Materials and Methods

Criteria for selection of cases—The medical records database at the University of California, Davis, School of Veterinary Medicine Veterinary Medical Teaching Hospital was searched for anesthetized cats that had received iodinated contrast media IV for computed tomography or GD-based contrast media for magnetic resonance imaging procedures between April 2005 and April 2006. Cats were included in the study population if their medical records contained information regarding HR or PSBP before (baseline) and at 5-minute intervals following IV administration of contrast media.

The medical records database was also searched for cats undergoing magnetic resonance imaging but not receiving IV administration of contrast media to provide control data. For control cats, baseline was arbitrarily defined as the measurement recorded 15 minutes after the start of the magnetic resonance imaging procedure. Values from control cats were used to establish the normal variation in HR and PSBP in anesthetized cats undergoing noncontrast imaging.

Procedure—Medical records were reviewed for information regarding breed, sex, body weight, and history. Heart rate and PSBP, as determined by Doppler, oscillometric, or direct techniques, were recorded immediately before (baseline) and for four 5-minute intervals (20 minutes) after contrast medium administration. An alteration in HR outside of reported reference range values (< 100 beats/min or > 200 beats/min) and representing at least a 20% change from baseline was defined as a reaction. An alteration in PSBP outside of reported reference range values (< 90 mm Hg or > 170 mm Hg) and representing at least a 20% change from baseline was defined as a reaction. The percentage change from baseline was included so that each cat served as its own control. Comments in the record indicating a perceived response to contrast media administration on the part of the anesthetist were noted. Conditions such as chronic bronchitis or allergic skin disease were recorded as indicators of potential hypersensitivity. The rate of reaction for each contrast medium group was further divided into cats with conditions potentially predisposing to hypersensitivity. Cats with conditions considered as potential predisposing factors for hypersensitivity were assessed for an association between allergic conditions and contrast medium–induced reactions.

When results of serum biochemical analyses were available, the serum total bilirubin (to assess for GD-induced hemolysis), BUN, and creatinine (to assess for renal effects of contrast media) concentrations were recorded for precontrast and postcontrast imaging time points. For inclusion, precontrast biochemical information must have been obtained within 5 days of the imaging procedure. The time between the collection of blood samples was noted.

Statistical analysis—Values are reported as mean ± SD. An ANOVA was used to compare age and weight of cats between the different contrast medium groups. Values of P < 0.05 were considered significant.

Results

During the inclusion period, 107 cats received GD contrast medium^a (gadopentetate dimeglumine, 469.01 mg/mL [285 mOsm/kg of water]) IV during magnetic resonance imaging, 83 of which met the inclusion criteria. One hundred and fourteen cats received iodine contrast media IV during computed tomography examinations, 100 of which were given IIC medium^b (iothalamate sodium, 400 mg iodine/mL [2,300 mOsm/kg of water]) and 14 of which were given NIC medium^c (iopamidol 41%, 200 mg iodine/mL [413 mOsm/kg of water]). Of the 100 cats that received IIC medium, 60 met the inclusion criteria. Because the number of cats that received NIC was low, medical records were searched back to June 2002, and an additional 11 cats were evaluated for inclusion. Of the 25 total cats that received NIC media, 12 met the inclusion criteria. Contrast media were administered by hand at an approximate rate of 2 mL/min. Sixty-five cats undergoing magnetic resonance imaging without contrast medium administration but with at least 20 minutes of HR and PSBP data were included as a control group. All cats were hemodynamically supported with IV administration of fluid during anesthesia.

A variety of breeds were represented in each of the contrast medium and control groups, with domestic shorthair and longhair cats making up most of the population of all groups. Age for control (ie, cats receiving no contrast medium), IIC, NIC, and GD-contrast group cats was 9.5 ± 5.5 years, 8.9 ± 4.5 years, 9.1 ± 4.1 years, and 8.7 ± 5.3 years, respectively. Body weight for control, IIC, NIC, and GD-contrast group cats was 4.1 ± 1.0 kg, 5.1 ± 1.5 kg, 6.1 ± 2.3 kg, and 4.6 ± 1.6 kg, respectively. No significant differences were found in age among groups. Cats in the control group weighed significantly less than cats in the IIC (P = 0.002) and NIC (P < 0.001) groups. Cats in the GD-contrast group weighed significantly less than cats in the IIC group (P = 0.007).

Of cats receiving IIC medium, 1 of 60 (2%) became tachycardic (HR of 200 beats/min at 15 minutes after contrast medium administration) and none became bradycardic. None of the 12 cats receiving NIC medium had alterations in HR. Of cats receiving GD contrast medium, 1 of 83 (1%) became tachycardic (HR of 215 beats/min at 20 minutes after contrast medium administration) and 4 of 83 (5%) became bradycardic (HR of 92, 79, 95, and 86 beats/min at 10, 15, 15, and 20 minutes, respectively, after contrast medium administration). None of the 65 control cats had alterations in HR.

Of cats receiving IIC medium, 2 of 60 (3%) became hypotensive (PSBP of 80 and 84 mm Hg at 10 minutes after contrast medium administration) and 2 of 60 (3%) became hypertensive (PSBP of 195 and 190 mm Hg at 5 and 15 minutes, respectively, after contrast medium administration). Of cats receiving NIC medium, 2 of 12 became hypotensive (PSBP of 70 and 80 mm Hg at 10 and 20 minutes, respectively, after contrast medium administration); 1 cat was hypertensive at 15 and 20 minutes after contrast medium administration with a PSBP of 175 and 176 mm Hg, respectively. Of cats receiving GD contrast medium, 4 of 83 (5%) became hypertensive (PSBP of 195, 202, 205, and 250 mm Hg at 15, 15, 20, and 20 minutes, respectively, after contrast medium administration,). Three of 83 (4%) cats that received GD contrast medium became hypotensive; 1 cat had a PSBP of 82, 87, 86, and 82 mm Hg at 5, 10, 15, and 20 minutes, respectively, after contrast medium administration; 1 cat had a PSBP of 62 and 65 mm Hg at 10 and 20 minutes, respectively, after contrast medium administration; and 1 cat had a PSBP of 48 mm Hg at 20 minutes after contrast medium administration. None of the 65 control cats had alterations in PSBP.

When cats with substantial changes in either HR or PSBP were evaluated for the presence or absence of preexisting hypersensitivity conditions, it was found that, of cats receiving GD contrast medium, 6 of 83 had preexisting conditions that might predispose to contrast medium– induced hypersensitivity (ie, 2 had previous vaccine reactions, 2 had chronic bronchitis, 1 had a flea product allergy, and 1 had a flea allergy). None of the 6 cats had substantial alterations in HR or PSBP. Of cats receiving IIC medium, 2 of 60 had preexisting conditions that might predispose to contrast medium–induced hypersensitivity (ie, 1 had dermatitis and 1 had chronic bronchitis), neither of which had substantial alterations in HR or PSBP. Of cats receiving NIC medium, none had preexisting conditions that might predispose to contrast medium–induced hypersensitivity. No apparent relationship was found between the presence of a predisposing condition and the development of HR or PSBP alterations.

The anesthetist documented a perceived response to contrast medium administration in 5 cats receiving IIC medium. Specific changes in the 5 cats included 2 with increased PSBP (1 cat had an increase from 135 to 164 mm Hg at 5 minutes, and the other had an increase from 120 to 190 mm Hg at 20 minutes and was included in the group of cats identified as having a response) and 3 with decreased PSBP (in all 3 cats, the notes of the anesthetists indicated an immediate but transient response, although all recorded values were within reference range). None of the 5 cats had preexisting hypersensitivity conditions. No cats given NIC or GD contrast medium had perceived reactions to the contrast medium noted in the anesthesia record.

Of the cats that received GD contrast medium, 16 of 83 had preimaging and postimaging values for serum total bilirubin concentration; there was a mean of 67 ± 95 days (range, 3 to 270 days) between collection of blood samples. Three cats had high serum total bilirubin concentrations (reference range, 0 to 0.2 mg/dL) before imaging. Other liver enzymes were high in 2 of the 3 cats, indicating underlying liver disease. Of the 3 cats, serum total bilirubin concentration increased after imaging in 1 cat (170 days after imaging) and decreased (4 days after imaging) in another; the third cat had a serum total bilirubin concentration that returned to within the reference range 5 days after imaging. Only 1 of the 16 cats that had serum total bilirubin concentrations within the reference range before imaging had a value that was greater than the reference range at 5 days after GD contrast medium administration. A cause for this was not identified. The BUN and serum creatinine concentrations were available before and after imaging for 27 of the 83 cats; there was a mean of 51 ± 78 days (range, 3 to 270 days) between collection of blood samples. Eight of the 27 cats had high BUN concentrations (reference range, 18 to 33 mg/dL) before imaging. Only 2 of the 8 cats with high BUN concentrations also had high serum creatinine concentrations (reference range, 1.1 to 2.2 mg/dL) before imaging. The BUN concentration decreased but remained greater than the reference range in 4 of the 8 cats (4, 11, 16, and 24 days after imaging) and increased in 4 of the 8 cats (2, 5, 60, and 61 days after imaging). Both cats that had high serum creatinine concentration and high BUN concentrations before imaging had decreases in BUN concentrations at 4 and 11 days after imaging, but values remained greater than the reference range.

Of cats that received IIC medium, 19 of 60 had preimaging and postimaging values for serum total bilirubin concentration; there was a mean of 105 ± 106 days (range, 10 to 340 days) between collection of blood samples. Four of the 19 cats had high serum total bilirubin concentration before imaging. Three of the 4 cats had serum total bilirubin concentrations that were within reference range 36, 96, and 340 days after imaging. The fourth cat had a higher serum total bilirubin concentration 215 days after imaging. The BUN and serum creatinine concentrations were available before and after imaging for 19 of 60 cats; there was a mean of 105 ± 106 days (range, 10 to 340 days) between collection of blood samples. Three of the 19 cats had high BUN concentrations before IIC medium administration. All 3 cats had BUN concentrations that returned to the reference range 15, 18, and 50 days after imaging. An additional 3 cats with BUN concentrations within reference range before imaging developed elevated BUN concentrations 150, 215, and 320 days after imaging. No cats that received the IIC medium had high creatinine concentration before or after imaging.

Of the cats that received NIC medium, 4 of 12 had preimaging and postimaging values for serum total bilirubin concentration; there was a mean of 7 ± 4 days (range, 3 to 12 days) between collection of blood samples. One of the 4 cats had a high serum total bilirubin concentration before imaging, which decreased into the reference range 6 days after imaging. One of the 4 cats had a normal serum total bilirubin concentration before imaging that was elevated 3 days after imaging. Six of the 12 cats that received NIC medium had a history of chronic or acute renal disease listed in their records. The BUN and serum creatinine concentrations were available before and after imaging for 4 of 12 cats; there was a mean of 3 ± 2 days (range, 1 to 6 days) between collection of blood samples. The BUN concentration was high in 4 of the 4 cats and serum creatinine concentration high in 3 of the 4 cats before imaging. The 3 cats with elevated BUN and serum creatinine concentrations were undergoing imaging to assess ureteral obstruction. The BUN and serum creatinine concentration increased in 2 cats (1 and 2 days) and decreased in 2 cats (2 and 6 days) after imaging. Removal of the ureteral obstruction was performed between imaging and follow-up blood work in 1 cat that had increasing BUN and serum creatinine concentrations and 1 cat that had decreasing BUN and serum creatinine concentrations. The third cat with ureteral obstruction and increasing BUN and serum creatinine concentrations following imaging did not undergo ureteral surgery, developed pleural effusion, and was euthanatized on day 3 following imaging.

Discussion

Results of this study indicate that physiologically important changes in HR and PSBP occur subsequent to IV administration of contrast media in anesthetized cats. The PSBP appears to be more commonly affected than HR. The frequency of changes in HR and PSBP following contrast medium administration was similar between all of the media with the exception of NIC medium, which more frequently resulted in an increase in PSBP in cats, compared with the other contrast media. It is important to note that 6 of the 12 cats receiving the NIC medium had preexisting renal disease, making them more susceptible to hemodynamic consequences. More specifically, hypertension is known to result from renal disease.¹¹ Conversely, many of the cats receiving IIC and GD contrast media were undergoing imaging for cancer staging or neurologic evaluation and did not have marked disease-associated compromise. Furthermore, cats with renal failure are selectively given NIC media at our institution because studies^9,12,13 performed in people indicate that both acute and systemic adverse effects are less for such contrast media. Thus, the population of cats within the NIC group is inherently less hemodynamically stable, likely skewing the results to reflect an increased number of acute adverse effects. Although the frequency of acute events, as defined in this study, was similar between groups, notable reactions as perceived by the anesthetist were only reported in the IIC group cats and not the NIC or GD-contrast group cats. Therefore, the increased frequency of reactions reported in the NIC group cats may reflect an association with their underlying disease. Further studies involving standardized populations of cats would be necessary to define the true relationship between illness and the effect on acute contrast medium reaction.

The percentage of cats having substantial changes in PSBP associated with administration of all types of contrast media is high in comparison with that seen in people¹⁰ and dogs.⁷ The cause for this is unknown. It is possible that cats are more sensitive to the total volume and injection rate than dogs given their comparatively smaller size and total blood volume. Alternatively, the relatively high frequency of hemodynamic alteration may also be related to the fact that cats in this study were under anesthesia and changes in HR and PSBP can occur in relation to anesthetic depth and type. It has been previously shown that the type of anesthesia can substantially affect hemodynamic variables.¹⁴ Perhaps cats are more sensitive to the type and depth of anesthesia. Intravenous administration of fluids is a standard protocol at this institution; however, the rate was not always available for assessment. It is possible that IV administration of fluids, in terms of volume and rate, may have also contributed to alterations in HR and PSBP. Given that none of the control cats developed substantial alterations in PSBP and HR, it is more likely that the contrast media are the underlying cause for hemodynamic alterations.

The temporal relationship between changes in HR or PSBP and IV administration of contrast medium is longer than contrast agent–induced reactions in people that most often occur within the first 5 minutes.⁴ This phenomenon was seen in a similar study⁷ looking at anesthetized dogs. Although it is feasible that the changes in HR and PSBP at the 15- and 20-minute time points were unrelated to contrast medium administration, the absence of change in the control group cats and the presence of PSBP alterations even at the early (5- and 10-minute) time points in all contrast medium group cats lend supportive evidence linking contrast medium administration and these hemodynamic changes.

There was no detectable relationship between the presence of a condition predisposing to contrast medium–induced hypersensitivity and acute contrast medium reaction. In people, it has been shown that certain conditions such as food allergies, asthma, and atopy appear to predispose to acute GD and iodinated contrast agent–induced reactions.^1,2,5 In fact, asthma is the most important predisposing factor for severe acute iodinated contrast medium reaction in people.¹⁵ The prevalence of chronic bronchitis (feline asthma) in the cat population is consequently of concern as a potential contraindication for the administration of contrast media. Three cats in our study receiving 2 types of contrast media had a history of chronic bronchitis, yet none of them had pronounced effects from the administration of contrast media. Given that the incidence of reaction even in asthmatic people is low, the small number of cats in our study precludes identification of a significant relationship between predisposing conditions and an increased likelihood of reaction.

As was seen in a recent study⁷ performed in anesthetized dogs, hypotension and hypertension can be seen subsequent to contrast medium administration. In people, transient hypertension occurs with contrast medium administration as a result of the osmotic effect of the medium pulling fluid from the extracellular to the intravascular space. This is followed by hypotension secondary to generalized vasodilation¹⁶ with inhibition of acetylcholinesterase in blood and tissues¹⁷ and histamine release.^18,19 This mechanism may be responsible for the early hypertension and hypotension seen in cats, but the cause of hypertension at the later time points is unknown. Further studies would be necessary to better understand the cause of hypertension in cats receiving contrast media.

Hemolytic and renal adverse effects associated with contrast medium administration were not detected in the cats in this study. However, it is important to note that the number of cats with serum biochemical data available before and after contrast medium administration was low, thereby limiting the ability to make accurate assessments of the likelihood of a connection between medium administration and untoward effects. There was 1 cat in each group that developed elevated serum total bilirubin concentration subsequent to contrast medium administration without clear explanation. Contrast medium–induced hemolysis in people has been reported only with the administration of GD contrast medium.⁸ Thus, the link to the contrast medium administration is tenuous. Likewise, no clear relationship is present between contrast medium administration and the development or progression of renal disease in our study. Gadolinium and iodinated contrast medium–induced renal adverse effects most commonly occur in people with existing kidney disease.^20,21 Contrast medium–induced nephrotoxicosis secondary to iodinated contrast medium administration occurs in 0% to 10% of people with normal renal function but 12% to 27% of people with preexisting renal compromise.⁵ A severe late adverse reaction to GD contrast medium, nephrogenic systemic fibrosis, has recently been reported. This disease develops in people with end-stage renal disease that receive GD contrast medium and results in necrotizing dermatitis and renal sclerosis 2 to 75 days following contrast medium administration.⁹ Should a similar predisposition be present in cats, the NIC group cats in our study would be prone to contrast medium– induced nephrotoxicosis. However, the low number of cats in this group limits the ability to identify such a response, and additional studies would be necessary to further understand such a connection.

In conclusion, changes in HR and PSBP occur in association with IV administration of IIC, NIC, and GD contrast media in anesthetized cats. Both increases and decreases in HR and PSBP occurred with most contrast media, although changes in PSBP were more common. Ionic-iodinated contrast medium more frequently prompted concern and notation on the part of the anesthetist. Studies involving larger numbers of cats would be necessary to determine the importance of conditions predisposing to hypersensitivity in regard to contrast agent–induced reactions. Adverse systemic effects associated with contrast medium administration were not detected in our study cats.