Impact of withholding early parenteral nutrition on 2-year mortality and functional outcome in critically ill adults.

PURPOSE: In critically ill adults, withholding parenteral nutrition until 1 week after intensive care admission (Late-PN) facilitated recovery as compared with early supplementation of insufficient enteral nutrition with parenteral nutrition (Early-PN). However, the impact on long-term mortality and functional outcome, in relation to the estimated nutritional risk, remains unclear. METHODS: In this prospective follow-up study of the multicenter EPaNIC randomized controlled trial, we investigated the impact of Late-PN on 2-year mortality (N = 4640) and physical functioning, assessed by the 36-Item Short Form Health Survey (SF-36; in 3292 survivors, responding 819 [738-1058] days post-randomization). To account for missing data, we repeated the analyses in two imputed models. To identify potential heterogeneity of treatment effects, we investigated the impact of Late-PN in different nutritional risk subgroups as defined by Nutritional Risk Screening-2002-score, modified NUTrition Risk in the Critically Ill-score, and age (above/below 70 years), and we evaluated whether there was statistically significant interaction between classification to a nutritional risk subgroup and the effect of the randomized intervention. Secondary outcomes were SF-36-derived physical and mental component scores (PCS & MCS). RESULTS: Two-year mortality (20.5% in Late-PN, 19.8% in Early-PN; P = 0.54) and physical functioning (70 [40-90] in both study-arms; P = 0.99) were similar in both groups, also after imputation of missing physical functioning data. Likewise, Late-PN had no impact on 2-year mortality and physical functioning in any nutritional risk subgroup. PCS and MCS were similar in both groups. CONCLUSION: Late-PN did not alter 2-year survival and physical functioning in adult critically ill patients, independent of anticipated nutritional risk.

Prospective multicenter study to describe the prevalence, outcomes, and management of phosphate disorders in intensive care patients: Study protocol for part B of the international GUTPHOS study.

BACKGROUND: Aberrations in blood phosphate (Pi) levels, whether presenting as hypo- or hyperphosphatemia, appear to be associated with clinical complications and adverse outcomes in patients admitted to an intensive care unit (ICU). However, the prevalence of Pi disorders and the association with subsequent factors and organ failures leading to death in ICU patients are poorly described. Despite endeavors to understand the etiology and treatment of low Pi levels from systematic reviews and meta-analyses, the literature lacks comprehensive guidance for managing hypophosphatemia. Hyperphosphatemia, on the other hand, appears to be associated with higher mortality among critically ill patients, yet its prevalence among ICU patients, particularly following phosphate repletion, remains unknown. The present study aims to investigate the prevalence of Pi abnormalities upon ICU admission and their incidence during the first week of ICU stay, the factors associated with Pi alterations, and the effect of phosphate repletion on the normalization of Pi levels, and its associations with clinical outcomes. METHODS: This multicentre, prospective, non-interventional cohort study will include at least 1000 consecutive adult ICU patients (≥18 years) as part B of the GUTPHOS study. Sites are eligible if an anticipated minimal inclusion of 50 eligible patients during eight weeks from January 2024 until June 2024 and daily phosphate measurements during the first seven days of ICU stay are expected. All consecutive adult patients admitted to a participating ICU during the recruitment period, lasting up to eight weeks, or up to 120 patients if enrollment reaches that limit earlier, will be included. Study parameters include study site characteristics, patient demographics, daily assessment of Pi levels, Pi-related treatment, feeding details, renal replacement therapy details, the incidence of refeeding-associated hypophosphatemia and administered medication (during the first seven calendar days of ICU stay). There will be a follow-up period of a maximum of 90 days to document 28- and 90-day all-cause mortality as the primary outcome. Multiple logistic regression will be used to assess independent associations with mortality in addition to Receiver Operating Characteristics curves to identify cut-off Pi values associated with mortality and overcorrection. Linear mixed models will be conducted to assess Pi treatment effects. Subgroup analyses will be performed based on Pi abnormalities observed during ICU admission, categorized as normo-, hypo-, hyper-, or mixed, along with its severity (mild, moderate, or severe). DISCUSSION: The GUTPHOS study will be the first multicentre, prospective observational cohort study to investigate the prevalence, management practices, and consequent outcomes associated with Pi abnormalities during the first week of ICU admission. Its results may bridge the current evidence gap in repletion protocols while establishing the groundwork for a subsequent randomized controlled trial. CLINICAL TRIAL REGISTRY: NCT05909722.

Prospective multicenter study to validate the gastrointestinal dysfunction score (GIDS) in intensive care patients: Study protocol for Part A of the international GUTPHOS study.

BACKGROUND: While gastrointestinal (GI) dysfunction is commonly encountered among critically ill patients, a uniform prospectively validated scoring system is lacking. The present study aims to validate the recently developed Gastrointestinal Dysfunction Score (GIDS) in a multicenter, prospective cohort of consecutive adult patients admitted to intensive care units (ICU). METHODS: GUTPHOS is a prospective, multicenter, non-interventional cohort study in which at least 1400 consecutive adult patients (age ≥18 years) admitted to the ICU will be monitored daily for abdominal signs and symptoms of GI dysfunction. The previously developed GIDS constructed from these signs and symptoms will be tested in relation to mortality and duration of ICU dependency and parenteral nutrition (PN) dependency. Between January and June 2024, each participating clinical site will include 50-120 consecutive patients over an eight-week period. Study data will be collected in three phases: baseline data upon ICU admission, daily observations throughout a maximum of 7 days in ICU or until discharge, and a follow-up period of 90 days. The primary outcomes are 28- and 90-day all-cause mortality. Secondary outcomes include ICU and hospital mortality, ICU and hospital length of stay, days alive and free of ICU by day 28 and day 90, days alive and free of hospital by day 28 and day 90, and days alive and free of organ support and PN dependency by day 28. DISCUSSION: The GUTPHOS study will be the first worldwide, multicenter, prospective, observational cohort study to validate the GIDS in adult patients admitted to ICUs against 28- and 90-day mortality. The availability of a validated tool will allow its use in interventional studies that are currently hindered by the lack of a validated measurement tool for GI dysfunction. CLINICAL TRIAL REGISTRY: NCT05909722.

LLL 44 - Module 3: Micronutrients in Chronic disease.

Micronutrients (MN), i.e. trace elements and vitamins, are essential organic molecules, which are required in the diet in relatively small amounts in any form of nutrition (oral, enteral, parenteral). The probability of MN depletion or deficiencies should be considered in all chronic illnesses, especially in those that can interfere with intake, digestion, or intestinal absorption. Low socio-economic status and food deprivation are recognized as the most prevalent reasons for MN deficiencies world-wide. Elderly multimorbid patients with multimodal therapy, as well as patients with long-lasting menu restrictions, are at high risk for both disease related malnutrition as well as multiple MN deficiencies, needing careful specific follow-up. The importance of monitoring MN blood levels along with CRP is essential for optimal care. Drug interactions are also highlighted. In patients with chronic conditions depending on medical nutrition therapy, the provision of adequate dietary reference intakes (DRI) of MN doses and monitoring of their adequacy belongs to standard of care.

LLL 44-1 Micronutrients in clinical nutrition: Trace elements.

BACKGROUND: Trace elements are an essential component of metabolism and medical nutrition therapy, with key roles in metabolic pathways, antioxidation, and immunity, which the present course aims at summarizing. RESULTS: Medical nutrition therapy includes the provision of all essential trace elements. The clinical essential issues are summarized for Copper, Iron, Selenium, Zinc, Iodine, Chromium, Molybdenum, and Manganese: the optimal analytical techniques are presented. The delivery of all these elements occurs nearly automatically when the patient is fed with enteral nutrition, but always requires separate prescription in case of parenteral nutrition. Isolated deficiencies may occur, and some patients have increased requirements, therefore a regular monitoring is required. The clinicians should always consider the impact of inflammation on blood levels, mostly lowering them even in absence of deficiency. CONCLUSION: This text summarises the most relevant clinical manifestations of trace element depletion and deficiency, the difficulties in assessing status, and makes practical recommendations for provision for enteral and parenteral nutrition.

LLL 44 - 2 - Micronutrients in clinical nutrition: Vitamins.

Vitamins are essential organic molecules, which are required in the diet in relatively small amounts in any form of nutrition (oral, enteral, parenteral). Despite the small amounts that are required, the vitamins are essential both for maintenance of health, growth, and treatment of disease. After reminding about the principal function of all the vitamins, their needs and the clinical consequences of their deficit, the text present some common clinical problems: the impact of inflammation on the assessment of status. The reasons and diseases which cause increased requirements are presented, with the indications to monitoring of blood levels which remain the classical way to assess status in clinical settings. The text summarises the most relevant clinical manifestations of vitamins depletion and deficiency, the difficulties in assessing status, and makes recommendations for provision for medical nutrition therapy.

LLL 44-4 : Micronutrients in acute disease and critical illness.

Micronutrients (MN), i.e. trace elements and vitamins, are essential components of the diet in relatively small amounts in any form of nutrition, with special needs in critically ill patients. Critical illness is characterised by the presence of inflammation and oxidative stress. MNs are tightly involved in antioxidant and immune defences. In addition, some conditions, and treatments result in large losses of biological fluids containing MNs: therefore, acute renal injury requiring renal replacement therapy, acute intestinal failure, and major burns and trauma are at high risk of acute depletion of body stores, and of deficiency. MN requirements are increased above standard DRI. Blood level interpretation is complicated by inflammation: some biomarkers assist the status determination. Due to the acute challenges of critical illness, it of utmost importance to cover the needs to maintain the organism's endogenous immune and antioxidant defences, and capacity to repair tissues. Practical strategies are proposed.

ESPEN practical short micronutrient guideline.

BACKGROUND: Trace elements and vitamins, named together micronutrients (MNs), are essential for human metabolism. The importance of MNs in common pathologies is recognized by recent research, with deficiencies significantly impacting the outcome. OBJECTIVE: This short version of the guideline aims to provide practical recommendations for clinical practice. METHODS: An extensive search of the literature was conducted in the databases Medline, PubMed, Cochrane, Google Scholar, and CINAHL for the initial guideline. The search focused on physiological data, historical evidence (for papers published before PubMed release in 1996), and observational and/or randomized trials. For each MN, the main functions, optimal analytical methods, impact of inflammation, potential toxicity, and provision during enteral or parenteral nutrition were addressed. The SOP wording was applied for strength of recommendations. RESULTS: The limited number of interventional trials prevented meta-analysis and led to a low level of evidence for most recommendations. The recommendations underwent a consensus process, which resulted in a percentage of agreement (%): strong consensus required of >90 % of votes. Altogether the guideline proposes 3 general recommendations and specific recommendations for the 26 MNs. Monitoring and management strategies are proposed. CONCLUSION: This short version of the MN guideline should facilitate handling of the MNs in at-risk diseases, whilst offering practical advice on MN provision and monitoring during nutritional support.

Diagnosis and Management of Esophageal Fistulas After Lung Transplantation: A Case Series.

Background: Lung transplantations are highly complex procedures, often conducted in frail patients. Through the addition of immunosuppressants, healing can be compromised, primarily leading to the development of bronchopleural fistulas. Although esophageal fistulas (EFs) after lung transplantation remain rare, they are associated with significant morbidity. We aimed to investigate the clinical presentation, diagnostic approaches, and treatment strategies of EF after lung transplantation. Methods: All patients who developed EF after lung transplantation at the University Hospitals Leuven between January 2019 and March 2022 were retrospectively reviewed and the clinical presentations, diagnostic approaches, and treatment strategies were summarized. Results: Among 212 lung transplantation patients, 5 patients (2.4%) developed EF. Three patients were male and median age was 39 y (range, 34-63). Intraoperative circulatory support was required in 3 patients, with 2 needing continued support postoperatively. Bipolar energy devices were consistently used for mediastinal hemostasis. All EFs were right-sided. Median time to diagnosis was 28 d (range, 12-48) and 80% of EFs presented as recurrent respiratory infections or empyema. Diagnosis was made through computed tomography (n = 3) or esophagogastroscopy (n = 2). Surgical repair with muscle flap covering achieved an 80% success rate. All patients achieved complete resolution, with only 1 patient experiencing a fatal outcome during a complicated EF-related recovery. Conclusion: Although EF after lung transplantation remains rare, vigilance is crucial, particularly in cases of right-sided intrathoracic infection. Moreover, caution must be exercised when applying thermal energy in the mediastinal area to prevent EF development and mitigate the risk of major morbidity. Timely diagnosis and surgical intervention can yield favorable outcomes.