Hydroxyethyl Starch and Perioperative Complications: a Systematic Review and Meta-analysis

Background: Based on renal injury reported in critically ill and septic patients, the Food and Drug Administration issued a black box warning regarding hydroxyethyl starch (HES 130/0.4) use in 2013, and expanded the warning to surgical and trauma patients in 2021. Similarly, the European Medicines Agency initiated withdrawal of hydroxyethyl starch in 2022. We therefore conducted a new meta-analysis focused on renal injury designed to complement a 2021 meta-analysis of perioperative hydroxyethyl starch use, adding 45 trials and 6895 patients. Our focus was acute kidney injury and preoperative-to-postoperative change in creatinine concentration in surgical patients. Methods: We searched 4 publication databases in 6 languages using predefined criteria. Standard meta-analytic techniques were used to evaluate trial quality and publication bias. Trial selection and evaluation were conducted by independent investigators with adjudication as necessary. Selected trials all used HES 130/0.4 or HES 130/0.42, without restriction on type of surgery or solution type. Analyses were conducted in Review Manager (RevMan5) using random-effect models and results are reported with 95% confidence intervals (CIs). Results: After screening 1,114 studies, we included 114 trials (2009-2026) with 13,951 patients. Most were at low risk of bias and there was no evidence of publication bias. Patients had major cardiac (30%), major abdominal (46%) and other surgical procedures (24%). Nearly all trials restricted HES administration to <24 hours. HES 130/0.4 or HES 130/0.42 did not significantly increase the risk of acute kidney injury (relative risk 1.02 [0.91, 1.16]) or worsen preoperative-to-postoperative creatinine concentration (-0.62 [-3.82, 2.57] µmol/L). Trial sequential analysis indicated strong non-inferiority for the change in creatinine concentration and adequate information size. HES did not meaningfully worsen any other outcome we evaluated including overall or severe adverse events or mortality. Conclusion: Current hydroxyethyl starch solutions do not provoke renal injury in surgical patients.