Controlled Trial of Intrapleural Streptokinase in the Treatment of Pleural Empyema and Complicated Parapneumonic Effusions (Discussion)

3 Jan
2014

Controlled Trial of Intrapleural Streptokinase in the Treatment of Pleural Empyema and Complicated Parapneumonic Effusions (Discussion)Previous reports on the use of intrapleural thrombolysis as an adjunctive modality in the treatment of empyema suggested that it may be highly effective with success rates ranging from about 50 to 100%. These include a multicenter report of 30 patients from Mexico by Jerjes-Sanchez et al (SK was used) and a large series of 84 patients with multiloculated effusions from Denver described by Moulton et al (urokinase was used). The overall success rate of 70% (SK group, n = 23) in this study is comparable to that reported from elsewhere. None of these previous studies, however, directly compared the clinical outcomes of adjunctive thrombolysis with closed tube drainage alone. From the consistently encouraging comments in the literature, we had anticipated a clear improvement in patient outcome with the use of intrapleural SK. This was not the case.

The administration of SK did increase the volume of pleural fluid drained from our patients. In some cases, this increase was dramatic (Fig 1). However, this did not result in any significant improvement in the key measures of clinical outcome such as duration of hospital stay, the need for open surgical drainage, or mortality (Table 3). Our results are very similar to those of another yet unpublished randomized controlled trial discussed by Davies et al at the American Thoracic Society meeting in May 1996. In 23 patients (10 with frank empyema), they compared three daily doses of intrapleural SK with chest tube drainage and found that while SK treatment drained more pleural fluid (cumulative volumes of 2.5 L vs 1.0 L, very similar to this study; see Table 3), it did not significantly affect duration of hospitalization and success rates. Thus, two separate controlled studies have confirmed that pleural fibrinolysis improves fluid drainage but not clinical outcome.

Strange and colleagues have shown, in a rabbit model of pleural sepsis, that intrapleural thrombolytic agents caused two clinically significant effects. They increased plasminogen-dependent fibrinolytic activity in the pleura and thus reduced the number of pleural adhesions. They also, for yet unknown reasons, increased the volume of pleural fluid independent of drainage (from 4.8 [1.7] mL to 18.8 [5.1] mL). We think that both these effects were important in our patients and accounted for the marked difference in volume of fluid drainage between the two groups of patients. The effect of SK in increasing pleural fluid production may not in itself be deleterious provided effective overall drainage is achieved and patients show rapid clinical and radiologic improvement. It is possible, however, that SK treatment could have been carried on for longer than appropriate in some patients. If the administration of SK were to result, each time, in a large volume of “positive” fluid drained, this might delay decisions regarding tube removal or the need for further intervention. The average number of doses of SK administered in this study (5.3 [2.7]) was comparable to most other series (4.9 in Moulton et al and 5.1 in Jerjes-Sanchez et al). This suggests that we were not unduly prolonging the SK regimen in our patients in comparison with current practice. Furthermore, Davies et al, who used three doses of SK (over 3 days) for all patients, achieved very similar patient outcomes. It is possible, however, as suggested by Moulton et al, that a better result might be achieved by administering two to three doses of the thrombolytic agent within 24 h. This might achieve a more intense fibrinolysis in the pleural cavity over a shorter time and avoid any tendency to delay. This approach will require more frequent clinical and radiologic review of the patients at closer intervals.

We think that while the use of intrapleural thrombolytic agents may not have a major impact on the clinical outcome in all patients with pleural empyema, it did facilitate the evacuation of loculated effusions and some patients did respond dramatically with prompt and complete clearance of the pleural infection. Failure of the empyema to resolve, both clinically and radiologically, within 48 to 72 h following the repeated use of intrapleural thrombolytic agents may be an indication for further intervention. We suggest that it may be appropriate, at this stage, to consider either early thoracoscopic debridement and evacuation or open surgical drainage in surgically fit patients with multiloculated empyemas. While results of thoracoscopic management of empyemas have been encouraging, no controlled studies have been reported (to our knowledge).’ The role of thoracoscopy in the management of empyema is thus, unclear. Randomized trials are needed to compare chest tube drainage with fibrinolytic agents vs either early thoracoscopic or open debridement and drainage.

This study has several limitations. It was not a formal randomized controlled trial since the different treatment regimens were not instituted in parallel but in series. The patients in the SK treatment group were younger and there were a larger number of patients with multiloculated empyemas than in the Drain protocol. These differences were not statistically significant, however, and we think overall, the two groups of patients had diseases of comparable severity. With regards to outcome, there were no marked differences between the two groups with failure rates (defined as either death or surgical intervention) of 30% and 34% (Table 3). Furthermore, the results of this study were very similar to those reported from the randomized controlled study by Davies et al. The higher mortality rate (especially death rates from septicemia which were also not significantly greater than in the SK group) in the group that did not receive SK may be related to older age rather than less effective treatment. It is possible that a randomized trial involving a larger number of patients may be needed to demonstrate the therapeutic impact of intrapleural fibrinolysis.

We conclude that, in the treatment of pleural empyema, in comparison with simple closed-tube drainage, the adjunctive treatment with daily administration of intrapleural SK significantly increased the volume of pleural fluid drainage, but did not markedly reduce mortality, morbidity, or the need for surgical intervention.

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