van Meenen DMP, et al. - The researchers sought to assess if a strategy that uses nebulization for clinical indication (on-demand) is noninferior to one that uses preventive (routine) nebulization among Intensive Care Unit (ICU) patients receiving invasive ventilation. On-demand compared with routine nebulization of acetylcysteine with salbutamol did not lead to an inferior number of ventilator-free days among the ICU patients who were expected to not be extubated within 24 hours. Findings suggested on-demand nebulization to be a reasonable alternative to routine nebulization.

Methods

• Researchers performed randomized clinical trial enrolling adult patients expected to need invasive ventilation for more than 24 hours at 7 ICUs in the Netherlands.
• Interventions in this study included on-demand nebulization of acetylcysteine or salbutamol (based on strict clinical indications, n = 471) or routine nebulization of acetylcysteine with salbutamol (every 6 hours until end of invasive ventilation, n = 473).
• The number of ventilator-free days at day 28, with a noninferiority margin for a difference between groups of -0.5 days was assessed as the primary outcome.
• Length of stay, mortality rates, occurrence of pulmonary complications, and adverse events were included as secondary outcome measures.

Results

• Researchers enrolled 922 patients (34% women; median age, 66 (interquartile range [IQR], 54-75 years); all of these patients completed follow-up.
• Patients in the on-demand group had a median 21 (IQR, 0-26) ventilator-free days, and patients in the routine group had a median 20 (IQR, 0-26) ventilator-free days at 28 days (1-sided 95% CI, -0.00003 to ∞).
• No significant difference was observed in length of stay or mortality, or in the proportion of patients developing pulmonary complications, between the 2 groups.
• With routine nebulization, more frequent adverse events were reported(13.8% vs 29.3%; difference, -15.5% [95% CI, -20.7% to -10.3%]; P < .001); these were mainly related to tachyarrhythmia (12.5% vs 25.9%; difference, -13.4% [95% CI, -18.4% to -8.4%]; P < .001) and agitation (0.2% vs 4.3%; difference, -4.1% [95% CI, -5.9% to -2.2%]; P < .001).