BACKGROUND: Recent studies have reported a high prevalence of relative adrenal insufficiency in patients with liver cirrhosis. However, the effect of corticosteroid replacement on mortality in this high-risk group remains unclear. We examined the effect of low-dose hydrocortisone in patients with cirrhosis who presented with septic shock. METHODS: We enrolled patients with cirrhosis and septic shock aged 18 years or older in a randomized double-blind placebo-controlled trial. Relative adrenal insufficiency was defined as a serum cortisol increase of less than 250 nmol/L or 9 μg/dL from baseline after stimulation with 250 μg of intravenous corticotropin. Patients were assigned to receive 50 mg of intravenous hydrocortisone or placebo every six hours until hemodynamic stability was achieved, followed by steroid tapering over eight days. The primary outcome was 28-day all-cause mortality. RESULTS: The trial was stopped for futility at interim analysis after 75 patients were enrolled. Relative adrenal insufficiency was diagnosed in 76% of patients. Compared with the placebo group (n = 36), patients in the hydrocortisone group (n = 39) had a significant reduction in vasopressor doses and higher rates of shock reversal (relative risk [RR] 1.58, 95% confidence interval [CI] 0.98-2.55, p = 0.05). Hydrocortisone use was not associated with a reduction in 28-day mortality (RR 1.17, 95% CI 0.92-1.49, p = 0.19) but was associated with an increase in shock relapse (RR 2.58, 95% CI 1.04-6.45, p = 0.03) and gastrointestinal bleeding (RR 3.00, 95% CI 1.08-8.36, p = 0.02). INTERPRETATION:Relative adrenal insufficiency was very common in patients with cirrhosis presenting with septic shock. Despite initial favourable effects on hemodynamic parameters, hydrocortisone therapy did not reduce mortality and was associated with an increase in adverse effects. (Current Controlled Trials registry no. ISRCTN99675218.).
RCT Entities:
BACKGROUND: Recent studies have reported a high prevalence of relative adrenal insufficiency in patients with liver cirrhosis. However, the effect of corticosteroid replacement on mortality in this high-risk group remains unclear. We examined the effect of low-dose hydrocortisone in patients with cirrhosis who presented with septic shock. METHODS: We enrolled patients with cirrhosis and septic shock aged 18 years or older in a randomized double-blind placebo-controlled trial. Relative adrenal insufficiency was defined as a serum cortisol increase of less than 250 nmol/L or 9 μg/dL from baseline after stimulation with 250 μg of intravenous corticotropin. Patients were assigned to receive 50 mg of intravenous hydrocortisone or placebo every six hours until hemodynamic stability was achieved, followed by steroid tapering over eight days. The primary outcome was 28-day all-cause mortality. RESULTS: The trial was stopped for futility at interim analysis after 75 patients were enrolled. Relative adrenal insufficiency was diagnosed in 76% of patients. Compared with the placebo group (n = 36), patients in the hydrocortisone group (n = 39) had a significant reduction in vasopressor doses and higher rates of shock reversal (relative risk [RR] 1.58, 95% confidence interval [CI] 0.98-2.55, p = 0.05). Hydrocortisone use was not associated with a reduction in 28-day mortality (RR 1.17, 95% CI 0.92-1.49, p = 0.19) but was associated with an increase in shock relapse (RR 2.58, 95% CI 1.04-6.45, p = 0.03) and gastrointestinal bleeding (RR 3.00, 95% CI 1.08-8.36, p = 0.02). INTERPRETATION: Relative adrenal insufficiency was very common in patients with cirrhosis presenting with septic shock. Despite initial favourable effects on hemodynamic parameters, hydrocortisone therapy did not reduce mortality and was associated with an increase in adverse effects. (Current Controlled Trials registry no. ISRCTN99675218.).
Authors: E Rivers; B Nguyen; S Havstad; J Ressler; A Muzzin; B Knoblich; E Peterson; M Tomlanovich Journal: N Engl J Med Date: 2001-11-08 Impact factor: 91.245
Authors: J Briegel; H Forst; M Haller; G Schelling; E Kilger; G Kuprat; B Hemmer; T Hummel; A Lenhart; M Heyduck; C Stoll; K Peter Journal: Crit Care Med Date: 1999-04 Impact factor: 7.598
Authors: G Fernández-Esparrach; M Guevara; P Sort; A Pardo; W Jiménez; P Ginès; R Planas; D Lebrec; A Geuvel; A Elewaut; M Adler; V Arroyo Journal: J Hepatol Date: 1997-03 Impact factor: 25.083
Authors: Paul E Marik; Stephen M Pastores; Djillali Annane; G Umberto Meduri; Charles L Sprung; Wiebke Arlt; Didier Keh; Josef Briegel; Albertus Beishuizen; Ioanna Dimopoulou; Stylianos Tsagarakis; Mervyn Singer; George P Chrousos; Gary Zaloga; Faran Bokhari; Michael Vogeser Journal: Crit Care Med Date: 2008-06 Impact factor: 7.598
Authors: Djillali Annane; Stephen M Pastores; Bram Rochwerg; Wiebke Arlt; Robert A Balk; Albertus Beishuizen; Josef Briegel; Joseph Carcillo; Mirjam Christ-Crain; Mark S Cooper; Paul E Marik; Gianfranco Umberto Meduri; Keith M Olsen; Sophia Rodgers; James A Russell; Greet Van den Berghe Journal: Intensive Care Med Date: 2017-09-21 Impact factor: 17.440
Authors: Sara Blasco-Algora; José Masegosa-Ataz; María Luisa Gutiérrez-García; Sonia Alonso-López; Conrado M Fernández-Rodríguez Journal: World J Gastroenterol Date: 2015-11-14 Impact factor: 5.742
Authors: Sofie Louise Rygård; Ethan Butler; Anders Granholm; Morten Hylander Møller; Jeremy Cohen; Simon Finfer; Anders Perner; John Myburgh; Balasubramanian Venkatesh; Anthony Delaney Journal: Intensive Care Med Date: 2018-05-14 Impact factor: 17.440