Adverse Events to the Gadolinium-based Contrast Agent Gadoxetic Acid: Systematic Review and Meta-Analysis.

Background Gadoxetic acid is classified by the American College of Radiology as a group III gadolinium-based contrast agent (GBCA), which indicates that there are limited data regarding nephrogenic systemic fibrosis (NSF) risk, but there are few if any unconfounded cases of NSF. Purpose To perform a systematic review and meta-analysis of gadoxetic acid adverse events, including immediate hypersensitivity reactions, NSF, and intracranial gadolinium retention. Materials and Methods Original research studies, case series, and case reports that reported adverse events in patients undergoing gadoxetic acid-enhanced MRI were searched in MEDLINE (1946-2019), Embase (1947-2019), CENTRAL (March 2019), and Scopus (1946-2019). The study protocol was registered at Prospero (number 162811). Risk of bias was evaluated by using Quality Assessment of Diagnostic Accuracy Studies-2, or QUADAS-2. Meta-analysis of proportions was performed by using random-effects modeling. Upper bound of 95% confidence interval (CI) for risk of NSF was determined. Results Seventy-one studies underwent full-text review. From 17 studies reporting 14 850 administrations, hypersensitivity reactions occurred in 0.3% (31 of 14 850; 95% CI: 0.2%, 0.4%) with zero deaths. From four studies reporting 106 administrations in patients with stage 4 or 5 chronic kidney disease or undergoing dialysis, the upper bound 95% CI for the risk of NSF was 2.8%. Five studies evaluating intracranial retention of gadolinium after gadoxetic acid administration were at high risk of bias. Conclusion Gadoxetic acid had a similar safety profile to American College of Radiology group 2 gadolinium-based contrast agents for hypersensitivity reactions and nephrogenic systemic fibrosis (NSF) but had lower confidence for risk of NSF because of fewer administrations in patients with severe kidney impairment. There is incomplete information documenting intracranial gadolinium retention in patients administered gadoxetic acid. © RSNA, 2020 Online supplemental material is available for this article.