Reevaluating the Role of Corticosteroids in Septic Shock: An Updated Meta-Analysis of Randomized Controlled Trials

Abstract

What Is Known and Objective. To reevaluate the benefits and risks of corticosteroid treatment in adult patients with septic shock. Methods. This study was performed based on PRISMA guidelines. Randomized controlled trials (RCTs) of corticosteroids versus placebo were retrieved from PubMed, MEDLINE, EMBASE, Web of Science, the Cochrane Central RCTs, and ClinicalTrials.gov from January 1980 to April 2018. We also conducted a trial sequential analysis to indicate the possibility of type I or II errors and calculate the information size. Grading of Recommendations, Assessment, Development and Evaluation approach (GRADE) was applying to assess the certainty of evidence at the primary outcome level. Results. Twenty-one RCTs were identified and analyzed. Patients treated with corticosteroid had a 7% reduction in relative risk in 28-day all-cause mortality compared to controls (RR 0.93, 95% CI 0.88 to 0.99). However, there were no significant differences for the intensive care unit (ICU) mortality (RR 0.97, 95% CI 0.86 to 1.09) or in-hospital mortality (RR 1.01, 95% CI 0.92 to 1.11). Corticosteroids shortened the length of ICU stay by 1.04 days (RR -1.04, 95% CI -1.72 to -0.36) and the length of hospital stay by 2.49 days (RR -2.49, 95% CI -4.96 to -0.02). Corticosteroids increased the risk of hyperglycemia (RR 1.11, 95% CI 1.06 to 1.16) but not gastroduodenal bleeding (RR 1.06, 95% CI 0.82 to 1.37) or superinfection (RR 1.04, 95% CI 0.94 to 1.15). However, some date on secondary outcomes were unavailable because they were not measured or not reported in the included studies which may cause a lack of power or selective outcome reporting. The information size was calculated at 10044 patients. Trial sequential analysis showed that the meta-analysis was conclusive and the risk of type 2 error was minimal. What Is New and Conclusion. Corticosteroids are likely to be effective in reducing 28-day mortality and attenuating septic shock without increasing the rate of life-threatening complications. TSA showed that the risk of type II error in this meta-analysis was minimal and the result was conclusive.

Figure 1

Study flow diagram.

Figure 2

Risk of bias summary and graph in each domain for individual studies. (Green + = adequate. Red - = inadequate. Yellow? = unclear). Other biases refer to either academic or funding bias.

Figure 3

Funnel plot with 95% confidence interval (CI) to assess publication bias.

Figure 4

Forest plots of comparison corticosteroids versus control for 28-day all-cause mortality.

Figure 5

Results of trial sequential analysis for 28-day all-cause mortality. A diversity-adjusted information size of 10044 patients was calculated based on an anticipated RRR of 7% (event proportion of 40% in the control arm, α=0.05 [two-sided]; β=0.20 [power 80%]).