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Intrapleural fibrinolytic agents have been advocated in the management of pleural infection in many respiratory society guidelines. However, the evidence base for this recommendation stems from case series and small trials which do not have adequate statistical power.
The MIST1 study was a double blind, randomised, controlled trial with 454 patients enrolled in 52 centres in the UK. The inclusion criteria were the presence of macroscopically purulent pleural fluid, positive pleural fluid bacterial culture or gram stain, or a pleural fluid pH <7.2. All patients received IV antibiotics and underwent chest tube insertion. Patients enrolled received either 250 000 IU streptokinase administered through the chest tube every 12 hours (maximum 6 doses) or matched placebo. The primary outcome measure used was the number of patients who died or required surgical drainage at 3 months. Secondary end points included death or surgery at 12 months, duration of hospital stay, the severity of residual chest radiographic changes, and dynamic lung volumes 3 months after randomisation. Also noted were levels of antistreptokinase antibody from baseline to 3 months and any bleeding after surgical drainage of the empyema.
Statistical analysis was performed on 430 subjects (the 24 excluded either died, underwent surgery, or withdrew consent before receiving the drug). Results evaluated after 3 and 12 months revealed, rather unexpectedly, that there was no improvement in outcomes with streptokinase. In fact, there was an increase in adverse events—notably chest pain and allergic reactions. Also, the elevated antibody response raises concerns for receiving streptokinase in any future thrombotic events. The authors therefore conclude that intrapleural streptokinase should generally be avoided in pleural infections.