Impact of early enteral versus parenteral nutrition on mortality in patients requiring mechanical ventilation and catecholamines: study protocol for a randomized controlled trial (NUTRIREA-2)

BACKGROUND: Nutritional support is crucial to the management of patients receiving invasive mechanical ventilation (IMV) and the most commonly prescribed treatment in intensive care units (ICUs). International guidelines consistently indicate that enteral nutrition (EN) should be preferred over parenteral nutrition (PN) whenever possible and started as early as possible. However, no adequately designed study has evaluated whether a specific nutritional modality is associated with decreased mortality. The primary goal of this trial is to assess the hypothesis that early first-line EN, as compared to early first-line PN, decreases day 28 all-cause mortality in patients receiving IMV and vasoactive drugs for shock. METHODS/DESIGN: The NUTRIREA-2 study is a multicenter, open-label, parallel-group, randomized controlled trial comparing early PN versus early EN in critically ill patients requiring IMV for an expected duration of at least 48 hours, combined with vasoactive drugs, for shock. Patients will be allocated at random to first-line PN for at least 72 hours or to first-line EN. In both groups, nutritional support will be started within 24 hours after IMV initiation. Calorie targets will be 20 to 25 kcal/kg/day during the first week, then 25 to 30 kcal/kg/day thereafter. Patients receiving PN may be switched to EN after at least 72 hours in the event of shock resolution (no vasoactive drugs for 24 consecutive hours and arterial lactic acid level below 2 mmol/L). On day 7, all patients receiving PN and having no contraindications to EN will be switched to EN. In both groups, supplemental PN may be added to EN after day 7 in patients with persistent intolerance to EN and inadequate calorie intake. We plan to recruit 2,854 patients at 44 participating ICUs. DISCUSSION: The NUTRIREA-2 study is the first large randomized controlled trial designed to assess the hypothesis that early EN improves survival compared to early PN in ICU patients. Enrollment started on 22 March 2013 and is expected to end in November 2015. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01802099 (registered 27 February 2013)

Improved atmospheric circulation over Europe by the new generation of CMIP6 earth system models

ABSTRACT: Global Climate Models (GCMs) generally exhibit significant biases in the representation of large-scale atmospheric circulation. Even after a sensible bias adjustment these errors remain and are inherited to some extent by the derived downscaling products, impairing the credibility of future regional projections. In this study we perform a process-based evaluation of state-of-the-art GCMs from CMIP5 and CMIP6, with a focus on the simulation of the synoptic climatological patterns having a most prominent effect on the European climate. To this aim, we use the Lamb Weather Type Classification (LWT, Lamb British isles weather types and a register of the daily sequence 736 of circulation patterns 1861-1971. METEOROL OFF, GEOPHYS MEM; 737 GB; DA 1972; NO 116; PP 1-85; BIBL 2P1/2, 1972), a subjective classification of circulation weather types constructed upon historical simulations of daily mean sea level pressure. Observational uncertainty has been taken into account by considering four different reanalysis products of varying characteristics. Our evaluation unveils an overall improvement of salient atmospheric circulation features consistent across observational references, although this is uneven across models and large frequency biases still remain for the main LWTs. Some CMIP6 models attain similar or even worse results than their CMIP5 counterparts, although in most cases consistent improvements have been found, demonstrating the ability of the new models to better capture key synoptic conditions. In light of the large differences found across models, we advocate for a careful selection of driving GCMs in downscaling experiments with a special focus on large-scale atmospheric circulation aspects.We acknowledge the World Climate Research Pro-gram’s Working Group on Coupled Modelling, which is responsible for CMIP, and we thank the climate modeling groups (listed in Table 1) 3538 J. A. Fernandez-Granja et al.1 3for producing and making available their model output. J.A.F., A.C and J.B. acknowledge funding from the Project INDECIS, part of Euro-pean Research Area for Climate Services Consortium (ERA4CS) with co-funding by the European Union Grant 690462. J.F. acknowledges support from the Spanish R&D Program through project INSIGNIA (CGL2016-79210-R), co-funded by the European Regional Develop-ment Fund (ERDF/ FEDER). We also thank the Santander Climate Data Service (http://scds.es) and our colleagues Antonio Cofiño and Ezequiel Cimadevilla for their support. Sixto Herrera and José M. Gutiérrez provided useful comments on earlier stages of this study. Finally, we thank two anonymous referees for their insightful comments that helped to improve the original manuscrip