Comparison of nonionic contrast agents iohexol and iotrolan for cisternal myelography in dogs

During this investigation, the use of iohexol was compared with iotrolan for canine cisternal myelography. Iohexol and iotrolan myelography was done in 6 dogs by cisternal puncture with a 6-week interval between both procedures; each dog served as its own control. Cerebrospinal fluid (CSF) was collected for baseline analysis from each dog immediately before the contrast agent was injected. Cerebrospinal fluid samples were obtained at 1, 3, 7, and 14 days after injection of each contrast medium for cytologic and chemical analysis. Total CSF leucocyte count and glucose concentration did not change significantly in comparison with baseline data in any of the samples. After the injection of iohexol, protein concentration increased significantly in the 24-hour sample, and lactate dehydrogenase activity increased significantly in the 3-day sample. Significant difference was not found between the different samples collected at 1, 3, 7, and 14 days, compared with both contrast media. None of the dogs had seizure activity during a 5-hour postmyelographic observation period. Pathologic changes were not found by gross or microscopic examination of the spinal cord. Although a degradation in time of radiographic quality of all myelograms took place, the average radiographic score decreased more rapidly with iohexol. The average score at 90 minutes with iotrolan was comparable with the score at 45 minutes with iohexol, and the average score at 150 minutes with iotrolan was better than the score at 90 minutes with iohexol. At 5 and 10 minutes after cisternal injection, no significant difference was observable between the myelograms, but from 45 minutes onward, myelograms with iotrolan were superior.     

Effect of contrast media formulation on computed tomography angiographic contrast enhancement.

The characteristics of contrast media formulation (mgI/ml, osmolarity, and viscosity) are generally not considered important in computed tomography (CT) angiography in animals. The purpose of this study was to assess the contrast effect in CT angiography as a function of contrast media formulation, with a constant iodine dose. The contrast effects of three contrast media with different iodine concentrations were compared by administering identical iodine dosages (mgI/kg). The contrast effects of the three contrast media differed, and the area under the time-attenuation curve of iohexol 350 mgI/ml, which had the highest iodine concentration, was the lowest. It was hypothesized that the contrast effect of a contrast medium decreases with higher iodine concentration because of the high amount of residual iodine present in the circulatory system from the injection site to the portion immediately before the great vessels. In addition, the influence of osmotic dilution on contrast media with high osmolarity was also considered. In conclusion, the contrast effect varies with different contrast media formulations, even when the same iodine dosage is administered.     

IOHEXOL AND IOPAMIDOL MYELOGRAPHY IN THE DOG: A CLINICAL TRIAL COMPARING ADVERSE EFFECTS AND MYELOGRAPHIC QUALITY

In a blind clinical trial, adverse effects after iohexol and iopamidol myelography were evaluated in 151 dogs. Eighty-one dogs were given iohexol (240 mgI/ml) and 70 dogs were given iopamidol (200 mgI/ml) by pre-determined assignment. Each dog was evaluated postmyelographically for seizures, hyperthermia, prolonged recovery from anesthesia and intensification of pre-existing neural signs. Myelographic quality was evaluated with a subjective scoring method. In comparing iohexol and iopamidol groups, there was not a statistically significant difference in the incidence of adverse effects or in myelographic quality. Iopamidol and iohexol appeared to be equally efficacious for routine canine myelography.     

Complications associated with the use of iohexol for myelography of the cervical vertebral column in dogs: 66 cases (1988-1990).

Medical records of 66 dogs that had undergone myelography, using iohexol (240 mg of iodine/ml, 0.3 to 0.5 ml/kg of body weight) during a 2-year period, were reviewed. In 3 dogs, myelography was performed twice during different anesthetic procedures. Neurologic abnormalities were more pronounced the day after myelography in dogs with caudal cervical spondylomyelopathy (P less than 0.01), meningitis (P less than 0.01), or extradural tumors (P less than 0.05). Neither anesthetic regimen nor duration of anesthesia significantly affected the frequency of complications. Seizures occurred after myelography in 6 dogs, and 1 dog had seizures after each of 2 myelographic procedures. The frequency of seizures was significantly greater in male Doberman Pinschers afflicted with caudal cervical spondylomyelopathy. Male dogs (P less than 0.01) and Doberman Pinschers (P less than 0.001) had higher prevalence of seizures. Caudal cervical spondylomyelopathy was associated with higher prevalence of seizures, compared with all other diagnoses (P less than 0.001). Seizures were significantly more prevalent when body weight was greater than or equal to 29 kg (P less than 0.001), when greater than or equal to 2 injections of contrast medium were administered (P less than 0.016), or when 2 injections of contrast medium were given at the cisterna magna (P less than 0.015). The 10% prevalence of seizures after myelography with iohexol in the study reported here is greater than in previous reports, but is lower than that reported after myelography using metrizamide.     

Use of iohexol for myelography in the horse

The use of iohexol as a contrast agent for myelography is reported in two groups of horses. Group 1 (n = 6) were used only for myelography and to assess the clinical and pathological effects of intrathecal administration of iohexol. A volume of 20 ml at a concentration of 300 or 350 mg iodine/ml gave satisfactory myelographic detail with no serious clinical or neurological side effects. Only a minimal inflammatory response could be demonstrated in cerebrospinal fluid at four and 14 days after injection. At post mortem examination 14 days after myelography there was no evidence of meningitis nor was any other pathological change detected. Group 2 (n = 19) comprised a series of clinical cases of suspected cervical vertebral malformation. The only untoward sequelae recorded involved two horses in which iohexol was diluted with sterile water prior in intrathecal injection. A progressive necrotising meningitis developed in both cases which necessitated euthanasia. It was concluded that the major advantages of iohexol for use in the horse were its diagnostic quality, safety and low cost.     

A PROSPECTIVE CLINICAL TRIAL COMPARING METRIZAMIDE AND IOHEXOL FOR EQUINE MYELOGRAPHY

A prospective clinical trial comparing adverse postmyelographic effects and myelographic quality of metrizamide and iohexol was conducted. Using a predetermined, randomized assignment, 24 horses exhibiting neurologic signs were administered either metrizamide (180 mgl/ml) or iohexol (180 mgl/ml) via cerebellomedullary puncture. Each horse was evaluated postmyelographically for adverse effects. Myelographic quality was assessed by a numerical scoring method. Adverse effects were observed more frequently with metrizamide (21) compared with iohexol (6) myelography (p < 0.05). Seizures, intensification of preexisting neurologic signs and prolonged anesthetic recovery were the most common complications after myelography. There was no difference in myelographic quality (p > 0.05). We conclude that iohexol is safer than metrizamide for equine myelography and that quality myelograms can be obtained with either contrast medium.     

IOHEXOL MYELOGRAPHY IN THE DOG

Myelography with iohexol (180 mg iodine/ml, 0.25 ml/kg), a new nonionic radiologic contrast medium, was performed in 100 dogs of 33 different breeds. In 96 of the dogs the iohexol mixed evenly with the cerebrospinal fluid, providing an homogeneous, continuous column of contrast medium within the subarachnoid space, and a radiologic diagnosis of a normal myelogram or disease involving the spinal cord was made. Pooling of iohexol in the dorsal part of the subarachnoid space occurred in four dogs; whether this was related to poor mixing of contrast medium with cerebrospinal fluid or disease of the spinal cord and meninges requires further study. Postmyelographic signs of central nervous system irritation (fasciculations of the temporal muscles and three episodes of seizure activity) were observed in only one dog and were controlled with diazepam. The presenting neurologic signs were aggravated after myelography in four other dogs, two of which were eventually killed. This study provided further evidence of the increased safety of iohexol compared with metrizamide, the first of the nonionic media, as a contrast medium for myelography in the dog.     

Estimation of glomerular filtration rate in healthy cats using single-slice dynamic CT and Patlak plot analysis

Commonly used clinical indicators of renal disease are either insensitive to early dysfunction or have delayed results. Decreased glomerular filtration rate (GFR) indicates renal dysfunction before there is a loss of 50% of functional nephrons. Most tests evaluate global rather than individual kidney function. Dynamic computed tomography (CT) and Patlak plot analysis allows for individual GFR to be tested. Our objectives were to establish a procedure and provide reference values for determination of global GFR in 10 healthy cats using dynamic CT (CTGFR). This method of GFR determination was compared against serum iohexol clearance (SIC). A single CT slice centered on both kidneys and the aorta was acquired every fifth second during and after a bolus injection of iohexol (240 mgI/ml; 300 mgI/kg) for 115 s. Using data from this dynamic acquisition, Patlak plots were obtained, GFR was calculated, and results were compared to global GFR determined by iohexol clearance. The average global CTGFR estimate was 1.84 ml/min x kg (SD = 0.43; range = [1.22, 2.45]). The average global GFR measured using SIC was 2.45 ml/min x kg (SD = 0.58; range = [1.72, 3.69]). GFR measurements estimated by both dynamic CT and SIC were positively associated (estimated Spearman rank correlation coefficient = 0.72; P = 0.0234). The CTGFR method consistently underestimated GFR with a bias of -0.62 (SE = 0.1307) when compared to SIC (P = 0.0011). In healthy cats, CTGFR was capable of determining individual kidney function and appears clinically promising.     

CT thoracic duct lymphography in cats by popliteal lymph node iohexol injection

Three different doses (1.0, 1.5, and 2.0 ml) of iohexol (300 mgl/ml) were injected percutaneously into the popliteal lymph node of eight adult cats under ultrasound guidance. Serial transverse CT images of five regions of interest (L3, T13, T8, T4, and T1 level) were performed at 2-min intervals, and the attenuation in Hounsfield Units (HU) of the lymphatic vessels was measured for determination of the optimal dose of iohexol and CT scan parameters. The optimal dose was 1.5 ml and helical CT acquisition is recommended to be performed as soon as possible after iohexol injection. In helical scans, the thoracic duct was characterized by variable branch numbers that formed a single trunk and entered the venous system at variable levels. CT lymphography using this protocol was performed in a cat with chylothorax. The thoracic duct was tortuous and focally dilated, and leakage of contrast medium was observed. Percutaneous CT lymphography using ultrasound-guided administration of iohexol into the popliteal lymph node appears reliable for delineation of the thoracic duct in cats.     

Iohexol myelography in the horse

Iohexol, a water soluble non-ionic contrast agent, was evaluated for myelography in the horse. Both 300 and 350 mg iodine/ml iohexol gave diagnostic cervical myelograms. Pathological changes were limited to extradural oedema and an increase in the number of white blood cells and specific gravity in the cerebrospinal fluid two days after myelography. This increase in white blood cells in the cerebrospinal fluid was, however, much less than that recorded by other authors using metrizamide and iopamidol contrast media. These findings indicate that iohexol is a less irritant myelographic contrast agent than those previously evaluated in the horse.     

Risk factors associated with development of seizures after use of iohexol for myelography in dogs: 182 cases (1998)

OBJECTIVE: To determine prevalence of seizures after use of iohexol for myelography and identify associated risk factors in dogs. DESIGN: Retrospective study. ANIMALS: 182 dogs that received iohexol for myelography in 1998. PROCEDURE: Medical records were reviewed for age, breed, sex, weight, dose and total volume of iohexol, injection site, number of injections, lesion type and location, total duration of anesthesia, duration from time of iohexol injection to recovery, presence and number of seizures, and whether surgery followed the myelogram. RESULTS: 39 (21.4%) dogs had at least 1 generalized seizure during or after myelography. Injection site was strongly associated with prevalence of seizures, and risk of seizure was significantly higher after cerebellomedullary injections, compared with lumbar injections. Mean total volume of iohexol administered to dogs that had seizures was significantly higher, compared with that administered to dogs that did not have seizures, although dosage did not differ between groups. Weight was significantly correlated with risk of seizure, and dogs that weighed > 20 kg (44 lb) had higher prevalence of seizures than dogs that weighed < 20 kg. CONCLUSIONS AND CLINICAL RELEVANCE: It is preferential to administer iohexol via the L5-6 intervertebral space to minimize the risk of seizures. Higher prevalence of seizures in large dogs, compared with smaller dogs, may be caused by administration of larger total volumes of contrast agent per volume of CSF.     

TOXICITY OF THE RADIOGRAPHIC CONTRAST MEDIA IOPAMIDOL, IOHEXOL AND METRIZAMIDE TO CELL CULTURES

Cultured murine embryonal carcinoma cells were exposed to the tri-iodinated radiographic contrast media iopamidol, iohexol and metrizamide at concentrations below those used for clinical myelography and examined by light and electron microscopy. Cytologic changes consisting of swelling and vacuolation of mitochondria and other cytoplasmic organelles were observed within 1 h of exposure to the contrast media. By 12 h of incubation cells altered shape, lifted from the culture dish and eventually died. These changes occurred irrespective of the osmolarity of the incubation medium and did not occur when cells were incubated in the presence of 1.16 mM EDTA or 10 mM Tris, which are present in commercial preparations of iopamidol and iohexol. Similar cytological changes were observed in cultures of neurons derived from embryonal carcinoma cells and in cultures of rat dorsal root ganglion cells. The results indicate that iopamidol, iohexol and metrizamide are cytotoxic to cells in culture at less than 20% of the concentration used for myelography and this could contribute to the adverse reactions to myelography seen in people and animals.     

Comparison of metrizamide and iohexol for cisternal myelographic examination of dogs

A double-blind study, using metrizamide, iohexol, or Ringer's solution (control) as cisternal myelographic agents, was performed on 25 dogs. Before myelographic examination was done, each dog was subjected to physical, clinical pathologic, and neurologic examinations, as well as examinations by electroencephalography and computerized tomography. These were repeated 24 hours after completion of the myelographic examination. The group of dogs given metrizamide (group II) had a significantly greater occurrence of seizure activity (6 of 10) than did the control dogs (group I; 0 of 5) or dogs given iohexol (group III; 0 of 10; P less than 0.003). In group II, the CSF microprotein concentration was significantly greater 24 hours after myelography was done than were the values in groups I and III (P less than 0.003). Myelograms of the group II dogs (metrizamide) and group III dogs (iohexol) had similar diagnostic qualities. At 24 hours after myelographic examination was done, computerized tomography scan revealed that each dog given metrizamide and iohexol had myelographic contrast material in the brain and cervical spinal cord parenchyma. Seemingly, iohexol has good diagnostic quality, but is less epileptogenic than metrizamide when used in cervical myelographic examinations of dogs.     

Relationship between plasma iohexol clearance and urinary exogenous creatinine clearance in dogs

The objective of this study was to determine if plasma iohexol clearance, computed by a 1-compartment model defined by 3 plasma samples. was an accurate measure of glomerular filtration rate (GFR) in dogs. Twenty-two adult Beagle dogs of both genders were studied. Ten dogs had intact kidneys, and 12 dogs had surgically reduced renal mass. A bolus injection of iohexol was made, and blood was obtained for plasma iohexol assay after 120, 180, and 240 minutes. Plasma was analyzed for iohexol concentration by means of 3 assay methods: chemical, high-performance liquid chromatography (HPLC), and inductively coupled plasma emission spectroscopy (ICP). Urinary clearance of exogenous creatinine was used to measure GFR for three 30-minute periods occurring between 150 and 240 minutes after iohexol injection. Plasma clearance of iohexol and renal clearance of creatinine were compared by linear regression analysis and by limits of agreement techniques. Plasma iohexol clearance and urinary exogenous creatinine clearance were significantly correlated (chemical R2 = .90; HPLC R2 = .96; and ICP R2 = .96). The 1-compartment iohexol clearance:exogenous creatinine clearance ratios were 1.04 +/- 0.17, 1.05 +/- 0.14, and 1.10 +/- 0.15 for the chemical, HPLC, and ICP methods of assay, respectively, indicating that plasma iohexol clearance slightly overestimated GFR. Assuming a +/- 2 standard deviation interval for error, corrected plasma iohexol clearance measured GFR with +/-34% accuracy for the chemical, +/-26% accuracy for the HPLC, and +/-27% accuracy for the ICP method. These results indicate that plasma iohexol clearance should have utility for detection of renal dysfunction earlier in the course of progressive renal disease than is possible with measurement of plasma creatinine or urea concentrations.     

Comparison of excretory urographic contrast effects of dimeric and monomeric non-ionic iodinated contrast media in dogs

In excretory urography, the osmolarity of contrast media has rarely been treated as important in veterinary medicine. In this study, the contrast effect of two contrast media (monomeric iohexol and dimeric iodixanol) in the renal cortex and aorta were compared using computed tomography (CT). Five beagle dogs were used and the study employed a cross-over method for each contrast media. The results showed that there was no difference between the media in the aorta, but iodixanol showed higher CT value and a longer contrast effect than iohexol in the renal cortex, in spite of having the same iodine dosage. It is believed that iodixanol, with its low osmolarity, is diluted less by osmotic diuresis than monomeric iohexol. It is important to consider the osmolarity of the contrast media when evaluating the contrast effect, and it is essential to use the same contrast media for each examination, or the renal excretory speed will be under/overestimated.     

Anatomical study of the gastrointestinal tract of a pudu (Pudu puda) using contrast-enhanced abdominal computed tomography

The pudu (Pudu puda), which is the smallest deer in the world and inhabits central and southern Chile and Argentina, is a ruminant and a browsing herbivore. The aim of this study was to provide a reference for interpretation of the normal anatomy of the pudu's gastrointestinal tract as imaged by abdominal computed tomography (CT). For the study, one adult female pudu was used. After a 24-h fast, the pudu was anaesthetized and positioned in sternal recumbency at the CT table. Image acquisition began immediately after intravenous injection of contrast media (MD-76(?); 370 mgI/ml) into the cephalic vein. Injection of contrast material was administered as a biphasic protocol. First, a manual bolus of contrast material was injected at a rate of 4 ml/s. Then, an additional continuous infusion injection (0.1 ml/min) was performed for adequate opacification of vascular structures. Transverse images of 5 mm thickness and 5 mm interval were obtained with a fourth-generation CT scanner, from the ninth thoracic vertebra (T9) until the first sacral (S1) vertebrae. CT images were labelled and compared with anatomical reference images for ruminants. Structures that were identified in the abdominal cavity included the stomach with its four compartments (rumen, reticulum, omasum and abomasum), the small and large intestines, liver, spleen, kidneys and some major blood vessels (aorta, caudal vena cava). The distal loop of the ascending colon, the transverse colon, the pancreas and lymph nodes could not be identified. The resulting CT images provide a reference for normal cross-sectional abdominal anatomy of the adult pudu.     

Comparison of different doses of iohexol with amidotrizoate for excretory urography in cats.

In five cats with normal renal function, doses of 200, 400, 600 and 800 mg iodine kg(-1)bodyweight of iohexol (350 mg iodine ml(-1)) were assessed in comparison to a dose of 880 mg iodine kg(-1)bodyweight of meglumine-sodium amidotrizoate (370 mg iodine ml(-1)) to determine the smallest dose which produces diagnostically adequate results for excretory urography. Urographic quality, haematologic and biochemical parameters, urinalysis and urinary osmolality, pulse and respiratory rates, blood pressure and adverse effects were determined. Iohexol presented fewer adverse reactions and influenced blood pressure less than amidotrizoate. The smallest dose of iohexol which provided urograms of similar quality to amidotrizoate was 400 mg iodine kg(-1)bodyweight. This study suggests that iohexol is safer and produces urograms of better quality than amidotrizoate.     

EVALUATION OF IOHEXOL AS A GASTROINTESTINAL CONTRAST MEDIUM IN NORMAL CATS

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.     

Effects of hyperosmolar ionic and low osmolar non-ionic contrast media on coagulation times and some blood parameters in dogs: an in vivo study

The purpose of this study is to evaluate the effects of hyperosmolar ionic contrast media (CM) (diatrizoate) and low osmolar non-ionic CM (iohexol and ioxilan) on coagulation time and some blood parameters in dogs in vivo. The animals were divided into three groups in equal numbers. The dogs in groups I, II and III received diatrizoate, iohexol and ioxilan at the dose of 700 mgI/kg intravenously (IV) as a bolus, respectively. Administration of contrast media and blood samples were collected from vena cephalica antebrachii prior to CM administration and thereafter at 3, 15, 30, 60, 90 and 180 min and 24 h to measure the coagulation factors [activated partial thromboplastin time (APTT), prothorombin time (PT), fibrinogen and fibrinogen degradation products] and some other blood parameters [red blood cells, platelet, white blood cells, haematocrit (Ht) and haemoglobin (Hb)]. While a statistically significant decrease was observed on APTT at 15 min in group III, no significant differences were found in groups I and II. All the groups had insignificant alterations for PT, fibrinogen and fibrinogen degradation product, following CM administration. Significant decreases were observed for platelet at 3 min in all groups. This decrease was also significant at 15- and 30- min intervals in group I. There were significant decreases for erythrocytes, Ht and Hb measurements within 30 min, and no significant alterations were observed for leucocytes within 60 min in all groups compared with baseline values. No differences were observed with regard to coagulation times and some blood parameters as far as long-lasting and major effects of each CM are concerned.     

Simplified methods for estimation of plasma clearance of iohexol in dogs and cats

The purpose of this study was to evaluate simplified methods for iohexol plasma clearance estimation in dogs and cats. Serial blood samples were taken before and 5, 20, 40, 60, 80, 100, 120, 150, 180, and 240 minutes after a bolus injection of iohexol in 51 dogs and 25 cats. Iohexol plasma concentration was determined with X-ray fluorescence. Clearance was calculated by dividing the injected dose by the area under the plasma tracer elimination curve estimated with a 2-compartment pharmacologic model. Clearance was normalized to body surface area (BSA). The 10-point clearance was used as a reference for the evaluation of simplified methods. A 2-sample method based on a single exponential fit and a single-sample method based on a linear quadratic model were investigated. Simplified methods were evaluated by calculating the standard deviation of the difference (SDD) between the clearances obtained with the simplified methods and the 10-point reference method. All combinations of sampling times were evaluated. The best sampling times were chosen for dogs and cats as the ones yielding the lowest SDD. Linear regression analysis was performed between the reference method and the optimized simplified methods. The best combination of time for the 2-sample method was 5 and 120 minutes in dogs and 20 and 180 minutes in cats. The best time for sampling in the single-sample method was 120 minutes in dogs and 80 minutes in cats. Plasma clearance of iohexol can be estimated in dogs and cats from 1 or 2 blood samples with a reasonable margin of error.