Recently reported results in the New England Journal of Medicine from the Multicenter Intrapleural Sepsis Trial (MIST1) showed that intrapleural administration of streptokinase does not improve mortality, rate of surgery, or length of stay among patients with pleural infection. Referral to surgical drainage was one of the primary studied outcomes. The decision to refer was made by managing physicians locally at the 52 centers. Our study investigated the potential effects and contributions from procedure and practice variance on the surgical drainage referral decision.
Criteria for surgery referral from MIST1 were based on persistent fever and/or raised blood inflammatory markers, and residual pleural fluid. Probabilistic risk assessment (PRA) was used to model and quantify the surgical drainage decision making process. Event tree analysis was employed to simulate different decision branch points based on the referral criteria. Each of these branch points were evaluated by fault tree analysis. The MIST1 result was adopted as the baseline reference case in our study.
Results from PRA analysis show that the decision to refer to surgical drainage is complex and depends on the managing physician’s perceived importance of several parameters, including the severity and duration of fever, the extent of elevated blood inflammatory markers, and the degree of residual effusion. The non ambiguous decisions of referral or no referral constitute between 60 to 80 percent of the total. The balance is more arbitrary. This introduced a substantial variability and uncertainty into the final results. Our study further shows that by refining the definitions of fever, residual effusion, and inflammatory markers, the relative contributions to the streptokinase and placebo groups could vary up to 40 percent.
This study suggests that the primary outcome selected in MIST1 to compare streptokinase with placebo may be sensitive to how the surgical drainage referral criteria are defined.
Modified definitions of residual effusion, fever, and elevated inflammatory markers could potentially alter the conclusion on the efficacy of streptokinase as a fibrinolytic agent for complicated pleural effusions.
Kelvin Shiu, None.