Hydrocortisone Reduces 28-day Mortality in Septic Patients: A Systemic Review and Meta-analysis

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, I 2 =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.

Do We Need to Administer Fludrocortisone in Addition to Hydrocortisone in Adult Patients With Septic Shock? An Updated Systematic Review With Bayesian Network Meta-Analysis of Randomized Controlled Trials and an Observational Study With Target Trial Emulation*

“…However, their results were based on a meta-analysis of only five RCTs. Systematic reviews with meta-analyses published after 2018 have shown inconsistent results regarding short-term mortality linked to hydrocortisone use in patients with sepsis (12,(47)(48)(49)(50). These disparities may arise from factors, such as the use of different steroids, application of varied statistical methods, and inclusion of participants beyond just adults with septic shock.…”

“…Our findings indicate that hydrocortisone alone demonstrated marginal benefits over placebo. In a systematic review conducted in 2019, Siddiqui et al ( 47 ) concluded that the administration of hydrocortisone significantly reduced the 28-day mortality rate among patients with refractory septic shock. However, their results were based on a meta-analysis of only five RCTs.…”

Navigating the Landscape of Hydrocortisone Administration in Septic Shock: Current Concepts and Future Directions

“…Such limitations make it challenging to draw definitive conclusions about the efficacy and safety of hydrocortisone. The variability in study designs and patient characteristics has hindered the ability to extrapolate findings to broader septic shock populations [ 16 ].…”

“…Mortality reduction: The impact of hydrocortisone on mortality rates among septic shock patients remains a subject of ongoing debate and further investigation. While findings may exhibit variability across studies, certain trials, and systematic reviews have reported reduced mortality rates among specific subgroups of septic shock patients receiving hydrocortisone [ 16 ]. This observation underscores the nuanced and potentially lifesaving role that hydrocortisone can play in specific clinical contexts.…”

Does hydrocortisone reduce mortality in mechanically ventilated patients with septic shock?

“…A 2019 systemic review and meta-analysis included five randomized controlled trials (RCTs) comparing the effects of treatment with hydrocortisone to placebo on 28-day all-cause mortality in adult intensive care unit (ICU) patients (N=5,838). 1 Patients were approximately 64 years old and 64% male. The active treatment protocol varied in the studies with two trials using hydrocortisone 50 mg IV every six hours plus fludrocortisone 50 µg via nasogastric (NG) tube for seven days (n=1,570), two trials using hydrocortisone 200 mg daily continuous IV (1 trial for 7 days, and 1 for 6 days with additional 6 day taper; n=3,801), and one trial using hydrocortisone 50 mg IV every six hours for five days followed by a six-day taper (n=499).…”