Safety of Intrathecal Administration of Gadolinium-based Contrast Agents: A Systematic Review and Meta-Analysis.

Background The use of MR cisternography with intrathecal administration of gadolinium-based contrast agents (GBCAs) is limited by a lack of understanding of the relationship between intrathecal GBCA exposure and dose-related adverse events. Purpose To perform a systematic review to establish an understanding of the dose-response relationship of intrathecal GBCAs and to characterize related adverse events, particularly at higher doses. Materials and Methods Medline, Embase, CINAHL, and Central databases were searched for studies reporting intrathecal GBCA use. Data extraction included studies focused on rates and types of adverse events after intrathecal GBCA exposure. A two-tailed independent sample t test statistic was used to evaluate the relationship between GBCA dose and the presence of serious versus nonserious adverse events. Meta-analysis was used to determine the overall incidence of adverse events. Study quality and publication bias were assessed using the modified Newcastle-Ottawa scale and a funnel plot (effect size measured using Hedges' g followed by the Egger test), respectively. Results Fifty-three studies with a total of 1036 patients were included for analysis. The overall rate of adverse events after intrathecal administration of GBCA was 13% (95% confidence interval [CI]: 9.3%, 18%). Meta-analysis revealed moderate heterogeneity (I2 = 62%). Serious adverse event rates could not be determined with meta-analysis. They were reported in 10 studies and were primarily neurologic in nature, with two cases of coma-one resulting in death. Serious adverse events were associated with significantly higher GBCA doses when compared with nonserious adverse events (mean difference, 4.5 mmol; 95% CI: 2.3 mmol, 6.6 mmol; P = .008). For serious adverse events, there was no clear dose-dependent increase in severity above 2.0 mmol. Conclusion Overall, intrathecal administration of GBCAs at doses greater than 1.0 mmol are associated with serious neurotoxic complications with relative clinical safety at lower doses. © RSNA, 2020 Online supplemental material is available for this article. See also the editorial by Kanal in this issue.