Other
Contrast Media
June 2001

Trends in Adverse Events After IV Administration of Contrast Media

Abstract

OBJECTIVE. Data collected from 1985 to 1999 on adverse events after the IV administration of contrast media were evaluated to identify trends.
MATERIALS AND METHODS. Data collected on 391 adverse events after 90,473 administrations of iodinated contrast media and 19 events after 28,340 administrations of gadolinium were evaluated. Reactions were graded as mild, moderate, or severe. Data were also collected regarding contrast extravasation.
RESULTS. When only ionic iodinated contrast material was used, the adverse reaction rate was 6-8%. With the selective use of contrast material, the adverse reaction rate was 0.6% and 0.7%, respectively, for ionic and nonionic agents. The rate decreased to 0.2% with the universal use of nonionic agents. More than 90% of adverse reactions were allergic-like. Seven severe reactions (0.05%) and no deaths occurred in the ionic group. During the selective use period, one death occurred in the nonionic group. No severe reactions or deaths occurred during the first 5 years of universal nonionic use. Since then, 10 severe reactions (0.02%) and one death have occurred. Seven reactions occurred in patients after helical CT angiography. The extravasation rate for iodinated contrast material has remained constant at 0.3-0.4% annually. The adverse reaction rate to gadolinium contrast material was 0.06%.
CONCLUSION. Mild and moderate adverse events are more common with ionic contrast material than with nonionic. Most reactions are allergic-like. Severe reactions are seen equally with ionic and nonionic contrast material but differ in type. The reactions were allergic-like in the ionic group but were predominantly attributable to cardiopulmonary decompensation in the nonionic group. Helical CT angiography may play a role in reactions.

Introduction

As part of our department quality assurance program, adverse events involving contrast agents have been monitored from 1985 to the present. The purpose of this study was to identify trends in adverse events from the IV administration of contrast material on the basis of the data collected.

Materials and Methods

Documentation of adverse events associated with iodinated contrast material administration began in the genitourinary section of our institution in 1985 and included all CT scanners by 1988. Only ionic contrast material was used in 1985 and 1986. From 1987 through 1990, both ionic and nonionic agents were being administered by selective use. By 1991, virtually all IV iodinated contrast material was nonionic.
Adverse events were reported on a standardized form that requested information about the nature of the event and the treatment given, the name and amount of contrast material administered, and patient identification. All adverse events were evaluated and treated by physicians. Forms were completed by the technologist or nurse. Data collection regarding extravasation of contrast material began in 1993. Data collection regarding gadolinium-based MR contrast agents also began in 1993. Internal review board approval was obtained for this study. Because the study involved retrospective chart review and analysis, with the patient's confidentiality preserved, the internal review board did not require patients to give informed consent.
Adverse reactions that were categorized as allergic-like included sneezing and nasal congestion; hives, itching, rash, and swelling; laryngeal edema; bronchospasm; and anaphylaxis. Other reactions included rigors (shaking, chills, fever); seizure; numbness; malaise and achiness; pulmonary edema; chest pain; and hypertension. With the administration of ionic contrast material, nausea, vomiting, and arm pain were also reported. Reactions were graded as mild when no therapy was required; moderate when therapy was given and the patient was sent home from the radiology department; and severe when intravascular epinephrine was used in emergent treatment or when urgent therapy was required and the patient was subsequently followed up in the emergency department or admitted to the hospital.
A chi-square test for homogeneity of proportions was used. Results were considered significant when the p value was less than 0.05.

Results

For 1985 through 1999, IV iodinated contrast media were administered in 90,473 patients in the genitourinary and CT sections. We recorded 12,916 doses of ionic contrast media, 73,039 doses of nonionic contrast media, and 4518 doses in which the type of contrast material was unknown. We noted 391 adverse reactions (0.4%).
In 1985 and 1986, when only ionic contrast media were used for excretory urography, the reaction rate was 11-12% when nausea, vomiting, and arm pain were included and 6-8% when they were excluded. Ninety-six percent of the reactions were allergic-like. The adverse reaction rate for 1987-1990, when nonionic contrast material was used selectively, was 0.6% for ionic contrast material and 0.7% for nonionic. For 1991 through 1999, when nonionic agents were used universally in our department, the adverse reaction rate averaged 0.2% (Table 1). The differences among these three groups (ionic only, selective use of nonionic, and nonionic only) are statistically significant (p < 0.001). Ninety-two percent of these adverse reactions were allergic-like. For 1992-1999, we recorded three instances (0.08%) of mild cutaneous reactions in 3607 doses of nonionic contrast media in pediatric radiology.
TABLE 1 Iodinated Contrast Media: Adverse Reaction Summary, 1985-1999
YearIonicNonionicAgent UnknownOverall
InjectionsAdverse ReactionsInjectionsAdverse ReactionsInjectionsAdverse ReactionsInjectionsAdverse Reaction Rate (%)
19990NA11,894350011,8940.3
19980NA10,749180010,7490.2
19970NA9,62527009,6250.3
19960NA8,79221008,7920.2
19950NA5,98015005,9800.3
19940NA6,4737006,4730.1
19930NA4,2267004,2260.2
19920NA6,19911006,1990.2
19910NA4,76314004,7630.3
19902,460182,54021005,0000.8
19897,191231,39821,134169,7230.4
19881,8122840062,51494,7260.9
19870NA0NA870128701.4
19867025500007027.8
1985
751
46
0
0
0
0
751
6.1
Total
12,916
170
73,039
184
4,518
37
90,473
0.43
Note.—NA = not applicable.
Data collected separately for genitourinary and CT sections from 1988 to 1991 allowed limited comparison of adverse events. In the genitourinary section, the reaction rates were 0.4% with ionic contrast material, 0.7% with nonionic, 0.8% with unknown agents, and 0.6% overall. In the CT section, the reaction rates were 0.6% with ionic contrast material, 0.4% with nonionic, 0.7% with unknown agents, and 0.6% overall. No statistically significant differences were noted among the three groups or overall when comparing reaction rates in the genitourinary section with those in the CT section.
In the genitourinary section, injections were performed manually until 1992. We converted to mechanical injectors in the CT section during 1989. Using data from 1987 to 1990 when nonionic contrast material was used selectively, and excluding 1989, more reactions occurred using hand injection than using mechanical injections for both ionic (1.5% vs. 0.7%) (p = 0.02) and nonionic (1.5% vs. 0.8%) (p = 0.02) agents and overall (1.1% vs. 0.8%) (p = 0.06). In 1990, the reaction rate using manual injections was 1.4% in the genitourinary section and 0.7% in the CT section (p = 0.02).
When the severe reactions and deaths were evaluated separately (Table 2), seven severe reactions (0.04%) and no deaths occurred in the ionic contrast material group. Ten severe reactions and two deaths occurred in the nonionic contrast group. All but one severe reaction occurred during an outpatient study. No severe reactions or deaths occurred with nonionic contrast material from 1991 to 1995, when contrast material was administered in 27,641 patients. For 1996 through 1999, ten severe reactions (0.02%) and one death occurred in 41,060 contrast material doses. Seven of the ten severe reactions occurred in patients undergoing helical CT angiography. The difference in the number of severe reactions for ionic versus nonionic agents is not statistically significant. The difference between no deaths in the ionic groups and two deaths in the nonionic group is not statistically significant (p = 0.16).
TABLE 2 Iodinated Contrast Media: Severe Reactions and Deaths in 90,473 Doses
ReactionNo.
Ionic 
Severe facial edema2
Laryngeal edema3
Bronchospasm2
Nonionic 
Bronchospasm1
Oral edema1
Seizure1
Pulmonary edema2
Chest pain4
Cardiac arrhythmia1
Death
2
Patients with severe reactions were referred to the emergency department for further treatment and examination. Both pulmonary edema reactions progressed to respiratory arrest in the emergency department. One required admission to the intensive care unit after the patient was given intubation and treated with a mechanical respirator. The four patients with chest pain were admitted to the coronary care unit for monitoring and to rule out myocardial infarction. Two of these patients showed reversible ischemia on stress tests.
The death involved a 54-year-old man who fainted 1 hr after undergoing CT urography (with negative findings) for flank pain. When he was found unconscious, his blood pressure was 220 over 110 mm Hg and 5 min later returned to 150 over 100 mm Hg. He was admitted to the hospital and had a seizure the following day. Intraventricular hemorrhage was diagnosed on CT, and he was declared brain-dead the following day. There was also one death after nonionic contrast material administration in the period of selective use. This death occurred in a 74-year-old man who had a seizure after chest CT to evaluate a lung nodule. The patient had ventricular fibrillation, and cardiopulmonary resuscitation was administered. He was transported to the emergency department, where his pupils were determined to be fixed and dilated. Mechanical ventilation was stopped 5 days later.
From 1993 to 1999, 181 contrast material extravasations (0.3%) occurred during the IV administration of nonionic contrast material with power injectors in 57,739 patients. The extravasation rate has remained stable at 0.3-0.4% annually (Table 3).
TABLE 3 Iodinated Contrast Media Extravasation, 1993-1999
YearExtravasationNo. of Doses
No.Rate
1999460.3911,894
1998340.3210,749
1997410.439,625
1996320.368,792
1995200.335,980
199470.116,473
1993
1
0.02
4,226
Total
181
0.31
57,739
From 1993 to 1999, 19 adverse reactions (0.07%) occurred in 28,340 doses of gadolinium-based MR imaging contrast material. These reactions were urticaria and itching (n = 14), nausea and vomiting (n = 4), and bronchospasm (n = 1) (Table 4). All contrast material was administered by hand injection. Extravasation occurred in 15 instances (0.05%).
TABLE 4 Gadolinium Use and Reactions, 1993-1999
YearNo. of DosesReactions (n)
19996,3096
19985,1385
19974,6824
19964,5100
19953,3542
19942,8881
1993
1,459
1
Total
28,340
19

Discussion

Significantly more mild and moderate reactions were noted with ionic contrast media than with nonionic agents. Our 6-8% adverse reaction rate for ionic contrast media and 0.2% for nonionic media are similar to rates reported in large series by Palmer [1], Katayama et al. [2], and two other groups of researchers [3, 4]. When nausea, vomiting, and arm pain reactions are excluded, most reactions are allergic-like.
Our data show that in the ionic contrast group, adverse reactions decrease significantly—from 6-8% when the general population is given ionic contrast material to 0.7%—when selective use is applied. Conversely, a significantly higher rate (0.7%) of adverse reactions was seen with nonionic contrast material during the period of selective use when high-risk patients were administered nonionic contrast material compared with the period of universal use of nonionic contrast material (0.2%). Palmer [1] reported similar findings.
We experienced more adverse reactions to iodinated contrast material when it was hand-injected than when a mechanical injector was used. However, we had fewer extravasations with hand injection of gadolinium compared with power injection of iodinated contrast material. Other groups have reported lower reaction rates with rapid injection than with slow injection [5, 6].
Severe reaction rates with ionic compared with nonionic contrast media have not been significantly different at our institution. In the first 5 years of universal nonionic contrast material use, fewer severe reactions occurred in the nonionic group than in the ionic group, which is in keeping with the findings of Palmer [1] and Katayama et al. [2]. However, since 1996, little difference is seen in severe reaction rates, which is in keeping with more recent reports by Jacobs et al. [7] and Grant and Camamo [8].
However, the types of severe reactions differed in the ionic and nonionic groups at our institution. Although all seven severe reactions in the ionic contrast group were allergic-like, only two of the ten severe reactions in the nonionic group were allergic-like. Seven of the ten severe reactions and one death in the nonionic group can be attributed to decompensation of the cardiopulmonary system. A helical CT scanner was installed in the outpatient area in 1996, and seven of the ten severe reactions occurred in patients undergoing CT angiography. Because this is a retrospective study, we do not know how many CT examinations were performed using CT angiography protocols or general CT protocols. The cluster of severe reactions in the last few years may be a statistical quirk. Alternatively, the rates and volume of contrast material used with helical CT may indicate that certain populations of patients are at greater risk. The nature of the patient population receiving contrast material may also have changed over the years.
The risk of death is very low, and no significant difference is noted in the death rates for ionic and nonionic contrast material [6, 9, 10]. Deaths average 3/100,000 for ionic contrast material and 1/100,000 for nonionic. Two deaths occurring after the use of nonionic contrast material are not outside the expected range.
Our extravasation rate of 0.3% is within the range reported in the literature of 0.25-0.6% [7, 8, 11]. We have a protocol in place for the local administration of hyaluronidase in cases of large extravasation (>50 mL). Hyaluronidase temporarily breaks down the interstitial barriers, which increases the rate of reabsorption of contrast media out of the soft tissue. To our knowledge, the use of this protocol has not resulted in any untoward consequences of extravasation.
Our adverse reaction rate of 0.07% with gadolinium-based MR contrast material is less than that reported by Murphy et al. [12] but higher than the 0.0003% reported by Neindorf et al. [13]. If nausea and vomiting reactions are excluded, our reaction rate is 0.05%.
In summary, we identified several parameters associated with differences in adverse events after the IV administration of contrast material. More mild and moderate reactions occurred with ionic contrast material than with nonionic. More mild and moderate reactions occurred with hand injection (regardless of class of contrast material) than with mechanical injection. Severe reactions were predominantly allergic-like in the ionic group but predominantly caused by cardiopulmonary decompensation in the nonionic group. Most severe reactions with nonionic contrast material occurred after helical CT angiography. More extravasations occurred with the mechanical injection of iodinated contrast material than with the manual injection of gadolinium contrast material.
Although the incidence of reactions with nonionic contrast media is low, we can still expect to experience infrequent serious adverse events. Because serious reactions are infrequent, it is important to review treatment protocols regularly (annually). Equipment and drugs need to be checked at regular intervals for expiration and availability. Drugs for initial treatment should be immediately available in rooms in which contrast material is administered. Training in basic life support or radiology life support is recommended. Knowledge, training, and preparation are crucial for appropriate aggressive therapy to control adverse reactions to contrast media.

Footnotes

Presented at the annual meeting of the American Roentgen Ray Society, Washington, DC, May 2000.
Address correspondence to S. T. Cochran.

References

1.
Palmer FJ. The RACR survey of intravenous contrast media reactions: final report. Australas Radiol 1988; 32:426-428
2.
Katayama H, Yamaguchi K, Kozuka T, Takashima T, Seez P, Matsuura K. Adverse reactions to ionic and nonionic contrast media: a report from the Japanese committee on the safety of contrast media. Radiology 1990; 175:621-628
3.
Pedersen SH, Svaland MG, Reiss AL, Andrew E. Late allergy-like reactions following vascular administration of radiography contrast media. Acta Radiol 1998; 39:344-348
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Federle MP, Willis LL, Swanson DP. Ionic versus nonionic contrast media: a prospective study of the effect of rapid bolus injection on nausea and anaphylactoid reactions. J Comput Assist Tomogr 1998; 22:341-345
5.
Ayabe Z, Nishitani H, Onitsuka H, et al. Reactions to contrast media according to injection time: incidence and clinical characteristics. Nippon Igaku Hoshasen Gakkai Zasshi 1982; 42:766-772
6.
Lawrence V, Matthai W, Hartmaier S. Comparative safety of high-osmolality and low-osmolality radiographic contrast agents: report of a multidisciplinary working group. Invest Radiol 1992; 27:2-28
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Jacobs JE, Birnbaum BA, Langlotz CP. Contrast media reactions and extravasation: relationship to intravenous injection rates. Radiology 1998; 209:411-416
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Grant KL, Camamo JM. Adverse events and cost savings three years after implementation of guidelines for outpatient contrast-agent use. Am J Health Syst Pharm 1997; 54:1395-1401
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Caro JJ, Trindade E, McGregor M. The risks of death and of severe nonfatal reactions with high- vs low-osmolality contrast media: a meta-analysis. AJR 1991; 156:825-832
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Cashman JD, McCredie J, Henry DA. Intravenous contrast media: use and associated mortality. Med J Aust 1991; 155:618-623
11.
Cohan RH, Bullard MA, Ellis JH, et al. Local reactions after injection of iodinated contrast material: detection, management and outcome. Acad Radiol 1997; 4:711-718
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Murphy KJ, Brunberg JA, Cohan RH. Adverse reactions to gadolinium contrast media: a review of 36 cases. AJR 1996; 167:847-849
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Neindorf HP, Haustein J, Cornelius I, Alhassan A, Clauss W. Safety of gadolinium-DTPA: extended clinical experience. Magn Reson Med 1991; 22:222-228

Information & Authors

Information

Published In

American Journal of Roentgenology
Pages: 1385 - 1388
PubMed: 11373197

History

Submitted: September 21, 2000
Accepted: November 8, 2000

Authors

Affiliations

Sachiko T. Cochran
Department of Radiological Sciences, UCLA School of Medicine, 10833 Le Conte Ave., Los Angeles, CA 90095-1721.
Karen Bomyea
Department of Radiological Sciences, UCLA School of Medicine, 10833 Le Conte Ave., Los Angeles, CA 90095-1721.
James W. Sayre
Department of Radiological Sciences, UCLA School of Medicine, 10833 Le Conte Ave., Los Angeles, CA 90095-1721.
Department of Biostatistics, UCLA School of Medicine, Los Angeles, CA 90095-1721.

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