Adverse reactions after intravascular iodinated contrast media administration and their management.

Endovascular interventions and diagnostic examinations using iodinated contrast media (ICM) are standard of care in current vascular medicine. Although ICM use is generally considered safe, it may be associated with adverse reactions, vary from minor disturbances to rare, but severe life-threatening complications. This position paper of European Society of Vascular Medicine integrates current knowledge and summarizes the key information related to the use of intravascular ICM, serving as recommendation on prevention and management of acute, late, and very late adverse reactions. It should help the health professionals in all fields of vascular medicine to make decisions in daily practice for safe use of contrast media.

Delayed hypersensitivity reactions to iodinated contrast media: A diagnostic approach by skin tests.

BACKGROUND: Adverse drug reactions to iodinated contrast media (ICM) have risen due to their increasing use in x-ray-based imaging modalities. Delayed hypersensitivity reactions are mainly caused by nonionic monomeric compounds and represent an issue impacting the diagnostic-therapeutic pathways of cancer, cardiology and surgery patients. OBJECTIVES: To prospectively evaluate the usefulness of skin tests in delayed hypersensitivity reactions to ICM and to evaluate the tolerability of iobitridol, a monomeric nonionic low osmolality compound, as a possible safe alternative. METHODS: Patients with delayed hypersensitivity reactions to ICM referred to us from 2020 to 2022 were prospectively enrolled in the study. All patients underwent patch test and, if negative, intradermal test with the culprit ICM and iobitridol as alternative. RESULTS: A total of 37 patients (females 24, 64.9%) were enrolled in the study. Iodixanol and iomeprol were the most frequently involved ICM (48.5% and 35.2%, respectively); 62.2% of patients presented maculopapular eruption, while 37.8% reported delayed urticaria-like rash. Skin tests resulted positive to the culprit ICM in 19 patients (51.4%), 16 to patch test and 3 to intradermal test. Skin tests with iobitridol, tested as alternative, resulted positive in 3/19 patients (15.8%). All 16 patients with negative results to iobitridol were administered this ICM and tolerated it. CONCLUSIONS: In at least half of patients, delayed-type hypersensitivity was demonstrated by skin tests, particularly by patch test. This diagnostic approach resulted simple, cost-effective and safe, not only to confirm the culprit ICM but also to identify iobitridol as feasible alternative.

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

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.

Non-immediate hypersensitivity reactions to iomeprol: Diagnostic value of skin tests and cross-reactivity with other iodinated contrast media.

BACKGROUND: Iodinated contrast media produce non-immediate hypersensitivity reactions (NIHR). The goal of this prospective study was to determine the utility of skin tests and the subsequent tolerance to negative skin-tested iodinated contrasts in patients with NIHR caused by iomeprol. METHODS: Prick and intradermal tests with iomeprol, iopamidol, iopromide, and iobitridol were performed in all patients. IV challenge with the causative contrast (iomeprol in 90%) was made if skin tests were negative. In case of a positive skin test with the causal contrast, or a positive challenge test with it, IV challenge test with an alternative, negative skin-tested contrast was performed in all patients. RESULTS: Skin tests were positive in 47.6% (20/42) of patients with NIHR induced by iomeprol. Of the 66 challenge tests performed with negative skin-tested iodinated contrasts, tolerance was confirmed in 35 (53%): 32 iomeron, 2 iobitridol, 1 iopamidol. Cross-reactivity between iomeprol and iopamidol was 22% (4/20 in patients with positive skin tests and 5/21 in patients with negative skin tests). CONCLUSIONS: Sensitivity of the skin tests was less than 50% NIHRs due to iomeprol, while the negative predictive value of skin tests in patients who tolerated challenges with alternative contrasts (mainly iopamidol) was 53% (35 tolerated out of 66 performed). The cross-reactivity between iomeprol and iopamidol is high.

A Retrospective Study to Compare the Effects of Methylprednisolone and Dexamethasone in 35 Patients with Anaphylactic Shock Due to Iodinated Contrast Media During Cardiac Catheterization.

BACKGROUND This retrospective study aimed to compare the effects of methylprednisolone and dexamethasone in 35 patients with anaphylactic shock due to iodinated contrast media (ICM) during cardiac catheterization. MATERIAL AND METHODS Thirty-five patients diagnosed with ICM-related anaphylactic shock were enrolled. Nineteen patients received methylprednisolone, while 16 patients received dexamethasone. RESULTS The mean age of patients was 59.8 years in the methylprednisolone group and 57.2 years in the dexamethasone group (P=0.502). Most patients were male (82.9% [26/35]). The groups were matched for cardiac function, kidney function, comorbidities, prior contrast, previous radiocontrast media reactions, and allergic tendencies (all P>0.05). The severity of coronary artery disease, assessed using the SYNTAX II score, was similar between groups (P=0.620). Six patients died from ICM-induced anaphylactic shock. There was no significant difference in mortality between the 2 groups (P=1.000). CONCLUSIONS There was no significant difference in patient mortality from anaphylactic shock associated with ICM during cardiac catheterization between the methylprednisolone and dexamethasone groups.

Isn't it time to consider oncological status as a new risk factor of iodinated contrast media hypersensitivity?

SUMMARY: Background. The literature describes several risk factors for hypersensitivity (HS) reactions to iodinated contrast media (ICM). Objective. To analyze the characteristics of patients experiencing HS reactions to ICM with a focus on oncological status. Methods. All patients (n = 80) with suspected HS to ICM who underwent an allergy evaluation in a Belgian University Hospital over a 5-year period were retrospectively included. Results. Overall, forty patients (50%) had a history of neoplasia, and this group was characterized by less atopy (p less than 0.004). No significant difference was observed between oncological and non-oncological patients in terms of gender, age, cardiovascular diseases, medical treatment, and number of previous exposures or reactions to ICM. Conclusions. A high proportion of oncological patients was observed in our population with HS to ICM. They did not have other known risk factors, and they were less atopic. Larger multicentric studies should explore cancer as a potential new risk factor.

Practice parameters for diagnosing and managing iodinated contrast media hypersensitivity.

Immediate and nonimmediate hypersensitivity reactions to iodinated contrast media (ICM) have been reported to occur in a frequency of about 0.5%-3% of patients receiving nonionic ICM. The diagnosis and management of these patients vary among guidelines published by various national and international scientific societies, with recommendations ranging from avoidance or premedication to drug provocation test. This position paper aims to give recommendations for the management of patients with ICM hypersensitivity reactions and analyze controversies in this area. Skin tests are recommended as the initial step for diagnosing patients with immediate and nonimmediate hypersensitivity reactions; besides, they may also help guide on tolerability of alternatives. Re-exposition or drug provocation test should only be done with skin test-negative ICMs. The decision for performing either re-exposition or drug provocation test needs to be taken based on a risk-benefit analysis. The role of in vitro tests for diagnosis and pretreatment for preventing reactions remains controversial.

Use of Intravenous Iodinated Contrast Media in Patients with Kidney Disease: Consensus Statements from the American College of Radiology and the National Kidney Foundation.

Intravenous iodinated contrast media are commonly used with CT to evaluate disease and to determine treatment response. The risk of acute kidney injury (AKI) developing in patients with reduced kidney function following exposure to intravenous iodinated contrast media has been overstated. This is due primarily to historic lack of control groups sufficient to separate contrast-induced AKI (CI-AKI; ie, AKI caused by contrast media administration) from contrast-associated AKI (CA-AKI; ie, AKI coincident to contrast media administration). Although the true risk of CI-AKI remains uncertain for patients with severe kidney disease, prophylaxis with intravenous normal saline is indicated for patients who have AKI or an estimated glomerular filtration rate less than 30 mL/min/1.73 m2 who are not undergoing maintenance dialysis. In individual high-risk circumstances, prophylaxis may be considered in patients with an estimated glomerular filtration rate of 30-44 mL/min/1.73 m2 at the discretion of the ordering clinician. This article is a simultaneous joint publication in Radiology and Kidney Medicine. The articles are identical except for stylistic changes in keeping with each journal's style. Either version may be used in citing this article.

Diagnostic approach to hypersensitivity reactions to iodinated contrast media: a single-center experience on 98 patients.

Summary: Adverse reactions to iodinated contrast media (ICM) are reported in 1%-3% of diagnostic procedures. They represent a relevant problem involving patients' safety as well as relevant costs for healthcare systems. Premedication with antihistamines and corticosteroids is still widely used, but evidence of its efficacy is lacking and there is a risk for under-estimation of possible severe adverse reactions to ICM in those who undergo premedication. Data from 98 patients with a previous reaction to ICM that consecutively referred to our unit between 2015 and 2018 were retrospectively analyzed. They underwent an allergologic workup comprehending skin tests and drug provocation tests (DPT) with ICM. The skin test showed a very high negative predictive value (NPV) compared to DPT in patients with a previous immediate adverse reaction, while the NPV in patients with a previous delayed adverse reaction was lower. After completion of the allergologic workup, 94 patients (95.9%) could tolerate a DPT with the culprit or alternative ICM. Subsequently, 90 patients were reached by phone to assess if they had been re-exposed to ICM for radiologic procedure. Thirty-nine patients had been re-exposed, without any premedication in 13 cases: 12 of them had tolerated the ICM, while one reacted again despite a negative DPT with the same ICM. Overall, the NPV of this protocol was elevated (92.3%) for patients undergoing DPT and subsequent exposure to the same ICM in a real-life setting. Collaboration between the prescribing physician, the radiologist and the allergist, and an accurate allergologic workup are essential to ensure maximum safety for the patient.

Hypersensitivity Reactions to Iodinated Contrast Media: A Multicenter Study of 196 081 Patients.

Background Multicenter studies may be required for establishing guidelines for safe usage of iodinated contrast media (ICM). Purpose To identify the prevalence, patterns, risk factors, and preventive measures for ICM-related hypersensitivity reactions (HSRs). Materials and Methods Between March 2017 and October 2017, a total of 196 081 patients who underwent ICM administration were enrolled from seven participating institutions. The occurrence of HSRs and baseline patient information were recorded. χ2 and Student t test were performed, and logistic regression analyses were used to identify risk factors that predict occurrence and recurrence of HSR. Results Among 196 081 patients (mean age ± standard deviation, 59.1 years ± 16.0; 105 014 men and 91 067 women) who underwent ICM administration, the overall prevalence of HSRs was 0.73% (1433 of 196 081), and severe reactions occurred in 0.01% (17 of 196 081). Conditional logistic regression for patients with HSR (n = 1433) and a control group (1:1 matched group for age, sex, ICM product, and institution) demonstrated that a patient's previous individual history of an ICM-related HSR (adjusted odds ratio [OR], 198.8; P < .001), hyperthyroidism (adjusted OR, 3.6; P = .04), drug allergy (adjusted OR, 3.5; P < .001), and other allergic diseases (adjusted OR, 6.8; P < .001) and a family history of ICM-related HSRs (adjusted OR, 14.0; P = .01) were predictors of HSR occurrence. Logistic regression analysis showed that use of premedication with antihistamine (OR, 0.5; P = .01) and change in the generic profile of ICM (OR, 0.5; P < .001) were preventive against recurrent HSR. Conclusion Family history as well as previous individual history of hypersensitivity reactions (HSRs) to iodinated contrast media (ICM) were risk factors for HSR occurrence, suggesting a potential genetic predisposition. A change in the culprit ICM and premedication with antihistamine are useful for reducing the recurrence of HSRs. © RSNA, 2019 Online supplemental material is available for this article.

Relationship between Lower Dose and Injection Speed of Iodinated Contrast Material for CT and Acute Hypersensitivity Reactions: An Observational Study.

BackgroundThere are few data on the relationship between acute hypersensitivity reactions and the dose and injection rate of iodinated contrast material for CT.PurposeTo determine the relationship between lower dose and injection speed of iodinated contrast material for CT and the rate of acute hypersensitivity reactions.Materials and MethodsThis retrospective study included adults (age ≥18 years) undergoing nonionic iodinated contrast material-enhanced abdominal CT between August 2016 and January 2017 (control period) and between August 2017 and January 2018 (intervention period); all examinations were conducted in an outpatient setting. Compared with CT during the control period, CT during the intervention period involved a reduced dose of contrast material achieved by lowering the CT tube voltage. CT examinations in the control period were performed with 120 kVp, a contrast material dose of 2 mL/kg (maximum, 150 mL), and an injection speed of 3 or 4 mL/sec. CT examinations in the intervention period were performed with 100 kVp, a contrast material dose of 1.5 mL/kg (maximum, 130 mL), and an injection speed of 2.5 or 3 mL/sec. Per-examination rates of acute hypersensitivity reactions to iodinated contrast material were compared between the control and intervention periods with use of a multivariable Poisson regression model, the parameters of which were estimated by using generalized estimating equations with an independence correlation structure.ResultsA total of 21947 adults (mean age ± standard deviation, 59 years ± 12; 8797 women [40%]) underwent 25119 CT examinations during the control period; 23019 adults (mean age, 59 years ± 12; 9538 women [41%]) underwent 26491 CT examinations during the intervention period. The rate of acute hypersensitivity reactions was 1.42% (376 of 26491 examinations; 95% confidence interval [CI]: 1.28%, 1.57%) in the intervention period and 1.86% (468 of 25119 examinations; 95% CI: 1.70%, 2.04%) in the control period, with a multivariable-adjusted relative risk of 0.85 (95% CI: 0.74, 0.99; P = .03).ConclusionReduction in the dose and injection speed of iodinated contrast material for CT was associated with a lower rate of acute hypersensitivity reactions to iodinated contrast material.© RSNA, 2019Online supplemental material is available for this article.

Intravascular Iodinated Contrast Is an Independent Cause of Acute Kidney Injury Following Coronary Angiography.

OBJECTIVES: Recent studies have questioned whether intravascular iodinated contrast remains an independent cause of acute kidney injury (AKI). We sought to assess whether iodinated contrast administered during coronary angiography is an independent cause of AKI. METHODS: We identified all of the patients who underwent coronary angiography between July 1, 2015 and June 30, 2017 with a discharge diagnosis of AKI that developed within 7 days following angiography. Using chart review, we categorized patients as having multifactorial AKI if ≥1 insults other than intravascular contrast potentially contributed to kidney injury or contrast-induced AKI (CI-AKI) if the only insult was contrast administration. We compared the severity of AKI and renal function upon discharge between patients with CI-AKI and multifactorial AKI. RESULTS: We identified 78 patients who experienced AKI within 7 days following angiography, 10 (13%) of whom had CI-AKI and 68 of whom (87%) experienced multifactorial AKI. Nine (90%) patients with CI-AKI manifested stage 1 disease, 1 (10%) had stage 2 disease, and 9 (90%) experienced full recovery of kidney function. More patients with multifactorial AKI developed stage 2 or 3 disease (42% vs 10%, χ2 = 3.73, P = 0.05) and experienced either partial recovery of kidney function or persistent kidney impairment compared with patients with CI-AKI (25% vs 10%, χ2 = 1.9, P = 0.17), although the latter comparison was not statistically significant. CONCLUSIONS: The intravascular administration of iodinated contrast remains an independent cause of AKI. Compared with those with multifactorial AKI, patients with CI-AKI appear to be more likely to experience mild decrements in kidney function that recover completely.

Contrast induced-acute kidney injury following peripheral angiography with carbon dioxide versus iodinated contrast media: A meta-analysis and systematic review of current literature.

OBJECTIVE: We conducted a meta-analysis to compare the incidence of acute kidney injury (AKI) with carbon dioxide (CO2 ) versus iodinated contrast media (ICM). BACKGROUND: Contrast induced-acute kidney injury (CI-AKI) is a known complication following endovascular procedures with ICM. CO2 has been employed as an alternative imaging medium as it is nontoxic to the kidneys. METHODS: Search of indexed databases was performed and 1,732 references were retrieved. Eight studies (7 observational, 1 Randomized Controlled Trial) formed the meta-analysis. Primary outcome was AKI. Fixed effect model was used when possible in addition to analysis of publication bias. RESULTS: In this meta-analysis, 677 patients underwent 754 peripheral angiographic procedures. Compared with ICM, CO2 was associated with a decreased incidence of AKI (4.3% vs. 11.1%; OR 0.465, 95% CI: 0.218-0.992; P = 0.048). Subgroup analysis of four studies that included granular data for patients with chronic kidney disease (CKD) did not demonstrate a decreased incidence of AKI with CO2 (4.1% vs. 10.0%; OR 0.449, 95% CI: 0.165-1.221, P = 0.117). Patients undergoing CO2 angiography experienced a higher number of nonrenal events including limb/abdominal pain (11 vs. 0; P = 0.001) and nausea/vomiting (9 vs. 1; P = 0.006). CONCLUSIONS: In comparison to ICM, CO2 use is associated with a modestly reduced rate of AKI with more frequent adverse nonrenal events. In studies that use CO2 as the primary imaging agent, the average incidence of AKI remained high at 6.2%-supporting the concept that factors other than renal toxicity from ICM may contribute to renal impairment following peripheral angiography. © 2017 Wiley Periodicals, Inc.

Risk for adverse reaction to iodinated contrast media: a validation study. / Risco de reação adversa ao meio de contraste iodado: um estudo de validação.

OBJECTIVES: To validate the content of the nursing diagnosis, Risk for adverse reaction to iodinated contrast media, and its nursing interventions and outcomes according to standardized terminologies. METHOD: Fehring's (1987) model of diagnosis content validation was used, with the participation of experts including registered nurses and physicians. RESULTS: Seventy-four experts validated the title and the definition of the diagnosis, and assessed 28 risk factors, five of which were validated as primary, 22 as secondary, and one was discarded. The inclusion of the diagnosis in the NANDA International Taxonomy II was evaluated by 41 registered nurses and validated for Area II - Safety/ Protection and Class 2 - Physical Injury. Sixty-three experts validated seven nursing interventions as primary and one as secondary, and seven nursing outcomes as principal and one as minor. CONCLUSION: The title, definition, and risk factors of the diagnosis were validated, in addition to eight interventions and eight nursing outcomes.

Immediate hypersensitivity to iodinated contrast media: diagnostic accuracy of skin tests and intravenous provocation test with low dose.

BACKGROUND: The diagnosis of HSR to iodinated contrast media (ICM) is challenging based on clinical history and skin tests. OBJECTIVE: This study evaluates the negative predictive value (NPV) of skin tests and intravenous provocation test (IPT) with low-dose ICM in patients with suspected immediate hypersensitivity reaction (HSR) to ICM. METHODS: Thirty-seven patients with suspected immediate hypersensitivity reaction to ICM were included retrospectively. Skin tests and a single-blind placebo-controlled intravenous provocation test (IPT) with low-dose iodinated contrast media (ICM) were performed. RESULTS: Skin tests with ICM were positive in five cases (one skin prick test and five intradermal test). Thirty-six patients were challenged successfully by IPT, and only one patient had a positive challenge result, with a grade I reaction by the Ring and Messmer classification. Ten of 23 patients followed up by telephone were re-exposed to a negative tested ICM during radiologic examination; two experienced a grade I immediate reaction. CONCLUSIONS & CLINICAL RELEVANCE: For immediate hypersensitivity reaction to ICM, the NPV for skin tests and IPT with low dose was 80% (95% CI 44-97%).

The effects of combining fusion imaging, low-frequency pulsed fluoroscopy, and low-concentration contrast agent during endovascular aneurysm repair.

OBJECTIVE: This study evaluated the effects of a combined imaging protocol using low-frequency pulsed fluoroscopy, fusion imaging, and low-concentration iodine contrast for endovascular aneurysm repair (EVAR) of aortic aneurysms of varying complexity. METHODS: The study retrospectively reviewed the data of 103 patients treated between May 2013 and November 2014 with the combined imaging protocol (group A) with low-dose fluoroscopy at 3.75 frames/s, fusion imaging, and iodine contrast of 140 mg iodine/mL. A control group (group B) consisted of 123 consecutive patients who underwent EVAR before the combined imaging protocol was introduced by matching the type of procedure. In group B, low-dose 7.5 frames/s fluoroscopy, no fusion imaging, and 200 mg iodine/mL contrast were used. All patients were reviewed for preoperative, intraoperative, and postoperative variables, with emphasis on intraoperative radiation (dose area product) and iodine exposure, fluoroscopy, and operation times, as well as technical success. Values are presented as median and interquartile range (IQR) when not stated otherwise. RESULTS: Group A included 22 infrarenal EVARs, 17 iliac branch devices, 10 thoracic endovascular aortic repairs, 21 fenestrated EVARs, and 33 thoracoabdominal branched/fenestrated EVARs. Groups A and B were similar in types of procedure, body mass index (P > .05), and intraoperative technical success (92% and 92%, respectively; P > .05). Operation time (230 [IQR, 138-331] minutes vs 235 [IQR, 158-364] minutes) and fluoroscopy time (66 [IQR, 33-101] minutes vs 72 [IQR, 42-102] minutes) were similar in both groups (P > .05), but radiation exposure (19,934 [IQR, 11,340-30,615] µGym(2) vs 32,856 [IQR, 19,562-55,677] µGym(2); P < .0001), contrast volume usage (63 [IQR, 103-145] mL vs 215 [IQR, 166-280] mL; P < .0001), and iodine dose (14.5 [IQR, 8.8-20.4] g iodine vs 43.0 [IQR, 32.2-56.0] g iodine; P < .0001) were lower in group A than in group B. The differences were uniform throughout the different procedure types, with the exception of fenestrated grafts, where radiation exposure was similar between group A and B; however, group A had a much higher involvement of the superior mesenteric artery in the repairs (81% vs 17%; P < .0001) explaining this finding. Fluoroscopic frame rate reduction contributed to a median reduction of the dose area product by 22%. Only four of the group A patients (3.9%) showed a decrease in the glomerular filtration rate ≥30% after EVAR, although 32% of the entire group had at least moderately impaired renal function preoperatively. CONCLUSIONS: Combining low-frequency pulsed fluoroscopy, fusion imaging, low-concentration, and iodine contrast medium during EVAR reduces the exposure to radiation and iodine.