Publications by authors named "Mette M Berger"

146 Publications

Exudative Glutamine losses contribute to the high needs after burn injury.

JPEN J Parenter Enteral Nutr 2021 Jul 20. Epub 2021 Jul 20.

Service of Adult Intensive Care, Lausanne University Hospital (CHUV), Lausanne, Switzerland.

Background: Burn patients characteristically have increased energy, glucose and protein requirements. Glutamine supplementation is strongly recommended during early phase treatment and is associated with improved immunity, wound healing, and reduced mortality. This study evaluated if early burn exudative losses might contribute to higher supplementation needs.

Methods: Patients admitted to the burn intensive care unit (ICU) had exudate collection from tight bandages applied to arms or legs during the first week (exudate aliquot twice daily). Seven amino acids (alanine, arginine, cystine, glutamine, leucine, lysine, methionine) were quantified by liquid chromatography-mass spectrometry. Descriptive analysis of all results is provided as in medians and interquartile ranges or in value ranges.

Results: Eleven patients aged 19 to 77 years, presenting with burns on 18 to 70% of body surface, with a median SAPSII 33 (range 16 to 56) were included during the study period. The highest amino acid losses were observed during the first 3 days with an important inter- and intra-patient variability. Glutamine and alanine losses were highest, followed by leucine and lysine in all patients: amino acid exudate concentrations were in the range of normal plasma concentrations and stable over time. Total glutamine losses were correlated to burned surface (r2 = 0.552, p = 0.012), but not to enteral glutamine supplements.

Conclusions: The study shows significant exudative losses during early stage burn recovery and particularly for glutamine and alanine. Glutamine loss generally decreased with wound closure and subsequent decline of exudation and evolving size of burn surfaces. This article is protected by copyright. All rights reserved.
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http://dx.doi.org/10.1002/jpen.2227DOI Listing
July 2021

Magnitude of gluconeogenesis and endogenous glucose production: are they predictable in clinical settings?

Clin Nutr 2021 Jun 3;40(6):3807-3814. Epub 2021 Jun 3.

Service of Adult Intensive Care, Lausanne University Hospital (CHUV), Lausanne, Switzerland.

Introduction: Regulation of endogenous glucose production (EGP) is essential for glucose homeostasis. It includes gluconeogenesis (GNG) from non-carbohydrate substrates and hepatic glycogenolysis. Both these pathways are dysregulated in acute stress, but the magnitude of this deregulation cannot be assessed in clinical practice. The study aims at identifying clinically available variables predictive of EGP and GNG magnitude by modeling routinely available data.

Methods: This exploratory study is based on the data from the Supplemental Parenteral Nutrition study 2 (SPN2), which measured EGP and GNG at days 4 and 10 in 23 critically ill patients. The correlation between EGP and GNG and 83 potential clinical indicators were explored, using single-stage and multivariate analysis.

Results: On single-stage analysis, the strongest correlations were noradrenaline dose at day 4 with GNG (R = 0.71; P = 0.0004) and Nutrition risk screening score (NRS) with EGP (R = 0.42; P = 0.05). At day 10, VO (R = 0.59, P = 0.04) was correlated with GNG and VCO with EGP (R = 0.85, P = 0.00003). Cumulated insulin dose between days 5 and 9 was correlated to EGP at day 10 (R = 0.55, P = 0.03). Our multivariate model could predict EGP at day 4 (VCO, glucose and energy intake) with an error coefficient (e.c.) between 7.8% and 23.4% (minimal and maximal error), and GNG at day 10 (age, mean and basal blood glucose), with an e.c. of 18.5% and 29.9%. GNG at day 4 and EGP at day 10 could not be predicted with an e.c. < 40%.

Conclusion: This preliminary exploratory study shows that GNG and EGP have different predictors on days 4 and 10; EGP is more correlated with the metabolic level, while GNG is dependent on external factors. Nevertheless, a bundle of variables could be identified to empirically assess the magnitude of both values. Our results suggest that a robust model might be built, but requires a prospective study including a larger number of patients.
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http://dx.doi.org/10.1016/j.clnu.2021.05.016DOI Listing
June 2021

Nutrients and micronutrients at risk during renal replacement therapy: a scoping review.

Curr Opin Crit Care 2021 08;27(4):367-377

Department of Anesthesiology and Surgery, Duke University School of Medicine, Durham, North Carolina, USA.

Purpose Of Review: Malnutrition is frequent in patients with acute kidney injury. Nutrient clearance during renal replacement therapy (RRT) potentially contributes to this complication. Although losses of amino acid, trace elements and vitamins have been described, there is no clear guidance regarding the role of micronutrient supplementation.

Recent Findings: A scoping review was conducted with the aim to review the existing literature on micronutrients status during RRT: 35 publications including data on effluent losses and blood concentrations were considered relevant and analysed. For completeness, we also included data on amino acids. Among trace elements, negative balances have been shown for copper and selenium: low blood levels seem to indicate potential deficiency. Smaller size water soluble vitamins were found in the effluent, but not larger size liposoluble vitamins. Low blood values were frequently reported for thiamine, folate and vitamin C, as well as for carnitine. All amino acids were detectable in effluent fluid. Duration of RRT was associated with decreasing blood values.

Summary: Losses of several micronutrients and amino acids associated with low blood levels represent a real risk of deficiency for vitamins B1 and C, copper and selenium: they should be monitored in prolonged RRT. Further Research is urgently required as the data are insufficient to generate strong conclusions and prescription recommendations for clinical practice.
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http://dx.doi.org/10.1097/MCC.0000000000000851DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8270509PMC
August 2021

Strengthening the immunity of the Swiss population with micronutrients: A narrative review and call for action.

Clin Nutr ESPEN 2021 06 24;43:39-48. Epub 2021 Mar 24.

Department of Internal Medicine, University Medical Center Groningen, Groningen, the Netherlands. Electronic address:

Background: The enormous health impact of the COVID-19 pandemic has refocused attention on measures to optimize immune function and vaccine response. Dietary deficiencies of micronutrients can weaken adaptive immunity. The aim of this review was to examine links between micronutrients, immune function and COVID-19 infection, with a focus on nutritional risks in subgroups of the Swiss population.

Methods: Scoping review on the associations between selected micronutrients (vitamins D and C, iron, selenium, zinc, and n-3 PUFAs) and immunity, with particular reference to the Swiss population. These nutrients were chosen because previous EFSA reviews have concluded they play a key role in immunity.

Results: The review discusses the available knowledge on links between sufficient nutrient status, optimal immune function, and prevention of respiratory tract infections. Because of the rapid spread of the COVID-19 pandemic, controlled intervention studies of micronutrients in the context of COVID-19 infection are now underway, but evidence is not yet available to draw conclusions. The anti-inflammatory properties of n-3 PUFAs are well established. In Switzerland, several subgroups of the population are at clear risk of nutrient deficiencies; e.g., older adults, multiple comorbidities, obesity, pregnancy, and institutionalized. Low intakes of n-3 PUFA are present in a large proportion of the population.

Conclusion: There are clear and strong relationships between micronutrient and n-3 PUFA status and immune function, and subgroups of the Swiss population are at risk for deficient intakes. Therefore, during the COVID-19 pandemic, as a complement to a healthy and balanced diet, it may be prudent to consider supplementation with a combination of moderate doses of Vitamins C and D, as well as of Se, Zn and n-3 PUFA, in risk groups.
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http://dx.doi.org/10.1016/j.clnesp.2021.03.012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7987506PMC
June 2021

Comprehensive metabolic amino acid flux analysis in critically ill patients.

Clin Nutr 2021 May 18;40(5):2876-2897. Epub 2021 Mar 18.

Dept of Adult Intensive Care, Lausanne University Hospital (CHUV), Lausanne, Switzerland.

Amino acid (AA) metabolism is severely disturbed in critically ill ICU patients. To be able to make a more scientifically based decision on the type of protein or AA nutrition to deliver in ICU patients, comprehensive AA phenotyping with measurements of plasma concentrations and whole body production (WBP) is needed. Therefore, we studied ICU patients and matched control subjects using a novel pulse isotope method to obtain in-depth metabolic analysis. In 51 critically ill ICU patients (SOFA~6.6) and 49 healthy controls, we measured REE and body composition/phase-angle using BIA. In the postabsorptive state, we collected arterial (ized) blood for CRP and AA. Then, we administered an 8 mL solution containing 18 stable AA tracers as a pulse and calculated WBP. Enrichments: LC-MS/MS and statistics: t-test, ANCOVA. Compared to healthy, critically ill ICU patients had lower phase-angle (p < 0.00001), and higher CRP (p < 0.0001). Most AA concentrations were lower in ICU patients (p < 0.0001), except tau-methylhistidine and phenylalanine. WBP of most AA were significantly (p < 0.0001) higher with increases in glutamate (160%), glutamine (46%), and essential AA. Remarkably, net protein breakdown was lower. There were only weak relationships between AA concentrations and WBP. Critically ill ICU patients (SOFA 8-16) had lower values for phase angle (p = 0.0005) and small reductions of most plasma AA concentrations, but higher tau-methylhistidine (p = 0.0223) and hydroxyproline (p = 0.0028). Remarkably, the WBP of glutamate and glutamine were lower (p < 0.05), as was their clearance, but WBP of tau-methylhistidine (p = 0.0215) and hydroxyproline (p = 0.0028) were higher. Our study in critically ill ICU patients shows that comprehensive metabolic phenotyping was able to reveal severe disturbances in specific AA pathways, in a disease severity dependent way. This information may guide improving nutritional compositions to improve the health of the critically ill patient. CLINICAL TRIAL REGISTRY: Data are from the baseline measurements of study NCT02770092 (URL: https://clinicaltrials.gov/ct2/show/NCT02770092) and NCT03628365 (URL: https://clinicaltrials.gov/ct2/show/NCT03628365).
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http://dx.doi.org/10.1016/j.clnu.2021.03.015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8172442PMC
May 2021

Hypermetabolism not so common anymore in trauma patients?

JPEN J Parenter Enteral Nutr 2021 Apr 29. Epub 2021 Apr 29.

Unité de Nutrition, Geneva University Hospital, Geneva, Switzerland.

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http://dx.doi.org/10.1002/jpen.2134DOI Listing
April 2021

Massive burns: retrospective analysis of changes in outcomes indicators across 18 years.

J Burn Care Res 2021 Apr 22. Epub 2021 Apr 22.

Department of Plastic, Reconstructive and Hand Surgery, Lausanne University Hospital, Switzerland.

Background: The treatment and management of massive burns, defined as burns affecting≥ 50% of total body surface area (TBSA) has considerably changed since the 90s. This study aimed at analyzing if the length of intensive care unit (ICU) stay, the success of skin grafting operations and the mortality changed in the last 18 years.

Methods: Between 2000 and 2018, 77 patients were admitted for massive burns to the ICU of a university hospital. Transfers and early care withdrawal precluded inclusion for 38 patients, leaving 39 for analysis. Study variables were year of admission, demographics, burn characteristics, critical care treatment (fluid resuscitation, ventilation and nutrition) and surgical therapy. Association between outcomes and year of admission were assessed through correlation and logistic regression analysis. Potential confounders were assessed through stepwise linear regression.

Results: Patients' characteristics were stable over time with a median age of 36[25.0, 48.0] years, burns 65% [55.0, 83.0] TBSA and deep burns 55% [50.0, 68.0] TBSA . Length of ICU stay remained stable at 0.97 [0.6, 1.5] days/%TBSA. Mortality was stable as well. Energy and carbohydrate delivery decreased in parallel with the number of infectious episodes per patient. Number of operations was stable but the take rate of skin grafts increased significantly. The multivariate analysis retained year of admission, weight, total number of infections, daily lipid intakes and fluid resuscitation as independent predicting variables.

Conclusion: Length of ICU stay and mortality did not change over time but skin grafts take rates improved significantly.
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http://dx.doi.org/10.1093/jbcr/irab072DOI Listing
April 2021

Amino acids and vitamins status during continuous renal replacement therapy: An ancillary prospective observational study of a randomised control trial.

Anaesth Crit Care Pain Med 2021 04 12;40(2):100813. Epub 2021 Feb 12.

CHU de Bordeaux, Service Anesthésie et Réanimation SUD, Centre médico-chirurgical Magellan, Bordeaux, France. Electronic address:

Background: Continuous renal replacement therapy (CRRT) is associated with micronutrients loss. Current recommendations are to administer 1-1.5g/kg/day of proteins during CRRT. We aim to evaluate the net effect of CRRT on amino acids (AA), vitamins A and C (Vit A, Vit C) levels.

Methods: This is a prospective observational study embedded within a randomised controlled trial comparing two CRRT doses in patients with septic shock. CRRT was provided in continuous veno-venous haemofiltration mode at a dose of either 35ml/kg/h or 70ml/kg/h. All patients received parenteral nutrition with standard trace elements and vitamins (protein intake 1g/kg/d). We measured serum levels of glutamine, valine and alanine as well as Vit A and Vit C upon randomisation, study day four and eight. In addition, we measured a larger panel of AA in a subset of 11 patients.

Results: We included 30 patients (17 allocated to 70ml/kg/h and 13 to 35ml/kg/h CRRT). Before CRRT initiation, mean plasma levels of glutamine and valine, Vit A and Vit C were low. CRRT was not associated with any significant change in AA levels except for a decrease in cystein. It was associated with an increase in Vit A and a decrease in Vit C levels. CRRT dose had no impact on those nutrients blood levels.

Conclusions: Irrespective of dose, CRRT was associated with a decrease in cysteine and Vit C and an increase in Vit A with no significant change in other AA. Further studies should focus on lean mass wasting during CRRT.
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http://dx.doi.org/10.1016/j.accpm.2021.100813DOI Listing
April 2021

Micronutrients early in critical illness, selective or generous, enteral or intravenous?

Curr Opin Clin Nutr Metab Care 2021 03;24(2):165-175

Hospital de Clínicas, University Hospital, UdelaR, Montevideo, Uruguay.

Purpose Of Review: Micronutrients have essential antioxidant and immune functions, while low blood concentrations are frequently observed in critically ill patients. This has led to the concepts of complementation, repletion, or even pharmacological supplementation. Over the last three decades, many clinical studies have tested the latter strategy, with controversial or negative results. Therefore, this review aims at evaluating micronutrient-related interventions that are mandatory or need to be assessed in future trials or clinical registries in all or specific critically ill patients.

Recent Findings: In the critically ill, low plasma/serum micronutrient levels not always reflect a true deficiency in the absence of demonstrable losses. Current practices of micronutrient provision and monitoring in critical care, vary substantially across the world. Also, recent clinical trials testing high dose as monotherapy (selenium, thiamine, vitamin C, vitamin D) or in combination have failed to demonstrate clinical benefits in sepsis. However, these studies have not applied a physiological integrative approach of micronutrient action.

Summary: Micronutrients are essential in nutrition but their administration and monitoring are difficult. So far, different well designed RCTs on intravenous and oral high dose micronutrient supplementation have been conducted. Nevertheless, very high-dose single micronutrients cannot be advocated at this stage in sepsis, or any other critical condition. By contrast, studies using combination of moderate doses of micronutrients in specific diseases, such as burns and trauma have been associated with improved outcomes. Intravenous administration seems to be the most efficient route. Future clinical trials need to integrate the physiology underlying the interconnected micronutrient activity, and choose more specific primary and secondary endpoints.
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http://dx.doi.org/10.1097/MCO.0000000000000724DOI Listing
March 2021

Hypophosphatemia in critically ill adults and children - A systematic review.

Clin Nutr 2021 Apr 8;40(4):1744-1754. Epub 2020 Oct 8.

Service of Adult Intensive care & Burns, Lausanne University Hospital, Lausanne, Switzerland. Electronic address:

Background & Aims: Phosphate is the main intracellular anion essential for numerous biological processes. Symptoms of hypophosphatemia are non-specific, yet potentially life-threatening. This systematic review process was initiated to gain a global insight into hypophosphatemia, associated morbidity and treatments.

Methods: A systematic review was conducted (PROSPERO CRD42020163191). Nine clinically relevant questions were generated, seven for adult and two for pediatric critically ill patients, and prevalence of hypophosphatemia was assessed in both groups. We identified trials through systematic searches of Medline, EMBASE, Scopus, Cochrane Central Register of Controlled Trials, CINAHL, and Web of Science. Quality assessment was performed using the Cochrane risk of bias tool for randomized controlled trials and the Newcastle-Ottawa Scale for observational studies.

Results: For all research questions, we identified 2727 titles in total, assessed 399 full texts, and retained 82 full texts for evidence synthesis, with 20 of them identified for several research questions. Only 3 randomized controlled trials were identified with two of them published only in abstract form, as well as 28 prospective and 31 retrospective studies, and 20 case reports. Relevant risk of bias regarding selection and comparability was identified for most of the studies. No meta-analysis could be performed. The prevalence of hypophosphatemia varied substantially in critically ill adults and children, but no study assessed consecutive admissions to intensive care. In both critically ill adults and children, several studies report that hypophosphatemia is associated with worse outcome (prolonged length of stay and the need for respiratory support, and higher mortality). However, there was insufficient evidence regarding the optimal threshold upon which hypophosphatemia becomes critical and requires treatment. We found no studies regarding the optimal frequency of phosphate measurements, and regarding the time window to correct hypophosphatemia. In adults, nutrient restriction on top of phosphate repletion in patients with refeeding syndrome may improve survival, although evidence is weak.

Conclusions: Evidence on the definition, outcome and treatment of clinically relevant hypophosphatemia in critically ill adults and children is scarce and does not allow answering clinically relevant questions. High quality clinical research is crucial for the development of respective guidelines.
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http://dx.doi.org/10.1016/j.clnu.2020.09.045DOI Listing
April 2021

First international meeting of early career investigators: Current opportunities, challenges and horizon in critical care nutrition research.

Clin Nutr ESPEN 2020 12 22;40:92-100. Epub 2020 Sep 22.

Department of Adult Intensive Care Medicine and Burns, Lausanne University Hospital CHUV, Lausanne, Switzerland.

Background: Appropriate nutritional support is a key component of care for critically ill patients. While malnutrition increases complications, impacting long term outcomes and healthcare-related costs, uncertainties persist regarding optimal provision of nutritional support in this setting.

Methods: An international group of healthcare providers (HCPs) from critical care specialties and nutrition researchers convened to identify knowledge gaps and learnings from studies in critical care nutrition. Clinical research needs were identified in order to better inform future nutrition practices.

Results: Challenges in critical care nutrition arise, in part, from inconsistent outcomes in several large-scale studies regarding the optimal amount of calories and protein to prescribe, the optimal time to initiate nutritional support and the role of parental nutrition to support critically ill patients. Furthermore, there is uncertainty on how best to identify patients at nutritional risk, and the appropriate outcome measures for ICU nutrition studies. Given HCPs have a suboptimal evidence base to inform the nutritional management of critically ill patients, further well-designed clinical trials capturing clinically relevant endpoints are needed to address these knowledge gaps.

Conclusions: The identified aspects for future research could be addressed in studies designed and conducted in collaboration with an international team of interdisciplinary nutrition experts. The aim of this collaboration is to address the unmet need for robust clinical data needed to develop high-quality evidence-based nutritional intervention recommendations to better inform the future management of critically ill patients.
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http://dx.doi.org/10.1016/j.clnesp.2020.09.006DOI Listing
December 2020

Stress ulcer prophylaxis: Is mortality a useful endpoint?

Intensive Care Med 2020 11 28;46(11):2058-2060. Epub 2020 Sep 28.

Division of Intensive Care and Emergency Medicine, Department of Internal Medicine, Medical University Innsbruck, Anichstrasse 35, 6020, Innsbruck, Austria.

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http://dx.doi.org/10.1007/s00134-020-06250-9DOI Listing
November 2020

Nutrition and Micronutrient Therapy in Critical Illness Should Be Individualized.

Authors:
Mette M Berger

JPEN J Parenter Enteral Nutr 2020 11 17;44(8):1380-1387. Epub 2020 Sep 17.

Department of Adult Intensive Care Medicine, Lausanne University Hospital (CHUV), Lausanne, Switzerland.

Critically ill (intensive care unit [ICU]) patients are characterized by organ failure, intense inflammatory response, insulin resistance, and altered metabolic response. The sicker the patient, the higher the threat to nutrition and micronutrient status. In addition, many patients start the ICU stay with an altered nutrition status, which requires assessment upon admission. Nutrition needs vary among patients as well as during hospitalization, as the metabolic response changes over time. Shock and acute organ failure result in a metabolic shift toward intense catabolism: endogenous glucose production aiming at ensuring the basal adenosine triphosphate production starts immediately and occurs at the expense of the lean body mass using amino acids for neoglucogenesis. Later, the stabilization and recovery phases are characterized by higher energy and substrate needs. Indirect calorimetry is the only tool enabling determination of the metabolic level. When and how should feeding be started? Recent research shows that the route does not matter much, with equipoise between enteral and parenteral nutrition (PN) as long as overfeeding is avoided. As micronutrients are an integral part of metabolism and antioxidant defenses, their delivery must be ensured: whereas needs are well defined for healthy individuals, needs for illness remain poorly defined. PN that contains only macrosubstrates requires the daily prescription of multimicronutrient complements to qualify as total PN. Achievement of goals requires minimal monitoring, consisting of the daily verification of energy and protein goal delivery achievement and daily follow-up determining blood glucose and phosphate levels and insulin requirements.
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http://dx.doi.org/10.1002/jpen.2002DOI Listing
November 2020

Indirect calorimetry: The 6 main issues.

Clin Nutr 2021 01 2;40(1):4-14. Epub 2020 Jul 2.

Clinical Nutrition, Geneva University Hospital, Geneva, Switzerland.

Background And Aims: Optimal nutritional therapy, including the individually adapted provision of energy, is associated with better clinical outcomes. Indirect calorimetry is the best tool to measure and monitor energy expenditure and hence optimize the energy prescription. Similarly to other medical techniques, indications and contra-indications must be acknowledged to optimise the use of indirect calorimetry in clinical routine. Measurements should be repeated to enable adaptation to the clinical evolution, as energy expenditure may change substantially. This review aims at providing clinicians with the knowledge to routinely use indirect calorimetry and interpret the results.

Method: We performed a bibliographic research of publications referenced in PubMed using the following terms: "indirect calorimetry", "energy expenditure", "resting energy expenditure", "VCO", "VO", "nutritional therapy". We included mainly studies published in the last ten years, related to indirect calorimetry principles, innovations, patient's benefits, clinical use in practice and medico-economic aspects.

Results: We have gathered the knowledge required for routine use of indirect calorimetry in clinical practice and interpretation of the results. A few clinical cases illustrate the decision-making process around its application for prescription, and individual optimisation of nutritional therapy. We also describe the latest technical innovations and the results of tailoring nutrition therapy according to the measured energy expenditure in medico-economic benefits.

Conclusion: The routine use of indirect calorimetry should be encouraged as a strategy to optimize nutrition care.
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http://dx.doi.org/10.1016/j.clnu.2020.06.024DOI Listing
January 2021

Monitoring and parenteral administration of micronutrients, phosphate and magnesium in critically ill patients: The VITA-TRACE survey.

Clin Nutr 2021 02 14;40(2):590-599. Epub 2020 Jun 14.

KU Leuven, Department of Cellular and Molecular Medicine, Laboratory of Intensive Care Medicine, Leuven, Belgium. Electronic address:

Background & Aims: Despite the presumed importance of preventing and treating micronutrient and mineral deficiencies, it is still not clear how to optimize measurement and administration in critically ill patients. In order to design future comparative trials aimed at optimizing micronutrient and mineral management, an important first step is to gain insight in the current practice of micronutrient, phosphate and magnesium monitoring and administration.

Methods: Within the metabolism-endocrinology-nutrition (MEN) section of the European Society of Intensive Care Medicine (ESICM), the micronutrient working group designed a survey addressing current practice in parenteral micronutrient and mineral administration and monitoring. Invitations were sent by the ESICM research department to all ESICM members and past members.

Results: Three hundred thirty-four respondents completed the survey, predominantly consisting of physicians (321 [96.1%]) and participants working in Europe (262 [78.4%]). Eighty-one (24.3%) respondents reported to monitor micronutrient deficiencies through clinical signs and/or laboratory abnormalities, and 148 (44.3%) reportedly measure blood micronutrient concentrations on a routine basis. Two hundred ninety-two (87.4%) participants provided specific data on parenteral micronutrient supplementation, of whom 150 (51.4%) reported early administration of combined multivitamin and trace element preparations at least in selected patients. Among specific parenteral micronutrient preparations, thiamine (146 [50.0%]) was reported to be the most frequently administered micronutrient, followed by vitamin B complex (104 [35.6%]) and folic acid (86 [29.5%]). One hundred twenty (35.9%) and 113 (33.8%) participants reported to perform daily measurements of phosphate and magnesium, respectively, whereas 173 (59.2%) and 185 (63.4%) reported to routinely supplement these minerals parenterally.

Conclusion: The survey revealed a wide variation in current practices of micronutrient, phosphate and magnesium measurement and parenteral administration, suggesting a risk of insufficient prevention, diagnosis and treatment of deficiencies. These results provide the context for future comparative studies, and identify areas for knowledge translation and recommendations.
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http://dx.doi.org/10.1016/j.clnu.2020.06.005DOI Listing
February 2021

Nutrition Status Affects COVID-19 Patient Outcomes.

Authors:
Mette M Berger

JPEN J Parenter Enteral Nutr 2020 09 15;44(7):1166-1167. Epub 2020 Jul 15.

Department of Adult Intensive Care Medicine, Lausanne University Hospital (CHUV), Lausanne, Switzerland.

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http://dx.doi.org/10.1002/jpen.1954DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7361441PMC
September 2020

Trace element and vitamin deficiency: quantum medicine or essential prescription?

Curr Opin Crit Care 2020 08;26(4):355-362

Service of Adult Intensive Care Medicine, Lausanne University Hospital (CHUV), University of Lausanne, Lausanne, Switzerland.

Purpose Of Review: In critical care, micronutrients remain perceived as 'quantum' part, that is, a little pertinent component of therapy. Some micronutrients have attracted more attention because of their antioxidant properties. During the last decade, some large size trials have tested their therapeutic potential, generally as 'single high-dose micronutrient intervention', with variable success. This review aims at taking stock of most recent.

Recent Findings: Micronutrient blood levels are generally low in ICU patients, which has prompted the concept of replenishing or compensating deficits, or even realizing a pharmacological action. Single micronutrient trials have been conducted in large cohorts with selenium (≥1000 μg/day), with limited success but no harm. Other trials have tested high-dose vitamin D (>400 000 IU), with nonconvincing results despite selecting patients with very low blood levels. High-dose vitamin C has been tested in septic shock (+/- thiamine, hydrocortisone) with variable results. A problem encountered in all studies is definition of deficiency based on blood levels as majority of the patients suffer inflammation, which causes redistribution of the micronutrients away from the circulating compartment in the absence of real deficiency.

Summary: Micronutrients are essential in the ICU. Due to their antioxidant properties and to the high prevalence of low blood concentrations suggestive of deficiency, several large-size RCTs have been conducted with variable success. Further research must clarify the respective importance of deficiency and inflammation.
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http://dx.doi.org/10.1097/MCC.0000000000000737DOI Listing
August 2020

Gastrointestinal dysfunction in the critically ill: a systematic scoping review and research agenda proposed by the Section of Metabolism, Endocrinology and Nutrition of the European Society of Intensive Care Medicine.

Crit Care 2020 05 15;24(1):224. Epub 2020 May 15.

The University of Melbourne, Department of Medicine, Royal Melbourne Hospital, Parkville, Victoria, 3050, Australia.

Background: Gastrointestinal (GI) dysfunction is frequent in the critically ill but can be overlooked as a result of the lack of standardization of the diagnostic and therapeutic approaches. We aimed to develop a research agenda for GI dysfunction for future research. We systematically reviewed the current knowledge on a broad range of subtopics from a specific viewpoint of GI dysfunction, highlighting the remaining areas of uncertainty and suggesting future studies.

Methods: This systematic scoping review and research agenda was conducted following successive steps: (1) identify clinically important subtopics within the field of GI function which warrant further research; (2) systematically review the literature for each subtopic using PubMed, CENTRAL and Cochrane Database of Systematic Reviews; (3) summarize evidence for each subtopic; (4) identify areas of uncertainty; (5) formulate and refine study proposals that address these subtopics; and (6) prioritize study proposals via sequential voting rounds.

Results: Five major themes were identified: (1) monitoring, (2) associations between GI function and outcome, (3) GI function and nutrition, (4) management of GI dysfunction and (5) pathophysiological mechanisms. Searches on 17 subtopics were performed and evidence summarized. Several areas of uncertainty were identified, six of them needing consensus process. Study proposals ranked among the first ten included: prevention and management of diarrhoea; management of upper and lower feeding intolerance, including indications for post-pyloric feeding and opioid antagonists; acute gastrointestinal injury grading as a bedside tool; the role of intra-abdominal hypertension in the development and monitoring of GI dysfunction and in the development of non-occlusive mesenteric ischaemia; and the effect of proton pump inhibitors on the microbiome in critical illness.

Conclusions: Current evidence on GI dysfunction is scarce, partially due to the lack of precise definitions. The use of core sets of monitoring and outcomes are required to improve the consistency of future studies. We propose several areas for consensus process and outline future study projects.
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http://dx.doi.org/10.1186/s13054-020-02889-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7226709PMC
May 2020

The clinical evaluation of the new indirect calorimeter developed by the ICALIC project.

Clin Nutr 2020 10 31;39(10):3105-3111. Epub 2020 Jan 31.

Nutrition Unit, Geneva University Hospital, Rue Gabrielle-Perret-Gentil 4, 1211, Geneva, Switzerland. Electronic address:

Background & Aims: The ICALIC project was initiated for developing an accurate, reliable and user friendly indirect calorimeter (IC) and aimed at evaluating its ease of use and the feasibility of the EE measurements in intensive care unit (ICU).

Methods: This was a prospective unblinded, observational, multi-center study. Simultaneous IC measurements in mechanically ventilated ICU patients were performed using the new IC (Q-NRG®) and currently used devices. Time required to obtain EE was recorded to evaluate the ease of use of Q-NRG® versus currently used ICs and EE measurements were compared. Conventional descriptive statistics were used: data as mean ± SD.

Results: Six centers out of nine completed the required number of patients for the primary analysis. Mean differences in the time needed by Q-NRG® against currently used ICs were -32.3 ± 2.5 min in Geneva (vs. Deltatrac®; p < 0.01), -32.3 ± 3.1 in Lausanne (vs. Quark RMR®; p < 0.05), -33.7 ± 1.4 in Brussels (vs. V-Max Encore®; p < 0.05), -26.4 ± 7.8 in Tel Aviv (vs. Deltatrac®; p < 0.05), -28.5 ± 3.5 in Vienna (vs. Deltatrac®; p < 0.05), and 0.3 ± 1.2 in Chiba (vs. E-COVX®; p = 0.17). EE (kcal/day) measurements by the Q-NRG® were similar to the Deltatrac® in Geneva and Vienna (mean differences±SD: -63.1 ± 157.8 (p = 0.462) and -22.9 ± 328.2 (=0.650)), but significantly different in Tel Aviv (307.4 ± 324.5, p < 0.001). Significant differences were observed in Lausanne (Quark RMR® -224.4 ± 514.9, p = 0.038) and in Brussels (V-max®: -449.6 ± 667.4, p < 0.001), but none was found in Chiba (E-COVX®; 55.0 ± 204.1, p = 0.165).

Conclusion: The Q-NRG® required a much shorter time than most other ICs to determine EE in mechanically ventilated ICU patients. The Q-NRG® is the only commercially available IC tested against mass spectrometry to ensure gas accuracy, while being very easy-to use.
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http://dx.doi.org/10.1016/j.clnu.2020.01.017DOI Listing
October 2020

Micronutriments au quotidien: quoi de neuf ?

Authors:
Mette M Berger

Rev Med Suisse 2020 Jan;16(679):226-227

Service de médecine intensive adulte et brûlés, CHUV, 1011 Lausanne.

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January 2020

Do micronutrient deficiencies contribute to mitochondrial failure in critical illness?

Authors:
Mette M Berger

Curr Opin Clin Nutr Metab Care 2020 03;23(2):102-110

Service of Adult Intensive Care, Lausanne University Hospital CHUV, Lausanne, Switzerland.

Purpose Of Review: Mitochondrial dysfunction seems to be the common denominator of several critical care conditions and particularly of sepsis. Faced with relative failure, and limited progress of sepsis therapies aiming at blocking some oxidative and/or inflammatory pathways, the question of antioxidants micronutrient therapy, particularly of selenium, ascorbic acid and thiamine remains open.

Recent Findings: The rationale for the essentiality of numerous micronutrients within the mitochondria is well established. Many studies have tested single micronutrients in animal and in-vitro models and provide positive evidences in favor of reduction of organ failure (cardiac and renal mainly). In clinical settings, high-dose selenium administration in sepsis has been disappointing. The most recent high dose, short-term ascorbic acid trial in sepsis is promising though, with an associated reduction of mortality, but analysis of the impact of this intervention on the various organs remains to be conducted.

Summary: Results from animal and human studies indicate that there are indeed intervention options at the level of the mitochondria, but neither the optimal dose nor the optimal combination of micronutrients is yet identified.
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http://dx.doi.org/10.1097/MCO.0000000000000635DOI Listing
March 2020

Adjuvant vitamin C for sepsis: mono or triple?

Crit Care 2019 12 27;23(1):425. Epub 2019 Dec 27.

Service of Intensive Care Medicine and Burns, Lausanne University Hospital (CHUV), Rue du Bugnon 46, CH-1011, Lausanne, Switzerland.

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http://dx.doi.org/10.1186/s13054-019-2717-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6935178PMC
December 2019

Nutrition determines outcome after severe burns.

Authors:
Mette M Berger

Ann Transl Med 2019 Sep;7(Suppl 6):S216

Service of Adult Intensive Care and Burns, Lausanne University hospital - CHUV, Lausanne, Switzerland.

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http://dx.doi.org/10.21037/atm.2019.08.57DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6789337PMC
September 2019

Indirect Calorimetry in Clinical Practice.

J Clin Med 2019 Sep 5;8(9). Epub 2019 Sep 5.

Clinical Nutrition, Geneva University Hospital (HUG), 1205 Geneva, Switzerland.

Indirect calorimetry (IC) is considered as the gold standard to determine energy expenditure, by measuring pulmonary gas exchanges. It is a non-invasive technique that allows clinicians to personalize the prescription of nutrition support to the metabolic needs and promote a better clinical outcome. Recent technical developments allow accurate and easy IC measurements in spontaneously breathing patients as well as in those on mechanical ventilation. The implementation of IC in clinical routine should be promoted in order to optimize the cost-benefit balance of nutrition therapy. This review aims at summarizing the latest innovations of IC as well as the clinical indications, benefits, and limitations.
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http://dx.doi.org/10.3390/jcm8091387DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6780066PMC
September 2019

Metabolic and Nutritional Characteristics of Long-Stay Critically Ill Patients.

J Clin Med 2019 Jul 7;8(7). Epub 2019 Jul 7.

Service of Adult Intensive Care Medicine and Burns, Lausanne University Hospital (CHUV), 1011 Lausanne, Switzerland.

Background: insufficient feeding is frequent in the intensive care unit (ICU), which results in poor outcomes. Little is known about the nutrition pattern of patients requiring prolonged ICU stays. The aims of our study are to describe the demographic, metabolic, and nutritional specificities of chronically critically ill (CCI) patients defined by an ICU stay >2 weeks, and to identify an early risk factor.

Methods: analysis of consecutive patients prospectively admitted to the CCI program, with the following variables: demographic characteristics, Nutrition Risk Screening (NRS-2002) score, total daily energy from nutritional and non-nutritional sources, protein and glucose intakes, all arterial blood glucose values, length of ICU and hospital stay, and outcome (ICU and 90-day survival). Two phases were considered for the analysis: the first 10 days, and the next 20 days of the ICU stay.

Statistics: parametric and non-parametric tests.

Results: 150 patients, aged 60 ± 15 years were prospectively included. Median (Q1, Q3) length of ICU stay was 31 (26, 46) days. The mortality was 18% at ICU discharge and 35.3% at 90 days. Non-survivors were older ( = 0.024), tended to have a higher SAPSII score ( = 0.072), with a significantly higher NRS score ( = 0.033). Enteral nutrition predominated, while combined feeding was minimally used. All patients received energy and protein below the ICU's protocol recommendation. The proportion of days with fasting was 10.8%, being significantly higher in non-survivors (2 versus 3 days; = 0.038). Higher protein delivery was associated with an increase in prealbumin over time ( = 0.19, = 0.027).

Conclusions: High NRS scores may identify patients at highest risk of poor outcome when exposed to underfeeding. Further studies are required to evaluate a nutrition strategy for patients with high NRS, addressing combined parenteral nutrition and protein delivery.
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http://dx.doi.org/10.3390/jcm8070985DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6679172PMC
July 2019

Micronutrient Deficiencies in Medical and Surgical Inpatients.

J Clin Med 2019 Jun 28;8(7). Epub 2019 Jun 28.

Service of Adult Intensive Care Medicine and Burns, Lausanne University Hospital (CHUV), BH 08.612, Rue du Bugnon 46, 1011 Lausanne, Switzerland.

Inpatients are threatened by global malnutrition, but also by specific micronutrient (i.e., trace element and vitamins) deficiencies that frequently are overseen in the differential diagnosis of major organ dysfunctions. Some of them are related to specific geographic risks (iodine, iron, selenium, zinc, vitamin A), while others are pathology related, and finally many are associated with specific feeding patterns, including low dose enteral feeding. Among the pathologies in which laboratory blood investigations should include a micronutrient outwork, anemia is in the front line, followed by obesity with bariatric surgery, chronic liver disease, kidney disease, inflammatory bowel disease, cardiomyopathies and heart failure. The micronutrients at the highest risk are iron, zinc, thiamine, vitamin B12 and vitamin C. Admission to hospital has been linked with an additional risk of malnutrition-feeding below 1500 kcal/day was frequent and has been associated with a structural additional risk of insufficient micronutrient intake to cover basal needs. Although not evidence based, systematic administration of liberal thiamine doses upon admission, and daily complementation of inpatients' food and enteral feeding solutions with multi-micronutrient tablets might be considered.
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http://dx.doi.org/10.3390/jcm8070931DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6678268PMC
June 2019

Copper Deficiency: Causes, Manifestations, and Treatment.

Nutr Clin Pract 2019 Aug 17;34(4):504-513. Epub 2019 Jun 17.

Adult Intensive Care and Burn Unit, Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne, Switzerland.

Background: The metabolism of the essential trace element copper remains incompletely understood and, until recently, nearly ignored in acute medicine. Menkes disease was for long the only known copper deficiency condition, but several case reports and investigations conducted over the last 2 decades have shown that deficiency is more frequent than previously suspected, with devastating individual consequences and potential public health consequences. The copper needs in healthy individuals are 0.9 mg/d, which translates to 0.3 mg/d intravenously in parenteral nutrition; the present review aims at gathering actual knowledge.

Method And Results: A review of literature was conducted in PubMed and Cochrane systematic reviews to identify the most recent information about copper deficiency and generate a narrative review. Copper deficiency has hereditary and acquired origins, the latter being the most frequent. Clinical manifestations are nonspecific but affect all organs and systems, particularly the hematologic (anemia) and the neurologic (myeloneuropathy) systems. Deficiency also affects the cardiovascular, cutaneous, and immune systems. Severe copper deficiency due to reduced absorption after bariatric bypass surgery has become frequent.

Conclusion: Deficiency is more frequent than previously recognized, probably because of changing nutrition patterns but also because of some treatments that have become very common such as bypass bariatric surgery and, in acute medicine, prolonged continuous renal replacement therapy. The patients may present with severe hematologic and neurologic complications that go untreated because copper deficiency was not considered in the differential diagnosis: These complications often need active intravenous repletion with doses 4-8 times the usual nutrition recommendations.
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http://dx.doi.org/10.1002/ncp.10328DOI Listing
August 2019

Feeding should be individualized in the critically ill patients.

Curr Opin Crit Care 2019 08;25(4):307-313

Clinical Nutrition, Geneva University Hospital, Geneva, Switzerland.

Purpose Of Review: Any critical care therapy requires individual adaptation, despite standardization of the concepts supporting them. Among these therapies, nutrition care has been repeatedly shown to influence clinical outcome. Individualized feeding is the next needed step towards optimal global critical care.

Recent Findings: Both underfeeding and overfeeding generate complications and should be prevented. The long forgotten endogenous energy production, maximal during the first 3 to 4 days, should be integrated in the nutrition plan, through a slow progression of feeding, as full feeding may result in early overfeeding. Accurate and repeated indirect calorimetry is becoming possible thanks to the recent development of a reliable, easy to use and affordable indirect calorimeter. The optimal timing of the prescription of the measured energy expenditure values as goal remains to be determined. Optimal protein prescription remains difficult as no clinically available tool has yet been identified reflecting the body needs.

Summary: Although energy expenditure can now be measured, we miss indicators of early endogenous energy production and of protein needs. A pragmatic ramping up of extrinsic energy provision by nutrition support reduces the risk of overfeeding-related adverse effects.
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http://dx.doi.org/10.1097/MCC.0000000000000625DOI Listing
August 2019

Parenteral Provision of Micronutrients to Adult Patients: An Expert Consensus Paper.

JPEN J Parenter Enteral Nutr 2019 03;43 Suppl 1:S5-S23

Faculty of Biology and Medicine, Service of Intensive Care Medicine & Burns, University of Lausanne Hospitals (CHUV), Lausanne, Switzerland.

Background: Micronutrients, an umbrella term used to collectively describe vitamins and trace elements, are essential components of nutrition. Those requiring alternative forms of nutrition support are dependent on the prescribed nutrition regimen for their micronutrient provision. The purpose of this paper is to assist clinicians to bridge the gap between the available guidelines' recommendations and their practical application in the provision of micronutrients via the parenteral route to adult patients.

Methods: Based on the available evidenced-based literature and existing guidelines, a panel of multidisciplinary healthcare professionals with significant experience in the provision of parenteral nutrition (PN) and intravenous micronutrients developed this international consensus paper.

Results: The paper addresses 14 clinically relevant questions regarding the importance and use of micronutrients in various clinical conditions. Practical orientation on how micronutrients should be prescribed, administered, and monitored is provided.

Conclusion: Micronutrients are a critical component to nutrition provision and PN provided without them pose a considerable risk to nutrition status. Obstacles to their daily provision-including voluntary omission, partial provision, and supply issues-must be overcome to allow safe and responsible nutrition practice.
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http://dx.doi.org/10.1002/jpen.1525DOI Listing
March 2019

Agreement between activated partial thromboplastin time and anti-Xa activity in critically ill patients receiving therapeutic unfractionated heparin.

Thromb Res 2019 Mar 7;175:53-58. Epub 2019 Jan 7.

Service of Intensive Care and Burn Unit, Lausanne University Hospital (CHUV) and Faculty of Biology & Medicine, University of Lausanne, Lausanne, Switzerland. Electronic address:

Background: No study supports the use of either aPTT or anti-Xa activity for heparin monitoring in critical care patients. There are no strong data on the agreement between aPTT and anti-Xa. The aims of this study were to: 1. Analyse the agreement between aPTT and anti-Xa in a large population of critically ill patients under unfractionated heparin therapy (UFH), 2. Identify clinical and biological factors associated to agreement or disagreement, and 3. Analyse the impact of anti-Xa availability on the use of aPTT and UFH therapy.

Methods: Retrospective study in a 35 beds mixed-ICU population between 2006 and 2016 in a University teaching hospital.

Inclusion Criteria: delivery of a UFH dose >15,000 U/24 h during at least one day with one anti-Xa determination.

Data: demographic variables, aPTT, anti-Xa, laboratory variables, presence of extracorporeal devices (ECD). Pairs of simultaneously dosed aPTT and anti-Xa [aPTT:anti-Xa] were analysed on the basis of their agreement within the sub-therapeutic, therapeutic (aPTT 50-80″, anti-Xa 0.3-0.7 U/ml) or supra-therapeutic ranges.

Results: 2283 patient admissions (2085 patients) were analysed. 35,595 [aPTT:anti-Xa] pairs were found. The overall [aPTT:anti-Xa] agreement was 59.6% and lowest (54.3%) in presence of ECD compared to non-ECD patients (61.6%; p < 0.001). Sixteen demographic and biological variables were analysed and were not predictive of [aPTT:anti-Xa] agreement. No significant difference in administered UFH dose was observed after anti-Xa introduction.

Conclusion: In this large cohort, the [aPTT:anti-Xa] agreement is <60% and significantly lower in patients with ECD. None of the variables identified as potentially affecting the agreement were predictive. Availability of anti-Xa had neither effect on aPTT use nor on UFH-dose. These results call for a prospective study to determine the optimal UFH-therapy monitoring tool.
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http://dx.doi.org/10.1016/j.thromres.2019.01.002DOI Listing
March 2019
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