% reduction in hepatic IL-6 mRNA expression ( P < 0.05), compared with intoxicated and burn-injured mice without PIK. This mitigation of hepatic damage was associated with a 49% decline in pulmonary neutrophil infiltration ( P < 0.05) and decreased alveolar wall thickening compared with matched controls. These results were reproduced by prophylactic reduction of the bacterial load in the intestines with oral antibiotics before intoxication and burn injury. Overall, these data suggest that the gut-liver axis is deranged when intoxication precedes burn injury and that limiting bacterial translocation in this setting attenuates hepatic damage and pulmonary inflammation.

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Arginine in burn injury improves cardiac performance and prevents bacterial translocation

Journal of Applied Physiology ◽

10.1152/jappl.1998.84.2.695 ◽

1998 ◽

Vol 84 (2) ◽

pp. 695-702 ◽

Cited By ~ 35

Author(s):

Jureta W. Horton ◽

Jean White ◽

David Maass ◽

Billy Sanders

Keyword(s):

Blood Pressure ◽

Bacterial Translocation ◽

Fluid Resuscitation ◽

Burn Injury ◽

Total Body Surface Area ◽

Cardiac Performance ◽

Pharmacological Intervention ◽

Adult Rats ◽

Burn Trauma ◽

Cardiac Contractile

Horton, Jureta W., Jean White, David Maass, and Billy Sanders. Arginine in burn injury improves cardiac performance and prevents bacterial translocation. J. Appl. Physiol. 84(2): 695–702, 1998.—This study examined the effects of arginine supplement of fluid resuscitation from burn injury on cardiac contractile performance and bacterial translocation after a third-degree burn comprising 43% of the total body surface area in adult rats. Before burn injury, rats were instrumented to measure blood pressure; after burn (or sham injury), paired groups of sham-burned and burned rats were given vehicle (saline), l-arginine,d-arginine, or N-methyl-l-arginine (300 mg/kg in 0.3 ml of saline 30 min, 6 h, and 23 h postburn) plus fluid resuscitation; sham-burned rats received drug only. Twenty-four hours after burn trauma, hemodynamics were measured; the animals were then killed and randomly assigned to Langendorff heart studies or to studies examining translocation of gut bacteria. Burn rats treated with vehicle,d-arginine, or N-methyl-l-arginine had well-defined cardiocirculatory responses that included hypotension, tachycardia, respiratory compensation for metabolic acidosis, hypocalcemia, cardiac contractile depression, and significant bacterial translocation. Compared with values measured in vehicle-treated burn rats, l-arginine given after burn improved blood pressure, prevented tachycardia, reduced serum lactate levels, improved cardiac performance, and significantly reduced bacterial translocation, confirming thatl-arginine administration after burn injury provided significant cardiac and gastrointestinal protection. Circulating neutrophil counts fell after burn trauma and serum glucagon levels rose, but these changes were not altered by pharmacological intervention. Our finding of significantly higher coronary perfusate guanosine 3′,5′-cyclic monophosphate concentration inl-arginine-treated burn rats suggests that the beneficial effects ofl-arginine were mediated by nitric oxide production.

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Kupffer Cell p38 Mitogen-Activated Protein Kinase Signaling Drives Postburn Hepatic Damage and Pulmonary Inflammation When Alcohol Intoxication Precedes Burn Injury

Critical Care Medicine ◽

10.1097/ccm.0000000000001817 ◽

2016 ◽

Vol 44 (10) ◽

pp. e973-e979 ◽

Cited By ~ 5

Author(s):

Michael M. Chen ◽

Eileen B. O’Halloran ◽

Jill A. Shults ◽

Elizabeth J. Kovacs

Keyword(s):

Protein Kinase ◽

Kupffer Cell ◽

Burn Injury ◽

Alcohol Intoxication ◽

Pulmonary Inflammation ◽

Hepatic Damage ◽

Mitogen Activated Protein Kinase ◽

Kinase Signaling ◽

Mitogen Activated Protein ◽

Protein Kinase Signaling

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Gut-associated lymphoid T cell suppression enhances bacterial translocation in alcohol and burn injury

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.00235.2001 ◽

2002 ◽

Vol 282 (6) ◽

pp. G937-G947 ◽

Cited By ~ 83

Author(s):

Mashkoor A. Choudhry ◽

Nadeem Fazal ◽

Masakatsu Goto ◽

Richard L. Gamelli ◽

Mohammed M. Sayeed

Keyword(s):

T Cell ◽

Lymph Nodes ◽

Intestinal Permeability ◽

Bacterial Translocation ◽

Burn Injury ◽

Alcohol Exposure ◽

Immune Defense ◽

Intestinal Morphology ◽

Mesenteric Lymph Nodes ◽

Mesenteric Lymph

The mechanism of alcohol-mediated increased infection in burn patients remains unknown. With the use of a rat model of acute alcohol and burn injury, the present study ascertained whether acute alcohol exposure before thermal injury enhances gut bacterial translocation. On day 2postinjury, we found a severalfold increase in gut bacterial translocation in rats receiving both alcohol and burn injury compared with the animals receiving either injury alone. Whereas there were no demonstrable changes in intestinal morphology in any group of animals, a significant increase in intestinal permeability was observed in ethanol- and burn-injured rats compared with the rats receiving either injury alone. We further examined the role of intestinal immune defense by determining the gut-associated lymphoid (Peyer's patches and mesenteric lymph nodes) T cell effector responses 2 days after alcohol and burn injury. Although there was a decrease in the proliferation and interferon-γ by gut lymphoid T cells after burn injury alone; the suppression was maximum in the group of rats receiving both alcohol and burn injuries. Furthermore, the depletion of CD3+cells in healthy rats resulted in bacterial accumulation in mesenteric lymph nodes; such CD3+cell depletion in alcohol- and burn-injured rats furthered the spread of bacteria to spleen and circulation. In conclusion, our data suggest that the increased intestinal permeability and a suppression of intestinal immune defense in rats receiving alcohol and burn injury may cause an increase in bacterial translocation and their spread to extraintestinal sites.

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Kupffer Cell p38 MAPK Drives Hepatic Damage and Pulmonary Inflammation after Intoxication and Burn Injury

The FASEB Journal ◽

10.1096/fasebj.29.1_supplement.1004.5 ◽

2015 ◽

Vol 29 (S1) ◽

Author(s):

Michael Chen ◽

Eileen O'halloran ◽

Elizabeth Kovacs

Keyword(s):

P38 Mapk ◽

Kupffer Cell ◽

Burn Injury ◽

Pulmonary Inflammation ◽

Hepatic Damage

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Treatment of Anaemia in Patients with Acute Burn Injury: A Study of Blood Transfusion Practices

Journal of Clinical Medicine ◽

10.3390/jcm10030476 ◽

2021 ◽

Vol 10 (3) ◽

pp. 476

Author(s):

Ioana Tichil ◽

Samara Rosenblum ◽

Eldho Paul ◽

Heather Cleland

Keyword(s):

Blood Transfusion ◽

Surgical Management ◽

Burn Injury ◽

Total Body Surface Area ◽

Perioperative Period ◽

Hospital Length ◽

Hospital Length Of Stay ◽

Burn Care ◽

Transfusion Requirements ◽

Total Body

Objective: To determine blood transfusion practices, risk factors, and outcomes associated with the use of blood products in the setting of the acute management of burn patients at the Victorian Adult Burn Service. Background: Patients with burn injuries have variable transfusion requirements, based on a multitude of factors. We reviewed all acute admissions to the Victorian Adult Burns Service (VABS) between 2011 and 2017: 1636 patients in total, of whom 948 had surgery and were the focus of our analysis. Method and results: Patient demographics, surgical management, transfusion details, and outcome parameters were collected and analyzed. A total of 175 patients out of the 948 who had surgery also had a blood transfusion, while 52% of transfusions occurred in the perioperative period. The median trigger haemoglobin in perioperative was 80mg/dL (IQR = 76–84.9 mg/dL), and in the non-perioperative setting was 77 mg/dL (IQR = 71.61–80.84 mg/dL). Age, gender, % total body surface area (TBSA) burn, number of surgeries, and intensive care unit and hospital length of stay were associated with transfusion. Conclusions: The use of blood transfusions is an essential component of the surgical management of major burns. As observed in our study, half of these transfusions are related to surgical procedures and may be influenced by the employment of blood conserving strategies. Furthermore, transfusion trigger levels in stable patients may be amenable to review and reduction. Risk adjusted analysis can support the implementation of blood transfusion as a useful quality indicator in burn care.

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531 The Effect of Burn Wound Size on Caloric Requirements: A Correlation of Nutritional Changes to the Clinical State

Journal of Burn Care & Research ◽

10.1093/jbcr/irab032.181 ◽

2021 ◽

Vol 42 (Supplement_1) ◽

pp. S113-S114

Author(s):

Marc R Matthews ◽

Sara Calder ◽

Areta Kowal-Vern ◽

Philomene Spadafore ◽

Karen J Richey ◽

...

Keyword(s):

Injury Severity ◽

Burn Injury ◽

Recovery Period ◽

Total Body Surface Area ◽

Caloric Intake ◽

Retrospective Chart Review ◽

Clinical State ◽

Apache Score ◽

Burn Wound ◽

Caloric Requirements

Abstract Introduction Caloric intake has been a vital component for burn wound healing and recovery. The hypothesis was that caloric requirements are based on injury severity & post-burn week as predicated by indirect calorimetry (IC)/predictive equations. Methods This was a retrospective chart review of 115 burn patients (2012–2017). Caloric requirements were determined by the Curreri equation [which includes % total body surface area (TBSA)] and IC for a 5-week period provided mainly by enteral nutrition. Patients received supplements and total parenteral nutrition as needed. Results The mean ±sd age was 43±18 years, 41±18 % TBSA, Body Mass Index of 28±7 kg/m2, and mortality of 26 (23%). The major mechanisms of injury were flame/flash/explosions. There were 59 (51%) of patients with < 40 % TBSA burns, [median Injury Severity Score (ISS) 9; Apache score 14], and 56 (49%) with ≥40 % TBSA (median ISS 25; Apache score 21), p < .0001. The Respiratory Quotient (RQ) had a median of 0.94 (range 0.79 to 1.02). The median number of surgeries for the < 40 % TBSA group was 5 versus 12 for the ≥40 % TBSA, p < .0001. The Injury Factor did not differ from weeks 1–5 (1.8 for < 40 % TBSA and 2.0 for the ≥ 40 % TBSA). The Curreri equation calculation for this study was a median 3640 (range 2161–5950) calories. The Curreri equation resulted in significantly increased caloric recommendations for the ≥ 40 %TBSA compared to the < 40 %TBSA patients, p < .0001. The < 40 %TBSA group had caloric requirements ranging between 1500- 2700 calories compared to the ≥ 40 %TBSA group, whose calories ranged between 2000–3700. The total daily caloric recommendations were also significantly increased in the ≥40 %TBSA compared to the < 40 %TBSA patients. The maximum levels of resting energy expenditure (REE) from IC, total daily calories recommended by the dietitian and average calories ranged between 3000–4500 in the < 40 %TBSA group and 3600–6700 in the ≥ 40 %TBSA group. The caloric recommendations increased for all patients from week 1 to week 3 and leveled off during weeks 4–5. Conclusions Patient caloric requirements were dependent not only on the severity of the burn injury but also the post-burn hospitalization during which surgeries, debridement/grafting, and infectious complications occurred. They increased until the third week post-burn and leveled off in the recovery period. The study caloric recommendations and requirements were consistent with the REE and Curreri equation assessments.

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11 Vitamin D Deficiency on Admission and the Association with Length of Stay in Patients with Thermal Injury: A Multi-center Analysis

Journal of Burn Care & Research ◽

10.1093/jbcr/irab032.016 ◽

2021 ◽

Vol 42 (Supplement_1) ◽

pp. S13-S14

Author(s):

Sarah Zavala ◽

Kate Pape ◽

Todd A Walroth ◽

Melissa A Reger ◽

Katelyn Garner ◽

...

Keyword(s):

Vitamin D ◽

Length Of Stay ◽

Vitamin D Deficiency ◽

Burn Injury ◽

Total Body Surface Area ◽

Inhalation Injury ◽

Hospital Length Of Stay ◽

Burn Patients ◽

Comfort Care ◽

The Impact

Abstract Introduction In burn patients, vitamin D deficiency has been associated with increased incidence of sepsis. The objective of this study was to assess the impact of vitamin D deficiency in adult burn patients on hospital length of stay (LOS). Methods This was a multi-center retrospective study of adult patients at 7 burn centers admitted between January 1, 2016 and July 25, 2019 who had a 25-hydroxyvitamin D (25OHD) concentration drawn within the first 7 days of injury. Patients were excluded if admitted for a non-burn injury, total body surface area (TBSA) burn less than 5%, pregnant, incarcerated, or made comfort care or expired within 48 hours of admission. The primary endpoint was to compare hospital LOS between burn patients with vitamin D deficiency (defined as 25OHD < 20 ng/mL) and sufficiency (25OHD ≥ 20 ng/mL). Secondary endpoints include in-hospital mortality, ventilator-free days of the first 28, renal replacement therapy (RRT), length of ICU stay, and days requiring vasopressors. Additional data collected included demographics, Charlson Comorbidity Index, injury characteristics, form of vitamin D received (ergocalciferol or cholecalciferol) and dosing during admission, timing of vitamin D initiation, and form of nutrition provided. Dichotomous variables were compared via Chi-square test. Continuous data were compared via student t-test or Mann-Whitney U test. Univariable linear regression was utilized to identify variables associated with LOS (p < 0.05) to analyze further. Cox Proportional Hazard Model was utilized to analyze association with LOS, while censoring for death, and controlling for TBSA, age, presence of inhalation injury, and potential for a center effect. Results Of 1,147 patients screened, 412 were included. Fifty-seven percent were vitamin D deficient. Patients with vitamin D deficiency had longer LOS (18.0 vs 12.0 days, p < 0.001), acute kidney injury (AKI) requiring RRT (7.3 vs 1.7%, p = 0.009), more days requiring vasopressors (mean 1.24 vs 0.58 days, p = 0.008), and fewer ventilator free days of the first 28 days (mean 22.9 vs 25.1, p < 0.001). Univariable analysis identified burn center, AKI, TBSA, inhalation injury, admission concentration, days until concentration drawn, days until initiating supplementation, and dose as significantly associated with LOS. After controlling for center, TBSA, age, and inhalation injury, the best fit model included only deficiency and days until vitamin D initiation. Conclusions Patients with thermal injuries and vitamin D deficiency on admission have increased length of stay and worsened clinical outcomes as compared to patients with sufficient vitamin D concentrations.

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Burn-induced heterotopic ossification from incidence to therapy: key signaling pathways underlying ectopic bone formation

Cellular & Molecular Biology Letters ◽

10.1186/s11658-021-00277-6 ◽

2021 ◽

Vol 26 (1) ◽

Author(s):

Xianglin Hu ◽

Zhengwang Sun ◽

Fengfeng Li ◽

Chaoyin Jiang ◽

Wangjun Yan ◽

...

Keyword(s):

Growth Factor ◽

Heterotopic Ossification ◽

Transforming Growth Factor ◽

Burn Injury ◽

Hypoxia Inducible Factor ◽

Total Body Surface Area ◽

Adaptive Immune System ◽

Transforming Growth Factor Β1 ◽

Mesenchymal Transition ◽

Endothelial To Mesenchymal Transition

AbstractBurn injury is one of the potential causes of heterotopic ossification (HO), which is a rare but debilitating condition. The incidence ranges from 3.5 to 5.6 depending on body area. Burns that cover a larger percentage of the total body surface area (TBSA), require skin graft surgeries, or necessitate pulmonary intensive care are well-researched risk factors for HO. Since burns initiate such complex pathophysiological processes with a variety of molecular signal changes, it is essential to focus on HO in the specific context of burn injury to define best practices for its treatment. There are numerous key players in the pathways of burn-induced HO, including neutrophils, monocytes, transforming growth factor-β1-expressing macrophages and the adaptive immune system. The increased inflammation associated with burn injuries is also associated with pathway activation. Neurological and calcium-related contributions are also known. Endothelial-to-mesenchymal transition (EMT) and vascularization are known to play key roles in burn-induced HO, with hypoxia-inducible factor-1 (HIF-1) and vascular endothelial growth factor (VEGF) as potential initiators. Currently, non-steroidal anti-inflammatory drugs (NSAIDs) and radiotherapy are effective prophylaxes for HO. Limited joint motion, ankylosis and intolerable pain caused by burn-induced HO can be effectively tackled via surgery. Effective biomarkers for monitoring burn-induced HO occurrence and bio-prophylactic and bio-therapeutic strategies should be actively developed in the future.

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Pediatric burn resuscitation: past, present, and future

Burns & Trauma ◽

10.1186/s41038-017-0091-y ◽

2017 ◽

Vol 5 ◽

Cited By ~ 15

Author(s):

Kathleen S. Romanowski ◽

Tina L. Palmieri

Keyword(s):

Fluid Resuscitation ◽

Burn Injury ◽

Total Body Surface Area ◽

Burn Shock ◽

Basic Principles ◽

Future Directions ◽

Number Of Children ◽

History Of ◽

Adults And Children ◽

Total Body

Abstract Burn injury is a leading cause of unintentional death and injury in children, with the majority being minor (less than 10%). However, a significant number of children sustain burns greater than 15% total body surface area (TBSA), leading to the initiation of the systemic inflammatory response syndrome. These patients require IV fluid resuscitation to prevent burn shock and death. Prompt resuscitation is critical in pediatric patients due to their small circulating blood volumes. Delays in resuscitation can result in increased complications and increased mortality. The basic principles of resuscitation are the same in adults and children, with several key differences. The unique physiologic needs of children must be adequately addressed during resuscitation to optimize outcomes. In this review, we will discuss the history of fluid resuscitation, current resuscitation practices, and future directions of resuscitation for the pediatric burn population.

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