title: Comparison of sedation strategies for critically ill patients: a protocol for a systematic review incorporating network meta-analyses.
abstract: Sedatives and analgesics are administered to provide sedation and manage agitation and pain in most critically ill mechanically ventilated patients. Various sedation administration strategies including protocolized sedation and daily sedation interruption are used to mitigate drug pharmacokinetic limitations and minimize oversedation, thereby shortening the duration of mechanical ventilation. At present, it is unclear which strategy is most effective, as few have been directly compared. Our review will use network meta-analysis (NMA) to compare and rank sedation strategies to determine their efficacy and safety for mechanically ventilated patients.
  
  
  
  We will search the following from 1980 to March 2016: Ovid MEDLINE, CINAHL, Embase, PsycINFO, and Web of Science. We will also search the Cochrane Library, gray literature, and the International Clinical Trials Registry Platform. We will use a validated randomized control trial search filter to identify studies evaluating any strategy to optimize sedation in mechanically ventilated adult patients. Authors will independently extract data from eligible studies in duplicate and complete the Cochrane Risk of Bias tool. Our outcomes of interest include duration of mechanical ventilation, time to first extubation, ICU and hospital length of stay, re-intubation, tracheostomy, mortality, total sedative and opioid exposure, health-related quality of life, and adverse events. To inform our NMA, we will first conduct conventional pair-wise meta-analyses using random-effects models. Where appropriate, we will perform Bayesian NMA using WinBUGS software.
  
  
  
  There are multiple strategies to optimize sedation for mechanically ventilated patients. Current ICU guidelines recommend protocolized sedation or daily sedation interruption. Our systematic review incorporating NMA will provide a unified analysis of all sedation strategies to determine the relative efficacy and safety of interventions that may not have been compared directly. We will provide knowledge users, decision makers, and professional societies with ranking of multiple sedation strategies to inform future sedation guidelines.
  
  
  
  PROSPERO CRD42016037480.
authors.affiliation: Clinical Epidemiology Program, Ottawa Hospital Research Institute, The Ottawa Hospital, General Campus, 501 Smyth Rd, Ottawa, ON, K1H8L6, Canada. bhutton@ohri.ca.|School of Epidemiology, Public Health and Preventive Medicine, University of Ottawa, Ottawa, ON, Canada. bhutton@ohri.ca.
authors.forename: Brian
authors.identifier: 0000-0001-5662-8647
authors.initials: B
authors.lastname: Hutton
authors.affiliation: Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, ON, Canada.|Department of Pharmacy, Mount Sinai Hospital, 600 University Avenue, Toronto, ON, M5G1X5, Canada.
authors.forename: Lisa D
authors.initials: LD
authors.lastname: Burry
authors.affiliation: Clinical Epidemiology Program, Ottawa Hospital Research Institute, The Ottawa Hospital, General Campus, 501 Smyth Rd, Ottawa, ON, K1H8L6, Canada.|Department of Pharmacy, The Ottawa Hospital, Ottawa, ON, Canada.
authors.forename: Salmaan
authors.initials: S
authors.lastname: Kanji
authors.affiliation: Department of Medicine, Interdepartmental Division of Critical Care, University of Toronto, Toronto, ON, Canada.|Department of Medicine, Division of Critical Care, Mount Sinai Hospital, Toronto, ON, Canada.
authors.forename: Sangeeta
authors.initials: S
authors.lastname: Mehta
authors.affiliation: Department of Pharmacy, Mount Sinai Hospital, 600 University Avenue, Toronto, ON, M5G1X5, Canada.
authors.forename: Melanie
authors.initials: M
authors.lastname: Guenette
authors.affiliation: Department of Medicine, Division of Critical Care, Schulich School of Medicine and Dentistry, Western University, London, ON, Canada.|Lawson Health Research Institute, London Health Sciences Centre, London, ON, Canada.
authors.forename: Claudio M
authors.initials: CM
authors.lastname: Martin
authors.affiliation: Clinical Epidemiology Program, Ottawa Hospital Research Institute, The Ottawa Hospital, General Campus, 501 Smyth Rd, Ottawa, ON, K1H8L6, Canada.|Department of Medicine, University of Ottawa, Ottawa, ON, Canada.|Centre for Practice-Changing Research, Ottawa Hospital Research Institute, Ottawa, ON, Canada.
authors.forename: Dean A
authors.initials: DA
authors.lastname: Fergusson
authors.affiliation: Department of Medicine, Interdepartmental Division of Critical Care, University of Toronto, Toronto, ON, Canada.|Department of Critical Care Medicine, Sunnybrook Health Sciences Centre, Toronto, ON, Canada.|Evaluative Clinical Sciences, Trauma, Emergency and Critical Care Research Program, Sunnybrook Research Institute, Toronto, ON, Canada.
authors.forename: Neill K
authors.initials: NK
authors.lastname: Adhikari
authors.affiliation: University of Copenhagen, Rigshospitalet, Neurointensive Intensive Care, Copenhagen O, Denmark.
authors.forename: Ingrid
authors.initials: I
authors.lastname: Egerod
authors.affiliation: Faculté de Pharmacie, Université de Montréal, Montreal, QC, Canada.|Département de Pharmacie, Hôpital du Sacré-Coeur, Montreal, QC, Canada.
authors.forename: David
authors.initials: D
authors.lastname: Williamson
authors.affiliation: Knowledge Translation Program, Li Ka Shing Knowledge Institute, Saint Michael's Hospital, Toronto, ON, Canada.
authors.forename: Sharon
authors.initials: S
authors.lastname: Straus
authors.affiliation: Clinical Epidemiology Program, Ottawa Hospital Research Institute, The Ottawa Hospital, General Campus, 501 Smyth Rd, Ottawa, ON, K1H8L6, Canada.|School of Epidemiology, Public Health and Preventive Medicine, University of Ottawa, Ottawa, ON, Canada.|Centre for Practice-Changing Research, Ottawa Hospital Research Institute, Ottawa, ON, Canada.
authors.forename: David
authors.initials: D
authors.lastname: Moher
authors.affiliation: Department of Medicine, Vanderbilt University Medical Center, Health Services Research Center, Nashville, TN, USA.
authors.forename: E Wesley
authors.initials: EW
authors.lastname: Ely
authors.affiliation: Department of Critical Care Medicine, Sunnybrook Health Sciences Centre, Toronto, ON, Canada.|Evaluative Clinical Sciences, Trauma, Emergency and Critical Care Research Program, Sunnybrook Research Institute, Toronto, ON, Canada.|Lawrence S. Bloomberg Faculty of Nursing, University of Toronto, Toronto, ON, Canada.|Institute for Clinical Evaluative Sciences, Toronto, ON, Canada.|Provincial Centre of Weaning Excellence, Toronto East General Hospital, Toronto, ON, Canada.
authors.forename: Louise
authors.initials: L
authors.lastname: Rose
mesh_terms: D016292:Procedural Sedation / Q000379:methods*; D016638:Critical Illness / Q000628:therapy*; D006801:Humans; D007902:Length of Stay; D011788:Quality of Life; D012121:Respiration, Artificial; D000078202:Systematic Reviews as Topic; D000071076:Network Meta-Analysis as Topic
keywords: Daily sedation interruption; Intensive care; Mechanical ventilation; Network meta-analysis; Sedation protocol; Systematic review