Summary Introduction Better tools are needed to assist in the identification of critically ill patients most likely to benefit from artificial nutrition therapy. Recently, the Nutrition Risk in ...Critically ill (NUTRIC) score has been developed for such purpose. The objective of this study was to externally validate a modified version of the NUTRIC score in a second database. Methods We conducted a post hoc analysis of a database of a randomized control trial of intensive care unit (ICU) patients with multi-organ failure. Data for all variables of the NUTRIC score with the exception of IL-6 levels were collected. These included age, APACHE II score, SOFA score, number of co-morbidities, days from hospital admission to ICU admission. The NUTRIC score was calculated using the exact same thresholds and point system as developed previously except the IL-6 item was omitted. A logistic model including the NUTRIC score, the nutritional adequacy and their interaction was estimated to assess if the NUTRIC score modified the association between nutritional adequacy and 28-day mortality. We also examined the association of elevated NUTRIC scores and 6-month month mortality and the interaction between NUTRIC score and nutritional adequacy. Results A total of 1199 patients were analyzed. The mean total calories prescribed was 1817 cal (SD 312) with total mean protein prescribed of 98.3 g (SD 23.6). The number of patients who received PN was 9.5%. The overall 28-day mortality rate in this validation sample was 29% and the mean NUTRIC score was 5.5 (SD 1.6). Based on the logistic model, the odds of mortality at 28 days was multiplied by 1.4 (95% CI, 1.3–1.5) for every point increase on the NUTRIC score. The mean (SD) nutritional adequacy was 50.2 (29.5) with an interquartile range from 24.8 to 74.1. The test for interaction confirmed that the association between nutritional adequacy and 28-day mortality is significantly modified by the NUTRIC score (test for interaction p = 0.029). In particular, there is a strong positive association between nutritional adequacy and 28 day survival in patients with a high NUTRIC score but this association diminishes with decreasing NUTRIC score. Higher NUTRIC scores are also significantly associated with higher 6-month mortality (p < 0.0001) and again the positive association between nutritional adequacy and 6 month survival was significantly stronger (and perhaps only present) in patients with higher NUTRIC score (test for interaction p = 0.038). Conclusion The NUTRIC scoring system is externally validated and may be useful in identifying critically ill patients most likely to benefit from optimal amounts of macronutrients when considering mortality as an outcome.
There is evidence from human twin and family studies as well as mouse and rat selection experiments that there are considerable interindividual differences in the response of cardiorespiratory ...fitness (CRF) and other cardiometabolic traits to a given exercise programme dose. We developed this consensus statement on exercise response variability following a symposium dedicated to this topic. There is strong evidence from both animal and human studies that exercise training doses lead to variable responses. A genetic component contributes to exercise training response variability.In this consensus statement, we (1) briefly review the literature on exercise response variability and the various sources of variations in CRF response to an exercise programme, (2) introduce the key research designs and corresponding statistical models with an emphasis on randomised controlled designs with or without multiple pretests and post-tests, crossover designs and repeated measures designs, (3) discuss advantages and disadvantages of multiple methods of categorising exercise response levels-a topic that is of particular interest for personalised exercise medicine and (4) outline approaches that may identify determinants and modifiers of CRF exercise response. We also summarise gaps in knowledge and recommend future research to better understand exercise response variability.
To develop a scoring method for quantifying nutrition risk in the intensive care unit (ICU).
A prospective, observational study of patients expected to stay > 24 hours. We collected data for key ...variables considered for inclusion in the score which included: age, baseline APACHE II, baseline SOFA score, number of comorbidities, days from hospital admission to ICU admission, Body Mass Index (BMI) < 20, estimated % oral intake in the week prior, weight loss in the last 3 months and serum interleukin-6 (IL-6), procalcitonin (PCT), and C-reactive protein (CRP) levels. Approximate quintiles of each variable were assigned points based on the strength of their association with 28 day mortality.
A total of 597 patients were enrolled in this study. Based on the statistical significance in the multivariable model, the final score used all candidate variables except BMI, CRP, PCT, estimated percentage oral intake and weight loss. As the score increased, so did mortality rate and duration of mechanical ventilation. Logistic regression demonstrated that nutritional adequacy modifies the association between the score and 28 day mortality (p = 0.01).
This scoring algorithm may be helpful in identifying critically ill patients most likely to benefit from aggressive nutrition therapy.
Critically ill patients have considerable oxidative stress. Glutamine and antioxidant supplementation may offer therapeutic benefit, although current data are conflicting.
In this blinded 2-by-2 ...factorial trial, we randomly assigned 1223 critically ill adults in 40 intensive care units (ICUs) in Canada, the United States, and Europe who had multiorgan failure and were receiving mechanical ventilation to receive supplements of glutamine, antioxidants, both, or placebo. Supplements were started within 24 hours after admission to the ICU and were provided both intravenously and enterally. The primary outcome was 28-day mortality. Because of the interim-analysis plan, a P value of less than 0.044 at the final analysis was considered to indicate statistical significance.
There was a trend toward increased mortality at 28 days among patients who received glutamine as compared with those who did not receive glutamine (32.4% vs. 27.2%; adjusted odds ratio, 1.28; 95% confidence interval CI, 1.00 to 1.64; P=0.05). In-hospital mortality and mortality at 6 months were significantly higher among those who received glutamine than among those who did not. Glutamine had no effect on rates of organ failure or infectious complications. Antioxidants had no effect on 28-day mortality (30.8%, vs. 28.8% with no antioxidants; adjusted odds ratio, 1.09; 95% CI, 0.86 to 1.40; P=0.48) or any other secondary end point. There were no differences among the groups with respect to serious adverse events (P=0.83).
Early provision of glutamine or antioxidants did not improve clinical outcomes, and glutamine was associated with an increase in mortality among critically ill patients with multiorgan failure. (Funded by the Canadian Institutes of Health Research; ClinicalTrials.gov number, NCT00133978.).
The largest cohort of critically ill patients evaluating intragastric and small intestinal delivery of nutrients was recently reported. This systematic review included recent data to compare the ...effects of small bowel and intragastric delivery of enteral nutrients in adult critically ill patients.
This is a systematic review of all randomised controlled studies published between 1990 and March 2013 that reported the effects of the route of enteral feeding in the critically ill on clinically important outcomes.
Data from 15 level-2 studies were included. Small bowel feeding was associated with a reduced risk of pneumonia (Relative Risk, RR, small intestinal vs. intragastric: 0.75 (95% confidence interval 0.60 to 0.93); P=0.01; I2=11%). The point estimate was similar when only studies using microbiological data were included. Duration of ventilation (weighted mean difference: -0.36 days (-2.02 to 1.30); P=0.65; I2=42%), length of ICU stay (WMD: 0.49 days, (-1.36 to 2.33); P=0.60; I2=81%) and mortality (RR 1.01 (0.83 to 1.24); P=0.92; I2=0%) were unaffected by the route of feeding. While data were limited, and there was substantial statistical heterogeneity, there was significantly improved nutrient intake via the small intestinal route (% goal rate received: 11% (5 to 16%); P=0.0004; I2=88%).
Use of small intestinal feeding may improve nutritional intake and reduce the incidence of ICU-acquired pneumonia. In unselected critically ill patients other clinically important outcomes were unaffected by the site of the feeding tube.
Purpose
The objective of this study was to examine the relationship between the amount of energy and protein administered and clinical outcomes, and the extent to which pre-morbid nutritional status ...influenced this relationship.
Methods
We conducted an observational cohort study of nutrition practices in 167 intensive care units (ICUs) across 37 countries. Patient demographics were collected, and the type and amount of nutrition received were recorded daily for a maximum of 12 days. Patients were followed prospectively to determine 60-day mortality and ventilator-free days (VFDs). We used body mass index (BMI, kg/m
2
) as a marker of nutritional status prior to ICU admission. Regression models were developed to evaluate the relationship between nutrition received and 60-day mortality and VFDs, and to examine how BMI modifies this relationship.
Results
Data were collected on 2,772 mechanically ventilated patients who received an average of 1,034 kcal/day and 47 g protein/day. An increase of 1,000 cal per day was associated with reduced mortality odds ratio for 60-day mortality 0.76; 95% confidence intervals (CI) 0.61–0.95,
p
= 0.014 and an increased number of VFDs (3.5 VFD, 95% CI 1.2–5.9,
p
= 0.003). The effect of increased calories associated with lower mortality was observed in patients with a BMI <25 and ≥35 with no benefit for patients with a BMI 25 to <35. Similar results were observed when comparing increasing protein intake and its effect on mortality.
Conclusions
Increased intakes of energy and protein appear to be associated with improved clinical outcomes in critically ill patients, particularly when BMI is <25 or ≥35.
Enteral nutrition (EN) is recommended as the preferred route for early nutrition therapy in critically ill adults over parenteral nutrition (PN). A recent large randomized controlled trial (RCT) ...showed no outcome differences between the two routes. The objective of this systematic review was to evaluate the effect of the route of nutrition (EN versus PN) on clinical outcomes of critically ill patients.
An electronic search from 1980 to 2016 was performed identifying relevant RCTs. Individual trial data were abstracted and methodological quality of included trials scored independently by two reviewers. The primary outcome was overall mortality and secondary outcomes included infectious complications, length of stay (LOS) and mechanical ventilation. Subgroup analyses were performed to examine the treatment effect by dissimilar caloric intakes, year of publication and trial methodology. We performed a test of asymmetry to assess for the presence of publication bias.
A total of 18 RCTs studying 3347 patients met inclusion criteria. Median methodological score was 7 (range, 2-12). No effect on overall mortality was found (1.04, 95 % CI 0.82, 1.33, P = 0.75, heterogeneity I(2) = 11 %). EN compared to PN was associated with a significant reduction in infectious complications (RR 0.64, 95 % CI 0.48, 0.87, P = 0.004, I(2) = 47 %). This was more pronounced in the subgroup of RCTs where the PN group received significantly more calories (RR 0.55, 95 % CI 0.37, 0.82, P = 0.003, I(2) = 0 %), while no effect was seen in trials where EN and PN groups had a similar caloric intake (RR 0.94, 95 % CI 0.80, 1.10, P = 0.44, I(2) = 0 %; test for subgroup differences, P = 0.003). Year of publication and methodological quality did not influence these findings; however, a publication bias may be present as the test of asymmetry was significant (P = 0.003). EN was associated with significant reduction in ICU LOS (weighted mean difference WMD -0.80, 95 % CI -1.23, -0.37, P = 0.0003, I(2) = 0 %) while no significant differences in hospital LOS and mechanical ventilation were observed.
In critically ill patients, the use of EN as compared to PN has no effect on overall mortality but decreases infectious complications and ICU LOS. This may be explained by the benefit of reduced macronutrient intake rather than the enteral route itself.
The optimal amount of calories required by critically ill patients continues to be controversial. The objective of this study is to examine the relationship between the amount of calories ...administered and mortality.
Prospective, multi-institutional audit.
Three hundred fifty-two intensive care units from 33 countries.
A total of 7,872 mechanically ventilated, critically ill patients who remained in the intensive care unit for at least 96 hrs.
None.
We evaluated the association between the amount of calories received and 60-day hospital mortality using various sample restriction and statistical adjustment techniques and demonstrate the influence of the analytic approach on the results. In the initial unadjusted analysis, we observe a significant association between increased caloric intake and increased mortality (odds ratio 1.28; 95% confidence interval 1.12-1.48 for patients receiving more than two-thirds of their caloric prescription vs. those receiving less than one-third of their prescription). Excluding days after permanent progression to oral intake attenuated the estimates of harm (unadjusted analysis: odds ratio 1.04; 95% confidence interval 0.90-1.20). Restricting the analysis to patients with at least 4 days in the intensive care unit before progression to oral intake and excluding days of observation after progression to oral intake resulted in a significant benefit to increased caloric intake (unadjusted odds ratio 0.73; 95% confidence interval 0.63-0.85). When further adjusting for both evaluable days and other important covariates, patients who received more than two-thirds of their caloric prescription are much less likely to die than those receiving less than one-third of their prescription (odds ratio 0.67; 95% confidence interval 0.56-0.79; p < .0001). When treated as a continuous variable, the overall association between the percent of the caloric prescription received and mortality is highly statistically significant with increasing calories associated with decreasing mortality (p < .0001).
The estimated association between the amount of calories and mortality is significantly influenced by the statistical methodology used. The most appropriate available analyses suggest that attempting to meet caloric targets may be associated with improved clinical outcomes in critically ill patients.
To examine the association between short-term nutritional adequacy received while in the ICU and long-term outcomes including 6-month survival and health-related quality of life in critically ill ...patients requiring prolonged mechanical ventilation.
Retrospective analysis of data prospectively collected in the context of a multicenter randomized controlled trial.
An international sample of ICUs.
Adult patients who were mechanically ventilated for more than 8 days in the ICU.
None.
Nutritional adequacy was obtained from the average proportion of prescribed calories received over the amount prescribed during the first 8 days. Survival status and health-related quality of life as assessed using the Short-Form 36 v2 were obtained at 3- and 6 months post ICU admission. Of the 1,223 patients enrolled in the randomized controlled trial, 475 met the inclusion criteria for this study. At 6-month follow-up, 302 of the 475 patients (64%) were alive. Survival time in those who received low nutritional adequacy was significantly shorter than those who received high nutritional adequacy while adjusting for important covariates (adjusted hazard ratio, 1.7; 95% CI, 1.1-2.6). At 3-month follow-up, a 25% increase in nutritional adequacy was associated with improvements in Physical Functioning and Role Physical of 7.3 (p = 0.02) and 8.3 (p = 0.004) points, respectively. At 6-month follow-up, adjusted increases in Physical Functioning and Role Physical scores for every 25% increase in nutrition adequacy became smaller and were no longer statistically significant (adjusted estimate for Physical Functioning = 4.2, p = 0.14; for Role Physical = 3.2, p = 0.25).
Greater amounts of nutritional intake received during the first week in the ICU were associated with longer survival time and faster physical recovery to 3 months but not 6 months post ICU discharge in critically ill patients requiring prolonged mechanical ventilation. Current recommendations to underfeed critically ill patients may cause harm in some long-stay patients.
Summary Background & aims Adverse consequences may be experienced by critically ill patients who are underfed during their stay in the intensive care unit. The objective of this study is to determine ...the prevalence of iatrogenic underfeeding (receiving <80% of prescribed energy requirements) and the variation of these rates in different geographic regions of the world and in different nutritionally ‘at-risk’ patient populations. Methods This was a prospective, multi-institutional study in 201 units from 26 countries. We included 3390 mechanically ventilated patients who remained in the unit and received artificial nutrition for at least 96 h. We report time to start of enteral nutrition and % nutrition received in various geographic regions of the world and we focus on subgroups of ‘high risk’ patients (those with >7 days of mechanical ventilation, body mass index of <25 or ≥35, and those with a Nutrition Risk In the Critically ill (NUTRIC) score of ≥5). We report rates of novel enteral nutrition delivery techniques and supplemental parenteral nutrition in these high risk patients. Results On average, enteral feedings were started 38.8 h (standard deviation: 39.6) after admission, patients received 61.2% of calories and 57.6% of protein prescribed, and 74.0% of patients failed to meet the quality metric of receiving at least 80% of energy targets. There were significant differences in nutrition outcomes across different geographic regions. There were no clinically important differences in nutrition outcomes or rates of iatrogenic underfeeding in patients in different BMI groups nor by NUTRIC score. Of all at-risk patients, 14% were ever prescribed volume-based feeds, and 15% of patients ever received supplemental parenteral nutrition. Conclusions Worldwide, the majority of critically ill patients, including high nutritional risk patients, fail to receive adequate nutritional intake. There is low uptake of strategies designed to optimize nutrition delivery in these patients.
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