Comparison of pharmacological and non-pharmacological interventions to prevent delirium in critically ill patients: a protocol for a systematic review incorporating network meta-analyses.
Delirium is characterized by acute changes in mental status including inattention, disorganized thinking, and altered level of consciousness, and is highly prevalent in critically ill adults. Delirium has adverse consequences for both patients and the healthcare system; however, at this time, no effective treatment exists. The identification of effective prevention strategies is therefore a clinical and research imperative. An important limitation of previous reviews of delirium prevention is that interventions were considered in isolation and only direct evidence was used. Our systematic review will synthesize all existing data using network meta-analysis, a powerful statistical approach that enables synthesis of both direct and indirect evidence.



We will search Ovid MEDLINE, CINAHL, Embase, PsycINFO, and Web of Science from 1980 to March 2016. We will search the PROSPERO registry for protocols and the Cochrane Library for published systematic reviews. We will examine reference lists of pertinent reviews and search gr﻿ey literature and the International Clinical Trials Registry Platform for unpublished studies and ongoing trials. We will include randomized and quasi-randomized trials of critically ill adults evaluating any pharmacological, non-pharmacological, or multi-component intervention for delirium prevention, administered in or prior to (i.e., peri-operatively) transfer to the ICU. Two authors will independently screen search results and extract data from eligible studies. Risk of bias assessments will be completed on all included studies. To inform our network meta-analysis, we will first conduct conventional pair-wise meta-analyses for primary and secondary outcomes using random-effects models. We will generate our network meta-analysis using a Bayesian framework, assuming a common heterogeneity parameter across all comparisons, and accounting for correlations in multi-arm studies. We will perform analyses using WinBUGS software.



This systematic review will address the existing knowledge gap regarding best practices for delirium prevention in critically ill adults by synthesizing evidence from trials of pharmacological, non-pharmacological, and multi-component interventions administered in or prior to transfer to the ICU. Use of network meta-analysis will clarify which delirium prevention strategies are most effective in improving clinical outcomes while causing least harm. The network meta-analysis is a novel approach and will provide knowledge users and decision makers with comparisons of multiple interventions of delirium prevention strategies.



PROSPERO CRD42016036313.
Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, ON, Canada.|Department of Pharmacy, Mount Sinai Hospital, 600 University Ave, Rm 18-377, Toronto, ON, M5G1X5, Canada.
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Burry
Clinical Epidemiology Program, Ottawa Hospital Research Institute, The Ottawa Hospital - General Campus, 501 Smyth Rd, Room L1288, Ottawa, ON, K1H8L6, Canada. bhutton@ohri.ca.|School of Epidemiology, Public Health and Preventive Medicine, University of Ottawa, Ottawa, ON, Canada. bhutton@ohri.ca.
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0000-0001-5662-8647
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Hutton
Department of Pharmacy, Mount Sinai Hospital, 600 University Ave, Rm 18-377, Toronto, ON, M5G1X5, Canada.
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Guenette
Faculté de pharmacie, Université de Montréal, Montreal, QC, Canada.|Département de pharmacie, hôpital du Sacré-Coeur, Montreal, QC, Canada.
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Williamson
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.
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Mehta
University of Copenhagen, Rigshospitalet, Neurointensive Intensive Care, Blegdamsvej 9, DK-2100, Copenhagen O, Denmark.
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Egerod
Clinical Epidemiology Program, Ottawa Hospital Research Institute, The Ottawa Hospital - General Campus, 501 Smyth Rd, Room L1288, Ottawa, ON, K1H8L6, Canada.|Department of Pharmacy, The Ottawa Hospital, Ottawa, ON, Canada.
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Kanji
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 & Critical Care Research Program, Sunnybrook Research Institute, Toronto, ON, Canada.
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Adhikari
Clinical Epidemiology Program, Ottawa Hospital Research Institute, The Ottawa Hospital - General Campus, 501 Smyth Rd, Room L1288, Ottawa, ON, K1H8L6, Canada.|School of Epidemiology, Public Health and Preventive Medicine, University of Ottawa, Ottawa, ON, Canada.
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Moher
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.
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Martin
Department of Critical Care Medicine, Sunnybrook Health Sciences Centre, Toronto, ON, Canada.|Evaluative Clinical Sciences, Trauma, Emergency & 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.
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Rose
D016638:Critical Illness / Q000523:psychology / Q000628:therapy*; D003693:Delirium / Q000188:drug therapy* / Q000517:prevention & control*; D006801:Humans; D007362:Intensive Care Units; D000078202:Systematic Reviews as Topic; D016896:Treatment Outcome; D000071076:Network Meta-Analysis as Topic
Delirium; Intensive care unit; Network meta-analysis; Prevention