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

Based on renal injury reported in critically ill and septic patients, the U.S. 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. This study was a new meta-analysis focused on renal injury designed to complement a 2021 meta-analysis of perioperative hydroxyethyl starch use, adding 45 trials and 6,895 patients. The focus was acute kidney injury and preoperative-to-postoperative change in creatinine concentration in surgical patients.

This study searched four publication databases in six 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 the results are reported with 95% CI values.

After screening 1,114 studies, 114 trials (2009 to 2026) with 13,951 patients were included. Most trials were at low risk of bias, and there was no evidence of publication bias. Patients had major cardiac surgeries (30%), major abdominal surgeries (46%), and other surgical procedures (24%). Nearly all trials restricted HES administration to less than 24 h. HES 130/0.4 or HES 130/0.42 did not significantly increase the risk of acute kidney injury (relative risk, 1.02; 95% CI, 0.91 to 1.16) or worsen preoperative-to-postoperative creatinine concentration (-0.62 µmol/l; 95% CI, -3.82 to 2.57 µmol/l). Trial sequential analysis indicated strong noninferiority for the change in creatinine concentration and adequate information size. HES did not meaningfully worsen any other outcome evaluated, including overall or severe adverse events or mortality.

Current hydroxyethyl starch solutions do not provoke renal injury in surgical patients.