Adverse Reactions Following Administration of an Ionic Iodinated Contrast Media in Anesthetized Dogs

Introduction

Iodine-based contrast agents are commonly used in contrast-enhanced computed tomography (CT) and can be subdivided into ionic and nonionic categories. Prior to a CT scan, the iodinated contrast medium is administered to the patient IV so that areas of high vascularity and increased vascular permeability are more clearly visualized, facilitating diagnosis.¹ Although ionic iodinated contrast (IIC) agents provide significant diagnostic benefits, there is some risk of contrast medium-related adverse events in a small percentage of canine patients.^2,3 Adverse effects associated with IIC agents range from mild reactions such as fever, skin manifestations, tachycardia, bradycardia, hypotension, hypertension, and acute gastrointestinal tract disturbances to more severe reactions such as bronchospasm, shock, and cardiac and respiratory arrest.²

Adverse events linked to IIC agents are well documented in human patients and can be classified as either acute or delayed.^4–6 Acute reactions are more prevalent and usually occur within the first hour following contrast medium administration. In fact, 70% of reactions occur within the first 5 min.⁴ Acute reactions are further subdivided into mild, intermediate, and severe reactions.⁵ Mild reactions usually do not require treatment whereas both intermediate and severe reactions often require medical intervention and hemodynamic support.⁵ Delayed reactions are uncommon, typically involve skin rashes, and occur >1 hr postadministration but within 7 days of contrast medium administration.⁵ Previous investigations involving human patients reported that mild reactions following IV administration of IIC agents were experienced by 1–2% of the general population.⁷ Severe and very severe reactions were more uncommon, affecting only 0.22% and 0.04% of the population, respectively.⁴ In one large retrospective study, reactions secondary to ionic contrast media occurred at four times the rate of reactions secondary to nonionic contrast media.⁴

Despite the abundance of studies investigating the adverse effects of iodinated contrast medium in people, there is a dearth of information regarding adverse reactions in animals within the veterinary literature. One recently published case report documented the development of an acute severe systemic reaction in two canine patients administered an IIC.² Both dogs developed marked changes in heart rate (HR) and systolic arterial blood pressure (SAP) either during or immediately following the IV injection of the contrast medium. One recent retrospective study suggested that hemodynamic alterations are relatively common following IV administration of contrast agent in anesthetized dogs.³ In that study, 3% of dogs that received an IIC agent developed a HR outside the normal range that was a ≥20% change from the baseline HR. In addition, 4% of dogs developed a SAP outside the normal range within 20 min of agent administration that was a ≥20% change from baseline SAP. Changes in HR and peak systolic blood pressure were less common in dogs that received a nonionic iodinated contrast agent. In the authors’ clinical experience, the incidence of either hypotension or hypertension in response to contrast injection is dramatically higher than previously reported.

The purpose of this study was to identify the frequency of hemodynamic alterations associated with the IV administration of IIC media in anesthetized canine patients instrumented with direct arterial pressure monitoring. It was hypothesized that dogs would experience a relatively high rate of complications following injection of an IIC agent.

Materials and Methods

Results

After reviewing medical records for patients administered an IV IIC media (sodium iothalamate, 400 mg I/mL^d) during a CT scan, a total of 49 dogs met the inclusion criteria. A variety of breeds was represented in this study, with no breed being substantially overrepresented. The mean age (and standard deviation [SD]) was 7.3±3.6 yr, and body weight was 22.0±12.8 kg. Body temperature at the time of injection was 38.5±0.8°. The sex distribution of the patients was 20 castrated males, 14 males, 12 spayed females, and 3 females. The mean duration of anesthesia was 152±107 min, and the contrast dose was 1.94±0.38 mL/kg (776±152 mg I/kg). All dogs were hemodynamically supported with IV fluids during anesthesia.

In total, 28/49 dogs (57%) experienced an increase from baseline hemodynamic conditions (either HR or MAP increasing 10% or more), 18/49 dogs (37%) experienced a decrease from baseline hemodynamic conditions, and 3/49 dogs (6%) experienced no change after administration of an IIC media. Four dogs (8%) became tachycardic, experiencing a ≥20% increase in HR from the baseline value, and two dogs (4%) became bradycardic, experiencing a ≥20% decrease from the baseline value. Eight dogs (16%) became hypertensive, experiencing a ≥20% increase in MAP from the baseline value, and two dogs (4%) became hypotensive, experiencing a ≥20% decrease from the baseline value. In all, 18 dogs (37%) developed a ≥20% change in either HR or MAP, but no dog developed a ≥20% change in both HR and MAP. For RPP, 18 dogs (37%) had an increase of ≥10%, 12 dogs (24%) had a decrease of ≥10%, and 17 dogs (35%) had no change. Thirteen patients (27%) had an increase in RPP ≥20% from the baseline value, and four patients (8%) had a decrease in RPP ≥20% from the baseline value. Ten dogs (20%) received treatment for a change in either HR or MAP. Treatment consisted of dobutamine^d (n=5), intermittent positive-pressure ventilation (n=2), atropine^e (n=1), change in body position (n=1), and reducing the IV fluid rate (n=1).

There were no significant differences in the variables recorded between dogs experiencing an increase in hemodynamic conditions versus dogs experiencing a decrease in hemodynamic conditions for any of the variables tested. There were no significant differences between dogs that had a 10% change from baseline versus those who did not for any of the variables tested. There were no significant differences between dogs experiencing an AR versus those who did not experience an AR.

Discussion

Results of this study indicate that physiologically important changes in HR and blood pressure occurred following IV administration of an IIC media in anesthetized canine patients. The percentage of dogs in this study developing significant alterations in hemodynamic conditions was considerably higher than in previous studies involving humans or dogs.^3,8 The canine patients included in this study developed both increases and decreases in HR and arterial pressure in association with IIC media administration. The mechanism through which these alterations occur is currently unknown. Contrast-induced reactions are vaguely understood in humans and are likely to be related to a combination of factors, including peripheral effects on the vasculature and primary effects on the myocardium.⁹ The pathophysiology of IIC media reactions is still under debate, although most are considered nonallergic hypersensitivity (anaphylactoid) reactions because no previous exposure is necessary to trigger this type of event and antibody-antigen complexes have not been demonstrated.⁴ Anaphylactoid responses are typically related to the osmolality, viscosity, and chemotoxic effects of the medium. The IV introduction of hyperosmolar substances, specifically iodinated contrast media, results in rapid expansion of the plasma volume through osmosis of extravascular and intracellular fluid.⁹ The hyperosmolality of the intravascular medium results in peripheral vasodilation with subsequent hypotension, followed by the release of vasoactive substances (such as histamine) and the inhibition of acetylcholinesterase.⁶ Contrast medium injection is also associated with cardiac electrophysiologic alterations, including changes in sinus rate, intracardiac conduction velocity, and duration of the ventricular depolarization-repolarization process. These changes result in a subsequent predisposition to tachyarrhythmias, which is of more concern when performing selective angiocardiography.^9,10

In 20% of the patients included in this report, the supervising anesthetist found the changes in HR and blood pressure sufficient enough to warrant treatment. This finding emphasizes that these changes are clinically significant and may result in profound effects on the patient. There were no identifiable factors that separated the dogs that had a severe reaction from those that did not. This finding has not been previously investigated in dogs. In people, a history of allergies, cardiac disease, renal disease, dehydration, age extremes, anxiety, and medication administration are considered risk factors for an adverse reaction to IIC.⁵ Allergy history is not typically obtained in the authors’ hospital so that variable could not be pursued. However, no other factors, such as breed, age, or sex, were identified as risk factors, suggesting that reactions to the IIC are idiosyncratic in dogs. The sample size was relatively small in this study, which means that subtle risk factors may have eluded statistical significance as a result.

The frequency and intensity of hemodynamic alterations in canine patients in response to administration of IIC media were considerably higher in the current study than in previously published studies involving both human and canine patients.^3,4 A deeper level of anesthesia produces greater cardiovascular depression on a dose-dependent basis, and end-tidal inhalant anesthesia concentrations were not measured in this study.¹¹ A difference in anesthetic protocol, region of the country, or type of patient between this study and the previous study in dogs may explain the observed difference in the reaction rate to IIC. The same contrast medium, dose, and rate of injection were used in both studies, indicating that the difference in reaction rate noted in this report is not due to the contrast agent.

Direct arterial pressure was chosen as an inclusion criterion for this study to minimize the bias introduced by noninvasive blood pressure monitoring techniques. Direct arterial blood pressure is considered the gold standard for pressure monitoring. Noninvasive techniques are generally considered sufficient for most clinical monitoring, but may be too variable to rely on for high-fidelity data required for research on which clinical decisions may be based. Noninvasive monitoring has been shown to have greater variability compared with direct blood pressure monitoring in dogs.¹²

Conclusion

A large number of anesthetized dogs used in this study experienced a ≥20% change in HR and/or blood pressure from baseline within 15 min following IV administration of an IIC media. Both increases and decreases in HR and blood pressure occurred. Because there was no significant difference between dogs experiencing an increase in HR and blood pressure versus dogs experiencing a decrease in HR and blood pressure for sex, ASA, anesthetic drugs, age, weight, duration of anesthesia, dose of IIC, or body temperature, there appears to be no way to predict what patients are more likely to have a reaction. As advanced imaging techniques become more common in veterinary practice and the administration of IIC media is performed more frequently, an understanding of the frequency and types of reactions following contrast medium administration becomes increasingly valuable.