Meta-analysis: The effect of steroids on survival and shock during sepsis depends on the dose

Background: Previous meta-analyses demonstrated that highdose glucocorticoids were not beneficial in sepsis. Recently, lowerdose glucocorticolds have been studied. Purpose: To compare recent trials of glucocorticoids for sepsis with previous glucocorticoid trials. Data Sources: Systematic MEDLINE search for studies published between 1988 and 2003. Study Selection: Randomized, controlled trials of sepsis that examined the effects of glucocorticoids on survival or vasopressor requirements. Data Extraction: Two investigators independently collected data on patient and study characteristics, treatment interventions, and outcomes. Data Synthesis: The 5 included trials revealed a consistent and beneficial effect of glucocorticoids on survival (l(2) = 0%; relative benefit, 1.23, [95% Cl, 1.01 to 1.50]; P= 0.036) and shock reversal (l(2) = 0%; relative benefit, 1.71 [Cl, 1.29 to 2.26]; P < 0.001). These effects were the same regardless of adrenal function. In contrast, 8 trials published before 1989 demonstrated a survival disadvantage with steroid treatment (l(2) = 14%; relative benefit, 0.89 [Cl, 0.82 to 0.97]; P = 0.008). In comparison with the earlier trials, the more recent trials administered steroids later after patients met enrollment criteria (median, 23 hours vs. <2 hours; P = 0.02), for longer courses (6 days vs. 1 day; P = 0.01), and in lower total dosages (hydrocortisone equivalents, 1209 mg vs. 23 975 mg; P = 0.01) to patients with higher control group mortality rates (mean, 57% vs. 34%; P = 0.06) who were more likely to be vasopressor-dependent (100% vs. 65%; P = 0.03). The relationship between steroid dose and survival was linear, characterized by benefit at low doses and increasing harm at higher doses (P = 0.02). Limitations: We could not analyze time-related improvements in medical care and potential bias secondary to nonreporting of negative study results. Conclusions: Although short courses of high-dose glucocorticolds decreased survival during sepsis, a 5- to 7-day course of physiologic hydrocortisone doses with subsequent tapering increases survival rate and shock reversal in patients with vasopressor-dependent septic shock.