Salbutamol therapy and mortality in critical ill patients with acute respiratory failure: a retrospective study

Acute respiratory failure (ARF) represents a leading cause of intensive care unit (ICU) admissions globally, with high associated mortality. While β2-agonists like salbutamol are established for managing chronic airway diseases, their impact on mortality in severe ARF remains unclear. This study aimed to evaluate the association between salbutamol therapy and all-cause mortality in critically ill patients with ARF. A retrospective cohort study was conducted using data from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database. Adult patients (≥ 18 years) with a documented diagnosis of ARF were included. Propensity score matching (PSM) was applied to balance baseline characteristics between salbutamol-exposed and non-exposed groups. The primary outcome was 28-day all-cause mortality, assessed using multivariable Cox regression models. Secondary outcomes included ICU mortality, 90-day and 1-year mortality, and length of stay. Subgroup analyses were performed to explore effect modifications by ethnicity, weight, mechanical ventilation status, and arterial partial pressure of carbon dioxide (PaCO2) levels. Of 73,181 screened patients, 13,480 with ARF were identified, including 6256 who received salbutamol. After PSM, 3915 matched pairs were analyzed. Salbutamol exposure was associated with significantly reduced 28-day mortality (unadjusted OR: 0.88; 95% CI 0.82–0.95; adjusted OR: 0.76; 95% CI 0.71–0.82). Consistent benefits were observed for 90-day mortality (30.5% vs. 36.6%, P < 0.001) and 1-year mortality (39.8% vs. 45.9%, P < 0.001). Subgroup analyses indicated enhanced survival benefits in non-White individuals, patients with higher body weight (> 78.6 kg), those requiring mechanical ventilation, and those with hypercapnia (PaCO2 > 49 mmHg). Salbutamol therapy is independently associated with reduced all-cause mortality in patients with severe ARF, particularly among high-risk subgroups. These findings support the adjunctive use of salbutamol in ARF management and highlight the need for prospective randomized trials to validate its efficacy and underlying mechanisms.