PURPOSE: To assess long-term outcomes of restrictive versus standard intravenous (IV) fluid therapy in adult intensive care unit (ICU) patients with septic shock included in the European Conservative versus Liberal Approach to Fluid Therapy in Septic Shock in Intensive Care (CLASSIC) trial. METHODS: We conducted the pre-planned analyses of mortality, health-related quality of life (HRQoL) using EuroQol (EQ)-5D-5L index values and EQ visual analogue scale (VAS), and cognitive function using Mini Montreal Cognitive Assessment (Mini MoCA) test at 1 year. Deceased patients were assigned numerical zero for HRQoL as a state equal to death and zero for cognitive function outcomes as worst possible score, and we used multiple imputation for missing data on HRQoL and cognitive function. RESULTS: Among 1554 randomized patients, we obtained 1-year data on mortality in 97.9% of patients, HRQoL in 91.3%, and cognitive function in 86.3%. One-year mortality was 385/746 (51.3%) in the restrictive-fluid group versus 383/767 (49.9%) in the standard-fluid group, absolute risk difference 1.5%-points [99% confidence interval (CI) - 4.8 to 7.8]. Mean differences were 0.00 (99% CI - 0.06 to 0.05) for EQ-5D-5L index values, - 0.65 for EQ VAS (- 5.40 to 4.08), and - 0.14 for Mini MoCA (- 1.59 to 1.14) for the restrictive-fluid group versus the standard-fluid group. The results for survivors only were similar in both groups. CONCLUSIONS: Among adult ICU patients with septic shock, restrictive versus standard IV fluid therapy resulted in similar survival, HRQoL, and cognitive function at 1 year, but clinically important differences could not be ruled out.

1st Department of Anaesthesiology and Intensive Therapy Medical University Lublin Lublin Poland

Anaesthesia and Intensive Care Medicine IRCCS Humanitas Research Hospital Rozzano Milan Italy

Anesthesia and Intensive Care Unit Azienda Ospedaliero Universitaria Delle Marche Ancona Italy

Anesthesia and Intensive Care Unit Humanitas Research Hospital Castellanza Italy

Clinical Trial Unit Intensive Care National Audit and Research Centre London UK

Collaboration for Research in Intensive Care Copenhagen Denmark

Copenhagen Academy for Medical Education and Simulation Rigshospitalet Copenhagen Denmark

Copenhagen Trial Unit Centre for Clinical Intervention Research Copenhagen University Hospital Rigshospitalet Copenhagen Denmark

Department of Anaesthesia and Intensive Care Aalborg University Hospital Aalborg Denmark

Department of Anaesthesia and Intensive Care Capio St Görans Hospital Stockholm Sweden

Department of Anaesthesia and Intensive Care Copenhagen University Hospital Bispebjerg Copenhagen Denmark

Department of Anaesthesia and Intensive Care Copenhagen University Hospital North Zealand Hilleroed Denmark

Department of Anaesthesia and Intensive Care Herning Hospital Herning Denmark

Department of Anaesthesia and Intensive Care Holbæk Hospital Holbæk Denmark

Department of Anaesthesia and Intensive Care Humanitas Gavazzeni Hospital Bergamo Bergamo Italy

Department of Anaesthesia and Intensive Care Kolding University Hospital of Southern Denmark Odense Denmark

Department of Anaesthesia and Intensive Care Randers Hospital Randers Denmark

Department of Anaesthesia and Intensive Care Viborg Hospital Viborg Denmark

Department of Anaesthesia and Intensive Care Zealand University Hospital Køge Denmark

Department of Anaesthesia and Intensive Care Zealand University Hospital Roskilde Denmark

Department of Anesthesia and Intensive Care Medicine Hospital Østfold Kalnes Grålum Norway

Department of Anesthesia and Intensive Care Oslo University Hospital Ullevål Oslo Norway

Department of Biomedical Sciences and Public Health Università Politecnica Delle Marche Ancona Italy

Department of Biomedical Sciences Humanitas University Pieve Emanuele Milan Italy

Department of Cardiothoracic Anaesthesia and Intensive Care Copenhagen University Hospital Rigshospitalet Denmark

Department of Clinical Medicine University of Copenhagen Copenhagen Denmark

Department of Clinical Science and Education Södersjukhuset Medical Intensive Care Unit Center for Resuscitation Science Karolinska Institutet Solna Sweden

Department of Emergency Medicine Capio St Görans Hospital Stockholm Sweden

Department of Intensive Care Copenhagen University Hospital Rigshospitalet Blegdamsvej 9 2100 Copenhagen Denmark

Department of Intensive Care Guy's and St Thomas' Hospital London UK

Department of Intensive Care Hospital Innland Hamar Hamar Norway

Department of Intensive Care Medicine Stavanger University Hospital Stavanger Norway

Department of Intensive Care Medicine University Hospital Bern University of Bern Bern Switzerland

Department of Intensive Care Medicine University Hospital Brussels Jette Belgium

Department of Perioperative Medicine and Intensive Care Karolinska University Hospital Huddinge Stockholm Sweden

Department of Perioperative Medicine and Intensive Care Karolinska University Hospital Solna Sweden

Division of Emergencies and Critical Care Department of Anaesthesiology and Intensive Care Medicine Oslo University Hospital Rikshospitalet Oslo Norway

Division of Emergencies and Critical Care Department of Research and Development Oslo University Hospital Oslo Norway

Division of Emergencies and Critical Care Department of Research and Development Oslo University Hospital Rikshospitalet Oslo Norway

Division of Nephrology Faculty of Medicine Excellence Centre in Critical Care Nephrology King Chulalongkorn Memorial Hospital Bangkok Thailand

Faculty of Medicine and Pharmacy Vrije Universiteit Brussel Brussels Belgium

Institute of Clinical Medicine University of Oslo Oslo Norway

Intensive Care Unit Basel University Hospital Basel Switzerland

Medical Intensive Care Unit 1st Department of Internal Medicine Faculty of Medicine Teaching Hospital and Biomedical Center in Pilsen Charles University Pilsen Czech Republic

Section of Anaesthesia and Intensive Care Department of Clinical Science and Education Karolinska Institutet Södersjukhuset Stockholm Sweden

Section of Biostatistics Department of Public Health University of Copenhagen Copenhagen Denmark

Acta Anaesthesiol Scand. 2020 Mar;64(3):410-416. doi: 10.1111/aas.13519. PubMed

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