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Original research
Mucoactive agents for acute respiratory failure in the critically ill: a systematic review and meta-analysis
  1. Rohan Anand1,
  2. Daniel F McAuley1,
  3. Bronagh Blackwood1,
  4. Chee Yap1,
  5. Brenda ONeill2,
  6. Bronwen Connolly1,3,4,
  7. Mark Borthwick5,
  8. Murali Shyamsundar1,
  9. John Warburton6,
  10. David van Meenen7,
  11. Frederique Paulus7,
  12. Marcus J Schultz7,8,9,
  13. Paul Dark10,
  14. Judy M Bradley1
  1. 1 Wellcome-Wolfson Institute for Experimental Medicine, Queen's University Belfast, Belfast, UK
  2. 2 Centre for Health and Rehabilitation Technologies, Institute of Nursing and Health Research, Ulster University, Newtownabbey, UK
  3. 3 Department of Physiotherapy, The University of Melbourne, Melbourne, Victoria, Australia
  4. 4 Lane Fox Respiratory Unit, Guy's and Saint Thomas' NHS Foundation Trust, London, UK
  5. 5 Oxford Critical Care, Oxford University Hospitals NHS Foundation Trust, Oxford, Oxfordshire, UK
  6. 6 Bristol Royal Infirmary, University Hospitals Bristol NHS Foundation Trust, Bristol, UK
  7. 7 University of Amsterdam, Academic Medical Center Department of Intensive Care Medicine, Amsterdam, Noord-Holland, Netherlands
  8. 8 Mahidol University, Mahidol Oxford Tropical Medicine Research Unit, Bangkok, Thailand
  9. 9 Nuffield Department of Medicine, Oxford University, Oxford, Oxfordshire, UK
  10. 10 Division of Infection, Immunity and Respiratory Medicine, NIHR Manchester Biomedical Research Centre, The University of Manchester, Manchester, UK
  1. Correspondence to Rohan Anand, Queen's University Belfast Wellcome-Wolfson Institute for Experimental Medicine, Belfast BT9 7BL, UK; ranand01{at}


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.

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

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  • Contributors All authors fulfilled ICMJE guidelines for authorship criteria. RA, DM, JB, BB, CY, BO and BC contributed to the conception, data collection, data analysis, drafting the article and critical revisions. MB, MS and JW contributed to conception and provided critical revisions to the article. DvM, FP and MJS contributed to provisional data collection and critical revisions. PD provided critical revisions to the article.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests JB, DM, BO and RA are investigators in an NIHR HTA funded trial of mucoactives in bronchiectasis.

  • Patient consent for publication Not required.

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

  • Data availability statement All data relevant to the study are included in the article or uploaded as online supplementary information. Any additional details are available on reasonable request.

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