a b s t r a c t

Objectives: Adverse reactions to intravenous (IV) iodinated contrast media are classified by the American College of Radiology (ACR) Manual on Contrast Media as either allergic-like (ALR) or physiologic (PR). Premedication may be beneficial for patients who have prior documented mild or moderate ALR. We sought to perform a retro- spective analysis of patients who received computed tomography (CT) imaging in our emergency department (ED) to establish whether listing of an iodinated contrast media allergy results in a delay in care, increases the use of non-contrast studies, and to quantify the incidence of listing iodinated contrast allergies which do not necessitate premedication.

Methods: We performed a retrospective analysis of CT scans performed in our academic medical center ED during a 6-month period. There were 12,737 unique patients of whom 454 patients had a listed iodinated contrast al- lergy. Of these, 106 received IV contrast and were categorized as to whether premedication was necessary. De- scriptive statistics were used to evaluate patient demographics, clinical characteristics, and operational outcomes. A Multivariate linear regression model was used to predict time from order to start (OTS time) of CT imaging while controlling for co-variates.

Results: Non-allergic patients underwent contrast-enhanced CT imaging at a significantly higher rate than allergic patients (45.9% vs. 23.3%, p < 0.01). The OTS time for allergic patients who underwent contrast-enhanced CT imaging was 360 min and significantly longer than the OTS time for non-allergic patients who underwent contrast-enhanced CT imaging (118 min, p < 0.001). Of the 106 allergic patients who underwent contrast- enhanced CT imaging, 27 (25.5%) did not meet ACR criteria for necessitating premedication. The average OTS time for these 27 patients was 296 min, significantly longer than the OTS for non-allergic patients (118 min, p < 0.01) and did not differ from the OTS time for the 79 patients who did meet premedication criteria (382 min, p = 0.23). A multivariate linear regression showed that OTS time was significantly longer if a contrast allergy was present (p < 0.001).

Conclusion: A chart-documented iodinated contrast allergy resulted in a significant increase in time to obtain a contrast-enhanced CT study. This delay persisted among patients who did not meet ACR criteria for premedication. Appropriately deferring premedication could potentially reduce the ED length-of-stay by over4h for these patients.

(C) 2022

1. Introduction

Computed tomography (CT) imaging use has increased substantially over the past two decades and is commonly the primary tool used by

* Corresponding author at: 55 Fruit St., Boston, MA 02114, USA.

E-mail address: [email protected] (A.M. Prabhakar).

emergency physicians to confirm or rule-out a diagnosis [1,2]. The use of intravenous (IV) iodinated contrast media is essential for the evalua- tion of patients presenting to the emergency department (ED) with concerns for vascular pathology such as aortic dissection, pulmonary embolism, or cerebrovascular accident (CVA) and crucial for better di- agnostic quality for many other conditions such as intra-abdominal or skin and soft tissue infections [3,4].

https://doi.org/10.1016/j.ajem.2022.08.052

0735-6757/(C) 2022

There are over 70 million CT scans estimated to be performed annu- ally in the United States and about 75 million doses of iodinated contrast media injected annually [5,6]. The safety of iodinated contrast media is

Table 1

Cohort demographics.

Full Cohort

well-established with acute adverse reactions estimated to be between 0.15%-0.7% with >95% of those being mild and self-limited [7-10]. Fur- thermore, deaths from administration of iodinated contrast media are estimated to be between 2 and 9 per one million administrations [11,12]. The safety of contrast media has significantly improved since 1995 with the advent of low-osmolality contrast media (LOCM), with incidence of reactions now 10-fold lower than with high-osmolality contrast media (HOCM) that has been largely phased out of use [13].

Adverse reactions to IV iodinated contrast media are classified by the American College of Radiology (ACR) Manual on Contrast Media as ei- ther allergic-like (ALR) or physiologic (PR) [13]. Each is classified by the ACR on a spectrum of severity as mild, moderate, or severe. Exam- ples of ALR include urticaria, pruritis, “scratchy” throat, rhinorrhea, con- junctivitis, and anaphylaxis. Examples of PR includes nausea, vomiting, flushing, warmth, chills, headache, dizziness, anxiety, hypertension, chest pain, and vasovagal reactions. A recent ED-based study confirmed the incidence of allergic-like contrast reactions (ALR) to be 0.2% [14].

Patients with a prior documented ALR or unknown contrast reaction are at a five-fold greater risk of a future ALR [13,15,16]. Given the indis- pensability of IV contrast media use there exist two premedication reg- imens that are commonly used: a standard 12-13 h oral regimen typically used in the outpatient setting and an IV 4-5 h regimen often used in the emergency department [13]. Expert consensus is that premedication to reduce the risk of a reaction is recommended and may be beneficial for patients who have prior documented mild or mod- erate ALR, albeit with a number needed to treat to prevent a death esti- mated to be about 50,000 [13,17,18]. There is no benefit for premedication in the event of prior PR and premedication is not known to prevent future PR [13].

It is well established that allergies to shellfish, seafood, and topical io- dine do not increase risk of an adverse reaction to iodinated contrast [19-24]. Nevertheless, there is a common misconception among both pa- tients and medical providers that allergies to these should result in premedication for iodinated contrast media. A 2008 study of faculty radiol- ogists and cardiologists at six academic medical centers found that 69% of these physicians ask about a history of allergies to seafood before ordering iodinated contrast, and 37% would withhold contrast or premedicate if a history of seafood allergies is indicated by the patient [25,26]. Similarly, a survey of emergency physicians (EP) and radiologists in 2019 found that the majority indicated that patient-reported iodine allergy limited ability to receive iodinated contrast media or required premedication [26].

At our institution it is common practice to perform a premedication protocol if choosing to proceed with an IV contrast injection in a patient with a listed allergy to iodinated contrast regardless of the listed allergy. It is likely that this results in providers choosing suboptimal non- contrast studies to avoid delays in care even if patients could have ap- propriately skipped premedication and received a contrast-enhanced CT study. We sought to perform a retrospective analysis of patients who received CT imaging in our emergency department to establish whether listing of an iodinated contrast media allergy results in a delay in care or increases the use of non-contrast studies. We addition- ally aimed to quantify the incidence of iodinated contrast media aller- gies listed which do not necessitate premedication by ACR guidelines.

1. Methods

This study was evaluated by our Institutional Review Board and approved with exemption.

• 1. Setting and design

This study was conducted at a large academic medical center which has 1019 licensed operational beds and carries level 1 trauma,

Number in Cohort 12,737

Age mean (Q1-Q3) in years 59 (43-74) Sex

Male 6335 (49.7%)

Female 6401 (50.3%)

Unreported 1 (0%)

Contrast Allergy Reported

Yes 454 (3.6%)

No 12,283 (96.4%)

Contrast Administered

Yes 5749 (45.1%)

No 6988 54.9%)

STEMI-receiving center, and stroke center designations. Its emergency department sees approximately 110,000 visits per year.

We performed a retrospective analysis of CT scans performed in this ED between 3/1/2019 and 8/31/2019. We queried the electronic medi- cal record (Epic Systems, Verona, Wisconsin) for all CT scans performed in the ED during our 6-month study period along with pertinent patient information and demographics including age, sex, CT protocol details, and contrast allergy status (Table 1).

The initial query yielded 20,760 entries during the 6-month study period, with each entry corresponding to a different CT scan. Of these, there were 12,737 unique patients. A total of 454 of these patients had a listed iodinated contrast allergy, of which 106 received IV contrast. Pa- tients with an erroneously listed gadolinium contrast allergy or iodin- ated contrast allergy listed on or after the date of the index scan were excluded from the study.

• 1. Categorization

The 106 patients who had a contrast allergy and received IV contrast were each categorized as to whether premedication for that patient was necessary based on ACR guidelines. A chart-review was performed by the authors (YB, DCW, JAF) to manually extract all available information from the allergy tab within the EMR regarding the listed iodinated con- trast allergy. Each patient was then categorized independently by two authors (YB and JAF) as to whether premedication was necessary based on ACR guidelines. The authors agreed on classification for 85/ 106 (80.2%). The remaining 21 were categorized by a blinded third au- thor who is a fellowship-trained board-certified emergency radiologist (MDS).

• 1. Statistical analysis

Descriptive statistics were used to categorize patient demographics, clinical characteristics, and operational outcomes. We assessed for sta- tistically significant differences among different patient groups using the two-tailed Student’s t-test for continuous variables. A multivariate linear regression model was used to predict time from order to start of CT scan (OTS time) while controlling for several co-variates. All statistics were performed either in Microsoft Excel, R, or SAS Analytics Software.

1. Results

The fraction of patients without listed contrast allergies (non-aller- gic patients) who underwent contrast-enhanced CT imaging was 5643/12283 (45.9%) and was significantly higher than the fraction of patients with a listed contrast allergy (allergic patients) who underwent contrast-enhanced CT imaging (45.9% vs. 23.3%, p < 0.01).

The average OTS time for all patients regardless of contrast use was 113 min. The OTS time for allergic patients who received IV contrast was 360 min and significantly longer than the OTS time for non- allergic patients who received IV contrast (Table 2, 118 min, p < 0.001).

Table 2

Average time from order to start of CT imaging (OTS time).

N Average OTS time (min)

P-value

At our institution, allergies can be added to the electronic medical re- cord by patients or any clinical employee – whether a physician, nurse, advanced practice provider, or technician. Given wide-spread miscon- ceptions about iodinated contrast allergies, many entries lack critical in-

Full cohort 12,737 113 –

Allergic and received contrast 106 360 p < 0.001

Non-allergic and received contrast 5643 118

formation regarding the origin of the allergy. Listed “allergies” may instead actually represent physiologic adverse reactions, allergies to seafood or iodine, allergies to unrelated contrast media such as gadolin-

Allergic, received contrast, met ACR criteria

for premedication

Allergic, received contrast, did not meet

79 382

p = 0.23

ium, or relative contraindications such as chronic kidney disease. Once listed, these allergies are often carried forward indefinitely and can

ACR criteria for premedication 27 296

lead to unnecessary delays in obtaining contrast-enhanced CT studies

Allergic, received contrast, did not meet ACR criteria for premedication

27 296

p < 0.001

or suboptimal images from non-contrast scans.

While we found that over a quarter of patients in our cohort with a

Non-allergic and received contrast 5643 118

Of the 106 allergic patients who received IV contrast, 27 (25.5%) did not meet ACR criteria for necessitating premedication prior to the ad- ministration of contrast. The average OTS time for these 27 patients was 296 min, significantly longer than the OTS for non-allergic patients who received contrast (Table 2, 118 min, p < 0.01) and did not differ from the OTS time for the 79 allergic patients who did meet ACR criteria for premedication (Table 2, 382 min, p = 0.23). Of these 27 patients, 5 did not need premedication as their allergy listing was an unrelated re- action (i.e., eye burning sensation after exam), 4 had an incorrect agent listed (i.e., topical iodine, shellfish, gastrografin), 4 had a relative contra- indication listed (i.e., kidney injury), and 14 had a physiologic reaction (i.e., nausea, hypertension, etc.).

A multivariate linear regression showed that OTS time was signifi- cantly longer if a contrast allergy was present (p < 0.001) even while controlling for age, contrast administration, and the interaction between contrast allergies and contrast administration.

1. Discussion

Due to the severity of ED crowding in the United States and its many known negative effects on patient care [27-34], efforts to decrease ED length of stay have become a top priority for Hospital systems and emergency departments. Our study assessed the impact of chart- documented iodinated contrast allergies on emergency department operations. In our single site study, we demonstrated that a chart- documented iodinated contrast allergy resulted in a significant increase in time to obtain a contrast-enhanced CT study and that this effect persisted among patients who did not meet ACR criteria for premedication. There are several important conclusions from this study:

First, we showed that listing of an iodinated contrast allergy in the medical chart results in a delay in time from order to start of contrast- enhanced CT imaging by an average of >4 h.

Second, we demonstrated that in our cohort over 25% of patients who had a listed iodinated contrast allergy did not meet ACR criteria for premedication but nevertheless experienced a major delay in care. There was no difference in time from order to start of contrast- enhanced CT imaging between those patients’ necessitating preme- dication by ACR criteria and those who do not.

Third, we showed that the fraction of patients undergoing CT imag- ing who also receive IV contrast is significantly larger among patients without a listed iodinated contrast allergy compared to patients with a listed contrast allergy (45.9% vs. 23.3%). As there is no reason to suspect that patients with contrast allergies require different imaging modali- ties than patients without contrast allergies, this finding strongly sug- gests that clinicians may choose non-contrast-enhanced imaging in patients with a listed iodinated contrast allergy for cases when they would typically order contrast-enhanced imaging otherwise. This may stem from the ordering clinician trying to avoid the anticipated delay in care resulting from the premedication protocol and may result in sub- optimal imaging studies.

listed iodinated contrast allergy who underwent contrast-enhanced CT imaging did not necessitate premedication, this likely undercounts the true percentage of patients who can forego premedication. A large num- ber of contrast allergy entries did not include detailed information about the allergy; we treated these as true allergic-type reactions to be conser- vative. Due to the importance of maintaining patient safety, only those allergy entries which specifically included adequate information to de- termine that premedication was not necessary were counted as such in our study. Efforts to clarify and recategorize reaction types with pa- tients in the ED might yield a much higher percentage not requiring pre-medication.

There are several limitations to our study. First, this is a single-site retrospective study which may limit generalizability. Second, we only performed chart-review on patients with listed iodinated contrast aller- gies who received contrast-enhanced imaging. It is possible that there is a selection bias for those with relatively less severe allergies in this group and that we are overestimating the fraction of patients who can forego premedication. Third, it is possible that at institutions outside of our own there are better protocols in place to appropriately identify patients with listed allergies that do not necessitate premedication, lim- iting the generalizability of our study. Fourth, it is conceivable that pa- tients without listed iodinated contrast allergies are undergoing unnecessary contrast-enhanced CT imaging, which could account for some of the difference in proportion of contrast-enhancement among those with and without listed allergies to contrast.

Our results show that one potential area for improvement in ED op- erational efficiency is to appropriately defer premedication in patients who have clearly documented physiologic-type reactions or relative contraindications to iodinated contrast media, potentially reducing ED length-of-stay by over 4 h for these patients. Future studies are needed to assess the clinical impact of the decreased use of contrast-enhanced CT imaging among patients with listed allergies to iodinated contrast, to determine the effectiveness and operational impact of a policy to identify patients who can forego premedication, and to determine whether our results are generalizable to other institutions.

Sources of support/funding

Summary conflict of interest statement: None. Prior abstract publication/presentation: None.

Conflict of Interest Disclosure: All authors report no conflict of interest.

CRediT authorship contribution statement

Yosef Berlyand: Conceptualization, Data curation, Formal analysis, Investigation, Methodology, Validation, Writing – original draft, Writing – review & editing. John Anthony Fraga: Data curation, Formal analysis, Writing – original draft, Writing – review & editing. Marc D. Succi: Con- ceptualization, Data curation, Formal analysis, Investigation, Methodol- ogy, Supervision, Writing – original draft, Writing – review & editing. Brian J. Yun: Data curation, Formal analysis, Investigation, Methodol- ogy, Writing – review & editing. Andy Hung-Yi Lee: Conceptualization, Methodology, Writing – review & editing. Joshua J. Baugh:

Conceptualization, Formal analysis, Investigation, Methodology, Writ- ing – review & editing. David Whitehead: Conceptualization, Formal analysis, Writing – review & editing. Ali S. Raja: Data curation, Writing – review & editing. Anand M. Prabhakar: Data curation, Formal analy- sis, Investigation, Methodology, Supervision, Writing – original draft, Writing – review & editing.

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