Mortality rate of birds following intravenous administration of iodinated contrast medium for computed tomography

Julianne E. McCready From the Department of Clinical Studies (McCready, Appleby, Beaufrère) and Health Sciences Centre (Gardhouse), Ontario Veterinary College, University of Guelph, Guelph, ON N1G 2W1, Canada.

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Sara M. Gardhouse From the Department of Clinical Studies (McCready, Appleby, Beaufrère) and Health Sciences Centre (Gardhouse), Ontario Veterinary College, University of Guelph, Guelph, ON N1G 2W1, Canada.

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Ryan Appleby From the Department of Clinical Studies (McCready, Appleby, Beaufrère) and Health Sciences Centre (Gardhouse), Ontario Veterinary College, University of Guelph, Guelph, ON N1G 2W1, Canada.

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Hugues Beaufrère From the Department of Clinical Studies (McCready, Appleby, Beaufrère) and Health Sciences Centre (Gardhouse), Ontario Veterinary College, University of Guelph, Guelph, ON N1G 2W1, Canada.

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Abstract

OBJECTIVE

To identify potential risk factors for death following IV or intraosseous (IO) administration of contrast medium in birds undergoing CT scans.

ANIMALS

120 birds that underwent 134 contrast-enhanced CT scans.

PROCEDURES

Medical records of birds of any species that underwent a CT scan which included administration of nonionic iodinated contrast medium from June 2013 to February 2020 were included. Information on birds and use of contrast medium was extracted from the medical records as well as information on deaths following IV or IO administration of contrast medium.

RESULTS

6 birds died shortly following administration of contrast medium. Necropsies were performed in 3 birds (2 cockatiels and 1 macaw), and all had lesions associated with the respiratory tract. When body weight was used as a binary variable to compare odds of death between small birds (≤ 150 g [0.33 lb]) and large birds (> 150 g), small birds had a 97-fold increased odds (OR, 97.5; 95% CI, 9.8 to 966.0) of dying following contrast medium administration. Following 131 CT scans with contrast medium administration (3 scans were excluded because of perivascular or subcutaneous leakage of contract medium), small birds had a mortality rate of 45.4% (5/11), compared with a mortality rate of 0.8% (1/120) for large (> 150 g) birds. Other variables (ie, sex, age, anesthesia or sedation, sedation protocol, and type of contrast medium) were not significantly associated with death after contrast medium administration.

CONCLUSIONS AND CLINICAL RELEVANCE

Although the administration of contrast medium cannot be conclusively confirmed as the cause of death in these birds, the high mortality rate for small birds coupled with the temporality of the event following contrast medium administration justifies the cautious use of contrast medium in small sick psittacine birds. (J Am Vet Med Assoc 2021;259:77–83)

Abstract

OBJECTIVE

To identify potential risk factors for death following IV or intraosseous (IO) administration of contrast medium in birds undergoing CT scans.

ANIMALS

120 birds that underwent 134 contrast-enhanced CT scans.

PROCEDURES

Medical records of birds of any species that underwent a CT scan which included administration of nonionic iodinated contrast medium from June 2013 to February 2020 were included. Information on birds and use of contrast medium was extracted from the medical records as well as information on deaths following IV or IO administration of contrast medium.

RESULTS

6 birds died shortly following administration of contrast medium. Necropsies were performed in 3 birds (2 cockatiels and 1 macaw), and all had lesions associated with the respiratory tract. When body weight was used as a binary variable to compare odds of death between small birds (≤ 150 g [0.33 lb]) and large birds (> 150 g), small birds had a 97-fold increased odds (OR, 97.5; 95% CI, 9.8 to 966.0) of dying following contrast medium administration. Following 131 CT scans with contrast medium administration (3 scans were excluded because of perivascular or subcutaneous leakage of contract medium), small birds had a mortality rate of 45.4% (5/11), compared with a mortality rate of 0.8% (1/120) for large (> 150 g) birds. Other variables (ie, sex, age, anesthesia or sedation, sedation protocol, and type of contrast medium) were not significantly associated with death after contrast medium administration.

CONCLUSIONS AND CLINICAL RELEVANCE

Although the administration of contrast medium cannot be conclusively confirmed as the cause of death in these birds, the high mortality rate for small birds coupled with the temporality of the event following contrast medium administration justifies the cautious use of contrast medium in small sick psittacine birds. (J Am Vet Med Assoc 2021;259:77–83)

Introduction

Diagnostic imaging is an integral part of the diagnostic workup, treatment plan, and prognosis determination in veterinary patients, and avian patients are no exception. The traditional imaging modality used for birds has been radiography, which is useful for evaluating the skeletal system and most of the coelomic organs. However, although radiography is widely available to veterinary practitioners, it has several disadvantages including the problem of superim-position and limited detail for certain organs in birds, such as the lungs.1 Ultrasonography is often limited in birds by the size of the patient in comparison with the footprint of the ultrasound probe, as well as the presence of air sacs and the large ventrally located keel bone. Together, these factors severely limit available acoustic windows and limit the visualization of coelomic organs.2 Computed tomography has been increasingly used in avian patients. Although the spatial resolution tends to be lower, it offers some marked advantages over conventional radiography such as the elimination of superimposition, improved detail, and ability to create a 3-D reconstruction.3,4Computed tomographic scans have been invaluable in planning complex surgeries in birds.57 Computed tomographic scans are often enhanced by means of injection of the patient with a parenteral contrast medium. The contrast medium is useful for distinguishing between organs and providing more information about lesions and abnormal vascularization. Although nonionic iodinated contrast media are generally considered safe in mammals, we have encountered several deaths in small birds immediately after contrast medium administration at our institution. Because CT scans are the preferred diagnostic imaging modality for birds at our hospital, these concerns in small birds provided the incentive to perform a retrospective study of death following IV or IO administration of nonionic iodinated contrast medium in birds.

The objective of this retrospective observational study was to identify potential risk factors for death following contrast medium administration to birds undergoing CT scans. It was hypothesized that the mortality rate immediately following IV or IO administration of iodinated contrast medium would be low but would be greater in small birds (body weight, ≤ 150 g [0.33 lb]).

Materials and Methods

Inclusion criteria

Medical records of birds of any species that underwent a CT scan with administration of nonionic iodinated contrast medium, from June 2013 to February 2020, were reviewed for inclusion in the present study. Cases were found by searching the hospital's digital imaging databasea and selecting CT for imaging modality and searching for the term avian. Evidence of contrast medium administration was obtained by reviewing the medical records for mention of contrast medium administration and screening CT studies for postcontrast images.

Medical record review

Demographic information for the included birds was obtained from the electronic medical records. Signalment information included date of birth (used to calculate age at the time of CT scan), species, sex, and body weight (ideally body weight on the day of CT, but other recorded patient weights were used if not available). Sex was classified as unknown if the bird species in question was not sexually dimorphic and the bird had not been sexed (either surgically or via DNA sexing) or laid eggs, as noted in the medical records. Necropsy reports were reviewed, if available, to determine or confirm the sex of the birds. The species was recorded if known, but birds were grouped by family for the purposes of analysis because of the large number of species included. Several birds had multiple CT scans performed. Each scan was recorded separately; therefore, the total number of CT scans performed is greater than the total number of birds.

The electronic medical records were also reviewed to gather information relating to the CT procedure and outcome. This included the presenting complaint, whether the bird was sedated or anesthetized, whether the bird received nonionic iodinated contrast medium, route of contrast medium administration (IV or IO), volume of contrast medium, type of contrast medium (either iohexolb or iopamidolc), whether the contrast medium was diluted in sterile saline (0.9% NaCl) solution, whether the bird died immediately following contrast medium administration, CT findings, and histopathologic diagnosis from necropsy (if available).

Sedation was defined as IM or intranasal administration of sedatives and could include any combination of a benzodiazepine, an opioid, and a dissociative drug. Deep sedation was defined as additional IV or IO administration of propofol boluses, which could also include any of the aforementioned sedatives but did not include gas anesthesia. Anesthesia was defined as the use of volatile gas anesthetics, which could be delivered through a face mask or endotracheal tube and could be administered alone or with any of the previously mentioned drugs. For general anesthesia, birds were typically monitored by use of a pulse oximeterd and capnographye if intubated as well as with cardiopulmonary auscultation and visual monitoring of respiratory movements. If birds were not breathing spontaneously, pressure-controlled ventilationf was provided during the CT scan. A Doppler unit was not used for cardiac monitoring because it would create imaging artifacts (ie, beam-hardening artifacts) and the unit could not be placed far enough from the region of interest in small birds undergoing whole-body CT.

Contrast medium–related deaths were defined as those that could be reasonably related to the iodinated contrast medium administration on the basis of the time frame between administration and death (ie, ≤ 5 minutes, as used by Scarabelli et al8 to define contrast medium reactions in dogs and cats). A bird that was noticed to have died within seconds to a few minutes after contrast medium administration, as best as could be gathered from the medical records, was included in this group. Birds that died during anesthetic recovery or hours after CT were not included in this group. It was noted whether CPR was attempted, whether resuscitation was successful, and whether a necropsy was performed.

Statistical analysis

The effects of body weight and other variables (age, sex, anesthesia or sedation, sedation protocol, type of contrast medium) on the probability of death was assessed by use of univariate logistic regression. Odds ratios were obtained by exponentiation of the parameter estimates. Presence of outliers was assessed on residuals plots. The body weight variable was assessed as a continuous variable and as a binary variable (small birds ≤ 150 g [0.33 lb] and large birds > 150 g). This weight cutoff was selected somewhat arbitrarily; however, it was thought that 150 g would be a reasonable cutoff between birds in which it was reasonably easy versus difficult to routinely place an IV catheter. A Fisher exact test was also performed on the body weight binary variable (small birds vs large birds) to confirm the results of the logistic regression because the sample size of birds that died was small.

The sample size of birds with the outcome of interest (n = 6) was not high enough for multivariate logistic regression modeling.9

An α value of 0.05 was used to define statistical significance. Statistical software was used for statistical analysis.g

Results

Animals

One hundred sixty-eight CT scans were performed on 155 birds from June 2013 to February 2020. Of these, 134 CT scans on 120 birds were performed with contrast medium administration and therefore met the inclusion criteria. Ten birds had multiple contrast-enhanced CT scans performed during that time period (2 CT scans, 7 birds; 3 CT scans, 2 birds; and 4 CT scans, 1 bird). The remaining 110 birds had a single contrast-enhanced CT during the study period. In 3 birds, contrast medium administration was attempted, but a large amount was noticed to be SC or perivascular; these birds were included in the descriptive statistics but excluded from the mortality rate analysis.

The median age at the time of contrast-enhanced CT was 13.4 years (range, 0.2 to 40.4 years). Of the 134 CT scans performed with contrast medium, 70 were performed on female birds, 41 on male birds, and 23 on birds of unknown sex. The distribution of birds across avian families was summarized (Table 1). Median body weight of birds was 518 g (1.14 lb; range, 60 g to 16 kg [0.13 to 35.2 lb]). Contrast medium was administered IV in 109 birds and IO in 9 birds; route of administration was not recorded for 2 birds. All 3 instances of perivascular leakage of contrast medium occurred in birds that underwent IO administration. The specific contrast medium was iohexol in 30 CT scans and iopamidol in 50 CT scans; it was not recorded for 54 CT scans.

Table 1

Frequency distribution of families and genera of birds that underwent 134 CT scans with contrast medium administration.

Families Genera No. of birds
Accipitridae (n = 2) Buteo 1
Haliaeetus 1
Anatidae (n = 4) Anas 1
Anser 1
Cairina 1
Cygnus 1
Cacatuidae (n = 26) Cacatua 21
Calpytorhynchus 1
Eolophus 1
Nymphicus 3
Colombidae (n = 2) Columba 2
Falconidae (n = 5) Falco 5
Musophagidae (n = 1) Musophago 1
Phasianidae (n = 21) Gallus 14
Meleagris 7
Psittacidae (n = 62) Amazona 18
Ara 12
Aratinga 3
Deroptyus 1
Myiopsitta 3
Pionus 5
Poicephalus 1
Primolius 1
Psittacus 16
Pyrrhura 2
Psittaculidae (n = 4) Chalcopsitta 1
Eclectus 1
Eos 1
Trichoglossus 1
Strigidae (n = 7) Asio 1
Bubo 1
Megascops 2
Strix 3

Death following contrast medium administration

Birds in which contrast medium administration was attempted but large amounts of contrast medium were noticed to be perivascular or SC, resulting in poor or no contrast enhancement of the CT scans, were excluded from the mortality rate analysis (n = 3). Therefore, of 134 contrast-enhanced CT scans, 131 CT scans and 117 birds were included in the mortality rate analysis. Six birds died following administration of iodinated contrast medium (Table 2). All 6 birds that died were psittacine birds (Supplementary Appendix S1, available at: avmajournals.avma.org/doi/suppl/10.2460/javma.259.1.77). The types of birds included the following: cockatiels (Nymphicus hollandicus; n = 2), Quaker parrots (Myiopsitta mona-chus; 2), green-cheeked conure (Pyrrhura molinae; 1), and blue-and-gold macaw (Ara ararauna; 1). All of the birds were clinically ill when they were evaluated. Dyspnea was a part of the clinical presentation in 4 of 6 birds. Other clinical signs that were noticed included paresis and ataxia, falling off the perch, seizures, anorexia, body weight loss, lethargy, regurgitation, and straining to defecate.

Five of 6 birds that died had been placed under general anesthesia. All of these birds were intubated with an endotracheal tube. Most birds (4/5) that died during anesthesia had their end-tidal partial pressure of carbon dioxide monitored with a capnograph. In the remaining bird, whether capnography was used was not noted in the medical record. Two birds were mechanically ventilated, 1 bird was noticed to be breathing spontaneously, and for 2 birds, it was not noted whether they ventilated spontaneously. The remaining bird (a blue-and-gold macaw) received sedation with midazolam, butorphanol, and ketamine (Table 2).

Table 2

Rate of death following contrast medium administration for 131 CT scans in 117 birds summarized by anesthetic and sedative protocols.

Anesthetic protocol No. of CT scans
Birds recovered Birds died
General anesthesia 67 5
Sedation (midazolam) 1 0
Sedation (midazolam-butorphanol) 31 0
Sedation (midazolam-butorphanol-ketamine) 17 1
Sedation (midazolam-hydromorphone) 1 0
Sedation (midazolam-ketamine) 1 0
Deep sedation (including propofol) 7 0

Of the 6 birds that died, 2 received iohexol and 1 received iopamidol; for the other 3 birds, the type of contrast medium was not recorded. Computed tomographic findings in the 6 birds that died included the following: a mass in the lung extending to the air sac and vertebral canal with lysis of the vertebral bodies; a severely displaced short oblique right coracoid fracture penetrating the coelomic cavity; a soft tissue mass at the lateral aspect of the duodenum, hepatomegaly, and increased lung density; right-sided pulmonary density; patchy right lung consolidation; and normal findings. The bird with the soft tissue mass near the duodenum and hepatomegaly was also noticed to have a mildly to moderately enlarged heart on the postcontrast series.

Cardiopulmonary resuscitation was attempted in all 6 birds that died. A necropsy was approved by the owners of 3 birds. These 3 birds (2 cockatiels and 1 macaw) had lesions associated with the respiratory system on necropsy. Necropsy findings in the first cockatiel included neoplasia (a peripheral nerve sheath tumor in the thoracic spinal cord), along with peribronchitis, anthracosis, and air sacculitis. The second cockatiel and the macaw had respiratory tract lesions of unknown etiology. These lesions included lymphoplasmacytic and heterophilic bronchitis and air sacculitis, lymphoplasmacytic tracheitis, and mild multifocal pulmonary edema in the second cockatiel and parabronchial epithelial degeneration and regeneration and fibrosis in the macaw. No etiologic agent was identified for these 2 birds, but chronic irritation of the respiratory tract was postulated.

Decreasing body weight significantly (OR, 1.83; 95% CI, 1.08 to 3.11; P = 0.025) increased the odds of death by 83% per 100 g (0.22 lb) of body weight after contrast medium administration. When body weight was used as a binary variable to compare small birds (≤ 150 g) with large birds (> 150 g), small birds had a 97-fold increased odds (OR, 97.5; 95% CI, 9.8 to 966.0; P < 0.001) of dying following contrast medium administration, compared with large birds. The Fisher exact test confirmed that the association was signifi-cant (P < 0.001). For 131 CT scans, 45.4% (5/11) of small birds died following IV or IO administration of contrast medium, compared with 0.8% (1/120) of all the larger (> 150 g) birds.

All other variables (sex, age, anesthesia or sedation, sedation protocol, and type of contrast medium) were not significantly associated with death after contrast medium administration.

Discussion

In the present retrospective study, small birds (body weight ≤ 150 g [0.33 lb]) had significantly increased odds of dying shortly following the administration of contrast medium for the purposes of a CT scan, compared with larger birds. The overall rate of death was 4.6%, but it was lower (0.8%) for large birds than for small birds (45.4%).

Iodinated contrast media are highly water-soluble, carbon-based benzene ring compounds.10 They may be divided into 4 types as follows: high-osmolality ionic, low-osmolality nonionic, low-osmolality ionic, and isomolar nonionic media.11 Ionic contrast media dissociate in aqueous solution, have higher osmolarity, and are associated with a greater risk of adverse effects.1215 The contrast media used in the present study, iohexol and iopamidol, are nonionic contrast media.10,13,15

Various iodinated contrast medium administration protocols have been described for birds. In 1 study, African grey parrots received IV administration of iopamidol (2 mL; 370 mg of iodine/mL), with a mean volume of 4.6 mL/kg (2.09 mL/lb; 1,681.8 mg of iodine/kg [764.45 mg iodine/lb]).16 This dose is higher than other reported doses for angiography in birds. In Hispaniolan Amazon parrots, a test bolus of iohexol of 1 mL/kg (0.45 mL/lb) followed by the remainder of the dose (3 mL/kg [1.36 mL/lb]; 240 g of iodine/mL) was recommended for CT angiography (total dose, 960 mg of iodine/kg [436.36 mg of iodine/lb]).17 Other authors have made similar recommendations (iopamidol, 2 to 4 mL/kg [0.9 to 1.8 mL/ lb]; 250 mg of iodine/mL).13 It should be noted that birds in those studies were considered healthy on the basis of physical examination findings and diagnostic testing results, whereas birds undergoing CT scans in clinical practice are usually not healthy.

It is usually recommended that contrast medium be rapidly administered IV over the course of a few seconds to birds for maximum image contrast enhancement because of their rapid heart rates and high cardiac output.16,17 In a study16 of African grey parrots, the protocol that was considered most successful in terms of satisfactory image contrast enhancement of the major arteries involved administration of 2 mL of iopamidol followed by 0.4 mL of saline solution, with an injection time of 8 seconds (0.3 mL/s). In that study,16 the scans were started manually once peak image contrast enhancement was reached. This injection time is slower than previously described for Hispaniolan Amazon parrots, in which a 3-mL/kg dose of contrast medium was administered IV over 3 seconds, with peak arterial image contrast enhancement at 1 second.17 In practice, contrast medium is sometimes administered at a slower rate with good reported image contrast enhancement; a conference proceeding describes a protocol for iopamidol administration of 4 to 5.3 mL/kg (1.8 to 2.4 mL/lb) delivered over 120 seconds, with the CT scan started 30 seconds into the contrast medium delivery.18 However, to the authors’ knowledge, there is no published peer-reviewed information on slower rates and associated image contrast enhancement in birds, and because the image contrast enhancement peak in the abdominal aorta is very rapid, quick injection times are generally recommended.17

In a previous study,17 no adverse effects were observed in Hispaniolan Amazon parrots given a total iohexol dose of 4 mL/kg.17 In another study,16 2 of 9 African grey parrots developed mild bilateral lung crackling following administration of 2.8 mL of saline solution as a preflush, 2 mL of iopamidol, and then 0.2 mL of saline solution (total volume, 5 mL), but otherwise recovered well. In that study,16 no lung crackling was auscultated in African grey parrots given 2 mL of iopamidol followed by 0.4 mL of saline solution (total volume, 2.4 mL) or 2.8 mL of saline solution and then 2 mL of iopamidol (total volume, 4.8 mL).

The present study provided evidence that a bolus injection of nonionic iodinated contrast medium was associated with a substantial rate of deaths in small unhealthy psittacine birds. In humans, acute adverse reactions following iodinated contrast medium administration are defined as those that occur within 1 hour following injection.19 The most severe and fatal reactions in humans occur within 20 minutes of injection12 and often occur immediately following injection.20 Given the retrospective nature of the present study and the fact that necropsies were performed on only 3 birds, it was not possible to definitively determine whether the deaths were attributable to the administration of the contrast medium itself or secondary to an underlying disease or anesthetic complications. For the birds in which necropsies were performed, there was evidence of preexisting disease, which made determining whether the cause of death could be linked to contrast medium administration challenging. On the other hand, birds that underwent CT scans at our institution were rarely healthy, and severe preexisting diseases, including respiratory diseases, were also seen routinely in birds that did not die following contrast medium administration. In addition, death caused by contrast medium administration will not lead to specific histopatho-logic lesions; thus, it may be difficult to conclusively prove causation.

It was also challenging to draw conclusions related to an association between signalment and death following contrast medium administration because of the small number of birds that died and the wide CIs of the OR. However, small birds had significantly increased odds of death following contrast medium administration. In the group of birds that died, 2 species of birds (ie, Quaker parrots and cockatiels) had > 1 individual. These birds were relatively small but still large enough to undergo placement of IV catheters. Birds much smaller than this were unlikely to have contrast medium administered for practical reasons. Alternatively, it is possible that these species commonly have an underlying disease that puts them at higher risk of death with anesthesia or drug administration. Three of 6 birds that died following contrast medium administration underwent necropsy and had lesions associated with the respiratory system on histologic examination. Birds with respiratory disease may be at an increased risk of death following contrast medium administration or simply have an increased risk of dying. However, temporality of death subsequent to contrast medium administration provided strong evidence, although still circumstantial, that these deaths were linked to contrast medium administration. There were also a substantial number of larger birds with severe or advanced disease that underwent contrast-enhanced CT with no complications. All of the birds that died following contrast medium administration had CPR performed, which can make interpretation of necropsy findings more difficult.

The overall prevalence of death following contrast medium administration in the present study was 4.6%, but it was 45.4% in small birds. In humans, the prevalence of severe reactions following nonionic contrast medium administration is 0.01% to 0.04%.12,19 Deaths following contrast medium administration are rare in humans21 and occur at a rate from 1 in 137,473 patients19 to 1.1 to 1.2 per 1 million contrast packages distributed,22 depending on the study. Less information is available regarding the safety of iodinated contrast medium in veterinary species. In 1 study,8 0.8% of dogs and 0% of cats receiving iohexol during anesthesia had a severe reaction (defined as hemodynamic or respiratory alterations that required immediate treatment); no life-threatening reactions or deaths occurred. Another study15 did not find any severe acute adverse reactions in dogs receiving ionic or nonionic iodinated contrast medium. Compared with dogs, a higher percentage of cats experienced substantial changes in peak systolic blood pressure after contrast medium administration; this was speculated by the authors to be potentially related to their smaller size and blood volume.23 The prevalence of contrast medium–related severe reactions in dogs (0.8%)8 is comparable to the death rate that was observed in birds (excluding small birds) of the present study (0.8%). The higher prevalence of death for birds, compared with other species, may be related to their size, the fact that they are more debilitated when brought for medical care, or an underlying sensitivity to contrast medium that is heightened in small birds.

One factor that has been postulated to be a potential reason for death following contrast medium administration is the osmolality of the contrast medium and rapid shifts in the plasma osmolality,11 which may be exacerbated by the rapid injection of contrast medium through an IV route. Rapid expansion of the plasma volume may lead to baroreceptor activation and bradycardia.8 In 1 bird of the present report, the contrast medium was diluted with saline solution in an attempt to reduce this risk, but the patient still died. In humans with diabetes, the prevalence of adverse events, including ischemic stroke and cardiovascular events, was significantly lower with iso-osmolar contrast medium, compared with low-osmolar contrast medium.24 The contrast media typically used in birds and the types of media used in the present study (iohexol and iopamidol) are low- osmolar contrast media.10,24 Iso-osmolar contrast media, such as iodixanol, were not used in the present study because of lack of availability. In humans, isoosmolar contrast media are recommended for the highest-risk patients.10

In humans, adverse reactions related to iodinated contrast medium may be classified as mild (nausea, mild vomiting, urticaria, pruritus, pallor, and pain at injection site), moderate (severe vomiting, marked urticaria, bronchospasm, facial and laryngeal edema, vasovagal attack, and dyspnea), or severe (pulmonary edema, arrhythmias, hypotensive shock, respiratory arrest, cardiac arrest, convulsions, and unconsciousness).12,25 Allergy-like or pseudoallergic contrast medium reactions are not thought to be type I hyper-sensitivity reactions, but are rather suspected to be a result of direct molecular toxicosis from the contrast medium.11,12,25 Prior warming of several contrast media (iopromide 370, iopamidol 730, and iohexol 350) to 37°C (98.6°F) substantially reduced adverse reactions and allergic-like reactions, but not physiologic reactions.25 These contrast media have high dynamic viscosity at room temperature, and warming reduces their viscosity.25 Warming of iopromide 300 did not reduce the risk of adverse reactions possibly because of its low viscosity, compared with the aforementioned contrast media.25 Nonwarmed contrast medium may also serve as cold irritants, which can increase heart rate and blood pressure.25 Birds have a higher physiologic body temperature than humans,26 which may increase their susceptibility to such adverse effects. Treatment of severe allergic-like contrast medium reactions in humans involves administration of epinephrine and oxygen and IV administration of isotonic fluids.21 Pretreatment of people with corticosteroids to prevent adverse reactions to contrast medium is a controversial practice.11,21,27

Risk factors for acute adverse reactions to contrast medium in humans include young or old age, asthma, allergies, dehydration, heart disease, kidney disease, hematologic disease, diabetes, and the use of certain drugs.11,12,20,27 In the blue-and-gold macaw that died following contrast medium administration in the present study, necropsy results did not indicate a definitive cause for the dyspnea, but changes in the right lung were suggestive of a chronic irritant. One of the cockatiels also had changes suggestive of chronic, nonspecific irritation of the respiratory tract on necropsy. It is possible that birds with preexisting respiratory disease may be at increased risk for adverse reactions to contrast medium, similar to humans with asthma.11 All 4 human patients who died following administration of contrast medium for excretory urography in 1 study20 had a history of respiratory disease or a respiratory component to their reaction. In the present study, results on necropsy indicated that all of the birds that died following contrast medium administration had respiratory lesions.

The decision on whether to administer contrast medium was at the discretion of the clinician and may have been influenced by a number of factors. In small birds, IV access may be difficult and carries a risk of substantial blood loss. Small birds may undergo placement of IO catheters, but this can lead to complications such as signs of pain, bone infection, and fracture. Therefore, the clinician may elect not to administer contrast medium to a small bird for a CT scan. In addition, once several deaths following contrast medium administration had been observed, the clinicians may have become hesitant to administer contrast medium to small birds. It is possible that small birds have more severe illnesses when they present or have a higher risk of anesthetic death. However, in a study28 of 352 birds that underwent inhalation anesthesia, body weight was not found to be significantly associated with risk of anesthesia-related death. In the present study, there was also a noticeable temporal effect between the administration of contrast medium and death. In addition, general anesthesia, compared with sedation, was not associated with an increased odds of death in the present study. Because it was more common to anesthetize rather than sedate small birds, this is a potential confounding factor. Small birds do not undergo sedation as reliably as large birds and require much higher doses of sedatives29; therefore, general anesthesia is often elected. Similar to cats,23 it could be speculated that small birds may be more sensitive to hemodynamic alterations from contrast medium injection because of the smaller size and therefore smaller blood volume.

One limitation of the present study is the fact that the type and volume of contrast medium were not always recorded in the medical records; however, most birds at our hospital received a dose of 2 mL/kg. It is worth noting that adverse reactions to contrast medium in humans are considered idiosyncratic and not dose dependent.11,12 Lack of recording the name of the contrast medium given is similarly a problem in human medicine.22 The type of contrast medium given may be clinically important. In 1 study,27 changing the type of contrast medium administered during a subsequent exposure substantially reduced the rate of hypersensitivity reactions among people who previously had a moderate to severe reaction.27 Un fortunately in the present study, the type of contrast medium administered was not recorded for 3 of 6 birds that died after receiving it, but it was most likely iopamidol on the basis of historical use at the time for birds in our service. It should be noted that both contrast medium types were represented among the birds that died. Additionally, it was often difficult to determine when exactly the bird died, as it was typical for the contrast medium to be administered rapidly and for personnel to immediately leave the CT room because of concern that the contrast medium would be cleared from the intravascular space, as a result of the high cardiac output of birds, and thus reduce the quality of the CT scan. After several instances of death, it became more common at our hospital to auscultate birds during or immediately after contrast medium administration. Thus, for the most recent death (the blue-and-gold macaw), the bird was observed to initially have a normal heart rate, followed by bradyarrhythmia and cardiorespiratory arrest. Unfortunately, monitoring capabilities during CT scan are limited. Personnel have to leave the room during image acquisition during CT because of the risk of exposure to ionizing radiation. In addition, anesthetic monitoring equipment such as a Doppler ultrasound monitor can cause a beam-hardening artifact and cannot be used during a whole-body CT scan or CT scan in small birds. The typical duration for the postcontrast CT scan is about 1 minute with the CT scanner used in this retrospective study. Factors such as the speed of injection could not be evaluated as this was rarely recorded in the medical record. Another limitation of the present study is that the CI for the odds of dying when comparing small and large birds was wide because of the small number of birds that died, so the estimation is imprecise. Furthermore, in the present study, there were far fewer small birds than large birds, which could cause a bias in the analysis.

The deaths of birds in the present study, if related to contrast medium administration, are thought to most likely have occurred because of a severe allergic-like reaction or osmolar stress, on the basis of findings in humans. Death attributable to underlying disease or anesthetic complications cannot be definitively ruled out, and it would be difficult to completely rule out these complications in subsequent studies as well. Although this retrospective study included only 6 deaths during 131 contrast-enhanced CT examinations, the high mortality rate observed in small birds associated with contrast medium administration warrants caution when performing contrast-enhanced CT in small sick psittacine birds. Further areas of study may include prospective randomized clinical trials or experimental studies that investigate the safety of iso-osmolar contrast media in birds or the effect of prewarming the contrast medium prior to administration.

Abbreviations

IO

Intraosseous

Acknowledgments

No financial support was received for the study. The authors declare that there were no conflicts of interest.

Footnotes

a.

Enterprise Imaging, Agfa Healthcare, Mortsel, Belgium.

b.

Omnipaque 240, GE Healthcare Canada Inc, Mississauga, ON, Canada.

c.

Isovue 300, Bracco Imaging Canada, Montreal, QC, Canada.

d.

Model 2500A Vet, Nonin Medical Inc, Plymouth, Minn.

e.

Nellcor, Covidien, Mansfield, Mass.

f.

BASi Vetronics, Bioanalytical Systems Inc, West Lafayette, Ind.

g.

R: a language and environment for statistical computing, version 3.6.3, 2019, R Foundation for Statistical Computing, Vienna, Austria. Available at: www.r-project.org.

References

  • 1.

    Krautwald-Junghanns M-E, Schumacher F, Tellhelm B. Evaluation of the lower respiratory tract in psittacines using radiology and computed tomography. Vet Radiol Ultrasound 1993;34:382390.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 2.

    Helmer P. Advances in diagnostic imaging. In: Harrison GJ, Lightfoot TL, eds. Clinical avian medicine. Vol 2. Palm Beach, Fla: Spix Publishing, 2006;653659.

    • Search Google Scholar
    • Export Citation
  • 3.

    Krautwald-Junghanns ME, Kostka VM, Dörsch B. Comparative studies on the diagnostic value of conventional radiography and computed tomography in evaluating the heads of psittacine and raptorial birds. J Avian Med Surg 1998;12:149157.

    • Search Google Scholar
    • Export Citation
  • 4.

    Dos Santos GJ, da Silva JP, Hippólito AG, et al. Computed tomo-graphic and radiographic morphometric study of cardiac and coelomic dimensions in captive blue-fronted Amazon parrots (Amazona aestiva, Linnaeus, 1758) with varying body condition scores. Anat Histol Embryol 2020;49:299306.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 5.

    Laniesse D, Beaufrère H, Mackenzie S, et al. Perforating foreign body in the ventriculus of a pet pigeon (Columba livia domestica). J Am Vet Med Assoc 2018;253:16101616.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 6.

    Beaufrère H, Laniesse D, Kabakchiev C, et al. Multiple fractures and luxations of palatofacial bones in a hawk-headed parrot (Deroptyus accipitrinus). J Am Vet Med Assoc 2019;254:251256.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 7.

    Barboza TK, Beaufrère H, Chalmers H. True coelomic hernia and herniorrhaphy in a yellow-crowned Amazon parrot (Amazona ochrocephala). J Avian Med Surg 2018;32:221225.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 8.

    Scarabelli S, Cripps P, Rioja E, et al. Adverse reactions following administration of contrast media for diagnostic imaging in anaesthetized dogs and cats: a retrospective study. Vet Anaesth Analg 2016;43:502510.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 9.

    Agresti A. An introduction to categorical data analysis. 2nd ed. Hoboken, NJ: John Wiley & Sons, 2007.

  • 10.

    McCullough PA, Choi JP, Feghali GA, et al. Contrast-induced acute kidney injury. J Am Coll Cardiol 2016;68:14651473.

  • 11.

    Morcos SK, Thomsen HS. Adverse reactions to iodinated contrast media. Eur Radiol 2001;11:12671275.

  • 12.

    Namasivayam S, Kalra MK, Torres WE, et al. Adverse reactions to intravenous iodinated contrast media: an update. Curr Probl Diagn Radiol 2006;35:164169.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 13.

    Krautwald-Junghanns ME, Schloemer J, Pees M. Iodine-based contrast media in avian medicine. J Exot Pet Med 2008;17:189197.

  • 14.

    Pollard RE, Pascoe PJ. Severe reaction to intravenous administration of ionic iodinated contrast agent in two anesthetized dogs. J Am Vet Med Assoc 2008;233:274278.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 15.

    Pollard RE, Puchalski SM, Pascoe PJ. Hemodynamic and serum biochemical alterations associated with intravenous administration of three types of contrast media in anesthetized dogs. Am J Vet Res 2008;69:12681273.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 16.

    Yu PH, Lee YL, Chen CL, et al. Comparison of three computed tomographic angiography protocols to assess diameters of major arteries in African grey parrots (Psittacus erithacus). Am J Vet Res 2018;79:4253.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 17.

    Beaufrère H, Rodriguez D, Pariaut R, et al. Estimation of intrathoracic arterial diameter by means of computed tomographic angiography in Hispaniolan Amazon parrots. Am J Vet Res 2011;72:210218.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 18.

    Kirk N, Echols S, Wilcox C, et al. Comparison of different doses and delivery methods of IsoVue 370 IV for CT contrast study in birds, in Proceedings. ExoticsCon 2019 2019;103.

    • Search Google Scholar
    • Export Citation
  • 19.

    Zhang B, Dong Y, Liang L, et al. The incidence, classification, and management of acute adverse reactions to the low-osmolar iodinated contrast media Isovue and Ultravist in contrast-enhanced computed tomography scanning. Medicine (Baltimore) 2016;95:e31709.

    • Search Google Scholar
    • Export Citation
  • 20.

    Hartman GW, Hattery RR, Witten DM, et al. Mortality during urography: Mayo Clinic experience. AJR Am J Roentgenol 1982;139:919922.

  • 21.

    Masch WR, Wang CL, Davenport MS. Severe allergic-like contrast reactions: epidemiology and appropriate treatment. Abdom Radiol (NY) 2016;41:16321639.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 22.

    Wysowski DK, Nourjah P. Deaths attributed to x-ray contrast media on US death certificates. AJR Am J Roentgenol 2006;186:613615.

  • 23.

    Pollard RE, Puchalski SM, Pascoe PJ, et al. Hemodynamic and serum biochemical alternations associated with intravenous administration of three types of contrast media in anesthetized cats. Am J Vet Res 2008;69:12741278.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 24.

    Zhao F, Lei R, Yang SK, et al. Comparative effect of iso-osmolar versus low-osmolar contrast media on the incidence of contrast-induced acute kidney injury in diabetic patients: a systematic review and meta-analysis. Cancer Imaging 2019;19:38.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 25.

    Zhang B, Liu J, Dong Y, et al. Extrinsic warming of low-osmolality iodinated contrast media to 37°C reduced the rate of allergic-like reaction. Allergy Asthma Proc 2018;39:e55e63.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 26.

    O’Malley B. Avian anatomy and physiology. In: O’Malley B, ed. Clinical anatomy and physiology of exotic species: structure and function of mammals, birds, reptiles and amphibians. London: Elsevier Ltd, 2005;97161.

    • Search Google Scholar
    • Export Citation
  • 27.

    Park HJ, Park JW, Yang MS, et al. Re-exposure to low osmolar iodinated contrast media in patients with prior moderate-to-severe hypersensitivity reactions: a multicentre retrospective cohort study. Eur Radiol 2017;27:28862893.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 28.

    Seamon AB, Hofmeister EH, Divers SJ. Outcome following inhalation anesthesia in birds at a veterinary referral hospital: 352 cases (2004–2014). J Am Vet Med Assoc 2017;251:814817.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 29.

    Carpenter JW. Exotic animal formulary. 5th ed. St Louis: Elsevier, 2018.

Supplementary Materials

Contributor Notes

Address correspondence to Dr. Beaufrère (beaufrer@uoguelph.ca).
  • 1.

    Krautwald-Junghanns M-E, Schumacher F, Tellhelm B. Evaluation of the lower respiratory tract in psittacines using radiology and computed tomography. Vet Radiol Ultrasound 1993;34:382390.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 2.

    Helmer P. Advances in diagnostic imaging. In: Harrison GJ, Lightfoot TL, eds. Clinical avian medicine. Vol 2. Palm Beach, Fla: Spix Publishing, 2006;653659.

    • Search Google Scholar
    • Export Citation
  • 3.

    Krautwald-Junghanns ME, Kostka VM, Dörsch B. Comparative studies on the diagnostic value of conventional radiography and computed tomography in evaluating the heads of psittacine and raptorial birds. J Avian Med Surg 1998;12:149157.

    • Search Google Scholar
    • Export Citation
  • 4.

    Dos Santos GJ, da Silva JP, Hippólito AG, et al. Computed tomo-graphic and radiographic morphometric study of cardiac and coelomic dimensions in captive blue-fronted Amazon parrots (Amazona aestiva, Linnaeus, 1758) with varying body condition scores. Anat Histol Embryol 2020;49:299306.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 5.

    Laniesse D, Beaufrère H, Mackenzie S, et al. Perforating foreign body in the ventriculus of a pet pigeon (Columba livia domestica). J Am Vet Med Assoc 2018;253:16101616.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 6.

    Beaufrère H, Laniesse D, Kabakchiev C, et al. Multiple fractures and luxations of palatofacial bones in a hawk-headed parrot (Deroptyus accipitrinus). J Am Vet Med Assoc 2019;254:251256.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 7.

    Barboza TK, Beaufrère H, Chalmers H. True coelomic hernia and herniorrhaphy in a yellow-crowned Amazon parrot (Amazona ochrocephala). J Avian Med Surg 2018;32:221225.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 8.

    Scarabelli S, Cripps P, Rioja E, et al. Adverse reactions following administration of contrast media for diagnostic imaging in anaesthetized dogs and cats: a retrospective study. Vet Anaesth Analg 2016;43:502510.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 9.

    Agresti A. An introduction to categorical data analysis. 2nd ed. Hoboken, NJ: John Wiley & Sons, 2007.

  • 10.

    McCullough PA, Choi JP, Feghali GA, et al. Contrast-induced acute kidney injury. J Am Coll Cardiol 2016;68:14651473.

  • 11.

    Morcos SK, Thomsen HS. Adverse reactions to iodinated contrast media. Eur Radiol 2001;11:12671275.

  • 12.

    Namasivayam S, Kalra MK, Torres WE, et al. Adverse reactions to intravenous iodinated contrast media: an update. Curr Probl Diagn Radiol 2006;35:164169.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 13.

    Krautwald-Junghanns ME, Schloemer J, Pees M. Iodine-based contrast media in avian medicine. J Exot Pet Med 2008;17:189197.

  • 14.

    Pollard RE, Pascoe PJ. Severe reaction to intravenous administration of ionic iodinated contrast agent in two anesthetized dogs. J Am Vet Med Assoc 2008;233:274278.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 15.

    Pollard RE, Puchalski SM, Pascoe PJ. Hemodynamic and serum biochemical alterations associated with intravenous administration of three types of contrast media in anesthetized dogs. Am J Vet Res 2008;69:12681273.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 16.

    Yu PH, Lee YL, Chen CL, et al. Comparison of three computed tomographic angiography protocols to assess diameters of major arteries in African grey parrots (Psittacus erithacus). Am J Vet Res 2018;79:4253.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 17.

    Beaufrère H, Rodriguez D, Pariaut R, et al. Estimation of intrathoracic arterial diameter by means of computed tomographic angiography in Hispaniolan Amazon parrots. Am J Vet Res 2011;72:210218.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 18.

    Kirk N, Echols S, Wilcox C, et al. Comparison of different doses and delivery methods of IsoVue 370 IV for CT contrast study in birds, in Proceedings. ExoticsCon 2019 2019;103.

    • Search Google Scholar
    • Export Citation
  • 19.

    Zhang B, Dong Y, Liang L, et al. The incidence, classification, and management of acute adverse reactions to the low-osmolar iodinated contrast media Isovue and Ultravist in contrast-enhanced computed tomography scanning. Medicine (Baltimore) 2016;95:e31709.

    • Search Google Scholar
    • Export Citation
  • 20.

    Hartman GW, Hattery RR, Witten DM, et al. Mortality during urography: Mayo Clinic experience. AJR Am J Roentgenol 1982;139:919922.

  • 21.

    Masch WR, Wang CL, Davenport MS. Severe allergic-like contrast reactions: epidemiology and appropriate treatment. Abdom Radiol (NY) 2016;41:16321639.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 22.

    Wysowski DK, Nourjah P. Deaths attributed to x-ray contrast media on US death certificates. AJR Am J Roentgenol 2006;186:613615.

  • 23.

    Pollard RE, Puchalski SM, Pascoe PJ, et al. Hemodynamic and serum biochemical alternations associated with intravenous administration of three types of contrast media in anesthetized cats. Am J Vet Res 2008;69:12741278.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 24.

    Zhao F, Lei R, Yang SK, et al. Comparative effect of iso-osmolar versus low-osmolar contrast media on the incidence of contrast-induced acute kidney injury in diabetic patients: a systematic review and meta-analysis. Cancer Imaging 2019;19:38.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 25.

    Zhang B, Liu J, Dong Y, et al. Extrinsic warming of low-osmolality iodinated contrast media to 37°C reduced the rate of allergic-like reaction. Allergy Asthma Proc 2018;39:e55e63.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 26.

    O’Malley B. Avian anatomy and physiology. In: O’Malley B, ed. Clinical anatomy and physiology of exotic species: structure and function of mammals, birds, reptiles and amphibians. London: Elsevier Ltd, 2005;97161.

    • Search Google Scholar
    • Export Citation
  • 27.

    Park HJ, Park JW, Yang MS, et al. Re-exposure to low osmolar iodinated contrast media in patients with prior moderate-to-severe hypersensitivity reactions: a multicentre retrospective cohort study. Eur Radiol 2017;27:28862893.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 28.

    Seamon AB, Hofmeister EH, Divers SJ. Outcome following inhalation anesthesia in birds at a veterinary referral hospital: 352 cases (2004–2014). J Am Vet Med Assoc 2017;251:814817.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 29.

    Carpenter JW. Exotic animal formulary. 5th ed. St Louis: Elsevier, 2018.

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