Nebulized heparin and salbutamol versus salbutamol alone in acute exacerbations of chronic obstructive pulmonary disease requiring mechanical ventilation: a double-blind randomized controlled trial

BACKGROUND: Nebulized heparin has been effectively used in the management of many pulmonary diseases. However, its effect on mechanically ventilated patients with acute exacerbation chronic obstructive pulmonary disease (AECOPD) has never been studied. This study aimed to assess the efficacy of nebulized heparin and salbutamol to increase ventilator-free days (VFD) in mechanically ventilated AECOPD patients and the effect of nebulized heparin on respiratory and coagulation functions. METHODS: In this double-blind controlled study, 60 mechanically ventilated adult patients with AECOPD were randomly allocated into two groups; heparin and salbutamol (HS) group and salbutamol only (S) group. In the Group HS, patients received nebulized heparin (25,000 IU) and salbutamol (5 mg) every 6 hours. Patients in the Group S received nebulized salbutamol only (5 mg). The treatment was continued while patients remained ventilated for a maximum of 14 days. The primary outcome was VFDs at day 14. PaCO(2), PaO(2)/FiO(2) ratio, number of nebulizations withheld, C-reactive protein (CRP) titer and activated partial thromboplastin time (APTT) were secondary outcomes. RESULTS: Patients in the Group HS had significantly more VFDs (4.7 ± 3.3) compared with those in the Group S (2.4 ± 2.6), P = 0.007. PaCO(2) levels, PaO(2)/FiO(2), the decrease in the CRP level and the increase in the APTT from the baseline showed no evidence of difference in both groups. CONCLUSIONS: The co-administration of nebulized heparin and salbutamol, compared with salbutamol alone, significantly increased (VFDs) among mechanically ventilated AECOPD patients without increasing bleeding risks.