Editor—In their editorial on intrapleural streptokinase for pleural infection Bouros and Light raise several points about the results of the MIST1 trial.1,2
They say that a treatment effect may have been overlooked since MIST1 enrolled a representative population of patients with pleural infection, including those with late “organised” disease. The analysis in the primary publication describing our trial result shows that this is not true.2 In the online data repository, a subgroup analysis in 208 patients with a presentation history of less than 14 days (a sample about five times larger than any previous trial) in whom late stage disease is unlikely showed there was no treatment effect.
Data showing that streptokinase is unlikely to have had a therapeutic effect in the subgroup of patients with early loculated empyema is also presented in the online data repository.2 No evidence of any treatment benefit was found in 318 patients with unequivocally loculated pleural fluid on chest radiography.
Our patients were not unrepresentatively old. The mean age of patients in the MIST1 trial was 60, which is in the range reported previously.3-5
The prevalence of comorbidity in MIST1 does not imply a particularly frail population. Many of the comorbid diseases are minor (such as gastro-oesophageal reflux). A high prevalence of such symptoms is related to the care taken to describe the population accurately.
Both large and small chest tubes were used at the doctor's discretion. Which tube size was used did not predict outcome (unpublished data). An adequately powered, randomised trial is required to assess whether image guided chest tube insertion leads to better outcomes.
Patients were referred for surgery using the same criteria as outlined in the previous small (31 patients) trial.5
The overall result of MIST1 showed no evidence of a benefit from intrapleural streptokinase. If there are benefits in one substantial subgroup, there must be commensurate disadvantages in other subgroups to produce the overall trial result. Thus streptokinase should not be used for empyema for any subset of patients without well executed randomised trials defining patients who will benefit.
Competing interests: None declared.
References
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