Effect of Hydrocortisone on Development of Shock Among Patients With Severe Sepsis The HYPRESS Randomized Clinical Trial

被引:165
作者
Keh, Didier [1 ]
Trips, Evelyn [2 ]
Marx, Gernot [3 ]
Wirtz, Stefan P. [4 ]
Abduljawwad, Emad [4 ]
Bercker, Sven [5 ]
Bogatsch, Holger [2 ]
Briegel, Josef [6 ]
Engel, Christoph [7 ]
Gerlach, Herwig [8 ]
Goldmann, Anton [1 ]
Kuhn, Sven-Olaf [9 ]
Huter, Lars [10 ]
Meier-Hellmann, Andreas [11 ]
Nierhaus, Axel [12 ]
Kluge, Stefan [12 ]
Lehmke, Josefa [13 ]
Loeffler, Markus [7 ]
Oppert, Michael [14 ]
Resener, Kerstin [15 ]
Schadler, Dirk [16 ]
Schuerholz, Tobias [3 ]
Simon, Philipp [5 ]
Weiler, Norbert [16 ]
Weyland, Andreas [17 ]
Reinhart, Konrad [18 ]
Brunkhorst, Frank M. [19 ]
机构
[1] Charite, Dept Anesthesiol & Intens Care Med, Berlin, Germany
[2] Clin Trial Ctr Leipzig, Leipzig, Germany
[3] Univ Hosp RWTH Aachen, Dept Intens Care & Intermediate Care, Aachen, Germany
[4] HELIOS Hosp Bad Saarow, Dept Intens Care Med, Bad Saarow Pieskow, Germany
[5] Univ Leipzig, Dept Anesthesiol & Intens Care Med, Leipzig, Germany
[6] Klinikum Ludwig Maximilians Univ, Dept Anesthesiol, Munich, Germany
[7] Inst Med Informat Stat & Epidemiol, Leipzig, Germany
[8] Vivantes Klinikum Neukolln, Dept Anesthesia Intens Care Med & Pain Management, Berlin, Germany
[9] Ernst Moritz Arndt Univ, Dept Anesthesiol & Intens Care Med, Greifswald, Germany
[10] Zentralklin Bad Berka, Dept Anesthesia & Intens Care, Bad Berka, Germany
[11] HELIOS Hosp Erfurt, Intens Care Med & Pain Management, Erfurt, Germany
[12] Univ Med Ctr Hamburg Eppendorf, Dept Intens Care Med, Hamburg, Germany
[13] Vivantes Humboldt Klinikum, Dept Cardiol & Intens Care Med, Berlin, Germany
[14] Klinikum Ernst von Bergmann, Dept Emergency & Intens Care Med, Potsdam, Germany
[15] HELIOS Hosp Berlin Buch, Dept Intens Care Med, Berlin, Germany
[16] Univ Med Ctr Schleswig Holstein, Dept Anesthesiol & Intens Care Med, Campus Kiel, Kiel, Germany
[17] Carl von Ossietzky Univ Oldenburg, Klinikum Oldenburg Med Campus, Dept Anesthesiol Intens Care Med Emergency Med &, Oldenburg, Germany
[18] Jena Univ Hosp, Dept Anesthesiol & Intens Care Med, Jena, Germany
[19] Jena Univ Hosp, Ctr Sepsis Control & Care, Ctr Clin Studies, Jena, Germany
来源
JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION | 2016年 / 316卷 / 17期
关键词
COMMUNITY-ACQUIRED PNEUMONIA; INFLAMMATORY RESPONSE SYNDROME; INTENSIVE-CARE-UNIT; SEPTIC SHOCK; ORGAN FAILURE; DOUBLE-BLIND; CORTICOSTEROIDS; DELIRIUM; THERAPY; DEXAMETHASONE;
D O I
10.1001/jama.2016.14799
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
IMPORTANCE Adjunctive hydrocortisone therapy is suggested by the Surviving Sepsis Campaign in refractory septic shock only. The efficacy of hydrocortisone in patients with severe sepsis without shock remains controversial. OBJECTIVE To determine whether hydrocortisone therapy in patients with severe sepsis prevents the development of septic shock. DESIGN, SETTING, AND PARTICIPANTS Double-blind, randomized clinical trial conducted from January 13, 2009, to August 27, 2013, with a follow-up of 180 days until February 23, 2014. The trial was performed in 34 intermediate or intensive care units of university and community hospitals in Germany, and it included 380 adult patients with severe sepsis who were not in septic shock. INTERVENTIONS Patients were randomly allocated 1: 1 either to receive a continuous infusion of 200mg of hydrocortisone for 5 days followed by dose tapering until day 11 (n = 190) or to receive placebo (n = 190). MAIN OUTCOMES AND MEASURES The primary outcome was development of septic shock within 14 days. Secondary outcomes were time until septic shock, mortality in the intensive care unit or hospital, survival up to 180 days, and assessment of secondary infections, weaning failure, muscle weakness, and hyperglycemia (blood glucose level > 150mg/dL [to convert to millimoles per liter, multiply by 0.0555]). RESULTS The intention-to-treat population consisted of 353 patients (64.9% male; mean [SD] age, 65.0 [14.4] years). Septic shock occurred in 36 of 170 patients (21.2%) in the hydrocortisone group and 39 of 170 patients (22.9%) in the placebo group (difference, -1.8%; 95% CI, -10.7% to 7.2%; P = .70). No significant differences were observed between the hydrocortisone and placebo groups for time until septic shock; mortality in the intensive care unit or in the hospital; or mortality at 28 days (15 of 171 patients [8.8%] vs 14 of 170 patients [8.2%], respectively; difference, 0.5%; 95% CI, -5.6% to 6.7%; P = .86), 90 days (34 of 171 patients [19.9%] vs 28 of 168 patients [16.7%]; difference, 3.2%; 95% CI, -5.1% to 11.4%; P = .44), and 180 days (45 of 168 patients [26.8%] vs 37 of 167 patients [22.2%], respectively; difference, 4.6%; 95% CI, -4.6% to 13.7%; P = .32). In the hydrocortisone vs placebo groups, 21.5% vs 16.9% had secondary infections, 8.6% vs 8.5% had weaning failure, 30.7% vs 23.8% had muscle weakness, and 90.9% vs 81.5% had hyperglycemia. CONCLUSIONS AND RELEVANCE Among adults with severe sepsis not in septic shock, use of hydrocortisone compared with placebo did not reduce the risk of septic shock within 14 days. These findings do not support the use of hydrocortisone in these patients.
引用
收藏
页码:1775 / 1785
页数:11
相关论文
共 40 条
  • [1] Influence of systemic inflammatory response syndrome and sepsis on outcome of critically ill infected patients
    Alberti, C
    Brun-Buisson, C
    Goodman, SV
    Guidici, D
    Granton, J
    Moreno, R
    Smithies, M
    Thomas, O
    Artigas, A
    Le Gall, JR
    [J]. AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, 2003, 168 (01) : 77 - 84
  • [2] Corticosteroids for severe sepsis and septic shock: a systematic review and meta-analysis
    Annane, D
    Bellissant, E
    Bollaert, PE
    Briegel, J
    Keh, D
    Kupfer, Y
    [J]. BMJ-BRITISH MEDICAL JOURNAL, 2004, 329 (7464): : 480 - 484
  • [3] Effect of treatment with low doses of hydrocortisone and fludrocortisone on mortality in patients with septic shock
    Annane, D
    Sébille, V
    Charpentier, C
    Bollaert, PE
    François, B
    Korach, JM
    Capellier, G
    Cohen, Y
    Azoulay, E
    Troché, G
    Chaumet-Riffaut, P
    Bellissant, E
    [J]. JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION, 2002, 288 (07): : 862 - 871
  • [4] Corticosteroids for treating sepsis
    Annane, Djillali
    Bellissant, Eric
    Bollaert, Pierre Edouard
    Briegel, Josef
    Keh, Didier
    Kupfer, Yizhak
    [J]. COCHRANE DATABASE OF SYSTEMATIC REVIEWS, 2015, (12):
  • [5] [Anonymous], 2013, Clinical trials: a practical approach
  • [6] Adjunct prednisone therapy for patients with community-acquired pneumonia: a multicentre, double-blind, randomised, placebo-controlled trial
    Blum, Claudine Angela
    Nigro, Nicole
    Briel, Matthias
    Schuetz, Philipp
    Ullmer, Elke
    Suter-Widmer, Isabelle
    Winzeler, Bettina
    Bingisser, Roland
    Elsaesser, Hanno
    Drozdov, Daniel
    Arici, Birsen
    Urwyler, Sandrine Andrea
    Refardt, Julie
    Tarr, Philip
    Wirz, Sebastian
    Thomann, Robert
    Baumgartner, Christine
    Duplain, Herve
    Burki, Dieter
    Zimmerli, Werner
    Rodondi, Nicolas
    Mueller, Beat
    Christ-Crain, Mirjam
    [J]. LANCET, 2015, 385 (9977) : 1511 - 1518
  • [7] A CONTROLLED CLINICAL-TRIAL OF HIGH-DOSE METHYLPREDNISOLONE IN THE TREATMENT OF SEVERE SEPSIS AND SEPTIC SHOCK
    BONE, RC
    FISHER, CJ
    CLEMMER, TP
    SLOTMAN, GJ
    METZ, CA
    BALK, RA
    [J]. NEW ENGLAND JOURNAL OF MEDICINE, 1987, 317 (11) : 653 - 658
  • [8] DEFINITIONS FOR SEPSIS AND ORGAN FAILURE AND GUIDELINES FOR THE USE OF INNOVATIVE THERAPIES IN SEPSIS
    BONE, RC
    BALK, RA
    CERRA, FB
    DELLINGER, RP
    FEIN, AM
    KNAUS, WA
    SCHEIN, RMH
    SIBBALD, WJ
    [J]. CHEST, 1992, 101 (06) : 1644 - 1655
  • [9] Intensive insulin therapy and pentastarch resuscitation in severe sepsis
    Brunkhorst, Frank M.
    Engel, Christoph
    Bloos, Frank
    Meier-Hellmann, Andreas
    Ragaller, Max
    Weiler, Norbert
    Moerer, Onnen
    Gruendling, Matthias
    Oppert, Michael
    Grond, Stefan
    Olthoff, Derk
    Jaschinski, Ulrich
    John, Stefan
    Rossaint, Rolf
    Welte, Tobias
    Schaefer, Martin
    Kern, Peter
    Kuhnt, Evelyn
    Kiehntopf, Michael
    Hartog, Christiane
    Natanson, Charles
    Loeffler, Markus
    Reinhart, Konrad
    [J]. NEW ENGLAND JOURNAL OF MEDICINE, 2008, 358 (02) : 125 - 139
  • [10] The Stress Response to Surgery and Postoperative Delirium: Evidence of Hypothalamic-Pituitary-Adrenal Axis Hyperresponsiveness and Decreased Suppression of the GH/IGF-1 Axis
    Cerejeira, Joaquim
    Batista, Pedro
    Nogueira, Vasco
    Vaz-Serra, Adriano
    Mukaetova-Ladinska, Elizabeta B.
    [J]. JOURNAL OF GERIATRIC PSYCHIATRY AND NEUROLOGY, 2013, 26 (03) : 185 - 194