{
  "abstract": "Introduction Inhaled anaesthetics can be used in mechanically ventilated critically ill patients to provide sedation. This approach to sedation potentially improves patient and health system outcomes, but further supportive evidence is needed. The objective of the SAVE-ICU clinical trial is to compare the effectiveness of inhaled versus intravenous sedation in ventilated adults with acute hypoxaemic respiratory failure.Methods and analysis SAVE-ICU is a multicentre, open-label, pragmatic, randomised controlled trial conducted in 15 intensive care units (ICUs) in Canada and the USA. Eligible patients include mechanically ventilated and sedated adults with acute hypoxemic respiratory failure from COVID-19 or non-COVID causes with PaO 2/FIO2 ratio <300 mm Hg. Patients are excluded with a history of malignant hyperthermia, allergy to sedative agents, raised intracranial pressure, need for concomitant prostacyclin, low tidal volumes (<200 mL), one-lung ventilation or pneumonectomy, severe neuromuscular disorder (eg, amyotrophic lateral sclerosis, Guillain-Barré syndrome), pregnancy or moribund status (unlikely to survive >12 hour). A hierarchy of outcomes was identified at the time of trial design, as the trial was launched during the COVID-19 pandemic when study drug shortages, staffing challenges and healthcare system pressures were prevalent and there was a requirement for rapid evidence generation and implementation on this topic. The primary outcome and highest in the hierarchy is hospital mortality (requiring 758 participants). Secondary and lower hierarchical outcomes are ventilator-free days at day 30 (200 patients), quality of life at 3 months (144 participants) and ICU-free days at day 30 (128 participants). Additional secondary outcomes include median daily oxygenation at day 3 (PaO2/FIO2 ratio), need for adjunctive acute respiratory distress syndrome therapies (prone positioning, inhaled nitric oxide, paralysis with a neuromuscular blocking agent and extracorporeal membrane oxygenation) during ICU stay, days alive and free from delirium and coma at day 14, hospital-free days at day 60 and disability score at 3 months and 12 months after enrolment.Ethics and dissemination The protocol was approved by all hospital ethics committees and by Health Canada. Informed consent will be obtained from substitute decision makers or deferred consent (as permitted by site ethics board). Trial findings will be shared at the end of the study using peer-review publications, conference presentations and social media as part of the trial knowledge translation plan.Trial registration number NCT04415060.",
  "authors": [
    {
      "affiliations": [
        "Department of Anesthesiology and Pain Medicine, Sunnybrook Research Institute, Toronto, Ontario, Canada",
        "Department of Anesthesiology and Pain Medicine, University of Toronto Temerty Faculty of Medicine, Toronto, Ontario, Canada",
        "Sunnybrook Research Institute, Toronto, Ontario, Canada"
      ],
      "name": "Angela Jerath"
    },
    {
      "affiliations": [
        "Lawson Health Research Institute, London, Ontario, Canada",
        "Medicine, Western University, London, Ontario, Canada"
      ],
      "name": "Marat Slessarev"
    },
    {
      "affiliations": [
        "Lawson Health Research Institute, London, Ontario, Canada",
        "Medicine, Western University, London, Ontario, Canada"
      ],
      "name": "Claudio Martin"
    },
    {
      "affiliations": [
        "Anesthesiology, Universite de Sherbrooke Faculte de medecine et des sciences de la sante, Sherbrooke, Quebec, Canada"
      ],
      "name": "Frederick D’Aragon"
    },
    {
      "affiliations": [
        "Anesthesiology, Centre Hospitalier de l’Universite de Montreal, Montreal, Québec, Canada"
      ],
      "name": "Francois Martin Carrier"
    },
    {
      "affiliations": [
        "Grey Nuns Community Hospital, Edmonton, Alberta, Canada"
      ],
      "name": "Janek Senaratne"
    },
    {
      "affiliations": [
        "The Ottawa Hospital Research Institute, Ottawa, Ontario, Canada"
      ],
      "name": "Hilary Meggison"
    },
    {
      "affiliations": [
        "The Ottawa Hospital Research Institute, Ottawa, Ontario, Canada"
      ],
      "name": "Jonathan Hooper"
    },
    {
      "affiliations": [
        "Hopital du Sacre-Coeur de Montreal, Montreal, Québec, Canada"
      ],
      "name": "Yiorgos Alexandros Cavayas"
    },
    {
      "affiliations": [
        "Toronto General Hospital, Toronto, Ontario, Canada"
      ],
      "name": "Ewan C Goligher"
    },
    {
      "affiliations": [
        "IUCPQ-ULaval, Québec City, Quebec, Canada"
      ],
      "name": "Etienne J Couture"
    },
    {
      "affiliations": [
        "Toronto Western Hospital, Toronto, Ontario, Canada"
      ],
      "name": "Ian Randall"
    },
    {
      "affiliations": [
        "Royal Victoria Hospital, Montreal, Québec, Canada"
      ],
      "name": "Roupen Hatzakorzian"
    },
    {
      "affiliations": [
        "University of Alberta Hospital, Edmonton, Alberta, Canada"
      ],
      "name": "Michael Jacka"
    },
    {
      "affiliations": [
        "Massachusetts General Hospital, Boston, Massachusetts, USA"
      ],
      "name": "Jeanine Wiener-Kronish"
    },
    {
      "affiliations": [
        "Massachusetts General Hospital, Boston, Massachusetts, USA"
      ],
      "name": "Zhongcong Xie"
    },
    {
      "affiliations": [
        "Sunnybrook Research Institute, Toronto, Ontario, Canada"
      ],
      "name": "Ruxandra L Pinto"
    },
    {
      "affiliations": [
        "Department of Anesthesiology and Pain Medicine, University of Toronto Temerty Faculty of Medicine, Toronto, Ontario, Canada",
        "Sunnybrook Research Institute, Toronto, Ontario, Canada"
      ],
      "name": "Brian Cuthbertson"
    },
    {
      "affiliations": [],
      "name": "SAVE-ICU Investigators and the Canadian Critical Care Trials Group"
    }
  ],
  "title": "Sedating with volatile anaesthetics for COVID-19 and non-COVID-19 acute hypoxaemic respiratory failure patients in ICU (SAVE-ICU): protocol for a randomised clinical trial",
  "uid": "8eb1fb31-f40b-55bc-8e64-22ee88fb8c1d"
}