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 non-serious 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 (I-2 = 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. (C) RSNA, 2020