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Meta-Analysis: The Effect of Steroids on Survival and Shock during Sepsis Depends on the Dose
- Peter C. Minneci, MD;
- Katherine J. Deans, MD;
- Steven M. Banks, PhD;
- Peter Q. Eichacker, MD; and
- Charles Natanson, MD
- From the Clinical Center, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland, and Massachusetts General Hospital, Boston, Massachusetts.
Abstract
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.
Article and Author Information
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Note: Drs. Minneci and Deans contributed equally to the creation of this manuscript; the order of their names is arbitrary.
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Potential Financial Conflicts of Interest: None disclosed.
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Requests for Single Reprints: Peter C. Minneci, MD, Critical Care Medicine Department, National Institutes of Health, 10 Center Drive, Building 10, Room 7D43, Bethesda, MD 20892; e-mail, pminneci{at}mail.cc.nih.gov.
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Current Author Addresses: Drs. Minneci, Deans, Banks, Eichacker, and Natanson: Critical Care Medicine Department, National Institutes of Health, 10 Center Drive, Building 10, Room 7D43, Bethesda, MD 20892.
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