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Open Access 01-12-2015 | Research

Clinical impact of stress dose steroids in patients with septic shock: insights from the PROWESS-Shock trial

Authors: Pedro Póvoa, Jorge I F Salluh, Maria L Martinez, Raquel Guillamat-Prats, Dianne Gallup, Hussein R Al-Khalidi, B Taylor Thompson, V Marco Ranieri, Antonio Artigas

Published in: Critical Care | Issue 1/2015

Abstract

Introduction

The aim of our study was to evaluate the clinical impact of the administration of intravenous steroids, alone or in conjunction with drotrecogin-alfa (activated) (DrotAA), on the outcomes in septic shock patients.

Methods

We performed a sub-study of the PROWESS-Shock trial (septic shock patients who received fluids and vasopressors above a predefined threshold for at least 4 hours were randomized to receive either DrotAA or placebo for 96 hours). A propensity score for the administration of intravenous steroids for septic shock at baseline was constructed using multivariable logistic regression. Cox proportional hazards model using inverse probability of treatment weighting of the propensity score was used to estimate the effect of intravenous steroids, alone or in conjunction with DrotAA, on 28-day and 90-day all-cause mortality.

Results

A total of 1695 patients were enrolled of which 49.5% received intravenous steroids for treatment of septic shock at baseline (DrotAA + steroids N = 436; DrotAA + no steroids N = 414; placebo + steroids N = 403; placebo + no steroids N = 442). The propensity weighted risk of 28-day as well as 90-day mortality in those treated vs. those not treated with steroids did not differ among those randomized to DrotAA vs. placebo (interaction p-value = 0.38 and p = 0.27, respectively) nor was a difference detected within each randomized treatment. Similarly, the course of vasopressor use and cardiovascular SOFA did not appear to be influenced by steroid therapy. In patients with lung infection (N = 744), abdominal infection (N = 510), Gram-positive sepsis (N = 420) and Gram-negative sepsis (N = 461), the propensity weighted risk of 28-day as well as 90-day mortality in those treated vs. those not treated with steroids did not differ among those randomized to DrotAA vs. placebo nor was a difference detected within each randomized treatment.

Conclusions

In the present study of septic shock patients, after adjustment for treatment selection bias, we were unable to find noticeable positive impact from intravenous steroids for treatment of septic shock at baseline either in patients randomized for DrotAA or placebo.

Trial registration

Clinicaltrials.gov NCT00604214. Registered 24 January 2008.

Angus DC, Linde-Zwirble WT, Lidicker J, Clermont G, Carcillo J, Pinsky MR. Epidemiology of severe sepsis in the United States: analysis of incidence, outcome, and associated costs of care. Crit Care Med. 2001;29:1303–10.CrossRefPubMedCentral

Wang HE, Shapiro NI, Angus DC, Yealy DM. National estimates of severe sepsis in United States emergency departments. Crit Care Med. 2007;35:1928–36.CrossRefPubMedCentral

Asfar P, Meziani F, Hamel JF, Grelon F, Megarbane B, Anguel N, et al. High versus low blood-pressure target in patients with septic shock. N Engl J Med. 2014;370:1583–93.CrossRefPubMedCentral

Caironi P, Tognoni G, Masson S, Fumagalli R, Pesenti A, Romero M, et al. Albumin replacement in patients with severe sepsis or septic shock. N Engl J Med. 2014;370:1412–21.CrossRefPubMedCentral

Pro CI, Yealy DM, Kellum JA, Huang DT, Barnato AE, Weissfeld LA, et al. A randomized trial of protocol-based care for early septic shock. N Engl J Med. 2014;370:1683–93.CrossRef

Ferrer R, Artigas A, Levy MM, Blanco J, Gonzalez-Diaz G, Garnacho-Montero J, et al. Improvement in process of care and outcome after a multicenter severe sepsis educational program in Spain. JAMA. 2008;299:2294–303.CrossRefPubMedCentral

Levy MM, Dellinger RP, Townsend SR, Linde-Zwirble WT, Marshall JC, Bion J, et al. The Surviving Sepsis Campaign: results of an international guideline-based performance improvement program targeting severe sepsis. Intensive Care Med. 2010;36:222–31.CrossRefPubMedCentral

Dellinger RP, Levy MM, Rhodes A, Annane D, Gerlach H, Opal SM, et al. Surviving sepsis campaign: international guidelines for management of severe sepsis and septic shock: 2012. Crit Care Med. 2013;41:580–637.CrossRefPubMedCentral

Kaukonen KM, Bailey M, Suzuki S, Pilcher D, Bellomo R. Mortality related to severe sepsis and septic shock among critically ill patients in Australia and New Zealand, 2000–2012. JAMA. 2014;311:1308–16.CrossRefPubMedCentral

10.

Bernard GR, Vincent JL, Laterre PF, LaRosa SP, Dhainaut JF, Lopez-Rodriguez A, et al. Efficacy and safety of recombinant human activated protein C for severe sepsis. N Engl J Med. 2001;344:699–709.CrossRefPubMedCentral

11.

Annane D, Sebille V, Charpentier C, Bollaert PE, Francois B, Korach JM, et al. Effect of treatment with low doses of hydrocortisone and fludrocortisone on mortality in patients with septic shock. JAMA. 2002;288:862–71.CrossRefPubMedCentral

12.

Dellinger RP, Carlet JM, Masur H, Gerlach H, Calandra T, Cohen J, et al. Surviving Sepsis Campaign guidelines for management of severe sepsis and septic shock. Crit Care Med. 2004;32:858–73.CrossRefPubMedCentral

13.

Dellinger RP, Levy MM, Carlet JM, Bion J, Parker MM, Jaeschke R, et al. Surviving Sepsis Campaign: international guidelines for management of severe sepsis and septic shock: 2008. Crit Care Med. 2008;36:296–327.CrossRefPubMedCentral

14.

Sprung CL, Annane D, Keh D, Moreno R, Singer M, Freivogel K, et al. Hydrocortisone therapy for patients with septic shock. N Engl J Med. 2008;358:111–24.CrossRefPubMedCentral

15.

Ranieri VM, Thompson BT, Barie PS, Dhainaut JF, Douglas IS, Finfer S, et al. Drotrecogin alfa (activated) in adults with septic shock. N Engl J Med. 2012;366:2055–64.CrossRefPubMedCentral

16.

Annane D, Timsit JF, Megarbane B, Martin C, Misset B, Mourvillier B, et al. Recombinant human activated protein C for adults with septic shock: a randomized controlled trial. Am J Respir Crit Care Med. 2013;187:1091–7.CrossRefPubMedCentral

17.

Mason PE, Al-Khafaji A, Milbrandt EB, Suffoletto BP, Huang DT. CORTICUS: the end of unconditional love for steroid use? Crit Care. 2009;13:309.CrossRefPubMedCentral

18.

Toma A, Stone A, Green RS, Gray S. Steroids for patients in septic shock: the results of the CORTICUS trial. CJEM. 2011;13:273–6.CrossRefPubMedCentral

19.

Cole SR, Hernan MA. Adjusted survival curves with inverse probability weights. Comput Meth Programs Biomed. 2004;75:45–9.CrossRef

20.

Shore S, Nelson DP, Pearl JM, Manning PB, Wong H, Shanley TP, et al. Usefulness of corticosteroid therapy in decreasing epinephrine requirements in critically ill infants with congenital heart disease. Am J Cardiol. 2001;88:591–4.CrossRefPubMedCentral

21.

Russell JA, Walley KR, Singer J, Gordon AC, Hebert PC, Cooper DJ, et al. Vasopressin versus norepinephrine infusion in patients with septic shock. N Engl J Med. 2008;358:877–87.CrossRefPubMedCentral

22.

Cruz DN, Antonelli M, Fumagalli R, Foltran F, Brienza N, Donati A, et al. Early use of polymyxin B hemoperfusion in abdominal septic shock: the EUPHAS randomized controlled trial. JAMA. 2009;301:2445–52.CrossRefPubMedCentral

23.

Austin PC. The relative ability of different propensity score methods to balance measured covariates between treated and untreated subjects in observational studies. Med Decis Making. 2009;29:661–77.CrossRefPubMedCentral

24.

Patel GP, Balk RA. Systemic steroids in severe sepsis and septic shock. Am J Respir Crit Care Med. 2012;185:133–9.CrossRefPubMedCentral

25.

Annane D, Bellissant E, Bollaert PE, Briegel J, Confalonieri M, De Gaudio R, et al. Corticosteroids in the treatment of severe sepsis and septic shock in adults: a systematic review. JAMA. 2009;301:2362–75.CrossRefPubMedCentral

26.

Beale R, Janes JM, Brunkhorst FM, Dobb G, Levy MM, Martin GS, et al. Global utilization of low-dose corticosteroids in severe sepsis and septic shock: a report from the PROGRESS registry. Crit Care. 2010;14:R102.CrossRefPubMedCentral

27.

Sligl WI, Milner Jr DA, Sundar S, Mphatswe W, Majumdar SR. Safety and efficacy of corticosteroids for the treatment of septic shock: A systematic review and meta-analysis. Clin Infect Dis. 2009;49:93–101.CrossRefPubMedCentral

28.

Bollaert PE, Charpentier C, Levy B, Debouverie M, Audibert G, Larcan A. Reversal of late septic shock with supraphysiologic doses of hydrocortisone. Crit Care Med. 1998;26:645–50.CrossRefPubMedCentral

29.

Briegel J, Forst H, Haller M, Schelling G, Kilger E, Kuprat G, et al. Stress doses of hydrocortisone reverse hyperdynamic septic shock: a prospective, randomized, double-blind, single-center study. Crit Care Med. 1999;27:723–32.CrossRefPubMedCentral

30.

Oppert M, Schindler R, Husung C, Offermann K, Graf KJ, Boenisch O, et al. Low-dose hydrocortisone improves shock reversal and reduces cytokine levels in early hyperdynamic septic shock. Crit Care Med. 2005;33:2457–64.CrossRefPubMedCentral

31.

Yildiz O, Doganay M, Aygen B, Guven M, Kelestimur F, Tutuu A. Physiological-dose steroid therapy in sepsis [ISRCTN36253388]. Crit Care. 2002;6:251–9.CrossRefPubMedCentral

32.

Katsenos CS, Antonopoulou AN, Apostolidou EN, Ioakeimidou A, Kalpakou GT, Papanikolaou MN, et al. Early administration of hydrocortisone replacement after the advent of septic shock: impact on survival and immune response. Crit Care Med. 2014;42:1651–7.CrossRefPubMedCentral

33.

Funk D, Doucette S, Pisipati A, Dodek P, Marshall JC, Kumar A, et al. Low-dose corticosteroid treatment in septic shock: a propensity-matching study. Crit Care Med. 2014;42:2333–41.CrossRefPubMedCentral

34.

Greenberg SB, Coursin DB. Timing of corticosteroids in refractory septic shock: a key or wishful thinking? Crit Care Med. 2014;42:1733–5.CrossRefPubMedCentral

35.

Allen KS, Kinasewitz GT. The pendulum of corticosteroids in sepsis swings again? Crit Care Med. 2014;42:2442–3.CrossRefPubMedCentral

36.

Briegel J, Sprung CL, Annane D, Singer M, Keh D, Moreno R, et al. Multicenter comparison of cortisol as measured by different methods in samples of patients with septic shock. Intensive Care Med. 2009;35:2151–6.CrossRefPubMedCentral

37.

Marik PE. Critical illness-related corticosteroid insufficiency. Chest. 2009;135:181–93.CrossRefPubMedCentral

38.

Hamrahian AH, Oseni TS, Arafah BM. Measurements of serum free cortisol in critically ill patients. N Engl J Med. 2004;350:1629–38.CrossRefPubMedCentral

39.

Boonen E, Vervenne H, Meersseman P, Andrew R, Mortier L, Declercq PE, et al. Reduced cortisol metabolism during critical illness. N Engl J Med. 2013;368:1477–88.CrossRefPubMedCentral

Title: Clinical impact of stress dose steroids in patients with septic shock: insights from the PROWESS-Shock trial
Authors: Pedro Póvoa
Jorge I F Salluh
Maria L Martinez
Raquel Guillamat-Prats
Dianne Gallup
Hussein R Al-Khalidi
B Taylor Thompson
V Marco Ranieri
Antonio Artigas
Publication date: 01-12-2015
Publisher: BioMed Central
Published in: Critical Care / Issue 1/2015
Electronic ISSN: 1364-8535
DOI: https://doi.org/10.1186/s13054-015-0921-x

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Clinical impact of stress dose steroids in patients with septic shock: insights from the PROWESS-Shock trial

Abstract

Introduction

Methods

Results

Conclusions

Trial registration

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Introduction

Methods

Results

Conclusions

Trial registration

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