Carbocisteine or Hypertonic Saline for Acute Respiratory Failure

@article{connolly2026carbocisteine,
  title = {{Carbocisteine or Hypertonic Saline for Acute Respiratory Failure}},
  author = {Bronwen Connolly and Naomi Dickson and Christina Campbell and Judy M Bradley and Brenda O’Neill and Ashley Agus and Mike Barker and Jeremy S Bewley and Bronagh Blackwood and Mark Borthwick and Luigi Camporota and Marc Chikhani and Mike Clarke and Paul Dark and Lisa Higgins and Penelope Lambert and Thomas Lunn and Cliona McDowell and Margaret McFarland and Una McShane and Reena Mehta and Ben Messer and Ben Morton and Nehal Patel and Gavin D Perkins and Deborah Rowley and Murali Shyamsundar and Jonathan A Silversides and Gordon Sturmey and John Warburton and Barry Williams and Ranjit Lall and Daniel F McAuley},
  journal = {The New England journal of medicine},
  year = {2026},
  month = jun,
  doi = {10.1056/nejmoa2603406},
  url = {https://europepmc.org/article/PMC/PMC7619674},
  note = {CC BY},
}

TY  - JOUR
TI  - Carbocisteine or Hypertonic Saline for Acute Respiratory Failure
AU  - Bronwen Connolly
AU  - Naomi Dickson
AU  - Christina Campbell
AU  - Judy M Bradley
AU  - Brenda O’Neill
AU  - Ashley Agus
AU  - Mike Barker
AU  - Jeremy S Bewley
AU  - Bronagh Blackwood
AU  - Mark Borthwick
AU  - Luigi Camporota
AU  - Marc Chikhani
AU  - Mike Clarke
AU  - Paul Dark
AU  - Lisa Higgins
AU  - Penelope Lambert
AU  - Thomas Lunn
AU  - Cliona McDowell
AU  - Margaret McFarland
AU  - Una McShane
AU  - Reena Mehta
AU  - Ben Messer
AU  - Ben Morton
AU  - Nehal Patel
AU  - Gavin D Perkins
AU  - Deborah Rowley
AU  - Murali Shyamsundar
AU  - Jonathan A Silversides
AU  - Gordon Sturmey
AU  - John Warburton
AU  - Barry Williams
AU  - Ranjit Lall
AU  - Daniel F McAuley
PY  - 2026
DA  - 2026/06/10
JO  - The New England journal of medicine
DO  - 10.1056/nejmoa2603406
UR  - https://europepmc.org/article/PMC/PMC7619674
AB  - Background: Mucoactives are widely used in acute respiratory failure despite limited evidence of effectiveness or safety.  Methods: 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.  Results: 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).  Conclusions: 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).
SN  - 0028-4793
SN  - 1533-4406
ER  -