Dataset Information

Effects of low-dose hydrocortisone and hydrocortisone plus fludrocortisone in adults with septic shock: a protocol for a systematic review and meta-analysis of individual participant data.

ABSTRACT: Introduction: The benefits and risks of low-dose hydrocortisone in patients with septic shock have been investigated in numerous randomised controlled trials and trial-level meta-analyses. Yet, the routine use of this treatment remains controversial. To overcome the limitations of previous meta-analyses inherent to the use of aggregate data, we will perform an individual patient data meta-analysis (IPDMA) on the effect of hydrocortisone with or without fludrocortisone compared with placebo or usual care on 90-day mortality and other outcomes in patients with septic shock.

Methods and analysis: To assess the benefits and risks of hydrocortisone, with or without fludrocortisone for adults with septic shock, we will search major electronic databases from inception to September 2020 (Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE and Latin American Caribbean Health Sciences Literature), complimented by a search for unpublished trials. The primary analysis will compare hydrocortisone with or without fludrocortisone to placebo or no treatment in adult patients with septic shock. Secondary analyses will compare hydrocortisone to placebo (or usual care), hydrocortisone plus fludrocortisone to placebo (or usual care), and hydrocortisone versus hydrocortisone plus fludrocortisone. The primary outcome will be all cause mortality at 90?days. We will conduct both one-stage IPDMA using mixed-effect models and machine learning with targeted maximum likelihood analyses. We will assess the risk of bias related to unshared data and related to the quality of individual trial.

Ethics and dissemination: This IPDMA will use existing data from completed randomised clinical trials and will comply with the ethical and regulatory requirements regarding data sharing for each of the component trials. The findings of this study will be submitted for publication in a peer-review journal with straightforward policy for open access.

Prospero registration number: CRD42017062198.

SUBMITTER: Annane D

PROVIDER: S-EPMC7713227 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

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Effects of low-dose hydrocortisone and hydrocortisone plus fludrocortisone in adults with septic shock: a protocol for a systematic review and meta-analysis of individual participant data.

Annane Djillali D Pirracchio Romain R Billot Laurent L Waschka Andre A Chevret Sylvie S Cohen Jeremy J Finfer Simon S Gordon Anthony A Hammond Naomi N Myburgh John J Venkatesh Balasubramanian B Delaney Anthony A

BMJ open 20201202 12

<h4>Introduction</h4>The benefits and risks of low-dose hydrocortisone in patients with septic shock have been investigated in numerous randomised controlled trials and trial-level meta-analyses. Yet, the routine use of this treatment remains controversial. To overcome the limitations of previous meta-analyses inherent to the use of aggregate data, we will perform an individual patient data meta-analysis (IPDMA) on the effect of hydrocortisone with or without fludrocortisone compared with placeb ...[more]

PMID: 33268422

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Project description:BackgroundWhile recommended by international societal guidelines in the paediatric population, the use of venoarterial extracorporeal membrane oxygenation (VA ECMO) as mechanical circulatory support for refractory septic shock in adults is controversial. We aimed to characterise the outcomes of adults with septic shock requiring VA ECMO, and identify factors associated with survival.MethodsWe searched Pubmed, Embase, Scopus and Cochrane databases from inception until 1st June 2021, and included all relevant publications reporting on > 5 adult patients requiring VA ECMO for septic shock. Study quality and certainty in evidence were assessed using the appropriate Joanna Briggs Institute checklist, and the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach, respectively. The primary outcome was survival to hospital discharge, and secondary outcomes included intensive care unit length of stay, duration of ECMO support, complications while on ECMO, and sources of sepsis. Random-effects meta-analysis (DerSimonian and Laird) were conducted.Data synthesisWe included 14 observational studies with 468 patients in the meta-analysis. Pooled survival was 36.4% (95% confidence interval [CI]: 23.6%-50.1%). Survival among patients with left ventricular ejection fraction (LVEF) < 20% (62.0%, 95%-CI: 51.6%-72.0%) was significantly higher than those with LVEF > 35% (32.1%, 95%-CI: 8.69%-60.7%, p = 0.05). Survival reported in studies from Asia (19.5%, 95%-CI: 13.0%-26.8%) was notably lower than those from Europe (61.0%, 95%-CI: 48.4%-73.0%) and North America (45.5%, 95%-CI: 16.7%-75.8%). GRADE assessment indicated high certainty of evidence for pooled survival.ConclusionsWhen treated with VA ECMO, the majority of patients with septic shock and severe sepsis-induced myocardial depression survive. However, VA ECMO has poor outcomes in adults with septic shock without severe left ventricular depression. VA ECMO may be a viable treatment option in carefully selected adult patients with refractory septic shock.

Project description:ImportanceIt is unclear whether vitamin C, hydrocortisone, and thiamine are more effective than hydrocortisone alone in expediting resolution of septic shock.ObjectiveTo determine whether the combination of vitamin C, hydrocortisone, and thiamine, compared with hydrocortisone alone, improves the duration of time alive and free of vasopressor administration in patients with septic shock.Design, setting, and participantsMulticenter, open-label, randomized clinical trial conducted in 10 intensive care units in Australia, New Zealand, and Brazil that recruited 216 patients fulfilling the Sepsis-3 definition of septic shock. The first patient was enrolled on May 8, 2018, and the last on July 9, 2019. The final date of follow-up was October 6, 2019.InterventionsPatients were randomized to the intervention group (n?=?109), consisting of intravenous vitamin C (1.5 g every 6 hours), hydrocortisone (50 mg every 6 hours), and thiamine (200 mg every 12 hours), or to the control group (n?=?107), consisting of intravenous hydrocortisone (50 mg every 6 hours) alone until shock resolution or up to 10 days.Main outcomes and measuresThe primary trial outcome was duration of time alive and free of vasopressor administration up to day 7. Ten secondary outcomes were prespecified, including 90-day mortality.ResultsAmong 216 patients who were randomized, 211 provided consent and completed the primary outcome measurement (mean age, 61.7 years [SD, 15.0]; 133 men [63%]). Time alive and vasopressor free up to day 7 was 122.1 hours (interquartile range [IQR], 76.3-145.4 hours) in the intervention group and 124.6 hours (IQR, 82.1-147.0 hours) in the control group; the median of all paired differences was -0.6 hours (95% CI, -8.3 to 7.2 hours; P?=?.83). Of 10 prespecified secondary outcomes, 9 showed no statistically significant difference. Ninety-day mortality was 30/105 (28.6%) in the intervention group and 25/102 (24.5%) in the control group (hazard ratio, 1.18; 95% CI, 0.69-2.00). No serious adverse events were reported.Conclusions and relevanceIn patients with septic shock, treatment with intravenous vitamin C, hydrocortisone, and thiamine, compared with intravenous hydrocortisone alone, did not significantly improve the duration of time alive and free of vasopressor administration over 7 days. The finding suggests that treatment with intravenous vitamin C, hydrocortisone, and thiamine does not lead to a more rapid resolution of septic shock compared with intravenous hydrocortisone alone.Trial registrationClinicalTrials.gov Identifier: NCT03333278.

Dataset Information

Effects of low-dose hydrocortisone and hydrocortisone plus fludrocortisone in adults with septic shock: a protocol for a systematic review and meta-analysis of individual participant data.

Publications

Effects of low-dose hydrocortisone and hydrocortisone plus fludrocortisone in adults with septic shock: a protocol for a systematic review and meta-analysis of individual participant data.

Similar Datasets

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