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Corticosteroid prophylaxis for contrast media reactions
Clinical Radiology (1994) 49, 508-510
Correspondence Letters are published at the discretion of the Editor. Opinions expressed by correspondents are not necessarily those of the Editor. Unduly long letters may be returned to the authors for shortening. Letters in response to a paper may be sent to the author of the paper so that the reply can be published in the same issue. Letters should be typed double spaced and should be signed by all authors personally. References should be given in the style specified in the Instructions to Authors at the front of the Journal.
CORTICOSTEROID PROPHYLAXIS FOR CONTRAST MEDIA REACTIONS
S m - I read the review by Dawson and Sidhu [1] with interest but I am not convinced that prophylactic corticosteroid therapy should be abandoned in high-risk patients when non-ionic media are used. Although non-ionic media are undoubtedly safer, they may cause severe reactions and even death. The statistical criticism of Lasser's paper [2] by Ackroyd [3] and Rose [4] has been effectively answered in a reply by Lasser [5]. Moreover, Wolf [6] showed a similar trend to Lasser's findings with a 22% reduction in severe reactions using steroid prophylaxis with diatrizoate, but the sample size was too small for statistical significance. In a recent rigidly controlled study of non-ionic media by Lasser [7], 580 patients received a two dose corticosteroid regimen and 575 received a placebo. For 'all reactions' and for 'Grade 1' reactions, there was a protective effect of the premedication. Unfortunately due to difficulties in recruiting, there were too few patients to evaluate statistical significance in the more severe reactions. Dawson and Sidhu state that 'there is no evidence at all to suggest that the possible small advantages ofcorticosteroid prophylaxis and the more certain gains from the use of a non-ionic agent may be combined by using both'. In a series of 140 patients with a previous history of moderate or severe reactions to contrast media, Greenberger [8] attained a rate of repeat reactions as low as 0.7% using the combination of non-ionic media with a prophylactic regime of prednisone 50 mg orally at 13, 7 and I h, and diphenhydramine 50mg, 1 h, before repeat contrast administration. This was a non-randomized and unblinded study but the results are impressive and compare favourably with Wolf's [6] rate of 2.5% for iohexol alone. Patients with asthma are at particular risk from contrast media. The reported risk ratios for a severe reaction in patients with a history of asthma range from 4.5 to 10.09 [9 11], with an incidence of 1.88% for ionic media and 0.23% for non-ionic media [12]. The value of corticosteroids in the prophylaxis and treatment of asthma is well established clinically, but corticosteroid therapy may also cause adrenal suppression requiring booster therapy before stress situations. I have personally witnessed a case of severe bronchospasm with cardiovascular collapse following the administration of iopamidol without corticosteroid prophylaxis to an asthmatic patient who had recently received corticosteroid therapy. Fortunately, resuscitation was successful. Greenberger [14] reportbd an analogous case in a patient with Crohn's disease, receiving prednisone 10mg daily, who developed a severe anaphylactoid reaction due to iopamidol. Following resuscitation, prednisone was increased to 50 mg daily for 4 days and at 13, 7 and 1 h before a repeat examination with iopamidol at which there was no reaction. It should also be noted that interleukin-2 may induce hypersensitivity to both ionic and non-ionic contrast media and that corticosteroids have been reported to be effective in the prophylaxis and treatment of reactions in sensitized patients [ 14-16]. Providing that there is no clinical contra-indication to the use of corticosteroids, it is my considered opinion that prophylactic corticosteroid therapy should be combined with the use of non-ionic media when contrast examinations are essential in high-risk patients. At the same time, there must be adequate provision to treat any reaction which might occur. G. ANSELL
101 Childwall Park Avenue Liverpool L16 OJF
References
1 Dawson P, Sidhu PS. Review: Is there a role for corticosteroid prophylaxis in patients at increased risk of adverse reactions to intravascular contrast agents? Clinical Radiology 1993;48:225226.
2 Lasser EC, Berry CC, Talner LB et al. Pretreatment with corticosteroids to alleviate reactions to intravenous contrast material. New England Journal of Medicine 1987;217:845-849. 3 Ackroyd JF. Letter to the Editor. New England Journal of Medicine 1988;318:856. 4 Rose TG. Letter to the Editor. New England Journal of Medicine 1988;318:856. 5 Lasser EC, Berry CC, Talner LB. Letter to the Editor. New England Journal of Medicine 1988;318:856-857. 6 Wolf GL, Mishkin MM, Roux SG et al. Comparison of the rates of adverse drug reactions. Ionic contrast agents, ionic agents combined with steroids and nonionic agents. Investigative Radiology 1991; 26:404-410. 7 Lasser EC. Personal communication. 12th October, 1993. 8 Greenberger PA, Patterson R. The prevention of immediate generalized reactions to radiocontrast media in high-risk patients. Journal of Allergy and Clinical Immunology 1991;87:867-872. 9 Lang DM, Alpern MB, Visintainer PF et al. Increased risk of anaphylactoid reaction from contrast media in patients on betaadrenergic blockers or with asthma. Annals of Internal Medicine 1991;115:270-276. 10 Ansell G, Tweedie MCK, West CR et al. The current status of reactions to intravenous contrast media. Investigative Radiology Supplement 1980;15:$32-$39. 11 Katayama H, Yamaguchi K, Kozuka T et al. Full-scale investigation into adverse reaction in Japan. Risk factor analysis. Investigative Radiology 1991;26:$33-$36. 12 Katayama H, Yamaguchi K, Kozuka T et al. Adverse reactions to ionic and non-ionic contrast media. A report from the Japanese Committee on the Safety of Contrast Media. Radiology 1990; 175:621-628. 13 Greenberger PA, Gutt L, Meyers SL. An immediate generalized reaction to iopamidol. Archives of Internal Medicine 1987; 147:2208-2209. 14 Zukiwski AA, David CL, Coan J e t aL Increased incidence o f hypersensitivity to iodine-containing radiographic contrast media after interleukin-2 administration. Cancer 1990;65:1521-1524. 15 Fishman JE, Abere DR, Moldawer NP et al. Atypical contrast reactions associated with systemic interleukin-2 therapy. American Journal of Roentgenology 1991;156:833-834. 16 Abi-Aad A, Figlin RA, Belldegrun A e t al. Metastatic renal cancer, interleukin-2 toxicity induced by contrast agent injection. Journal of Immunotherapy 1991;10:292-295.
SIR - I read with great interest the recent review by Dawson and Sidhu on the role of corticosteroid prophylaxis in patients at increased risk of adverse reactions to intravascular contrast agents [1]. However, I am rather surprised that in their literature search they have failed to include an important study which may have influenced their final recommendation of abandoning the corticosteroid prophylaxis in addition to the use of non-ionic contrast agents. Greenberger and Patterson in 1991 [2] found that pre-treatment with corticosteroid (Prednisone 50mg orally, 13, 7 and l h before administration of contrast) and the use of a single dose of the antihistamine diphenhydramine (50 mg orally 1 h before contrast), in addition to the administration of low osmolar contrast media, reduced the risk of repeated immediate generalized reactions to contrast agents from 9.1% when conventional contrast media were used with the same pre-treatment to 0.5% and they did not experience any severe reactions. In an earlier large-scale study Katayama et al. found that when low osmolar contrast media were used alone in patients with a history of adverse reactions to contrast the prevalence of all reactions was 11.24% and severe reactions was 0.18 % [3]. Nevertheless, it can be argued that the evidence for accumulative protective effect of the combined use of low osmolar contrast agents and corticosteroid prophylaxis in patients at increased risk of contrast reactions is not conclusive. Equally it can be pointed out that no strong case has yet been made against such a policy. The only means to settle this argument is through a large-scale prospective study in
Correspondence Letters are published at the discretion of the Editor. Opinions expressed by correspondents are not necessarily those of the Editor. Unduly long letters may be returned to the authors for shortening. Letters in response to a paper may be sent to the author of the paper so that the reply can be published in the same issue. Letters should be typed double spaced and should be signed by all authors personally. References should be given in the style specified in the Instructions to Authors at the front of the Journal.
CORTICOSTEROID PROPHYLAXIS FOR CONTRAST MEDIA REACTIONS
S m - I read the review by Dawson and Sidhu [1] with interest but I am not convinced that prophylactic corticosteroid therapy should be abandoned in high-risk patients when non-ionic media are used. Although non-ionic media are undoubtedly safer, they may cause severe reactions and even death. The statistical criticism of Lasser's paper [2] by Ackroyd [3] and Rose [4] has been effectively answered in a reply by Lasser [5]. Moreover, Wolf [6] showed a similar trend to Lasser's findings with a 22% reduction in severe reactions using steroid prophylaxis with diatrizoate, but the sample size was too small for statistical significance. In a recent rigidly controlled study of non-ionic media by Lasser [7], 580 patients received a two dose corticosteroid regimen and 575 received a placebo. For 'all reactions' and for 'Grade 1' reactions, there was a protective effect of the premedication. Unfortunately due to difficulties in recruiting, there were too few patients to evaluate statistical significance in the more severe reactions. Dawson and Sidhu state that 'there is no evidence at all to suggest that the possible small advantages ofcorticosteroid prophylaxis and the more certain gains from the use of a non-ionic agent may be combined by using both'. In a series of 140 patients with a previous history of moderate or severe reactions to contrast media, Greenberger [8] attained a rate of repeat reactions as low as 0.7% using the combination of non-ionic media with a prophylactic regime of prednisone 50 mg orally at 13, 7 and I h, and diphenhydramine 50mg, 1 h, before repeat contrast administration. This was a non-randomized and unblinded study but the results are impressive and compare favourably with Wolf's [6] rate of 2.5% for iohexol alone. Patients with asthma are at particular risk from contrast media. The reported risk ratios for a severe reaction in patients with a history of asthma range from 4.5 to 10.09 [9 11], with an incidence of 1.88% for ionic media and 0.23% for non-ionic media [12]. The value of corticosteroids in the prophylaxis and treatment of asthma is well established clinically, but corticosteroid therapy may also cause adrenal suppression requiring booster therapy before stress situations. I have personally witnessed a case of severe bronchospasm with cardiovascular collapse following the administration of iopamidol without corticosteroid prophylaxis to an asthmatic patient who had recently received corticosteroid therapy. Fortunately, resuscitation was successful. Greenberger [14] reportbd an analogous case in a patient with Crohn's disease, receiving prednisone 10mg daily, who developed a severe anaphylactoid reaction due to iopamidol. Following resuscitation, prednisone was increased to 50 mg daily for 4 days and at 13, 7 and 1 h before a repeat examination with iopamidol at which there was no reaction. It should also be noted that interleukin-2 may induce hypersensitivity to both ionic and non-ionic contrast media and that corticosteroids have been reported to be effective in the prophylaxis and treatment of reactions in sensitized patients [ 14-16]. Providing that there is no clinical contra-indication to the use of corticosteroids, it is my considered opinion that prophylactic corticosteroid therapy should be combined with the use of non-ionic media when contrast examinations are essential in high-risk patients. At the same time, there must be adequate provision to treat any reaction which might occur. G. ANSELL
101 Childwall Park Avenue Liverpool L16 OJF
References
1 Dawson P, Sidhu PS. Review: Is there a role for corticosteroid prophylaxis in patients at increased risk of adverse reactions to intravascular contrast agents? Clinical Radiology 1993;48:225226.
2 Lasser EC, Berry CC, Talner LB et al. Pretreatment with corticosteroids to alleviate reactions to intravenous contrast material. New England Journal of Medicine 1987;217:845-849. 3 Ackroyd JF. Letter to the Editor. New England Journal of Medicine 1988;318:856. 4 Rose TG. Letter to the Editor. New England Journal of Medicine 1988;318:856. 5 Lasser EC, Berry CC, Talner LB. Letter to the Editor. New England Journal of Medicine 1988;318:856-857. 6 Wolf GL, Mishkin MM, Roux SG et al. Comparison of the rates of adverse drug reactions. Ionic contrast agents, ionic agents combined with steroids and nonionic agents. Investigative Radiology 1991; 26:404-410. 7 Lasser EC. Personal communication. 12th October, 1993. 8 Greenberger PA, Patterson R. The prevention of immediate generalized reactions to radiocontrast media in high-risk patients. Journal of Allergy and Clinical Immunology 1991;87:867-872. 9 Lang DM, Alpern MB, Visintainer PF et al. Increased risk of anaphylactoid reaction from contrast media in patients on betaadrenergic blockers or with asthma. Annals of Internal Medicine 1991;115:270-276. 10 Ansell G, Tweedie MCK, West CR et al. The current status of reactions to intravenous contrast media. Investigative Radiology Supplement 1980;15:$32-$39. 11 Katayama H, Yamaguchi K, Kozuka T et al. Full-scale investigation into adverse reaction in Japan. Risk factor analysis. Investigative Radiology 1991;26:$33-$36. 12 Katayama H, Yamaguchi K, Kozuka T et al. Adverse reactions to ionic and non-ionic contrast media. A report from the Japanese Committee on the Safety of Contrast Media. Radiology 1990; 175:621-628. 13 Greenberger PA, Gutt L, Meyers SL. An immediate generalized reaction to iopamidol. Archives of Internal Medicine 1987; 147:2208-2209. 14 Zukiwski AA, David CL, Coan J e t aL Increased incidence o f hypersensitivity to iodine-containing radiographic contrast media after interleukin-2 administration. Cancer 1990;65:1521-1524. 15 Fishman JE, Abere DR, Moldawer NP et al. Atypical contrast reactions associated with systemic interleukin-2 therapy. American Journal of Roentgenology 1991;156:833-834. 16 Abi-Aad A, Figlin RA, Belldegrun A e t al. Metastatic renal cancer, interleukin-2 toxicity induced by contrast agent injection. Journal of Immunotherapy 1991;10:292-295.
SIR - I read with great interest the recent review by Dawson and Sidhu on the role of corticosteroid prophylaxis in patients at increased risk of adverse reactions to intravascular contrast agents [1]. However, I am rather surprised that in their literature search they have failed to include an important study which may have influenced their final recommendation of abandoning the corticosteroid prophylaxis in addition to the use of non-ionic contrast agents. Greenberger and Patterson in 1991 [2] found that pre-treatment with corticosteroid (Prednisone 50mg orally, 13, 7 and l h before administration of contrast) and the use of a single dose of the antihistamine diphenhydramine (50 mg orally 1 h before contrast), in addition to the administration of low osmolar contrast media, reduced the risk of repeated immediate generalized reactions to contrast agents from 9.1% when conventional contrast media were used with the same pre-treatment to 0.5% and they did not experience any severe reactions. In an earlier large-scale study Katayama et al. found that when low osmolar contrast media were used alone in patients with a history of adverse reactions to contrast the prevalence of all reactions was 11.24% and severe reactions was 0.18 % [3]. Nevertheless, it can be argued that the evidence for accumulative protective effect of the combined use of low osmolar contrast agents and corticosteroid prophylaxis in patients at increased risk of contrast reactions is not conclusive. Equally it can be pointed out that no strong case has yet been made against such a policy. The only means to settle this argument is through a large-scale prospective study in