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Streptokinase Versus Unfractionated Heparin Nebulization in Patients With Severe Acute Respiratory Distress Syndrome (ARDS): A Randomized Controlled Trial With Observational Controls.

OBJECTIVE
To examine and compare nebulizing heparin versus streptokinase for reversing alveolar collapse nonresponsive to recruitment.


DESIGN
A clinical trial at a tertiary intensive care unit (ICU). Sixty patients with severe acute respiratory distress syndrome (ARDS) (PaO2/FIO2 <100) nonresponsive to recruitment maneuver (RM), prone position, and neuromuscular block (NMB) were randomized into intervention arms or the standard-of-care arm.


SETTING
The ICU at Beni-Suef University Hospital.


PARTICIPANTS
Sixty patients with severe ARDS (PaO2/FIO2 <100) nonresponsive to RM, PP, and NMB.


INTERVENTIONS
Nebulized heparin (10,000 IU/4 h), nebulized streptokinase (250,000 IU/4 h), and conservative management.


MEASUREMENTS AND MAIN RESULTS
The primary outcome was the change in PaO2/FIO2; the secondary outcomes included the change in compliance, plateau pressure, coagulation, and ICU mortality. The PaO2/FIO2 was significantly higher in the streptokinase group from day 1 to day 8 compared to the heparin and standard-of-care groups. Streptokinase produced PaO2/FIO2>100 at day 1, >200 at day 5, and >300 at day 7. The heparin group achieved a PaO2/FIO2 >100 at day 5 but remained <200 until day 8. The standard-of-care group did not achieve a PaO2/FIO2>100 after 8 days. Streptokinase significantly reduced plateau pressure and improved compliance at day 8. Only streptokinase decreased PaCO2 (p < 0.0001). Moreover, ICU mortality was significantly lower in streptokinase patients compared to other groups. Additionally, no heparin-induced thrombocytopenia was observed in all groups.


CONCLUSION
Inhaled streptokinase serves as rescue therapy in patients with severe ARDS with improving oxygenation and lung mechanics more quickly than heparin or conventional management.