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.     

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.     

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.     

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.     

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.     

A COMPARISON OF IOPAMIDOL AND METRIZAMIDE FOR CERVICAL MYELOGRAPHY IN THE DOG

Cervical myelography using iopamidol, a new nonionic contrast medium, was studied in nine dogs. Postmyelographic seizure activity, motor evoked potentials, and rectal temperatures were monitored, and myelographic quality was subjectively evaluated. The results were compared with data from eight dogs that had metrizamide myelography. The iopamidol group had fewer seizures ( p < 0.01) but exhibited no difference in motor evoked potential or rectal temperature recordings. Myelographic quality was similar for iopamidol and metrizamide. The study suggests that iopamidol was less neurotoxic than metrizamide for canine cervical myelography.     

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.     

The difference of contrast effects of myelography in normal dogs: comparison of iohexol (180 mgI/ml), iohexol (240 mgI/ml) and iotrolan (240 mgI/ml)

The contrast effects of three different contrast media preparations (iohexol 180 mgI/ml, iohexol 240 mgI/ml and iotrolan 240 mgI/ml) in conventional and CT myelography were compared. Three beagle dogs were used and the study employed a cross-over method (total of 9) for each contrast media. The result of CT myelography showed that the contrast effect of iohexol (180 mgI/ml), which had low viscosity, was highest in cranial sites, and the contrast effect of high-viscosity iotrolan (240 mgI/ml) was highest in caudal sites 5 min after injection of the contrast media preparations. This shows that the diffusion of contrast media preparations in the subarachnoid space is influenced by viscosity. The results of conventional myelography also showed that the diffusion of contrast media preparations is influenced by viscosity. Therefore, it is important to identify the location of spinal lesions in veterinary practice, and low viscosity contrast medium preparation with wide spread contrast effects is considered suitable for myelography.     

Iohexol myelography in the dog and cat: a series of one hundred cases, and a comparison with metrizamide and iopamidol

Iohexol has been found to be a safe and radiographically satisfactory myelographic contrast medium in man and some experimental animals. This study has shown it is also suitable for the dog and cat. No adverse side effects were encountered and radiographic quality was good. A random comparison found it superior in radiographic quality to metrizamide. Iohexol is recommended as the contrast medium of choice for small animal myelography.     

MYELOGRAPHY IN THE CAT

Metrizamide myelographic examinations were performed on five normal cats using sequential cisternal and lumbar injections at weekly intervals to determine the dose of contrast medium required, adverse effects, and quality of the myelographic study. The normal myelographic appearance in the cat is described. All spinal cords were examined histopathologically after the termination of the study, and variable mild lesions were found. Doses of 0.2 ml/kg, 0.35 ml/kg, and 0.4 ml/kg metrizantide, respectively, for lumbar, thoracolumbar, and complete spinal studies are recommended when performing lumbar injection. Recommended doses using cisternal injection for cervical, cervicothoracic, and complete spinal studies are 0.2, 0.45, and 0.5 ml/kg, respectively. Subjectively, lumbar injection produced higher-quality thoracolumbar myelograms and cisternal injection produced higher-quality cervical studies. Clinical complications during the study included one seizure following cisternal myelography and mild neurologic deficits in all cats, which resolved within 36–48 hours.     

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.     

COMPLICATIONS OF METRIZAMIDE MYELOGRAPHY IN THE DOG: A SUMMARY OF 107 CLINICAL CASE HISTORIES

The case histories of 107 dogs undergoing metrizamide myelography at two veterinary hospitals were reviewed. Twenty-three variables, including body weight, injection site, dose of contrast medium, and medical complications during and after recovery from anesthesia, were submitted to statistical analysis by computer. Partial or generalized seizures were the most common medical complications, occurring in 54 percent of the dogs weighing more than 29 kg. Other less frequent medical complications were exacerbation of neurologic signs the day following myelography (11 percent), transient apnea during contrast medium injection (9 percent), vomiting (5 percent), hyperesthesia (3 percent), pyrexia (1 percent), and death (1 percent). The incidence of medical complications associated with metrizamide myelography in this study is higher than in previous reports. The most likely variables associated with seizures were high injection volumes and metrizamide injection at the cisterna magna. The preanesthetic administration of intramuscular pentobarbital did not significantly reduce seizure incidence. Seizures were controlled by anticonvulsant medication.     

COMPARISON OF MAGNETIC RESONANCE IMAGING AND MYELOGRAPHY IN 18 DOBERMAN PINSCHER DOGS WITH CERVICAL SPONDYLOMYELOPATHY

Eighteen Doberman pinscher dogs with clinical signs of cervical spondylomyelopathy (wobbler syndrome) underwent cervical myelography and magnetic resonance (MR) imaging. Cervical myelography was performed using iohexol, followed by lateral and ventrodorsal radiographs. Traction myelography was performed using a cervical harness exerting 9 kg of linear traction. MR imaging was performed in sagittal, transverse, and dorsal planes using a 1.5 T magnet with the spine in neutral and traction positions. Three reviewers independently evaluated the myelographic and MR images to determine the most extensive lesion and whether the lesion was static or dynamic. All reviewers agreed with the location of the most extensive lesion on MR images (100%), while the agreement using myelography was 83%. The myelogram and MR imaging findings agreed in the identification of the affected site in 13-16 dogs depending on the reviewer. MR imaging provided additional information on lesion location because it allowed direct examination of the spinal cord diameter and parenchyma. Spinal cord signal changes were seen in 10 dogs. Depending on the reviewer, two to four dogs had their lesions classified as dynamic on myelography but static on MR images. Myelography markedly underscored the severity of the spinal cord compression in two dogs, and failed to identify the cause of the signs in another. The results of this study indicated that, although myelography can identify the location of the lesion in most patients, MR imaging appears to be more accurate in predicting the site, severity, and nature of the spinal cord compression.     

EFFECTS OF POSTMYELOGRAPHIC REMOVAL OF METRIZAMIDE IN DOGS

Using a paired crossover trial, the effects of postmyelographic removal of metrizamide injected via the cerebellomedullary cistern were studied in 16 normal dogs. Each animal received a routine and a withdrawal myelogram. Seizure activity, changes in spinal evoked motor potentials and body temperature were measured following each myelogram. The amount of metrizamide removed was determined by densitometrically analyzing radiographs of cerebrospinal fluid/metrizamide aliquots recovered during the withdrawal procedure. There was a significant decrease in the number of seizures for withdrawal versus nonwithdrawal myelography (p < 0.01). The mean amount of metrizamide withdrawn per dog was 29% of the total injected.     

Cerebrospinal fluid changes after iopamidol and metrizamide myelography in clinically normal dogs.

Cerebrospinal fluid samples from 2 groups of clinically normal dogs were compared after iopamidol (n = 9) and metrizamide (n = 8) myelography. Iopamidol (200 mg of I/ml) and metrizamide (170 mg of I/ml) were administered by cerebellomedullary injection at dosage of 0.45 ml/kg of body weight. In dogs of both groups, postmyelographic CSF changes included high specific gravity, Pandy score, protein concentration, and WBC count. The high specific gravity and Pandy score were false-positive effects attributed to nonionic contrast media. Although postmyelographic protein concentration and total WBC count were greater in CSF samples from dogs given metrizamide than in those given iopamidol, differences were not statistically significant. The differential WBC counts were consistent with mild, acute leptomeningitis; these findings were supported by results of histologic examination. Iopamidol and metrizamide should be considered low-grade leptomeningeal irritants in dogs.     

EFFECTS OF METRIZAMIDE MYELOGRAPHY ON CEREBROSPINAL FLUID ANALYSIS IN THE DOG

The effect of metrizamide myelography on the composition of cerebrospinal fluid (CSF) was studied. Seven dogs received an intracisternal injection of metrizamide. An intracisternal puncture was performed in three additional dogs that did not receive metrizamide. CSF was collected before myelography and 24, 72, and 144 hours after myelography from all dogs. A significant increase in the percentage of neutrophils (p<0.05) and a pleocytosis noted 24 hours after myelography (p<0.02) were attributed to the effect of metrizamide. Significant increases in total protein concentration (p<0.001) and erythrocyte count (p<0.05), and a decrease in the percentage of small mononuclear cells (p<0.01) were attributed to repeated intracisternal puncture. No significant changes were observed for CSF creatine phosphokinase activity or the percentage of large mononuclear cells.     

Influence of anesthetic regimen on the frequency of seizures after cervical myelography in the dog

We examined the influence of various anesthetic drug combinations on the frequency of seizures in dogs after cervical myelography with metrizamide. Over a 12-month period, 78 dogs admitted to the teaching hospital for cervical myelography were assigned randomly to 1 of 6 anesthetic protocols. Myelography was performed, and the dogs were observed for signs of seizure activity after recovery from anesthesia. The person making the decision as to whether or not a dog had had a seizure was unaware of the anesthetic protocol that had been used. Preanesthetic treatment with pentobarbital (5.0 mg/kg) and maintenance of anesthesia with methoxyflurane significantly reduced the frequency of seizures (P less than 0.05). No reduction in seizure frequency was seen with any anesthetic protocol using halothane as the maintenance agent.     

Prevention of postmetrizamide myelographic seizures in dogs, using 5% dextrose solution

Diuresis by IV administration of 5% dextrose in a balanced electrolyte solution (BES) reduced the frequency of occurrence of postmyelographic seizures in dogs. In the first study, a single myelogram was obtained in 8 dogs without dextrose diuresis. Two of these dogs weighed greater than 15 kg and both had seizures after metrizamide myelography. The remaining 6 dogs weighed less than 15 kg and only 2 had seizures. Greater body weight may have increased the risk of postmyelographic convulsions. In a crossover study, myelograms were obtained in 12 dogs weighing 20 to 31 kg. Six dogs were given 5% dextrose in BES (20 ml/kg of body weight/hr [diuresed]) and 6 were given BES alone (10 ml/kg/hr [not diuresed]). When myelography was repeated 10 days later, the 6 dogs that had been given 5% dextrose in BES were given BES only and the 6 dogs that had been given BES alone were given 5% dextrose in BES. The frequency of convulsions after metrizamide myelography was lower when dogs were given dextrose (33%) than when they were not (100%).     

Cerebrospinal fluid response following metrizamide myelography in normal dogs: effects of routine myelography and postmyelographic removal of contrast medium

The effect of metrizamide myelography on 90-minute postmyelographic cerebrospinal fluid (CSF) samples was evaluated in a paired crossover study in 16 normal dogs. Each dog received a routine cervical myelogram (nonwithdrawal myelography) and a myelogram followed by contrast medium removal via aspiration from the subarachnoid space (withdrawal myelogram). Following nonwithdrawal myelography, the CSF was characterized by mild inflammation with a mixed pleocytosis and increased protein concentration. Compared with the nonwithdrawal CSF samples, the postmyelographic CSF of the withdrawal dogs had a more severe inflammatory response with significant increases (p < 0.05) in absolute numbers of neutrophils, monocytoid cells, eosinophils, lymphocytes, and protein concentration. The withdrawal procedure may have contributed an additional mechanical effect on the leptomeninges producing the more severe inflammatory response in the withdrawal dogs. Although seizure data are not reported here, postmyelographic seizures were more frequent following non-withdrawal myelography as compared with withdrawal myelography (p < 0.05), suggesting a decrease in metrizamide-induced neurotoxicity for the withdrawal dogs.     

MECHANICAL ASPECTS OF SUBARACHNOID SPACE PUNCTURE IN THE DOG

Lumbar subarachnoid space puncture using two different techniques was performed repeatedly on a dog following injection of metrizamide into the subarachnoid space at the cervical cistern. The lumbar needle punctures were observed fluoroscopically and recorded on 100-mm spot films at a rate of 2/sec. The needle tip indented the dura, depressing it several millimeters before penetration. A hemilaminectomy was performed on a cadaver, to expose the cord and intact meninges for confirmation of this compression. Cord compression and penetration during subarachnoid space puncture may contribute to the exacerbation or aggravation of neurologic signs that sometimes follows myelography.