title: The use of volatile anesthetic agents for long-term critical care sedation (VALTS): study protocol for a pilot randomized controlled trial.
abstract: BACKGROUND
  Sedatives are administered to 85% of intensive care unit (ICU) patients. The most commonly used sedatives are intravenous benzodiazepines and propofol. These agents are associated with over-sedation in 40 to 60% of patients, which can lead to prolonged intubation, delirium and drug-induced hypotension. Evidence is increasing that volatile anesthetic agents are associated with faster extubation times, improved cardiovascular stability with no end-organ toxicity in comparison to our standard intravenous agents for short-term critical care sedation. Use of volatile agents within the ICU is a novel technique using a specialized delivery and scavenging system, which requires staff training and cultural acceptance. This pilot randomized controlled trial aims to assess the safety and feasibility of delivering volatile agents for long-term patient sedation in the ICU with limited or no experience of this technique.
  
  
  METHODS
  This is a prospective multicenter pragmatic pilot RCT that is blinded to the data analyst. This study aims to recruit 60 adult ICU patients requiring mechanical ventilation and sedation for more than 48 h. Patients will be randomized 2:1 to receive inhaled isoflurane (40 patients) or intravenous midazolam and/or propofol (20 patients) sedation. Sedation is titrated to a targeted Sedation Analgesia Score (SAS) using an explicit sedation-analgesia algorithm until extubation or tracheostomy. Primary safety and feasibility outcomes will assess atmospheric volatile concentration levels and adherence to our sedation-analgesia protocol. Secondary outcomes include time to extubation, duration of ventilation, quality of sedation, delirium, vasoactive drug support, length of stay, serum fluoride levels and mortality.
  
  
  CONCLUSIONS
  This pilot project will serve as the basis for a larger RCT that will be powered for important clinical outcomes.
  
  
  BACKGROUND
  ClinicalTrials.gov, NCT01983800 (registration date 2 July 2013).
authors.affiliation: Department Anesthesia and Pain Medicine, Toronto General Hospital, 200 Elizabeth St, Toronto, Ontario, M5G 2C4, Canada. Angela.Jerath@uhn.ca.
authors.forename: Angela
authors.initials: A
authors.lastname: Jerath
authors.affiliation: Department Critical Care Medicine, Toronto General Hospital, 200 Elizabeth St, Toronto, Ontario, M5G 2C4, Canada. Niall.Ferguson@uhn.ca.
authors.forename: Niall D
authors.initials: ND
authors.lastname: Ferguson
authors.affiliation: Department Critical Care Medicine and Anesthesia, Toronto General Hospital, 200 Elizabeth St, Toronto, Ontario, M5G 2C4, Canada. Andrew.steel@uhn.ca.
authors.forename: Andrew
authors.initials: A
authors.lastname: Steel
authors.affiliation: Department Anesthesia and Pain Medicine, Toronto General Hospital, 200 Elizabeth St, Toronto, Ontario, M5G 2C4, Canada. Duminda.Wijeysundera@uhn.ca.
authors.forename: Duminda
authors.initials: D
authors.lastname: Wijeysundera
authors.affiliation: Department Anesthesia, University of Ottawa Heart Institute, 40 Ruskin St, Ottawa, Ontario, K1Y 4W7, Canada. jmacdonald@ottawaheart.ca.
authors.forename: John
authors.initials: J
authors.lastname: Macdonald
authors.affiliation: Department Anesthesia and Pain Medicine, Toronto General Hospital, 200 Elizabeth St, Toronto, Ontario, M5G 2C4, Canada. marcin.wasowicz@uhn.ca.
authors.forename: Marcin
authors.initials: M
authors.lastname: Wasowicz
mesh_terms: D060666:Airway Extubation; D018685:Anesthetics, Inhalation / Q000008:administration & dosage* / Q000009:adverse effects; D018686:Anesthetics, Intravenous / Q000008:administration & dosage; D002985:Clinical Protocols; D003422:Critical Care / Q000379:methods*; D054810:Deep Sedation / Q000009:adverse effects / Q000379:methods*; D005240:Feasibility Studies; D006801:Humans; D007362:Intensive Care Units; D007530:Isoflurane / Q000008:administration & dosage* / Q000009:adverse effects; D008134:Long-Term Care / Q000379:methods*; D008874:Midazolam / Q000008:administration & dosage; D009864:Ontario; D010865:Pilot Projects; D015742:Propofol / Q000008:administration & dosage; D011446:Prospective Studies; D012107:Research Design; D012121:Respiration, Artificial; D013997:Time Factors; D014139:Tracheostomy; D016896:Treatment Outcome; D014835:Volatilization
chemical_list: D018685:Anesthetics, Inhalation; D018686:Anesthetics, Intravenous; D007530:Isoflurane; D008874:Midazolam; D015742:Propofol