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.

Prone positioning for non-intubated spontaneously breathing patients with acute hypoxaemic respiratory failure: a systematic review and meta-analysis.

BACKGROUND: Prone positioning in non-intubated spontaneously breathing patients is becoming widely applied in practice alongside noninvasive respiratory support. This systematic review and meta-analysis evaluates the effect, timing, and populations that might benefit from awake proning regarding oxygenation, mortality, and tracheal intubation compared with supine position in hypoxaemic acute respiratory failure. METHODS: We conducted a systematic literature search of PubMed/MEDLINE, Cochrane Library, Embase, CINAHL, and BMJ Best Practice until August 2021 (International Prospective Register of Systematic Reviews [PROSPERO] registration: CRD42021250322). Studies included comprise least-wise 20 adult patients with hypoxaemic respiratory failure secondary to acute respiratory distress syndrome or coronavirus disease (COVID-19). Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed, and study quality was assessed using the Newcastle-Ottawa Scale and the Cochrane risk-of-bias tool. RESULTS: Fourteen studies fulfilled the selection criteria and 2352 patients were included; of those patients, 99% (n=2332/2352) had COVID-19. Amongst 1041 (44%) patients who were placed in the prone position, 1021 were SARS-CoV-2 positive. The meta-analysis revealed significant improvement in the PaO2/FiO2 ratio (mean difference -23.10; 95% confidence interval [CI]: -34.80 to 11.39; P=0.0001; I2=26%) after prone positioning. In patients with COVID-19, lower mortality was found in the group placed in the prone position (150/771 prone vs 391/1457 supine; odds ratio [OR] 0.51; 95% CI: 0.32-0.80; P=0.003; I2=48%), but the tracheal intubation rate was unchanged (284/824 prone vs 616/1271 supine; OR 0.72; 95% CI: 0.43-1.22; P=0.220; I2=75%). Overall proning was tolerated for a median of 4 h (inter-quartile range: 2-16). CONCLUSIONS: Prone positioning can improve oxygenation amongst non-intubated patients with acute hypoxaemic respiratory failure when applied for at least 4 h over repeated daily episodes. Awake proning appears safe, but the effect on tracheal intubation rate and survival remains uncertain.

Should nutrition therapy be modified to account for mitochondrial dysfunction in critical illness?

Metabolic dysfunction, and its associated muscle atrophy, remains the most common complication of critical care. At the center of this is mitochondrial dysfunction, secondary to hypoxia and systemic inflammation. This leads to a bioenergetic crisis, with decreased intramuscular adenosine triphosphate content and a reduction in the highly energy-dependent process of protein synthesis. Numerous methods have been studied to try and reduce these effects, with only limited success. Trials investigating the use of increased energy and protein administration have instead found a decrease in relative lean body mass and a potential increase in morbidity and mortality. Ketone bodies have been proposed as alternative substrates for metabolism in critical illness, with promising results seen in animal models. They are currently being investigated in critical care patients in the Alternative Substrates in the Critically Ill Subjects trial (ASICS). The evidence to date suggests that individualized feeding regimens may be key in the nutrition approach to critical illness. Consideration of individual patient factors will need to be combined with personalized protein content, total energy load received, and the timing of such feeds. This review covers mitochondrial dysfunction in critical illness, how it contributes to muscle wasting and the resultant morbidity and mortality, and the scientific basis of why current nutrition approaches to date have not been successful in negating this effect. These two factors underpin the need for consideration of alternative nutrition strategies in the critically ill patient.

Novel methods to identify and measure catabolism.

PURPOSE OF REVIEW: Assess current potential catabolism-biomarkers to characterize patients developing prolonged critical illness. RECENT FINDINGS: A raised urea-to-creatinine ratio (UCR) during critical illness is negatively associated with muscle mass with greater increases in UCR seen patients developing persistent critical illness. Similarly, sarcopenia index (a ratio of creatinine to cystatin-c concentrations) correlates well to muscle mass in intensive care populations. Elevated growth/differentiation factor-15 (GDF-15) has been inconsistently associated with muscle loss. Although GDF-15 was a poor marker of feeding tolerance, it has been associated with worse prognosis in intensive care. SUMMARY: UCR is an available and clinically applicable biomarker of catabolism. Similarly, sarcopenia index can be used to assess muscle mass and indirectly measure catabolism based on readily available biochemical measurements. The utility of novel biomarkers, such as GDF-15 is less established.