Abstract
The goal of this study was to determine the utility of hydrocortisone in septic shock and its effect on mortality. We performed a systematic search from inception until March 01, 2018, according to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines comparing hydrocortisone to placebo in septic shock patients and selected studies according to our pre-defined inclusion and exclusion criteria. Four reviewers extracted data into the predefined tables in the Microsoft Excel (Microsoft Corp., New Mexico, US) sheet. We used RevMan software to perform a meta-analysis and draw Forest plots. We used a random effects model to estimate risk ratios. A two-sided p-value of ≤ 0.05 was considered statistically significant. A total of five randomized control trials (RCTs) with 5,838 patients were included in our analysis. The primary outcome was mortality at 28 days. Secondary outcomes were intensive care unit (ICU) and in-hospital mortality, mortality at 90 days and one year, reversal of shock, intensive care unit (ICU) and hospital length of stay, incidence of superinfections, and incidence of limb and/or cerebral ischemia. The 28-day mortality was significantly reduced with hydrocortisone, 808 vs. 880 with placebo, Risk Ratio (RR)=0.92, confidence interval (CI) =0.85-0.99, p=0.04, I2=0%. There was no difference in ICU mortality (RR=0.93, CI=0.81-1.08), in-hospital mortality (RR=0.95, CI=0.84-1.08), 90-day mortality (RR=0.93, CI=0.84-1.02, p=0.10), and one-year mortality (RR=0.97, CI=0.84-1.12). Superinfections were significantly common with hydrocortisone, RR=1.16, CI=1.05-1.28, p=0.003. In conclusion, the use of hydrocortisone showed a significant reduction in mortality at 28 days and a trend toward reduced ICU mortality. This mortality reduction was observed at the cost of significantly higher superinfections.
Highlights
Sepsis is a significant health concern globally with an associated mortality of 14.7% to 29.9% [1]
The 28-day mortality was significantly reduced with hydrocortisone, 808 vs. 880 with placebo, Risk Ratio (RR)=0.92, confidence interval (CI) =0.85-0.99, p=0.04, I2=0%
There was a total of 1,688 deaths with a significantly reduced number of deaths in the hydrocortisone and fludrocortisone arm as compared to the placebo arm
Summary
Sepsis is a significant health concern globally with an associated mortality of 14.7% to 29.9% [1]. Other than the respiratory support with mechanical ventilation, hemodynamic support with fluid resuscitation and vasopressors, and source control of the infection with antibiotics and surgical evacuation of infection, there is no additional approved treatment for either sepsis or septic shock [2]. A study from 1976 by Schumer et al showed a significant reduction in mortality in septic shock with high dose steroids given for a short duration [5]. Several subsequent studies, including systematic reviews, meta-analysis, and randomized control trials (RCTs), have not shown consistent evidence for or against steroids in sepsis and septic shock [10,11,12]. Current surviving sepsis guidelines recommend the use of steroids when fluid resuscitation and vasopressors are not effective in correcting hemodynamic instability, but this remains a weak recommendation [2].
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