[show abstract][hide abstract] ABSTRACT: Obesity influences metabolism and increases the incidence of clinical complications and worsens outcomes in pediatric burn patients.
Retrospective, single-center study.
In all, 592 severely burned pediatric patients who had burns covering more than 30% of the total body surface area and who were treated between 2001 and 2008 were enrolled in this study. Patients were divided into ≥85th percentile (n=277) and normal (n=315) weight groups based on body mass index (BMI) percentiles.
Patients stratified below (normal) and ≥85th percentile had similar age, gender distribution and total burn size. No significant differences were detected in the incidence of sepsis (11% for obese vs 10% for normal), the incidence of multiple organ failure (MOF) (21% for obese and 16% for normal) or mortality (11% for obese vs 8% for normal). Compared with the normal group, the ≥85th percentile group had low levels of constitutive proteins (α2macroglobulin and Apolipoprotein A1) (P<0.05 for both) as well as high levels of triglycerides and the acute-phase protein, C-reactive protein (P<0.05 for both) up to 60 days after injury. Patients ≥85th percentile showed a significant higher loss of bone mineral density and lipolysis compared with normal individuals. Stepwise logistic regression analysis revealed that BMI had a positive predictive value towards the maximum DENVER2 score, an index of organ failure (P<0.001).
BMI≥85th percentile altered the post-burn acute phase and catabolic response but did not increase the incidence of sepsis, MOF or mortality in pediatric burn patients. Our results suggest that impaired metabolism and an altered inflammatory response already exists in patients starting at the 85th percentile BMI.
International journal of obesity (2005) 12/2011; 36(4):485-90. · 5.22 Impact Factor
[show abstract][hide abstract] ABSTRACT: Human survival from injury requires an appropriate inflammatory and immune response. We describe the circulating leukocyte transcriptome after severe trauma and burn injury, as well as in healthy subjects receiving low-dose bacterial endotoxin, and show that these severe stresses produce a global reprioritization affecting >80% of the cellular functions and pathways, a truly unexpected "genomic storm." In severe blunt trauma, the early leukocyte genomic response is consistent with simultaneously increased expression of genes involved in the systemic inflammatory, innate immune, and compensatory antiinflammatory responses, as well as in the suppression of genes involved in adaptive immunity. Furthermore, complications like nosocomial infections and organ failure are not associated with any genomic evidence of a second hit and differ only in the magnitude and duration of this genomic reprioritization. The similarities in gene expression patterns between different injuries reveal an apparently fundamental human response to severe inflammatory stress, with genomic signatures that are surprisingly far more common than different. Based on these transcriptional data, we propose a new paradigm for the human immunological response to severe injury.
Journal of Experimental Medicine 11/2011; 208(13):2581-90. · 13.21 Impact Factor
[show abstract][hide abstract] ABSTRACT: Aggressive nutrition support is recommended following severe burn injury. Initially, such injury results in a prolonged and persistent hypermetabolic response mediated by a 10- to 20-fold elevation in plasma catecholamines, cortisol, and inflammatory mediators. This response leads to twice-normal metabolic rates, whole-body catabolism, muscle wasting, and severe cachexia. Thus, it is relevant to review the literature on nutrition in burns to adjust/update treatment. Failure to meet the increased substrate requirements may result in impaired wound healing, multiorgan dysfunction, increased susceptibility to infection, and death. Therefore, aggressive nutrition support is essential to ensure adequate burn care, attenuate the hypermetabolic response, optimize wound healing, minimize devastating catabolism, and reduce morbidity and mortality. Here, the authors provide nutrition recommendations gained from prospective trials, retrospective analyses, and expert opinions based on the authors' practices in Galveston, Texas, and Vienna, Austria.
Journal of Parenteral and Enteral Nutrition 11/2011; 35(6):704-14. · 2.49 Impact Factor
[show abstract][hide abstract] ABSTRACT: Burn injury leads to vast changes in both metabolic and inflammatory responses and is associated with increased morbidity and mortality. Insulin resistance (IR) and hyperglycemia are major components of the hypermetabolic response found in burn-injured patients and subsequently contribute to adverse outcomes. Studies have shown that increased systemic retinol binding protein (RBP) levels are associated with IR and hyperinflammation in diabetic and obese patients. The aim of this study was to determine RBP profiles and to test the hypothesis that elevated RBP levels are associated with both IR and the inflammatory response in burned patients.
RBP was measured in 372 patients during the acute stay postburn. Patients' demographics, glucose levels, and insulin administration were recorded. Cytokines, hormones, plasma proteins, and organ markers were measured. The average of all measurements of RBP (2.1 mg/dL) was used to divide patients into high and low groups. Statistical analysis was performed by Student t test. Statistical significance was accepted at P < .05.
Fifty-one patients (high group) had elevated RBP levels during acute hospitalization and demonstrated a significant higher incidence of multiorgan failure, sepsis, and mortality (P < .05). Moreover, in the high group, a significant increase of IR, inflammatory cytokines, and catabolic and organ-specific markers were detected (P < .05).
Increased RBP levels postburn correlate with increased IR, inflammatory and catabolic responses, incidence of multiorgan failure, and mortality. RBP may be a novel biomarker to monitor these detrimental responses postburn.
Journal of Parenteral and Enteral Nutrition 11/2011; 35(6):695-703. · 2.49 Impact Factor
[show abstract][hide abstract] ABSTRACT: The Growth Hormone and Insulin-like Growth Factor-1 (IGF-1) axis plays a pivotal role in critical illness, with a derangement leading to profound changes in metabolism. Protein wasting with skeletal muscle loss, delayed wound healing, and impaired recovery of organ systems are some of the most feared consequences. The use of human recombinant Growth Hormone (rhGH) and Insulin-like Growth Factor-1 (IGF-1) - alone and in combination - has been studied extensively in preclinical and clinical trials. This article reviews the current knowlegde and clinical practice of the use of rhGh and IGF-1 in critically ill patients, with a special focus on the trauma and burns patient population.
Best practice & research. Clinical endocrinology & metabolism 10/2011; 25(5):759-67. · 3.89 Impact Factor
[show abstract][hide abstract] ABSTRACT: Our goal was to assess the validity of the enrichments of plasma free palmitate and intramuscular (IM) fatty acid metabolites as precursors for calculating the IM triglyceride fractional synthetic rate. We infused U-¹³C₁₆-palmitate in anesthetized rabbits for 3 h and sampled adductor muscle of legs using both freeze-cut and cut-freeze approaches. We found that IM free palmitate enrichment (0.70 ± 0.07%) was lower (P < 0.0001) than IM palmitoyl-CoA enrichment (2.13 ± 0.17%) in samples taken by the freeze-cut approach. The latter was close (P = 0.33) to IM palmitoyl-carnitine enrichment (2.42 ± 0.16%). The same results were obtained from the muscle samples taken by the cut-freeze approach, except the enrichment of palmitoyl-CoA (2.21 ± 0.08%) was lower (P = 0.02) than that of palmitoyl-carnitine (2.77 ± 0.17%). Plasma free palmitate enrichment was ∼2-fold that of IM palmitoyl-CoA enrichment and palmitoyl-carnitine enrichment (P < 0.001). These findings indicate that plasma free palmitate overestimated IM precursor enrichment owing to in vivo IM lipid breakdown, whereas IM free palmitate enrichment underestimated the precursor enrichment because of lipid breakdown during muscle sampling and processing. IM palmitoyl-carnitine enrichment was an acceptable surrogate of the precursor enrichment because it was less affected by in vitro lipid breakdown after sampling.
The Journal of Lipid Research 09/2011; 53(1):119-25. · 4.39 Impact Factor
[show abstract][hide abstract] ABSTRACT: Transforming growth factor-β1 (TGF-β1) plays a key role in hypertrophic scar formation. A lot of studies have shown that TGF-β1 stimulates fibroblast proliferation, collagen production, and α-smooth muscle actin (α-SMA) expression, inhibits matrix degradation and eventually leads to scar formation. Smad proteins are important intracellular mediators of TGF-β1 signaling, and Smad ubiquitination regulatory factor 2 (Smurf2), an ubiquitin ligase for Smads, plays critical roles in the regulation of TGF-β1/Smad signaling. It was reported that Smurf2 was abnormally expressed during the process of liver fibrosis and lung fibrosis. Hypertrophic scarring is a fibroproliferative disorder of the dermis that occurs following wounding. However, little is known about the expression of Smurf2 in hypertrophic scarring. We hypothesized that TGF-β1 signaling cannot be disrupted after wound epithelialization probably due to abnormal expression of Smurf2 in hypertrophic scar fibroblasts. In the present study, we found that hypertrophic scar fibroblasts exhibited increased Smurf2 protein and mRNA levels compared with normal fibroblasts, and the expression of Smurf2 gradually increased in hypertrophic scar fibroblasts after TGF-β1 stimulation. Furthermore, we transfected Smurf2 siRNA into hypertrophic scar fibroblasts, and we found that silencing the expression of Smurf2 in hypertrophic scar fibroblasts dramatically reduced TGF-β1 production, inhibited TGF-β1-induced α-SMA expression and inhibited TGF-β1-induced collagen I synthesis. Our results suggest that the enhanced expression of Smurf2 is involved in the progression of hypertrophic scarring.
Burns: journal of the International Society for Burn Injuries 09/2011; 38(2):236-46. · 1.95 Impact Factor
[show abstract][hide abstract] ABSTRACT: The objective of the study was to investigate pulmonary responses to Pseudomonas aeruginosa and methicillin-resistant Staphylococcus aureus (MRSA) using ovine and mice models of sepsis with emphasis on lung cytokine expression, asymmetric dimethylarginine (ADMA) concentration, and the arginase pathway. Sheep were instilled with either MRSA, P. aeruginosa, or saline under deep anesthesia; mechanically ventilated; resuscitated with fluid; and killed after 24 h. Mice were instilled with either MRSA, P. aeruginosa, or saline under deep anesthesia and killed after 8 h. Lungs were assessed for ADMA concentration, arginase activity, oxidative stress, and cytokine expression, and plasma was assessed for nitrate/nitrite concentrations. The severity of lung injury was more pronounced in P. aeruginosa sepsis compared with MRSA. The significant changes in sheep lung function after P. aeruginosa sepsis were associated with significantly increased ADMA concentrations and arginase activity compared with MRSA. However, the plasma concentration of nitrites and nitrates were significantly increased in MRSA sepsis compared with P. aeruginosa sepsis. In the mice model, P. aeruginosa significantly increased lung cytokine expression (IL-1 and IL-13), protein oxidation, and arginase activity compared with MRSA. Our data suggest that the greater expression of cytokines and ADMA concentrations may be responsible for severity of acute lung injury in P. aeruginosa sepsis. The lack of arginase activity may explain the greater nitric oxide production in MRSA sepsis.
[show abstract][hide abstract] ABSTRACT: Immunodeficient patients with severe burn injuries are extremely susceptible to infection with Candida albicans. In addition to Th1 cells, IL-17-producing CD4(+) T cells (Th17 cells) have recently been described as an important effector cell in host anti-Candida resistance. In this study, therefore, we tried to induce Th17 cells in cultures of severely burned patient PBMC by stimulation with the C. albicans Ag (CAg). In the results, the biomarkers for Th17 cells (IL-17 production and intracellular expression of IL-17 and retinoic acid receptor-related orphan receptor γt) were not displayed by burn patient PBMC stimulated with CAg, whereas these biomarkers of Th17 cells were detected in cultures of healthy donor PBMC stimulated with CAg. Burn patient sera were shown to be inhibitory on CAg-stimulated Th17 cell generation in healthy donor PBMC cultures; however, Th17 cells were induced by CAg in healthy donor PBMC cultures supplemented with burn patient sera that were previously treated with anti-IL-10 mAb. Also, the biomarkers of Th17 cells were not induced by CAg in healthy donor PBMC cultures supplemented with rIL-10. IL-10 was detected in serum specimens derived from severely burned patients. These results indicate that Th17 cells are not generated in burn patient PBMC cultures supplemented with CAg. IL-10, produced in response to burn injuries, is shown to be inhibitory on Th17 cell generation. The high susceptibility of severely burned patients to C. albicans infection might be influenced if burn-associated IL-10 production is intervened.
The Journal of Immunology 09/2011; 187(5):2155-61. · 5.52 Impact Factor
[show abstract][hide abstract] ABSTRACT: Cutaneous scarring is an enormous medical problem with approximately 100 million patients acquiring scars each year. Scar prevention/reduction represents a significant, and largely unmet, clinical need. Research into the prophylactic modulation of scar outcome differs from research into other disease processes as the scar is not present at the start of the study; measurements of changes from baseline are impossible. Final scar morphology is influenced by many variables. A fundamental principle that should be observed in the prospective evaluation of scar prevention/reduction therapies is that, if left untreated, wounds in treatment and control groups should have healed with identical scars. Observation of this principle will allow the detection of true treatment effects. The many variables that influence scar morphology mean that the evaluation of potential pharmaceutical products for this indication favors the use of self-controlled designs in clinical trials. In this article, we review variables that affect scar morphology and recommend the self-controlled design for clinical trials aiming to establish proof of efficacy of scar prevention and reduction pharmaceuticals. With no pharmaceutical products currently licensed for this indication, this represents a new therapeutic area. The principles discussed will also have direct relevance to the wider fields of wound healing and regenerative medicine.
[show abstract][hide abstract] ABSTRACT: Previous studies have shown that starvation induces small bowel atrophy, and that atrophy diminishes with aging. In this experiment, we assessed whether starvation-induced atrophy of proximal gut mucosa is associated with the Interleukin-1 receptor (IL-1R) signaling pathway in aged mice.
Thirty 26-month-old IL-1R knockout mice and age-matched wild-type C57BL/6 mice were randomly divided into two groups: ad libitum fed and fasted. Mice were euthanized 12 or 48 hours after starvation. The proximal small bowel was harvested for morphologic analysis. Gut epithelial cell proliferation was detected using immunohistochemical staining for proliferating cell nuclear antigen (PCNA), and apoptosis was identified using terminal deoxyuridine nick-end labeling (TUNEL) staining.
Aged IL-1R knockout mice were larger than aged-matched wild-type mice (P < 0.05). Proximal gut mucosal height and mucosal cell number were not different between aged IL-1R knockout and wild-type groups. The apoptosis index in gut epithelial cells was higher in fed IL-1R knockout versus wild-type mice (P < 0.05), while there was no significant difference in cell proliferation between both groups. Mucosal atrophy was induced in both aged IL-1R knockout and wild-type groups by starvation (P < 0.05), however, aged IL-1R knockout mice experienced greater loss in proximal gut weight, mucosal length, and corresponding cell number than did wild-type mice at the 12-h time point (P < 0.05). The apoptosis index in gut epithelial cells significantly increased in both groups after starvation (P < 0.05). Starvation decreased cell proliferation in IL-1R knockout mice (P < 0.05), but not in wild-type mice.
The response in aged IL-1R knockout mice differs from wild-type mice in that starvation increases atrophy and is associated with decreased cell proliferation rather than increased apoptosis.
Journal of Surgical Research 08/2011; 169(2):209-13. · 2.02 Impact Factor
[show abstract][hide abstract] ABSTRACT: Children with burn injuries receive a broad range of medications, from analgesics to antipsychotics, but how utilization of these drugs differs from one pediatric burn center to another is unclear. This study examined utilization patterns of six categories of medication administered acutely to burned children as a first step in creating evidence-based practice guidelines. Six medications administered to pediatric patients enrolled in a multicenter study were recorded from patient charts using a standardized chart review template. The medication categories included opiates, benzodiazepines, antidepressants, beta-blockers, two different anesthetics, and antipsychotics. Data were analyzed by χ and logistical regression analysis. Analysis of data from three sites and 470 patients revealed significant differences in prescription patterns across hospitals for all medication groups except opiates. Differences were significant for benzodiazepines and antidepressants (χ = 7.3; P < .01 for both) controlling for age, gender, race, language, burn size, and length of stay. Differences in prescribing patterns for beta-blockers and the anesthetics ketamine and propofol failed to reach statistical significance; however, the results did trend in that direction (χ = 3.8 and 3.4, respectively; P < .10 for both). The pharmacotherapeutic agents described in this study are an integral part of acute pediatric burn care, and yet there is variation in use of these medications among the centers. The differences in prescribing indicate that, for certain drugs, a range of approaches to pharmacotherapeutics is being used and suggest that evidence-based guidelines for administration of these agents need to be developed.
Journal of burn care & research: official publication of the American Burn Association 08/2011; 32(5):519-28. · 1.54 Impact Factor
[show abstract][hide abstract] ABSTRACT: This study was performed to determine if there is an age-related specificity in the response of muscle protein metabolism to severe burn injury during acute hospitalization. This is a retrospective analysis of previously published data.
Nineteen adult and 58 pediatric burn-injured patients (age 43.3 ± 14.3 vs. 7.2 ± 5.3 years, adult vs. children) participated in stable isotope [ring-(2)H(5)]phenylalanine (Phe) infusion studies. Femoral arterial and venous blood samples and muscle biopsy samples were collected throughout the study. Data are presented as means ± standard deviation (SD). A p value less than 0.05 was considered statistically significant.
Muscle net protein balance (NB) was higher in children (adult vs. children, -43 ± 61 vs. 8 ± 68 nmol Phe/min/100 ml leg volume, p < 0.05). Muscle protein fractional synthesis rate (FSR) was higher in children (adult vs. children, 0.11 ± 0.05 vs. 0.16 ± 0.10 %/h, p < 0.05). Leg muscle protein breakdown was not different between the groups (adult vs. children, 179 ± 115 vs. 184 ± 124 nmol Phe/min/100 ml leg volume, p > 0.05); synthesis rate was 134 ± 96 and 192 ± 128 nmol Phe/min/100 ml leg volume in adults and children, respectively (p = 0.07). Age significantly correlated with muscle protein NB (p = 0.01) and FSR (p = 0.02); but not with breakdown (p = 0.67) and synthesis (p = 0.07) rates measured by using a three-pool model.
In burn injury, the muscle protein breakdown may be affected to the same extent in adults and children, whereas synthesis may have age-related specificities, resulting in a better but still low NB in children.
European Journal of Intensive Care Medicine 06/2011; 37(8):1317-22. · 5.17 Impact Factor
[show abstract][hide abstract] ABSTRACT: The hypermetabolic response to severe burn injury is characterized by hyperdynamic circulation and profound metabolic, physiologic, catabolic, and immune system derangements. Failure to satisfy overwhelming energy and protein requirements after, and during, severe burn injury results in multiorgan dysfunction, increased susceptibility to infection, and death. Attenuation of the hypermetabolic response by various pharmacologic modalities is emerging as an essential component of the management of patients with severe burn injury. This review focuses on the more recent advances in therapeutic strategies to attenuate the hypermetabolic response and its postburn-associated insulin resistance.
Surgical Clinics of North America 06/2011; 91(3):609-29. · 2.02 Impact Factor
[show abstract][hide abstract] ABSTRACT: Autograft take and rapid wound closure is essential for the survival of severely burned patients. Loss of skin grafts typically occurs during the first few days after coverage, mainly due to shear forces and inadequate contact with the wound bed. Slow-clotting fibrin sealant, applied with a spray-on device, has been shown to improve healing of skin grafts in large wounds. However, its use in burn wounds has not been studied so far.
To evaluate the effectiveness of sprayed fibrin sealant in excised and grafted full-thickness burns.
Ten female Yorkshire pigs (30-45 kg) received a full-thickness contact burn of approximately 15% total body surface area. The burns were excised to the level of the muscular fascia after 24 h and covered with meshed skin autograft (mesh ratio 1:3). Wounds were randomized to either fibrin sealant (n=20) or standard skin staples (n=16) for graft fixation. Fibrin sealant was used as a slow-clotting spray (4 IU thrombin/ml). Outcome measurements included clinical scoring at days 2, 5, 9 and 14 postoperatively, planimetric analysis of wound closure, and histological examination of epidermal and dermal thickness 14 days after autografting.
In the fibrin sealant group, graft adherence scores were significantly increased (p<0.02) and graft dislocation scores significantly decreased (p<0.01) at days 2 and 5 postoperatively, when compared to controls. Planimetric analysis of remaining open mesh interstices showed acceleration of wound closure in the fibrin sealant group but did not reach statistical significance (day 14 p=0.04 at significance level p<0.025). Wound contraction, occurrence of hematoma, and dermal as well as epidermal thickness were not different between the groups at 14 days postoperatively.
The results indicate that the use of slow-clotting fibrin sealant spray for autograft fixation is advantageous over skin staples. Easy handling and reduced graft dislocation at early time points are key qualities of this method.
Burns: journal of the International Society for Burn Injuries 05/2011; 37(8):1360-6. · 1.95 Impact Factor
[show abstract][hide abstract] ABSTRACT: Monitoring of hemodynamic and volumetric parameters after severe burns is of critical importance. Pulmonary artery catheters, however, have been associated with many risks. Our aim was to show the feasibility of continuous monitoring with minimally invasive transpulmonary thermodilution (TPTD) in severely burned pediatric patients.
This prospective cohort study was conducted in patients with severe burns over 40% of the total body surface area (TBSA) who were admitted to the hospital within 96 hours after sustaining the injury. TPTD measurements were performed using the PiCCO system (Pulsion Medical Systems, Munich, Germany). Cardiac Index (CI), Intrathoracic Blood Volume Index (ITBVI) (Stewart-Hamilton equation), Extravascular Lung Water Index (EVLWI) and Systemic Vascular Resistance Index (SVRI) measurements were recorded twice daily. Statistical analysis was performed using one-way repeated measures analysis of variance with the post hoc Bonferroni test for intra- and intergroup comparisons.
Seventy-nine patients with a mean age (±SD) of 9 ± 5 years and a mean TBSA burn (±SD) of 64% ± 20% were studied. CI significantly increased compared to level at admission and was highest 3 weeks postburn. ITBVI increased significantly starting at 8 days postburn. SVRI continuously decreased early in the perioperative burn period. EVLWI increased significantly starting at 9 days postburn. Young children (0 to 5 years old) had a significantly increased EVLWI and decreased ITBVI compared to older children (12 to 18 years old). EVLWI was significantly higher in patients who did not survive burn injury.
Continuous PiCCO measurements were performed for the first time in a large cohort of severely burned pediatric patients. The results suggest that hyperdynamic circulation begins within the first week after burn injury and continues throughout the entire intensive care unit stay.
Critical care (London, England) 04/2011; 15(2):R118. · 4.72 Impact Factor
[show abstract][hide abstract] ABSTRACT: The hypermetabolic response in critically ill patients is characterized by hyperdynamic circulatory, physiologic, catabolic and immune system responses. Failure to satisfy overwhelming energy and protein requirements after, and during critical illness, results in multiorgan dysfunction, increased susceptibility to infection, and death. Attenuation of the hypermetabolic response by various pharmacologic modalities is emerging as an essential component of the management of severe burn patients. This review focuses on the more recent advances in therapeutic strategies to attenuate the hypermetabolic response and its associated insulin resistance postburn.
At present, beta-adrenergic blockade with propranolol represents probably the most efficacious anticatabolic therapy in the treatment of burns. Other pharmacological strategies include growth hormone, insulin-like growth factor, oxandrolone and intensive insulin therapy.
Novel approaches to the management of critical illness by judicious glucose control and the use of pharmacologic modulators to the hypercatabolic response to critical illness have emerged. Investigation of alternative strategies, including the use of metformin, glucagon-like-peptide-1 and the PPAR-γ agonists are under current investigation.
Current opinion in clinical nutrition and metabolic care. 03/2011; 14(2):176-81.
[show abstract][hide abstract] ABSTRACT: To evaluate leg muscle, whole-body muscle, and whole-body nonmuscle protein response to anabolic signaling of amino acids in pediatric burn patients at 6 months after injury.
Burn injury is associated with a catabolic state persisting years after the injury. The tissue response to nutritional signaling (eg, amino acids) plays a critical role in tissue protein net balance via coordination of protein synthesis and breakdown mechanisms.
A total of 10 patients (7.4 ± 3.8 years; 27.4 ± 14.7 kg) and 5 healthy young males (22 ± 3 years; 76 ± 15 kg) underwent an 8-hour stable isotope infusion study. During the last 3 hours, an amino acid solution (10% Travasol, Clintec Nutrition, Deerfield, IL) was infused. Femoral arterial and venous blood samples and muscle biopsy samples were collected throughout the study. A P value of less than 0.05 was considered statistically different.
During amino acid infusion, leg muscle protein synthesis rate significantly increased (P < 0.05) in both groups, however, in the burn group, protein breakdown also increased, although nonsignificantly. As a result, protein net balance remained negative. In the control group, breakdown nonsignificantly decreased resulting in a significant increase (P < 0.05) in muscle protein net balance. Whole-body protein breakdown was significantly higher in the burn patients.
In pediatric burn patients at 6 months postinjury, leg muscle protein net deposition is unresponsive to amino acid infusion; and whole-body protein breakdown is significantly higher than in the control group.
Annals of surgery 03/2011; 253(3):592-7. · 7.90 Impact Factor
[show abstract][hide abstract] ABSTRACT: The aim of the study was to compare a low fat/high-carbohydrate diet and a high-fat diet on clinical outcomes by a retrospective cohort study.
Nine hundred forty-four children with burns ≥ 40% of their total body surface area (TBSA) were divided into two groups: patients receiving Vivonex T.E.N. (low-fat/high-carbohydrate diet; n = 518) and patients receiving milk (high-fat diet; n = 426). Patient demographics, caloric intake, length of hospital stay, and incidence of sepsis, mortality, hepatic steatosis, and organomegaly at autopsy were determined.
Demographics and caloric intake were similar in both groups. Patients receiving Vivonex T.E.N. had shorter (intensive care unit) ICU stays (Vivonex T.E.N.: 31 ± 2 d; milk: 47 ± 2 d; P < 0.01), shorter ICU stay per % TBSA burn (Vivonex T.E.N.: 0.51 ± 0.02 d/%; milk: 0.77 ± 0.03 d/%; P < 0.01), lower incidence of sepsis (Vivonex T.E.N.: 11%; milk: 20%; P < 0.01), and lived significantly longer until death than those receiving milk (Vivonex T.E.N.: 20 ± 3 d; milk: 10 ± 2 d; P < 0.01). There was no difference in overall mortality between the two groups (Vivonex T.E.N.:15% versus milk: 13%; P < 0.9). Autopsies revealed decreased hepatic steatosis and decreased enlargement of kidney and spleen in patients receiving Vivonex T.E.N.
The period with a low-fat/high-carbohydrate diet was associated with lower LOS, decreased incidence of organomegaly, infection, and hepatic steatosis post-burn compared with the period when a high-fat diet was used. These associations indicate the benefit of high carbohydrate/low fat nutrition; however, the findings in these time periods can also be likely due to the multifactorial effects of advances in burn care. We believe that these results have some relevance because high fat is associated with poorer outcomes compared with low fat.
Journal of Surgical Research 03/2011; 166(1):e83-90. · 2.02 Impact Factor
[show abstract][hide abstract] ABSTRACT: Severe burn is followed by profound cardiac stress. Propranolol, a nonselective β(1,) β(2)-receptor antagonist, decreases cardiac stress, but little is known about the dose necessary to cause optimal effect. Thus, the aim of this study was to determine in a large, prospective, randomized, controlled trial the dose of propranolol that would decrease heart rate ≥15% of admission heart rate and improve cardiac function. Four-hundred six patients with burns >30% total body surface area were enrolled and randomized to receive standard care (controls; n = 235) or standard care plus propranolol (n = 171).
Dose-response and drug kinetics of propranolol were performed. Heart rate and mean arterial pressure (MAP) were measured continuously. Cardiac output (CO), cardiac index, stroke volume, rate-pressure product, and cardiac work (CW) were determined at regular intervals. Statistical analysis was performed using analysis of variance with Tukey and Bonferroni corrections and the Student t test when applicable. Significance was accepted at P < .05.
Propranolol given initially at 1 mg/kg per day decreased heart rate by 15% compared with control patients, but was increased to 4 mg/kg per day within the first 10 days to sustain treatment benefits (P < .05). Propranolol decreased CO, rate-pressure product, and CW without deleterious effects on MAP. The effective plasma drug concentrations were achieved in 30 minutes, and the half-life was 4 hours.
The data suggest that propranolol is an efficacious modulator of the postburn cardiac response when given at a dose of 4 mg/kg per day, and decreases and sustains heart rate 15% below admission heart rate.
Surgery 02/2011; 149(2):231-9. · 3.37 Impact Factor