Low-dose hydrocortisone in patients with cirrhosis and septic shock: a randomized controlled trial.
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).


CONCLUSIONS
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.).
Department of Intensive Care Medicine, King Saud Bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia. yaseenarabi@yahoo.com
Yaseen M
YM
Arabi
Abdulrahman
A
Aljumah
Ousama
O
Dabbagh
Hani M
HM
Tamim
Asgar H
AH
Rishu
Abdulmajeed
A
Al-Abdulkareem
Bandar Al
BA
Knawy
Ali H
AH
Hajeer
Waleed
W
Tamimi
Antoine
A
Cherfan
D000309:Adrenal Insufficiency / Q000188:drug therapy* / Q000209:etiology / Q000401:mortality; D002423:Cause of Death / Q000639:trends; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D005938:Glucocorticoids / Q000008:administration & dosage*; D006801:Humans; D006854:Hydrocortisone / Q000008:administration & dosage*; D007275:Injections, Intravenous; D007902:Length of Stay / Q000639:trends; D008103:Liver Cirrhosis / Q000150:complications / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D012307:Risk Factors; D012529:Saudi Arabia / Q000453:epidemiology; D012772:Shock, Septic / Q000150:complications / Q000188:drug therapy* / Q000401:mortality; D016896:Treatment Outcome
D005938:Glucocorticoids; D006854:Hydrocortisone