Immediate Allergic Reactions to Gadolinium-based Contrast Agents: A Systematic Review and Meta-Analysis

Purpose To perform a systematic review and meta-analysis to determine if there are differences in rates of immediate allergic events between classes of gadolinium-based contrast agents (GBCAs). Materials and Methods PubMed and Google Scholar databases were searched for studies in which rates of immediate adverse events to GBCAs were reported. The American College of Radiology classification system was used to characterize allergic-like events as mild, moderate, or severe, and the total number of administrations of each GBCA was recorded. Where necessary, authors of studies were contacted to clarify data and eliminate physiologic reactions. Relative risks of GBCA types were estimated by using the Mantel-Haenszel type method. Results Nine studies in which immediate reactions to GBCA were recorded from a total of 716 978 administrations of GBCA met the criteria for inclusion and exclusion. The overall and severe rates of GBCA allergic-like adverse events were 9.2 and 0.52 per 10 000 administrations, respectively: 81% (539 of 662) were mild, 13% (86 of 662) were moderate, and 6% (37 of 662) were severe reactions. The nonionic linear chelate gadodiamide had the lowest rate of reactions, at 1.5 (95% confidence interval [CI]: 0.74, 2.4) per 10 000 administrations, which was significantly less than that of linear ionic GBCAs at 8.3 (95% CI: 7.5, 9.2) per 10 000 administrations (relative risk, 0.19 [95% CI: 0.099, 0.36]; P < .00001) and less than that for nonionic macrocyclic GBCAs at 16 (95% CI: 14, 19) per 10 000 administrations (relative risk, 0.12 [95% CI: 0.05, 0.31]; P < .001). GBCAs known to be associated with protein binding had a higher rate of reactions, at 17 (95% CI: 15, 20) per 10 000 administrations compared with the same chelate classification without protein binding, at 5.2 (95% CI: 4.5, 6.0) per 10 000 administrations (relative risk, 3.1 [95% CI: 2.4, 3.8]; P < .0001). Conclusion These data show the lowest rate of immediate allergic adverse events with use of the nonionic linear GBCA gadodiamide in comparison with those of ionic linear or nonionic macrocyclic GBCAs. A higher rate of immediate allergic adverse events was associated with ionicity, protein binding, and macrocyclic structure.