Sequential Changes in the Metabolic Response in Critically Injured Patients During the First 25 Days After Blunt Trauma

Monk, David; Plank, Lindsay D.; Franch-Arcas, Guzmán; Finn, Patrick; Streat, Stephen; Hill, Graham L.

doi:10.1097/00000658-199604000-00008

Cited by 210 publications

(147 citation statements)

References 24 publications

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“…However, large improvements in GFR from baseline after critical illness would seem implausible, whereas large and sustained falls in creatinine generation have been shown in animal models of sepsis (14), patients with advanced CKD (15), and critically ill humans (16)(17)(18), with greatest decrease occurring in the sickest patients (16). Skeletal muscle is the major source of creatinine production, and critical illness is associated with profound loss of skeletal muscle protein (10,19,20), with muscle thickness steadily decreasing over time after ICU admission (10,21,22). Loss of muscle mass can persist long after hospital discharge (23).…”

Section: Study Findingsmentioning

confidence: 99%

Serum Creatinine Changes Associated with Critical Illness and Detection of Persistent Renal Dysfunction after AKI

Prowle

Kolic²,

Purdell-Lewis³

et al. 2014

Clinical Journal of the American Society of Nephrology

137

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Background and objectives AKI is a risk factor for development or worsening of CKD. However, diagnosis of renal dysfunction by serum creatinine could be confounded by loss of muscle mass and creatinine generation after critical illness.Design, setting, participants, & measurements A retrospective, single center analysis of serum in patients surviving to hospital discharge with an intensive care unit admission of 5 or more days between 2009 and 2011 was performed.Results In total, 700 cases were identified, with a 66% incidence of AKI. In 241 patients without AKI, creatinine was significantly lower (P,0.001) at hospital discharge than admission (median, 0.61 versus 0.88 mg/dl; median decrease, 33%). In 160 patients with known baseline, discharge creatinine was significantly lower than baseline in all patients except those patients with severe AKI (Kidney Disease Improving Global Outcomes category 3), who had no significant difference. In a multivariable regression model, median duration of hospitalization was associated with a predicted 30% decrease (95% confidence interval, 8% to 45%) in creatinine from baseline in the absence of AKI; after allowing for this effect, AKI was associated with a 29% (95% confidence interval, 10% to 51%) increase in predicted hospital discharge creatinine. Using a similar model to exclude the confounding effect of prolonged major illness on creatinine, 148 of 700 patients (95% confidence interval, 143 to 161) would have eGFR,60 ml/min per 1.73 m 2 at hospital discharge compared with only 63 of 700 patients using eGFR based on unadjusted hospital creatinine (a 135% increase in potential CKD diagnoses; P,0.001).Conclusion Critical illness is associated with significant falls in serum creatinine that persist to hospital discharge, potentially causing inaccurate assessment of renal function at discharge, particularly in survivors of AKI. Prospective measurements of GFR and creatinine generation are required to confirm the significance of these findings.

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Section: Study Findingsmentioning

confidence: 99%

Serum Creatinine Changes Associated with Critical Illness and Detection of Persistent Renal Dysfunction after AKI

Prowle

Kolic²,

Purdell-Lewis³

et al. 2014

Clinical Journal of the American Society of Nephrology

137

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“…Critical injury causes hypermetabolism and hypercatabolism, resulting in an increase in resting energy expenditure and decrease in body cell mass. 1 Patients sustaining major trauma had a mean body protein loss of 1.62 kg (16%) over 21 days, with skeletal muscle accounting for the largest percentage. 1 Specialized nutrition support (parenteral, enteral) is given to these patients to minimize this protein loss.…”

Section: ! ! !mentioning

confidence: 99%

“…1 Patients sustaining major trauma had a mean body protein loss of 1.62 kg (16%) over 21 days, with skeletal muscle accounting for the largest percentage. 1 Specialized nutrition support (parenteral, enteral) is given to these patients to minimize this protein loss. Quantities as high as 2-3 g/kg/day of protein have been administered in attempts to produce net anabolism.…”

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confidence: 99%

Oxandrolone in Trauma Patients

et al. 2000

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Study Objective. To determine the effect of oxandrolone administration on nutritional and clinical outcomes after multiple trauma. Design. Prospective, randomized, double‐blind, placebo‐controlled study. Setting. Level 1 trauma center in a university teaching hospital. Patients. Sixty‐two patients requiring enteral nutrition, 60 of whom completed the study. Intervention. Patients were randomized to receive either oxandrolone 10 mg or placebo twice/day for a maximum of 28 days. Measurements and Main Results. Total urinary nitrogen, prealbumin, nitrogen balance, total body water, and body cell mass were measured on day 1 of enteral nutrition and then at day 7, day 10, and study exit. Patients were assessed daily for metabolic and infectious complications. The two groups were similar for demographics and dosage of enteral nutrition. Measurement of total urinary nitrogen at study entry showed both groups to be highly catabolic (oxandrolone 17.2 ± 4.9, placebo 19.1 ± 10.8 g/day, NS). On days 7 and 10, total urinary nitrogen increased in both groups; however, there was no significant difference between groups. Nitrogen balance was negative throughout the study in each group. Body cell mass decreased slightly in both groups over the study period. Prealbumin serum concentrations increased significantly in both groups at day 10 and study exit compared with study entry. The groups did not differ significantly for length of hospital stay (oxandrolone 30.8 ± 17.9, placebo 27.0 ± 25.7 days), length of intensive care unit stay (oxandrolone 17.1 ± 7.8, placebo 15.5 ± 9.7 days), and frequency of pneumonia or sepsis (oxandrolone 48, placebo 43 episodes). Conclusion. Oxandrolone 20 mg/day does not have obvious benefit in nutritional and clinical outcomes during the first month after multiple trauma.

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“…Typical features of the response include increased body temperature, recruitment of neutrophils, changes in lipid metabolism, increased gluconeogenesis, and stimulation of protective pathways such as coagulation and complement activation, hormonal changes, and increased muscle catabolism (32). These changes lead to increased energy expenditure and futile substrate cycling, with depletion of nutritional and functional fat and protein stores (5,30). Protein catabolism is increased after a severe burn, leading to a breakdown of functional structural proteins that results in the loss of lean muscle mass (10,21).…”

mentioning

confidence: 99%

Gene expression profiles and protein balance in skeletal muscle of burned children after β-adrenergic blockade

Herndon

Dasu

Wolfe

et al. 2003

American Journal of Physiology-Endocrinology and Metabolism

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Propranolol, a nonselective β-blocker, has been shown effective in hypermetabolic burn patients by decreasing cardiac work, protein catabolism, and lipolysis. This study investigates the effect of propranolol on gene and protein expression changes in skeletal muscle of burned children by use of high-density oligonucleotide arrays to establish the genetic profiles and stable isotope technique to quantitate protein synthesis. Thirty-seven children (mean age 9.7 ± 1.1 yr) were randomized into groups to receive placebo ( n = 23) or propranolol ( n = 14) titrated to reduce heart rate by 15%. Children had >40% total body surface area burns (mean 43 ± 5.6%). Protein net balance was determined by stable-isotope infusion technique. Total RNA from muscle biopsies was isolated, labeled, and cRNA hybridized to the HG-U95Av2 Affymetrix array. Mean net balance of protein synthesis and breakdown was –14.3 ± 12.9 nmol · min–1 · 100 ml leg volume–1 for placebo and +69.3 ± 34.9 nmol · min–1 · 100 ml leg volume–1 in the propranolol-treated children ( P = 0.012). Comparison of 12,000 genes in burned children receiving placebo showed increased expression of two genes with time, whereas children receiving propranolol showed increased expression of nine genes with a decrease in five genes. We conclude that burned children receiving propranolol showed a significant upregulation in genes involved in muscle metabolism and downregulation of an important enzyme involved in gluconeogenesis and insulin resistance compared with burned children receiving placebo. The upregulation of genes involved in muscle metabolism correlates well with the increase in net protein balance across the leg.

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Sequential Changes in the Metabolic Response in Critically Injured Patients During the First 25 Days After Blunt Trauma

Cited by 210 publications

References 24 publications

Serum Creatinine Changes Associated with Critical Illness and Detection of Persistent Renal Dysfunction after AKI

Serum Creatinine Changes Associated with Critical Illness and Detection of Persistent Renal Dysfunction after AKI

Oxandrolone in Trauma Patients

Gene expression profiles and protein balance in skeletal muscle of burned children after β-adrenergic blockade

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