Early goal-directed nutrition in icU patients (EAT-ICU):protocol for a randomised trial

INTRODUCTION: Extensive weight loss has been documented in intensive care unit (ICU) survivors, primarily as the result of muscle loss, leading to impaired physical function and reduced quality of life. The aim of the EAT-ICU trial is to test the effect of early goal-directed protein-energy nutrition based on measured requirements on short-term clinical outcomes and long-term physical quality of life in ICU patients. METHODS: The EAT-ICU trial is a single-centre, randomised, parallel-group trial with concealed allocation and blinded outcome assessment. A total of 200 consecutive, acutely admitted, mechanically ventilated intensive care patients will be randomised 1: 1 to early goal-directed nutrition versus standard of care to show a potential 15% relative risk reduction in the primary outcome measure (physical function) at six months (two-sided significance level alpha = 0.05; power beta = 80%). Secondary outcomes include energy-and protein balances, metabolic control, new organ failure, use of life support, nosocomial infections, ICU- and hospital length of stay, mortality and cost analyses. CONCLUSION : The optimal nutrition strategy for ICU patients remains unsettled. The EAT-ICU trial will provide important data on the effects of early goal-directed proteinenergy nutrition based on measured requirements in these patients.Copenhagen University Hospital; Rigshospitalet; Fresenius Kabi A/S; European Society for Clinical Nutrition and Metabolism (ESPEN)SCI(E)[email protected]

Acute onset and rapid progression of multiple organ failure in a young adult with undiagnosed disseminated colonic adenocarcinoma

Colourectal cancer (CRC) is the fourth most common cause of death from cancer worldwide. While rates for CRC in adults age 50 and older have been declining, incidence rates in young adults, a population routinely not screened, has been increasing. We report a rare case of high-grade CRC in a previously healthy 27-year-old man, presented to us with symptoms of increasing abdominal pain and distension. Extensive diagnostic investigation revealed hepatomegaly with multiple processes, signs of vasculitis, extensive liver necrosis, enlarged retroperitoneal and mesenteric lymph nodes, splenomegaly, ascites and multiple vein thrombosis. The patient passed away shortly after admission due to treatment-resistant tumour lysis syndrome and multiple organ failure. Biopsy results revealed disseminated adenocarcinoma of the colon, with metastases to lymph nodes, liver, lungs and pleura. CRC in younger patients tend to present at a later stage and appears to be more aggressive, with a poorer pathological differentiation

Early goal-directed nutrition versus standard of care in adult intensive care patients:the single-centre, randomised, outcome assessor-blinded EAT-ICU trial

Purpose: We assessed the effects of early goal-directed nutrition (EGDN) vs. standard nutritional care in adult intensive care unit (ICU) patients. Methods: We randomised acutely admitted, mechanically ventilated ICU patients expected to stay longer than 3 days in the ICU. In the EGDN group we estimated nutritional requirements by indirect calorimetry and 24-h urinary urea aiming at covering 100% of requirements from the first full trial day using enteral and parenteral nutrition. In the standard of care group we aimed at providing 25 kcal/kg/day by enteral nutrition. If this was not met by day 7, patients were supplemented with parenteral nutrition. The primary outcome was physical component summary (PCS) score of SF-36 at 6 months. We performed multiple imputation for data of the non-responders. Results: We randomised 203 patients and included 199 in the intention-to-treat analyses; baseline variables were reasonably balanced between the two groups. The EGDN group had less negative energy (p < 0.001) and protein (p < 0.001) balances in the ICU as compared to the standard of care group. The PCS score at 6 months did not differ between the two groups (mean difference 0.0, 95% CI -5.9 to 5.8, p = 0.99); neither did mortality, rates of organ failures, serious adverse reactions or infections in the ICU, length of ICU or hospital stay, or days alive without life support at 90 days. Conclusions: EGDN did not appear to affect physical quality of life at 6 months or other important outcomes as compared to standard nutrition care in acutely admitted, mechanically ventilated, adult ICU patients.Rigshospitalet; Fresenius Kabi; European Society for Clinical Nutrition and Metabolism (ESPEN); COSMED; Medinor/MedGraphics; CSL Behring; Ferring PharmaceuticalsSCI(E)ARTICLE111637-16474

Long-term mortality and health-related quality of life of lower versus higher oxygenation targets in ICU patients with severe hypoxaemia

Purpose: We assessed outcomes after 1 year of lower versus higher oxygenation targets in intensive care unit (ICU) patients with severe hypoxaemia. Methods: Pre-planned analyses evaluating 1-year mortality and health-related quality-of-life (HRQoL) outcomes in the previously published Handling Oxygenation Targets in the ICU trial which randomised 2928 adults with acute hypoxaemia to targets of arterial oxygen of 8 kPa or 12 kPa throughout the ICU stay up to 90 days. One-year all-cause mortality was assessed in the intention-to-treat population. HRQoL was assessed using EuroQol 5 dimensions 5 levels (EQ-5D-5L) questionnaire and EQ visual analogue scale score (EQ-VAS), and analyses were conducted in both survivors only and the intention-to-treat population with assignment of the worst scores to deceased patients. Results: We obtained 1-year vital status for 2887/2928 (98.6%), and HRQoL for 2600/2928 (88.8%) of the trial population. One year after randomisation, 707/1442 patients (49%) in the lower oxygenation group vs. 704/1445 (48.7%) in the higher oxygenation group had died (adjusted risk ratio 1.00; 95% confidence interval 0.93–1.08, p = 0.92). In total, 1189/1476 (80.4%) 1-year survivors participated in HRQoL interviews: median EQ-VAS scores were 65 (interquartile range 50–80) in the lower oxygenation group versus 67 (50–80) in the higher oxygenation group (p = 0.98). None of the five EQ-5D-5L dimensions differed between groups. Conclusion: Among adult ICU patients with severe hypoxaemia, a lower oxygenation target (8 kPa) did not improve survival or HRQoL at 1 year as compared to a higher oxygenation target (12 kPa)

Phase-3 trial of recombinant human alkaline phosphatase for patients with sepsis-associated acute kidney injury (REVIVAL)

Purpose: Ilofotase alfa is a human recombinant alkaline phosphatase with reno-protective effects that showed improved survival and reduced Major Adverse Kidney Events by 90 days (MAKE90) in sepsis-associated acute kidney injury (SA-AKI) patients. REVIVAL, was a phase-3 trial conducted to confirm its efficacy and safety. Methods: In this international double-blinded randomized-controlled trial, SA-AKI patients were enrolled < 72 h on vasopressor and < 24 h of AKI. The primary endpoint was 28-day all-cause mortality. The main secondary endpoint was MAKE90, other secondary endpoints were (i) days alive and free of organ support through day 28, (ii) days alive and out of the intensive care unit (ICU) through day 28, and (iii) time to death through day 90. Prior to unblinding, the statistical analysis plan was amended, including an updated MAKE90 definition. Results: Six hundred fifty patients were treated and analyzed for safety; and 649 for efficacy data (ilofotase alfa n = 330; placebo n = 319). The observed mortality rates in the ilofotase alfa and placebo groups were 27.9% and 27.9% at 28 days, and 33.9% and 34.8% at 90 days. The trial was stopped for futility on the primary endpoint. The observed proportion of patients with MAKE90A and MAKE90B were 56.7% and 37.4% in the ilofotase alfa group vs. 64.6% and 42.8% in the placebo group. Median [interquartile range (IQR)] days alive and free of organ support were 17 [0–24] and 14 [0–24], number of days alive and discharged from the ICU through day 28 were 15 [0–22] and 10 [0–22] in the ilofotase alfa and placebo groups, respectively. Adverse events were reported in 67.9% and 75% patients in the ilofotase and placebo group. Conclusion: Among critically ill patients with SA-AKI, ilofotase alfa did not improve day 28 survival. There may, however, be reduced MAKE90 events. No safety concerns were identified