Corticosteroid prophylaxis for patients with increased risk of adverse reactions to intravascular contrast agents: A survey of current practice in the UK

Corticosteroid prophylaxis for patients with increased risk of adverse reactions to intravascular contrast agents: A survey of current practice in the UK

Clinical Radiology (1994) 49, 791-795 Corticosteroid Prophylaxis for Patients With Increased Risk of Adverse Reactions to Intravascular Contrast Agen...

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Clinical Radiology (1994) 49, 791-795

Corticosteroid Prophylaxis for Patients With Increased Risk of Adverse Reactions to Intravascular Contrast Agents: A Survey of Current Practice in the UK R. SEYMOUR, S. F. HALPIN, J. A. HARDMAN, J. M. COOTE, M. S. T. RUTTLEY and G. M. ROBERTS

Department of Radiology, University Hospital of Wales, Heath Park, Cardiff There is no definite experimental evidence that prophylactic corticosteroids reduce the frequency or severity of adverse effects from low-osmolar contrast agents in patients at increased risk of reaction. There is no consensus in terms of how prophylaxis should be conducted. We have studied current radiologists' practice in the UK by sending postal questionnaires to 212 radiologists randomly selected from a list of current consultants who are Fellows of the Royal College of Radiologists. One hundred and seventy (80.2%) of the 212 questionnaires were completed. The majority of radiologists routinely use non-ionic low osmolar contrast media for intravenous administration, only 30 (17.6%) routinely using conventional ionic agents and six (3.5%) ionic low osmolar agents. All 170 use low osmolar contrast media for those patients perceived to be at increased risk of adverse reactions. Seventy-six radiologists (44.7%) never use steroid cover. There is no consistent practice amongst the 94 consultants (55.3%) who do use steroid cover. The indications for prophylaxis vary, as do the corticosteroid used and the dose regime employed. The total dose used varied from the equivalent of 7.5 mg to 400 mg of prednisolone, and the duration of prophylaxis varied from a single dose.to a 4 day course. One hundred and forty-two radiologists (83.5%) would welcome nationally agreed guidelines for the use of steroid cover. The great variation in the use of steroid cover in the UK reflects the lack of clear evidence of its benefit in combination with low osmolar contrast media. Seymour, R., Halpin, S.F., Hardman, J.A., Coote, J.M., Ruttley, M.S.T. & Roberts, G.M. (1994). Clinical Radiology 49, 791-795. Corticosteroid Prophylaxis for Patients With Increased Risk of Adverse Reactions to Intravascular Contrast Agents: A Survey of Current Practice in the UK

Acceptedfor Publication 25 July 1994

The use of non-ionic, low-osmolar iodinated contrast agents for investigations involving patients considered to be at increased risk of adverse reaction is now well accepted [1]. However, there is still no clear consensus as to the value of prophylactic corticosteroids. Dawson and Sidhu conclude that there is no convincing evidence that corticosteroids add to the benefit achieved by using non-ionic agents [2]. We felt that it would be informative to review the current practice of consultant radiologists in this country by means of a questionnaire. METHODS

A list of 424 consultant Fellows of the Royal College of Radiologists was provided by the Royal College and questionnaires were sent to 212 consultants randomly selected from this list. (The questionnaire is reproduced in Appendix 1.) Postal reminders were sent to all those not replying within 3 months. In order to define the population of radiologists responding, we asked for details of the individuals' specialist field and the type of hospital that the Correspondence to: Dr R. Seymour, Department of Radiology, University Hospital of Wales, Heath Park, Cardiff CF4 4XW.

respondent works in. We also enquired about local steroid prophylaxis policies. Before defining the pattern of individual steroid use, we determined the type of contrast agent used either routinely or for patients considered to be at increased risk of adverse reaction. We assessed each radiologist's use of steroid prophylaxis by asking about their normal practice when administering an i.v. contrast agent to various categories of 'at-risk' patients, and also when administering contrast media by intra-arterial or other routes. We obtained details of the steroid regimes employed. We assessed the likely demand for agreed guidelines for the use of steroid prophylaxis. RESULTS One hundred and seventy-five (82.5%) of the 212 questionnaires were returned. Of these, three were not completed because the intended recipient is no longer in clinical practice, and two because the consultant replying did not use iodinated contrast media, giving a response rate of 80.2% (a total of 170 out of 212). The respondents represent a cross-section o~ UK radiologists, 65 working mainly in teaching hospitals, 85 in district general hospitals, and 20 in district general

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CLINICAL RADIOLOGY

Table 1 - Corticosteroid prophylaxis in various categories of patient; breakdown for the 94 radiologists who use steroid cover for intravenous contrast

a b c d e f g h i j

Previous history of asthma, not currently being treated Mild asthma, currently requiring inhaled beta agonists Asthma currently requiring inhaled corticosteroids Asthma currently requiring oral corticosteroids Previous history of asthma severeenough to require ITU admission Previous mild adverse reaction to contrast agent Previous severe adverse reaction to contrast agent Drug or other allergy Hayfever Eczema

No steroid cover

Oral steroid cover

Intravenous cover

Would not perform the investigation*

87 71 52 51 25 53 0 84 90 89

6 18 31 25 40 34 48 8 3 3

1 6 11 17 18 5 29 2 1 2

0 0 0 1 11 2 17 0 0 0

*This option was not investigated, but was spontaneously offered by some respondents. hospitals affiliated to a teaching hospital. The majority are general radiologists, but there are representatives of all specialist fields. In answer to question 3, regarding the type of contrast agent routinely used for i.v. administration, only 30 of the 170 radiologists (17.6%) use hyperosmolar contrast media and even fewer (6; 3.5%) routinely use ionic low osmolar agents. The great majority prefer to use nonionic low osmolar contrast media for all their i.v. work, even in the absence of identifiable risk factors for adverse reactions. All of those not routinely using non-ionic contrast agents do so for patients they perceive to be at increased risk, in accordance with the Royal College of Radiologists' current guidelines [1]. In 53 (31.2%) of the consultants' departments there is a policy regarding the use of corticosteroid prophylaxis. This proportion varies depending on the type of hospital; 44.6% in teaching hospitals, 30.0% in district general hospitals affiliated to a teaching hospital, 23.5% in district general hospitals. We documented the use of prophylactic corticosteroids by offering a choice of oral, i.v., or no steroid cover for various categories of patient when using i.v. contrast media (Question 7). Deciding not to perform a contrast examination was not offered as an option in our questionnaire but this was spontaneously volunteered in some cases. Seventy-three out of 170 (44.7%) never use steroid cover. The practices of the 94 consultants who do use steroid cover vary greatly depending on the clinical scenario, as is shown in Table 1. There is a trend of increasing numbers of radiologists using steroid cover with increasing severity of asthma (categories (a) to (e) in Table 1). This pattern is also generally observed within individuals' responses. However, the case of an asthmatic patient currently requiring oral corticosteroid treatment (category (d)) produced a dichotomy of responses. Eleven radiologists who give steroid cover for patients with milder asthma would not do so for this category of patient. Conversely, 11 radiologists first give steroid cover at this level o f asthma severity; eight orally, three intravenously. The pattern of steroid usage in a patient with a history of previous mild contrast reaction is similar to that for an asthmatic currently on inhaled steroids. However, a previous severe contrast reaction produced by far the most aggressive pretreatment. In fact, for 21 radiologists, it is the only situation in which steroid cover is used. I f this category is excluded on the basis that a contrast examination would usually be avoided, the number of

radiologists using steroid cover falls to 73 out of 170 (42.9%), and to 61 (35.9%) if previous mild contrast reactions are also excluded. Allergies to other drugs or substances, hayfever and eczema, prompted a very low rate of steroid prophylaxis. We also assessed radiologists' usual practice when administering contrast media by other routes (Question 8). Total numbers are less than 170 as each route is not used by all those who replied. Thirty-six of 153 (24.2%) give steroid cover for intra-arterial contrast. Two of these are radiologists who do not give cover for i.v. contrast. Fourteen of 139 (10.1%) give cover for intrathecal contrast (three would not perform the investigation at all in at-risk patients). Sixteen of 149 (10.7%) give cover for contrast instilled into other cavities (for example, hysterosalpingography or antegrade pyelography). We asked all those using steroid prophylaxis for details of the regimes used. All 96 radiologists who use steroid cover stated the drug, or drugs used, as shown in Table 2. Exact dosage regimes were given for 97 of the 114 individual drug choices. In terms of drug, dosage and timing of administration, there was a total of 67 different regimes; the total steroid doses used, expressed as an equivalent dose of prednisolone [3], varied from 7.5 mg to 400mg. Thirty-three radiologists specified an i.v. regime. The commonest, used by 19 of 33, was 100mg hydrocortisone, given 0-20 min before injection of the contrast agent. There was great variation in the oral drug regimes given. O f the 72 radiologists using oral corticosteroid prophylaxis, 64 specified the dose regime used; 55 of these were different. The commonest regime stated was prednisolone, 10mg three times daily for 3 days

Table 2 - Cortieosteroids used for prophylaxis

No. of No. who No. of radiologists specified different using drug dose regime regimes given

Oral dexamethasone 6 Oral prednisolone 65 Oral hydrocortisone 1 Intravenous hydrocortisone 40 Intravenous dexamethasone 2

5 58 1 32 1

4 50 1 11 1

Total of 96 radiologists, maximum of two drugs cited by any individual.

CORTICOSTEROID PROPHYLAXIS

Table 3 - Summary of results 170 (80.2%) of questionnaires completed 65 teaching hospital consultants 20 consultants from DGH affiliated to teaching hospital 85 DGH consultants For routine intravenous use: 30 (17.6%) use hyperosmolar contrast agents 6 (3.5%) use ionic low osmolar agents 134 (78.8%) use non-ionic low osmolar contrast media 53 (31.2%) have local departmental policy regarding steroid cover 44.6% of teaching hospitals 30.0% of DGHs affiliated to teaching hospital 23.5% of DGHs 76 (44.7%) never use steroid cover for i.v. contrast media 94 (55.3%) use steroid cover, but with great variation in practice 97 steroid regimes specified; 67 of them different

before the injection of contrast agent (used by three radiologists). The total dose of prednisolone prescribed varied from 10mg to 200rag, the commonest being 120mg (used in nine of the 58 regimes given for oral prednisolone). There was also great variation in the timing of the steroid doses (either just before, or both before and after the injection of contrast media), and the length of course used (the longest lasting 4 days). Finally, we asked 'would you welcome nationally agreed guidelines for the use of steroid cover?' One hundred and forty-two (83.5%) answered 'yes' to this question. Despite the leading nature of the question, 18 (10.6%) replied 'no', and in 10 cases (5.9%) the reply was equivocal. The results of this survey are summarized in Table 3. DISCUSSION All those who replied to our questionnaire follow the current guidelines issued by the Royal College of Radiologists [1] regarding the use of low osmolar contrast media, and the majority have abandoned altogether the i.v. use of ionic agents. However, the results of this survey confirm that there is no consensus amongst UK radiologists in the use of corticosteroid prophylaxis for contrast investigations in patients considered to be at increased risk of adverse reactions. Whilst a small majority of radiologists do use steroid cover, we have shown how the use of steroid prophylaxis varies with different levels of perceived risk of adverse reaction. This raises the question whether the degree of severity of a patient's asthma, for example, has any influence on that patient's likelihood of having a contrast reaction, and how it influences the supposed efficacy of steroid prophylaxis. Intra-arterial, intrathecal and other non-vascular routes of administration of contrast agent generally result in less use of steroid prophylaxis. The most dramatic variation in practice is in the corticosteroid regime used. Dawson and Sidhu [2] have reviewed the literature and have concluded that the evidence in favour of steroid prophylaxis is, at best, flimsy. At the time of their review, the only regime shown in a properly controlled trial to have any

793

potential value is the administration of two doses of 32mg methylprednisolone orally approximately 12 and 2 h before the injection of contrast agent [4], although the results of this study are disputed [5-8]. It is of interest that, of the 90 radiologists in our survey who use steroid cover, none uses this precise regime (or its equivalent using two doses of 40 mg prednisolone, 6 mg dexamethasone or 160 mg hydrocortisone [3]). Lasser et al.'s study only examined the combination of steroids with ionic contrast media and Dawson and Sidhu make the point that it is not possible to extrapolate this possible beneficial effect to the use of non-ionic, low osmolar contrast agents. In a more recent study, Lasser et al. [9] have attempted to address this question. In their randomized, blinded study of 1155 patients undergoing urography or contrast-enhanced CT using non-ionic contrast media, they showed a reduction in the incidence of mild reactions and overall reactions in those patients receiving pretreatment with two 32mg oral doses of methylprednisolone, 6-24 and 2 h before the injection of contrast agent. They did not demonstrate a statistically significant reduction in the incidence of moderate or severe reactions. Their classification of mild reactions includes only sneezing, nausea, vertigo or a single episode of emesis. Nausea and vomiting are usually either of little clinical significance or are easily treated, and we do not believe corticosteroid pretreatment for all patients is indicated to reduce the incidence of vertigo and sneezing. In discussing this study, Dunnick and Cohan [10] conclude that corticosteroid pretreatment is recommended for patients at increased risk of adverse reactions. Lasser et al. did not, however, compare the effect of pretreatment with either placebo or corticosteroid in high-risk patients. Their results cannot, therefore, be interpreted as offering evidence for a beneficial effect in this group of patients. We have demonstrated a wide variety of practice in this country and a desire for consensus in the form of guidelines. There seems to be general acceptance of the current advice regarding the use of low osmolar contrast agents, but there is difficulty in formulating guidelines for concomitant steroid prophylaxis as there is no experimental evidence regarding the effect of corticosteroid prophylaxis in high risk patients receiving low osmolar contrast agents. Several consultants in our survey commented that they had already forsaken steroid prophylaxis on the strength of Dawson and Sidhu's review which was published in October 1993. Others made the point that guidelines in a matter such as this would result in unhelpful medicolegal restraints. Perhaps the only conclusion that can be drawn currently is that, at least in the UK, there is a body of opinion that supports the abandonment of corticosteroid prophylaxis. We believe that there is justification for a controlled trial of the effect of corticosteroid pretreatment for highrisk patients receiving low osmolar contrast agents. Acknowledgements. We thank Bernadette Dickinson and Rachel Ashcroft of the Medical Audit Department, University Hospital of Wales, for their assistance.

REFERENCES 1 Dawson P, Grainger RG. Guidelines for use o f low osmolar contrast agents. Faculty of Clinical Radiology of Royal College of Radiologists, 1992.

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CLINICAL RADIOLOGY 6 Wolf GF. Letter to the Editor. New England Journal of Medicine 1988;318:856. 7 Baudoin CJ, Wilkins RA. Letter to the Editor. New England Journal of Medicine 1988;318:856. 8 Ackroyd JF. Letter to the Editor. New England Journal of Medicine 1988;318:856. 9 Lasser EC, Berry CC, Mishkin MM et al. Pretreatment with corticosteroids to prevent adverse reactions to nonionic contrast media. American Journal of Roentgenotogy 1994; 162:523-526. 10 Dunnick NR, Cohan RH. Cost, corticosteroids, and contrast media. American Journal of Roentgenology 1994; 162:527-529.

2 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;48:225-226. 3 British National Formulary, No. 26. British Medical Association and Royal Pharmaceutical Society of Great Britain, September, 1993: 261. 4 Lasser EC, Berry CC, Talner LB et al. Pretreatment with corticosteroids to alleviate reactions to intravenous contrast material. New England Journal of Medicine 1988;317:845-849. 5 Rose TG. Letter to the Editor. New England Journal of Medicine 1988;318:856.

APPENDIX 1 Survey of the Use of 'Steroid Cover' for Radiologieal Contrast Investigations 1 Do you work mainly in a: (a) (b) (c) (d)

Teaching hospital D G H affiliated to teaching hospital DGH Private hospital

[] [] [] []

2 Please indicate if you work mainly in a specialist area of clinical radiology, if so, what?

3 What family of water soluble contrast media (CM) do you use routinely for intraVENOUS administration? (a) 'Conventional' high osmolarity CM (b) Ionic low osmolarity (LO) CM (c) Non-ionic LOCM

[] [] []

4 If your answer is 'Yes' to (a) or (b), do you change to LOCM for patients with increased risk of adverse reactions to CM?

Yes No

[] []

5 Does the department in which you work have a policy regarding steroid prophylaxis ('steroid cover') for patients with increased risk of adverse reactions to CM?

Yes No

[] []

6 Regardless of departmental policy, do you yourself ever give 'steroid cover'?

Yes No

[] []

7 If your answer is 'Yes' to question 5 or 6, please indicate your practice when using intraVENOUS CM in the following circumstances: Oral steroid cover

Intravenous steroid cover

No steroid cover

(a) Previous history of mild asthma, not currently being treated.

[]

[]

[]

(b) Mild asthma requiring occasional treatment with inhalers.

[]

[]

[]

(c) Asthma currently requiring treatment with inhaled steroids.

[]

[]

[]

(d) Asthma currently requiring treatment with oral steroids.

[]

[]

[]

(e) Previous history of severe asthma, e.g. requiring ITU treatment.

[]

[]

[]

(f) Previous mild contrast reaction.

[]

[]

[]

(g) Previous severe contrast reaction.

[]

[]

[]

(h) Known drug or other allergy.

[]

[]

[]

(i) History of hayfever.

[]

[]

[]

(j) History of eczema.

[]

[]

[]

you give 'steroid cover' for patients with increased risk of adverse reaction when you administer CM by the following routes: Do

(a) Intra-arterial contrast

Yes

[]

No

[]

(b) Intra-thecal contrast

Yes

[]

No

[]

(c) Other body cavities (e.g. hysterosalpingography, antegrade pyelography)

Yes

[]

No

[]

CORTICOSTEROID PROPHYLAXIS

9 Please indicate the steroid(s) you use and the dose regime(s) you use.

Drug

Dose regime

Oral Prednisolone

[]

Oral Dexamethasone

[]

Intravenous Dexamethasone Oral Hydrocortisone

[]

Intravenous Hydrocortisone

[]

Other (please specify)

[]

10 Would you welcome nationally agreed guidelines for the use of steroid cover? Yes

[]

11 Comments:

No

[]

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