Mucoactive agents for acute respiratory failure in the critically ill: a systematic review and meta-analysis

Rohan Anand, Daniel F Mcauley, Bronagh Blackwood, Chee Yap, Brenda Oneill, Bronwen Connolly, Mark Borthwick, Murali Shyamsundar, John Warburton, David Van Meenen, Frederique Paulus, Marcus J Schultz, Paul Dark, Judy M Bradley

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PURPOSE: Acute respiratory failure (ARF) is a common cause of admission to intensive care units (ICUs). Mucoactive agents are medications that promote mucus clearance and are frequently administered in patients with ARF, despite a lack of evidence to underpin clinical decision making. The aim of this systematic review was to determine if the use of mucoactive agents in patients with ARF improves clinical outcomes.

METHODS: We searched electronic and grey literature (January 2020). Two reviewers independently screened, selected, extracted data and quality assessed studies. We included trials of adults receiving ventilatory support for ARF and involving at least one mucoactive agent compared with placebo or standard care. Outcomes included duration of mechanical ventilation. Meta-analysis was undertaken using random-effects modelling and certainty of the evidence was assessed using Grades of Recommendation, Assessment, Development and Evaluation.

RESULTS: Thirteen randomised controlled trials were included (1712 patients), investigating four different mucoactive agents. Mucoactive agents showed no effect on duration of mechanical ventilation (seven trials, mean difference (MD) -1.34, 95% CI -2.97 to 0.29, I2=82%, very low certainty) or mortality, hospital stay and ventilator-free days. There was an effect on reducing ICU length of stay in the mucoactive agent groups (10 trials, MD -3.22, 95% CI -5.49 to -0.96, I2=89%, very low certainty).

CONCLUSION: Our findings do not support the use of mucoactive agents in critically ill patients with ARF. The existing evidence is of low quality. High-quality randomised controlled trials are needed to determine the role of specific mucoactive agents in critically ill patients with ARF.
PROSPERO registration number CRD42018095408.
Original languageEnglish
Pages (from-to)623-631
Number of pages9
Issue number8
Early online date8 Jun 2020
Publication statusPublished - 15 Jul 2020

Bibliographical note

Funding Information:
1Wellcome-Wolfson institute for experimental Medicine, Queen’s University Belfast, Belfast, UK 2centre for health and rehabilitation Technologies, institute of nursing and health research, Ulster University, newtownabbey, UK 3Department of Physiotherapy, The University of Melbourne, Melbourne, Victoria, australia 4lane Fox respiratory Unit, guy’s and saint Thomas’ nhs Foundation Trust, london, UK 5Oxford critical care, Oxford University hospitals nhs Foundation Trust, Oxford, UK 6Bristol royal infirmary, University hospitals Bristol nhs Foundation Trust, Bristol, UK 7University of amsterdam, academic Medical center Department of intensive care Medicine, amsterdam, noord-holland, netherlands 8Mahidol University, Mahidol Oxford Tropical Medicine research Unit, Bangkok, Thailand 9nuffield Department of Medicine, Oxford University, Oxford, UK 10Division of infection, immunity and respiratory Medicine, nihr Manchester Biomedical research centre, The University of Manchester, Manchester, UK Acknowledgements We would like to thank rebecca lancaster from Queen’s University Belfast for help with the translation and screening of german language papers. We also thank the neBUlae investigators for providing subgroup data for their trial that was funded by a grant from The netherlands Organisation for health research and Development (ZonMW). We would also like to acknowledge the Professor John glover award for support. lastly we acknowledge previous publication of preliminary data via conference posters in abstract books (anand r et al. should mucoactives be used in acute respiratory failure in the critically ill? results from a systematic review. 2019; anand r et al. should mucoactives be used in acute respiratory failure in the critically ill: preliminary results from a systematic review? 2018).

Publisher Copyright:
© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Copyright 2020 Elsevier B.V., All rights reserved.


  • ARDS
  • assisted ventilation
  • critical care
  • non invasive ventilation


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