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 44-1 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.

Potential impact of a new sepsis prediction model for the primary care setting: early health economic evaluation using an observational cohort.

OBJECTIVES: To estimate the potential referral rate and cost impact at different cut-off points of a recently developed sepsis prediction model for general practitioners (GPs). DESIGN: Prospective observational study with decision tree modelling. SETTING: Four out-of-hours GP services in the Netherlands. PARTICIPANTS: 357 acutely ill adult patients assessed during home visits. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome is the cost per patient from a healthcare perspective in four scenarios based on different cut-off points for referral of the sepsis prediction model. Second, the number of hospital referrals for the different scenarios is estimated. The potential impact of referral of patients with sepsis on mortality and hospital admission was estimated by an expert panel. Using these study data, a decision tree with a time horizon of 1 month was built to estimate the referral rate and cost impact in case the model would be implemented. RESULTS: Referral rates at a low cut-off (score 2 or 3 on a scale from 0 to 6) of the prediction model were higher than observed for patients with sepsis (99% and 91%, respectively, compared with 88% observed). However, referral was also substantially higher for patients who did not need hospital assessment. As a consequence, cost-savings due to referral of patients with sepsis were offset by increased costs due to unnecessary referral for all cut-offs of the prediction model. CONCLUSIONS: Guidance for referral of adult patients with suspected sepsis in the primary care setting using any cut-off point of the sepsis prediction model is not likely to save costs. The model should only be incorporated in sepsis guidelines for GPs if improvement of care can be demonstrated in an implementation study. TRIAL REGISTRATION NUMBER: Dutch Trial Register (NTR 7026).

The effect of an intervention of porcine protein versus maltodextrin supplement on CONvalescence of FUnCtional outcomes after IcU Stay (CONFUCIUS): Study protocol for a randomized controlled, single-center, double-blind trial.

BACKGROUND: Patients discharged from the Intensive Care Unit (ICU) frequently suffer from ICU-acquired weakness because of immobilization and massive inflammation-induced muscle mass loss. Consequently, rehospitalization, reduced quality of life (QoL), increased disabilities, and higher post-ICU mortality is observed. Exercise rehabilitation and optimal nutrition, particularly protein intake, are pivotal to regaining muscle mass and function. Studies have shown that protein requirements in the post-ICU phase are often unmet. Furthermore, protein supplementation in other patient groups has shown beneficial effects. However, a study on protein supplementation during the post-ICU period is lacking. This study aims to investigate the effect of a six-week intervention of daily porcine protein supplementation versus an isocaloric control (maltodextrin) on functional outcomes in the post-ICU period in patients with moderately severe ICU-acquired weakness. METHODS: 72 post-ICU patients with moderately severe ICU-acquired weakness of Hospital Gelderse Vallei will be randomly assigned to either the intervention or the control group (36 per arm). The intervention group receives a porcine protein supplement twice a day. The control group receives a maltodextrin supplement twice a day. The intervention starts on the first day in the general ward and lasts 42 days (6 weeks). The primary outcome is the between-group difference in physical function at hospital discharge (t;=2), the end of the intervention (t;=3, day 42), and the 3-month follow-up (t;=4) expressed as a composite score consisting of handgrip strength, muscle strength leg, muscle strength arm and exercise capacity. Secondary outcomes encompass physical function, QoL, Activity of daily living (ADL), and plasma amino acids concentrations. Lastly, ICU readmission after ICU discharge, hospital readmission after hospital discharge, and overall survival status will be considered. Linear mixed models will be used to test the treatment effect for the primary and secondary outcome measures. DISCUSSION: This trial will be the first to investigate porcine protein supplementation compared with carbohydrate supplementation in the post-ICU period aiming to improve functional outcomes of ICU survivors with moderately severe ICU-acquired weakness. TRIAL REGISTRATION: The study has been registered at ClinicalTrials.gov. Number: NCT05405764.

The accuracy and feasibility of respiratory rate measurements in acutely ill adult patients by GPs: a mixed-methods study.

BACKGROUND: Tachypnoea in acutely ill patients can be an early sign of a life-threatening condition such as sepsis. Routine measurement of the respiratory rate by GPs might improve the recognition of sepsis. AIM: To assess the accuracy and feasibility of respiratory rate measurements by GPs. DESIGN & SETTING: Observational cross-sectional mixed-methods study in the setting of out-of-hours (OOH) home visits at three GP cooperatives in The Netherlands. METHOD: GPs were observed during the assessment of acutely ill patients, and semi-structured interviews were performed. The GP-assessed respiratory rate was compared with a reference measurement. In the event that the respiratory rate was not counted, GPs were asked to estimate the rate (dichotomised as ≥22 breaths per minute or <22 breaths per minute). RESULTS: Observations of 130 acutely ill patients were included, and 14 GPs were interviewed. In 33 patients (25%), the GP counted the respiratory rate. A mean difference of 0.27 breaths per minute (95% confidence interval [CI] = -5.7 to 6.3) with the reference measurement was found. At a cut-off point of ≥22 breaths per minute, a sensitivity of 86% (95% CI = 57% to 98%) was found when the GP counted the rate, and a sensitivity of 43% (95% CI = 22% to 66%) when GPs estimated respiratory rates. GPs reported both medical and practical reasons for not routinely measuring the respiratory rate. CONCLUSION: GPs are aware of the importance of assessing the respiratory rate of acutely ill adult patients, and counted measurements are accurate. However, in most patients the respiratory rate was not counted, and the rate was often underestimated when estimated.

Protein requirements and provision in hospitalised COVID-19 ward and ICU patients: Agreement between calculations based on body weight and height, and measured bioimpedance lean body mass.

BACKGROUND: A large proportion of hospitalised COVID-19 patients are overweight. There is no consensus in the literature on how lean body mass (LBM) can best be estimated to adequately guide nutritional protein recommendations in hospitalised patients who are not at an ideal weight. We aim to explore which method best agrees with lean body mass as measured by bioelectric impedance (LBMBIA) in this population. METHODS: LBM was calculated by five commonly used methods for 150 hospitalised COVID-19 patients previously included in the BIAC-19 study; total body weight, regression to a BMI of 22.5, regression to BMI 27.5 when BMI>30, and the equations described by Gallagher and the ESPEN ICU guideline. Error-standard plots were used to assess agreement and bias compared to LBMBIA. The actual protein provided to ICU patients during their stay was compared to targets set using LBMBIA and LBM calculated by other methods. RESULTS: All methods to calculate LBM suffered from overestimation, underestimation, fixed- and proportional bias and wide limits of agreement compared to LBMBIA. Bias was inconsistent across sex and BMI subgroups. Twenty-eight ICU patients received a mean of 51.19 (95%-BCa CI 37.1;64.1) grams of protein daily, accumulating to a mean of 61.6% (95%-BCa CI 43.2;80.8) of TargetBIA during their ICU stay. The percentage received of the target as calculated by the LBMGallagher method for males was the only one to not differ significantly from the percentage received of TargetBIA (mean difference 1.4% (95%-BCa CI -1.3;4.6) p = 1.0). CONCLUSIONS: We could not identify a mathematical method for calculating LBM that had an acceptable agreement with LBM as derived from BIA for males and females across all BMI subgroups in our hospitalised COVID-19 population. Consequently, discrepancies when assessing the adequacy of protein provision in ICU patients were found. We strongly advise using baseline LBMBIA to guide protein dosing if possible. In the absence of BIA, using a method that overestimates LBM in all categories may be the only way to minimise underdosing of nutritional protein. TRIAL REGISTRATION: The protocol of the BIAC-19 study, of which this is a post-hoc sub-analysis, is registered in the Netherlands Trial Register (number NL8562).

New clinical prediction model for early recognition of sepsis in adult primary care patients: a prospective diagnostic cohort study of development and external validation.

BACKGROUND: Recognising patients who need immediate hospital treatment for sepsis while simultaneously limiting unnecessary referrals is challenging for GPs. AIM: To develop and validate a sepsis prediction model for adult patients in primary care. DESIGN AND SETTING: This was a prospective cohort study in four out-of-hours primary care services in the Netherlands, conducted between June 2018 and March 2020. METHOD: Adult patients who were acutely ill and received home visits were included. A total of nine clinical variables were selected as candidate predictors, next to the biomarkers C-reactive protein, procalcitonin, and lactate. The primary endpoint was sepsis within 72 hours of inclusion, as established by an expert panel. Multivariable logistic regression with backwards selection was used to design an optimal model with continuous clinical variables. The added value of the biomarkers was evaluated. Subsequently, a simple model using single cut-off points of continuous variables was developed and externally validated in two emergency department populations. RESULTS: A total of 357 patients were included with a median age of 80 years (interquartile range 71-86), of which 151 (42%) were diagnosed with sepsis. A model based on a simple count of one point for each of six variables (aged >65 years; temperature >38°C; systolic blood pressure ≤110 mmHg; heart rate >110/min; saturation ≤95%; and altered mental status) had good discrimination and calibration (C-statistic of 0.80 [95% confidence interval = 0.75 to 0.84]; Brier score 0.175). Biomarkers did not improve the performance of the model and were therefore not included. The model was robust during external validation. CONCLUSION: Based on this study's GP out-of-hours population, a simple model can accurately predict sepsis in acutely ill adult patients using readily available clinical parameters.

Bioelectric impedance body composition and phase angle in relation to 90-day adverse outcome in hospitalized COVID-19 ward and ICU patients: The prospective BIAC-19 study.

BACKGROUND & AIMS: Gaining insight into readily obtainable baseline characteristics that allow prediction of adverse outcome in COVID-19 aids both treatment and healthcare planning. Bioelectric impedance (BIA) Phase Angle (PhA) is correlated with outcome in a multitude of diseases and may be of added value in predicting adverse outcome of COVID-19. We aimed to associate baseline body composition parameters with 90-day adverse outcome of COVID-19 including ICU-admission and to explore the added predictive value of baseline PhA. METHODS: We performed a prospective observational study, conducting BIA amongst COVID-19 patients within 24 hours of hospital admission, with a follow-up of 90 days. Data were compared between ward-only and ICU-patients. Regression models were used to assess the associations between baseline characteristics, body composition and 90-day adverse outcome, including a composite outcome score of morbidity, ICU-admission, and mortality. An ROC-curve was used to explore the added predictive value of PhA to other clinical parameters at baseline for the prediction of adverse outcome. RESULTS: One-hundred-and-fifty patients were included. Mean age was 68 (66-70) years, 67% were male. Forty-one (27%) patients were admitted to ICU and 77 (51%) met the criteria of the composite outcome score. In multiple regression, PhA was independently, inversely correlated with risk of ICU-admission (OR .531, p = .021), complications (OR .579, p = .031), hospital length of stay (OR .875, p = .037) and the composite outcome score (OR .502, p = .012). An ROC-curve showed that the incorporation of PhA in a composite risk-score improved the discriminative power for the composite outcome from poor to fair, compared to individual predictors (AUC 0.79 (95% CI 0.71-0.87)). CONCLUSION: BIA measurements including Phase Angle are independently correlated with an adverse outcome of COVID-19. Interpretation of Phase Angle can be a valuable addition to risk assessment of adverse outcome of COVID-19 at hospital admission. CLINICAL TRIAL REGISTRATION: Netherlands Trial Register number NL8562, registered 2020-04-21.

Current evidence on ω-3 fatty acids in enteral nutrition in the critically ill: A systematic review and meta-analysis.

Fish oil exerts anti-inflammatory and immunomodulatory properties that may be beneficial for critically ill patients, thus multiple randomized controlled trials and meta-analyses have been performed. However, controversy remains as to whether fish oil-enriched enteral nutrition can improve clinical outcomes in adult critically ill patients in intensive care units (ICUs). The aim of this study was to provide an up-to-date systematic review and meta-analysis of all randomized controlled trials of fish oil-containing enteral nutrition addressing relevant clinical outcomes in critically ill patients. A systematic literature search was conducted. The primary outcome was 28-d mortality. Secondary outcomes were ICU and hospital mortality, ICU and hospital length of stay (LOS), ventilation duration, and infectious complications. Predefined subgroup and sensitivity analyses were performed. Twenty-four trials, enrolling 3574 patients, met the inclusion criteria. The assessment of risk for bias showed that most of included studies were of moderate quality. The overall results revealed no significant effects of enteral fish oil supplementation on 28-d, ICU or hospital mortality. However, ICU LOS and ventilation duration were significantly reduced in patients receiving fish oil supplementation. Furthermore, subgroup analysis revealed a significant reduction in 28-d mortality, ICU LOS, and ventilation duration in patients with acute respiratory distress syndrome but not in other subgroups. When comparing high- and low-quality trials, significant reductions in 28-d mortality and ventilation duration in low-quality trials only were observed. Regarding ICU LOS a significant reduction was observed in high-quality trials; whereas only a trend was observed in low-quality trials. No significant effects on hospital LOS or infectious complications were observed in overall or subgroup analyses. Enteral fish oil supplementation cannot be recommended for critically ill patients, as strong scientific evidence for improved clinical benefits was not found. There is a signal of mortality benefit in patients with acute respiratory distress syndrome; however, results are based on low-quality studies. Further research should focus on the relation between the individual critically ill patients' immune response, the administration of fish oil, and clinical outcomes.

Nutritional assessment of critically ill patients: validation of the modified NUTRIC score.

BACKGROUND/OBJECTIVES: In order to identify critically ill patients with high nutritional risk the modified NUTrition Risk in the Critically ill (mNUTRIC)-score was developed. This score aims to identify patients that will benefit from nutritional interventions. Few data are available on its validity. In The Netherlands, the MUST-score, a nutritional assessment tool for non-ICU patients, is commonly used in the ICU. To validate the mNUTRIC-score in Dutch ICU patients and compare its prognostic performance with the MUST-score. SUBJECTS/METHODS: A single-center retrospective cohort study among 475 mechanically ventilated patients. Prognostic performance of the mNUTRIC and MUST-scores were assessed and compared for discriminative abilities for 28-day mortality and prolonged mechanical ventilation (>2 days). RESULTS: The discriminative ability of the mNUTRIC-score for 28-day mortality is (ROC-AUC) 0.768 (95% CI 0.722-0.814) with an associated LR+ of 1.73 (95% CI 1.53-1.95) and LR- of 0.24 (95% CI 0.14-0.39) when comparing low with high (>4) scores. Comparing low with high MUST-scores (>1) a ROC-AUC of 0.513 (95% CI 0.445-0.587) and LR+ of 1.05 (95%CI 0.77-1.45) and LR- of 0.97 (95% CI 0.71-1.17) for mortality were found. The discriminative ability for prolonged ventilation was 0.666 (95% CI 0.616-0.716) and 0.532 (95% CI 0.469-0.594) for the mNUTRIC and MUST-scores, respectively. CONCLUSIONS: The prognostic performance of the mNUTRIC-score for 28-day mortality is fair and comparable to other validation studies. The association with prolonged ventilation was not confirmed by our results. The mNUTRIC-score has better performance than the commonly used MUST-score. Therefore, we suggest abandoning use of the MUST-score and to recommend introduction of the mNUTRIC-score for the nutritional risk assessment of critically ill patients.

Timing of (supplemental) parenteral nutrition in critically ill patients: a systematic review.

Supplemental parenteral nutrition (SPN) is used in a step-up approach when full enteral support is contraindicated or fails to reach caloric targets. Recent nutrition guidelines present divergent advices regarding timing of SPN in critically ill patients ranging from early SPN (<48 h after admission; EPN) to postponing initiation of SPN until day 8 after Intensive Care Unit (ICU) admission (LPN). This systematic review summarizes results of prospective studies among adult ICU patients addressing the best timing of (supplemental) parenteral nutrition (S)PN. A structured PubMed search was conducted to identify eligible articles. Articles were screened and selected using predetermined criteria and appraised for relevance and validity. After critical appraisal, four randomized controlled trials (RCTs) and two prospective observational studies remained. One RCT found a higher percentage of alive discharge from the ICU at day 8 in the LPN group compared to EPN group (p = 0.007) but no differences in ICU and in-hospital mortality. None of the other RCTs found differences in ICU or in-hospital mortality rates. Contradicting or divergent results on other secondary outcomes were found for ICU length of stay, hospital length of stay, infection rates, nutrition targets, duration of mechanical ventilation, glucose control, duration of renal replacement therapy, muscle wasting and fat loss. Although the heterogeneity in quality and design of relevant studies precludes firm conclusions, it is reasonable to assume that in adult critically ill patients, there are no clinically relevant benefits of EPN compared with LPN with respect to morbidity or mortality end points, when full enteral support is contraindicated or fails to reach caloric targets. However, considering that infectious morbidity and resolution of organ failure may be negatively affected through mechanisms not yet clearly understood and acquisition costs of parenteral nutrition are higher, the early administration of parenteral nutrition cannot be recommended.

How is intensive care reimbursed? A review of eight European countries.

Reimbursement schemes in intensive care are more complex than in other areas of healthcare, due to special procedures and high care needs. Knowledge regarding the principles of functioning in other countries can lead to increased understanding and awareness of potential for improvement. This can be achieved through mutual exchange of solutions found in other countries. In this review, experts from eight European countries explain their respective intensive care unit reimbursement schemes. Important conclusions include the apparent differences in the countries' reimbursement schemes-despite all of them originating from a DRG system-, the high degree of complexity found, and the difficulties faced in several countries when collecting the data for this collaborative work. This review has been designed to assist the intensivist clinician and researcher in understanding neighbouring countries' approaches and in putting research into the context of a European perspective. In addition, steering committees and decision makers might find this a valuable source to compare different reimbursement schemes.