Incidence of Iodinated Contrast Reactions in Radiological Examinations at a Teaching Hospital

INTRODUCTION

Radiological contrast media (RCM) are pharmacological agents administered to enhance the visibility of internal structures in medical imaging. Their primary role is to improve contrast resolution between tissues and between pathological and normal anatomy, thereby facilitating more accurate visualisation of organs, vessels, and lesions. Among the various types of contrast media, such as barium sulphate for gastrointestinal studies and gadolinium-based agents for magnetic resonance imaging (MRI), iodinated contrast media (ICM) remain the most widely employed, particularly in computed tomography (CT), angiography, and interventional radiology. Since their clinical introduction in the 1920s, ICM formulations have evolved considerably. Early high-osmolality ionic agents, though effective in enhancing image quality, were associated with frequent adverse reactions, ranging from mild symptoms such as nausea and vomiting to severe systemic complications, including cardiovascular collapse and renal dysfunction.^[1,2] The advent of non-ionic, low-osmolality contrast agents has substantially improved safety, reducing the overall incidence of severe adverse events. Nevertheless, hypersensitivity reactions continue to be reported and remain a source of clinical concern. Adverse reactions in this study were classified based on the American College of Radiology (ACR) Manual on Contrast Media, 2024 edition.^[3] Mild reactions were defined as self-limiting symptoms that generally did not require medical intervention, including transient nausea, vomiting, pruritus, flushing, and limited urticaria. Moderate reactions were characterised by more pronounced clinical manifestations such as generalised urticaria, facial oedema, bronchospasm, and tachycardia, which typically necessitated prompt pharmacologic management and close clinical observation. This standardised classification provided a structured framework for categorising reaction severity, ensuring consistency in reporting and enabling meaningful comparison with previously published studies.^[3] Globally, the incidence of adverse reactions to low-osmolality ICM ranges from 0.2% to 0.7%, with severe reactions occurring in approximately 0.04% of cases.^[4,5] In contrast, the rates with older high-osmolality ionic agents were reported as high as 12%.^[6] Within the Indian subcontinent, published data suggest variable reaction rates, with mild events observed in 1-3% of patients and severe reactions remaining rare but clinically significant.^[7-9] Such variability reflects differences in patient populations, comorbidities, contrast agents used, and institutional practices.

Adverse reactions are broadly categorised as immediate (within 1 h of administration) or delayed (after 1 h). Immediate reactions may be mild (pruritus, urticaria), moderate (bronchospasm, tachycardia), or severe (laryngeal edema, anaphylactic shock). Delayed reactions are predominantly dermatologic, often presenting as self-limiting rashes.^[10] Risk factors include patient-related variables (age, sex, asthma, diabetes, renal insufficiency, prior drug or contrast allergy) and procedural elements (contrast type, volume, route, and technical factors during injection).^[11,12] Importantly, most reactions are non-IgE-mediated hypersensitivity events rather than true allergies, underscoring the need for accurate risk stratification and prevention strategies.^[13] Despite the widespread use of ICM, there is limited systematically reported data from Indian clinical settings on the true incidence and spectrum of contrast reactions. Furthermore, existing studies often lack detailed stratification of reaction severity or identification of modifiable procedural risk factors. This knowledge gap highlights the need for institution-based evidence to guide local best practices and reinforce patient safety protocols.

The present cross-sectional study was therefore designed to evaluate the incidence and severity of iodinated contrast reactions and to identify key patient- and procedure-related risk factors. By doing so, it aims to contribute evidence-based insights into the safe administration of ICM and emphasise the importance of vigilance and preparedness in radiological practice.

MATERIAL AND METHODS

RESULTS

A total of 350 patients underwent contrast-enhanced radiological procedures during the study period. The mean age of the cohort was 52.3 ± 14.6 years (range: 18-82 years). The age distribution showed that 29.1% of patients were between 50-60 years, while 21.7% were aged >60 years. Sex distribution was nearly equal, with 186 males (53.1%) and 164 females (46.9%). Comorbidities were frequent, including hypertension (28.0%), diabetes mellitus (20.6%), and prior allergy history (11.4%), as summarised in Table 1.

Out of 350 patients, seven (2.0%; 95% CI: 0.8-4.1%) experienced adverse reactions to ICM. Among them, four were female (57.1%), and three were male (42.9%), with a mean age of 55.8 ± 6.9 years. Interestingly, five patients (71.4%) were aged 50-60 years, suggesting a higher susceptibility in older adults. A comparison between the entire cohort and the subgroup with reactions has been presented in Table 2.

Adverse reactions were distributed across different procedures. The highest number occurred in contrast-enhanced computed tomography (CECT) abdomen (3 cases, 42.9%), followed by CECT chest (2 cases, 28.6%), while CT angiography and intravenous urogram (IVU) contributed one case each. No reactions were observed in other CT procedures, such as brain or neck studies. This distribution is shown in Table 3.

When reactions were classified according to ACR criteria, four cases (57.1%) were mild, and three (42.9%) were moderate. Mild reactions included nausea, flushing, and localised pruritus, which were managed with reassurance and observation. Moderate reactions presented with urticaria, dyspnoea, and tachycardia, requiring treatment with antihistamines (n = 3) and supplemental oxygen (n = 2). Importantly, no severe or life-threatening reactions such as anaphylaxis, laryngeal oedema, or hypotension were reported. The classification and management of reactions have been presented in Table 4.

All reactions were classified as immediate hypersensitivity responses, occurring within 30 min of contrast administration. No delayed reactions were observed during the mandatory 30-min observation period or during the 24-h telephonic follow-up. This finding underscores the critical importance of immediate monitoring in the post-injection phase. Clinical outcomes were favourable for all seven patients. Symptoms resolved completely without hospital admission, corticosteroid therapy, or epinephrine administration. The absence of severe cases reinforces the effectiveness of using low-osmolality, non-ionic contrast agents and the role of early supportive interventions.

DISCUSSION

This study provides important insights into the incidence, nature, and associated factors of ICM reactions in a tertiary care radiology setting. Among 350 patients undergoing contrast-enhanced examinations, the observed reaction rate was 2%, with all cases classified as mild (n = 4) or moderate (n = 3). No severe or life-threatening reactions were reported. These findings underscore the favourable safety profile of modern non-ionic, low-osmolality agents compared to older ionic formulations. The observed 2% reaction rate aligns with previously published reports. Katayama et al.^[1], in a large multicentre prospective study of over 3,00,000 cases, reported an overall incidence of 3.13%, with severe reactions occurring in 0.04% of patients. More recent studies from Europe and North America have demonstrated rates ranging between 0.6% and 1.5% with low-osmolality non-ionic agents.^[2,3] Indian studies have documented comparable frequencies, typically between 1.5% and 2.8%.^[4,5] For instance, Sethi et al. observed an incidence of 1.9% among Indian patients undergoing CT procedures, while Gupta et al. reported 2.4% in a multicentre cohort.^[6,7] The absence of severe reactions in our cohort is consistent with some smaller regional studies^[8] and may reflect improvements in patient screening, staff preparedness, and standardised injection protocols.

Several risk factors for contrast hypersensitivity were identified. Age appeared to be an important determinant, as five of the seven affected patients were aged 50-60 years. Older patients may exhibit reduced renal clearance, altered cardiovascular function, and immune senescence, predisposing them to adverse reactions.^[9] Comorbidities also played a role; two patients with diabetes and one with coexisting hypertension developed reactions. Previous work has shown that metabolic disorders, especially diabetes, are linked with impaired renal clearance and increased susceptibility to drug hypersensitivity.^[10,11] A history of prior allergic reactions was documented in 3 of the affected patients. This aligns with published data indicating that patients with atopic or allergic diathesis have up to a 7-fold increased risk of ICM reactions compared to non-allergic individuals.^[12,13] Technical factors contributed in two cases, where rapid intravenous bolus injection and suboptimal venous access were implicated. Such findings are supported by evidence that injection speed and catheter-related factors influence the likelihood of adverse events by altering the hemodynamic and immunologic responses to contrast media.^[14] Interestingly, sex was not significantly associated with adverse outcomes in this study, although other investigations have suggested that women may be more susceptible, possibly due to hormonal and immunologic differences.^[15] The clinical manifestations in our cohort were consistent with American College of Radiology (ACR) guidelines.^[16] Mild reactions, such as nausea, pruritus, and flushing, were self-limiting, whereas moderate reactions, including urticaria and dyspnoea, required antihistamines and supplemental oxygen. No patients required corticosteroids, intravenous fluids, or epinephrine, and none required hospital admission. All reactions occurred within 30 min of contrast administration, consistent with the observation that most immediate hypersensitivity reactions manifest within this time frame.^[17] However, delayed reactions, which may present up to 24-48 h later, were not captured due to the limited follow-up period. This limitation suggests that the true incidence of reactions may be slightly underestimated.

The present study also highlights the role of pre-procedural screening and monitoring. All patients underwent medical history review, allergy screening, and renal function testing where indicated. While patients with renal dysfunction were screened pre-procedure, systematic post-procedural renal monitoring was not performed, leaving the possibility of under-detection of contrast-induced nephropathy (CIN). Previous meta-analyses have reported CIN rates ranging from 2-7% in at-risk populations, particularly among patients with diabetes and those with chronic kidney disease.^[18,19] Therefore, structured follow-up of renal parameters remains an area for improvement. This study has several limitations. It was a single-centre investigation, limiting generalisability across diverse populations. The relatively small sample size limited statistical power for detecting rare severe events, which occur in <0.05% of cases.^[20] Non-randomised sampling may have introduced bias, as high-risk patients may have been managed more cautiously. Reliance on immediate observation and self-reporting without biochemical or immunologic testing may have underestimated delayed or subclinical reactions. Moreover, systematic follow-up beyond 24 h was lacking, precluding assessment of delayed hypersensitivity and nephrotoxicity.

Despite these limitations, the findings carry clinical significance. The low incidence of ICM reactions supports the continued use of non-ionic low-osmolality agents as safe contrast agents in radiological practice. However, the presence of identifiable risk factors, older age, comorbidities, prior allergy history, and technical errors highlights the need for individualised risk assessment and preventive strategies. In high-risk patients, premedication with corticosteroids and antihistamines may be considered, though its use remains controversial and should be guided by clinical judgment.^[21] Furthermore, robust institutional protocols, including thorough documentation of prior reactions, staff preparedness, and availability of resuscitation drugs, are critical in ensuring patient safety. Future research should focus on multicentre studies with larger sample sizes to more accurately quantify rare severe events. Structured follow-up beyond 24-48 h would help capture delayed hypersensitivity and renal complications. Additionally, prospective evaluation of premedication protocols in high-risk groups would provide evidence for optimising preventive strategies.

LIMITATIONS

This study has a few limitations. Since it was conducted at a single centre, the results may not apply to all patient groups or hospital settings. The short follow-up period might have missed some delayed contrast reactions. Also, because advanced statistical models were not used, the study could not fully explore how different factors like age, medical conditions, and allergy history interact with each other. Even with these limitations, the study gives a clear and practical view of the safety of iodinated contrast in everyday radiology. It shows that proper precautions and monitoring help keep patients safe.

CONCLUSION

The findings of the present study indicate that the use of ICM, especially the newer non-ionic low-osmolality formulations, is associated with a high degree of safety and a very low rate of adverse reactions. In a cohort of 350 patients, only 2% experienced mild to moderate side effects, and no severe or life-threatening complications were encountered. These observations underscore that, when appropriate patient selection, comprehensive pre-procedural evaluation, and close post-administration monitoring are implemented, contrast-enhanced radiological examinations can be conducted with minimal risk. Factors such as increasing age, a history of diabetes, and previous allergic tendencies were identified as potential contributors to reaction susceptibility, highlighting the importance of individualised risk stratification. Ultimately, maintaining standardised safety protocols, ensuring readiness of medical personnel, and promoting patient awareness are essential components for preventing contrast-induced complications and sustaining safe imaging practices.