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Introduction Real-world evidence on the timing and efficacy of enteral nutrition (EN) practices in intensive care unit (ICU) patients with circulatory shock is limited. We hypothesized early EN (EEN), as compared to delayed EN (DEN), is associated with improved clinical outcomes in mechanically ventilated (MV) patients with circulatory shock. Methods We analyzed a dataset from an international, multicenter, pragmatic randomized clinical trial (RCT) evaluating protein dose in ICU patients. Data were collected from ICU admission, and EEN was defined as initiating 48 h. We identified MV patients in circulatory shock to evaluate the association between the timing of EN initiation and clinical outcomes. The regression analysis model controlled for age, mNUTRIC score, APACHE II score, sepsis, and Site. Results We included 626 patients, from 52 ICUs in 14 countries. Median age was 60 years [18–93], 55% had septic shock, 99% received norepinephrine alone, 91% received EN alone, and 50.3% were randomized to a usual protein dose. Forty-two percent of EEN patients had persistent organ dysfunction syndrome plus death at day 28, compared to 53% in the DEN group (p = 0.04). EEN was associated with more ICU-free days (9.3 ± 9.2 vs. 5.7 ± 7.9, p = 0.0002), more days alive and free of vasopressors (7.1 ± 3.1 vs. 6.3 ± 3.2, p = 0.007), and shorter duration of MV among survivors (9.8 ± 10.9 vs. 13.8 ± 14.5, p = 0.0002). This trend was no longer observed in the adjusted analysis. There were no differences in ICU/60-day mortality or feeding intolerance rates between groups. Conclusion In MV patients with circulatory shock, EEN, as compared to DEN, was associated with improved clinical outcomes, but no longer when adjusting for illness severity. RCTs comparing the efficacy of EEN to DEN in MV patients with circulatory shock are warranted.

Background The optimal protein dose in critical illness is unknown. We aim to conduct a systematic review of randomized controlled trials (RCTs) to compare the effect of higher versus lower protein delivery (with similar energy delivery between groups) on clinical and patient-centered outcomes in critically ill patients. Methods We searched MEDLINE, EMBASE, CENTRAL and CINAHL from database inception through April 1, 2021.We included RCTs of (1) adult (age ≥ 18) critically ill patients that (2) compared higher vs lower protein with (3) similar energy intake between groups, and (4) reported clinical and/or patient-centered outcomes. We excluded studies on immunonutrition. Two authors screened and conducted quality assessment independently and in duplicate. Random-effect meta-analyses were conducted to estimate the pooled risk ratio (dichotomized outcomes) or mean difference (continuous outcomes). Results Nineteen RCTs were included (n = 1731). Sixteen studies used primarily the enteral route to deliver protein. Intervention was started within 72 h of ICU admission in sixteen studies. The intervention lasted between 3 and 28 days. In 11 studies that reported weight-based nutrition delivery, the pooled mean protein and energy received in higher and lower protein groups were 1.31 ± 0.48 vs 0.90 ± 0.30 g/kg and 19.9 ± 6.9 versus 20.1 ± 7.1 kcal/kg, respectively. Higher vs lower protein did not significantly affect overall mortality [risk ratio 0.91, 95% confidence interval (CI) 0.75–1.10, p = 0.34] or other clinical or patient-centered outcomes. In 5 small studies, higher protein significantly attenuated muscle loss (MD −3.44% per week, 95% CI −4.99 to −1.90; p Conclusion In critically ill patients, a higher daily protein delivery was not associated with any improvement in clinical or patient-centered outcomes. Larger, and more definitive RCTs are needed to confirm the effect of muscle loss attenuation associated with higher protein delivery. PROSPERO registration number: CRD42021237530

Background 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. Methods 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. Results 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 I2 = 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, I2 = 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, I2 = 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, I2 = 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, I2 = 0 %) while no significant differences in hospital LOS and mechanical ventilation were observed. Conclusions 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. Electronic supplementary material The online version of this article (doi:10.1186/s13054-016-1298-1) contains supplementary material, which is available to authorized users.

Introduction 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. Methods 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. Results 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%). Conclusions 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.

Introduction To develop a scoring method for quantifying nutrition risk in the intensive care unit (ICU). Methods 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. Results 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). Conclusions This scoring algorithm may be helpful in identifying critically ill patients most likely to benefit from aggressive nutrition therapy.

Introduction: The purpose of this pilot study is to assess the feasibility, acceptability, and safety of a new feeding protocol designed to enhance the delivery of enteral nutrition (EN). Methods: In a prospective before and after study, we evaluated a new protocol compared to our standard feeding protocol. Innovative elements of the new protocol included setting daily volume based goals instead of hourly rate targets, initiating motility agents and protein supplements on Day 1, liberalizing the gastric residual volume threshold, and the option to use trophic feeds. Bedside nurses filled out questionnaires to assess the acceptability of the new approach and we assessed patients' nutritional and clinical outcomes. Results: We enrolled 20 mechanically ventilated patients who stayed in the Intensive Care Unit for more than three days in the before group and 30 such patients in the after group. On a scale where 1 = totally unacceptable and 10 = totally acceptable, 30 nurses rated the new protocol as 7.1 (range 1 to 10) and no incidents compromising patient safety were observed. In the before group, on average, patients received 58.8% of their energy and 61.2% of their protein requirements by EN compared to 67.9% and 73.6% in the after group (P = 0.33 and 0.13). When the subgroup of patients prescribed to receive full volume feeds in the after group were evaluated (n = 18), they received 83.2% and 89.4% of their energy and protein requirements by EN respectively (P = 0.02 for energy and 0.002 for protein compared to the before group). The rates of vomiting, regurgitation, aspiration, and pneumonia were similar between the two groups. Conclusions: This new feeding protocol seems to be safe and acceptable to critical care nurses. The adoption of this protocol may be associated with enhanced delivery of EN but further trials are warranted to evaluate its effect on nutritional and clinical endpoints. Trial registration: ClinicalTrials.gov NCT01102348

Background: Mitochondrial dysfunction may be causally related to the pathogenesis of organ failure in critically ill patients. Decreased mitochondrial DNA (mtDNA) levels have been associated with mitochondrial dysfunction and were investigated here in relation to short-term (31-day) survival. Methods: This was a prospective longitudinal cohort study of 28 mechanically ventilated critically ill adults admitted to a single center tertiary care intensive care unit (ICU) with hypotension secondary to cardiogenic (N = 13), septic (N = 14) or hypovolemic (N = 1) disease processes. Clinical data and blood were collected at baseline and patients were followed until they expired or left the ICU. Blood was collected every Monday, Wednesday and Friday, and the buffycoat relative mtDNA/nuclear DNA (nDNA) ratio was determined. An archived pool of healthy controls was also studied. Results: At baseline, the patients' mtDNA/nDNA ratio was 30% lower than a pool of 24 healthy controls (0.76 versus 1.09) and was not different between short-term survivors and non-survivors (0.74 ± 0.05 (N = 16) versus 0.79 ± 0.06 (N = 12), p = 0.49). By day 4, the percent mtDNA/nDNA change from baseline in survivors was significantly different from that in non-survivors (+29.5% versus -5.7%, p = 0.03). It also tended to be higher in survivors at last measurement (+38.4% versus +7.1%, p = 0.06). There was a weak correlation between within patient mtDNA/nDNA and platelet count (r = 0.20, p = 0.03) but not with Sequential Organ Failure Assessment (SOFA) scores (r = 0.12, p = 0.23). The mtDNA associations remained after adjustment for platelet. Conclusion: Blood mtDNA levels appeared initially low, increased over time in patients who ultimately survived, and remained low in those who did not. This is consistent with mitochondrial recovery being associated with survival and warrants further investigation as a marker of mitochondrial alterations and outcome in critical illness.

Delays in adequate antibiotic therapy for ventilator-associated pneumonia (VAP) are associated with poor outcomes, and early use of broad-spectrum antibiotics may improve clinical outcomes. However, indiscriminant use of broad-spectrum antibiotics is associated with the emergence of antibiotic-resistant bacteria, fungal infections, and increased healthcare costs. The purpose of this study was to determine optimal empiric treatment of VAP by comparing a strategy of combination therapy to monotherapy with broad-spectrum antibiotics.

Patients who develop ventilator-associated pneumonia (VAP) caused by either multidrug-resistant organisms (MDRO) or Pseudomonas may have poor clinical outcomes. We sought to further clarify this potential relationship using a database from a large multicenter trial of diagnostic and therapeutic strategies in patients who had suspected VAP.

Introduction Recombinant human activated protein C (APC) therapy has been shown to reduce short-term mortality in patients with severe sepsis. However, survivors of sepsis may have long-term complications affecting health-related quality of life (HRQoL) and resource utilization. The objective of this study was to evaluate prospectively the effect of APC on long-term HRQoL and resource utilization compared with a nonrandomized control group that received standard care. Methods This was an observational cohort study at nine Canadian intensive care units. Patients with severe sepsis who survived to 28 days were recruited. Patients who received APC formed the treatment group and those that did not formed the standard care group. Patients who did not receive APC because of central nervous system bleeding risk were excluded from the standard care group. HRQoL (determined using the 36-item Short Form) and resource use were recorded at 28 days, and 3, 5 and 7 months. Results One hundred patients were enrolled (64 in the standard care group and 36 in the APC group), with 70 patients completing all follow-up visits. Over the 6 months of follow up, APC-treated patients exhibited statistically significantly better scores for the physical component score (P = 0.04) and trends toward improvements in physical functioning (P = 0.12), role physical (P = 0.10) and bodily pain (P = 0.14) as compared with standard care patients. Shorter hospital length of stay was observed for the APC group (36 days versus 48 days; P = 0.05). Conclusion These findings challenge earlier assumptions suggesting equivalent HRQoL and resource use in APC-treated and standard care patients who survive severe sepsis.

Introduction Nosocomial pneumonia is a major source of morbidity and mortality after severe burns. Burned patients suffer trace element deficiencies and depressed antioxidant and immune defences. This study aimed at determining the effect of trace element supplementation on nosocomial or intensive care unit (ICU)-acquired pneumonia. Methods Two consecutive, randomised, double-blinded, supplementation studies including two homogeneous groups of 41 severely burned patients (20 placebo and 21 intervention) admitted to the burn centre of a university hospital were combined. Intervention consisted of intravenous trace element supplements (copper 2.5 to 3.1 mg/day, selenium 315 to 380 μg/day, and zinc 26.2 to 31.4 mg/day) for 8 to 21 days versus placebo. Endpoints were infections during the first 30 days (predefined criteria for pneumonia, bacteraemia, wound, urine, and other), wound healing, and length of ICU stay. Plasma and skin (study 2) concentrations of selenium and zinc were determined on days 3, 10, and 20. Results The patients, 42 ± 15 years old, were burned on 46% ± 19% of body surface: the combined characteristics of the patients did not differ between the groups. Plasma trace element concentrations and antioxidative capacity were significantly enhanced with normalisation of plasma selenium, zinc, and glutathione peroxidase concentrations in plasma and skin in the trace element-supplemented group. A significant reduction in number of infections was observed in the supplemented patients, which decreased from 3.5 ± 1.2 to 2.0 ± 1.0 episodes per patient in placebo group (p < 0.001). This was related to a reduction of nosocomial pneumonia, which occurred in 16 (80%) patients versus seven (33%) patients, respectively (p < 0.001), and of ventilator-associated pneumonia from 13 to six episodes, respectively (p = 0.023). Conclusion Enhancing trace element status and antioxidant defences by selenium, zinc, and copper supplementation was associated with a decrease of nosocomial pneumonia in critically ill, severely burned patients.

Introduction Current international sepsis guidelines recommend low-dose enteral nutrition (EN) for the first week. This contradicts other nutrition guidelines for heterogenous groups of ICU patients. Data on the optimal dose of EN in septic patients are lacking. Our aim was to evaluate the effect of energy and protein amount given by EN on clinical outcomes in a large cohort of critically ill septic patients.