Adverse reactions to intravenous iodinated contrast media: a primer for radiologists

Adverse reactions to intravenous iodinated contrast media may be classified as general and organ-specific, such as contrast-induced nephrotoxicity. General adverse reactions may be subclassified into acute and delayed types. Acute general adverse reactions can range from transient minor reactions to life-threatening severe reactions. Non-ionic contrast media have lower risk of mild and moderate adverse reactions. However, the risk of fatal reactions is similar for ionic and non-ionic contrast media. Adequate preprocedure evaluation should be performed to identify predisposing risk factors. Prompt recognition and treatment of acute adverse reactions is crucial. Risk of contrast induced nephrotoxicity can be reduced by use of non-ionic contrast media, less volume of contrast, and adequate hydration. The radiologist can play a pivotal role by being aware of predisposing factors, clinical presentation, and management of adverse reactions to contrast media.     

The use of iodinated and gadolinium contrast media during pregnancy and lactation

The use of iodinated or gadolinium-based contrast media in pregnant or lactating women often causes concerns in the radiology department because of the principle of not exposing a fetus or neonate to any drugs. Because of the uncertainty about the use of contrast media during pregnancy and lactation, the Contrast Media Safety Committee of the European Society of Urogenital Radiology decided to review the literature and draw up guidelines. An extensive literature search was carried out and summarized in a report. Based on the limited information available, simple guidelines have been drawn up. The report and guidelines were discussed at the 11th European Symposium on Urogenital Radiology in Santiago de Compostela, Spain. Mutagenic and teratogenic effects have not been described after administration of gadolinium or iodinated contrast media. Free iodide in radiographic contrast medium given to the mother has the potential to depress fetal/neonatal thyroid function. Neonatal thyroid function should be checked during the 1st week if iodinated contrast media have been given during pregnancy. No effect on the fetus has been seen after gadolinium contrast media. Only tiny amounts of iodinated or gadolinium-based contrast medium given to a lactating mother reach the milk, and only a minute proportion entering the babys gut is absorbed. The very small potential risk associated with absorption of contrast medium may be considered insufficient to warrant stopping breast-feeding for 24 h following either iodinated or gadolinium contrast agents.Members of the Committee: H.S. Thomsen (Chairman, Denmark), S.K. Morcos (Secretary, United Kingdom), T. Almén (Sweden), P. Aspelin (Sweden), M.F. Bellin (France), H. Flaten (Amersham Health, Norway), J.Å. Jakobsen (Norway), A. Löwe (Schering, Germany), R. Oyen (Belgium), A. Spinazzi (Bracco, Italy), F. Stacul (Italy), A.J. van der Molen (The Netherlands), J.A.W. Webb (United Kingdom).     

European Society of Urogenital Radiology (ESUR) guidelines on the safe use of iodinated contrast media

Since 1996 the Contrast Media Safety Committee of the European Society of Urogenital Radiology (ESUR) has released 19 guidelines regarding safety in relation to the use of radiographic, ultrasonographic as well as magnetic resonance contrast media. The committee has covered both renal and non-renal adverse events as well as other aspects of contrast media. The present paper is an overview of the work accomplished over the last 10 years regarding radiographic iodinated contrast media.     

Late adverse reactions to non-ionic contrast media: a cohort analytic study

In this cohort study early, intermediate and late reactions after intravenous injection of non-ionic contrast media were evaluated and compared with the nature and incidence of complaints stated by a control group investigated without contrast media. Study A was conducted by means of a questionnaire. In study B a physician interviewed a different group of patients. Early adverse reactions (day 1) occurred in 11.4% of patients to whom contrast (CM) media had previously been administered compared with 6.1% of patients who had not received a CM injection (study A). Late adverse reactions (up to day 7) were observed in 39.1% and 21.1% of the patients respectively. The incidence was 7.0% versus 0.9% on day 1 for the symptom increased diuresis. Between days 4 and 7, 4.8% and 2.6% of the patients respectively had this symptom, which is interpreted as an impairment of renal function. In study B the incidence of early adverse reactions was 3% and 1.5% respectively between days 2 and 3 (CM group). The authors conclude that more than half of the adverse reactions after (non-ionic) contrast media are due to the underlying disease and that a (clinically latent) impairment of renal function can be assumed.     

Effects of iodinated contrast media on blood and endothelium

The aim of the study was to assess the effects of iodinated contrast media on blood components and endothelium based on experimental and clinical studies and to produce clinically relevant guidelines for reducing thrombotic and hematologic complications following the intravascular use of contrast media. A report was drafted after review of the literature and discussions among the members of the Contrast Media Safety Committee of the European Society of Urogenital Radiology. The final report was produced following discussion at the 12th European Symposium on Urogenital Radiology in Ljubljana, Slovenia (2005). Experimental data indicate that all iodinated contrast media produce an anticoagulant effect and that this effect is greater with ionic contrast media. Several of the in vitro and experimental in vivo studies on haematological effects of contrast media have not been confirmed by clinical studies. Low- or iso-osmolar contrast media should be used for diagnostic and interventional angiographic procedures, including phlebography. Meticulous angiographic technique is the most important factor for reducing the thrombotic complications associated with angiographic procedures. Drugs and interventional devices that decrease the risk of thromboembolic complications during interventional procedures minimize the importance of the effects of contrast media.     

Management of acute adverse reactions to contrast media

When anaphylactoid and other severe adverse reactions to contrast media occur, prompt recognition and immediate treatment are essential. Simple guidelines for treatment have been requested by many radiologists, and therefore the Contrast Media Safety Committee has produced guidelines for treatment of acute adverse reactions to contrast media. The committee made an extensive review of the literature on treatment of adverse reactions to contrast media. Based on this, a report and guidelines were prepared. The resulting report was discussed at the 10th European Symposium on Urogenital Radiology in Uppsala. Sweden, September 2003. Guidelines for treatment of acute adverse reactions and a list of first-line drugs and equipment that should be available in the room where contrast medium is given are provided.The members of the Contrast Media Safety Committee of ESUR are H.S. Thomsen (Chairman, Denmark), S.K. Morcos (Secretary, United Kingdom), T. Almén (Sweden), P. Aspelin (Sweden), M.F. Bellin (France), H. Flaten (Amersham Health, Norway), J.Å. Jakobsen (Norway), G.P. Krestin (The Netherlands), A. Löwe (Schering, Germany), R. Oyen (Belgium), F. Stacul (Italy) and J.A.W. Webb (UK).     

Cardiovascular reactions to myelography with watersoluble contrast media

Summary Arterial blood pressure and heart rate were recorded for 5 to 7 h during myelography with iothalamate meglumine and metrizamide in 23 rabbits. After 0.6 ml iothalamate meglumine containing 280 mg I/ml a significant decrease in blood pressure and signs of circulatory failure were found. After identical doses of iothalamate meglumine to 0.4 ml containing 140 mg I/ml no significant fall in blood pressure was recorded. A decrease of blood pressure was always accompanied by a decrease of heart rate. Arterial blood pressure and heart rate during experimental myelography are suggested as useful variables in the evaluation and comparison of new contrast media for myelography.     

Adverse reactions to iodinated contrast media

Adverse reactions to iodinated contrast media (ICM) are more likely to develop in patients with asthma, a history of allergy or contrast reaction and in those who are debilitated or medically unstable. These reactions can be divided into renal and general, and the latter are subdivided into acute and delayed. Acute general reactions can be minor, intermediate or severe. Fatal reactions are rare. The introduction of low-osmolality agents has caused an overall reduction in the number of non-fatal contrast reactions. Prompt recognition and treatment of acute adverse side effects to ICM is invaluable and may prevent a reaction from becoming severe. Familiarity with cardiopulmonary resuscitation is essential for successful management of life-threatening reactions. Contrast-media-induced renal impairment can be reduced with the use of low-osmolality contrast media and extracellular volume expansion. The use of ICM in diabetic patients receiving metformin should be carried out with care to avoid metformin-induced lactic acidosis. However, this problem is mainly observed in patients with diabetic nephropathy.     

Contrast media safety-an update

The value of contrast agents has for long been documented by their common daily use in imaging departments worldwide. In principle, they should be injected and leave the body immediately after use in the same condition or undergo natural metabolism without making any harm to the patient. However, this is not the case. It is of utmost importance to reduce the prevalence to as close as possible to zero. This can be done by identifying the patients at risk before administration of contrast agents. For acute non-renal adverse reactions, it is also important to be prepared for treating them instantly. The current review is a short state of the art regarding adverse reactions to contrast agents.     

Optimum utilisation of intravascular radiological contrast media

The major current problem related to radiological contrast media is how best to achieve the optimum cost benefit efficiency in the deployment of contrast agents. Low osmolar contrast media (LOCM) are more comfortable for the patient and cause less adverse reactions than high osmolar contrast media (HOCM), but there is no statistically proven reduction in mortality. There is no improvement in diagnostic intravascular imaging when LOCM replaces HOCM. LOCM are 4–5 times more expensive than HOCM.It is therefore proposed that, until adequate finances become available, HOCM might well continue to be utilised for routine injections for intravenous urography (IVU), computed tomography (CT) and for visceral angiography, reserving LOCM for high-risk patients, high-risk procedures and for painful procedures. Offprint requests to: R. G. Grainger     

Late adverse reactions to intravascular iodine based contrast media: an update

DEFINITION: Late adverse reactions (LAR) to contrast media (CM) are defined as reactions occurring 1 h to 1 week after exposure. NEED FOR REVIEW: In view of more prospective studies of LAR and new data about their pathophysiology, the Contrast Medium Safety Committee (CMSC) of the European Society of Urogenital Radiology (ESUR) reviewed the literature on LAR and updated their guidelines. CLINICAL FEATURES AND PATHOLOGY: LAR after CM include symptoms such as nausea, vomiting, headache, itching, skin rash, musculoskeletal pain, and fever. Skin reactions are well-documented LAR to CM with an incidence of approximately 2%-4% after nonionic monomers. LAR are commoner by a factor of three to four after nonionic dimers. The commonest skin reactions are maculopapular rashes, erythema and skin swelling. These reactions are T cell-mediated immune reactions, and the diagnosis may be confirmed using skin tests (patch or delayed reading intradermal). The main risk factors for LAR are a previous reaction to contrast medium, a history of allergy, and interleukin-2 treatment. Most skin reactions are mild or moderate and self-limiting. MANAGEMENT: Management is symptomatic and similar to the management of other drug-induced skin reactions. To reduce the risk of repeat reactions avoidance of the relevant CM and any cross-reacting agents identified by skin testing is recommended.     

Role of hemolysis in potassium release by iodinated contrast medium

It has been demonstrated that an iodinated contrast medium (CM) causes release of potassium into blood vessel lumina, resulting in an increase in serum potassium. The purpose of the present study was to assess whether this potassium release is due to hemolysis. Fresh human blood was mixed in vitro with CM at a ratio of 10:2. Potassium release rates were determined, and serum haptoglobin and free hemoglobin were measured after 30 min of exposure to CM. To compare the potassium release curve between CM exposure and true hemolysis induced by distilled water, fresh human blood was also mixed with distilled water. The level of serum haptoglobin decreased due to hemodilution. Changes in haptoglobin were not correlated with potassium release rates. The serum free hemoglobin level did not increase significantly, and there was no correlation between changes in the free hemoglobin level and the rate of potassium release. Hemolysis caused by water occurred instantaneously, whereas potassium release caused by CM was a slow response, which was linearly correlated with exposure time. Potassium release from blood cannot be explained by hemolysis. Received: 4 June 1998; Revision received: 26 August 1998; Accepted: 16 December 1998     

Late adverse reactions to nonionic contrast media.

A prospective study of late adverse reactions to nonionic contrast media was conducted in 2,382 patients who underwent computed tomography (CT). Late reactions were defined as those that occurred more than 30 minutes but within 2 days after completion of CT. The overall rate of late reactions was 8.0% (165 of 2,052 patients), which was greater than the rate of immediate reactions (3.8% [90 of 2,382 patients]). Headache and rash were the most frequent manifestations. Three patients experienced severe vomiting, heavy drowsiness, or oliguria and required medical attention. Late reactions occurred more frequently in female patients, younger adults, and patients with histories of allergic reactions. This investigation shows that although late adverse reactions to nonionic contrast agents are not life threatening, these reactions are not uncommon. It is important that radiologists recognize these late reactions. Patients and referring physicians should be informed that late reactions can occur and may require medical attention.     

Delayed adverse reactions to iodinated contrast media and their risk factors

PURPOSE: The present prospective survey was performed to obtain information on delayed adverse reactions (DARs) to five types of low-osmolar iodinated contrast media, including their frequency, common manifestations, and the patient's history of allergy. METHODS: We investigated data from 15,890 consecutive patients who underwent contrast-enhanced computed tomography (CT) during a 15-month period. All patients were given a questionnaire asking about the occurrence of DARs, their symptoms and duration, and asked to consult a dermatologist if they had a skin reaction. RESULTS: Of 11,121 patients who returned the questionnaire (response rate, 70.0%), DARs were observed in 1,058 patients (9.5%). DARs tended to occur with higher incidence in patients with no previous history of examinations using contrast media, with past adverse reactions caused by contrast media, with a history of allergy, or with a serum creatinine level greater than 2.0 mg/dl. Among the 331 patients who reported skin reactions, 41 patients consulted a dermatologist. Skin reactions were observed significantly more frequently in patients for whom iotrolan was used, and 60% of these reactions were severe or moderate. CONCLUSIONS: Four risk factors for DARs were identified in the present investigation.     

MRI contrast media are used to improve visualization of abnormal structures or lesions in various parts of the body. Introduction

Until recently it was believed that extracellular gadolinium based contrast agents (Gd-CA) were safe for both the kidneys and all other organs within the dose range up to 0.3 mmol/kg body weight. However, in 2006, it was demonstrated that some Gd-CA may trig the development of nephrogenic systemic fibrosis, a generalized fibrotic disorder, in renal failure patients. This sub-section of European Journal of Radiology covers the current knowledge about NSF from many aspects. The prevention of NSF must be given high priority, but it should not lead to a denial of a well-justified, enhanced MRI examination with a stable agent.     

Delayed allergy-like reactions to X-ray contrast media: mechanistic considerations

Iodinated X-ray contrast media are among the most frequently used pharmaceuticals for intravascular administration. Although the newer low osmolality, nonionic contrast media, are generally well tolerated, it is well known that they, like the ionic contrast media, give rise to immediate or delayed adverse reactions in susceptible individuals. In the present review, the delayed allergy-like reactions, which by definition occur more than 1 h after contrast medium administration, are described, and the possible pathophysiological mechanisms discussed. Delayed allergy-like reactions to contrast media, which have been reported to occur in 0.5–2 % of recipients, are mainly mild to moderate skin reactions of the maculopapular exanthematous and urticarial/angioedematous types. Most of the reactions become apparent after a latency of 3 h to 2 days and disappear within 1 week. The incidence of more severe reactions is extremely low. Main risk factors for delayed allergy-like reactions appear to be a previous contrast medium reaction, a history of allergy, IL-2 treatment and being of Japanese descent. At present, the exact pathogenesis of these delayed reactions is still unclear. There is, however, increasing evidence that a significant proportion of the reactions are T-cell mediated. Received: 27 December 1999; Revised: 23 March 2000; Accepted: 26 May 2000     

The influence of buscopan on adverse reactions to intravascular contrast media

We have analysed the ability of prior intravenous Buscopan (hyoscine butylbromide) injection to influence the incidence and severity of adverse reactions to intravascularly administered, iodinated, ionic contrast medium in 258 consecutive digital subtraction angiographic (DSA) examinations. Adverse reactions were seen in 7.9% of the intravenous and 2.4% of the intra-arterial DSA examinations. The incidence of adverse reactions with and without prior Buscopan injection during intravenous DSA examinations was 8.2% and 7.1%, respectively and during intra-arterial DSA examinations was 5.6% and 1.5%, respectively. This difference is not statistically significant (chi 2-test). We conclude that prior intravenous injection of Buscopan has no influence on the incidence or severity of adverse reactions to intravascular contrast media.     

Late adverse reactions of non-ionic intravenous contrast media

A prospective study of late adverse reactions of non-ionic intravenous contrast media was performed. Information was collected from questionnaires returned by the patients, and also from further interviews. The incidence of adverse reactions was 8.3% in all patients, and was higher in female (11.1%) than male (5.8%). They were more frequent in the patients with age ranging from 20 to 49 than those older than 50. The most frequent symptom was headache, followed by itching, skin rashes, nausea, dizziness, and general fatigue. More than half of the reactions occurred within six hours after injection, but reactions a few days later were also reported.