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Hyperosmolar therapy for acute brain injury: study protocol for an umbrella review of meta-analyses and an evidence mapping
  1. Rafael Badenes1,2,3,
  2. Brian Hutton4,5,
  3. Giuseppe Citerio6,7,
  4. Chiara Robba8,
  5. Gerardo Aguilar1,3,
  6. Adolfo Alonso-Arroyo9,10,
  7. Fabio Silvio Taccone11,
  8. Carlos Tornero1,
  9. Ferrán Catalá-López3,5,12,13
  1. 1 Department of Anesthesiology and Surgical-Trauma Intensive Care, Hospital Clinic Universitari de València, University of Valencia, Valencia, Spain
  2. 2 Department of Surgery, Faculty of Medicine, University of Valencia, Valencia, Spain
  3. 3 INCLIVA Health Research Institute, Valencia, Spain
  4. 4 School of Epidemiology and Public Health, University of Ottawa, Ottawa, Ontario, Canada
  5. 5 Clinical Epidemiology Program, Ottawa Hospital Research Institute, Ottawa, Ontario, Canada
  6. 6 Neurointensive Care, San Gerardo Hospital, ASST-Monza, Monza, Italy
  7. 7 School of Medicine and Surgery, University Milano Bicocca, Milan, Italy
  8. 8 Department of Anesthesia and Intensive Care, IRCCS Policlinico San Martino, Genoa, Italy
  9. 9 Department of History of Science and Documentation, University of Valencia, Valencia, Spain
  10. 10 Information and Social and Health Research Unit (UISYS), University of Valencia and Spanish National Research Council (CSIC), Valencia, Spain
  11. 11 Department of Intensive Care, Erasme Hospital, Université Libre de Bruxelles, Brussels, Belgium
  12. 12 Department of Health Planning and Economics, National School of Public Health, Institute of Health Carlos III, Madrid, Spain
  13. 13 Department of Medicine, Faculty of Medicine, University of Valencia/CIBERSAM, Valencia, Spain
  1. Correspondence to Dr Ferrán Catalá-López; ferran_catala{at}


Introduction Acute brain injury is a challenging public health problem worldwide. Elevated intracranial pressure is a common complication after acute brain injury. Hyperosmolar therapy is one of the main therapeutic strategies for the management of intracranial hypertension. This study protocol outlines an umbrella review of meta-analyses which will investigate the benefits and harms of hyperosmolar therapy routinely used for the management of acute brain injury in the intensive care.

Methods and analysis We will search PubMed/MEDLINE, EMBASE and the Cochrane Database of Systematic Reviews. We will include meta-analyses of primary research studies (eg, randomised controlled trials, observational studies or both) that evaluate one or more hyperosmolar solutions (including hypertonic saline and/or mannitol) for the treatment of adult patients with acute brain injury of any severity. Two researchers will independently screen all citations, full-text articles and abstract data. Potential conflicts will be resolved through discussion with a third researcher. Primary outcomes will be mortality and neurological outcomes at discharge. Secondary outcomes will include control of intracranial pressure, cerebral perfusion pressure, length of stay (in hospital an intensive care unit) and any adverse event. Quality of the included meta-analyses will be assessed using the AMSTAR-2 tool. An overall summary of methods and results will be performed using tabular and graphical approaches and will be supplemented by narrative description. We will analyse whether published meta-analyses present an outline of available evidence (eg, cited, described and discussed any previous meta-analysis). Where objectives from two or more meta-analyses overlap, we will assess the causes of any noted discrepancies between meta-analyses.

Ethics and dissemination No ethical approval will be required. Findings from this study will be published in a peer-reviewed journal. All data will be deposited in a cross-disciplinary public repository.

PROSPERO registration number CRD42019148152.

  • brain injury
  • hyperosmolar therapy
  • hypertonic saline
  • mannitol
  • meta-analysis
  • systematic review

This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See:

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  • Contributors All authors contributed to conceptualising and designing the study. FC-L and RB drafted the manuscript. BH, GC, CR, GA, AA-A, FT and CT commented for important intellectual content and made revisions. All authors read and approved the final version of the manuscript. RB and FC-L accept full responsibility for the finished manuscript and controlled the decision to publish.

  • Funding FC-L is supported by the Institute of Health Carlos III/CIBERSAM. BH is supported by a New Investigator Award from the Canadian Institutes of Health Research and the Drug Safety and Effectiveness Network. The funders were not involved in the design of the protocol or decision to submit the protocol for publication, nor will they be involved in any aspect of the study conduct. The views expressed in this manuscript are those of the authors and many not be understood or quoted as being made on behalf of, or reflecting the position of, the funder(s) or any institution.

  • Competing interests None declared.

  • Patient consent for publication Not required.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data availability statement Data sharing not applicable as no data sets generated and/or analysed for this study.

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