Original ResearchFree Access

Iodinated Contrast Media Substitution to Prevent Recurrent Hypersensitivity Reactions: A Systematic Review and Meta-Analysis

Published Online:https://doi.org/10.1148/radiol.220370

Abstract

Background

Changing iodinated contrast media (ICM) may reduce the risk of recurrent ICM-induced hypersensitivity reactions in patients with a prior reaction.

Purpose

To perform a systematic review on the effectiveness of ICM change in comparison with no change to prevent recurrent ICM immediate hypersensitivity reactions.

Materials and methods

Multiple data bases were searched without language restriction between January 1990 and August 2021 to identify comparative studies of any design that included patients with a prior ICM hypersensitivity reaction to low-osmolality ICM and re-exposure to intravascular ICM. The methods used included a duplicate assessment of eligibility, double extraction of quantitative data, validity assessment, and random-effects meta-analysis. The primary outcome was the incidence of all-grade immediate recurrent hypersensitivity reactions. Secondary outcomes were the incidence of severe immediate recurrent hypersensitivity reactions and other adverse events associated with ICM change.

Results

Six retrospective observational studies at moderate to severe risk of bias assessed 7155 adult patients (4329 in the ICM change group and 2826 in the no-change group). Studies adopted nonstandardized switching methods, and the proportions of the ICM change group ranged between 19% (five of 27 examinations) and 80% (3104 of 3880 examinations). A Bayesian meta-analysis revealed that changing ICM was associated with a reduced risk of recurrent hypersensitivity reaction by 61% (risk ratio = 0.39; 95% credible interval [CrI]: 0.24, 0.58). The wide-ranging estimates of risk reduction were not explained by the risk of bias ratings, the event rates in the no-change group, the index-reaction severity, or the co-administered nonstandard premedication. Rare severe recurrent reactions (five studies with five events) precluded a conclusion (risk ratio = 0.34, favoring ICM change; CrI: 0.01, 3.74). Adverse events associated with ICM change were not reported.

Conclusion

In observational evidence of limited quality, iodinated contrast media (ICM)–change was associated with a reduced risk of recurrent immediate hypersensitivity reaction in patients with a prior ICM-induced hypersensitivity reaction.

© RSNA, 2022

Online supplemental material is available for this article.

See also the editorial by McDonald in this issue.

Summary

Observational evidence suggests that changing iodinated contrast media (ICM) is associated with a reduced risk of recurrent immediate hypersensitivity reaction in patients with a prior ICM-induced hypersensitivity reaction.

Key Results

  • ■ In a systematic review and Bayesian meta-analysis of six retrospective observational studies in 7155 adult patients with prior hypersensitivity reaction to low-osmolality iodinated contrast media (ICM) and re-exposure to intravascular ICM, changing ICM was associated with a reduced risk of all-grade immediate recurrent hypersensitivity reactions by 61%.

  • ■ Risk reduction from changing ICM was stable across multiple sensitivity analyses.

  • ■ The available published studies had a moderate to severe risk of bias; adverse events associated with ICM change were not systematically reported.

Introduction

Iodinated contrast media (ICM) are widely used in clinical practice to improve the accuracy of diagnostic imaging, with tens of millions of doses administered annually. A single administration of a modern nonionic ICM is unlikely to cause an immediate hypersensitivity reaction (1,2). However, due to the frequency of ICM administration, hypersensitivity reactions—even rare, life-threatening reactions—commonly occur in radiology practices (3). This requires processes to effectively diagnose and treat reactions as they occur and processes to reduce the risk of a repeat reaction in previously affected patients.

For patients with a prior ICM-induced hypersensitivity reaction, health care providers must balance the benefit of ICM reuse against the risk of a repeat reaction (3,4). When ICM readministration is indicated in this context, several options that may reduce the risk of recurrent hypersensitivity reactions exist. These options include premedication with corticosteroids and/or antihistamines and using an ICM that is different from the ICM that caused the index reaction (ie, ICM change) (5,6).

Although premedication with corticosteroids has been in clinical use since at least the 1980s, the evidence supporting it is weak (6). The only available randomized evidence supporting the preventive benefit of premedication is derived from two trials, conducted in 1987 (7) and 1994 (8). Both analyzed average-risk patients (not high-risk patients with a prior ICM reaction); additionally, the first trial assessed now outdated high-osmolality ICM, and the second was underpowered (7,8). There is a lack of high-quality evidence that premedication prevents reactions in high-risk patients receiving a modern ICM (9,10). If there is an effect of premedication on the prevention of recurrent hypersensitivity reactions to ICM, it is likely to be small (11).

In contrast to the weak evidence supporting premedication and its likely small effect size, several observational studies have reported that changing ICM away from the ICM that caused the index reaction is associated with a large reduction in the likelihood of a repeat reaction (1215). Clinical guidelines from major professional societies have started to endorse ICM change as a possible prevention strategy based on these findings (1,1619). However, existing studies have generally been single-center studies with moderate sample sizes. Therefore, we performed a systematic review and meta-analysis analyzing the effectiveness of ICM change in comparison with no change to prevent recurrent ICM immediate hypersensitivity reactions in patients with a prior ICM hypersensitivity reaction.

Materials and Methods

This systematic review followed the Preferred Reporting Items for Systemic Reviews and Meta-Analyses, or PRISMA, 2020 statement (20). An ethics review and informed consent were waived because this meta-analysis was a secondary analysis of publicly available data. The protocol was registered in the International Prospective Register of Systematic Reviews, or PROSPERO (protocol no. CRD42019134003), and the full protocol has been published elsewhere (21).

Search Strategy

We searched the PubMed, Embase, and Cochrane Central Register of Controlled Trials, or CENTRAL, data bases without language restrictions between January 1990 and August 2021. The complete search strategies and additional sources of information are available in Appendix E1 (online).

Study Selection

We included studies with a nonrandomized comparative design and a minimum of 10 patients, regardless of age, who had a prior ICM hypersensitivity reaction to low-osmolality ICM and were re-exposed to intravascular ICM. Included studies were required to assess potential associations between changing the culprit ICM to another one (ie, ICM change vs no ICM change) and immediate (<1 hour) recurrent hypersensitivity reactions in patients with a prior ICM-induced hypersensitivity reaction who received intravenous or intra-arterial nonionic ICM. We accepted studies that allowed the concurrent use of premedication therapies as a cointervention. Although we initially planned to include randomized clinical trials addressing this research question, none were eligible.

We excluded studies that assessed patients who received high-osmolality ICM. We also excluded single-group studies and questionnaire-based studies where the comparative effectiveness of ICM change (vs no change) was not assessable.

Study Selection Process

We performed a duplicate abstract screening and assessment of eligibility for screened-in full-text publications (see Appendix E1 [online] for details). Disagreements were resolved by consensus.

Data Extraction

One reviewer (H.U., a physician with 9 years of experience in medical imaging) extracted descriptive data; another reviewer (T.N., a physician with 24 years of experience in medical imaging) verified all extracted data. The extracted characteristics are described in Appendix E1 (online).

We operationally categorized the severity of ICM hypersensitivity reactions using the grading system proposed by the American College of Radiology; no study adopted the accepted general two-group (ie, types A and B) framework as we had planned. We post-operationally subcategorized the adopted premedication regimens into four groups, namely (a) no premedication, (b) corticosteroids alone, (c) antihistamines alone, and (d) any combination of corticosteroids and antihistamines, regardless of the adopted dosing. The dosing varied substantially and infrequently followed the guideline-recommended schedules.

Two reviewers (H.U., T.N.) independently extracted numerical data on the associations between ICM change and recurrent reactions. Any discrepancies not resolved by consensus were adjudicated by another reviewer (T.T., a physican with 24 years of experience in clinical medicine and evidence synthesis). Our primary outcome was the incidence of all-grade immediate recurrent hypersensitivity reactions. Secondary outcomes were the incidence of severe immediate recurrent hypersensitivity reactions and other adverse events associated with ICM change. For each study, we extracted both unadjusted and covariate-adjusted outcome data (see Appendix E1 [online] for details).

For any missing information or unresolved discrepancies, we contacted the authors of the primary studies for clarification or to request unpublished data. We considered that the request was rejected if two emails received no response.

Assessment of Risk of Bias

Two independent reviewers (T.N., T.T.) rated risk of bias using the Risk of Bias In Nonrandomized Studies of Interventions tool (22). See Appendix E1 (online) and Table E1 (online) for how each bias domain and overall risk of bias were rated. Discrepant ratings were resolved by consensus.

Statistical Analysis

Complete details of the statistical methods (all analyses were performed by T.T.) are provided in Appendix E1 (online). We calculated summary risk ratios and their 95% credible intervals (CrIs) and prediction intervals using a Bayesian study-level pairwise hierarchical random-effects model meta-analysis (23). In the main analysis, we applied the normal-normal hierarchical model to the covariate-adjusted data. In sensitivity analyses, we used the binomial-normal hierarchical model for the unadjusted binary count data. For the between-trial variance (tau2), we used an evidence-based informative prior (24) in the main analysis and a weakly informative prior (25) in sensitivity analyses. For meta-analysis of severe recurrent hypersensitivity reactions, we excluded studies with no events in both groups (ie, double-zero studies) in the main analysis. In the sensitivity analysis, we included double-zero studies and jointly modeled baseline and relative treatment effects to stabilize the meta-analytic model (26).

We graphically assessed between-study statistical heterogeneity and quantified it using the tau and I2 statistics, along with the 95% prediction intervals of the treatment effects. Fewer than 10 eligible studies precluded the planned tests for funnel plot asymmetry (27). To address statistical heterogeneity, we performed a random-effects univariable meta-regression for baseline risk and the rating of risk of bias. For grades of the index ICM reactions and specific premedication used for each patient, we performed a two-stage meta-analysis to directly synthesize treatment-covariate interactions at the patient level (28).

Meta-analyses were performed using OpenBUGS version 3.2.3 (OpenBUGS Project Management Group; https://www.mrc-bsu.cam.ac.uk/software/bugs/openbugs) from Stata version 17.1/SE (StataCorp) (29). A conventional, frequentist, two-tailed P = .05 corresponds to a Bayesian posterior probability of 0.025, which we considered the threshold of statistical significance.

Results

Study Selection and Characteristics

Our literature search identified six eligible studies (seven articles) (1215,3032) (Fig 1). Missing unpublished data were obtained from four studies (12,13,31,32). Data from two publications using the same study sample (15,30) were jointly assessed. Appendix E1 (online) provides a list of excluded publications.

Preferred Reporting Items for Systemic Reviews and Meta-Analyses, or                         PRISMA, flow diagram shows identification of studies by means of data bases                         and registers.

Figure 1: Preferred Reporting Items for Systemic Reviews and Meta-Analyses, or PRISMA, flow diagram shows identification of studies by means of data bases and registers.

Six eligible studies (from South Korea [n = 4], United States [n = 1], and Japan [n = 1]) retrospectively assessed 7155 patients with a prior ICM hypersensitivity reaction (4329 in the ICM change group and 2826 in the no-change group) who received ICM again primarily for enhanced CT (Table 1). Except for one study in which ICM reactions were assessed by a customized two-grade criteria (mild vs severe) (12), all studies adopted a version of the classification system of adverse events proposed by the American College of Radiology.

Table 1: Characteristics of Included Studies

Table 1:

Patient Characteristics

The number of assessed examinations per study ranged from 27 to 3880; most patients were middle aged (average age range, 52–66 years) (Table 2). Although the distribution of the index-reaction grades varied across studies, most patients experienced either mild or moderate reactions (range of sum of mild and moderate index reactions, 85% [278 of 328 examinations] to 100% [3880 of 3880 examinations]), except for one small study (52%; 14 of 27 examinations) (12). The inconsistently reported prevalence of other allergic diseases was low in general, except in one study in which 89% (1475 of 1656) of the examinations were performed in a patient with at least one allergy or allergic disease (32).

Table 2: Characteristics of Patients in the Included Studies

Table 2:

These six studies reported a wide range of alternative ICM use different from the culprit ICM (median, 46%; range, 19% [five of 27 patients] to 80% [3104 of 3880 patients]), with a median of five (range, two to seven) different ICM formulations. The ICM was changed nonuniformly across studies. Only one study reported a uniform substitution algorithm in which iopamidol was changed to iohexol (13), whereas all the other studies performed nonstandardized substitutions; two of these studies reported four and 15 specific ICM substitution pairs with varied proportions with use of four and six locally available ICM formulations, respectively (12,15).

Studies also included a heterogeneous mix of premedication therapies. Drug and dosing schedules as well as whether premedication was co-administered with ICM change varied substantially within and across studies (Table E2 [online]). Only one study (32) adopted the American College of Radiology guideline–recommended corticosteroid-based regimen for all patients.

Risk of Bias

All studies were deemed to have a possibility of residual confounding because of their nonrandomized design. Two studies incorporated only a few potential confounders and failed to account for repeated observations of individuals in the regression analysis (13,15,30) (Table E3 [online]). No studies described how missing data were handled. Overall, four studies were rated as having a moderate risk of bias and two studies as having a severe risk of bias (Fig 2).

Chart shows the risk of bias in eligible studies.

Figure 2: Chart shows the risk of bias in eligible studies.

Recurrent Hypersensitivity Reactions of Any Severity

The observed per-study incidence of immediate recurrent hypersensitivity reactions of any severity ranged from 11% (three of 27 examinations) to 34% (195 of 570 examinations) (14% [three of 22 examinations] to 43% [103 of 242 examinations] in the no-change group). In six studies that reported the severity of recurrent reactions, only 11 of 7155 examinations developed a severe reaction. The overall recurrent reaction rates were 10% (413 of 4329 examinations) in the ICM change group and 23% (654 of 2826 examinations) in the no-change group (Fig 3). A meta-analysis found that changing ICM was, on average, associated with a reduction in the likelihood of a recurrent reaction by 61% (adjusted summary risk ratio = 0.39; 95% CrI: 0.24, 0.58; P < .001), with a large across-study statistical heterogeneity of treatment effects (95% prediction interval: 0.15, 0.84; I2 = 54%; tau = 0.31).

Forest plot shows meta-analysis of reduction in recurrent                         hypersensitivity reactions by change in contrast media. The diamond                         represents the summary risk ratio (RR) centered on a combined estimate and                         extending to a 95% credible interval (CrI), with estimated 95% prediction                         intervals (PrIs) depicted as extending solid horizontal lines. Gray squares                         and dashed horizontal lines indicate reported (covariate-adjusted) risk                         ratios and 95% CIs. Black squares and solid horizontal lines indicate                         (study-specific) predicted risk ratios and 95% CrIs based on the posterior                         distribution for individual studies. The size of the square is proportional                         to the inverse of the variance of the log risk ratio of each                         study.

Figure 3: Forest plot shows meta-analysis of reduction in recurrent hypersensitivity reactions by change in contrast media. The diamond represents the summary risk ratio (RR) centered on a combined estimate and extending to a 95% credible interval (CrI), with estimated 95% prediction intervals (PrIs) depicted as extending solid horizontal lines. Gray squares and dashed horizontal lines indicate reported (covariate-adjusted) risk ratios and 95% CIs. Black squares and solid horizontal lines indicate (study-specific) predicted risk ratios and 95% CrIs based on the posterior distribution for individual studies. The size of the square is proportional to the inverse of the variance of the log risk ratio of each study.

Investigations of Heterogeneity

The reduced risk of recurrent reaction due to ICM change remained regardless of the control event rates (Fig 4). The baseline risk meta-regression failed to show whether the event rates in the group without ICM change increased or reduced the preventive effect (regression slope = 0.66; 95% CrI: –0.23, 1.53; P = .06). Furthermore, the observed heterogeneity was not explained by the risk of bias (relative odds ratio = 0.63; 95% CrI: 0.23, 1.54; P = .12, favoring studies with high [vs moderate] risk of bias).

Meta-analytic scatterplot shows baseline risk meta-regression of                         reduction in recurrent contrast-induced reactions by change in iodinated                         contrast media (ICM). Each study (circle) is plotted for the odds ratio (OR)                         for recurrent contrast-induced reaction events between the ICM-change and                         no-change groups against the proportion of events in the no-change group                         (ie, baseline risk). The meta-regression line is depicted in red with the                         individual study’s posterior odds ratio estimate (square). The size                         of the circle is proportional to the inverse of the variance of the log odds                         ratio of each study.

Figure 4: Meta-analytic scatterplot shows baseline risk meta-regression of reduction in recurrent contrast-induced reactions by change in iodinated contrast media (ICM). Each study (circle) is plotted for the odds ratio (OR) for recurrent contrast-induced reaction events between the ICM-change and no-change groups against the proportion of events in the no-change group (ie, baseline risk). The meta-regression line is depicted in red with the individual study’s posterior odds ratio estimate (square). The size of the circle is proportional to the inverse of the variance of the log odds ratio of each study.

Treatment-Covariate Interactions

Three studies provided data on the covariate effect of the index reaction (Fig 5). The reduced risk of recurrent reaction due to ICM change did not appear to be altered by index-reaction severity. There was no evidence of a difference between the risk of recurrent reaction in patients with a severe index reaction compared with those with a mild index reaction (relative odds ratio = 0.80; 95% CrI: 0.05, 16.05; P = .44, favoring patients with a severe index reaction) or those with a severe index reaction compared with those with a moderate index reaction (relative odds ratio = 0.48; 95% CrI: 0.09, 2.84; P = .20, favoring patients with a severe index reaction).

Forest plot shows meta-analysis of effects of index hypersensitivity                         reactions. Diamonds represent the summary relative odds ratio (OR) centered                         on a combined estimate and extending to 95% credible intervals (CrIs), with                         estimated 95% prediction intervals (PrIs) depicted as extending solid                         horizontal lines. Gray squares and dashed horizontal lines indicate reported                         (covariate-adjusted) relative odds ratios and 95% CIs. Black squares and                         solid horizontal lines indicate (study-specific) predicted relative odds                         ratios and 95% CrIs based on the posterior distribution for individual                         studies. The size of the square is proportional to the inverse of the                         variance of the log relative odds ratio of each study.

Figure 5: Forest plot shows meta-analysis of effects of index hypersensitivity reactions. Diamonds represent the summary relative odds ratio (OR) centered on a combined estimate and extending to 95% credible intervals (CrIs), with estimated 95% prediction intervals (PrIs) depicted as extending solid horizontal lines. Gray squares and dashed horizontal lines indicate reported (covariate-adjusted) relative odds ratios and 95% CIs. Black squares and solid horizontal lines indicate (study-specific) predicted relative odds ratios and 95% CrIs based on the posterior distribution for individual studies. The size of the square is proportional to the inverse of the variance of the log relative odds ratio of each study.

Four studies provided data on the covariate effect of co-administered and usually nonstandard premedication (Fig 6). Risk reduction did not appear to change with the use or nonuse of premedication. There was no evidence of a difference between the risk of recurrent reaction in patients cotreated with antihistamines (relative odds ratio = 0.90; 95% CrI: 0.29, 2.18; P = .39, favoring patients cotreated with antihistamines) or in patients cotreated with corticosteroids and antihistamines (relative odds ratio = 1.62; 95% CrI: 0.64, 3.71; P = .13, favoring patients with no premedication) compared with those with no premedication.

Forest plot shows meta-analysis of effects of co-administered                         premedication regimens. The antihistamine and corticosteroid regimens                         administered and analyzed were nonstandard, variable, and inconsistently                         used. Diamonds represent the summary relative odds ratio (OR) centered on a                         combined estimate and extending to 95% credible intervals (CrIs), with                         estimated 95% prediction intervals (PrIs) depicted as extending solid                         horizontal lines. Gray squares and dashed horizontal lines indicate reported                         (covariate-adjusted) relative odds ratios and 95% CIs. Black squares and                         solid horizontal lines indicate (study-specific) predicted relative odds                         ratios and 95% CrIs based on the posterior distribution for individual                         studies. The size of the square is proportional to the inverse of the                         variance of the log odds ratio of each study.

Figure 6: Forest plot shows meta-analysis of effects of co-administered premedication regimens. The antihistamine and corticosteroid regimens administered and analyzed were nonstandard, variable, and inconsistently used. Diamonds represent the summary relative odds ratio (OR) centered on a combined estimate and extending to 95% credible intervals (CrIs), with estimated 95% prediction intervals (PrIs) depicted as extending solid horizontal lines. Gray squares and dashed horizontal lines indicate reported (covariate-adjusted) relative odds ratios and 95% CIs. Black squares and solid horizontal lines indicate (study-specific) predicted relative odds ratios and 95% CrIs based on the posterior distribution for individual studies. The size of the square is proportional to the inverse of the variance of the log odds ratio of each study.

Severe-grade Recurrent Hypersensitivity Reactions and Adverse Events

Five studies provided unadjusted data (a total of five outcome events) on the incidence of severe immediate recurrent hypersensitivity reactions by ICM change versus no ICM change. A meta-analysis found no evidence of a difference (crude risk ratio = 0.34; 95% CrI: 0.01, 3.74; 95% prediction interval: 0.00, 5.65; P = .20, favoring the ICM group; tau = 0.38) (Fig E1 [online]). No studies reported adverse events caused by an ICM change.

Sensitivity Analysis

The meta-analysis of repeat immediate hypersensitivity reactions of any severity based on the unadjusted, binary data calculated estimates similar to the adjusted results obtained in the main analysis (summary risk ratio = 0.33; 95% CrI: 0.19, 0.54; P < .001) (Fig E2 [online]). The results were similar and stable when the alternative prior for tau was used or when double-zero studies were included (data available upon request).

Discussion

Single-center retrospective, observational studies have suggested a protective effect of changing iodinated contrast media (ICM) to reduce the likelihood of recurrent ICM hypersensitivity reactions, but those have primarily been single-center studies with moderate sample sizes. In our meta-analysis of over 7000 patients based on six retrospective observational studies with moderate to severe risk of bias, changing ICM was associated with a reduced risk of recurrent ICM hypersensitivity reaction of any severity by an average of 61%. This result did not materially change during sensitivity analyses. Because comparative evidence is scarce and events were rare, it is unclear whether changing ICM affects the likelihood of severe recurrent ICM hypersensitivity reactions. No studies reported adverse events directly associated with the ICM change itself.

The strengths of the current systematic review included a series of reliable study methodologies, including an explicit prospectively reported research question and methodology (21), a comprehensive literature search involving multiple data bases, dual-screen and dual-selection of eligible studies, dual-extraction of data, dual-assessment of risk of bias, and random-effects model meta-analysis of confounding-corrected data with use of a fully Bayesian framework. Our exploration of heterogeneity not only included clinically important study-level covariates, that is, risk of bias and baseline control risk, but also extended to context-specific patient-level confounders, such as index-reaction severity and co-administered premedication; such data were obtained at the patient level as long as the data were available (28).

Given the consistently observed, large, relative benefit of ICM switching (on average, approximately 60% reduction in recurrent ICM hypersensitivity reaction) and apparent absence of unexpected adverse events from this approach, our observational data support the guideline-recommended routine implementation of ICM change in patients with a prior hypersensitivity reaction. To effectively implement this approach, organizing a standardized and practical recording system that shares comprehensive and accurate documentation of individuals’ history of administration of ICM and any adverse reactions to specific ICM is a required first step. A further challenge is that the existing evidence is largely based on nonstandardized practice-based approaches to ICM change; thus, which substitution algorithms are better than others or whether ICM change should accompany a specific premedication regimen remains unclear.

Our review has several important limitations. First, our results were based on only six retrospective, nonrandomized, practice-based observational studies. Observational evidence is subject to bias and confounding, and even with adjustment for important confounders, given the unguaranteed comparability between the comparison groups, internal validity cannot be comparable to high-quality randomized evidence. For instance, physicians may have selectively applied a more aggressive prevention strategy, such as a standard-of-care premedication regimen combined with ICM change for patients at a higher risk of recurrent reactions and a less aggressive strategy for lower-risk patients. Second, although our results favored ICM change, we did not address whether specific ICM substitution pairs or algorithms were superior (or inferior) to others in preventing recurrent reactions; these data were generally scarce. Further, sparse data precluded assessing whether specific ICM pairs downgraded or upgraded a prior reaction (ie, effect of grade change). By default, avoiding severe, life-threatening reactions should be a part of the main goal of prevention strategies. However, the included studies largely failed to address this question, perhaps because of the rarity of severe reactions. Third, although our results found that the preventive effect of ICM change remained regardless of co-administered premedication, we meta-analyzed the treatment-covariate interactions only and failed to address whether specific premedication regimens were more effective than others when combined with ICM. Additionally, most premedication used in the included studies was nonstandard and variable. Due to the available data, we were unable to determine whether or how premedication should be performed, despite its clinical relevance (21).

In conclusion, changing the iodinated contrast media (ICM) from the culprit formulation that induced a prior reaction was associated with a large reduction in the risk of recurrent hypersensitivity reactions. Nevertheless, ICM changes cannot prevent all recurrent reactions, including severe reactions. Further research should explore specific approaches to selecting the best alternative ICM, as well as whether premedication continues to have a role in this context. Candidates include not only prespecified selection algorithms for selecting a particularICM formulation from a locally available lineup but also skin-testing–based approaches (33,34). Although conducting randomized clinical trials is the most reliable approach to assessing the comparative effectiveness of an intervention, creating large practice-based registries might be an alternative—and more realistic—option. In either case, the additional benefit of co-administering a specific premedication regimen, if such a formal assessment is necessary, should be assessed within this context to help establish reliable and comprehensive prevention strategies.

Disclosures of conflicts of interest: H.U. No relevant relationships. T.N. No relevant relationships. A.T. No relevant relationships. N.H. No relevant relationships. S.I. No relevant relationships. Y.T. No relevant relationships. S.N. Honoraria for lectures from Bayer, GE Healthcare, Eisai-Bracco, Guerbet, Siemens Healthineers, Canon Medical Systems, Fuji-Film Medical. M.S.D. Royalties for Wolters Kluwer and uptodate.com; board of directors for Society of Advanced Body Imaging; associate editor of Radiology. T.T. No relevant relationships.

Acknowledgments

The authors thank Shoko Abe, MD, PhD, Yoon-Seok Chang, MD, PhD, Whal Lee, MD, PhD, and Jennifer McDonald, PhD, for providing unpublished data from their original studies, and Hiroaki Ishiguchi, MD, PhD, Hironori Shimamoto, MD, and Takehiro Yamada, MD, PhD, for screening abstracts.

Author Contributions

Author contributions: Guarantors of integrity of entire study, H.U., T.T.; study concepts/study design or data acquisition or data analysis/interpretation, all authors; manuscript drafting or manuscript revision for important intellectual content, all authors; approval of final version of submitted manuscript, all authors; agrees to ensure any questions related to the work are appropriately resolved, all authors; literature research, H.U., T.N., S.I., S.N., M.S.D., T.T.; clinical studies, H.U., T.N., A.T., N.H., S.N., T.T.; statistical analysis, H.U., T.T.; and manuscript editing, H.U., T.N., A.T., N.H., Y.T., S.N., M.S.D., T.T.

T.N. and T.T. supported in part by the Ministry of Education, Culture, Sports, Science, and Technology, Japan (JSPS KAKENHI grants 26460755 and 19K07877).

Data sharing: All data generated or analyzed during the study are included in the published paper.

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Article History

Received: Feb 15 2022
Revision requested: Apr 12 2022
Revision received: May 17 2022
Accepted: May 24 2022
Published online: July 19 2022
Published in print: Nov 2022