Effect of adjunctive corticosteroids on clinical outcomes in adult patients with septic shock - a meta-analysis of randomized controlled trials and trial sequential analysis

Zhou, Xiaoyang; Hu, Caibao; Yao, Lina; Fan, Zhen; Sun, Lingling; Wang, Yan; Xu, Zhaojun

doi:10.1016/j.jcrc.2018.09.013

Cited by 10 publications

(16 citation statements)

References 38 publications

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“…However, results regarding long-term mortality were significantly different (Suffredini, 2018). The latest meta-analysis (Fang et al, 2019; Lyu et al, 2018; Ni et al, 2019; Rochwerg et al, 2018; Rygard et al, 2018; Xu et al, 2018; Zhou et al, 2018) with aggregated contradictory points also failed to reach a consensus on this disagreement. Meanwhile, the latest clinical practice guideline (Lamontagne et al, 2018) published in BMJ in 2018 stated that the optimal corticosteroid dose and duration of treatment are still uncertain.…”

Section: Discussionmentioning

confidence: 99%

“…Two unprecedented studies, the ADRENAL (Venkatesh et al, 2018) and APROCCHSS (Annane et al, 2018) trials published in 2018 in the New England Journal of Medicine , aimed to put an end to this historical controversy, but the uncertainty with dramatic difference (Suffredini, 2018) remained due to this difference in the number of patients enrolled appears to be related to different inclusion (i.e., high-dose norepinephrine or epinephrine in APROCCHS) and exclusion criteria (e.g., death likely from a pre-existing disease within 90 days in ADRENAL). Subsequent up-date meta-analyses (Fang et al, 2019; Lyu et al, 2018; Ni et al, 2019; Rochwerg et al, 2018; Rygard et al, 2018; Xu et al, 2018; Zhou et al, 2018) with aggregated contradictory points also made this unadorned conflicting conclusion more confusing and intriguing.…”

Section: Introductionmentioning

confidence: 99%

“…Together with the conflicting conclusions of previous systematic reviews (Annane et al, 2004a; Annane et al, 2009; Annane et al, 2015; Fang et al, 2019; Lyu et al, 2018; Ni et al, 2019; Rochwerg et al, 2018; Rygard et al, 2018; Xu et al, 2018; Zhou et al, 2018), we performed this meta-analysis involving dose-response meta-analysis with meta-regression and trial sequential analysis (TSA) to investigate the benefits and harms of corticosteroids for sepsis populations. Furthermore, our study also explored the optimal cumulative dose, daily dose, and duration of long course low-dose corticosteroid therapy that can reach the critical point of benefits amongst patients with sepsis, to provide better scientifically strategic guidelines for clinical practice.…”

Section: Introductionmentioning

confidence: 99%

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Impact and Beneficial Critical Points of Clinical Outcome in Corticosteroid Management of Adult Patients With Sepsis: Meta-Analysis and GRADE Assessment

et al. 2019

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Background: With new randomised pieces of evidence and the latest clinical practice guideline from the BMJ emerging in 2018, an updated analysis of best available evidence on the controversial effects of corticosteroids in sepsis is warranted.Objectives: To comprehensively evaluate whether corticosteroids are beneficial in reducing mortality and what cumulative dosage, daily dosage, and duration of corticosteroid treatment would enable adult patients with sepsis to reach the critical point of benefits.Methods: Ovid MEDLINE, Ovid EMbase, Cochrane Library, and LILACS database were searched until March 22, 2019.Results: Thirty RCTs with 8,836 participants were identified. Long course low-dose corticosteroid therapy could improve 28-day mortality (RR = 0.90, 95% CI = 0.84–0.97; high quality), intensive care unit mortality (RR = 0.87; 95% CI = 0.79–0.95; moderate quality), and in-hospital mortality (RR = 0.88, 95% CI = 0.79–0.997; high quality). However, we found no benefits for 90-day, 180-day, and 1-year mortality. Subgroup results of long course corticosteroid treatment in a population with septic shock and vasopressor-dependent septic shock, corticosteroid regimen with hydrocortisone plus fludrocortisone, corticosteroid dosing strategies including bolus dosing and infusion dosing, the strategies of abrupt discontinuation, timing of randomisation ≤24 h, impact factor of ≥10, and sample size ≥500 were associated with a marginally reduction in 28-day mortality.Conclusions: This meta-analysis found that the long course low-dose and not short course high-dose corticosteroid treatment could marginally improve short-term 28-day mortality with high quality, especially septic shock and vasopressor-dependent septic shock, and it is recommended that long course (about 7 days) low-dose (about 200–300mg per day) hydrocortisone (or equivalent) with cumulative dose (at least about 1,000mg) may be a viable management option for overall patients with sepsis, and it can be also adapted to patient with septic shock alone. Early hydrocortisone plus fludrocortisone administration, via continuous infusion or bolus dosing, is also particularly important for the prognosis. Abrupt discontinuation of corticosteroids, as opposed to the conventional tapered discontinuation, may be considered as a desirable option in 28-day mortality. The safety profile of long course low-dose corticosteroid treatment, including adverse hyperglycaemia and hypernatraemia events, remains a concern, although these events could be easily treated.Clinical Trial Registration: PROSPERO, identifier CRD 42018092849.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Impact and Beneficial Critical Points of Clinical Outcome in Corticosteroid Management of Adult Patients With Sepsis: Meta-Analysis and GRADE Assessment

et al. 2019

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“…Different from the previous meta-analysis [14][15][16][17], our study included the SUP-ICU trial [18], in which the number of the subject is more than 3000, which are larger than the total number of subjects in all previous trials. Therefore, our meta-analysis with a larger sample size would decrease the sampling errors and selective bias to some extent and reveal the outcome effects more objectively [21]. In addition, TSA suggests that sufficient events had been accrued in the current trials to draw a firm conclusion on the effect of SUP on the risk of overt GI bleeding, this benefit was more obvious in patients did not receive EN, however, convinced evidence regarding the efficacy of SUP in patients received EN are still lacking, hence this results could be referenced to guide future trial to focus on the use of SUP in critically ill patients received EN.…”

Section: Discussionmentioning

confidence: 99%

Stress ulcer prophylaxis with proton pump inhibitors or histamine 2 receptor antagonists in critically ill adults - A meta-analysis of randomized controlled trials with trial sequential analysis.

Zhou

Fang

et al. 2019

Preprint

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Background Proton pump inhibitors (PPI) and histamine 2 receptor antagonists (H2RA) have been widely used as stress ulcer prophylaxis (SUP) in critically ill patients, however, its efficacy and safety remain unclear. This study aimed to assess the effect of SUP on clinical outcomes in critically ill adults.Methods Literature search was conducted in PubMed, EMBASE, Web of Science, and the Cochrane database of clinical trials for randomized controlled trials (RCTs) that investigated SUP, with PPI or H2RA, versus placebo or no prophylaxis in critically ill patients from database inception through 1 June 2019. Study selection, data extraction and quality assessment were performed in duplicate. The primary outcomes were clinically important gastrointestinal (GI) bleeding and overt GI bleeding. Conventional meta-analysis with random-effects model and trial sequential analysis (TSA) were performed.Results Twenty-nine RCTs were identified, of which four RCTs were judged as low risk of bias. Overall, SUP could reduce the incident of clinically important GI bleeding [relative risk(RR)= 0.58; 95% confidence intervals (CI): 0.42–0.81] and overt GI bleeding (RR= 0.48; 95% CI: 0.36–0.63), these results were confirmed by the sub-analysis of trials with low risk of bias, TSA indicated a firm evidence on its beneficial effects on the overt GI bleeding (TSA-adjusted CI: 0.31–0.75), but lack of sufficient evidence on the clinically important GI bleeding (TSA-adjusted CI: 0.23–1.51). Among patients who received enteral nutrition (EN), SUP was associated with a decreased risk of clinically important GI bleeding (RR=0.61; 95% CI: 0.44–0.85; TSA-adjusted CI: 0.16–2.38) and overt GI bleeding (RR=0.64; 95% CI: 0.42–0.96; TSA-adjusted CI: 0.12–3.35), but these benefits disappeared after adjustment with TSA. Among patients who did not receive EN, SUP had only benefits in reducing the risk of overt GI bleeding (RR=0.37; 95% CI: 0.25–0.55; TSA-adjusted CI: 0.22–0.63), but not the clinically important GI bleeding (RR=0.27; 95% CI: 0.04–2.09).Conclusions SUP has benefits on the overt GI bleeding in critically ill patients who did not receive EN, however, its benefits on clinically important GI bleeding still needs more evidence to confirm.

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“…The risk of bias of each included studies were assessed by two independent authors (Hu C and Xu Z) for the primary outcomes (clinically important GI bleeding and overt GI bleeding) in the following six domains: adequate sequence generation, allocation concealment, blinding of participants and personnel, blinding of outcome assessment, incomplete outcome data, selective reporting, and other bias [20, 21]. Only studies that exhibited a low risk of bias in all domains were judged as low risk of bias.…”

Section: Methodsmentioning

confidence: 99%

Stress ulcer prophylaxis with proton pump inhibitors or histamine 2 receptor antagonists in critically ill adults - a meta-analysis of randomized controlled trials with trial sequential analysis

Zhou

Fang

et al. 2019

BMC Gastroenterol

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BackgroundProton pump inhibitors (PPI) and histamine 2 receptor antagonists (H2RA) have been widely used as stress ulcer prophylaxis (SUP) in critically ill patients, however, its efficacy and safety remain unclear. This study aimed to assess the effect of SUP on clinical outcomes in critically ill adults.MethodsLiterature search was conducted in PubMed, EMBASE, Web of Science, and the Cochrane database of clinical trials for randomized controlled trials (RCTs) that investigated SUP, with PPI or H2RA, versus placebo or no prophylaxis in critically ill patients from database inception through 1 June 2019. Study selection, data extraction and quality assessment were performed in duplicate. The primary outcomes were clinically important gastrointestinal (GI) bleeding and overt GI bleeding. Conventional meta-analysis with random-effects model and trial sequential analysis (TSA) were performed.ResultsTwenty-nine RCTs were identified, of which four RCTs were judged as low risk of bias. Overall, SUP could reduce the incident of clinically important GI bleeding [relative risk (RR) = 0.58; 95% confidence intervals (CI): 0.42–0.81] and overt GI bleeding (RR = 0.48; 95% CI: 0.36–0.63), these results were confirmed by the sub-analysis of trials with low risk of bias, TSA indicated a firm evidence on its beneficial effects on the overt GI bleeding (TSA-adjusted CI: 0.31–0.75), but lack of sufficient evidence on the clinically important GI bleeding (TSA-adjusted CI: 0.23–1.51). Among patients who received enteral nutrition (EN), SUP was associated with a decreased risk of clinically important GI bleeding (RR = 0.61; 95% CI: 0.44–0.85; TSA-adjusted CI: 0.16–2.38) and overt GI bleeding (RR = 0.64; 95% CI: 0.42–0.96; TSA-adjusted CI: 0.12–3.35), but these benefits disappeared after adjustment with TSA. Among patients who did not receive EN, SUP had only benefits in reducing the risk of overt GI bleeding (RR = 0.37; 95% CI: 0.25–0.55; TSA-adjusted CI: 0.22–0.63), but not the clinically important GI bleeding (RR = 0.27; 95% CI: 0.04–2.09).ConclusionsSUP has benefits on the overt GI bleeding in critically ill patients who did not receive EN, however, its benefits on clinically important GI bleeding still needs more evidence to confirm.

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Effect of adjunctive corticosteroids on clinical outcomes in adult patients with septic shock - a meta-analysis of randomized controlled trials and trial sequential analysis

Cited by 10 publications

References 38 publications

Impact and Beneficial Critical Points of Clinical Outcome in Corticosteroid Management of Adult Patients With Sepsis: Meta-Analysis and GRADE Assessment

Impact and Beneficial Critical Points of Clinical Outcome in Corticosteroid Management of Adult Patients With Sepsis: Meta-Analysis and GRADE Assessment

Stress ulcer prophylaxis with proton pump inhibitors or histamine 2 receptor antagonists in critically ill adults - A meta-analysis of randomized controlled trials with trial sequential analysis.

Stress ulcer prophylaxis with proton pump inhibitors or histamine 2 receptor antagonists in critically ill adults - a meta-analysis of randomized controlled trials with trial sequential analysis

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