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

BACKGROUND

Previous meta-analyses demonstrated that high-dose glucocorticoids were not beneficial in sepsis. Recently, lower-dose glucocorticoids 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 (I2 = 0%; relative benefit, 1.23, [95% CI, 1.01 to 1.50]; P = 0.036) and shock reversal (I2 = 0%; relative benefit, 1.71 [CI, 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 (I2 = 14%; relative benefit, 0.89 [CI, 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 glucocorticoids 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.