Corticosteroids in the Treatment of Severe Sepsis and Septic Shock in Adults A Systematic Review

被引:388
|
作者
Annane, Djillali [1 ]
Bellissant, Eric [2 ]
Bollaert, Pierre-Edouard [3 ]
Briegel, Josef [4 ]
Confalonieri, Marco [5 ]
De Gaudio, Raffaele [6 ]
Keh, Didier [7 ]
Kupfer, Yizhak [8 ]
Oppert, Michael [9 ]
Meduri, G. Umberto [10 ]
机构
[1] Univ Versailles, APHP, Crit Care Dept, Hop Raymond Poincare, F-92380 Garches, France
[2] Univ Rennes 1, Hop Pontchaillou, Ctr Hosp Univ, Pharmacol Dept,Clin Invest Ctr,INSERM 0203, Rennes, France
[3] Univ Nancy 1, Intens Care Unit, Hop Cent, Ctr Hosp Univ, Nancy, France
[4] Anasthesiol Klin, Dept Anesthesiol & Intens Care Med, Munich, Germany
[5] Univ Hosp Trieste, Dept Pneumol, Trieste, Italy
[6] Univ Florence AOUC Careggi, Dept Crit Care, Sect Anaesthesiol & Intens Care, Florence, Italy
[7] Charite Campus Virchow Clin, Intens Care Unit, Berlin, Germany
[8] Maimonides Hosp, Div Pulm & Crit Care Med, New York, NY USA
[9] Charite Campus Virchow Klinikum, Klin Schwerpunkt Nephrol & Internist Intens Med, Berlin, Germany
[10] Univ Tennessee, Ctr Hlth Sci, Div Pulm Crit Care & Sleep Med, Memphis, TN 38163 USA
来源
关键词
LOW-DOSE HYDROCORTISONE; COMMUNITY-ACQUIRED PNEUMONIA; DOUBLE-BLIND; STEROID-THERAPY; METHYLPREDNISOLONE; DEXAMETHASONE; MANAGEMENT; METAANALYSIS; MORTALITY; CONSENSUS;
D O I
10.1001/jama.2009.815
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Context The benefit of corticosteroids in severe sepsis and septic shock remains controversial. Objective We examined the benefits and risks of corticosteroid treatment in severe sepsis and septic shock and the influence of dose and duration. Data Sources We searched the CENTRAL, MEDLINE, EMBASE, and LILACS (through March 2009) databases as well as reference lists of articles and proceedings of major meetings, and we contacted trial authors. Study Selection Randomized and quasi-randomized trials of corticosteroids vs placebo or supportive treatment in adult patients with severe sepsis/septic shock per the American College of Chest Physicians/Society of Critical Care Medicine consensus definition were included. Data Extraction All reviewers agreed on trial eligibility. One reviewer extracted data, which were checked by the other reviewers and by the trials' authors whenever possible. Some unpublished data were obtained from the trials' authors. The primary outcome for this review was 28-day mortality. Results We identified 17 randomized trials (n=2138) and 3 quasi-randomized trials (n=246) that had acceptable methodological quality to pool in a meta-analysis. Twenty-eight-day mortality for treated vs control patients was 388/1099 (35.3%) vs 400/1039 (38.5%) in randomized trials (risk ratio [RR], 0.84; 95% confidence interval [CI], 0.71-1.00; P=.05; I-2=53% by random-effects model) and 28/121 (23.1%) vs 24/125 (19.2%) in quasi-randomized trials (RR, 1.05, 95% CI, 0.69-1.58; P=.83). In 12 trials investigating prolonged low-dose corticosteroid treatment, 28-day mortality for treated vs control patients was 236/629 (37.5%) vs 264/599 (44%) ( RR, 0.84; 95% CI, 0.72-0.97; P=.02). This treatment increased 28-day shock reversal ( 6 trials; 322/481 [66.9%] vs 276/471 [58.6%]; RR, 1.12; 95% CI, 1.02-1.23; P=.02; I-2=4%) and reduced intensive care unit length of stay by 4.49 days (8 trials; 95% CI, -7.04 to -1.94; P<.001; I-2=0%) without increasing the risk of gastroduodenal bleeding (13 trials; 65/800 [8.1%] vs 56/764 [7.3%]; P=.50; I-2=0%), superinfection (14 trials; 184/998 [18.4%] vs 170/950 [17.9%]; P=.92; I-2=8%), or neuromuscular weakness (3 trials; 4/407 [1%] vs 7/404 [1.7%]; P=.58; I-2=30%). Corticosteroids increased the risk of hyperglycemia (9 trials; 363/703 [51.6%] vs 308/670 [46%]; P<.001; I-2=0%) and hypernatremia (3 trials; 127/404 [31.4%] vs 77/401 [ 19.2%]; P<.001; I-2=0%). Conclusions Corticosteroid therapy has been used in varied doses for sepsis and related syndromes for more than 50 years, with no clear benefit on mortality. Since 1998, studies have consistently used prolonged low-dose corticosteroid therapy, and analysis of this subgroup suggests a beneficial drug effect on short-term mortality. JAMA. 2009;301(22):2362-2375 www.jama.com
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收藏
页码:2362 / 2375
页数:14
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