Carbocisteine or Hypertonic Saline for Acute Respiratory Failure

doi:10.1056/nejmoa2603406

Respiratory failure & ventilation

Carbocisteine or Hypertonic Saline for Acute Respiratory Failure

N Engl J MedPublished 10 Jun 2026Randomised controlled trial

Read the original article ↗PubMed

Cite

Authors' conclusion

Among critically ill patients with acute respiratory failure, neither carbocisteine nor HTS significantly reduced the duration of mechanical ventilation, and each was associated with harm.

Study context

Population: Critically ill, mechanically ventilated participants ≥16 years with acute respiratory failure and difficult-to-clear secretions2-by-2 factorial
Participants: 1,956 participants

Comparison: Carbocisteine vs no carbocisteine; nebulized hypertonic saline (HTS) vs no HTS, plus usual care
Carbocisteinen = 486
HTSn = 485
Both treatmentsn = 492
Usual caren = 493reference
Primary endpoint: Duration of mechanical ventilation (randomization to first successful unassisted breathing)

Methodological detailsmulticentre, open-label, 2-by-2 factorial

Multicentre
Open-label
2-by-2 factorial

Primary result

As reported in the abstract

Duration of mechanical ventilation

Carbocisteine (any)186.1median · 95% CI 168.3–196.6 · hours

No carbocisteine172.7median · 95% CI 165.2–190.4 · hours

HTS (any)184.5median · 95% CI 165.6–194.1 · hours

No HTS174.3median · 95% CI 166.9–192.7 · hours

Adjusted hazard ratio (95% CI)P value

Carbocisteine (any) vs No carbocisteine

0.96(0.87–1.05)

P = 0.34

HTS (any) vs No HTS

1.00(0.91–1.10)

P = 0.98

Further findings

Treatment interaction (carbocisteine × HTS)

No evidence of treatment interaction: HR 1.01 (95% CI 0.83 to 1.22; P = 0.91)

Safety

Outcome	Carbocisteine	HTS	← Lower risk ←→ Higher risk →	RR (95% CI)	P value
Clinically important upper gastrointestinal bleedingCarbocisteine vs No carbocisteine	1.4%		0.050.21520	6.51 (1.47–28.76)	P = 0.01
Denominator	965	— not stated in the abstract
Bronchoconstriction leading to bronchodilator useHTS vs No HTS		2.4%	0.050.21520	5.73 (1.99–16.52)	P = 0.001
Denominator	— not stated in the abstract	967
Hypoxemia during nebulizationHTS vs No HTS		4.1%	0.050.21520	13.29 (4.12–42.83)	P < 0.001
Denominator	— not stated in the abstract	967
			0.050.21520Relative risk (log scale)

— not stated in the abstract

Clinically important upper gastrointestinal bleeding: No carbocisteine 0.2% · denominator 966
Bronchoconstriction leading to bronchodilator use: No HTS 0.4% · denominator 964
Hypoxemia during nebulization: No HTS 0.3% · denominator 964

Serious adverse reaction

One serious adverse reaction reported in the combination group: 1

Original publication

Carbocisteine or Hypertonic Saline for Acute Respiratory Failure. N Engl J Med. Published 10 June 2026. doi:10.1056/nejmoa2603406

Read the original article ↗

Composed by AI from the published abstract and checked against it. How Briefs are made →