RecentRCT

MARCH

Carbocisteine or Hypertonic Saline for Acute Respiratory Failure

N Engl J Med, 2026 · Multicenter open-label 2×2 factorial randomized trial

Population: 1,956 mechanically ventilated participants aged ≥16 with acute respiratory failure and difficult-to-clear secretions; 1,903 in primary analysis
Intervention: Enteral carbocisteine and/or nebulized 6–7% hypertonic saline
Comparator: Usual care without the respective agent
Primary outcome: Time to successful unassisted breathing
Result: Neither agent shortened ventilation: adjusted HR 0.96 (95% CI 0.87–1.05) for carbocisteine and 1.00 (0.91–1.10) for hypertonic saline. Carbocisteine increased important upper-GI bleeding; hypertonic saline increased bronchoconstriction and nebulization-associated hypoxemia.

What the trial found

The tested mucoactive regimens provided no liberation benefit and caused adverse effects.

Clinical interpretation

Avoid routine use of these regimens to accelerate liberation in the trial population; do not generalize to every disease-specific mucoactive indication.

Limitations

Open-label design; applies to the tested concentrations, regimens and population.

Moderate certainty

Clinical Context & Relevant Topics (1)

Disease Reference

Invasive Mechanical Ventilation

Complete clinical topic overview. For the full 10-level interactive course, visit Master MV. Covers core ventilator modes, respiratory mechanics (Cstat, Raw, driving pressure), waveform dyssynchrony analysis, VILI prevention, and liberation protocols.

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