Contrast-enhanced imaging underpins modern diagnostics, yet adverse responses remain a safety concern. Immediate hypersensitivity reaction to contrast media (CM-IHR) occurs within one hour of administration and ranges from mild to severe, with potential for life-threatening outcomes if not promptly managed. A systematic evaluation consolidated findings from seven studies, covering 115,043 patients and 736,203 injections across iodinated contrast media (ICM) and gadolinium-based contrast agents (GBCA). Incidence varied by agent and analysis unit: overall 0.15% at patient level and 0.34% at injection level, with ICM higher than GBCA. Using predefined inclusion criteria, quality appraisal and pooled odds ratios (ORs) with confidence intervals (CIs), the analysis identified demographic, clinical and care setting factors associated with CM-IHR while highlighting areas of uncertainty that warrant caution in interpretation.
Evidence Base and Study Quality
The synthesis included four ICM-focused studies and three GBCA-focused studies, spanning prospective and retrospective designs and both patient-level and injection-level analyses. Methodological quality was predominantly high by Newcastle-Ottawa Scale ratings, with one study graded moderate. Definitions of IHR were aligned to reactions within one hour, with practical inclusion of studies observing up to 30–45 minutes in specific cohorts. Across the pooled dataset, ICM showed higher incidence than GBCA at both patient and injection levels. Importantly, heterogeneity was non-trivial for several pooled estimates, leading to the use of random-effects models and prespecified subgroup and sensitivity analyses when feasible. Funnel plot assessments did not indicate publication bias for key pooled outcomes such as sex, though the limited number of eligible studies constrained subgroup depth for several variables. These features support cautious generalisability while underscoring the need for consistent definitions and adjusted analyses in future work.
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Patient Demographics and Care Setting
Female sex emerged as a significant risk factor for CM-IHR, with pooled analysis showing increased odds (OR 1.46; 95% CI 1.33–1.59). This association persisted across sensitivity analyses and varied modestly by geographic subgroup, with higher estimates reported outside Asia. Age demonstrated an inverse relationship with risk when analysed as a continuous variable (OR 0.98; 95% CI 0.98–0.99), and categorical analyses from individual studies indicated elevated risk in adults under 50 years for both ICM-IHR and GBCA-IHR. In contrast, asthma history did not show a significant association with CM-IHR in pooled analysis (OR 1.12; 95% CI 0.95–1.33).
Care setting was differentially associated by contrast type. For ICM, outpatient status carried higher risk compared with inpatient and emergency settings (OR 3.08; 95% CI 1.13–8.44), although heterogeneity was high. For GBCA, pooled data did not demonstrate a significant difference between outpatients and inpatients. The analysis notes that detection and reporting dynamics may vary by setting, and concomitant treatments in inpatients could influence the clinical picture. These observations reinforce the relevance of context when planning monitoring immediately after contrast administration, particularly for ICM procedures undertaken in outpatient environments.
Prior Reactions and Scan-Related Determinants
The role of prior contrast reactions showed mixed signals. Pooled data from two studies suggested a non-significant trend toward increased risk of ICM-IHR with prior ICM hypersensitivity history (OR 7.49; 95% CI 0.42–135.09) accompanied by high heterogeneity, limiting firm conclusions. Individual reports indicated increased recurrence risk where prior immediate reactions had occurred for ICM, and higher repeated reaction rates for GBCA than first-time exposures, though designs did not always allow adjusted estimates or meta-analytic pooling. Taken together, evidence indicates possible elevated recurrence risk, but strength and precision remain limited by small numbers and heterogeneity.
Scan and dosing parameters were explored in individual studies. Prior intra-arterial ICM exposure was associated with higher IHR odds, whereas prior intravenous exposure was not. Higher ICM dose as a continuous measure correlated with increased risk, and higher ICM concentrations (350 mg I/mL and ≥370 mg I/mL versus 300 mg I/mL) were associated with higher incidence. Protocol factors also appeared relevant, with multiphase CT associated with lower IHR incidence than single-phase CT in one study. For patient allergy backgrounds, non-contrast drug or food allergies were linked to elevated ICM-IHR risk in one analysis and for GBCA, drug hypersensitivity and chronic urticaria showed associations on univariable analyses. Each of these factors was reported in single studies within the IHR context, so no pooled estimates were generated and findings should be interpreted cautiously.
Across a large aggregated cohort, female sex and younger age were consistently linked with higher risk of CM-IHR, while asthma history was not significantly associated. For ICM in particular, outpatient status was associated with increased risk, signalling a need for vigilant monitoring in that setting. Evidence around prior contrast hypersensitivity and scan-related determinants suggests potential influence on risk, yet heterogeneity and limited adjusted data constrain certainty. The findings support risk-aware planning around contrast selection, dosing and immediate post-administration observation, especially for younger females undergoing ICM-enhanced imaging in outpatient pathways. Further high-quality prospective studies with standardised definitions and adjusted analyses are needed to refine risk stratification and guide preventive strategies without overextending beyond the available evidence.
Source: European Journal of Radiology
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