British Journal of Radiology (2005) 78, 686-693
© 2005 British Institute of Radiology
doi: 10.1259/bjr/26301414
Acute serious and fatal reactions to contrast media: our current understanding
S K Morcos, FRCS, FRCR
Department of Diagnostic Imaging, Northern General Hospital, Sheffield Teaching Hospitals NHS Trust, Sheffield S5 7AU, UK
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Abstract
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Serious or fatal reactions to a contrast medium (CM) are unpredictable but fortunately rare. History of serious reaction to CM, bronchial asthma or multiple allergies increases the incidence of serious reactions by a factor of 5. Serious or fatal reaction to CM could be due to direct effect on basophils and mast cells or IgE mediated (type 1 hypersensitivity reaction). Activation of the kinin system leading to the formation of bradykinin could also be involved. Complement activation is unlikely to be a primary factor in initiating a serious reaction to CM. Avoiding CM administration in patients at high risk of serious reaction is advisable, but if the administration is deemed essential all precautions should be implemented and measures to treat serious reactions should be readily available. Oxygen supplementation, intravenous administration of physiological fluids and intramuscular injection of 0.5 ml adrenalin (1:1000) should be considered in the first line management of acute anaphylaxis. The ability to assess and treat serious CM reaction effectively is an essential skill that the radiologist should have and maintain.
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Introduction
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Acute severe life threatening or fatal reactions to a contrast medium (CM) are often unpredictable and not dose related. They are observed after intravenous or intra-arterial injection, but may also develop after alimentary or intracavitary administration as some of the CM particles may be absorbed into the circulation. These reactions are usually labelled anaphylactoid since they have all the features of anaphylaxis but are IgE negative in most cases. They usually develop within 5–30 min after exposure to CM and may present as generalized skin reactions, airway obstruction, angioedema or cardiovascular collapse [1–3].
In this review the incidence, risk factors, diagnosis and prevention of serious life threatening and fatal reactions to iodinated CM will be discussed. The current understanding of the pathophysiology will be explored. Treatment of serious reactions will also be discussed.
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Prevalence of life threatening and fatal reactions to contrast media
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In a large series of over 330 000 patients, Katayama et al found that the incidence of severe and very severe reactions following intravascular administration of CM was 0.22% and 0.04%, respectively, after high-osmolar contrast media (HOCM) and 0.04% and 0.004%, respectively, after low-osmolar contrast media (LOCM) [3]. The study concluded that the use of LOCM has resulted in reduction in the incidence of severe and very severe reactions by a factor of 10 in comparison with HOCM [3]. However, no difference was observed in the incidence of fatal reactions to both types of contrast media which were exceedingly rare (1:170 000) [3]. Fatal reactions to CM reported to the UK Committee on Safety of Medicines from 1963 to 1991 also failed to show any statistically significant difference in the incidence of deaths associated with ionic compared with non-ionic media [4]. Analysis of safety reports received by the Food and Drug Administration in the USA (FDA) from 1990 to 1994 on reactions to CM has also shown similar observations. The incidence (per million examinations) comparing high with low osmolar CM was 194 vs 44 for all reactions, 37 vs 11 for severe reactions and 3.9 vs 2.1 for fatal reactions. Interestingly, when high osmolar agents were compared with ioxaglate (a low osmolar ionic dimer), respectively, the incidence of total reactions was higher (194 vs 143), the incidence of severe reactions was almost the same (37 vs 34), and the incidence of fatal reactions was lower (3.9 vs 6.4) [4].
Thus, these studies demonstrate clearly that the introduction of low osmolar non ionic CM has caused an overall reduction in the number of contrast reactions, but there has been no definite reduction in fatal reactions, which are extremely rare. Nevertheless, iodinated CM are one of the top 10 drugs responsible for anaphylaxis/anaphylactoid reactions [5]. An epidemiological study of severe anaphylactic/anaphylactoid reactions among hospital patients found intermediate risk for anaphylaxis with CM. The incidence of anaphylaxis/anaphylactoid reactions due to contrast media in this report was 71 with HOCM and 35 with LOCM per 100 000 procedures [6].
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Risk factors
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There is a six-fold increase in reactions to both ionic and non-ionic CM in patients with a history of previous severe adverse reaction to a contrast agent. Asthma is also an important risk factor with a reported six- to ten-fold increase in the risk of a severe reaction in such patients [2]. Patients with a strong history of allergic reactions to different substances, including those with a history of troublesome hay fever, are also at risk of acute adverse reactions to CM [1–3]. In addition, patients treated with ß-adrenergic blockers [7, 8] and interleukin-2 (IL-2) [9] are at increased risk of acute adverse reactions to CM. Patients on ß-blocker including the ophthalmic preparations and receiving iodinated CM are three times more likely to have an anaphylactoid reaction than matched controls [7, 8].
Greater risk for severe anaphylactoid reaction has been observed with female gender. In one study, female patients comprised 21 of 22 cases with severe anaphylactoid reaction in a sample of 5264 consecutive patients (51% male and 49% female) who received CM during CT [10]. However, in a report investigating the subject of drug attributed anaphylaxis, found that the fatality rate was significantly higher in men than in women and it increased with age [5]. Race could also be a predisposing factor for CM reactions. Incidence of contrast reactions amongst patients of Indian origin and patients of Mediterranean origin in the UK was significantly higher in comparison with the endogenous white population [11]. There is no clear explanation for the racial differences in the incidence of contrast reactions. Malignant tumours may also increase the incidence of anaphylactoid reactions. This could be due to an increase in histamine release in tumour patients [12]. Important risk factors for serious reactions to CM are presented in Table 1
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Table 1. European Society of Urogenital Radiology (ESUR) guidelines on prevention of generalized contrast medium reactions in adults [13]
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Prediction of severe adverse reactions to contrast media
Pre-testing with an intravenous injection of a small amount of CM is not useful in predicting a severe reaction and should not be implemented [13, 14]. Awareness of risk factors is important in predicting serious reactions. High awareness among referring clinicians regarding risk factors of anaphylactoid reactions and contraindications to the intravascular administration of CM was recently documented [15].
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Pathophysiology of life threatening/fatal reactions to contrast media
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The pathophysiology of adverse effects to CM remains poorly understood. Hence, it is difficult to categorise these reactions. However, adverse reactions to drugs are generally classified into two types: type A reactions, dose dependent and predictable from the known pharmacology of the drug, and type B reactions, not dose dependent and unpredictable [16]. According to this classification, serious or fatal adverse reaction to CM can be labelled as type B. Recently, Aronson and Ferner proposed a new classification of drug reactions (DoTS) based on dose relatedness (Do), timing (T) and patient susceptibility (S) [17]. The details of this classification is beyond the scope of this review but it offers information about the properties of the drug (its known pharmacology and the dose dependence of its effects), the properties of the reaction (time course of its appearance and its severity) and properties of the individual (the genetic, pathological and other biological differences that confer susceptibility). Using the DoTS classification, adverse effects of CM can be considered Do-hyper susceptibility; T – first dose; S – not understood.
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Pathophysiology
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Serious reactions to CM follow the same clinical picture of type 1 hypersensitivity reaction (anaphylaxis) in which the reaction begins within minutes of antigen exposure and is mediated by a variety of chemotactic, vasoactive and spasmogenic compounds. Histamine seems to be the primary mediator of anaphylaxis/anaphylactoid reaction and is responsible for the intense immediate manifestations. Signs and symptoms of anaphylaxis can be reproduced by histamine infusion. Preformed histamine is present in basophils and mast cells and is released rapidly by degranulation of these cells in response to a variety of stimuli. There are several other biological mediators produced by mast cells and basophils which include leukotrienes, prostaglandins, enzymes and a variety of cytokines [18]. These substances act in autocrine, paracrine and endocrine fashion triggering a cascade of inflammatory mediators. They induce vasodilatation, increase in vascular permeability leading to oedema, contraction of smooth muscle cells precipitating bronchospasm and increase in mucus secretion of airways. The cytokines and chemotactic factors recruit leukocytes, eosinophils, basophils, monocytes and T cells which release additional waves of mediators and cytokines [18, 19].
The process by which CM activate basophils and mast cells to release histamine and other mediators remains uncertain and may include direct effect of CM particles on these cells or activation of immunological mechanisms involving IgE antibodies, thymus derived lymphocytes (T cells) or the complement system [18, 20, 21]. Direct effect of CM on basophils and mast cells leading to the release of histamine has been suggested as a probable mechanism for the adverse effects of CM and demonstrated in vitro using animal or human cells [20, 21]. In these studies the extent of the response was weaker with low osmolar CM in comparison with high osmolar media. There was also a trend for non ionic monomers to produce low levels of histamine release from basophils in comparison with high osmolar ionic monomers, low osmolar ionic dimer (ioxaglate) and iso-osmolar non-ionic dimer (iotrolan) [21]. Hyperosmolarity seems to be an important factor in stimulating the release of histamine from basophils and mast cells whereas hydrophilicity or protein binding characteristics of CM particles could not be correlated with the ability of these agents to induce histamine release [22]. It has also been suggested that histamine release induced by CM through a direct effect on basophils and mast cells is partially non-cytotoxic and an active secretory process may be involved [21, 23]. Interaction of CM with cell membrane receptors could be responsible for histamine release which depends on the degree of fit between the molecule and the membrane receptor [21, 23]. Increasing the size and complexity of the molecule may enhance the release of histamine [21, 23]. While contrast agents can act on basophils and mast cells as incomplete secretagogues, causing the release of preformed mediators (histamine and tryptase), their abilities to induce de novo synthesis of leukotrines and prostaglandins from these cells have been questioned [24].
The contribution of type 1 hypersensitivity to serious or fatal reactions to CM has been contentious because of lack of consistency in demonstrating antibodies to CM in animal studies and in sera of patients who have suffered adverse reactions to CM [2]. While some reports demonstrated that CM can induce antibodies [25–31] others failed to confirm these findings [32, 33]. The ability of CM to compete with a series of antigens against their respective antibodies has also been proposed [34, 35]. It was also suggested that CM may act as haptens. However, this is unlikely since contrast agents are generally non-reactive chemically and do not demonstrate strong covalent binding to proteins and would therefore not be likely candidates to form haptens [33].
Recently, it has been proposed that drugs which are unable to bind to peptides or proteins may directly activate T cells which bear receptors that can interact with the drug. This mechanism is referred to as pharmacological interaction of drugs with immune receptors (p-I concept) [36]. However, the involvement of T cells of the immune system in mediating acute life threatening CM reactions has not been widely investigated. A recent study investigated the effect of CM on cytokines released from T helper cells (TH) concluded that CM may have an effect on cytokines production of these cells [37]. Further studies are needed to evaluate the role of T cells in mediating acute reactions to CM.
It has also been suggested that CM may activate the complement system leading to the formation of anaphylatoxins (C3a, C4a and C5a) which induce release of histamine and other biological mediators from basophils and mast cells [38–43]. However, the results of studies investigating complement system activation by CM are somewhat confusing [29, 38–43]. In a landmark study of patients with acute life threatening reactions to CM no significant difference was found in the level of anaphylatoxins (C3a, C4a) between patients with reactions and control subjects [29].
Activation of factor XII (Hageman factor) of the clotting system by CM leading to activation of the kinin system and the production of bradykinin could also be involved in the pathogenesis of serious CM reactions [44–46]. Bradykinin can induce vasodilatation, bronchospasm and increase vascular permeability. It is also a potent activator of factor XII allowing autocatalytic amplification of the initial stimulus [18]. Bradykinin may also activate the arachidonic acid in some cellular membranes fuelling both the cyclooxygenase and lipooxygenase pathways leading to the synthesis of prostaglandins and leukotrienes [18]. Patients who are asthmatic or allergic have an increased concentration of low-level of factor XII products which may explain the greatly increased susceptibility of these patients to CM [45, 46].
Anxiety and an in vivo interaction with enzymes have also been suggested to be involved in CM reactions [47–49]. However, there is no conclusive evidence to support their involvement in the adverse effects of CM.
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Diagnosis of serious or fatal reaction to contrast media
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Upon mast cell activation, both preformed (histamine and tryptase) and newly synthesized mediators are secreted [50]. While histamine is released from both basophils and mast cells, tryptase is virtually absent from basophils but contained in the granules of mast cells together with histamine [29]. New assays are becoming available for measuring tryptase and histamine in plasma with great reliability [29]. Tryptase half-life is about 90 min and the best time for measuring tryptase is 1–2 h after the reaction (not greater than 6 h) [51]. A moderately elevated post-mortem tryptase concentration in the absence of anaphylaxis has been described. Therefore only very high concentrations of serum tryptase should be regarded as specific for fatal anaphylaxis/anaphylactoid reaction [52]. Histamine has a very short half life (about 2 min) and the best time for measuring its plasma level is between 10 min to 1 h after the reaction [29, 51]. The concentration of methylhistamine, the main metabolite of histamine, can also be accurately measured in urine [29].
Specific IgE antibodies may be identified in serum of some patients using a solid phase radioimmunoassay (a RAST assay) [29, 30, 53]. However, reliable drug RAST tests are not widely available [53]. Positive intradermal tests has been demonstrated in some cases of severe reaction to CM [29, 54].
In clinical practice it is advisable to measure serum tryptase routinely in patients who develop very severe or fatal reaction after CM administration to elucidate whether the event is caused by the CM or not. Massive myocardial infarction or severe vasovagal attack may develop during a contrast enhanced imaging examination and can be confused with serious or fatal CM adverse effect. Skin tests and IgE antibodies measurement (if facilities are available) may be considered in patients who survived a serious CM reaction with proved liberation of mediators [55].
Post-mortem findings of fatal reaction to contrast media
In the presence of a typical clinical history, absence of post-mortem findings does not exclude the diagnosis of anaphylaxis. High level of seum tryptase would be helpful to support that CM reaction is the cause of death [52]. Macroscopic findings may include pulmonary oedema, signs of asthma (mucous plugging and/or hyperinflated lungs), petechial haemorrhages and pharyngeal/laryngeal oedema [56, 57].
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Prevention of acute reactions to contrast media
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All precautions should be considered in high risk patients (those with history of previous moderate or severe contrast reactions, allergic conditions that require treatment or bronchial asthma) when CM administration is deemed essential [2, 13]. Imaging procedures which do not require the administration of iodinated CM should be considered. The use of carbon dioxide (CO2) [58], gadolinium based CM [59] or both [60] have been suggested as alternatives to iodinated CM. Carbon dioxide is well tolerated in angiography, but some unpleasant symptoms such as nausea, abdominal and leg pain may be observed with its administration [60]. Although the safe use of gadolinium based CM for radiographic examination has been documented in several reports, gadolinium CM should not be given intravascularly at a dose above 0.3 mmol kg–1 body weight as it may induce nephrotoxicity, particularly in patients with pre-existing renal impairment [61]. In addition, gadolinium based CM are not approved by the drug licensing authorities for intra-arterial administration or radiographic examinations [61]. Doses of gadolinium based CM above 0.3 mmol kg–1 body weight should be avoided until more data from clinical trials are available [62].
If the administration of iodinated CM is deemed essential, non-ionic contrast media should be used [3, 13]. The potential risks of the procedure should be explained to the patient, and the resuscitation team should be present when the CM is given [13]. Adequate provision to treat any reaction should be available. The prophylactic use of corticosteroids in these patients has been recommended by several authors [63–66]. The mechanism by which corticosteroid prophylaxis works is not completely understood. Corticosteroids, to become effective, must complex with the cytoplasmic receptor, the complex then migrate into the cell nucleus, the complex "message" must be transcribed to activate DNA dependent RNA synthesis, and subsequent accelerated formation of specific enzymes inhibitors must occur, all of which take time [66]. Pre-treatment with corticosteroid is accompanied by a significant elevation in functional C1-esterase inhibitor levels, which occurs over 12 h after steroid administration. This enzyme inhibits the activated form of factor XII, and has an important role in the inhibition of kallikrein that results in the production of bradykinin. The production of prostaglandins and leukotrienes, which are dependent on the mobilization of arachidonic acid from cell membranes, is also inhibited by corticosteroids. These and possible other effects may account in part for the protective effect of corticosteroid pre-treatment [66]. However, the use of steroids as pre-medication has not received a wide support [67, 68]. Some authors have concluded that non-ionic agents should be used in patients with definable risk factors and the value of corticosteroid prophylaxis is not proven and may reasonably be abandoned [67, 68].
Antihistamines (H1 and H2) and ephedrine have also been advocated for high-risk patients often in combination with corticosteroids [65]. However, the use of antihistamine H1 and H2 receptor antagonists as well as ephedrine to decrease the prevalence of adverse reactions to CM has not gained wide acceptance [13].
It is important to emphasise that severe life threatening reactions or even fatality may still occur in patients who received pre-medication and low osmolar CM [2, 13]. Prompt recognition and treatment of adverse side effects to CM can be invaluable in blunting the response and may prevent a reaction from becoming severe or even life threatening [13]. The patient should never be left alone for at least 20 min after CM injection and the venous access should be left in place. Knowledge, training and preparation are crucial in guaranteeing appropriate and effective therapy in the event of an adverse contrast related event [13]. The Contrast Media Safety Committee of the European Society or Urogenital Radiology (ESUR) has produced simple guidelines on prevention of generalized reactions to CM (Table 1
) [13].
Emergency administration of contrast media in high-risk patients
Emergency administration of CM in patients at high risk of severe reactions to CM, particularly those with a history of previous serious reaction to CM requiring essential procedures, precludes prolonged prophylaxis pre-treatment with corticosteroids. In these patients pre-treatment with hydrocortisone, 200 mg intravenously, immediately, and every 4 h until the procedure is completed, and diphenhydramine, 50 mg intravenously before the procedure and the use of low osmolar non-ionic CM has been recommended [69].
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Treatment of acute severe reactions to contrast media
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The vast majority of patients with acute severe reactions to CM recover if they are treated quickly and appropriately. The first-line drugs and equipment should be readily available in rooms in which contrast material is injected. A list of recommended drugs and equipment is given in Table 2 [70].
Important first-line management includes establishment of an adequate airway, oxygen supplementation, administration of intravascular physiological fluids and measuring the blood pressure and heart rate [70]. Hypoxia can be a major complicating factor in all these situations and can be induced by drugs such as adrenaline used for treating reactions. Intravascular fluid administration is also very important, and it alone has been reported to be the most effective treatment for hypotension. Starting intravenous fluid early before drug treatment is the highest priority in treating hypotension [70].
Adrenaline is an effective drug for treating certain serious contrast reactions. It increases blood pressure, reverses peripheral vasodilatation, decreases angioedema and urticaria, reverses bronchoconstriction, and produces positive inotropic and chronotropic cardiac effects [70–73]. Adrenaline should be avoided when possible for treating the pregnant patient with a severe contrast reaction and hypotension [74]. Only one concentration (1:1000) of adrenaline should be available in the radiology department. Intramuscular injection of 0.5 ml of 1:1000 adrenaline preparation is recommended in preference to intravenous administration in management of acute anaphylaxis/anaphylactoid reaction. Intravenous injection of adrenalin requires careful electrocardiogram (ECG) monitoring and should be administered very slowly, ideally by people experienced in its use. According to the Project Team of the Resuscitation Council in the UK, adrenaline 1:1000 should never be used intravenously because of the risk of arrhythmia, and subcutaneous administration is not helpful in acute life threatening situations [70, 75, 76].
Antihistamine H1 receptor blockers are used primarily to reduce symptoms from skin reactions [70]. Compared with adrenaline, the first-response medication of acute anaphylaxis, antihistamines have a slow onset of action, and they cannot block events that occur subsequent to histamine binding to its receptors [77]. The administration of H2-antagonists is not essential in the management of anaphylaxis/anaphylactoid reactions [73, 77].
Intravenous injection of high-dose corticosteroids may have an immediate stabilizing effect on the cell membrane and could be used in the second-line treatment. Standard doses can be effective in reducing delayed recurrent symptoms, which can be observed for as long as 48 h after an initial reaction [70]. Inhaled ß-2-adrenergic agonists such as albuterol, metaproterenol and terbutaline deliver large doses of bronchodilating ß-2-agonist drugs directly to the airways with minimal systemic absorption and therefore minimal cardiovascular effects.
Atropine blocks vagal stimulation of the cardiac conduction system. Large doses of aptropine (0.6–1.0 mg) are indicated, since low doses (e.g. less than 0.5 mg) of atropine can be detrimental for treating bradycardia associated with contrast media-induced vagal reactions [70, 78].
Guidelines for treatment of serious reactions to CM are presented in Table 3 [70].
In summary, serious adverse reactions to CM are fortunately rare and fatal reactions are extremely rare with incidence of one in 170 000 contrast examinations. History of previous serious reaction to CM, bronchial asthma or multiple allergies are important risk factors for developing major reactions to contrast administration. Dramatic increase in serum concentration of histamine and tryptase is found in association with severe reactions but identification of IgE antibodies has not been consistent. Avoiding CM administration in patients at high risk of serious reaction is advisable but if the administration is deemed essential all precautions should be implemented and measures to treat serious reactions should be readily available.
Received for publication February 16, 2005.
Revision received March 11, 2005.
Accepted for publication March 14, 2005.
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References
|
|---|
- Thomsen HS, Morcos SK. Radiographic contrast media. BJU Int 2000;86(Suppl. 1):1–10.
- Morcos SK, Thomsen HS. Adverse reactions to iodinated contrast media. Eur Radiol 2001;11:1267–75.[CrossRef][Medline]
- Katayama H, Yamaguchi K, Kozuka T, Takashima T, Seez P, Matsuura K. Adverse reactions to ionic and nonionic contrast media. Radiology 1990;175:621–8.[Abstract/Free Full Text]
- Lasser EC, Lyon SG, Berry CC. Reports on contrast media reactions: analysis of data from reports to the U.S. Food and Drug Administration. Radiology 1997;203:605–10 (erratum 876).[Abstract/Free Full Text]
- Wang DY, Forslund C, Persson U, Wiholm BE. Drug-attributed anaphylaxis. Pharmacoepidemiol Drug Saf 1998;7:269–74.[CrossRef][Medline]
- The International Collaborative Study of Severe Anaphylaxis. Risk of anaphylaxis in a hospital population in relation to the use of various drugs: an international study. Pharmacoepidemiol Drug Saf 2003;12:195–202.[CrossRef][Medline]
- Lang DM, Alpern MB, Visintainer PF, Smith ST. Increased risk for anaphylactoid reaction from contrast media in patients on ß-adrenergic blockers with asthma. Ann Intern Med 1991;115:270–6.
- Lang DM, Alpern MB, Visintainer PF, Smith ST. Elevated risk of anaphylactoid reaction from radiographic contrast media is associated with both beta-blocker exposure and cardiovascular disorders. Arch Intern Med 1993;153:2033–40.[Abstract/Free Full Text]
- Choyke PL, Miller DL, Lotze MT, et al. Delayed reactions to contrast media after Interleukin-2 immunotherapy. Radiology 1992;183:111–4.[Abstract/Free Full Text]
- Lang DM, Alpern MB, Visintainer PF, Smith ST. Gender risk for anaphylactoid reaction to radiographic contrast media. J Allergy Clin Immunol 1995;95:813–7.[CrossRef][Medline]
- Ansell G, Tweedie MC, West CR, Evans P, Couch L. The current status of reactions to intravenous contrast media. Invest Radiol 1980;15:S32–S39.[Medline]
- Celik I, Hoppe M, Lorenz W, Sitter H, Ishaque N, Jungraithmayr W, et al. Randomised study comparing a non-ionic with an ionic contrast medium in patients with malignancies: first answer with a new diagnostic approach. Inflamm Res 1999;48(Suppl. 1):S47–S48.
- Morcos SK, Thomsen HS, Webb JAW, Contrast Media Safety Committee of European Society of Urogenital Radiology. Prevention of generalized reactions to contrast media: a consensus report and guidelines. Eur Radiol 2001;11:1720–8.[CrossRef][Medline]
- Yamaguchi K, Katayama H, Takashima T, Kozuka T, Seez P, Matsuura K. Prediction of severe adverse reactions to ionic and nonionic contrast media in Japan: evaluation of pretesting. A report from the Japanese Committee on the Safety of Contrast Media. Radiology 1991;178:363–7.[Abstract/Free Full Text]
- Konen E, Konen O, Katz M, Levy Y, Rozenman J, Hertz M. Are referring clinicians aware of patients at risk from intravenous injection of iodinated contrast media? Clin Radiol 2002;57:132–5.[CrossRef][Medline]
- Rawlins MD. Clinical pharmacology: adverse reactions to drugs. BMJ 1981;282:974–6.
- Aronson JK, Ferner RE. Joining the DoTS: new approach to classifying adverse drug reactions. BMJ 2003;327:1222–5.[Free Full Text]
- Cotran RS, Kumar V, Collins T (editors). Robbins pathologic basis of disease (6th edn). Philadelphia, PA: W.B. Saunders Company, An Imprint of Elsevier Science, 1999:67–199.
- Luskin AT, Luskin SS. Anaphylaxis and anaphylactoid reactions: diagnosis and management. Am J Ther 1996;3:515–20.[Medline]
- Assem KSE, Bray K, Dawson P. The release of histamine from human basophils by radiological contrast agents. Br J Radiol 1983;56:647–52.[Abstract/Free Full Text]
- Peachell P, Morcos SK. Effect of radiographic contrast media on histamine release from human mast cells and basophils. Br J Radiol 1998;71:24–30.[Abstract]
- Krause W, Niehues D. Biochemical characterization of X-ray contrast media. Invest Radiol 1996;31:30–42.[CrossRef][Medline]
- Paton WDM. Histamine release by compounds of simple chemical structure. Pharmacol Rev 1957;9:269–328.[Free Full Text]
- Genovese A, Stellato C, Marsella CV, Adt M, Marone G. Role of mast cells, basophils and their mediators in adverse reactions to general anesthetics and radiocontrast media. Int Arch Allergy Immunol 1996;110:13–22.[Medline]
- Brasch CR. The case strengthens for allergy to contrast media. Radiology 1998;209:35–6.[Free Full Text]
- Kleinknecht D, Deloux J, Homberg JC. Acute renal failure after intravenous urography: Detection of antibodies against contrast media. Clin Nephrol 1974;2:116–9.[Medline]
- Wakkers-Garritsen BG, Houwerziji J, Nater JP, Wakerrs PJM. IgE-mediated adverse reactivity to a radiographic contrast medium-case report. Ann Allergy 1976;36:122–6.[Medline]
- Laroche D, Namour F, Lefrancois C, Aimone-Gastin I, Romano A, Sainte-Laudy J, et al. Anaphylactoid and anaphylactic reactions to iodinated contrast material. Allergy 1999;54(Suppl. 58):13–6.
- Laroche D, Aimone-Gastin I, Dubois F, Huet H, Gerard P, Vergnaud MC, et al. Mechanisms of severe, immediate reactions to iodinated contrast material. Radiology 1998;209:183–90.[Abstract/Free Full Text]
- Dewachter P, Mouton-Faivre C. Severe reactions to iodinated contrast agents: is anaphylaxis responsible? J Radiol 2001;82:973–7.[Medline]
- Mita H, Tadokoro K, Akiyama K. Detection of IgE antibody to a radiocontrast medium. Allergy 1998;53:1133–40.[Medline]
- Rodriguez RM, Gueant JL, Aimone-Gastin I, Gerard P, Amoghly F, Bellou A, et al. The increased histamine release in ischaemic heart disease patients undergoing coronaroangiography is not mediated by specific IgE. Allergy 2002;57(Suppl. 72):61–6.
- Carr HD, Walker CA. Contrast media reactions: experimental evidence against the allergy theory. Br J Radiol 1984;57:469–73.[Abstract/Free Full Text]
- Lasser EC. The radiocontrast molecule in anaphylaxis: a surprising antigen. Novartis Found Symp 2004;257:211–24; discussion 224–5, 276–85.[Medline]
- Lasser EC. The multipotential pseudoantigenicity of X-ray contrast media. Pseudoantigen excess may downregulate the release of hypotensive mediators. Int Arch Allergy Immunol 2000;123:282–90. Erratum in: Int Arch Allergy Immunol 2002;129:350.[CrossRef]
- Pichler WJ. Immune mechanism of drug hypersensitivity. Immunol Allergy Clin N Am 2004;24:373–97.[CrossRef][Medline]
- Bohm I, Speck U, Schild H. Cytokine profiles after nonionic dimeric contrast medium injection. Invest Radiol 2003;38:776–83.[Medline]
- Vik H, Froysa A, Sonstevold A, Toft K, Stahl SP, Ege T. Complement activation and histamine release following administration of roentgen contrast media. Acta Radiologica 1995;36(Suppl. 399):83–9.
- Eaton S, Tsay MH, Yost F, Tweedle FM. Assays for plasma complement activation by X-ray contrast media. Invest Radiol 1990;25:789–92.[CrossRef][Medline]
- Gonsette RE, Delmotte P. In vivo activation of serum complement by contrast media: a clinical study. Invest Radiol 1980;15(6 Suppl.):S26–8.
- Hoffmeister MH, Heller W. Radiographic contrast media and the coagulation and complement systems. Invest Radiol 1996;31, No.9:591–5.[CrossRef]
- Hoffmeister HM, Fuhrer G, Platten HP, Heller W. Complement activation after the intravascular administration of contrast media: a comparison between ionic and nonionic x-ray contrast media. ROFO Fortschr Geb Rontgenstr Nuklearmed 1987;147:673–5.
- Cogen FC, Norman ME, Dunsky E, Hirshfeld J, Zweiman B. Histamine release and complement changes following injection of contrast media in humans. J Allergy Clin Immunol 1979;64:299–303.[CrossRef][Medline]
- Lasser EC. Etiology of anaphylactoid responses. The promise of nonionics. Invest Radiol 1985;20(1 Suppl.):S79–S83.[CrossRef]
- Lasser EC. A coherent biochemical basis for increased reactivity to contrast material in allergic patients: a novel concept. AJR Am J Roentgenol 1987;149:1281–5.[Abstract/Free Full Text]
- Lasser EC. A general and personal perspective on contrast material research. Invest Radiol 1988;23 Suppl. 1:S71–S74.
- Howell MJ, Dawson P. Contrast agents and enzyme inhibition. II. Mechanisms. Br J Radiol 1985;58:845–8.[Abstract/Free Full Text]
- Mironidou M, Katsimba D, Kokkas B, Kaitartzis C, Karamanos G. Effects in vivo of iohexol and diatrizoate on human plasma acetyl-and butyryl-cholinesterase activity. Radiol Med 2001;101:183–6.[Medline]
- Moreau JF, Lesavre P, de Luca H, Hennessen U, Fischer AM, Giwerc M. General toxicity of water-soluble iodinated contrast media. Pathogenic concepts. Invest Radiol 1988;23 (Suppl. 1):S75–S78.
- Hogan AD, Schwartz LB. Markers of mast cell degranulation. Methods 1997;13:43–52.[CrossRef][Medline]
- Laroche D, Vergnaud MC, Sillard B, Soufarapis H, Bricard H. Biochemical markers of anaphylactoid reactions to drugs. Comparison of plasma histamine and tryptase. Anesthesiology 1991;75:945–9.[CrossRef][Medline]
- Brockow K, Vieluf D, Puschel K, Grosch J, Ring J. Increased postmortem serum mast cell tryptase in a fatal anaphylactoid reaction to nonionic radiocontrast medium. J Allergy Clin Immunol 1999;104:237–8.[CrossRef][Medline]
- Volcheck GW. Clinical evaluation and management of drug hypersensitivity. Immunol Allergy Clin N Am 2004;24:357–71.[CrossRef][Medline]
- Moneret-Vautrin DA, Kanny G, Morisset M, Beaudouin E, Renaudin JM. Anaphylactoid reactions and late skin reactions to iodinated contrast media: present state of the question--idea development. Rev Med Interne 2001;22:969–77.[Medline]
- Laroche D. Mechanism of severe, immediate reactions to iodinated contrast material. Allerg Immunol 1998;30:138–40.
- Shehadi WH. Death following intravascular administration of contrast media. Acta Radiol Diagn 1985;26:457–61.
- Pumphrey RS, Roberts IS. Postmortem findings after fatal anaphylactic reactions. J Clin Pathol 2000;53:273–6.[Abstract/Free Full Text]
- Dewald CL, Jensen CC, Park YH, Hanks SE, Harrell DS. Vena cavography with CO2 versus with iodinated contrast material for inferior vena cava filter placement: a prospective evaluation. Radiology 2000;216:752–7.[Abstract/Free Full Text]
- Ailawadi G, Stanley JC, Williams DM, Dimick JB, Henke PK, Upchurch GR Jr. Gadolinium as a nonnephrotoxic contrast agent for catheter-based arteriographic evaluation of renal arteries in patients with azotemia. J Vasc Surg 2003;37:346–52.[CrossRef][Medline]
- Spinosa DJ, Matsumoto AH, Angle JF, Hagspiel KD, McGraw JK, Ayers C. Renal insufficiency: usefulness of gadodiamide-enhanced renal angiography to supplement CO2-enhanced renal angiography for diagnosis and percutaneous treatment. Radiology 1999;210:663–72.[Abstract/Free Full Text]
- Thomsen HS, Almén T, Morcos SK, members of Contrast Media Safety Committee of European Society of Urogenital Radiology (ESUR). Gadolinium-containing contrast media for radiographic examinations: a position paper. Eur Radiol 2002;12:2600–5.[Medline]
- Strunk HM, Schild H. Actual clinical use of gadolinium-chelates for non-MRI applications. Eur Radiol 2004;14:1055–62.[CrossRef][Medline]
- Lasser EC, Berry CC, Lee B, Talner LB, Lewis C, Santani LC, et al. Pretreatment with corticosteroids to alleviate reactions to intravenous contrast material. New Engl J Med 1987;317:845–9.[Abstract]
- Lasser EC, Berry CC, Mishkin MM, Williamson B, Zheutlin N, Silverman JM. Pretreatment with corticosteroids to prevent adverse reactions to non-ionic contrast media. AJR Am J Roentgenol 1994;162:523–6.[Abstract/Free Full Text]
- Greenberger PA, Patterson R. The prevention of immediate generalized reactions to radiocontrast media in high-risk patients. J Allergy Clin Immunol 1991;87:867–72.[CrossRef][Medline]
- Lasser EC, Lang JH, Lyon SG, Hamblin E, Howard M. Glucocorticoid-induced elevations of C1-esterase inhibitor: a mechanism for protection against lethal dose range contrast challenge in rabbits. Invest Radiol 1981;16:20–3.[CrossRef][Medline]
- Wolf GL, Mishkin MM, Roux SG, Halpern EF, Gottlieb J, Zimmerman J, et al. Comparison of the rates of adverse drug reactions. Ionic agents, ionic agents combined with steroids and non-ionic agents. Invest Radiol 1991;26:404–10.[CrossRef][Medline]
- Dawson P, Sidhu PS. Is there a role for corticosteroid prophylaxis in patients at increased risk of adverse reactions to intravascular contrast agents? Clin Radiol 1993;48:225–6.[CrossRef][Medline]
- Greenberger PA, Halwig JM, Patterson R, Wallemark CB. Emergency administration of radiocontrast media in high-risk patients. J Allergy Clin Immunol 1986;77:630–4.[CrossRef][Medline]
- Thomsen HS, Morcos SK, members of Contrast Media Safety Committee of European Society of Urogenital Radiology (ESUR). Management of acute adverse reactions to contrast media. Eur Radiol 2004;14:476–81.[CrossRef][Medline]
- Smith NT, Corbascio A. The use and misuse of pressor agents. Anesthesiology 1970;33:58–101.[CrossRef][Medline]
- Bush WH, Swanson DP. Acute reactions to intravascular contrast media: types, risk factors, recognition, and specific treatment. AJR Am J Roentgenol 1991;157:1153–61.[Abstract/Free Full Text]
- Bush WH. Risk factors, prophylaxis and therapy of X-ray contrast media reactions. Adv X-ray Contrast 1996;3:44–53.
- Entman SS, Moise KJ. Anaphylaxis in pregnancy. South Med J 1984;77:402.[Medline]
- Project Team of the Resuscitation Council (UK). Emergency medical treatment of anaphylactic reactions. J Accid Emerg Med 1999;16:243–7.[Free Full Text]
- Hughes G, Fitzharris P. Managing acute anaphylaxis, new guidelines emphasize importance of intramuscular adrenaline. BMJ 1999;319:1–2.[Free Full Text]
- Winbery SL, Lieberman PL. Histamine and antihistamines in anaphylaxis. Clin Allergy Immunol 2002;17:287–317.[Medline]
- Bush WH, McClennan BL, Swanson DP. Contrast media reactions: prediction, prevention, and treatment. Postgrad Radiol 1993;13:137–47.
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Abstract
Introduction
