Association of postburn fatty acids and triglycerides with clinical outcome in severely burned children.
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ABSTRACT:
SUBMITTER: Kraft R
PROVIDER: S-EPMC3537101 | biostudies-literature | 2013 Jan
REPOSITORIES: biostudies-literature
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Association of postburn fatty acids and triglycerides with clinical outcome in severely burned children.
Kraft Robert R Herndon David N DN Finnerty Celeste C CC Hiyama Yaeko Y Jeschke Marc G MG
The Journal of clinical endocrinology and metabolism 20121112 1
<h4>Context</h4>Free fatty acids (FFAs) and triglycerides (TGs) are altered postburn, but whether these alterations are associated with postburn outcomes is not clear.<h4>Objective</h4>The aim of the present study was to analyze lipid metabolic profiles in pediatric burn patients and to correlate these profiles with patient outcomes and hospital courses.<h4>Design and setting</h4>We conducted a prospective cohort study at an academic pediatric hospital burn center.<h4>Patients</h4>Our study incl ...[more]
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Project description:Administration of oxandrolone, a nonaromatizable testosterone analog, to children for 12 months following severe burn injury has been shown to improve height, increase bone mineral content (BMC), reduce cardiac work, and augment muscle strength. Surprisingly, the increase in BMC persists well beyond the period of oxandrolone administration. This study was undertaken to determine if administration of oxandrolone for 2 years yields greater effects on long-term BMC and bone mineral density (BMD). Patients between 0 and 18 years of age with ?30% of total body surface area burned were consented to an IRB-approved protocol and randomized to receive either placebo (n = 84) or 0.1 mg/kg oxandrolone orally twice daily for 24 months (n = 35). Patients were followed prospectively from the time of admission until 5 years postburn in a single-center, intent-to-treat setting. Height, weight, BMC, and BMD were recorded annually through 5 years postinjury. The long-term administration of oxandrolone for 16 ± 1 months postburn (range, 12.1-25.2 months) significantly increased whole-body (WB) BMC (p < 0.02) and lumbar spine (LS) BMC (p < 0.05); these effects were significantly pronounced for a longer time in patients who were in growth spurt years (7-18 years). When adjusted for height, sex, and age, LS BMD was found to significantly increase with long-term oxandrolone administration (p < 0.0009). Fewer patients receiving oxandrolone exhibited LS BMD z scores below -2.0 as compared with controls, indicating a significantly reduced risk for future fracture with oxandrolone administration. Long-term oxandrolone patients had significantly greater height velocity than controls throughout the first 2-year postburn (p < 0.05). No adverse side effects were attributed to the long-term administration of oxandrolone. A comparison of the current patients receiving long-term oxandrolone to previously described patients receiving 12 months of oxandrolone revealed that long-term oxandrolone administration imparted significantly greater increases in WB-BMC, WB-BMD, and LS-BMD (p < 0.05). In conclusion, the administration of oxandrolone for up to 24 months to severely burned pediatric patients significantly improves WB BMC, LS BMC, LS BMD, and height velocity. The administration of long-term oxandrolone was more efficacious than administration for 12 months. Additionally, fewer patients in the oxandrolone cohort met the diagnostic criteria for pediatric osteoporosis, pointing to a reduced risk for future bone fracture. This study demonstrates that administering oxandrolone for up to 2 years following severe burn injury results in greater improvements in BMC, BMD, and height velocity.
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Project description:BackgroundPost-burn hyperglycemia leads to graft failure, multiple organ failure, and death. A hyperinsulinemic-euglycemic clamp is used to keep serum glucose between 60 and 110 mg/dL. Because of frequent hypoglycemic episodes, a less-stringent sliding scale insulin protocol is used to maintain serum glucose levels between 80 and 160 mg/dL after elevations >180 mg/dL.Study designWe randomized pediatric patients with massive burns into 2 groups, patients receiving sliding scale insulin to lower blood glucose levels (n = 145) and those receiving no insulin (n = 98), to determine the differences in morbidity and mortality. Patients 0 to 18 years old with burns covering ≥ 30% of the total body surface area and not randomized to receive anabolic agents were included in this study. End points included glucose levels, infections, resting energy expenditure, lean body mass, bone mineral content, fat mass, muscle strength, and serum inflammatory cytokines, hormones, and liver enzymes.ResultsMaximal glucose levels occurred within 6 days of burn injury. Blood glucose levels were age dependent, with older children requiring more insulin (p < 0.05). Daily maximum and daily minimum, but not 6 am, glucose levels were significantly different based on treatment group (p < 0.05). Insulin significantly increased resting energy expenditure and improved bone mineral content (p < 0.05). Each additional wound infection increased incidence of hyperglycemia (p = 0.004). There was no mortality in patients not receiving insulin, only in patients who received insulin (p < 0.004). Muscle strength was increased in patients receiving insulin (p < 0.05).ConclusionsBurn-induced hyperglycemia develops in a subset of severely burned children. Length of stay was reduced in the no insulin group, and there were no deaths in this group. Administration of insulin positively impacted bone mineral content and muscle strength, but increased resting energy expenditure, hypoglycemic episodes, and mortality. New glucose-lowering strategies might be needed.
| S-EPMC4045114 | biostudies-literature
Project description:Oxandrolone, an anabolic agent, has been administered for 1 year post burn with beneficial effects in pediatric patients. However, the long-lasting effects of this treatment have not been studied. This single-center prospective trial determined the long-term effects of 1 year of oxandrolone administration in severely burned children; assessments were continued for up to 4 years post therapy.Patients 0 to 18 years old with burns covering >30% of the total body surface area were randomized to receive placebo (n = 152) or oxandrolone, 0.1 mg/kg twice daily for 12 months (n = 70). At hospital discharge, patients were randomized to a 12-week exercise program or to standard of care. Resting energy expenditure, standing height, weight, lean body mass, muscle strength, bone mineral content (BMC), cardiac work, rate pressure product, sexual maturation, and concentrations of serum inflammatory cytokines, hormones, and liver enzymes were monitored.Oxandrolone substantially decreased resting energy expenditure and rate pressure product, increased insulin-like growth factor-1 secretion during the first year after burn injury, and, in combination with exercise, increased lean body mass and muscle strength considerably. Oxandrolone-treated children exhibited improved height percentile and BMC content compared with controls. The maximal effect of oxandrolone was found in children aged 7 to 18 years. No deleterious side effects were attributed to long-term administration.Administration of oxandrolone improves long-term recovery of severely burned children in height, BMC, cardiac work, and muscle strength; the increase in BMC is likely to occur by means of insulin-like growth factor-1. These benefits persist for up to 5 years post burn.
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Project description:Severe burn is followed by profound cardiac stress. Propranolol, a nonselective ?(1,) ?(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.
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Project description:The aim of this study was to quantify the effect of propranolol on hemodynamic parameters assessed using the PiCCO system in burned children.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.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).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.
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Project description:ObjectivesThe aim of this study was to determine the appropriate propranolol dosing strategy for reducing heart rate in severely burned adults.MethodsA total of 26 patients (≥18 years) with burns covering ≥30% of the total body surface area were included in this IRB-approved study. Plasma propranolol concentrations were determined in a placebo group (n=10) or following one of three dosing strategies: Q6 (n=4), Q8 (n=6), and Q24 (n=6). Blood was collected just before dosing and at regular intervals over two dosing periods with corresponding heart rate and blood pressure recordings. Statistical significance was determined by one-way ANOVA followed by the appropriate post-hoc test.ResultsHeart rate was 86±2 bpm for Q6, 93±3 bpm for Q8, and 90±4 bpm for Q24. The Q8 group had a significantly higher heart rate than the Q6 group (p=0.0001). Plasma propranolol concentrations were significantly higher in the Q6 dosing strategy than in the Q8 dosing strategy (p=0.02).ConclusionsHeart rate can be decreased to a similar degree with Q6 and Q24 dosing strategies, with the Q8 dosing strategy being less effective. Q6 dosing is recommended to maintain reduced heart rate throughout dosing periods.
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Project description:Hypernatremia is common in critical care, especially in severely burned patients. Its occurrence has been linked to increased mortality. Causes of hypernatremia involve a net gain of sodium or a loss of free water. Renal loss of electrolyte-free water due to urea-induced osmotic diuresis has been described as causative in up to 10% of hypernatremic critical ill patients. In this context, excessive urea production due to protein catabolism acts as major contributor. In severe burn injury, muscle wasting occurs as result of hypermetabolism triggered by ongoing systemic inflammation. In this retrospective study, severely burned patients were analysed for the occurrence of hypernatremia and subsequent signs of hypermetabolism. The urea: creatinine ratio-as a surrogate for hypermetabolism-sufficiently discriminated between two groups. Four of nine hypernatremic burn patients (44%) had a highly elevated urea: creatinine ratio, which was clearly associated with an increased urea production and catabolic index. This hypermetabolism was linked to hypernatremia via an elevated urea- and reduced electrolyte-fraction in renal osmole excretion, which resulted in an increased renal loss of electrolyte-free water. In hypermetabolic severely burned patients, the electrolyte-free water clearance is a major contributor to hypernatremia. A positive correlation to serum sodium concentration was shown.
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