EVALUATION OF IOHEXOL AS A GASTROINTESTINAL CONTRAST MEDIUM IN NORMAL CATS

JAMIE WILLIAMS, MS, DVM, DAVID S. BILLER, DVM, TAKAYOSHI MIYABAYASHI, BVS, MS, RENEE LEVEILLE, DVM'

The non-ionic, iodinated contrast medium, iohexol (240 mg I/ml) was evaluated as a gastrointestinal (GI) contrast medium in cats. Iohexol, both undiluted and diluted with tap water, was administered via a percutaneous endoscopically-placed gastrotomy (PEG) tube to 4 mature clinically normal cats. The dilution of contrast medium administered was 1:1, 1:2, and 1:3, and doses were 10 ml/kg and 5 ml/kg body weight. All combinations of dilution and dose of iohexol provided adequate visualization of the contrast medium column within the GI tract, and results were not significantly different than those observed using 30 % w/v barium sulfate. Dehydration and diarrhea were not observed after contrast medium administration, but vomiting occurred within 15-30 minutes after administration of undiluted iohexol in all experimental cats. Renal opacification did not occur on exposures made through a 2 hour period, and dilution in transit was not apparent. Veterinary Radiology & Ultrasound, Vol. 34, No. 5 , 1 9 9 3 , ~ ~ 310-314.

Key words: iohexol, non-ionic, upper gastrointestinal studies, cats, gastrointestinal contrast.

Introduction

ATS WITH SUSPECTED gastrointestinal (GI) disease C frequently are given barium sulfate suspension to eval- uate the GI tract. However, the use of barium is contrain- dicated whenever GI perforation is suspected, 1-3 because severe peritoneal reaction occurs following barium leak- age."6 Barium is not absorbed from the peritoneal cavity, and is difficult to remove from the omentum and serosal surfaces once it has gained access to the peritoneal cavity. Patients with a high risk of gastroesophageal reflux and secondary aspiration present another concern when barium is used because of the risk of aspiration pneumonia and pulmonary granuloma f~rmation.~" Another disadvantage of barium sulfate is its opacity which may obscure gastric mucosal visualization if endoscopy is attempted immedi- ately after an upper gastrointestinal (UGI) study.

Water-soluble iodinated contrast media (e.g., Gastrogra-

From the Department of Veterinary Clinical Sciences, College of Vet- erinary Medicine, The Ohio State University, 601 Vernon L. Tharp Street, Columbus, OH 43210-1089.

'Current address: Faculte de Medecine Veterinaire, Universite de Mon- treal, C.P. 5000, St-Hyacinthe, P.Q. Canada J2S 7C6.

Supported by Sanofi-Winthrop Pharmaceuticals and Eastman Kodak. Address correspondence to Dr. Jamie Williams, Department of Veteri-

nary Clinical Sciences, College of Veterinary Medicine, The Ohio State University, 601 Vernon L. Tharp Street, Columbus, OH 43210-1089. Address reprint requests to Dr. David Biller, Department of Veterinary Clinical Sciences, College of Veterinary Medicine, The Ohio State Uni- versity, 601 Vernon L. Tharp Street, Columbus, OH 43210-1089.

Received October 9, 1992; accepted for publication November 3, 1992.

fin") have been recommended in patients with suspected bowel p e r f ~ r a t i o n . ~ , ~ , ~ These agents cause less peritoneal irritation,'*6 and have a shorter GI transit time than bar- ium. 1,3,5,9,10 Endoscopic examination need not be delayed after use of these non-pigmented contrast agents. The dis- advantages of water-soluble iodinated contrast media are associated with their hypertonicity. The hypertonicity (1 900 Mosm/kg) of these compounds results in dilution of the contrast medium by body fluids drawn into the lumen of the intestine by This contrast dilution decreases opacity at the site of possible perforations. Diarrhea and dehydration have been reported as side effects of hypertonic iodinated contrast agent^,^.^.^^^^' '," and aspiration of hy- pertonic substances can result in severe pulmonary edema.738

Iohexo1,t a non-ionic iodinated contrast medium, has been used clinically for UGI studies in human patients, especially neonates, and has been shown to provide a con- trast column of good diagnostic quality.8,'0*'2 Langer et al. found the image quality with iohexol to be satisfactory, with good visualization of the stomach and small intestine in newborns and small infants.I2 No detectable dilution of the contrast medium in the distal ileum was found.'* Less bowel distention was seen with iohexol than with the hy- pertonic iodides, resulting in reduced stress to obstructed intestine^.'^,'^ In human patients, iohexol was rated equal

*Squibb diagnostics, New Brunswick, NJ 08903. tomnipaque, Sanofi-Winthrop Pharmaceuticals, New York, NY

10016.

310

VOL. 34, No. 5 IOHEXOL UGI STUDIES IN CATS 311

to barium and superior to Gastrografin in radiographic opac- ity and sharpness of the mucosal border, and superior to both barium and Gastrografin in overall quality of the ra- diographs. I 2 , l 3

Use of iohexol as a GI contrast medium in animals has only recently been The purpose of our study was to determine: 1) if in transit dilution, patient dehydra- tion, or diarrhea would occur using iohexol; 2) whether the resulting contrast medium column would be of diagnostic quality for detecting linear foreign body obstruction or in- testinal perforation; and 3) whether the overall quality of the study would be comparable to that obtained using 30% w/v barium sulfate.

Materials and Methods

Procedures were approved by the Institutional Laboratory Animal Care and Use Committee of the Ohio State Univer- sity. Four cats with percutaneous endoscopically-placed gastrotomy (PEG) tubes from a previous trial were used. Use of PEG tubes allowed a more accurate assessment of zero time radiographs after administration of contrast me- dium, and reduced the stress and irritation to each cat. The cats were clinically normal, in that they had no clinical evidence of gastrointestinal disease. Cats were deprived of food, but not water, overnight (at least 12 hours) prior to each UGI study. Their hydration status was evaluated by packed cell volume (PCV) and total protein concentration (TP) before and within 2 hours after conclusion of the stud- ies. Cats were monitored daily for any change in fecal con- sistency.

Iohexol (240 mg Uml) was diluted 1:1, 1:2 or 1:3 with water. Each cat received contrast medium on 7 occasions: 1) 10 ml/kg barium 30% w/v, 2) 10 ml/kg iohexol 1:1, 3) 5 ml/kg iohexol 1:1, 4) 10 ml/kg iohexol 1:2, 5) 5 ml/kg iohexol 1:2, 6) 10 ml/kg iohexol 1:3, and 7) 5 ml/kg iohexol 1:3. Both 10 ml/kg and 5 ml/kg undiluted iohexol were also administered, but all cats vomited within 15-30 minutes after contrast administration, so further evaluation of undi- luted iohexol was not done. There were at least 3 days between successive UGI studies in each cat. This resulted in a 4 X 2 factorial design, with each cat serving as its own control (Table 1). Each study included right lateral and ventrodorsal radiographs made every 15 minutes until con-

TABLE 1. Experimental Design

Dose

10 ml/kg 5 ml/kg

Iohexol 1:3 4 Iohexol 1.2 4 Iohexol 1:l 4 Iohexol 100% * Barium 30% 4

4 4 4 *

*Not completed because of vomiting within 15-30 minutes after contrast administration.

trast medium was seen in the large intestine or until 2 hours. Each study was independently evaluated by two board cer- tified radiologists and one board eligible radiologist. The radiologists were blinded to the protocol used in a given study. Overall quality of each study was scored as good, acceptable or unacceptable based on segmentation or floc- culation of contrast column, opacity of the contrast medium column, and residual coating of the mucosa. Complete gas- tric emptying time and small intestinal transit time were determined for each UGI study. Furthermore, each study was classified as to the perceived ability to diagnose ob- struction, linear foreign body, and intestinal perforation from the resulting contrast medium column. Opacity of the contrast medium in the ileum was compared to that in the duodenum (ileum > duodenum, ileum = duodenum, ileum < duodenum) in an attempt to evaluate contrast medium dilution.

Barium sulfate administered at a dose of 10 ml/kg was used as a standard for comparison. Each dilution-dose com- bination of iohexol was compared to the standard, and re- sults were analyzed for statistical significance using Chi square test. Significance was defined as p < 0.05. For the initial analysis, data for dilution in transit were grouped into two categories: 1) ileal opacity 2 duodenal opacity (no dilution observed) and 2) ileal opacity < duodenal opacity (dilution in transit). Overall quality of the study was grouped into 1) acceptable (good or acceptable) and 2) un- acceptable.

Results Diarrhea did not occur and patients did not become de-

hydrated, regardless of dilution or dose of iohexol admin- istered. However, all cats vomited within 15-30 minutes after administration of undiluted iohexol (240 mg I/ml) ne- cessitating abandonment of these studies. Further analysis of undiluted iohexol was not attempted.

No significant difference was found for dilution in transit or overall quality of the UGI, study, regardless of iohexol dilution at a dose of 10 ml/kg body weight. The number of UGI studies rated as good increased with increasing con- centration of iohexol, but this trend was not statistically significant. Villous borders were better visualized when us- ing iohexol, due to its decreased viscosity compared to bar-

TABLE 2. Complete Gastric Emptying (CGE) and Small Intestinal Transit (SIT) Times in Minutes. Mean and Standard Deviation

Dose ml/kg CGE SIT

Iohexol 1:3 10 60 * 30 60 * 15 Iohexol 1:2 10 60 * 30 45 k 30 Iohexol 1:l 10 60 t 30 45 f 30 Barium 30% 10 60 2 15 60 * 15 Iohexol 1:3 5 15 f 2.5 45 f 30 Iohexol 1:2 5 30 k 15 45 t 15 Iohexol 1 : 1 5 15 f 4 30 k 30

312

A

B

C

WILLIAMS ET AL 1993

FIG. 1. Lateral abdominal radiographs of the same cat demonstrating contrast medium throughout the GI tract. A = Iohexol 1:3, B = Iohexol 1:2, C = Iohexol 1:1, D = Barium sulfate 30%. Dose = 10 ml/kg. Time = 30 minutes.

D

VOL. 34, No. 5 IOHEXOL UGI STUDIES IN CATS 313

ium sulfate. This “halo” became more apparent with in- creasing dilution. Subjective evaluation of ability to diag- nose linear foreign body obstruction or intestinal perforation was not significantly different based on dilution of iohexol at 10 mlikg as compared to barium sulfate. Based on a power analysis, no significant difference would have been found if 32 cats were evaluated per treatment. Similarly, no significant difference was noted at the 5 mlikg dose com- pared to the standard. However, if 16 cats had been eval- uated per treatment, iohexol 1:l at the 5 ml/kg dose would have significant dilution in transit, a higher number of un- acceptable studies, and more studies thought to be non- diagnostic for linear foreign body obstruction. Intestinal distention was inadequate at the 5 mlikg dose, and segmen- tation of the contrast medium column was distracting and excessive.

Complete gastric emptying time was comparable between barium sulfate and the 10 ml/kg iohexol dose, independent of dilution. Small intestinal transit time was more rapid for iohexol than barium sulfate (Table 2). Complete gastric emptying time and small intestinal transit time were shorter for 5 ml/kg dose of iohexol than for the standard (Table 2).

Discussion Iohexol provided adequate diagnostic opacity in the GI

tract (Fig. 1) and exhibited all the advantages of other wa- ter-soluble contrast iodides without in transit dilution of the contrast medium column, diarrhea or dehydration. Presum- ably this was a consequence of the low osmolality and pre- administration dilution (Table 3). No additional information was obtained in studies performed in people in whom bar- ium sulfate was given after the use of iohexol.’ Further- more, there was no adverse pulmonary effect reported as- sociated with aspiration of iohexol,8212 due in part to its low osmolality (520 mOsm/kg). $ Diarrhea, pulmonary edema, and pneumonia secondary to aspiration have not been re- ported after use of iohexol as a GI contrast medium in human patients. ’’ Renal opacification secondary to gastro- intestinal absorption of iohexol was not seen in human pa- tients,” as was reported in cats with Gastrografin.’ We found no urinary tract opacification up to 2 hours after GI administration of dilute iohexol. Only 0.1-0.5% of the ad- ministered dose of iohexol is absorbed across the intact, normal gastric and small intestinal mucosa. D

The advantages of using iohexol as an UGI contrast me- dium include its safety, rapid transit time, absence of in transit dilution of the contrast medium column, acceptable quality of the contrast study, and low osmolality. On the basis of this study, iohexol was judged to provide adequate opacity with no dilution in transit. In fact, all 1:3 and half the 1:2 dilutions appeared to opacify in transit (i.e., ileal

$Iohexol 240 mg Uml. $Package insert, Iohexol, Sanofi-Winthrop.

TABLE 3. Expense, Concentration and Osmolality of Iohexol Dilutions Investigated

Cosffml ma Ilml Osmolalitv

130 mosmol Iohexol 1:3 $0.20 60 Iohexol 1:2 .26 80 173 mosmol Iohexol 1:l .39 120 260 mosmol lohexol undiluted .80 240 520 mosmol

285 mosmol Plasma ~~~ ~ ~

opacity was scored higher than duodenal opacity). This was felt to be due to mucosal absorption of the water used to dilute the iohexol before administration, and this conclusion was supported by lower PCV (1&20% decrease) and TP (5-8% decrease) values after contrast medium administra- tion. Furthermore, quality of the 10 ml/kg dose iohexol study was similar to that observed using barium sulfate. All dilutions of iohexol were subjectively felt to be adequate for diagnosis of linear foreign body obstruction or intestinal perforation. The only complications encountered were vom- iting when undiluted iohexol was administered, and seg- mentation and inadequate intestinal distention observed at the 5 mlikg dose. We found 1200 mg I, 800 mg I and 600 mg I per kilogram body weight to be adequate for UGI studies in cats. It is interesting that iohexol 1:3 at a dose of 10 ml/kg (600 nig Ilkg) was judged adequate, but iohexol 1: 1 at a dose of 5 mlikg (600 mg Iikg) was not, due to the previously mentioned segmentation and inadequate intesti- nal distention. In this instance, it would seem that volume, as it relates to concentration, is an important factor contrib- uting to the suitability of the contrast medium column.

Iohexol is more expensive than barium sulfate (i.e., ap- proximately $0.80 per ml for the 240 mg I/ml preparation). However, dilution with water reduces the cost of the total dose administered to the patient (Table 3). In our study on normal cats, evaluation of the contrast medium column as diagnostic for linear foreign body and intestinal perforation was subjective, based on opacity, absence of segmentation or flocculation, and rapidity of small intestinal transit time. We have used iohexol at our institution to establish the presence of GI obstruction and perforation in patients. l4 To date, no patients with perforation have been documented using iohexol or during surgery. We are continuing to in- vestigate iohexol in selected patients to better document its use in situations of suspected GI perforation. The advan- tages of iohexol justify its use as an UGI contrast medium in selected patients, despite its relative expense. A 1:3 di- lution at a dose of 10 mlikg will be adequate in most pa- tients in which a water-soluble iodide is indicated. The final dilution of iohexol must be based on the amount of gastric and intestinal fluid evident on survey radiographs. In ani- mals with increased intraluminal fluid, the 1:2 dilution at a dose of 10 ml/kg should be used. The 5 ml/kg dose is not recommended for UGI procedures because of inadequate intestinal distention and segmentation of the contrast me- dium column.

3 14 WILLIAMS ET AL 1993

REFERENCES

1. Morgan JP, Silverman S. Techniques of Veterinary Radiography. Ames: Iowa State University Press, 1989;284-287.

2. O’Brien TR, Biery DN, Park RD, Bartels JE. Radiographic Diag- nosis of Abdominal Disorders in the Dog and Cat: Radiographic Interpre- tation-Clinical Signs-Pathophysiology. Philadelphia: WB Saunders Co., 1978;204351.

3. Root CR, Morgan JP. Contrast radiography of the upper gastroin- testinal tract in the dog. A comparison of micropulverized barium sulfate and USP barium sulfate suspensions in clinically normal dogs. J Small Anim Pract 1969;10:279-286.

4. Moon M, Myer W. Gastrointestinal contrast radiology in small animals. Seminars in Vet Med and Surg (Small Animal) 1986;1(2):121- 143.

5. Thrall DE. Textbook of Veterinary Diagnostic Radiology. Phila- delphia: WB Saunders Co., 1986;473-510.

6. Noonan CD, Margalis AR. Small bowel transit time of water sol- uble iodinated contrast medium and barium sulfate in cats with simulated surgical acute abdomen. Am J Roentgen01 Rad Ther Nucl Med 1970;llO: 334-337.

7. Ginai AZ, ten Kate FJW, ten Berg RGM, Hoornstra K. Experi- mental evaluation of various available contrast agents for use in the upper gastrointestinal tract in case of suspected leakage. Effects on the lungs. Br J Radiol 1984;57:895-901.

8. Brick SH, Caroline DF, Lev-Toaff AS, et al. Esophageal disrup-

tion: Evaluation with iohexol esophagography. Radiology 1988;169:141- 143.

9 . Allan GS, Rendano VT, Quick CB, Meunier PC. Gastrografin as a gastrointestinal contrast medium in the cat. Am J Vet Radiol SOC 1979;11&116.

10. Laerum F, Stordahl A, Aase S. Water-soluble contrast media com- pared with barium in enteric follow-through. Acta Radiol 1988;29:603- 610.

11. Burk RL, Ackerman N. Small Animal Radiology. A Diagnostic Atlas and Text. New York: Churchill Livingston, 1986;14&178.

12. Langer R, Kaufmann HJ. Nonionic contrast media in gastrointes- tinal studies in newborns and small infants. Fortschr Geb Rontgenstr Nuklearmed Erganzungsband 1989;128:20&203.

13. Stordahl A, Laerum F. Comparison of water-soluble contrast media and barium in rats with small bowel obstruction or ischemia. Invest Radiol 1988;23:S22O-S223.

14. Williams J, Biller DS, Myer CW, Miyabayashi T, Leveille R. Use of iohexol as a gastrointestinal contrast agent in 3 dogs, 5 cats, and 1 bird. J Am Vet Med Assoc. 1993;202:624-627.

15. Agut A, Sanchez-Valverde MA, Lasaosa JM, Murciano J, Molina F. Use of iohexol as a gastrointestinal contrast medium in the dog. Vet Radiol and Ultrasound. 1993;34: 19 1-197.

16. Stordahl A, Laerum F, Gjolberg T, Enge 1. Water-soluble contrast media in radiography of small bowel obstruction. Acta Radiol 1988;29: 53-56.