Figure 2. Effects of steroids on survival in previous and recent sepsis trials. The relative survival benefits are shown with fixed-effects model and 95% CIs with glucocorticoid therapy in the sepsis trials. Both the fixed-effects estimate (to compare across studies) and the random-effects estimate (to generalize to other samples) of relative survival benefit are presented (40). Meta-analysis of all 13 trials demonstrated variability (I² = 70%) with no overall improvement in relative survival benefit (fixed-effects estimate, 1.01 [95% CI, 0.94 to 1.09]; random-effects estimate, 1.04 [CI, 0.90 to 1.20]). The effect of steroids in the trials published before 1989 compared with those published after 1997 significantly differed (P = 0.02). In the 4 trials published after 1997 (1 study did not report mortality data [33]), the effect of steroids on the relative survival benefit was consistently beneficial (I² = 0%) (fixed-effects estimate, 1.23 [CI, 1.01 to 1.50]; random-effects estimate, 1.19 [CI, 0.99 to 1.43]). The effects of steroids on the relative survival benefit in the 9 sepsis trials published before 1989 varied (I² = 75%; fixed-effects estimate, 0.97 [CI, 0.89 to 1.04]; random-effects estimate, 0.97 [CI, 0.81 to 1.16]). Excluding 1 trial (16), which was a statistically significant outlier, yields a homogeneous group of 8 trials (17-19, 35-39) with a consistent harmful effect of steroids on survival (I² = 14%; fixed-effects estimate, 0.89 [CI, 0.82 to 0.97]; random-effects estimate, 0.90 [CI, 0.80 to 1.02]). This excluded trial (16) had methodologic differences, including being performed by 1 investigator over an 8-year period and enrolling patients both prospectively and retrospectively. VA = Veterans Administration.

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