MARCH: Mucoactive Agents Fail and Harm in Ventilated Patients

The MARCH trial provides the first large randomized evidence that routine carbocisteine and nebulized hypertonic saline do not shorten mechanical ventilation and each causes measurable harm.

📅 Journal publication: Aug 20, 2026 (online Jun 10, 2026) · Last updated: Oct 7, 2026

★ Editor's Pickcarbocisteinehypertonic salinemucoactive agentsacute respiratory failuremechanical ventilationMARCH trialICUrandomized controlled trialsecretion clearanceupper GI bleedingbronchoconstriction Critical Care / ICU

Background Information

Mucoactive agents fail to improve ventilation in critical care.

Mucoactive agents like carbocisteine and hypertonic saline (HTS) are commonly used in acute respiratory failure despite limited evidence on their efficacy and safety. Carbocisteine and HTS did not significantly reduce duration of mechanical ventilation and were associated with increased risks: upper gastrointestinal bleeding with carbocisteine (1.4% vs. 0.2%) and bronchoconstriction with HTS (2.4% vs. 0.4%). This study highlights that neither carbocisteine nor HTS improve ventilation outcomes and both have significant safety concerns, indicating the need for cautious use in critical care settings. Carbocisteine and HTS do not reduce ventilation duration and pose safety risks in critically ill patients.

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Authors: Connolly B, Dickson N, Campbell C, Bradley JM, O'Neill B, Agus A, Barker M, Bewley JS, Blackwood B, Borthwick M, Camporota L, Chikhani M, Clarke M, Dark P, Higgins L, Lambert P, Lunn T, McDowell C, McFarland M, McShane U, Mehta R, Messer B, Morton B, Patel N, Perkins GD, Rowley D, Shyamsundar M, Silversides JA, Sturmey G, Warburton J, Williams B, Lall R, McAuley DF, MARCH Trial Investigators

Citation: Connolly B, Dickson N, Campbell C, et al. Carbocisteine or Hypertonic Saline for Acute Respiratory Failure. The New England journal of medicine. 2026;395(8):739-752. doi:10.1056/NEJMoa2603406

Article Links: PubMed · Journal / DOI

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