Association between early administration of mucoactive agents and in-hospital mortality in patients with pneumonia requiring mechanical ventilation: a nationwide cohort study.

Background: In patients with pneumonia requiring mechanical ventilation, increased airway secretions are associated with prolonged mechanical ventilation, but the effect of mucoactive agents remains unclear. The present study aimed to investigate the association between early administration of mucoactive agents and in-hospital mortality in patients with pneumonia requiring mechanical ventilation.

Methods: We conducted a retrospective cohort study using the Japanese Diagnosis Procedure Combination database, a nationwide inpatient database. Adult patients were eligible if they had a primary diagnosis of pneumonia and required invasive mechanical ventilation within 2 days of admission, with ventilation continued for ≥ 2 days between April 2012 and March 2023. Patients were divided into those who received at least one mucoactive agent within 2 days after the initiation of mechanical ventilation (mucoactive agent group) and those who did not (control group). Mucoactive agents included ambroxol (oral), bromhexine (oral, intravenous and nebulized), fudosteine (oral), carbocisteine (oral) and N-acetylcysteine (nebulized). We performed a propensity score overlap weighting analysis to compare in-hospital mortality. The number of ventilator-free days at 28 days was assessed as a secondary outcome. We also performed sensitivity analyses using inverse probability of treatment weighting, generalized estimating equations, and doubly robust methods.

Results: Eligible patients (n = 10,942) were categorized into the mucoactive agent group (n = 2246) or control group (n = 8696). The most commonly prescribed mucoactive agent was carbocisteine (oral). After overlap weighting, in-hospital mortality was significantly lower in the mucoactive agent group than in the control group (25.2% vs. 27.5%; risk difference, - 2.3%; 95% confidence interval, - 4.4% to - 0.3%; p = 0.028). Ventilator-free days at 28 days did not significantly differ between the mucoactive agent group and the control group. Sensitivity analyses yielded similar results.

Conclusions: In patients with ventilated pneumonia, early administration of mucoactive agents was associated with lower in-hospital mortality.