Streptokinase and urokinase for the treatment of pleural effusions and empyemas

It is evident from these studies that thrombolytics significantly increase the amount of drainage from pleural effusions or empyemas. The effect on other outcome measures, such as length of hospital stay, days before defervescence, days with chest tube, surgical procedures, and mortality is questionable. The lack of randomized, controlled trials comparing streptokinase and urokinase makes a true comparison rather difficult. Both agents are equally effective in increasing pleural drainage. Only one comparative trial demonstrated an increased incidence of fever with streptokinase, which was reversible on discontinuation. This reaction does not occur frequently based on the results of the published literature. Overall, the low incidence of adverse reactions associated with either agent may not justify the added expense of urokinase for this indication. A majority of the clinical trials can be criticized for their low numbers of patients along with lack of control groups. It is unknown whether statistical significance would have been obtained if adequate sample sizes were used. Inclusion criteria were not uniform, as characteristics of pleural fluid and presence of loculations may influence success. Volume of drainage is also less impressive when the amount used to instill the thrombolytic is subtracted from the amount of drainage. If this were considered, statistical significance could have been altered. Finally, therapeutic end points varied throughout the literature. Most studies used volume of drainage and X-ray findings as end points. However, such surrogate markers do not necessarily correlate with clinical improvement. The optimal dose of streptokinase is 250,000 units instilled through a chest tube (which is clamped for 2-4 h) on a daily basis until decreased drainage is obtained. The optimal dose of urokinase is not known and the administration methods vary throughout the literature, ranging from 50,000 to 250,000 units. The AWP of streptokinase is $122 for 250,000 units compared with $433 for 250,000 units of urokinase. In the only comparative trial, the average number of instillations was the same, so the cost of therapy with urokinase is significantly higher. The study by Bouros et al. poses an interesting observation. They successfully treated patients with 50,000 units of urokinase, which would be approximately the same cost as streptokinase. Further studies are needed to truly evaluate the efficacy of low-dose urokinase as well as comparative trials with these two agents. In conclusion, urokinase offers no significant benefits over streptokinase. The incidence of fever was greater in one comparative trial with streptokinase than with urokinase. Based on cost considerations and lack of comparative studies, urokinase infusions should be reserved for patients who develop fever when receiving continued therapy with streptokinase.