BACKGROUND: Very little direct evidence exists on use of corticosteroids in patients with coronavirus disease 2019 (COVID-19). Indirect evidence from related conditions must therefore inform inferences regarding benefits and harms. To support a guideline for managing COVID-19, we conducted systematic reviews examining the impact of corticosteroids in COVID-19 and related severe acute respiratory illnesses.
METHODS: We searched standard international and Chinese biomedical literature databases and prepublication sources for randomized controlled trials (RCTs) and observational studies comparing corticosteroids versus no corticosteroids in patients with COVID-19, severe acute respiratory syndrome (SARS) or Middle East respiratory syndrome (MERS). For acute respiratory distress syndrome (ARDS), influenza and community-acquired pneumonia (CAP), we updated the most recent rigorous systematic review. We conducted random-effects meta-analyses to pool relative risks and then used baseline risk in patients with COVID-19 to generate absolute effects.
RESULTS: In ARDS, according to 1 small cohort study in patients with COVID-19 and 7 RCTs in non-COVID-19 populations (risk ratio [RR] 0.72, 95% confidence interval [CI] 0.55 to 0.93, mean difference 17.3% fewer; low-quality evidence), corticosteroids may reduce mortality. In patients with severe COVID-19 but without ARDS, direct evidence from 2 observational studies provided very low-quality evidence of an increase in mortality with corticosteroids (hazard ratio [HR] 2.30, 95% CI 1.00 to 5.29, mean difference 11.9% more), as did observational data from influenza studies. Observational data from SARS and MERS studies provided very low-quality evidence of a small or no reduction in mortality. Randomized controlled trials in CAP suggest that corticosteroids may reduce mortality (RR 0.70, 95% CI 0.50 to 0.98, 3.1% lower; very low-quality evidence), and may increase hyperglycemia.
INTERPRETATION: Corticosteroids may reduce mortality for patients with COVID-19 and ARDS. For patients with severe COVID-19 but without ARDS, evidence regarding benefit from different bodies of evidence is inconsistent and of very low quality.
BACKGROUND: Very little direct evidence exists on use of corticosteroids in patients with coronavirus disease 2019 (COVID-19). Indirect evidence from related conditions must therefore inform inferences regarding benefits and harms. To support a guideline for managing COVID-19, we conducted systematic reviews examining the impact of corticosteroids in COVID-19 and related severe acute respiratory illnesses.
METHODS: We searched standard international and Chinese biomedical literature databases and prepublication sources for randomized controlled trials (RCTs) and observational studies comparing corticosteroids versus no corticosteroids in patients with COVID-19, severe acute respiratory syndrome (SARS) or Middle East respiratory syndrome (MERS). For acute respiratory distress syndrome (ARDS), influenza and community-acquired pneumonia (CAP), we updated the most recent rigorous systematic review. We conducted random-effects meta-analyses to pool relative risks and then used baseline risk in patients with COVID-19 to generate absolute effects.
RESULTS: In ARDS, according to 1 small cohort study in patients with COVID-19 and 7 RCTs in non-COVID-19 populations (risk ratio [RR] 0.72, 95% confidence interval [CI] 0.55 to 0.93, mean difference 17.3% fewer; low-quality evidence), corticosteroids may reduce mortality. In patients with severe COVID-19 but without ARDS, direct evidence from 2 observational studies provided very low-quality evidence of an increase in mortality with corticosteroids (hazard ratio [HR] 2.30, 95% CI 1.00 to 5.29, mean difference 11.9% more), as did observational data from influenza studies. Observational data from SARS and MERS studies provided very low-quality evidence of a small or no reduction in mortality. Randomized controlled trials in CAP suggest that corticosteroids may reduce mortality (RR 0.70, 95% CI 0.50 to 0.98, 3.1% lower; very low-quality evidence), and may increase hyperglycemia.
INTERPRETATION: Corticosteroids may reduce mortality for patients with COVID-19 and ARDS. For patients with severe COVID-19 but without ARDS, evidence regarding benefit from different bodies of evidence is inconsistent and of very low quality.
OBJECTIVE: To investigate the effectiveness and safety of corticosteroids therapy in adult critical ill patients with septic shock.
METHODS: The PUBMED, EMBASE, Web of Science, Cochrane Library databases were systematically searched from the inception dates to March 24, 2018. To identify randomized controlled trials that evaluating the role of corticosteroids therapy in adult critical ill patients with septic shock. The primary outcome was 28-day mortality. The second outcomes included 90-day mortality, ICU mortality, In-hospital mortality, length of stay in ICU, length of stay in hospital, reversal of shock and superinfection.
RESULTS: A total of eighteen randomized controlled trials involving 8128 adult critical ill patients with septic shock fulfilled the inclusion criteria. The outcomes of this meta-analysis showed that corticosteroids therapy didn't significantly reduce the 28-day mortality [RR = 0.94; 95%CI, 0.84 to 1.05; Z = 1.07(P = 0.285)]. However, corticosteroids therapy was associated with a significantly shorter length of stay in ICU [WMD = -1.55; 95%CI, -2.19 to -0.91; Z = 4.74(P = 0.000)]. 90-day mortality, ICU mortality, In-hospital mortality, length of stay in hospital, reversal of shock and superinfection had no significantly difference between the corticosteroids therapy and placebo therapy(p > 0.05). Similar results were obtained in subgroups of trials stratified according to the dose of corticosteroids (high dose or low does).
CONCLUSIONS: Based on the results of this meta-analysis, corticosteroids therapy was associated with a significantly shorter length of stay in ICU among adult cirtical ill patients with septic shock. The mortality was similar between the corticosteroids therapy and placebo.
OBJECTIVE: Corticosteroids have important effects on intermediate outcomes in critically ill patients, but their effect on survival is unknown. The objective of this meta-analysis was to analyze the effect on mortality of corticosteroids in critical and perioperative settings.
DESIGN: A meta-analysis of randomized trials.
SETTING: PubMed, Embase, BioMed Central, Google Scholar, and the Cochrane Central Register of Controlled Trials were searched to February 1, 2018, for randomized trials comparing corticosteroids with placebo or standard care.
PARTICIPANTS: Critically ill or surgical adult patients.
INTERVENTIONS: Corticosteroids compared with placebo or standard care.
MEASUREMENTS AND MAIN RESULTS: A total of 44,553 patients from 135 studies were included. Overall, mortality in the corticosteroid group and in the control group were similar (16% v 16%; p = 0.9). Subanalyses identified a beneficial effect of corticosteroids on survival in patients with respiratory system diseases (9% v 13%; p < 0.001) and bacterial meningitis (28% v 32%; p= 0.04), and a detrimental effect on survival in patients with traumatic brain injury (22% v 19%; p < 0.001). No differences in mortality were found in patients with cardiac diseases (7% v 6%; p = 0.7), in patients undergoing cardiac surgery (2.8% v 3.2% p = 0.14), and when treatment duration or patient age were considered.
CONCLUSIONS: This meta-analysis documents the safety of corticosteroids in the overall critically ill population with the notable exception of brain injury patients, a setting where the authors confirmed their detrimental effect on survival. A possible beneficial effect of corticosteroids on survival was found among patients with respiratory diseases and in patients with bacterial meningitis.
BACKGROUND: The benefits and adverse effects of corticosteroids in the treatment of severe community-acquired pneumonia (CAP) have not been well assessed. The aim of this systematic review of the literature and meta-analysis was to evaluate the clinical efficacy of adjuvant corticosteroid therapy in patients with severe CAP.
METHODS: The following databases were searched: PubMed, the Cochrane database, Embase, Wanfang, the China National Knowledge Infrastructure (CNKI), and the WeiPu (VIP) database in Chinese. Published randomized controlled clinical trial results were identified that compared corticosteroid therapy with conventional therapy for patients with severe CAP, up to November 2016. The relative risk (RR), weighted mean difference (WMD), and 95% confidence interval (CI) were evaluated. Statistical analysis was performed using STATA 10.0. The quality of the published studies was evaluated using the Oxford quality scoring system (Jadad scale).
RESULTS: Ten randomized controlled trials (RCTs) were identified that included 729 patients with severe CAP. Data analysis showed that corticosteroid therapy did not have a statistically significant clinical effect in patients with severe CAP (RR: 1.19; 95% CI: 0.99-1.42), mechanical ventilation time (WMD: -2.30; 95% CI: -6.09-1.49). However, corticosteroids treatment was significantly associated with reduced in-hospital mortality (RR: 0.49; 95% CI: 0.29-0.85), reduced length of hospital stay (WMD: -4.21; 95% CI: -6.61 to -1.81).
CONCLUSION: Corticosteroids adjuvant therapy in patients with severe CAP may reduce the rate of in-hospital mortality, reduce the length of hospital stay, and reduce CRP levels.
PURPOSE: To assess the effect of low dose corticosteroids on outcomes in adults with septic shock.
METHODS: We systematically reviewed randomised clinical trials (RCTs) comparing low-dose corticosteroids to placebo in adults with septic shock. Trial selection, data abstraction and risk of bias assessment were performed in duplicate. The primary outcome was short-term mortality. Secondary and tertiary outcomes included longer-term mortality, adverse events, quality of life, and duration of shock, mechanical ventilation and ICU stay.
RESULTS: There were 22 RCTs, including 7297 participants, providing data on short-term mortality. In two low risk of bias trials, the relative risk (RR) of short-term mortality with corticosteroid versus placebo was 0.98 [95% confidence interval (CI) 0.89-1.08, p = 0.71]. Sensitivity analysis including all trials was similar (RR 0.96; 95% CI 0.91-1.02, p = 0.21) as was analysis of longer-term mortality (RR 0.96; 95% CI 0.90-1.02, p = 0.18). In low risk of bias trials, the risk of experiencing any adverse event was higher with corticosteroids; however, there was substantial heterogeneity (RR 1.66; 95% CI 1.03-2.70, p = 0.04, I2 = 78%). No trials reported quality of life outcomes. Duration of shock [mean difference (MD) -1.52 days; 95% CI -1.71 to -1.32, p < 0.0001], duration of mechanical ventilation (MD -1.38 days; 95% CI -1.96 to -0.80, p < 0.0001), and ICU stay (MD -0.75 days; 95% CI -1.34 to -0.17, p = 0.01) were shorter with corticosteroids versus placebo.
CONCLUSIONS: In adults with septic shock treated with low dose corticosteroids, short- and longer-term mortality are unaffected, adverse events increase, but duration of shock, mechanical ventilation and ICU stay are reduced. PROSPERO registration no. CRD42017084037.
Previous clinical trials have investigated the effect of glucocorticoid therapy in acute respiratory distress syndrome (ARDS), with controversial results, particularly with regard to the early administration of low dose glucocorticoid. The present meta-analysis aimed to assess whether the application of glucocorticoid was able to reduce mortality in patients with ARDS. A literature search was performed using online databases, including MEDLINE, Embase, Cochrane and CNKI regardless of whether the studies were published in English or Chinese. Following assessment via inclusion and exclusion criteria, two reviewers screened controlled randomized trials which investigated glucocorticoid therapy in ARDS patients and independently extracted data. The quality of all of the included trials was evaluated based on blinding, randomization and other methods. A total of 14 studies with 1,441 patients met the inclusion criteria. The results of the meta-analysis demonstrated that glucocorticoid significantly reduced the overall mortality of patients with ARDS [relative ratio (RR), 0.68; 95% confidence interval (CI), 0.50-0.91; P<0.05], particularly with a low-dose of glucocorticoid (RR, 0.57; 95% CI, 0.39-0.84; P<0.05) at the early phase of ARDS (RR, 0.37; 95% CI, 0.16-0.86; P<0.05), and a longer duration of steroids (RR, 0.44; 95% CI, 0.30-0.64; P<0.05). Administration of steroids also significantly increased the number of days that patients remained alive and were off mechanical ventilation (RR, 3.08; 95% CI, 1.49-4.68; P<0.05) without significantly increasing the novel infection rate (RR, 1.00; 95% CI, 0.44-2.25; P<0.05). Due to inconsistencies and other limitations, the quality of the studies used for the meta-analysis of the effect of glucocorticoid on mortality was low. In conclusion, early use of low dose glucocorticoid may effectively reduce mortality in patients with ARDS. However, this conclusion may be affected by the limited quality of the studies included in the present meta-analysis.
Very little direct evidence exists on use of corticosteroids in patients with coronavirus disease 2019 (COVID-19). Indirect evidence from related conditions must therefore inform inferences regarding benefits and harms. To support a guideline for managing COVID-19, we conducted systematic reviews examining the impact of corticosteroids in COVID-19 and related severe acute respiratory illnesses.
METHODS:
We searched standard international and Chinese biomedical literature databases and prepublication sources for randomized controlled trials (RCTs) and observational studies comparing corticosteroids versus no corticosteroids in patients with COVID-19, severe acute respiratory syndrome (SARS) or Middle East respiratory syndrome (MERS). For acute respiratory distress syndrome (ARDS), influenza and community-acquired pneumonia (CAP), we updated the most recent rigorous systematic review. We conducted random-effects meta-analyses to pool relative risks and then used baseline risk in patients with COVID-19 to generate absolute effects.
RESULTS:
In ARDS, according to 1 small cohort study in patients with COVID-19 and 7 RCTs in non-COVID-19 populations (risk ratio [RR] 0.72, 95% confidence interval [CI] 0.55 to 0.93, mean difference 17.3% fewer; low-quality evidence), corticosteroids may reduce mortality. In patients with severe COVID-19 but without ARDS, direct evidence from 2 observational studies provided very low-quality evidence of an increase in mortality with corticosteroids (hazard ratio [HR] 2.30, 95% CI 1.00 to 5.29, mean difference 11.9% more), as did observational data from influenza studies. Observational data from SARS and MERS studies provided very low-quality evidence of a small or no reduction in mortality. Randomized controlled trials in CAP suggest that corticosteroids may reduce mortality (RR 0.70, 95% CI 0.50 to 0.98, 3.1% lower; very low-quality evidence), and may increase hyperglycemia.
INTERPRETATION:
Corticosteroids may reduce mortality for patients with COVID-19 and ARDS. For patients with severe COVID-19 but without ARDS, evidence regarding benefit from different bodies of evidence is inconsistent and of very low quality.
Systematic Review Question»Systematic review of interventions
