Massimo Girardis1, Stefano Busani1, Elisa Damiani2, Abele Donati2, Laura Rinaldi1, Andrea Marudi3, Andrea Morelli4, Massimo Antonelli5, Mervyn Singer6. 1. Intensive Care Unit, Department of Anaesthesiology and Intensive Care, University Hospital of Modena, Modena, Italy. 2. Anaesthesia and Intensive Care Unit, Department of Biomedical Sciences and Public Health, Università Politecnica delle Marche, Torrette di Ancona, Italy. 3. Intensive Care Unit, Department of Anaesthesiology and Intensive Care, NOCSAE Hospital, Modena, Italy. 4. Department of Anesthesiology and Intensive Care, University of Rome, La Sapienza, Rome, Italy. 5. Department of Anaesthesiology and Intensive Care, Catholic University of the Sacred Heart, A. Gemelli University Hospital, Rome, Italy. 6. Bloomsbury Institute of Intensive Care Medicine, University College London, London, United Kingdom.
Abstract
Importance: Despite suggestions of potential harm from unnecessary oxygen therapy, critically ill patients spend substantial periods in a hyperoxemic state. A strategy of controlled arterial oxygenation is thus rational but has not been validated in clinical practice. Objective: To assess whether a conservative protocol for oxygen supplementation could improve outcomes in patients admitted to intensive care units (ICUs). Design, Setting, and Patients: Oxygen-ICU was a single-center, open-label, randomized clinical trial conducted from March 2010 to October 2012 that included all adults admitted with an expected length of stay of 72 hours or longer to the medical-surgical ICU of Modena University Hospital, Italy. The originally planned sample size was 660 patients, but the study was stopped early due to difficulties in enrollment after inclusion of 480 patients. Interventions: Patients were randomly assigned to receive oxygen therapy to maintain Pao2 between 70 and 100 mm Hg or arterial oxyhemoglobin saturation (Spo2) between 94% and 98% (conservative group) or, according to standard ICU practice, to allow Pao2 values up to 150 mm Hg or Spo2 values between 97% and 100% (conventional control group). Main Outcomes and Measures: The primary outcome was ICU mortality. Secondary outcomes included occurrence of new organ failure and infection 48 hours or more after ICU admission. Results: A total of 434 patients (median age, 64 years; 188 [43.3%] women) receivedconventional (n = 218) or conservative (n = 216) oxygen therapy and were included in the modified intent-to-treat analysis. Daily time-weighted Pao2 averages during the ICU stay were significantly higher (P < .001) in the conventional group (median Pao2, 102 mm Hg [interquartile range, 88-116]) vs the conservative group (median Pao2, 87 mm Hg [interquartile range, 79-97]). Twenty-five patients in the conservative oxygen therapy group (11.6%) and 44 in the conventional oxygen therapy group (20.2%) died during their ICU stay (absolute risk reduction [ARR], 0.086 [95% CI, 0.017-0.150]; relative risk [RR], 0.57 [95% CI, 0.37-0.90]; P = .01). Occurrences were lower in the conservative oxygen therapy group for new shock episode (ARR, 0.068 [95% CI, 0.020-0.120]; RR, 0.35 [95% CI, 0.16-0.75]; P = .006) or liver failure (ARR, 0.046 [95% CI, 0.008-0.088]; RR, 0.29 [95% CI, 0.10-0.82]; P = .02) and new bloodstream infection (ARR, 0.05 [95% CI, 0.00-0.09]; RR, 0.50 [95% CI, 0.25-0.998; P = .049). Conclusions and Relevance: Among critically ill patients with an ICU length of stay of 72 hours or longer, aconservative protocol for oxygen therapy vs conventional therapy resulted in lower ICU mortality. These preliminary findings were based on unplanned early termination of the trial, and a larger multicenter trial is needed to evaluate the potential benefit of this approach. Trial Registration: clinicaltrials.gov Identifier: NCT01319643.
RCT Entities:
Importance: Despite suggestions of potential harm from unnecessary oxygen therapy, critically illpatients spend substantial periods in a hyperoxemic state. A strategy of controlled arterial oxygenation is thus rational but has not been validated in clinical practice. Objective: To assess whether a conservative protocol for oxygen supplementation could improve outcomes in patients admitted to intensive care units (ICUs). Design, Setting, and Patients: Oxygen-ICU was a single-center, open-label, randomized clinical trial conducted from March 2010 to October 2012 that included all adults admitted with an expected length of stay of 72 hours or longer to the medical-surgical ICU of Modena University Hospital, Italy. The originally planned sample size was 660 patients, but the study was stopped early due to difficulties in enrollment after inclusion of 480 patients. Interventions: Patients were randomly assigned to receive oxygen therapy to maintain Pao2 between 70 and 100 mm Hg or arterial oxyhemoglobin saturation (Spo2) between 94% and 98% (conservative group) or, according to standard ICU practice, to allow Pao2 values up to 150 mm Hg or Spo2 values between 97% and 100% (conventional control group). Main Outcomes and Measures: The primary outcome was ICU mortality. Secondary outcomes included occurrence of new organ failure and infection 48 hours or more after ICU admission. Results: A total of 434 patients (median age, 64 years; 188 [43.3%] women) received conventional (n = 218) or conservative (n = 216) oxygen therapy and were included in the modified intent-to-treat analysis. Daily time-weighted Pao2 averages during the ICU stay were significantly higher (P < .001) in the conventional group (median Pao2, 102 mm Hg [interquartile range, 88-116]) vs the conservative group (median Pao2, 87 mm Hg [interquartile range, 79-97]). Twenty-five patients in the conservative oxygen therapy group (11.6%) and 44 in the conventional oxygen therapy group (20.2%) died during their ICU stay (absolute risk reduction [ARR], 0.086 [95% CI, 0.017-0.150]; relative risk [RR], 0.57 [95% CI, 0.37-0.90]; P = .01). Occurrences were lower in the conservative oxygen therapy group for new shock episode (ARR, 0.068 [95% CI, 0.020-0.120]; RR, 0.35 [95% CI, 0.16-0.75]; P = .006) or liver failure (ARR, 0.046 [95% CI, 0.008-0.088]; RR, 0.29 [95% CI, 0.10-0.82]; P = .02) and new bloodstream infection (ARR, 0.05 [95% CI, 0.00-0.09]; RR, 0.50 [95% CI, 0.25-0.998; P = .049). Conclusions and Relevance: Among critically illpatients with an ICU length of stay of 72 hours or longer, a conservative protocol for oxygen therapy vs conventional therapy resulted in lower ICU mortality. These preliminary findings were based on unplanned early termination of the trial, and a larger multicenter trial is needed to evaluate the potential benefit of this approach. Trial Registration: clinicaltrials.gov Identifier: NCT01319643.
Authors: Samir Jaber; Giacomo Bellani; Lluis Blanch; Alexandre Demoule; Andrés Esteban; Luciano Gattinoni; Claude Guérin; Nicholas Hill; John G Laffey; Salvatore Maurizio Maggiore; Jordi Mancebo; Paul H Mayo; Jarrod M Mosier; Paolo Navalesi; Michael Quintel; Jean Louis Vincent; John J Marini Journal: Intensive Care Med Date: 2017-08-07 Impact factor: 17.440
Authors: Veli-Pekka Harjola; Wilfried Mullens; Marek Banaszewski; Johann Bauersachs; Hans-Peter Brunner-La Rocca; Ovidiu Chioncel; Sean P Collins; Wolfram Doehner; Gerasimos S Filippatos; Andreas J Flammer; Valentin Fuhrmann; Mitja Lainscak; Johan Lassus; Matthieu Legrand; Josep Masip; Christian Mueller; Zoltán Papp; John Parissis; Elke Platz; Alain Rudiger; Frank Ruschitzka; Andreas Schäfer; Petar M Seferovic; Hadi Skouri; Mehmet Birhan Yilmaz; Alexandre Mebazaa Journal: Eur J Heart Fail Date: 2017-05-30 Impact factor: 15.534