Anne-Françoise Rousseau

ESPEN endorsed recommendations: nutritional therapy in major burns.

BACKGROUND & AIMS Nutrition therapy is a cornerstone of burn care from the early resuscitation phase until the end of rehabilitation. While several aspects of nutrition therapy are similar in major burns and other critical care conditions, the patho-physiology of burn injury with its major endocrine, inflammatory, metabolic and immune alterations requires some specific nutritional interventions. The present text developed by the French speaking societies, is updated to provide evidenced-based recommendations for clinical practice. METHODS A group of burn specialists used the GRADE methodology (Grade of Recommendation, Assessment, Development and Evaluation) to evaluate human burn clinical trials between 1979 and 2011. The resulting recommendations, strong suggestions or suggestions were then rated by the non-burn specialized experts according to their agreement (strong, moderate or weak). RESULTS Eight major recommendations were made. Strong recommendations were made regarding, 1) early enteral feeding, 2) the elevated protein requirements (1.5-2 g/kg in adults, 3 g/kg in children), 3) the limitation of glucose delivery to a maximum of 55% of energy and 5 mg/kg/h associated with moderate blood glucose (target ≤ 8 mmol/l) control by means of continuous infusion, 4) to associated trace element and vitamin substitution early on, and 5) to use non-nutritional strategies to attenuate hypermetabolism by pharmacological (propranolol, oxandrolone) and physical tools (early surgery and thermo-neutral room) during the first weeks after injury. Suggestion were made in absence of indirect calorimetry, to use of the Toronto equation (Schoffield in children) for energy requirement determination (risk of overfeeding), and to maintain fat administration ≤ 30% of total energy delivery. CONCLUSION The nutritional therapy in major burns has evidence-based specificities that contribute to improve clinical outcome.

Critical care and vitamin D status assessment: What about immunoassays and calculated free 25OH-D?

BACKGROUND Interpretation of 25OH-D measurement during critical care (CC) may be problematic due to variations of binding protein concentrations (albumin, ALB, and vitamin D binding protein, VDBP). Determination of free 25OH-D concentration may thus be relevant in CC patients. The aim of this observational study was to evaluate effects of an acute hemodilution on vitamin D (VD) status. METHODS Blood samples were obtained before (T1) and after a crystalloid load (T2) administered at anesthesia induction for minor surgery. 25OH-D was measured with LC-MS/MS and with 3 immunoassays (IA): DiaSorin Liaison, IDS iSYS and bioMérieux Vidas. VDBP was measured with the R&D Elisa and ALB on Cobas. Free 25OH-D was calculated using published formula. Accuracy of each 25OH-D IA was calculated as the percentage of IA values within 20% of their respective LC-MS/MS values. Performances of the three AI were compared with LC-MC/MS using Bland-Altman analysis. RESULTS Twenty adults were included. Compared to T1 values, VDBP, ALB and LC-MS/MS values decreased in parallel by a mean of 23% at T2. IA values decreased less significantly (12, 14 and 15% for Liaison, iSYS and Vidas, respectively). IA-based calculated free 25OH-D significantly increased after dilution, while LC-MS/MS-based free values remained stable. At T1 and T2, bias were demonstrable for all IA. After hemodilution, bias would lead to overestimation for the three IA. Accuracy of IA decreased after dilution. CONCLUSIONS Due to matrix effects, compared to LC-MS/MS, IA results were impacted by hemodilution. In CC patients, LC-MS/MS seems to be the best option to measure 25OH-D. Specific LC-MS/MS method should be developed to measure free 25OH-D.

The role of biochemical of bone turnover markers in osteoporosis and metabolic bone disease: a consensus paper of the Belgian Bone Club

The exact role of biochemical markers of bone turnover in the management of metabolic bone diseases remains a topic of controversy. In this consensus paper, the Belgian Bone Club aimed to provide a state of the art on the use of these biomarkers in different clinical or physiological situations like in postmenopausal women, osteoporosis in men, in elderly patients, in patients suffering from bone metastasis, in patients with chronic renal failure, in pregnant or lactating women, in intensive care patients, and in diabetics. We also gave our considerations on the analytical issues linked to the use of these biomarkers, on potential new emerging biomarkers, and on the use of bone turnover biomarkers in the follow-up of patients treated with new drugs for osteoporosis.

Effects of cholecalciferol supplementation and optimized calcium intakes on vitamin D status, muscle strength and bone health: A one-year pilot randomized controlled trial in adults with severe burns

OBJECTIVE Burn patients are at risk of hypovitaminosis D and osteopenia or sarcopenia. Vitamin D pleiotropic effects may influence bone and muscle health. The aim of this pilot study was to assess effects of a cholecalciferol (VD3) supplementation and an optimized calcium (Ca) regimen on vitamin D (VD) status, bone and muscle health during sequelar stage of burn injury. DESIGN Monocentric randomized controlled trial. METHODS Fifteen adults with thermal burns dating from 2 to 5 years were randomized into two groups. For 12 months, they either received a quarterly IM injection of 200,000IU VD3 and daily oral Ca (Group D) or placebo (Group P). VD status and bone remodeling markers were assessed every 3 months. Knee muscle strength and bone mineral density were, respectively, assessed using isokinetic dynamometry and dual X-ray absorptiometry at initiation (M0) and completion (M12) of the protocol. RESULTS Of all the patients, 66% presented with VD deficiency and 53% (with 3 men <40y) were considered osteopenic at inclusion. After one year, calcidiol levels significantly increased in Group D to reach 40 (37-61)ng/ml. No significant change in bone health was observed in both groups while Group D significantly improved quadriceps strength when tested at high velocity. CONCLUSIONS This VD3 supplementation was safe and efficient to correct hypovitaminosis D in burn adults. When combined with optimized Ca intakes, it demonstrated positive effects on muscle health but not on bone health. A high prevalence of hypovitaminosis D and osteopenia in these patients, as well as their wide range of muscle performances, seem to be worrying when considering rehabilitation and quality of life.

Effect of cholecalciferol recommended daily allowances on vitamin D status and fibroblast growth factor-23: An observational study in acute burn patients

OBJECTIVE Burn patients are at risk of hypovitaminosis D. Optimal vitamin D (VD) intakes are not defined in burn nutrition guidelines and studies mostly focused on ergocalciferol (VD2) supplementation in burn children. Aim of our study was to describe adult burns VD status, to measure effects of our cholecalciferol (VD3) supplementation on VD metabolism during acute burn care, and to assess correlation between FGF23 and C-reactive protein (CRP). DESIGN Cohort study. METHODS From March 2012 to January 2013, patients >18 years, admitted within 24 h after injury with burn surface area (BSA) ≥10% were included. Patients daily received VD3 from oral or enteral nutrition (400-600 IU) and from oral or intravenous multivitamin complex (200-220 IU). Serum levels of 25(OH)-D, 1-25(OH)2-D, 3rd generation PTH, C-terminal FGF23, total calcium, phosphate, albumin and CRP were measured at admission (D0) and every week during 4 weeks of follow-up. Data are expressed as percentage or median (min-max). Paired data were compared using Wilcoxon test. Correlation between CRP and FGF23 was assessed using nonparametric Spearman test. A p value <0.05 was considered to be statistically significant. RESULTS We initially included 24 patients. Median age and BSA were, respectively, 46 [19-86] years and 15 [10-85]%. At D0, 75% presented a VD insufficiency (25(OH)-D 21-29 ng/ml) and 17% presented a deficiency (25(OH)-D ≤20 ng/ml). We followed 12 patients until day 28: 25(OH)-D was unchanged while 1-25(OH)2-D and FGF23 decreased without reaching significance. We observed a significant positive correlation between FGF23 and CRP (r=0.59, 95% CI: 0.22-0.82, p=0.0032). CONCLUSIONS Most of our adult burns presented hypovitaminosis D regardless of age. Nutrition supplemented with low dose of VD3 (intakes reaching recommended daily allowances) was insufficient to correct 25(OH)-D level. Moreover, an interesting correlation between CRP and FGF23 was found.

Vitamin D status after a high dose of cholecalciferol in healthy and burn subjects

BACKGROUND Burn patients are at risk of vitamin D (VD) deficiency and may benefit from its pleiotropic effects as soon as acute phase. Aim of this observational study was to assess effects of a cholecalciferol (VD3) bolus on VD status in adult burn patients (Group B, GB) after admission, compared to healthy subjects (Group H, GH). METHODS Both groups received an oral dose of 100,000 IU VD3. Blood samples were collected before (D0) and 7 days (D7) after bolus to measure 250H-D, 1,25(OH)2-D, parathyroid hormone (PTH) and fibroblast growth factor 23 (FGF23). Albumin (ALB) and VD binding protein (DBP) were measured and used to calculate free 25OH-D level. Data were expressed as median (min-max) or proportions. RESULTS A total of 49 subjects were included: 29 in GH and 20 in GB. At D0, prevalence of VD deficiency was higher in GB: 25OH-D was 21.5 (10.1-46.3) ng/ml in GH vs 11 (1.8-31.4) ng/ml in GB. DBP and ALB were lower in GB. At D7, DBP was stable in both groups while ALB decreased in GB. 25OH-D increased by 66.6 (13.5-260.3)% in GH. In GB, changes in 25OH-D extended from -36.7% to 333.3% with a median increase of 33.1%. Similar changes were observed in each group for free 25OH-D. High FGF23 levels were observed in GB. CONCLUSIONS This study highlighted the differences in VD status and in response to a high dose VD3 in burn patients when compared to healthy patients. Pitfalls in VD status assessment are numerous during acute burn care: 25OH-D measurement needs cautious interpretation and interest of free 25OH-D is still questionable. They should not prevent burn patients to receive VD supplements during acute care. Higher doses than general recommendations should probably be considered.

Toward targeted early burn care: lessons from a European survey.

During the year 2011, a survey was performed to describe current practices throughout Europe regarding three critical issues of acute burn care, namely fluid resuscitation, nutrition, and burn wound excision strategy. Thirty-eight questionnaires returned by burn centres from 17 different European countries were analyzed. The survey shows that Parkland remains the most commonly used formula to determine fluid needs in adults. All respondent centers use urine output to guide fluid resuscitation. While early excision of deep burns is the rule among centers, burn depth assessment by laser Doppler imaging is used in only a few centers. Indirect calorimetry and Toronto formula to estimate energy requirements do not have unanimous backing from respondents. Current literature encourages clinicians to move forward targeted and individualized therapies using a bundle of basic and advanced hemodynamic parameters, indirect calorimetry, and laser Doppler imaging. The results of this study suggest that such an approach is not common yet, and reinforce the subsequent need for large clinical trials that would evaluate the impact of such guided therapies to provide recommendations with a significant level of evidence.

Bone markers during acute burn care: Relevance to clinical practice?

OBJECTIVE Bone changes are increasingly described after burn. How bone markers could help to detect early bone changes or to screen burn patients at higher risk of demineralization is still not made clear. We performed an observational study assessing the changes in serum bone markers after moderate burn. METHODS Adults admitted in the first 24h following burn extended on >10% body surface area were included. Serum levels of collagen type 1 cross-linked C-telopeptide (CTX), tartrate-resistant acid phosphatase 5b (TRAP), type 1 procollagen N-terminal (P1NP) and bone alkaline phosphatase (b-ALP) were measured at admission and every week during the first month. Data are expressed as median [min-max]. RESULTS Bone markers were measured in 20 patients: 18 men, 2 women (including one post-menopausal). Age was 46 [19-86] years old, burn surface area reached 15 [7-85] %. Twelve patients completed the study. All biomarkers mainly remained into normal ranges during evolution. A huge variability was observed regarding biomarkers evolution. Patients evolution was not linear and could fluctuate from a decrease to an increase of blood concentrations. There was not necessarily a consistency between the two formation or the two resorption markers. Variations observed between two consecutive measurements were lesser than the accepted critical difference in almost one third of the cases. CONCLUSIONS Considering available data, role and interest of bone markers in management of burn related bone disease remain unclear.

Serum markers of sepsis in burn patients: it takes more to convince!

To the Editor: Diagnosis of septic complications during acute burn care remains a big challenge. Infectious biomarkers commonly used in a general population of critically ill patients are disappointing in burn patients. In this context, we read with interest the recent study published by Paratz et al (1). Authors emphasize the inefficiency of procalcitonin in sepsis diagnosis during burn care. However, procalcitonin should be better assessed during a de-escalation strategy of antibiotic treatment, as advocated in general intensive care (2). Authors also state that serum N-terminal pro-B-type natriuretic peptide (NT-proBNP) is an early indicator of sepsis in burn patients. We have some remarks regarding this statement. First, NT-proBNP may fluctuate according to age, gender, anemia, obesity, and, more importantly, renal insufficiency (3). The latter is an important confounder for interpretation of NTproBNP. However, there was no adjustment for renal function. Second, the time frame before infection occurrence as well as the diagnostic workup leading to source determination were not explicitly described. This could have lead to misinterpretation between colonization and infection, thus explaining a surprisingly high rate of early infections. Furthermore, prevalence of inhalation injury was higher among patients with sepsis. Subsequent exacerbated inflammatory response or right ventricular dysfunction may therefore have induced bias. In conclusion, it seems difficult to establish whether NTproBNP is a reliable predictive marker of burn sepsis or just a systemic inflammatory response syndrome marker, apart from being a marker of ventricular stretching. NT-proBNP is increasingly reported in critically ill patients. Paratz et al (1) focused their analysis on a very specific population. It calls for further studies aiming to define pathophysiology, role, and interest of NT-proBNP in burn patients. Meanwhile, we make a plea against using the otherwise expensive NT-proBNP assay to justify a liberal antibiotic prescription without evidence of infection. 3. Hartling L, Hamm M, Milne A, et al: Validity and Inter-Rater Reliability Testing of Quality Assessment Instruments. Rockville, 2012. Available at: http://www.ncbi.nlm.nih.gov/books/NBK92293/. Accessed October 7, 2014 4. Sanderson S, Tatt ID, Higgins JP: Tools for assessing quality and susceptibility to bias in observational studies in epidemiology: A systematic review and annotated bibliography. Int J Epidemiol 2007; 36:666–676 5. Olivo SA, Macedo LG, Gadotti IC, et al: Scales to assess the quality of randomized controlled trials: A systematic review. Phys Ther 2008; 88:156–175 6. Wells GA, Shea B, O’Connell D, et al: The Newcastle-Ottawa Scale (NOS) for assessing the quality of nonrandomised studies in metaanalyses. 2011. Available at: http://www.ohri.ca/programs/clinical_ epidemiology/oxford.asp. Accessed October 7, 2014 Assessment of Methodological Quality for Included Studies Is Necessary in a Systematic Review

Vitamin D status in critically ill patients: back to basics!

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