Effect of Hydrocortisone on Development of Shock Among Patients with Severe Sepsis

Shirin Faridian Zadeh, Mercer University College of Pharmacy

The place in therapy of corticosteroid treatment in patients with severe sepsis and septic shock is stated to remain unclear.1 The current Surviving Sepsis guideline recommends against using intravenous hydrocortisone as a treatment for adult septic shock patients if adequate fluid resuscitation and vasopressor therapy are able to restore hemodynamic stability. In cases where patients do not meet this criterion, the guidelines suggest intravenous hydrocortisone alone at a dose of 200mg per day.2  This study is the first randomized controlled trial investigating whether hydrocortisone prevents shock in patients with severe sepsis presenting without shock.3

Effect of Hydrocortisone on Development of Shock Among Patients with Severe Sepsis: The HYPRESS Randomized Clinical Trial 2
Design Multicenter, placebo-controlled double-blind randomized controlled trial; N= 380
Objective To determine whether hydrocortisone therapy in patients with severe sepsis prevents the development of septic shock
Study Groups Hydrocortisone (n= 190); placebo (n= 190)
Methods Patients were randomly assigned to receive either hydrocortisone or placebo. Patients with a confirmed infection, evidence of a systemic response to infection defined as at least two systemic inflammatory response syndrome criteria, and presence of organ dysfunction were included. Patients with septic shock were excluded. Septic shock was defined as sepsis-induced hypotension despite adequate volume status for longer than 4 hours, central venous pressure of 8mmHg or greater (≥12mmHg in ventilated patients), and a central venous oxygen saturation greater than 70%. The medication was administered as an intravenous bolus of 50 mg, followed by a 24-hour continuous infusion of 200 mg for 5 days, 100 mg on days 6 and 7, 50 mg on days 8 and 9, and 25 mg on days 10 and 11.
Duration January 13, 2009, to August 27, 2013
Primary Outcome Measure Development of septic shock within 14 days
Baseline Characteristics Hydrocortisone Placebo
Male, % 63.1 66.7
Mean Age, years (SD) 64.6 (14.6) 65.5 (14.2)
SIRS criteria, n/total (%)
Temperature ≤36°C or ≥38°C 141/176 (80.1) 129/177 (72.9)
Heart rate ≥90 beats/min 164/176 (93.2) 158/177 (89.3)
Tachypnea, hypocapnia, or mechanical ventilation 157/176 (89.2) 145/176 (82.4)
Leukocytosis, leukopenia, or left shift 132/176 (75.0) 131/177 (74.0)
Source of infection, n/total (n%)
Community 83/176 (47.2) 82/177 (46.3)
Nosocomial, ICU 52/176 (29.5) 41/177 (23.2)
Nosocomial, ward 41/176 (23.3) 54/177 (30.5)
Medication within 72 hours before randomization
Intravenous glucocorticoids, n/ total (%) 6/176 (3.4) 3/177 (1.7)
Median hydrocortisone equivalent, mg (range) 600 (392-1000) 200 (200-400)
Results Septic shock, n/total (%) [95% CI] Hydrocortisone Placebo p-value
Intention-to-treat population 36/170 (21.2)


39/170 (22.9)


Per-protocol population 29/155 (18.7)


33/156 (21.2)


0. 59
Adverse Events Common Adverse Events: blood glucose level >150mg/dL (9.4%)
Serious Adverse Events: severe hypertension (0.5%)
Percentage that Discontinued due to Adverse Events: N/A
Study Author Conclusions 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.


With the assumption that severe sepsis and septic shock reflect a disease continuum, many studies have hypothesized that early hydrocortisone administration might prevent shock development due to the diminution of an exaggerated inflammatory response. However, based on these findings the use of hydrocortisone in patients with severe sepsis is not beneficial.



  1. Annane D. Corticosteroids for severe sepsis: an evidence-based guide for physicians. Ann Intensive Care. 2011;1(1):7.
  2. Dellinger RP, Levy MM, Rhodes A, et al. Surviving sepsis campaign: international guidelines for management of severe sepsis and septic shock: 2012. Crit Care Med. 2013;41(2):580-637.
  3. Keh D, Trips E, Marx G, et al. Effect of Hydrocortisone on Development of Shock Among Patients with Severe Sepsis: The HYPRESS Randomized Clinical Trial. JAMA. 2016;14799.

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