Two widely used mucoactive agents did not help ventilated patients breathe independently sooner and were associated with increased adverse events, according to a large randomised trial published in the New England Journal of Medicine. The MARCH trial enrolled nearly 2,000 adults across 71 hospitals in the United Kingdom who were on mechanical ventilation due to acute respiratory failure and had difficulty clearing mucus. Researchers used a 2×2 factorial design to test carbocisteine and hypertonic saline (HTS), either alone, in combination, or compared with usual care, for up to 28 days.
Neither carbocisteine nor hypertonic saline reduced ventilator duration compared with standard care. Across all groups, patients were liberated from ventilation at approximately seven to eight days.
However, both treatments were associated with harm. Patients receiving carbocisteine were approximately seven times more likely to develop serious upper gastrointestinal bleeding than those who did not (1.4% versus 0.2%). Those treated with hypertonic saline experienced more respiratory complications, including bronchoconstriction requiring urgent rescue medication and dangerous drops in blood oxygen levels during administration. Neither agent improved survival or reduced ICU or hospital length of stay.
Mucoactive agents are used in more than 80% of intensive care units worldwide, administered to roughly one in four or five ventilated patients. However, evidence supporting their efficacy and safety in critically ill patients has been limited, with clinical use largely based on observation and experience rather than robust trial data.
The researchers concluded that routine use of these agents in clinical practice should be approached with caution and suggested that ICU protocols may need revision to reduce avoidable adverse effects.
Source: Medical Xpress / New England Journal of Medicine (2026)
