PROOF Copyright © European Society of Anaesthesiology. Unauthorized reproduction of this article is prohibited. ORIGINAL ARTICLE Safety and efficacy of peri-operative administration of hydroxyethyl starch in children undergoing surgery A systematic review and meta-analysis Michae ¨l Thy, Juliette Montmayeur, Florence Julien-Marsollier, Daphn e Michelet, Christopher Brasher, Souhayl Dahmani and Gilles Orliaguet BACKGROUND Hydroxyethyl starch (HES) solutions have shown their efficiency for intravascular volume expansion. However, a safety recommendation limiting their use in adult patients has recently been made. The aim of this meta- analysis was to assess the efficacy and adverse effects of HES when administered intra-operatively to paediatric patients. METHODS A search was performed for randomised con- trolled trials (RCTs) published before December 2016 involving paediatric patients who received 6% low molecular weight HES. Reviewers extracted valid data, including peri- operative total fluid intakes, mortality, renal function, coagu- lation tests, blood loss and length of hospital and ICU stay. All data were analysed using classical mean differences [and their 95% confidence intervals (CIs)] and trial sequential analysis. A Grading of Recommendations Assessment, Development and Evaluation (GRADE) classification was performed for all outcomes. RESULTS Nine RCTs involving 530 peri-operative paediat- ric patients were analysed. Compared with other fluids, HES did not significantly modify the amount of peri-operative fluid administered [mean difference 0.04; 95% CI (1.76 to 1.84) ml kg 1 ], urine output [mean difference 33; 95% CI (104 to 38) ml kg 1 ] or blood loss [mean difference 0.09; (0.32 to 0.15) ml kg 1 ]. Trial sequential analysis determined that the outcomes for peri-operative fluid and urine output were underpowered. Finally, all results were graded as very low quality of evidence. CONCLUSION Intravascular volume expansion with low molecular weight 6% HES did not appear to modify renal function, blood loss or transfusion when administered to children during the peri-operative period. However, given the lack of statistical power and the very low GRADE quality of evidence, more high-quality RCTs are needed to explore these outcomes. Published online xx month 2018 Introduction Hydroxyethyl starches (HES) have been shown to be effective for intravascular volume expansion for more than 20 years. However, recently several studies have suggested a risk of renal, hepatic or haemostatic toxicity in adult patients who received HES in different clinical settings. Following three adult studies published in the New England Journal of Medicine between 2008 and 2012, 1–3 the European Medicines Agency’s Pharmacov- igilance Risk Assessment Committee (PRAC) stated that HES should not be used in patients with sepsis, burns or critical illness but could still be used in patients with hypovolaemia caused by acute blood loss where treat- ment with crystalloids was not sufficient. 4 The European Society of Intensive Care Medicine recommend that HES should not be used for volume expansion due to the high risk for inducing kidney injury and bleeding. 5 Several meta-analyses confirmed that HES should not be used in sepsis, 6–8 but some authors consider that the interpretation of the results of the studies cited in support of the conclusions of the PRAC did not take Eur J Anaesthesiol 2018; 35:1–12 From the Department of Anaesthesia and Intensive Care, Necker Hospital (MT, JM, GO), Paris Descartes (Paris V) University (MT, JM, GO), Department of Anaesthesia and Intensive Care, Robert Debre Hospital (FJ-M, DM, SD), Denis Diderot (Paris VII) University, Paris, France (FJ-M, DM, SD), Department of Anaesthesia & Pain Management, Royal Children’s Hospital (CB), Anaesthesia and Pain Management Research Group, Murdoch Childrens Research Institute, Melbourne, Victoria, Australia (CB), DHU Protect (SD) and EA 08 Paris-Descartes, Pharmacologie et E ` valuation des th erapeutiques chez l’enfant et la femme enceinte, Paris, France (GO) Correspondence to Prof. Gilles Orliaguet, MD, PhD, Service d’Anesth esie R eanimation, Ho ˆ pital Universitaire Necker-Enfants Malades, 149 rue de Se ` vres, Paris 75743, France Tel: +33 144494458; fax: +33 144494170; e-mail: gilles.orliaguet@aphp.fr 0265-0215 Copyright ß 2018 European Society of Anaesthesiology. All rights reserved. DOI:10.1097/EJA.0000000000000780