Role of Early Enteral Nutrition in Mechanically Ventilated COVID-19 Patients.

Current guidance recommends initiation of early enteral nutrition (early EN) within 24-36 hours of ICU admission in critically ill COVID-19 patients. Despite this recommendation, there is quite limited evidence describing the effect of early EN on outcomes in COVID-19 patients. The association between early EN (within 3 d post intubation) and clinical outcomes in adult COVID-19 patients requiring mechanical ventilation (within 2 d post ICU admission) was evaluated. DESIGN: We performed a nationwide observational cohort study using a nationwide administrative-financial database (Premier) in United States. SETTING: Information pertaining to all COVID-19 patients admitted to ICU from 75 hospitals between April and December 2020 was analyzed. PATIENTS: A total of 861 COVID-19 patients were included. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Clinical outcomes were assessed via regression models to control for patient and hospital characteristics. We identified 513 COVID-19 ICU patients (59.2%) requiring mechanical ventilation who received early EN and had similar baseline characteristics to late EN group. Compared with late EN group, the early EN group had shorter ICU (hazard ratio [HR], 1.39; 95% CI, 1.15-1.68) and hospital length of stays (LOS) (HR, 1.53; 95% CI, 1.23-1.91), fewer mechanical ventilation days (HR, 1.25; 95% CI, 1.01-1.54), and lower cost (-$22,443; 95% CI, -$32,342 to -$12,534). All comparisons were statistically significant (p < 0.05). CONCLUSIONS: In patients with COVID-19 requiring mechanical ventilation, early EN is associated with earlier liberation from mechanical ventilation, shorter ICU and hospital LOS, and decreased cost. Our results are among the first to support guideline recommendations for initiation of early EN in COVID-19 ICU patients. Further, our data show nearly 40% of critically ill COVID-19 patients fail to have early EN initiated, even at 3 d post initiation of mechanical ventilation. These results emphasize the need for targeted strategies promoting initiation of early EN, as this may lead to improved clinical and economic outcomes in severe COVID-19 patients.

Recovery Focused Nutritional Therapy across the Continuum of Care: Learning from COVID-19.

Targeted nutritional therapy should be started early in severe illness and sustained through to recovery if clinical and patient-centred outcomes are to be optimised. The coronavirus disease 2019 (COVID-19) pandemic has shone a light on this need. The literature on nutrition and COVID-19 mainly focuses on the importance of nutrition to preserve life and prevent clinical deterioration during the acute phase of illness. However, there is a lack of information guiding practice across the whole patient journey (e.g., hospital to home) with a focus on targeting recovery (e.g., long COVID). This review paper is of relevance to doctors and other healthcare professionals in acute care and primary care worldwide, since it addresses early, multi-modal individualised nutrition interventions across the continuum of care to improve COVID-19 patient outcomes. It is of relevance to nutrition experts and non-nutrition experts and can be used to promote inter-professional and inter-organisational knowledge transfer on the topic. The primary goal is to prevent complications and support recovery to enable COVID-19 patients to achieve the best possible nutritional, physical, functional and mental health status and to apply the learning to date from the COVID-19 pandemic to other patient groups experiencing acute severe illness.

Prolonged progressive hypermetabolism during COVID-19 hospitalization undetected by common predictive energy equations.

BACKGROUND & AIMS: Indirect calorimetry (IC) is the gold-standard for determining measured resting energy expenditure (mREE) in critical illness. When IC is not available, predicted resting energy expenditure (pREE) equations are commonly utilized, which often inaccurately predict metabolic demands leading to over- or under-feeding. This study aims to longitudinally assess mREE via IC in critically ill patients with SARS-CoV-2 (COVID-19) infection throughout the entirety of, often prolonged, intensive care unit (ICU) stays and compare mREE to commonly utilized pREE equations. METHODS: This single-center prospective cohort study of 38 mechanically ventilated COVID-19 patients from April 1, 2020 to February 1, 2021. The Q-NRG® Metabolic Monitor was used to obtain IC data. The Harris-Benedict (HB), Mifflin St-Jeor (MSJ), Penn State University (PSU), and weight-based equations from the American Society of Parenteral and Enteral Nutrition - Society of Critical Care Medicine (ASPEN-SCCM) Clinical Guidelines were utilized to assess the accuracy of common pREE equations and their ability to predict hypo/hypermetabolism in COVID-19 ICU patients. RESULTS: The IC measures collected revealed a relatively normometabolic or minimally hypermetabolic mREE at 21.3 kcal/kg/d or 110% of predicted by the HB equation over the first week of mechanical ventilation (MV). This progressed to significant and uniquely prolonged hypermetabolism over successive weeks to 28.1 kcal/kg/d or 143% of HB predicted by MV week 3, with hypermetabolism persisting to MV week 7. Obese individuals displayed a more truncated response with significantly lower mREE versus non-obese patients in MV week 1 (19.5 ± 1.0 kcal/kg/d vs 25.1 ± 1.8 kcal/kg/d, respectively; p < 0.01), with little change in weeks 2-3 (19.5 ± 1.5 kcal/kg/d vs 28.0 ± 2.0 kcal/kg/d; p < 0.01). Both ASPEN-SCCM upper range and PSU pREE equations provided close approximations of mREE yet, like all pREE equations, occasionally over- and under-predicted energy needs and typically did not predict late hypermetabolism. CONCLUSIONS: Study results show a truly unique metabolic response in COVID-19 ICU patients, characterized by significant and prolonged, progressive hypermetabolism peaking at 3 weeks' post-intubation, persisting for up to 7 weeks in ICU. This pattern was more clearly demonstrated in non-obese versus obese patients. This response is unique and distinct from any previously described model of ICU stress response in its prolonged hypermetabolic nature. This data reaffirms the need for routine, longitudinal IC measures to provide accurate energy targets in COVID-19 ICU patients. The PSU and ASPEN-SCCM equations appear to yield the most reasonable estimation to IC-derived mREE in COVID-19 ICU patients, yet still often over-/under-predict energy needs. These findings provide a practical guide for caloric prescription in COVID-19 ICU patients in the absence of IC.

Indirect calorimetry in critical illness: a new standard of care?

PURPOSE OF REVIEW: Review recent literature on the role of indirect calorimetry in critical care nutrition management. RECENT FINDINGS: Critical illness demands objective, targeted nutritional therapy to prevent adverse effects of underfeeding/over feeding. Thus, all recent societal guidelines recommend indirect calorimetry use to determine energy needs. Very recently, indirect calorimetry technology has finally evolved to allow for accurate, simple, and routine utilization in a wider range of ICU patients. Recent data continues to confirm poor correlation between measured and equation-predicted energy expenditure emphasizing need for indirect calorimetry to be standard of care. This may be particularly true in COVID-19, where significant progressive hypermetabolism and variability in energy expenditure has been shown. Metabolic physiology can change frequently during ICU stay in response to changes in clinical condition or care. Thus, repeated longitudinal indirect calorimetry measures are needed throughout ICU stay to optimize care, with initial data showing improved clinical outcomes when indirect calorimetry targets are utilized. SUMMARY: Personalized ICU care demands objective data to guide therapy. This includes use of indirect calorimetry to determine energy expenditure and guide ICU nutrition therapy. Long-awaited new innovations in indirect calorimetry technology should finally lead to indirect calorimetry to becoming a fundamental component of modern ICU standard of care and clinical research moving forward.

Randomised, double-blind, placebo-controlled trial of Probiotics To Eliminate COVID-19 Transmission in Exposed Household Contacts (PROTECT-EHC): a clinical trial protocol.

INTRODUCTION: The COVID-19 pandemic has proven to be an unprecedented challenge to worldwide health, and strategies to mitigate the spread and severity of COVID-19 infection are urgently needed. Emerging evidence suggests that the composition of the gut microbiome and modification of microbial ecology via probiotics can affect susceptibility to a wide range of infections, including respiratory tract infections. In this study, we aim to evaluate the effects of the probiotic Lactobacillus rhamnosus GG (LGG) versus placebo on COVID-19 infection status and the gut microbiome in subjects with a household contact who has tested positive for COVID-19. METHODS AND ANALYSIS: In this double-blinded, randomised, placebo-controlled trial, we will randomise 1132 subjects having a household contact who has recently (≤7 days) tested positive for COVID-19 to daily oral LGG or placebo for 28 days. We hypothesise that taking LGG as a probiotic will protect against COVID-19 infection and reduce the severity of disease in those who become infected (primary endpoint: decreased symptoms), and will be associated with beneficial changes in the composition of the gut microbiome. Stool samples and nasal swabs will be collected to evaluate the microbiome by 16S rRNA sequencing and the presence of SARS-CoV-2 by PCR, respectively. We will also conduct multivariate analysis of demographic, behavioural, temporal, and other variables that may predict development of symptoms and other outcomes. ETHICS AND DISSEMINATION: This trial is conducted under a Food and Drug Administration Investigational New Drug for LGG, has received ethics approval by the institutional review board of Duke University and enrolment has begun. We plan to disseminate the results in peer-reviewed journals and at national and international conferences. TRIAL REGISTRATION NUMBER: NCT04399252.

Point-Counterpoint: Indirect Calorimetry Is Essential for Optimal Nutrition Therapy in the Intensive Care Unit.

Iatrogenic malnutrition and underfeeding are ubiquitous in intensive care units (ICUs) worldwide for prolonged periods after ICU admission. A major driver leading to the lack of emphasis on timely ICU nutrition delivery is lack of objective data to guide nutrition care. If we are to ultimately overcome current fundamental challenges to effective ICU nutrition delivery, we must all adopt routine objective, longitudinal measurement of energy targets via indirect calorimetry (IC). Key evidence supporting the routine use of IC in the ICU includes (1) universal societal ICU nutrition guidelines recommending IC to determine energy requirements; (2) data showing predictive equations or body weight calculations that are consistently inaccurate and correlate poorly with measured energy expenditure, ultimately leading to routine overfeeding and underfeeding, which are both associated with poor ICU outcomes; (3) recent development and worldwide availability of a new validated, accurate, easy-to-use IC device; and (4) recent data in ICU patients with coronavirus disease 2019 (COVID-19) showing progressive hypermetabolism throughout ICU stay, emphasizing the inaccuracy of predictive equations and marked day-to-day variability in nutrition needs. Thus, given the availability of a new validated IC device, these findings emphasize that routine longitudinal IC measures should be considered the new standard of care for ICU and post-ICU nutrition delivery. As we would not deliver vasopressors without accurate blood pressure measurements, the ICU community is only likely to embrace an increased focus on the importance of early nutrition delivery when we can consistently provide objective IC measures to ensure personalized nutrition care delivers the right nutrition dose, in the right patient, at the right time to optimize clinical outcomes.

Implications for Neuromodulation Therapy to Control Inflammation and Related Organ Dysfunction in COVID-19.

COVID-19 is a syndrome that includes more than just isolated respiratory disease, as severe acute respiratory syndrome-coronavirus 2 (SARS-CoV2) also interacts with the cardiovascular, nervous, renal, and immune system at multiple levels, increasing morbidity in patients with underlying cardiometabolic conditions and inducing myocardial injury or dysfunction. Emerging evidence suggests that patients with the highest rate of morbidity and mortality following SARS-CoV2 infection have also developed a hyperinflammatory syndrome (also termed cytokine release syndrome). We lay out the potential contribution of a dysfunction in autonomic tone to the cytokine release syndrome and related multiorgan damage in COVID-19. We hypothesize that a cholinergic anti-inflammatory pathway could be targeted as a therapeutic avenue. Graphical Abstract .