Postburn Day Research Articles

The time factor in the LDI (Laser Doppler Imaging) diagnosis of burns.

The not quite rare occurrence of inaccurate clinical diagnoses of burns in early post-burn days leads to an inappropriate conservative treatment strategy, or unnecessary surgery. LDI (Laser Doppler Imaging) objectively evaluates skin blood circulation, which correlates with the depth of the burn and the length of healing. The aim of this work was to suggest cutoff values for detecting burns without healing potential within 3 weeks, which should have undergone surgery. The burned area's average blood perfusion of 148 burns was measured on 115 patients, using the Laser Doppler Imager PIM III. A total of 268 measurements were performed from the one to the ninth post-burn day (PBD). The perfusion values were compared to the healing time or histology in the case of the surgical treatment. Cutoff values indicating surgery were investigated in various post-burn days; the ROC analysis was used. This work suggest statistically significant increasing cutoff values for indication to surgery (P = 0.05). From the third to the fifth day 148.5 perfusion units (PU), from the sixth to the seventh day 186.0 PU, from the eighth to the ninth PBD 269.5 PU. The cutoff value is not possible to establish until the second day. LDI is a useful method for wound healing prediction and an indication of the necessity of surgery. We have demonstrated that the diagnosis of the healing capacity of LDI needs to take into account the factor of time.

Enteral nutrition: what the dietitian prescribes is not what the burn patient gets!

Enteral nutrition (EN) is commonly interrupted in burn patients for many reasons, which leads to discrepancies between prescribed and actual EN delivery. The magnitude and origin of these discrepancies have never been well documented among burn patients. The purpose of this study was to examine differences between prescribed and actual EN delivery and to identify the specific causes of EN interruption and to quantify these. Retrospective review of patients treated between June 6, 2009 and June 6, 2012 at an adult regional American Burn Association-verified burn center who had ≥10% TBSA burns and who were prescribed EN for at least 24 hours. On postburn days (PBD) 0 to 14 the daily volume of EN prescribed by the dietitian was compared with the actual volume received by the patient. The cause and duration of interruptions to EN delivery were recorded. A total of 90 subjects, [mean (± SD) age 47 ± 18 years, 32% female, median %TBSA burn size 28, median %TBSA full-thickness burn size 11, and a 54% incidence of inhalation injury], were studied. EN was initiated at a median of 9.5 hours after burn center admission. Received calories were significantly less than prescribed calories on every study day. The median daily caloric deficit ranged between 172 and 930 kcal. The median percent of prescribed calories received each day ranged from 19% on PBD 0 to 91% on PBD 14. The mean (± SD) total duration of EN interruption was 8.9 ± 3.0 hours per day. Gradually increasing the feed rate to reach the prescribed EN goal rate ("ramping-in") was the most common cause of a discrepancy between prescribed and actual EN delivery, accounting for 35% of total discrepancy time. Interruptions for surgery accounted for 24% of total discrepancy time. Other causes of discrepancies were physician- or nurse-directed interruptions (16% of time), planned extubation (7%), feed intolerance (11%), tube malfunction (2%), bedside procedures (2%), and dressing changes (3%).Enterally fed burn patients received significantly less nutrition than prescribed. Some of the causes for discrepancies between prescribed and received EN are unavoidable, but many are not, suggesting the need for careful review and possible alteration of existing EN practices.

Clinical safety and efficacy of probiotic administration following burn injury.

Provision of probiotics has been limited postburn by questionable potential for bacterial translocation and risk of infection in an immune-compromised population. The purpose of this study was to evaluate the safety of probiotic administration in acutely burned, pediatric patients. Subjects were randomized to receive probiotic (n = 10) vs placebo (n = 10) twice daily. The investigational product was initiated within 10 days of burn, and daily supplementation continued until wound closure. Nursing staff was provided education regarding optimal procedures to minimize potential for study product cross contamination. Clinical outcomes (infection, antibiotic, antifungal, and operative days, tolerance, and mortality) were recorded. Length of stay was modified for burn size. Student's t-test, χ test, and nonparametric Wilcoxon's rank-sum test were used for comparative analysis. No differences were noted (probiotic; placebo) for age (7.1 ± 2.2; 6.9 ± 1.7), burn size (38.0 ± 5.9; 45.5 ± 4.45), full thickness (24.6 ± 5.6; 32.1 ± 5.4), postburn day admit (0.8 ± 0.4; 1.1 ± 0.4), or inhalation injury (10%; 20%). Infection days, antibiotic use, constipation, and emesis were similar between groups. Trends toward increased antifungal and laxative use as well as diarrhea incidence were evident in the controls (P < .30). Flatulence was statistically higher with probiotics. The control group trended toward higher requirement for excision/graft procedure. Medical length of stay was not significantly different between groups; however, time required to complete wound healing was shortened with probiotics. This study documents safety and provides preliminary efficacy data relative to probiotic supplementation postburn.

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

ObjectiveAn 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.MethodsResting 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.ResultsComparative 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).ConclusionThe 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 RegistrationThe study was registered on Chinese Clinical Trial Registry as ChiCTR-TRC-13003806.

Vecuronium Pharmacokinetics in Patients With Major Burns

Abstract Background Burn patients develop resistance to non-depolarizing neuromuscular blocking agents (NDNMBAs) and require a significantly large dose to produce a desired clinical response. Pathophysiological changes related to burn injury may alter pharmacokinetics (PK) and pharmacodynamics of NDNMBAs. The purpose of this study was to compare vecuronium PK in burns vs non-burns. Methods Twenty adults, aged 23–58 yr, with 27–81% total body surface area (TBSA) burn, were studied at 4–57 post-burn days and compared with age- and sex-matched, non-burn controls. Vecuronium 0.12 mg kg −1 was given i.v. as a single bolus within 10 s. Blood samples ( n =20) were collected over 12 h at predetermined time points. NONMEM was used to describe plasma drug concentration–time profiles for burns and non-burns. Results A three-compartment model best described vecuronium concentration–time profiles. Burn patients showed enhanced distributional clearance at the terminal phase (0.12 vs 0.095 litre min −1 , P vs 6.6 h, P Conclusions The altered drug distribution between tissues may partially explain the known resistance to vecuronium in patients with major burns.

Characterization of burns using hyperspectral imaging technique – A preliminary study

Surgical burn treatment depends on accurate estimation of burn depth. Many methods have been used to asses burns, but none has gained wide acceptance. Hyperspectral imaging technique has recently entered the medical research field with encouraging results. In this paper we present a preliminary study (case presentation) that aims to point out the value of this optical method in burn wound characterization and to set up future lines of investigation. A hyperspectral image of a leg and foot with partial thickness burns was obtained in the fifth postburn day. The image was analyzed using linear spectral unmixing model as a tool for mapping the investigated areas. The article gives details on the mathematical bases of the interpretation model and correlations with clinical examination pointing out the advantages of hyperspectral imaging technique. While the results were encouraging, further more extended and better founded studies are being prepared before recognizing hyperspectral imaging technique as an applicable method of burn wound assessment.

Energy expenditure prediction equations in burn patients; bibliographic review

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. we analyze the history and state of art of the use of REE predictive equations in burn patients, and determine their validity. bibliographic review of the studies and reviews written in English and Spanish between 1989 and 2013. 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. 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.

Vulval burn due to a recreational drug: gamma hydroxybutaric acid

Sir, Burns due to chemical agents account for 3 % of all burns, though they cause more than 30 % of burn deaths [1]. Genital burns are less frequently seen in comparison with other burns. In the study of Michielsen et al., it was 3 %, in the report of Peck et al. 5 % and Alghanem et al. 1 % [2–4]. Isolated genital burns due to chemical agents are extremely rare. Literature on burn due to gamma hydroxybutaric acid (GHB) is scarce, and we thought it is worth presenting this unusual complication. A 19-year-old girl presented with a 3-day-old burn involving the vulva, right inner thigh and buttock. She stated that she slept 2 days back with a bottle of liquid GHB in her underpants while under the influence of intravenous heroin and “ice” (methamphetamine hydrochloride). She felt severe pain around her vulval region around 1500 hours the next day. Pain had not subsided with water irrigation. She failed to give a proper history regarding the mechanism of burn as she was in an unarousable state at that night. Leakage of GHB was the most likely cause of her burns. Examination revealed patchy full-thickness burns over the right labium majus, labia minora, right inner thigh and buttock, with a total surface area of 1% (Figs. 1 and 2). There was no involvement of the urethral or vaginal orifices, and she had no difficulty in passing urine. She used to consume a cocktail of heroin, methamphetamine, benzodiazepine, ethanol and GHB. She had a past history of unsuccessful detoxification of heroin. There were no self-inflicted injuries or burn in the past. She was catheterized and the vulval burns were covered with silver sulfadiazine due to pain issue. The rest of the burn was dressed with silver-impregnated dressing. Initial management was done in the intensive care unit to treat withdrawal effects. The first theatre session took place on the fifth postburn day, and the debridement of all burn wounds was performed. Skin grafting was postponed as the depth of burn was not obvious. Thigh and buttock wounds were reexcised and mesh grafting done (postburn day 7), and the graft was secured with negative pressure wound therapy (75 mmHg). The vulval wounds were managed conservatively with regular application of povidone iodine ointment. She had an uneventful recovery and self-discharged. The first clinic review remarked complete wound healing. Unfortunately, she defaulted subsequent clinic visits to scrutinize the behaviour of scars following GHB burns. Gamma hydroxybutyric acid is a naturally occurring substance found in the human central nervous system. It is also categorized as an illegal drug in many countries and regulated in Australia, Canada, New Zealand, the USA and some European countries. It is used medically to treat conditions like narcolepsy and alcoholism. GHB is the active substance in prescribed medication sodium oxybate (Xyrem (Jazz Pharmaceuticals, Inc., Palo Alto, CA, USA), Alcover (Laboratorio

Vecuronium pharmacokinetics in patients with major burns

BackgroundBurn patients develop resistance to non-depolarizing neuromuscular blocking agents (NDNMBAs) and require a significantly large dose to produce a desired clinical response. Pathophysiological changes related to burn injury may alter pharmacokinetics (PK) and pharmacodynamics of NDNMBAs. The purpose of this study was to compare vecuronium PK in burns vs non-burns. MethodsTwenty adults, aged 23–58 yr, with 27–81% total body surface area (TBSA) burn, were studied at 4–57 post-burn days and compared with age- and sex-matched, non-burn controls. Vecuronium 0.12 mg kg−1 was given i.v. as a single bolus within 10 s. Blood samples (n=20) were collected over 12 h at predetermined time points. NONMEM was used to describe plasma drug concentration–time profiles for burns and non-burns. ResultsA three-compartment model best described vecuronium concentration–time profiles. Burn patients showed enhanced distributional clearance at the terminal phase (0.12 vs 0.095 litre min−1, P<0.0001), which yielded shorter elimination half-life for vecuronium (5.5 vs 6.6 h, P<0.001). BURN was the single most significant covariate that explained the altered vecuronium disposition in burns. ConclusionsThe altered drug distribution between tissues may partially explain the known resistance to vecuronium in patients with major burns.

Wound healing trajectories in burn patients and their impact on mortality.

The rate of wound healing and its effect on mortality has not been well described. The objective of this article is to report wound healing trajectories in burn patients and analyze their effects on in-hospital mortality. The authors used software (WoundFlow) to depict burn wounds, surgical results, and healing progression at multiple time points throughout admission. Data for all patients admitted to the intensive care unit with ≥ 20% TBSA burned were collected retrospectively. The open wound size (OWS), which includes both unhealed burns and unhealed donor sites, was measured. We calculated the rate of wound closure (healing rate), which we defined as the change in OWS/time. We also determined the time delay (DAYS) from day of burn until day on which there was a reduction in OWS < 10%. Data are medians [interquartile range]. There were 38 patients with complete data; 25 had documentation of successful healing (H), and 13 did not (NH). H differed from NH on age (38 years [32-57] vs 63 [51-74]), body mass index (27 [21-28] vs 32 [19-52]), 24-hour fluid resuscitation (12 L [10-16] vs 18 [15-20]), pressors during first 48 hours (72% vs 100%), use of renal replacement therapy (32% vs 92%), and mortality (4% vs 100%). Repeated measures analysis of covariance showed a significant difference between survivors and nonsurvivors on OWS as a function of time (P<.001). Patients with a positive healing rate (+2%/day) after postburn day 20 had 100% survival whereas those with a negative healing rate (-2%/day) had 100% mortality. For H patients, median DAYS was 41 (28-54); median DAYS/TBSA was 1.3 (1.0-1.9). Survivors had a 0.62% drop in OWS/day, or 4.3%/week. In this cohort of patients with ≥ 20% TBSA, there was a difference in mortality after postburn day 20, between patients with a positive healing rate (+2%/day, 100% survival) and those with a negative healing rate (-2%/day, 100% mortality, P < .05).

Activities of nonlysosomal proteolytic systems in skeletal and cardiac muscle during burn-induced hypermetabolism.

The aim of this study was to assess the activity of nonlysosomal proteolytic systems in skeletal and cardiac muscle during burn-induced hypermetabolism (BHM) in rats. Rats underwent 30% TBSA scald burn or sham injury and were observed for up to 42 days. Body weights and resting energy expenditures were determined weekly. Skeletal (soleus/pectoral) muscle and hearts were harvested on days 0 (=control), 7, 14, 21, and 42 after burn. Calpain, caspase-1, caspase-3/7, caspase-6, caspase-8, caspase-9, and proteasome peptidase activities were measured in tissue extracts. Hypermetabolism developed within 3 weeks after burns, as documented by increased resting energy expenditures and decreased body weights on postburn days 21 to 42 (P < 0.05 vs control). Calpain activities did not show significant alterations. Pan caspase activities increased by time and were significantly increased in skeletal and cardiac muscle extracts during hypermetabolism. Although increases in caspase-1, caspase-8, and caspase-9 activities were predominantly responsible for elevated pan caspase activities in skeletal muscle, increases in caspase-6 activities dominated in the heart. Proteasome peptidase activities in skeletal muscle extracts were not significantly altered. Proteasome peptidase activities in heart extracts increased time dependently and were significantly increased during BHM. Activation of caspase cascades during BHM constitutes a uniform response in skeletal and cardiac muscle and may contribute to enhanced metabolic protein turnover. Activation of myocardial proteasome activities may reflect persistent cardiac stress. Further exploration of caspase cascades and the proteasome as therapeutic targets to influence long-term consequences of BHM appears justified.

A study of prognostic factors for prediction of complications and outcomes in burn patients

Aim: The aim of the present study is to evaluate various prognostic factors in burn patients and predict prognosis and mortality of patients on the basis of prognostic factors. Materials and Methods: A study was conducted on 10 adults, total body surface area burns of >40% (40-90%) sequential thermal burn admissions at Burns Center. Blood samples were drawn from day of admission to discharge. Results and Statistics: (1) Fatal outcome in four patients, persistent serum cholesterol <100 mg%. (2) The difference in cholesterol values in patients with fatal outcome and survivors was significant. On comparing median cholesterol values for non-survivors and survivors on post-burn day-7, there was statistically significant difference (P = 0.039) by Mann-Whitney U-test. Serum cholesterol was significantly lower in fatal cases. (3) Infection or sepsis in patients correlated with the presence of toxic granules, toxic vacuoles on peripheral smear, raised total leukocyte count and low values of serum cholesterol. (4) Echinocytes (spiculated red blood cells [RBC]) were seen in all patients. In four patients, they persisted from post-burn day 4 until death. Progressive decrease in echinocytes, which correlated with rising cholesterol values was seen in survivors. Conclusion: Poor outcome in burn patients is related to persistently low serum cholesterol, high serum triglyceride and presence of echinocytes, toxic granules, toxic vacuoles and high white blood cell counts or vice-versa.

Upper gastrointestinal lesions and bleed in burn injuries: An endoscopic evaluation

Upper gastrointestinal lesions are a known complication in burn injuries and are considered to be caused by acid-peptic digestion of gastric mucosa. Antacids and H2- receptor blockers are administered to neutralize the gastric secretions. The study aims to observe the incidence of upper gastrointestinal lesions, their natural course, the influence of the early oral feeds, oral Sucralfate and parenteral Ranitidine, the clinical and endoscopic incidence of the bleed. This study was undertaken on 92 patients having burns varying between 10% and 70% of body surface area and admitted within 24 h of the injury. Patients were divided randomly into three groups. Group I: Ranitidine at a dose of 50 mg intravenously twice a day was commenced from the time of admission and oral feeds after 24 h. Group II: Oral feeds, and sucralfate, 2 g at four hourly interval were administered from the time of admission. Group III: Oral feeds alone were given from the time of admission. Endoscopy was done at weekly interval, starting after 3 rd postburn day, after stabilization of the patient. Upper Gastrointestinal lesions were seen in 46% of patients, and they lasted up to 6 weeks while only 8% developed bleed. The lesions showed a direct proportionate relationship to the percentage of burn. Both Group I and Group III patients developed bleed, the incidence of which was more on endoscopy than the clinical manifestation. Group II patients did not have any bleed.

Fire disaster following LPG tanker explosion at Chala in Kannur (Kerala, India): August 27, 2012

A fire disaster following LPG tanker explosion occurred at Chala bypass, Kannur, Kerala, India on August 27, 2012. The three chambered tanker with total 16tonnes (162.57 quintal) LPG collided with a road divider and exploded thrice. A total of 41 people became victims during first blast; out of which 20 died in various hospitals. Five people remained inside the house after first blast and escaped unhurt from the zone of accident before second blast. All the victims were transferred to various hospitals; of these, six were transferred to the burns unit of the Kasturba Hospital, Manipal (320km from Chala). Five (5/6) were transferred within 1–5 days at our burns unit suffered 31–72% total body surface area (TBSA) burn, none had external injuries. One (1/6) was transferred on 20th day as a follow up case of 15% TBSA burn with 4% residual raw area and diabetes mellitus. Except one, all were managed conservatively using Limited access dressings (LAD; Negative Pressure Wound Therapy). One of the patient wound bed prepared under LAD and on 41 post burn day underwent split skin grafting under LAD. Out of the six patients admitted at the burns unit, two (2/6) admitted patients expired (one due to inhalation injury and another due to sepsis with multiple organ failure). One survivor (1/4) developed sepsis related liver dysfunction with hepatomegaly but recovered well. The total hospital stay of survivors at the burns unit varied from 8 to 60 days (mean hospital stay 36.5 days). All the victims who developed psychological symptoms were treated by psychiatrists and counselled before discharge. Three of survivors developed psychological symptoms. Two of them (2/3) developed mixed anxiety-depression disorder (ICD 10 code F41.8) and one of these two showed grief reaction too (ICD 10 code F43.23). One victim (1/3) developed non-organic insomnia (ICD 10 code F51.0) and responded to counselling. The article describes the incident, mechanism of the incident, injuries sustained, author, explanations on pattern of burn and suggestions in relation to future safety measures.

Influence of granulocyte macrophagecolony stimulating factor on the expression of angiopoietin-1 in deep partial thickness burn wound in rats

Objective To investigate the influence of granulocyte macrophage colony stimulatingfactor （ GM-CSF） on the expression of angiopoietin-1 （Ang-1） in deep partial thickness bum wound in 1rats. Methods The models of deep partial thickness bum wounds on the back in Spregue-Dawley （ SD）rats were established. The paired wounds on the same rats were randomly divided into GM-CSF treatment（test） and control groups by self-control. Tissue samples were harvested from the wounds on the 1st,3rd,7th, 14th and 21st day respectively after bums. The mRNA expression of Ang-1 was detected by using re-al-time reverse transcriptase-polymerase chain reaction （ FQ-PCR） . And the protein expression of Ang-1was detected by immunohistochemical and western blot, the protein expression of CD31 by using immuno-histochemical staining,and the microvascular density was calculated. Results The mRNA expression levelof Ang-1 in the bum wounds was decreased slightly on the 1st and 3rd postbum days and that in test group（1. 44 ±0. 20,0. 30 ± 0. 17 ） was lower than that in control group （2. 36 ± 0. 18 , 1. 34 ± 0. 24） （P 〈0.05）. Then the Ang-1 mRNA expression was gradually increased on the 7 th and 14 th postbum days anddecreased slightly on the 21st postbum day, and the expression level in the test group at the above timepoints （4. 52 ±0. 21,8. 47 ±0. 14, 7. 52 ±0. 20） was higher than that in control group （2. 71 ±0. 12,3.69 ±0. 24,3. 07 ±0. 17）（p 〈0. 05）. The protein expression of Ang-1 was declined remarkably on the 1stand 3rd postburn days, which in test group （0. 491 ±0. 055, 0. 181 ±0. 025） was lower than that in control group （0. 735 ± O. 080, O. 436 ± 0. 071 ） （ P 〈 O. 05 ）. Then the Ang-1 protein expression was gradually in- creased and reached the peak on the 14th postburn day and the expression in the test group （0. 821 ±0. 060, 1. 257 ± 0. 225, 1. 126 ±0. 131 ） was higher than that in the control group （0. 701 ± 0. 078, 0. 825 ± 0. 072, 0. 733 ±0. 073 ） （P 〈 0. 05 ）. The microvascular number with positive CD31 expression was increased evi- dently from the 3rd postburn day in test group, and the counting of MVD was remarkably higher in the test group （9.5±1.8, 23.4±2.9, 38.4±3. 1,24.6±2.5） than in the control group （4.0±1.9, 10.5±2.0, 22. 9 ±2. 7, 15.1 ±2. 6） on the 3rd, 7th, 14th and 21st days respectively after burns （P 〈0. 05）. Conclu- sion GM-CSF inhibits the mRNA and protein expression of Ang-1 during the early stage of wound healing, which can be beneficial to the angiogenesis. And GM-CSF boosts Ang-1 expression during the middle and late stages of wound healing. This would be helpful to wound vascular maturation and wound healinz. Key words: Granulocyte macrophage colony stimulating factor; Angiopoietin; Burn; Woundhealing

Effect of Fasting on the Metabolic Response of Liver to Experimental Burn Injury

Liver metabolism is altered after systemic injuries such as burns and trauma. These changes have been elucidated in rat models of experimental burn injury where the liver was isolated and perfused ex vivo. Because these studies were performed in fasted animals to deplete glycogen stores, thus simplifying quantification of gluconeogenesis, these observations reflect the combined impact of fasting and injury on liver metabolism. Herein we asked whether the metabolic response to experimental burn injury is different in fed vs. fasted animals. Rats were subjected to a cutaneous burn covering 20% of the total body surface area, or to similar procedures without administering the burn, hence a sham-burn. Half of the animals in the burn and sham-burn groups were fasted starting on postburn day 3, and the others allowed to continue ad libitum. On postburn day 4, livers were isolated and perfused for 1 hour in physiological medium supplemented with 10% hematocrit red blood cells. The uptake/release rates of major carbon and nitrogen sources, oxygen, and carbon dioxide were measured during the perfusion and the data fed into a mass balance model to estimate intracellular fluxes. The data show that in fed animals, injury increased glucose output mainly from glycogen breakdown and minimally impacted amino acid metabolism. In fasted animals, injury did not increase glucose output but increased urea production and the uptake of several amino acids, namely glutamine, arginine, glycine, and methionine. Furthermore, sham-burn animals responded to fasting by triggering gluconeogenesis from lactate; however, in burned animals the preferred gluconeogenic substrate was amino acids. Taken together, these results suggest that the fed state prevents the burn-induced increase in hepatic amino acid utilization for gluconeogenesis. The role of glycogen stores and means to increase and/or maintain internal sources of glucose to prevent increased hepatic amino acid utilization warrant further studies.

CXCL12/CXCR4 axis promotes mesenchymal stem cell mobilization to burn wounds and contributes to wound repair

BackgroundBone marrow–derived mesenchymal stem cells (BM-MSCs) play a crucial role in tissue repair. Their role in thermal burn wound regeneration and the relevant mechanism, however, is rarely studied. MethodsBM-MSCs from green fluorescent protein transgenic male mice were transfused to irradiated recipient female C57BL/6 mice. Twenty-one days later, the female mice were inflicted with burn wounds. The size of the burned area was measured by an in vivo fluorescence imaging system, and BM-MSC chemotaxis and epithelialization were estimated by fluorescence in situ hybridization and immunofluorescence technology. The expression of CXCL12 and CXCR4 in the wound margin was detected by enzyme-linked immunosorbent assay and immunohistochemistry. The importance of CXCL12/CXCR4 signaling in BM-MSC chemotaxis was further estimated by blocking CXCR4 in vivo and in vitro. ResultsIn vivo imaging results showed that BM-MSCs migrated to the injured margins. Fluorescence in situ hybridization and immunofluorescence technology revealed that Y chromosome–positive cells derived from green fluorescent protein transgenic mice were detected to be colocalized with keratin protein. Enzyme-linked immunosorbent assay revealed increased levels of CXCL12 and CXCR4 protein in the wound sites of BM-MSC-treated chimeric mice after burn. Immunohistochemistry also disclosed that CXCL12 levels were elevated at postburn day 7 compared with day 0. Furthermore, pretreatment of the BM-MSCs with the CXCR4 antagonist AMD3100 significantly inhibited the mobilization of BM-MSCs in vitro and in vivo, which attenuated wound closure. ConclusionBM-MSC migration to the burned margins promotes the epithelialization of the wound, and mobilization of BM-MSCs is mediated by CXCL12/CXCR4 signaling.

Localization of Superantigen Virulence Factors in Kidney Tissue of Animals With Staphylococcus aureus–Infected Burn Wounds

Gram-positive organisms are often found in association with burn wounds. A paucity of information exists regarding the accumulation and fate of virulence factors from these bacteria. The superantigenic exotoxins produced by Staphylococcus aureus are potent immunomodulating proteins and have also been described to localize in the kidney. The aim of this work was to demonstrate renal accumulation of toxic shock syndrome toxin-1 (TSST-1) and staphylococcal enterotoxin B (SEB) in a methicillin-resistant S. aureus burn wound infection. Twelve Sprague Dawley rats were subjected to partial-thickness burns (2 × 2 cm) using an aluminum billet. On postburn day 1, the wounds were inoculated with a toxin-producing strain of methicillin-resistant Skin biopsies and serum were obtained on postburn days 3, 6, and 10 along with necropsies for three animals each day. An enzyme-linked immunosorbent assay was used to quantify amounts of TSST-1 and SEB. Immunohistochemistry was used to localize SEB, TSST-1, and cleaved caspase-3 in renal tissue, and quantitative real-time polymerase chain reaction was used to assess erythropoietin and endothelin-1 messenger RNA (mRNA) in renal tissue. Baseline skin and plasma levels of TSST-1 and SEB were not detectable. Skin biopsy TSST-1 levels were detected on all postburn days and peaked at a mean value of 39.35 ng/ml on day 6; SEB was found in the skin and kidney only on postburn days 6 and 10. An enzyme-linked immunosorbent assay of renal tissue for TSST-1 and SEB demonstrated significantly higher (P < .05) mean toxin concentrations on postburn day 10: 10.87 ng/ml for TSST-1 and 0.67 ng/ml for SEB. Immunohistochemistry of renal tissue demonstrated increased stain intensity for SEB, TSST-1, and cleaved caspase-3 over time. Quantitative real-time polymerase chain reaction demonstrated decreased expression erythropoietin mRNA and increased expression of endothelin-1 mRNA relative to negative controls (P < .01). In a burn wound infection model that is nonlethal and lacks bacteremia, TSST-1 and SEB traverse cutaneous wounds and localize to the kidney. These potent virulence factors may contribute to the induction of apoptosis, and may alter homeostasis via renal pathophysiology.

Albumin Supplementation for Hypoalbuminemia Following Burns

Following fluid resuscitation, patients with major burns frequently develop prolonged hypoalbuminemia. It is not known whether this should be corrected by albumin supplementation. The purpose of this study was to determine whether there are any benefits associated with albumin supplementation to correct hypoalbuminemia in burned adults. We conducted a retrospective comparison of patients with burns ≥ 20% TBSA admitted to an adult regional American Burn Association-verified burn center, from May 1, 2009, to September 30, 2010, where we did not routinely supplement albumin (control group), with patients admitted from October 1, 2010, to May 30, 2011, where we had instituted a protocol in which 5% human albumin was provided to maintain serum albumin levels >20 g/L (albumin group). Comparisons were made from postburn (PB) day 2 to day 30 inclusive. There were no significant differences between control (n = 26) and albumin (n = 17) in age (48 ± 15 vs 45 ± 21 years; P = .56), burn size (33 ± 13 vs 34 ± 13 %TBSA; P = .831), or full thickness burn size (19 ± 19 vs 23 ± 19 %TBSA; P = .581). Inhalation injury was significantly more frequent in the albumin group than in controls (71% vs 31%; P = .01). The groups did not differ significantly in need for admission escharotomy, admission Sequential Organ Failure Assessment (SOFA) score, number of surgical procedures/first 30 days, or 24 and 48 hours fluid resuscitation volume requirements. The overall mean daily serum albumin level from PB day 2 to 30 in the albumin group (26.9 ± 3.0 g/L) was significantly greater than in controls (21.9 ± 4.4 g/L; P < .001). There were no significant differences between the groups in daily SOFA score/first 30 days, peak SOFA score, ΔSOFA, hospital length of stay, time to wound healing, duration of mechanical ventilation, or 30-day and in-hospital mortality. The cost of routinely supplementing 5% albumin between PB day 2 to 30 in the albumin group was more than four times that for the controls where we did not routinely provide albumin (Can $65.50 vs Can $16.57 per patient per day). We conclude that routine supplementation of 5% human albumin to maintain a serum albumin level ≥ 20 g/L in burn patients is expensive and provides no benefit.

Population pharmacokinetic analysis of fluconazole to predict therapeutic outcome in burn patients with Candida infection.

The pharmacokinetic (PK) property of fluconazole might be significantly altered in major burn patients by medical interventions and physiologic changes. In this study, our aims were to investigate fluconazole PK in burn patients using a population approach and to recommend the optimal fluconazole regimen based upon the predicted therapeutic outcome. At steady state, blood samples for PK analysis were obtained from 60 burn patients receiving between 100 and ~400 mg fluconazole daily. A mixed-effect modeling was performed and the therapeutic outcome of antifungal therapy was predicted for 10,000 virtual patients using NONMEM (version 7.2). MIC values were sampled from the MIC distribution at the study site. An area under the free drug concentration-time curve (fAUC)/MIC measurement of >25 h was used as the criterion for therapeutic success. When the same dose was given, the plasma concentration of fluconazole was predicted to be lower in burn patients compared to the nonburn population because of the large PK parameter (clearance, volume of distribution) estimates and continuous renal replacement therapy (CRRT). This tendency was particularly predominant when the patients were within 30 postburn days. Based upon our findings, 400 mg/day fluconazole is recommended to obtain therapeutic successes in major burn patients.