Micronutrient deficiency and supplements in schoolchildren and teenagers.

PURPOSE OF REVIEW: The essential micronutrients are corner stones in the functional and physical development. Early deficiency has life-long consequences. While awareness about iron deficiency is relatively high, it remains lower for other micronutrients. This review aims at reporting on recent data and attracting attention to the high prevalence of micronutrient deficiencies in school-age and adolescent individuals. RECENT FINDINGS: Iron deficiency anaemia remains highly prevalent worldwide and the most frequent deficiency but can be corrected with simple tools ranging from food fortification, nutritional intervention, and to supplements. The link between micronutrient (MN) deficiency and neurobehavioral disorders is increasingly established and is worrying even in Western countries. Paediatric individuals are prone to imbalanced diets and picky eating behaviour, and their diets may then become incomplete: the highest risk for deficiency is observed for iron, zinc and vitamin D. SUMMARY: There is not much new information, but rather confirmation of the importance of health policies. Well conducted randomized controlled trials confirm that deficiencies can be corrected efficiently including with food fortification, and result in clinical benefits. Individual complementation should be considered in children and adolescents with proven deficiency.

Combining proteins with n-3 PUFAs (EPA + DHA) and their inflammation pro-resolution mediators for preservation of skeletal muscle mass.

The optimal feeding strategy for critically ill patients is still debated, but feeding must be adapted to individual patient needs. Critically ill patients are at risk of muscle catabolism, leading to loss of muscle mass and its consequent clinical impacts. Timing of introduction of feeding and protein targets have been explored in recent trials. These suggest that "moderate" protein provision (maximum 1.2 g/kg/day) is best during the initial stages of illness. Unresolved inflammation may be a key factor in driving muscle catabolism. The omega-3 (n-3) fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are substrates for synthesis of mediators termed specialized pro-resolving mediators or SPMs that actively resolve inflammation. There is evidence from other settings that high-dose oral EPA + DHA increases muscle protein synthesis, decreases muscle protein breakdown, and maintains muscle mass. SPMs may be responsible for some of these effects, especially upon muscle protein breakdown. Given these findings, provision of EPA and DHA as part of medical nutritional therapy in critically ill patients at risk of loss of muscle mass seems to be a strategy to prevent the persistence of inflammation and the related anabolic resistance and muscle loss.

An update on essential micronutrients in critical illness.

PURPOSE OF REVIEW: Numerous micronutrients are involved in antioxidant and immune defence, while their blood concentrations are frequently low in critically ill patients: this has fuelled many supplementation trials. Numerous observational, randomized studies have been published, which are presented herein. RECENT FINDINGS: Micronutrient concentrations must be analysed considering the context of the inflammatory response in critical illness. Low levels do not always indicate a deficiency without objective micronutrients losses with biological fluids. Nevertheless, higher needs and deficiencies are frequent for some micronutrients, such as thiamine, vitamins C and D, selenium, zinc and iron, and have been acknowledged with identifying patients at risk, such as those requiring continuous renal replacement therapy (CRRT). The most important trials and progress in understanding have occurred with vitamin D (25(OH)D), iron and carnitine. Vitamin D blood levels less than 12 ng/ml are associated with poor clinical outcomes: supplementation in deficient ICU patients generates favourable metabolic changes and decreases mortality. Single high-dose 25(OH)D should not be delivered anymore, as boluses induce a negative feedback mechanism causing inhibition of this vitamin. Iron-deficient anaemia is frequent and can be treated safely with high-dose intravenous iron under the guidance of hepcidin to confirm deficiency diagnosis. SUMMARY: The needs in critical illness are higher than those of healthy individuals and must be covered to support immunity. Monitoring selected micronutrients is justified in patients requiring more prolonged ICU therapy. Actual results point towards combinations of essential micronutrients at doses below upper tolerable levels. Finally, the time of high-dose micronutrient monotherapy is probably over.

Personalized nutrition therapy in critical care: 10 expert recommendations.

Personalization of ICU nutrition is essential to future of critical care. Recommendations from American/European guidelines and practice suggestions incorporating recent literature are presented. Low-dose enteral nutrition (EN) or parenteral nutrition (PN) can be started within 48 h of admission. While EN is preferred route of delivery, new data highlight PN can be given safely without increased risk; thus, when early EN is not feasible, provision of isocaloric PN is effective and results in similar outcomes. Indirect calorimetry (IC) measurement of energy expenditure (EE) is recommended by both European/American guidelines after stabilization post-ICU admission. Below-measured EE (~ 70%) targets should be used during early phase and increased to match EE later in stay. Low-dose protein delivery can be used early (~ D1-2) (< 0.8 g/kg/d) and progressed to ≥ 1.2 g/kg/d as patients stabilize, with consideration of avoiding higher protein in unstable patients and in acute kidney injury not on CRRT. Intermittent-feeding schedules hold promise for further research. Clinicians must be aware of delivered energy/protein and what percentage of targets delivered nutrition represents. Computerized nutrition monitoring systems/platforms have become widely available. In patients at risk of micronutrient/vitamin losses (i.e., CRRT), evaluation of micronutrient levels should be considered post-ICU days 5-7 with repletion of deficiencies where indicated. In future, we hope use of muscle monitors such as ultrasound, CT scan, and/or BIA will be utilized to assess nutrition risk and monitor response to nutrition. Use of specialized anabolic nutrients such as HMB, creatine, and leucine to improve strength/muscle mass is promising in other populations and deserves future study. In post-ICU setting, continued use of IC measurement and other muscle measures should be considered to guide nutrition. Research on using rehabilitation interventions such as cardiopulmonary exercise testing (CPET) to guide post-ICU exercise/rehabilitation prescription and using anabolic agents such as testosterone/oxandrolone to promote post-ICU recovery is needed.

Management of gastrointestinal failure in the adult critical care setting.

PURPOSE OF REVIEW: Gastrointestinal failure is a polymorphic syndrome with multiple causes. Managing the different situations from a practical, metabolic, and nutritional point of view is challenging, which the present review will try to address. RECENT FINDINGS: Acute gastrointestinal injury (AGI) has been defined and has evolved into a concept of gastrointestinal dysfunction score (GIDS) built on the model of Sequential Organ Failure Assessment (SOFA) score, and ranging from 0 (no risk) to 4 (life threatening). But there is yet no specific, reliable and reproducible, biomarker linked to it. Evaluating the risk with the Nutrition Risk Screening (NRS) score is the first step whenever addressing nutrition therapy. Depending on the severity of the gastrointestinal failure and its clinical manifestations, nutritional management needs to be individualized but always including prevention of undernutrition and dehydration, and administration of target essential micronutrients. The use of fibers in enteral feeding solutions has gained acceptance and is even recommended based on microbiome findings. Parenteral nutrition whether alone or combined to enteral feeding is indicated whenever the intestine is unable to process the needs. SUMMARY: The heterogeneity of gastrointestinal insufficiency precludes a uniform nutritional management of all critically ill patients but justifies its early detection and the implementation of individualized care.

Clinical nutrition issues in 2022: What is missing to trust supplemental parenteral nutrition (SPN) in ICU patients?

A multidisciplinary group of international physicians involved in the medical nutrition therapy (MNT) of adult critically ill patients met to discuss the value, role, and open questions regarding supplemental parenteral nutrition (SPN) along with oral or enteral nutrition (EN), particularly in the intensive care unit (ICU) setting. This manuscript summarizes the discussions and results to highlight the importance of SPN as part of a comprehensive approach to MNT in critically ill adults and for researchers to generate new evidence based on well-powered randomized controlled trials (RCTs). The experts agreed on several key points: SPN has shown clinical benefits, resulting in this strategy being included in American and European guidelines. Nevertheless, its use is heterogeneous across European countries, due to the persistence of uncertainties, such as the optimal timing and the risk of overfeeding in absence of indirect calorimetry (IC), which results in divergent opinions and barriers to SPN implementation. Education is also insufficient. The experts agreed on actions needed to increase evidence quality on SPN use in specific patients at a given time point during acute critical illness or recovery.

A Global Survey on Diagnostic, Therapeutic and Preventive Strategies in Intensive Care Unit-Acquired Weakness.

Background and Objectives: Intensive care unit-acquired weakness (ICU-AW) is one of the most frequent neuromuscular complications in critically ill patients. We conducted a global survey to evaluate the current practices of diagnostics, treatment and prevention in patients with ICU-AW. Materials and Methods: A pre-survey was created with international experts. After revision, the final survey was endorsed by the European Society of Intensive Care Medicine (ESICM) using the online platform SurveyMonkey®. In 27 items, we addressed strategies of diagnostics, therapy and prevention. An invitation link was sent by email to all ESICM members. Furthermore, the survey was available on the ESICM homepage. Results: A total of 154 healthcare professionals from 39 countries participated in the survey. An ICU-AW screening protocol was used by 20% (28/140) of participants. Forty-four percent (62/141) of all participants reported performing routine screening for ICU-AW, using clinical examination as the method of choice (124/141, 87.9%). Almost 63% (84/134) of the participants reported using current treatment strategies for patients with ICU-AW. The use of treatment and prevention strategies differed between intensivists and non-intensivists regarding the reduction in sedatives (80.0% vs. 52.6%, p = 0.002), neuromuscular blocking agents (76.4% vs. 50%, p = 0.004), corticosteroids (69.1% vs. 37.2%, p < 0.001) and glycemic control regimes (50.9% vs. 23.1%, p = 0.002). Mobilization and physical activity are the most frequently reported treatment strategies for ICU-AW (111/134, 82.9%). The availability of physiotherapists (92/134, 68.7%) and the lack of knowledge about ICU-AW within the medical team (83/134, 61.9%) were the main obstacles to the implementation of the strategies. The necessity to develop guidelines for the screening, diagnosing, treatment and prevention of ICU-AW was recognized by 95% (127/133) of participants. Conclusions: A great heterogeneity regarding diagnostics, treatment and prevention of ICU-AW was reported internationally. Comprehensive guidelines with evidence-based recommendations for ICU-AW management are needed.

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

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.

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

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.

A guide to enteral nutrition in intensive care units: 10 expert tips for the daily practice.

The preferential use of the oral/enteral route in critically ill patients over gut rest is uniformly recommended and applied. This article provides practical guidance on enteral nutrition in compliance with recent American and European guidelines. Low-dose enteral nutrition can be safely started within 48 h after admission, even during treatment with small or moderate doses of vasopressor agents. A percutaneous access should be used when enteral nutrition is anticipated for ≥ 4 weeks. Energy delivery should not be calculated to match energy expenditure before day 4-7, and the use of energy-dense formulas can be restricted to cases of inability to tolerate full-volume isocaloric enteral nutrition or to patients who require fluid restriction. Low-dose protein (max 0.8 g/kg/day) can be provided during the early phase of critical illness, while a protein target of > 1.2 g/kg/day could be considered during the rehabilitation phase. The occurrence of refeeding syndrome should be assessed by daily measurement of plasma phosphate, and a phosphate drop of 30% should be managed by reduction of enteral feeding rate and high-dose thiamine. Vomiting and increased gastric residual volume may indicate gastric intolerance, while sudden abdominal pain, distension, gastrointestinal paralysis, or rising abdominal pressure may indicate lower gastrointestinal intolerance.

Do micronutrient deficiencies contribute to mitochondrial failure in critical illness?

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.

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

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.

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.

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.

Feeding should be individualized in the critically ill patients.

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.

Parenteral nutrition in intensive care patients: medicoeconomic aspects.

PURPOSE OF REVIEW: Parenteral nutrition (PN) alone or as supplemental parenteral nutrition (SPN) has been shown to prevent negative cumulative energy balance, to improve protein delivery and, in some studies, to reduce infectious morbidity in ICU patients who fail to cover their needs with enteral nutrition (EN) alone. RECENT FINDINGS: The optimization of energy provision to an individualized energy target using either early PN or SPN within 3-4 days after admission has recently been reported to be a cost-saving strategy mediated by a reduction of infectious complications in selected intensive care patients. SUMMARY: EN alone is often insufficient, or occasionally contraindicated, in critically ill patients and results in growing energy and protein deficit. The cost benefit of using early PN in patients with short-term relative contraindications to EN has been reported. In selected patients SPN has been associated with a decreased risk of infection, a reduced duration of mechanical ventilation, a shorter stay in the ICU. Altogether four studies have investigated the costs associated with these interventions since 2012: two of them from Australia and Switzerland have shown that optimization of energy provision using SPN results in cost reduction, conflicting with other studies. The latter encouraging findings require further validation.

A randomized trial of glutamine and antioxidants in critically ill patients.

BACKGROUND: Critically ill patients have considerable oxidative stress. Glutamine and antioxidant supplementation may offer therapeutic benefit, although current data are conflicting. METHODS: In this blinded 2-by-2 factorial trial, we randomly assigned 1223 critically ill adults in 40 intensive care units (ICUs) in Canada, the United States, and Europe who had multiorgan failure and were receiving mechanical ventilation to receive supplements of glutamine, antioxidants, both, or placebo. Supplements were started within 24 hours after admission to the ICU and were provided both intravenously and enterally. The primary outcome was 28-day mortality. Because of the interim-analysis plan, a P value of less than 0.044 at the final analysis was considered to indicate statistical significance. RESULTS: There was a trend toward increased mortality at 28 days among patients who received glutamine as compared with those who did not receive glutamine (32.4% vs. 27.2%; adjusted odds ratio, 1.28; 95% confidence interval [CI], 1.00 to 1.64; P=0.05). In-hospital mortality and mortality at 6 months were significantly higher among those who received glutamine than among those who did not. Glutamine had no effect on rates of organ failure or infectious complications. Antioxidants had no effect on 28-day mortality (30.8%, vs. 28.8% with no antioxidants; adjusted odds ratio, 1.09; 95% CI, 0.86 to 1.40; P=0.48) or any other secondary end point. There were no differences among the groups with respect to serious adverse events (P=0.83). CONCLUSIONS: Early provision of glutamine or antioxidants did not improve clinical outcomes, and glutamine was associated with an increase in mortality among critically ill patients with multiorgan failure. (Funded by the Canadian Institutes of Health Research; ClinicalTrials.gov number, NCT00133978.).

Nutrition in burn injury: any recent changes?

PURPOSE OF REVIEW: After major progress in the 1980s of burn resuscitation resulting, the last years' research has focused on modulation of metabolic response and optimization of substrate utilization. The persisting variability of clinical practice is confirmed and results in difficult comparisons between burn centers. RECENT FINDINGS: Recent research explores intracellular mechanisms of the massive metabolic turmoil observed after burns: very early alterations at the mitochondrial level largely explain the hypermetabolic response, with a diminished coupling of oxygen consumption and ATP production. The metabolic alterations (elevated protein and glucose turnover) have been shown to be long lasting. Modulating this response by pharmacological tools (insulin, propranolol, and oxandrolone) results in significant clinical benefits. A moderate glucose control proves to be safe in adult burns; data in children remain uncertain as the risk of hypoglycemia seems to be higher. The enteral feeding route is confirmed as an optimal route: some difficulties are now clearly identified, such as the risk of not delivering sufficient energy by this route. SUMMARY: Major burn patients differ from other critically ill patients by the magnitude and duration of their inflammatory and metabolic responses, their energy and substrate requirements. Pieces of the metabolic puzzle finally seem to fit together.

Vitamin C supplementation in the critically ill patient.

PURPOSE OF REVIEW: Vitamin C is not only an essential nutrient involved in many anabolic pathways, but also an important player of the endogenous antioxidant defense. Low plasma levels are very common in critical care patients and may reflect severe deficiency states. RECENT FINDINGS: Vitamin C scavenges reactive oxygen species such as superoxide and peroxynitrite in plasma and cells (preventing damage to proteins, lipids and DNA), prevents occludin dephosphorylation and loosening of the tight junctions. Ascorbate improves microcirculatory flow impairment by inhibiting tumor-necrosis-factor-induced intracellular adhesion molecule expression, which triggers leukocyte stickiness and slugging. Clinical trials in sepsis, trauma and major burns testing high-dose vitamin C show clinical benefit. Restoration of normal plasma levels in inflammatory patients requires the administration of 3 g/day for several days, which is 30 times the daily recommended dose. SUMMARY: The recent research on the modulation of oxidative stress and endothelial protection offer interesting therapeutic perspectives, based on the biochemical evidence, with limited or even absent side-effects.

Metabolic and nutritional support of critically ill patients: consensus and controversies.

The results of recent large-scale clinical trials have led us to review our understanding of the metabolic response to stress and the most appropriate means of managing nutrition in critically ill patients. This review presents an update in this field, identifying and discussing a number of areas for which consensus has been reached and others where controversy remains and presenting areas for future research. We discuss optimal calorie and protein intake, the incidence and management of re-feeding syndrome, the role of gastric residual volume monitoring, the place of supplemental parenteral nutrition when enteral feeding is deemed insufficient, the role of indirect calorimetry, and potential indications for several pharmaconutrients.