{
  "abstract": "Background: Mucoactives are widely used in acute respiratory failure despite limited evidence of effectiveness or safety.\n\nMethods: In this open-label, randomized, full, two-by-two factorial, multicenter trial, critically ill mechanically ventilated adults with acute respiratory failure who had difficult-to-clear secretions were randomly assigned to usual care plus carbocisteine (750 mg three times daily enterally), nebulized hypertonic saline (4ml, 6% or 7% concentration, four times daily), or both interventions, for up to 28 days, or to usual care alone. The primary outcome was duration of mechanical ventilation (time from randomization until first successful unassisted breathing). Primary comparisons were between carbocisteine and no carbocisteine, and hypertonic saline and no hypertonic saline, with each comparison consisting of two groups.\n\nResults: 1956 participants were randomized; 486 to carbocisteine (472 analyzed), 485 to hypertonic saline (474 analyzed), 492 to carbocisteine and hypertonic saline (479 analyzed), and 493 to usual care alone (478 analyzed). There was no statistical evidence of treatment interaction (hazard ratio [HR] 1.01, 95% confidence interval [CI] 0.83 to 1.22, P = 0.91). The median duration of mechanical ventilation was 186.1 (95% CI 168.3 to 196.6) hours with carbocisteine and 172.7 (95% CI 165.2 to 190.4) hours with no carbocisteine (adjusted HR [95% CI], 0.96 [0.87 to 1.05; P = 0.345]), and 184.5 (95% CI 165.6 to 194.1) hours with hypertonic saline and 174.3 (95% CI 166.9 to 192.7) hours with no hypertonic saline (adjusted HR [95% CI], 1.00 [0.91 to 1.10]; P = 0.980). Clinically important upper gastrointestinal bleeding occurred significantly more often in participants allocated to carbocisteine (13/965 (1.4%) vs 2/966 (0.2%), risk ratio 6.51 (95% CI 1.47 to 28.76), P = 0.014). Bronchoconstriction requiring nebulized bronchodilators (23/967 (2.4%) vs 4/964 (0.4%), risk ratio 5.73 (95% CI 1.99 to 16.52), P = 0.001) and hypoxemia during nebulization (40/967 (4.1%) vs 3/964 (0.3%), risk ratio 13.29 (95% CI 4.12 to 42.83), P = <0.001) both occurred significantly more often among participants allocated to hypertonic saline. One serious adverse reaction was reported in the combination group (0.2% of patients).\n\nConclusions: In critically ill patients with acute respiratory failure, neither carbocosteine nor hypertonic saline significantly reduced duration of mechanical ventilation, but were each associated with harm. (Funded by the National Institute for Health and Care Research Health Technology Assessment Programme and others; ISRCTN Registry number, ISRCTN17683568).",
  "abstract_shown": true,
  "affiliations": [
    "Wellcome-Wolfson Institute for Experimental Medicine, , ,",
    "Northern Ireland Clinical Trials Unit, Belfast, UK",
    "Institute of Nursing and Health Research, , ,",
    "Pharmacy Department, , ,",
    "Intensive Care, Bristol Royal Infirmary, , ,",
    "Critical Care, , ,",
    "Critical Care and Anaesthesia, , ,",
    "Division of Immunology, Immunity to Infection and Respiratory Medicine, , ,",
    "Critical Care Unit, University Hospitals of North Midlands, Stoke-on-Trent, UK",
    "School of Cancer & Pharmaceutical Sciences, Faculty of Life Sciences and Medicine, , ,",
    "Royal Victoria Infirmary, , ,",
    "Department of Clinical Sciences, , ,",
    "Warwick Medical School, , ,",
    "Department of Critical Care, , ,",
    "Independent Patient Partner, UK",
    "Warwick Clinical Trials Unit, , ,"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 33,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Bronwen Connolly"
    },
    {
      "affs": [
        1
      ],
      "name": "Naomi Dickson"
    },
    {
      "affs": [
        1
      ],
      "name": "Christina Campbell"
    },
    {
      "affs": [
        0
      ],
      "name": "Judy M Bradley"
    },
    {
      "affs": [
        2
      ],
      "name": "Brenda O’Neill"
    },
    {
      "affs": [
        1
      ],
      "name": "Ashley Agus"
    },
    {
      "affs": [
        3
      ],
      "name": "Mike Barker"
    },
    {
      "affs": [
        4
      ],
      "name": "Jeremy S Bewley"
    },
    {
      "affs": [
        0
      ],
      "name": "Bronagh Blackwood"
    },
    {
      "affs": [
        3
      ],
      "name": "Mark Borthwick"
    },
    {
      "affs": [
        5
      ],
      "name": "Luigi Camporota"
    },
    {
      "affs": [
        6
      ],
      "name": "Marc Chikhani"
    },
    {
      "affs": [
        1
      ],
      "name": "Mike Clarke"
    },
    {
      "affs": [
        7
      ],
      "name": "Paul Dark"
    },
    {
      "affs": [
        8
      ],
      "name": "Lisa Higgins"
    },
    {
      "affs": [
        4
      ],
      "name": "Penelope Lambert"
    },
    {
      "affs": [
        4
      ],
      "name": "Thomas Lunn"
    },
    {
      "affs": [
        1
      ],
      "name": "Cliona McDowell"
    },
    {
      "affs": [
        3
      ],
      "name": "Margaret McFarland"
    },
    {
      "affs": [
        1
      ],
      "name": "Una McShane"
    },
    {
      "affs": [
        9
      ],
      "name": "Reena Mehta"
    },
    {
      "affs": [
        10
      ],
      "name": "Ben Messer"
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    {
      "affs": [
        11
      ],
      "name": "Ben Morton"
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    {
      "affs": [
        8
      ],
      "name": "Nehal Patel"
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    {
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        12
      ],
      "name": "Gavin D Perkins"
    },
    {
      "affs": [
        8
      ],
      "name": "Deborah Rowley"
    },
    {
      "affs": [
        13
      ],
      "name": "Murali Shyamsundar"
    },
    {
      "affs": [
        0
      ],
      "name": "Jonathan A Silversides"
    },
    {
      "affs": [
        14
      ],
      "name": "Gordon Sturmey"
    },
    {
      "affs": [
        4
      ],
      "name": "John Warburton"
    },
    {
      "affs": [
        14
      ],
      "name": "Barry Williams"
    },
    {
      "affs": [
        15
      ],
      "name": "Ranjit Lall"
    },
    {
      "affs": [
        0
      ],
      "name": "Daniel F McAuley"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/9bzfacatcxm6w.bib",
  "cited_by": 1,
  "doi": "10.1056/nejmoa2603406",
  "fulltext_url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7619674/?tool=EBI",
  "id": "9bzfacatcxm6w",
  "issns": [
    "0028-4793",
    "1533-4406"
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  "landing_url": "https://europepmc.org/article/PMC/PMC7619674",
  "language": "eng",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Article"
    ],
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      "openalex",
      "2740|Respiratory Support and Mechanisms"
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  "pdf_url": "https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7619674/pdf/?tool=EBI",
  "pmcid": "PMC7619674",
  "pmid": "42267821",
  "published": "2026-06-10",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/9bzfacatcxm6w.ris",
  "sources": [
    {
      "first_seen": "2026-11-03T15:20:51Z",
      "native_id": "PMC:PMC7619674",
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      "url": "https://europepmc.org/article/PMC/PMC7619674"
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  "subjects": [
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      "field": "medicine",
      "origin": "openalex:2740|Respiratory Support and Mechanisms",
      "subfield": "general"
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  ],
  "title": "Carbocisteine or Hypertonic Saline for Acute Respiratory Failure",
  "title_text": "Carbocisteine or Hypertonic Saline for Acute Respiratory Failure",
  "type": "peer-reviewed",
  "updated_at": "2026-11-06T12:20:42Z",
  "url": "https://research.draconitic.com/paper/9bzfacatcxm6w",
  "venue": "The New England journal of medicine",
  "versions": []
}