3 Prevention of Acute Reactions
Judith A. W. Webb
J. A. W. Webb
Department of Diagnostic Radiology, St Bartholomew’s Hos- pital, West Smithfi eld, London EC1A 7BE, UK
CONTENTS
3.1 Introduction 11
3.2 Iodinated Contrast Media 11
3.2.1 Types and Frequency of Acute Reactions 11 3.2.2 Risk Factors for Acute Idiosyncratic Reactions 11 3.2.2.1 Type of Contrast Agent 11
3.2.2.2 Previous Contrast Medium Reaction 12 3.2.2.3 Asthma 12
3.2.2.4 Allergy 12 3.2.2.5 Drugs 12
3.2.3 Prevention of Acute Idiosyncratic Reactions 13 3.2.3.1 Choice of Contrast Medium 13
3.2.3.2 Premedication 13
3.2.3.3 Pretesting and Injection Rate 14 3.2.4 Summary: Iodinated Contrast Media 14 3.3 Gadolinium Contrast Media 15 3.3.1 Types of Reaction and Frequency 15 3.3.2 Risk Factors for Reactions 15 3.3.2.1 Type of Contrast Medium 15 3.3.2.2 Patient Risk Factors 15 3.3.3 Prevention of Reactions 15
3.3.4 Summary: Gadolinium Contrast Media 15 References 16
3.1
Introduction
Most of this chapter is concerned with acute idi- osyncratic reactions to iodinated contrast media, particularly the factors predisposing to these reac- tions and the measures that may be taken to prevent them. At the end of the chapter acute reactions to gadolinium contrast media are also discussed.
3.2
Iodinated Contrast Media
3.2.1
Types and Frequency of Acute Reactions
Acute idiosyncratic systemic reactions (also described as allergy-like or anaphylactoid) are defined as unpre- dictable reactions which occur within 1 h of contrast medium administration, and which are unrelated to the amount of contrast medium above a certain level.
This definition aims to distinguish them from chemo- toxic reactions, which are dose-related and dependent on the physico-chemical properties of the contrast medium. However, in clinical practice, some reactions such as cardiovascular collapse may be difficult to characterise definitely into one or other group.
The mechanisms by which idiosyncratic reactions occur are not fully understood. However, they do appear to involve the release of active mediators, such as histamine, bradykinin, leucotrienes, prostagland- ins and complement factors. Available evidence sug- gests that there are a variety of complex interactions between the complement, contact, coagulation and immune systems (Lasser 1985, 1987; Almen 1994).
Acute idiosyncratic reactions are usually charac- terised as mild, moderate or severe. Mild or minor reactions include nausea, mild vomiting, urticaria and itching. Moderate reactions include more severe vom- iting, marked urticaria, bronchospasm, facial or laryn- geal oedema, and vasovagal reactions. Severe reactions include hypotensive shock, respiratory arrest, cardiac arrest and convulsions (Bush and Swanson 1991).
3.2.2
Risk Factors for Acute Idiosyncratic Reactions
3.2.2.1
Type of Contrast Agent
With the older high osmolality ionic agents the rate of
reactions of all types is in the range 5%–12% (Ansell
et al. 1980; Witten et al. 1973; Shehadi 1975;
Katayama et al. 1990; Cochran et al. 2001). The majority of reactions in these series were mild with moderate reactions occurring in 1%–2% and severe reactions in approximately 0.10%–0.15% (Ansell et al. 1980; Witten et al. 1973). Mortality with the ionic agents is in the range 1 in 14,000 to 1 in 169,000 (Shehadi 1975; Katayama et al. 1990) with 1 in 75,000 an often quoted figure (Hartman et al. 1982).
With the newer low osmolality nonionic agents, the reaction rates are lower, by a factor of approx- imately four to five times (Katayama et al. 1990;
Palmer 1988; Wolf et al. 1991; Bettman et al. 1997).
Thus in Katayama’s series of over 300,000 patients the reaction rates for ionic and nonionic agents were overall 12.66% and 3.13%, with severe reactions in 0.22% and 0.04%, respectively (Katayama et al.
1990). Based on a meta-analysis of all data published between 1980 and 1991, Caro et al. (1991) concluded that 80% of contrast media reactions could be pre- vented by using low osmolality agents. The very low mortality means that accurate mortality fig- ures are not yet available for the nonionic agents. In Katayama et al.’s (1990) series there was no sig- nificant difference in mortality between the ionic and nonionic agents, but other data suggests a lower mortality with nonionic agents (Lasser et al. 1997).
3.2.2.2
Previous Contrast Medium Reaction
A previous reaction to an iodinated contrast medium is the most important patient factor predisposing to an acute idiosyncratic reaction (Bettman et al.
1997). With ionic agents, the risk of a reaction in a patient who reacted previously has been stated to be 16%–35% (Witten et al. 1973; Shehadi 1975) and to be eleven times greater than the risk in a non-reactor (Ansell et al. 1980). When a patient who previously reacted to an ionic agent is given a nonionic agent, the risk of a repeat reaction is reduced to approxi- mately 5% (Siegle et al. 1991).
3.2.2.3 Asthma
Asthma is another important risk factor. Shehadi (1975) found that 11% of asthmatics had a reaction to ionic contrast media and Ansell et al. (1980) stated that the risk of reaction to ionic agents was increased five times in an asthmatic. In patients
with asthma, Katayama et al. (1990) described an 8.5 times increased risk with ionic agents and a 5.8 times increased risk with nonionics. Other condi- tions, such as hayfever, eczema, etc. are associated with an increased risk of reaction, but by a lesser amount than asthma (Ansell et al. 1980; Witten et al. 1973; Shehadi 1975).
3.2.2.4 Allergy
A history of allergy to foods, drugs or other sub- stances is associated with an increased risk of con- trast medium reaction, usually by a lesser amount than a history of asthma. Thus, Shehadi (1975) and Katayama et al. (1990) found a two-fold increase in risk of a reaction and Ansell et al. (1980) a four times increase in risk of a reaction.
Allergy to foodstuffs which contain iodine, e.g., seafood, often causes particular anxiety. However, the available data suggests that allergy to seafood is no more significant than allergy to other foodstuffs (Witten et al. 1973; Shehadi 1975; Leder 1997).
Allergy to topical iodine skin preparations is a type of contact dermatitis and does not seem to predispose to acute idiosyncratic contrast medium reactions (Thomsen and Bush 1998).
3.2.2.5 Drugs
Whether or not E blockers affect the incidence of idio- syncratic contrast medium reactions is controversial.
Greenberger et al. (1987) reported that neither E blockers nor calcium antagonists given separately or together increased the risk of reaction. Subsequently, however, Lang et al. (1991) found that E blockers did increase the risk of reaction. It is however agreed that the use of E blockers can impair the response to treat- ment if a reaction does occur (Thomsen and Bush 1998; Greenberger et al. 1987; Lang et al. 1991).
Patients who are receiving or have received inter- leukin-2 are at increased risk of adverse events fol- lowing iodinated contrast media. Some of these adverse events appear to recall the side-effects of interleukin-2 (e.g., fever, nausea, vomiting, diar- rhoea, pruritus and rash) (Zukiwski et al. 1990;
Fishman et al. 1991; Oldham et al. 1991; Choyke
et al. 1992). Reactions are often late, occurring more
than one hour after contrast medium, but can occur
within the first hour (Choyke et al. 1992).
3.2.3
Prevention of Acute Idiosyncratic Reactions In any patient at increased risk of contrast medium reaction, especially if there has been a previous reac- tion to an iodinated contrast agent, the possibil- ity of obtaining the necessary diagnostic informa- tion from another test not using iodinated contrast medium (e.g., ultrasonography, magnetic resonance imaging) must be considered. If iodinated contrast medium is still deemed essential the risk of an acute reaction can be reduced by an appropriate choice of contrast medium and premedication.
Since the majority of severe reactions occur within the first 20 min after contrast medium injec- tion (Hartman et al. 1982; Shehadi 1985), patients should remain in the Radiology Department for at least this period. In high-risk subjects, monitoring for the first hour is recommended.
3.2.3.1
Choice of Contrast Medium
The single most important method of reducing the risk of idiosyncratic contrast medium reactions is to use nonionic low osmolality agents which are associ- ated with a four to five times lower risk of reactions (Katayama et al. 1990; Palmer 1988; Wolf et al.
1991; Bettman et al. 1997). In many countries noni- onic agents are used for all intravascular adminis- tration of contrast material. Where this is not pos- sible, selective use of nonionic agents in patients at increased risk of reaction is recommended (King 1999). The principal categories of increased risk are previous contrast medium reaction, asthma or a his- tory of allergy (Ansell et al. 1980; Witten et al.
1973; Katayama et al. 1990; Morcos et al. 2001).
When there has been a previous reaction to nonionic iodinated contrast medium, the use of a different agent is appropriate (Thomsen and Bush 1998).
3.2.3.2 Premedication
3.2.3.2.1
Possible Regimes and Evidence for Their Efficacy
To reduce the incidence of idiosyncratic contrast medium reactions, a variety of premedication regimes have been used. Most frequently steroids with or without additional H1 antihistamines have
been recommended, and other drugs, such as ephe- drine and H2 antagonists have also been tried.
With ionic agents, there is good evidence that steroids reduce the rate of reactions. In a ran- domised study of 6763 unselected patients, Lasser et al. (1987) showed a reduction in the incidence of reactions to ionic contrast media from 9% to 6.4% when methylprednisolone was given 12 and 2 h before the contrast agent. In patients who have previously reacted to ionic contrast media, a com- bination of steroid and H1 antihistamine reduces the repeat reaction rate, estimated to be 16%–
35% without premedication (Witten et al. 1973;
Shehadi 1975). Greenberger et al. (1984) evalu- ated 657 procedures in 563 previous reactors using two premedication regimes before ionic contrast media. In patients given prednisone and antihista- mine the repeat reaction rate was reduced to 9.0%
and the addition of ephedrine further reduced the repeat reaction rate to 3.1%. However, because of anxieties about the possible adverse effects of ephe- drine in patients with hypertension or cardiovascu- lar disease, the use of ephedrine has not been widely adopted (Thomsen and Bush 1998). The addition of the H2 antagonist cimetidine to the steroid, antihis- tamine and ephedrine premedication was associ- ated with a higher risk of reaction (Greenberger et al. 1985). With the ionic low osmolality agent meg- lumine ioxaglate, Bertrand et al. (1992) found that the antihistamine hydroxyzine reduced the risk of urticaria from 12.5% to 1.0% in 200 subjects.
With the nonionic low osmolality agents there is less evidence about the value of premedication, but the available evidence does indicate that premedica- tion can further reduce the incidence of reactions.
In a randomised study of 1155 unselected patients,
Lasser et al. (1994) found a statistically significant
decrease in the total number of reactions from 4.9 to
1.7% when patients given nonionic contrast media
were premedicated with methylprednisolone given
12 and 2 h before the contrast agent. The numbers
of moderate and severe reactions were also less after
steroids but the numbers were small and no statis-
tically significant difference was found. In previ-
ous reactors, Greenberger and Patterson (1991)
found that the combined use of a nonionic agent
together with both prednisone and antihistamine or
prednisone, antihistamine and ephedrine reduced
the repeat reaction rate to 0.5% in 181 patients. In
patients who had previously reacted, or who had a
history of allergy or severe cardiopulmonary dis-
ease, H1 and H2 antagonists reduced the reaction
rate to 1.57% in 1047 patients, as compared to a reac-
tion rate of 4.37% in those who were not premedi- cated (Fink et al. 1992).
When steroid premedication is used, the steroids should be given at least 12 h before contrast medium.
The minimal effective time interval between steroids and contrast medium is considered unlikely to be less than 6 h (Lasser et al. 1987; Morcos et al. 2001). To be effective, steroids require time to affect the com- plex processes which underlie anaphylactoid reac- tions. For example, steroids cause induction of the C1 esterase inhibitor, which affects the production of the mediator bradykinin. The rise in C1 esterase inhibitor levels occurs over a 12-h period (Lasser et al. 1981).
3.2.3.2.2 Controversies
With the ionic agents, the higher risk of reaction and the stronger evidence for the value of premedica- tion meant that steroid premedication was widely recommended and used (Greenberger et al. 1984;
Lasser et al. 1987). With the nonionic agents the use of premedication is more controversial and prac- tice is variable (Dawson and Sidhu 1993; Lasser 1994, 1995; Dore et al. 1994 and 1995; Lasser and Berry 1994; Seymour et al. 1994; Cohan et al. 1995;
Dawson 2005; Radhakrishnan et al. 2005).
One point of view is that the risk of reaction with nonionic agents is very low and the evidence of the value of steroid premedication not sufficiently strong and therefore that premedication is no longer war- ranted (Dawson and Sidhu 1993; Dawson 2005).
An alternative point of view is that the admittedly imperfect evidence indicates that steroid premedi- cation further reduces the likelihood of a reaction to nonionic agents (Greenberger and Patterson 1991; Lasser et al. 1994; Lasser 1994; American College of Radiology 2004). Furthermore, high doses of steroids are used in the treatment of anaphy- laxis where their effect is attributed to the fact that they stabilise cell membranes and reduce the release of chemical mediators involved in anaphylaxis (Bush and Swanson 1991).
It is not possible to be dogmatic about whether patients at increased risk of reaction should receive steroid premedication before they are given noni- onic contrast media. In emergency situations the risk of not undertaking the investigation immedi- ately often outweighs the potential benefit of using steroids. Radiologists may also be influenced by the setting in which they practice. While facilities for resuscitation should be available in all settings where intravascular contrast medium is adminis-
tered, additional support facilities are more read- ily available in larger hospitals. The American College of Radiology Manual on Contrast Media (2004) states that the higher the risk of reac- tion, the stronger the case that can be made for pre- medication. The European Society of Urogenital Radi- ology guidelines indicate that opinion on this topic is divided and therefore do not issue a directive.
It must be remember that, even with steroid pre- medication, reactions to nonionic contrast media still occur, and are commoner in subjects with a his- tory of allergy (Freed et al. 2001).
3.2.3.3
Pretesting and Injection Rate
The practice of pretesting – giving a small prelimi- nary test dose of contrast medium intravenously before the full dose is given – has been shown to be of no value (Shehadi 1975; Fischer and Doust 1972; Yamaguchi et al. 1991). Fischer and Doust (1972) found the mortality after contrast medium was unaffected by pretesting and that deaths could occur following a negative pretest or following the pretest itself. Yamaguchi et al. (1991) found no benefit of pretesting either with ionic or nonionic agents.
Injection rate does not appear to have any effect on the rate of adverse reactions (Jacobs et al. 1998).
3.2.4
Summary: Iodinated Contrast Media
To reduce the risk of an acute reaction to intra- vascular iodinated contrast media, the important measures for all patients are:
• Use nonionic contrast media.
• Keep the patient in the Radiology Department for 30 min after contrast medium injection.
• Have the drugs and equipment for resuscitation readily available.
There is an increased risk of an acute reaction to intravascular iodinated contrast media in patients with a history of:
• Previous generalised reaction to iodinated con- trast medium, either moderate (e.g. urticaria, bronchospasm) or severe (e.g. hypertension, severe bronchospasm, pulmonary oedema, car- diovascular collapse, convulsions).
• Asthma.
• Allergy requiring medical treatment.
In patients with an increased risk of a reaction to intravascular iodinated contrast media:
• Is the use of iodinated contrast medium essen- tial? Would another test (e.g. ultrasonography, magnetic resonance imaging) give the diagnostic information needed?
• Use a different iodinated agent for previous reac- tors to contrast medium.
• Practice for the use of premedication is variable.
It should be considered for previous reactors to iodinated contrast media and high risk patients.
A suitable corticosteroid premedication regime is:
• Prednisolone 30 mg orally (or methylpredniso- lone 32 mg orally) given 12 and 2 h before con- trast medium.
• H2 antihistamines may also be used.
3.3
Gadolinium Contrast Media
3.3.1
Types of Reaction and Frequency
Adverse events following intravenous gadolinium contrast media are less common than following iodi- nated agents and are usually estimated to occur in less than 5% of patients. The majority of these adverse events are minor and self-limiting (Runge 2000).
Only a small proportion of patients develop allergy- like or anaphylactoid reactions. Reactions such as rash, urticaria or bronchospasm have been estimated to occur in 0.004%–0.7% and severe life-threaten- ing anaphylactoid reactions to occur in between 1 in 10,000 and 1 in 300,000 (ACR Manual 2004;
Niendorf et al. 1991; Murphy et al. 1996). Anaphy- lactoid reactions occur within the first 30 min of con- trast medium injection (Murphy et al. 1996). Only one fatal reaction definitely attributable to gadolin- ium has been reported (Jordan and Mintz 1995).
3.3.2
Risk Factors for Reactions
3.3.2.1
Type of Contrast Medium
There appears to be no significant difference between the incidence of reactions with the different gado- linium agents, both ionic and nonionic (Kirchin and Runge 2003).
3.3.2.2
Patient Risk Factors
A previous reaction to gadolinium contrast media was reported to increase the risk of adverse events from 2.4% to 21.3%, and a previous reaction to an iodinated contrast medium to increase the risk to 6.3% (Nelson et al. 1995). A history of asthma or allergy increased the risk to 3.7% in the same series (Nelson et al. 1995).
3.3.3
Prevention of Reactions
No evidence is available in the literature to indi- cate what measures should be taken to prevent a reaction to gadolinium. The measures to be taken when a patient has previously had a reaction to gadolinium or is considered to be at high risk are therefore based on similar principles to those for iodinated contrast agents (see ACR Manual 2004 and Sect. 3.3.4 below).
3.3.4
Summary: Gadolinium Contrast Media
The risk of an acute reaction to gadolinium con- trast media is very low, and much lower than the risk of a reaction to iodinated contrast media.
Nonetheless, for all patients the following is rec- ommended:
• Keep the patient in the Radiology Department for 20 min after contrast medium injection.
• Have the drugs and equipment for resuscitation readily available.
The type of contrast medium, ionic or nonionic, does not appear to affect the incidence of reactions to gadolinium agents.
In patients with a previous reaction to a gadolin- ium agent or who are considered at very high risk:
• Is the use of gadolinium contrast medium essen- tial? Would an unenhanced scan or other test give the diagnostic information needed?
• Choose a different gadolinium agent to that used before in previous reactions.
• Consider premedication.
A suitable corticosteroid premedication regime is:
• Prednisolone 30 mg (or methylprednisolone 32 mg) orally given 12 and 2 h before contrast medium.
• H2 antihistamines may also be used.
References
ACR Committee on Drugs and Contrast Media (2004) Manual on contrast media, 5th edn. American College of Radiol- ogy, Reston, VA
Almen T (1994) The etiology of contrast medium reactions.
Invest Radiol 19 [Suppl]:S37–S45
Ansell G, Tweedie MCK, West CR et al (1980) The current status of reactions to intravenous contrast media. Invest Radiol 15 [Suppl]:S32–S39
Bertrand PR, Soyer PM, Rouleau PJ et al (1992) Comparative randomised double-blind study of hydroxyzine versus placebo as premedication before injection of iodinated contrast media. Radiology 184:383–384
Bettman MA, Heeren T, Greenfield A, Gondey C (1997) Adverse events with radiographic contrast agents: results of the SCVIR Contrast Agent Registry. Radiology 203:611–620 Bush WH, Swanson DP (1991) Acute reactions to intravascular
contrast media: types, risk factors, recognition and spe- cific treatment. AJR Am J Roentgenol 157:1153–1161 Caro JJ, Trindade E, McGregor M (1991) The risks of death
and severe nonfatal reactions with high-vs low- osmolal- ity contrast media: a meta-analysis. AJR Am J Roentgenol 156:825–832
Choyke PL, Miller Dl, Lotze MT et al (1992) Delayed reactions to contrast media after interleukin-2 immunotherapy.
Radiology 183:111–114
Cochran ST, Bomyea K, Sayre JW (2001) Trends in adverse events after iv administration of contrast media. AJR Am J Roentgenol 176:1385–1388
Cohan RH, Ellis JH, Dunnick NR (1995) Use of low-osmolar agents and premedication to reduce the frequency of adverse reactions to radiographic contrast media: a survey of the Society of Uroradiology. Radiology 194:357–364 Dawson P (2005) Commentary: repeat survey of current prac-
tice regarding corticosteroid prophylaxis for patients at increased risk of adverse reaction to intravascular con- trast agents. Clin Radiol 60:56–57
Dawson P, Sidhu PS (1993) Is there a role for corticoster- oid prophylaxis in patients at increased risk of adverse reactions to intravascular contrast agents? Clin Radiol 48:225–226
Dore CJ, Sidhu PS, Dawson P (1994) Is there a role for cor- ticosteroid prophylaxis in patients at increased risk of adverse reactions to intravascular contrast agents? Clin Radiol 49:583–584
Dore CJ, Sidhu PS, Dawson P (1995) Is there a role for cor- ticosteroid prophylaxis in patients at increased risk of adverse reactions to intravascular contrast agents? Clin Radiol 50:198–199
Fink U, Fink BK, Lissner J (1992) Adverse reactions to nonionic contrast media with special regard to high-risk patients.
Eur Radiol 2:317–321
Fischer HW, Doust VL (1972) An evaluation of pretesting in the problem of serious and fatal reactions to excretory urography. Radiology 103:497–501
Fishman JE, Aberle DR, Moldawer NP et al (1991) Atypical contrast reactions associated with systemic interleukin-2 therapy. AJR Am J Roentgenol 156:833–834
Freed KS, Leder RA, Alexander C et al (2001) Breakthrough adverse reactions to low-osmolar contrast media after steroid premedication. AJR Am J Roentgenol 176:1389–
1392
Greenberger PA, Patterson R (1991) The prevention of imme- diate generalised reactions to radiocontrast media in high-risk patients. J Allergy Clin Immunol 87:867–872 Greenberger PA, Patterson R, Radin RR (1984) Two pre-treat-
ment regimens for high-risk patients receiving radio- graphic contrast media. J Allergy Clin Immunol 74:540–
543
Greenberger PA, Patterson R, Tapio CM (1985) Prophylaxis against repeated radiocontrast media reactions in 857 cases. Arch Intern Med 145:2197–2200
Greenberger PA, Meyers SN, Kramer BL et al (1987) Effects of beta-adrenergic and calcium antagonists on the develop- ment of anaphylactoid reactions from radiographic con- trast media. J Allergy Clin Immunol 80:698–702
Hartman GW, Hattery RR, Witten DM, Williamson B (1982) Mortality during excretory urography: Mayo Clinic expe- rience. AJR Am J Roentgenol 139:919–922
Jacobs JE, Birnbaum BA, Langlotz CP (1998) Contrast media reactions and extravasation: relationship to intravenous injection rates. Radiology 209:411–416
Jordan RM, Mintz RD (1995) Fatal reaction to gadopentetate dimeglumine. AJR Am J Roentgenol 164:734–744 Katayama H, Yamaguchi K, Kozuka T et al (1990) Adverse
reactions to ionic and nonionic contrast media. Radiol- ogy 175:621–628
King BF (1999) Intravascular contrast media and premedica- tion. In: Bush WH, Krecke KN, King BF, Bettman MA (eds) Radiology life support (RAD-LS): a practical approach.
Arnold, London/University Press, New York, p 15 Kirchin MA, Runge VM (2003) Contrast agents for magnetic
resonance imaging: safety update. Top Magn Reson Imag- ing 14:426–435
Lang DM, Alpern MB, Visintainer PF, Smith ST (1991) Increased risk for anaphylactoid reaction from contrast media in patients on E-adrenergic blockers or with asthma. Ann Intern Med 115:270–276
Lasser EC (1985) Etiology of anaphylactoid responses: the promise of nonionics. Invest Radiol 20 [Suppl]:S79–S82 Lasser EC (1987) A coherent biochemical basis for increased
reactivity to contrast material in allergic patients: a novel concept. AJR Am J Roentgenol 149:1281–1285
Lasser EC (1994) Is there a role for corticosteroid prophylaxis in patients at increased risk of adverse reactions to intra- vascular contrast agents? Clin Radiol 49:582–583 Lasser EC (1995) Is there a role for corticosteroid prophylaxis
in patients at increased risk of adverse reactions to intra- vascular contrast agents? Clin Radiol 50:199
Lasser EC, Berry CC (1994) Is there a role for corticosteroid prophylaxis in patients at increased risk of adverse reac- tions to intravascular contrast agents? Clin Radiol 49:584 Lasser EC, Lang JH, Lyon SG (1981) Glucocorticoid-induced
elevations of C1-esterase inhibitor: a mechanism for pro- tection against lethal dose range contrast challenge in rabbits. Invest Radiol 16:20–23
Lasser EC, Berry CC, Talner LB et al (1987) Pretreatment with corticosteroids to alleviate reactions to intravenous con- trast material. N Engl J Med 317:845–849
Lasser EC, Berry CC, Mishkin MM et al (1994) Pretreatment with corticosteroids to prevent adverse reactions to noni- onic contrast media. AJR Am J Roentgenol 162:523–526 Lasser EC, Lyon SG, Berry CC (1997) Reports on contrast
media reactions: analysis of data from reports to the US Food and Drug Administration. Radiology 203:605–610
Leder R (1997) Letter. AJR Am J Roentgenol 169:906–907 Morcos SK, Thomsen HS, Webb JAW et al (2001) Prevention
of generalised reactions to contrast media: a consensus report and guidelines. Eur Radiol 11:1720–1728
Murphy KJ, Brunberg JA, Cohan RH (1996) Adverse reactions to gadolinium contrast media: a review of 36 cases. AJR Am J Roentgenol 167:847–849
Nelson KL, Gifford LM, Lauber-Huber C et al (1995) Clinical safety of gadopentetate dimeglumine. Radiology 196:439–
443
Niendorf HP, Haustein J, Cornelius I et al (1991) Safety of gadolinium-DTPA: extended clinical experience. Magn Reson Med 22:222–228
Oldham RK, Brogley J, Braud E (1991) J Clin Oncol 8:942–943 Palmer FJ (1988) The RACR survey of intravenous contrast
media reactions: final report. Austr Radiol 32:426–428 Radhakrishnan S, Manoharan S, Fleet M (2005) Repeat survey
of current practice regarding corticosteroid prophylaxis for patients at increased risk of adverse reaction to intra- vascular contrast agents. Clin Radiol 60:58–63
Runge VM (2000) Safety of approved MR contrast media for intravenous injection. J Magn Reson Imaging 12:205–213 Seymour R, Halpin SF, Hardman JA et al (1994) Corticoster- oid prophylaxis in patients with increased risk of adverse reactions to intravascular contrast agents: a survey of cur- rent practice in the UK. Clin Radiol 49:791–795
Shehadi WH (1975) Adverse reactions to intravascularly administered contrast media. AJR Am J Roentgenol 124:145–152
Shehadi WH (1985) Death following intravascular administra- tion of contrast media. Acta Radiol Diagn 26:457–461 Siegle RL, Halvorsen RA, Dillon J et al (1991) The use of iohexol
in patients with previous reactions to ionic contrast mate- rial. Invest Radiol 26:411–416
Thomsen HS, Bush WH (1998) Adverse effects of contrast media: incidence, prevention and management. Drug Safety 19:313–324
Witten DM, Hirsch FD, Hartman GW (1973) Acute reactions to urographic contrast medium. AJR Am J Roentgenol 119:832–840
Wolf GL, Miskin MM, Roux SG et al (1991) Comparison of the rates of adverse drug reactions: ionic contrast agents, ionic agents combined with steroids and nonionic agents.
Invest Radiol 26:404–410
Yamaguchi K, Katayama H, Takashima T et al (1991) Predic- tion of severe adverse reactions to ionic and nonionic con- trast media in Japan: evaluation of prestesting. Radiology 178:363–367
Zukiwski AA, David CL, Coan J et al (1990) Increased inci- dence of hypersensitivity to iodine-containing radio- graphic contrast media after interleukin-2 administra- tion. Cancer 65:1521–1524
