title: Non-sedation versus sedation with a daily wake-up trial in critically ill patients receiving mechanical ventilation (NONSEDA Trial): study protocol for a randomised controlled trial.
abstract: BACKGROUND
  Through many years, the standard care has been to use continuous sedation of critically ill patients during mechanical ventilation. However, preliminary randomised clinical trials indicate that it is beneficial to reduce the sedation level. No randomised trial has been conducted comparing sedation with no sedation, a priori powered to have all-cause mortality as primary outcome.The objective is to assess the benefits and harms of non-sedation versus sedation with a daily wake-up trial in critically ill patients.
  
  
  METHODS
  The non-sedation (NONSEDA) trial is an investigator-initiated, randomised, clinical, parallel-group, multinational trial designed to include 700 patients from at least six ICUs in Denmark, Norway and Sweden.Inclusion criteria are mechanically ventilated patients with expected duration of mechanical ventilation >24 hours.Exclusion criteria are non-intubated patients, patients with severe head trauma, coma at admission or status epilepticus, patients treated with therapeutic hypothermia, patients with PaO2/FiO2 < 9 where sedation might be necessary to ensure sufficient oxygenation or place the patient in prone position.Experimental intervention is non-sedation supplemented with pain management during mechanical ventilation.Control intervention is sedation with a daily wake-up trial.The primary outcome will be all cause mortality at 90 days after randomization. Secondary outcomes will be: days until death throughout the total observation period; coma- and delirium-free days; highest RIFLE score; days until discharge from the intensive care unit (within 28 days); days until the participant is without mechanical ventilation (within 28 days); and proportion of patients with a major cardiovascular outcome. Explorative outcomes will be: all cause mortality at 28 days after randomisation; days until discharge from the intensive care unit; days until the participant is without mechanical ventilation; days until discharge from the hospital; organ failure.Trial size: we will include 700 participants (2 × 350) in order to detect or reject 25% relative risk reduction in mortality with a type I error risk of 5% and a type II error risk of 20% (power at 80%).
  
  
  CONCLUSIONS
  The trial investigates potential benefits of non-sedation. This might have large impact on the future treatment of mechanically ventilated critically ill patients.
  
  
  BACKGROUND
  ClinicalTrials.gov NCT0196768, 09.01.2014.
authors.affiliation: Department Anaesthesiology and Intensive Care, Odense University Hospital, Sdr, Boulevard 29, DK - 5000 Odense C, Denmark. Palle.Toft@rsyd.dk.
authors.forename: Palle
authors.initials: P
authors.lastname: Toft
authors.forename: Hanne Tanghus
authors.initials: HT
authors.lastname: Olsen
authors.forename: Helene Korvenius
authors.initials: HK
authors.lastname: Jørgensen
authors.forename: Thomas
authors.initials: T
authors.lastname: Strøm
authors.forename: Helle Lykkeskov
authors.initials: HL
authors.lastname: Nibro
authors.forename: Jacob
authors.initials: J
authors.lastname: Oxlund
authors.forename: Karl-Andre
authors.initials: KA
authors.lastname: Wian
authors.forename: Lars Marius
authors.initials: LM
authors.lastname: Ytrebø
authors.forename: Bjørn Anders
authors.initials: BA
authors.lastname: Kroken
authors.forename: Michelle
authors.initials: M
authors.lastname: Chew
mesh_terms: D002985:Clinical Protocols; D003243:Consciousness / Q000187:drug effects*; D016638:Critical Illness; D004334:Drug Administration Schedule; D017052:Hospital Mortality; D006801:Humans; D006993:Hypnotics and Sedatives / Q000008:administration & dosage* / Q000009:adverse effects; D007362:Intensive Care Units; D010351:Patient Discharge; D012107:Research Design; D012121:Respiration, Artificial / Q000009:adverse effects / Q000401:mortality; D012537:Scandinavian and Nordic Countries; D013997:Time Factors; D016896:Treatment Outcome; D015300:Ventilator Weaning
chemical_list: D006993:Hypnotics and Sedatives