Use of hydroxyethyl starch in sepsis research: Protocol for a systematic review

Abstract

Introduction:Hydroxyethyl starch (HES) 130/0.38-0.45 is a synthetic colloid, which has been on the market since 1999. In recent years, concern about the use of HES has been raised because of serious adverse events, including acute kidney injury, bleeding and even increased mortality with its use. In the outlined systematic review, we aim to assess if the adverse effects of HES 130/0.38-0.45 in patients with sepsis could have been discovered earlier. Methods:We will conduct a systematic review with meta-analysis of randomised clinical trials in animals and patients and observational studies in patients comparing HES 130/0.38-0.45 vs any crystalloid in sepsis. The primary outcome will be all-cause mortality at longest follow-up. We will systematically search EMBASE, MEDLINE and the Cochrane Library for relevant literature. We will follow the recommendations by the Cochrane Handbook, the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) statements and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. Discussion: With the outlined systematic review, we aim to assess whether the adverse effects of HES 130/0.38-0.45 could have been discovered earlier by comparing summary effect estimates of harm from observational studies in patients and randomised trials in animals and patients. The results may have implications for future drug development and approval processes. S U PP O RTI N G I N FO R M ATI O N Additional supporting information may be found online in the Supporting Information section at the end of the article. How to cite this article: Johansen JR, Perner A, Brodtkorb JH, Møller MH. Use of hydroxyethyl starch in sepsis research:Protocol for a systematic review. Acta Anaesthesiol Scand.

Use of hydroxyethyl starch in sepsis research: A systematic review with meta‐analysis

“…The review was registered in the International Prospective Register of Systematic Reviews (PROSPERO; https://www.crd.york.ac.uk/prospero/; registration number: CRD42018103422) and the protocol 14 was published before the literature search was carried out.…”

“…For the observational studies, we used the Risk of Bias in Non‐randomised Studies‐of Interventions (ROBINS‐I) risk of bias tool 15 . Additional details are provided in the published protocol 14 …”

“…We performed both fixed effects and random effects analyses and report only the most conservative summary effect estimate with the broadest CI for each outcome 16 . In order to explore the possible reasons for heterogeneity, we conducted predefined subgroup analyses with stratification of trials according to their type and risk of bias (details available in the published protocol) 14 12 …”

“…McMaster University, 2015 (developed by Evidence Prime, Inc.). Available from gradepro.org) to assess the quality of evidence for each outcome (additional details are available in the published protocol) 14 …”