What The Evidence Says:
Background:
Reactions to contrast can be classified as immediate (within 1 hour) or delayed (within 1 week). A variety of explanations have been proposed as causes of immediate reactions including IgE and non-IgE mediated mechanisms. Delayed reactions are well-known to be Type IV reactions (T-cell mediated). Neither of these reactions is anaphylactic, but rather anaphylactoid. Modern contrast-enhanced imaging uses nonionic contrast media. This has markedly reduced the prevalence of severe adverse drug reactions (ADR) in comparison to ionic contrast media (Meth 2006, Wolf 1991).
The Data
Nevertheless, hospitals use protocols to pretreat patients at risk for contrast reactions; usually with a combination of a steroid and antihistamine. These protocols typically require scans to be delayed by 4+ hours. It is widely accepted that definitive imaging should NEVER be delayed in patients who are at imminent risk to life or limb regardless of prior reactions. The risk benefit discussion in stable patients in need of emergency imaging is less clear.
Administration of steroids and antihistamines may help reduce the incidence of mild ADRs in all patients regardless of allergy history (i.e. lowers the incidence of hives or pruritus) (Greenberger 1991, Tramèr 2006). However, there is NO REDUCTION in severe ADRs (hypotension, airway compromise) requiring therapy; which is what makes a difference in the ED (Lasser 1987, Lasser 1994). Steroids may slightly decrease the already rare incidence of respiratory symptoms (~ 1% decrease) and those experiencing respiratory symptoms with hemodynamic compromise (~ 0.7% decrease), but have a number needed to treat of 100-150 (Tramèr 2006). This evidence is reflected by the American College of Radiology which recommends only treating patients with prior contrast ADRs and to avoid delaying emergency imaging for premedication in all patients (ACR 2023).
| Study | Format | Comparisons | Findings | Notes |
| Wolf et al 1991 | Observational study | Rates of ADR for ionic agent, diatrizoate/steroid, and iohexol alone (nonionic) | No difference between ADRs of any severity comparing ionic agent to diatrizoate/steroid. Only difference was between ionic and nonionic contrasts | OR for risk factors impacting ADR —
Contrast medium: 7.3 Prior ADR: 6.25 Atopy (hay fever) 2.3 |
| Greenberger and Patterson 1991 | Observational study | Rates of ADR for high-risk patients pretreated with prednisone-diphenhydramine or prednisone-diphenhydramine-ephedrine | One person developed urticaria in prednisone-diphenhydramine group, 0.5% reaction rate in pretreatment overall | Small sample size, no comparator, variety of pretreatments |
| Lasser et al 1987 | Prospective, multicenter, double-blinded RCT | Group 1 – steroid at T-12 and T-2 hours
Group 2 – steroid at T – 2 hours Groups 3/4 – placebo in above intervals |
Steroids reduced grade I* reactions for all patients, and decreased hives in high-risk patients. No difference in high-risk patients requiring therapy. Two-dose | Protocol changed to two groups halfway through because the two-dose steroid group showed superior efficacy. Omitted asthma patients in error. They ultimately compared two-dose group to combined placebo and 1-dose steroid group |
| Lasser et al 1994 | Prospective, multicenter, double-blinded RCT | Steroid T-6-24 and T-2 hours vs placebo | Reduction in grade I* reactions | |
| Tramèr et al 2006 | Systematic Review | Antihistamine or steroid, ionic or nonionic contrast
vs placebo or no treatment |
Steroids decreased rate of resp symptoms 1.4%-> 0.4% and resp + hemodynamic symptoms 0.9%->0.2%. Steroid or antihistamines decreased cutaneous symptoms | Average quality of all the trials is low and may overestimate the effect size. Severe reactions were rare, no reports of death, CPR, neuro deficits, or prolonged hospital stays. NNT is 100-150 |
*Grade I: nausea/emesis, sneezing, vertigo. Grade II: urticaria, erythema, emesis >1. Grade III: shock, bronchospasm, laryngospasm/edema, loss of consciousness, seizure, decreased/increased blood pressure, arrhythmia, angina, angioedema, pulmonary edema.
Bottom Line: Do not delay contrast-enhanced imaging in the emergency setting. The harm of delaying the contrast administration for pretreatment (which doesn’t reduce important ADRs) outweighs the potential benefits, even in patients with prior reactions.
Bonus Pearls: Iodine-allergy is a myth and is biologically impossible. Additionally, shellfish allergy does not predispose you to a contrast allergy (ACR 2023).
References
- Meth MJ, Maibach HI. Current understanding of contrast media reactions and implications for clinical management. Drug Saf. 2006;29(2):133-141. doi:10.2165/00002018-200629020-00003
- 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 [published correction appears in Invest Radiol 1991 Jul;26(7):673]. Invest Radiol. 1991;26(5):404-410. doi:10.1097/00004424-199105000-00003
- Greenberger PA, Patterson R. The prevention of immediate generalized reactions to radiocontrast media in high-risk patients. J Allergy Clin Immunol. 1991;87(4):867-872. doi:10.1016/0091-6749(91)90135-b
- Lasser EC, Berry CC, Talner LB, et al. Pretreatment with corticosteroids to alleviate reactions to intravenous contrast material. N Engl J Med. 1987;317(14):845-849. doi:10.1056/NEJM198710013171401
- Lasser EC, Berry CC, Mishkin MM, Williamson B, Zheutlin N, Silverman JM. Pretreatment with corticosteroids to prevent adverse reactions to nonionic contrast media. AJR Am J Roentgenol. 1994;162(3):523-526. doi:10.2214/ajr.162.3.8109489
- Tramèr MR, von Elm E, Loubeyre P, Hauser C. Pharmacological prevention of serious anaphylactic reactions due to iodinated contrast media: systematic review. BMJ. 2006;333(7570):675. doi:10.1136/bmj.38905.634132.AE
- American College of Radiology. ACR Manual on Contrast Media.; 2023. https://www.acr.org/-/media/ACR/Files/Clinical-Resources/Contrast_Media.pdf
Post Peer Reviewed By: Salim R. Rezaie, MD (Twitter/X: @srrezaie)
