Association between energy surplus and intensive care unit length of stay in critically ill patients: A retrospective cohort study.

BACKGROUND: Patients experiencing persistent critical illness have poor short-term and long-term outcomes and consume disproportionate amounts of health care resources. Nutrition optimization may improve outcomes, though few data exist on resting energy expenditure and nutrition requirements. We hypothesized that increased energy surplus per day is associated with increased intensive care unit (ICU) length of stay (LoS) in critically ill patients. METHODS: Patients from a single ICU at Royal London Hospital were included in this retrospective cohort study. EXPOSURE: energy surplus measured by serial indirect calorimetry (IC) and nutrition intake. INCLUSION CRITERIA: mechanical ventilation of ≥3 days and expected to remain ventilated. PRIMARY OUTCOME: ICU LoS. RESULTS: Across 30 patients (median LoS 21 days), increased ICU LoS was associated with actual daily energy intake surplus to resting energy expenditure (REE) (R2 0.16; P < 0.005). Median REE was less than predicted energy requirements: 24 kcal per day per kilogram of ideal body weight (IBW) (interquartile range [IQR], 20-28) vs 28 kcal/day/kg IBW (IQR, 26-29) (P < 0.001). Patients with COVID-19 had a median energy surplus (actual intake- REE) + 344 kcal/day (IQR 35-517) vs -57 kcal/day (IQR -324 to 211) in other patients (P = 0.011); however, they had a median LoS of 44 days (IQR 26-58) vs 10 days (IQR 7-24), respectively (P < 0.001). Patients with obesity had a median energy deficit of -32 kcal/day (IQR -384 to 335) vs +234 kcal/day (IQR -79 to 499) for nonobese patients (P = 0.021). CONCLUSION: Overfeeding represents an easily modifiable factor to improve outcomes in patients experiencing persistent critical illness, for which IC may be useful.

A pilot study of alternative substrates in the critically Ill subject using a ketogenic feed.

Bioenergetic failure caused by impaired utilisation of glucose and fatty acids contributes to organ dysfunction across multiple tissues in critical illness. Ketone bodies may form an alternative substrate source, but the feasibility and safety of inducing a ketogenic state in physiologically unstable patients is not known. Twenty-nine mechanically ventilated adults with multi-organ failure managed on intensive care units were randomised (Ketogenic n = 14, Control n = 15) into a two-centre pilot open-label trial of ketogenic versus standard enteral feeding. The primary endpoints were assessment of feasibility and safety, recruitment and retention rates and achievement of ketosis and glucose control. Ketogenic feeding was feasible, safe, well tolerated and resulted in ketosis in all patients in the intervention group, with a refusal rate of 4.1% and 82.8% retention. Patients who received ketogenic feeding had fewer hypoglycaemic events (0.0% vs. 1.6%), required less exogenous international units of insulin (0 (Interquartile range 0-16) vs.78 (Interquartile range 0-412) but had slightly more daily episodes of diarrhoea (53.5% vs. 42.9%) over the trial period. Ketogenic feeding was feasible and may be an intervention for addressing bioenergetic failure in critically ill patients. Clinical Trials.gov registration: NCT04101071.

Effect of intermittent or continuous feeding and amino acid concentration on urea-to-creatinine ratio in critical illness.

BACKGROUND: We sought to determine whether peaks in essential amino acid (EAA) concentration associated with intermittent feeding may provide anabolic advantages when compared with continuous feeding regimens in critical care. METHODS: We performed a secondary analysis of data from a multicenter trial of UK intensive care patients randomly assigned to intermittent or continuous feeding. A linear mixed-effects model was developed to assess differences in urea-creatinine ratio (raised values of which can be a marker of muscle wasting) between arms. To investigate metabolic phenotypes, we performed k-means urea-to-creatinine ratio trajectory clustering. Amino acid concentrations were also modeled against urea-to-creatinine ratio from day 1 to day 7. The main outcome measure was serum urea-to-creatinine ratio (millimole per millimole) from day 0 to the end of the 10-day study period. RESULTS: Urea-to-creatinine ratio trajectory differed between feeding regimens (coefficient -.245; P = .002). Patients receiving intermittent feeding demonstrated a flatter urea-to-creatinine ratio trajectory. With k-means analysis, the cluster with the largest proportion of continuously fed patients demonstrated the steepest rise in urea-to-creatinine ratio. Neither protein intake per se nor serum concentrations of EAA concentrations were correlated with urea-to-creatinine ratio (coefficient = .088 [P = .506] and coefficient <.001 [P = .122], respectively). CONCLUSION: Intermittent feeding can mitigate the rise in urea-to-creatinine ratio otherwise seen in those continuously fed, suggesting that catabolism may have been, to some degree, prevented.

Talking to multi-morbid patients about critical illness: an evolving conversation.

Conversations around critical illness outcomes and benefits from intensive care unit (ICU) treatment have begun to shift away from binary discussions on living versus dying. Increasingly, the reality of survival with functional impairment versus survival with a late death is being recognised as relevant to patients. Most ICU admissions are associated with new functional and cognitive disabilities that are significant and long lasting. When discussing outcomes, clinicians rightly focus on patients' wishes and the quality of life (QoL) that they would find acceptable. However, patients' views may encompass differing views on acceptable QoL post-critical illness, not necessarily reflected in standard conversations. Maintaining independence is a greater priority to patients than simple survival. QoL post-critical illness determines judgments on the benefits of ICU support but translating this into clinical practice risks potential conflation of health outcomes and QoL. This article discusses the concept of response shift and the implication for trade-offs between number/length of invasive treatments and change in physical function or death. Conversations need to delineate how health outcomes (e.g. tracheostomy, muscle wasting, etc.) may affect individual outcomes most relevant to the patient and hence impact overall QoL. The research strategy taken to explore decision-making for critically ill patients might benefit from gathering qualitative data, as a complement to quantitative data. Patients, families and doctors are motivated by far wider considerations, and a consultation process should relate to more than the simple likelihood of mortality in a shared decision-making context.

Effect of Intermittent or Continuous Feed on Muscle Wasting in Critical Illness: A Phase 2 Clinical Trial.

BACKGROUND: Acute skeletal muscle wasting in critical illness is associated with excess morbidity and mortality. Continuous feeding may suppress muscle protein synthesis as a result of the muscle-full effect, unlike intermittent feeding, which may ameliorate it. RESEARCH QUESTION: Does intermittent enteral feed decrease muscle wasting compared with continuous feed in critically ill patients? STUDY DESIGN AND METHODS: In a phase 2 interventional single-blinded randomized controlled trial, 121 mechanically ventilated adult patients with multiorgan failure were recruited following prospective informed consultee assent. They were randomized to the intervention group (intermittent enteral feeding from six 4-hourly feeds per 24 h, n = 62) or control group (standard continuous enteral feeding, n = 59). The primary outcome was 10-day loss of rectus femoris muscle cross-sectional area determined by ultrasound. Secondary outcomes included nutritional target achievements, plasma amino acid concentrations, glycemic control, and physical function milestones. RESULTS: Muscle loss was similar between arms (-1.1% [95% CI, -6.1% to -4.0%]; P = .676). More intermittently fed patients received 80% or more of target protein (OR, 1.52 [1.16-1.99]; P < .001) and energy (OR, 1.59 [1.21-2.08]; P = .001). Plasma branched-chain amino acid concentrations before and after feeds were similar between arms on trial day 1 (71 µM [44-98 µM]; P = .547) and trial day 10 (239 µM [33-444 µM]; P = .178). During the 10-day intervention period the coefficient of variation for glucose concentrations was higher with intermittent feed (17.84 [18.6-20.4]) vs continuous feed (12.98 [14.0-15.7]; P < .001). However, days with reported hypoglycemia and insulin usage were similar in both groups. Safety profiles, gastric intolerance, physical function milestones, and discharge destinations did not differ between groups. INTERPRETATION: Intermittent feeding in early critical illness is not shown to preserve muscle mass in this trial despite resulting in a greater achievement of nutritional targets than continuous feeding. However, it is feasible and safe. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT02358512; URL: www.clinicaltrials.gov.

An Exploratory Study of Long-Term Outcome Measures in Critical Illness Survivors: Construct Validity of Physical Activity, Frailty, and Health-Related Quality of Life Measures.

OBJECTIVE: Functional capacity is commonly impaired after critical illness. We sought to clarify the relationship between objective measures of physical activity, self-reported measures of health-related quality of life, and clinician reported global functioning capacity (frailty) in such patients, as well as the impact of prior chronic disease status on these functional outcomes. DESIGN: Prospective outcome study of critical illness survivors. SETTING: Community-based follow-up. PATIENTS: Participants of the Musculoskeletal Ultrasound Study in Critical Care: Longitudinal Evaluation Study (NCT01106300), invasively ventilated for more than 48 hours and on the ICU greater than 7 days. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Physical activity levels (health-related quality of life [36-item short-form health survey] and daily step counts [accelerometry]) were compared to norm-based or healthy control scores, respectively. Controls for frailty (Clinical Frailty Score) were non-morbid, age- and gender-matched to survivors. Ninety-one patients were recruited on ICU admission: 41 were contacted for post-discharge assessment, and data were collected from 30 (14 female; mean age, 55.3 yr [95% CI, 48.3-62.3]; mean post-discharge, 576 d [95% CI, 539-614]). Patients' mean daily step count (5,803; 95% CI, 4,792-6,813) was lower than that in controls (11,735; 95% CI, 10,928-12,542; p < 0.001), and lower in those with preexisting chronic disease than without (2,989 [95% CI, 776-5,201] vs 7,737 [95% CI, 4,907-10,567]; p = 0.013). Physical activity measures (accelerometry, health-related quality of life, and frailty) demonstrated good construct validity across all three tools. Step variability (from SD) was highly correlated with daily steps (r = 0.67; p < 0.01) demonstrating a potential boundary constraint. CONCLUSIONS: Subjective and objective measures of physical activity are all informative in ICU survivors. They are all reduced 18 months post-discharge in ICU survivors, and worse in those with pre-admission chronic disease states. Investigating interventions to improve functional capacity in ICU survivors will require stratification based on the presence of premorbidity.