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.     

Incidence of seizures associated with iopamidol or iomeprol myelography in dogs with intervertebral disk disease: 161 cases (2000–2002)

Objective – To compare the incidence of seizures in dogs with intervertebral disk disease after iopamidol or iomeprol myelography, and to assess whether the incidence of seizures differed between the 2 agents when severity of neurological deficits, location of cord compression, duration of anesthesia, site of myelogram, volume of contrast, and concentration of contrast were evaluated. Design – Retrospective study. Setting – Veterinary teaching hospital. Animals – One hundred and sixty‐one client‐owned dogs with intervertebral disk disease. Interventions – Subarachnoid injection of contrast medium. Measurements and Main Results – One hundred and sixty‐one dogs with intervertebral disk disease were subjected to myelography using iopamidol (n=74) or iomeprol (n=87). Cranial myelography was performed in 31 dogs, caudal myelography in 125 and both cranial and caudal myelography in 5. Seizures occurred in 23 of 161 (14%) dogs. There was no significant difference overall between iopamidol and iomeprol myelography. However, in dogs with thoracolumbar disk extrusion and paraplegia, seizures occurred more frequently after caudal myelography using iopamidol compared with iomeprol. Conclusions – Both iomeprol and iopamidol are suitable for myelography in dogs. Iomeprol is recommended for caudal myelography in paraplegic dogs with thoracolumbar disk extrusion due to the higher incidence of seizures in this group when iopamidol was used.     

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.     

Use of pentobarbital sodium to reduce seizures in dogs after cervical myelography with metrizamide

We conducted a prospective study to examine the effect of pentobarbital administration on the development of seizures in dogs that had undergone cervical myelography with metrizamide while anesthetized with halothane. Thirty dogs scheduled for cervical myelography were assigned to 3 groups. Dogs in group 1 received no pentobarbital. Those in group 2 were administered pentobarbital (5 mg/kg, IM) before induction of anesthesia, and those in group 3 received pentobarbital at the end of the procedure when the anesthetic vaporizer was turned off. Anesthesia was induced with thiamylal sodium in all dogs and was maintained with halothane. Dogs that underwent surgery immediately after the myelography were not included in the study. A significant difference was not found among the 3 groups in terms of number of dogs that had seizures, mean body weight of the dogs, duration of anesthesia after injection of metrizamide, time from extubation to first seizure, volume of metrizamide injected, or clinician performing the myelography.     

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%).     

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 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.     

Effect of intravenous administration of dextrose or lactated Ringer's solution on seizure development in dogs after cervical myelography with metrizamide

The effect of fluid (5% dextrose in water or lactated Ringer's solution) administered intravenously on the development of seizures after cervical myelography with metrizamide was studied in 10 dogs. In a crossover experimental design, 8 dogs were used twice. Urine output was measured during the second part of the study to determine whether diuresis was a factor affecting seizure development. Dogs given 5% dextrose in water had significantly (P less than 0.05) fewer seizures than did dogs given lactated Ringer's solution. This was attributed to an increase in CSF glucose concentration and was not associated with diuresis.     

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.     

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.     

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.     

EPIDUROGRAPHY IN THE NORMAL DOG: TECHNIC AND RADIOGRAPHIC FINDINGS

Ten clinically normal adult mongrel dogs were examined using lumbosacral epidurography in an effort to determine a reproducible technic and a normal radiographic appearance. The site of contrast medium injection was the ventral epidural space at the sacrococcygeal junction or the cranial coccygeal region. An initial dose of 0.15 ml/kg of metrizamide for the right lateral recumbent radiograph with 0.10 ml/kg additional metrizamide for additional right lateral or the subsequent dorsoventral radiographs was considered adequate. Two numerical values were observed for each normal epidurogram: the sacrovertebral angle; the ratio of the contrast medium column width to L6 body length. A statistically significant relationship between hindlimb positioning and the numerical value of the sacrovertebral angle was identified. Some advantages of epidurography for delineating the lumbosacral area are obvious: (1) it overcomes the limited value of lumbosacral area myelography; (2) it is technically easier than intraosseous vertebral venography; (3) there is minimal patient trauma; (4) there was no apparent adverse sequela to repeated contrast medium injections.     

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.     

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.     

STANDING MYELOGRAPHY IN THE HORSE USING A NONIONIC CONTRAST AGENT

Standing myelography in the horse has been previously described. In that study, metrizamide was used and significant complications were reported. In recent years, the introduction of less-toxic nonionic contrast media has reduced the incidence of complications. This study was undertaken to determine whether standing myelography using a nonionic contrast medium could provide a diagnostic study and be performed safely in the equine patient. Standing myelography was performed in eight horses. The contrast medium used was iohexol. In five horses a myelogram of diagnostic quality was achieved; in one horse contrast flowed only to the level of C6 and in two horses contrast medium did not reach the cervical subarachnoid space. Owing to the difficulty in achieving good flow of the contrast medium in some horses, this procedure may be of limited utility. However, if puncture of the lumbosacral subarachnoid space can be achieved easily and quickly, standing myelography may be a clinically useful procedure. It may be attempted in cases in which the economic value of the patient makes myelography under general anesthesia impractical. In patients presenting for evaluation of ataxia it may be possible to perform a standing myelogram at the time of CSF sample collection from the lumbosacral space.     

Myelographic localization of spinal cord compression in dogs. A comparison between cisternal and lumbar injections of metrizamide "Amipaque" in diagnosing and locating spinal cord compression.

Metrizamide is a new water-soluble contrast medium possessing unique properties, one of which is that even in an isotonic solution it has a radiographic density sufficient for a diagnostic myelogram. Whereas in the past myelography with water-soluble preparations invariably entailed lumbar injections, which are technically difficult in dogs, the fact that isotonic metrizamide causes so little tissue irritation has made it possible to inject the contrast solution into the cisterna magna. The author has compared metrizamide myelograms obtained with both cisternal and lumbar injections. Myelography with a cisternal injection is preferable for demonstrating cervical cord compressions and also in cases in which it is desirable to obtain myelographic information on both the cervical and the thoraco-lumbar areas. If, on the other hand, it is necessary to determine exactly the extent of a thoraco-lumbar compression before decompressive laminectomy, the contrast should be injected in the lumbar region in such an amount and at a pressure high enough to ensure that the contrast is forced past the site of the compression. The safety of metrizamide will probably enable a better prognosis following surgery than was previously possible.     

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.     

Transient leakage across the blood-cerebrospinal fluid barrier after intrathecal metrizamide administration to dogs

Cerebrospinal fluid samples from 9 dogs given 84 mg of metrizamide/kg of body weight intrathecally were collected at intervals from 3 hours to 30 days after treatment and were compared with CSF samples collected before metrizamide treatment (base line) and with samples taken at similar intervals from 2 nontreated control dogs. Increased CSF albumin (mean 19.2 mg/dl) and immunoglobulin (Ig) G (mean 5.91 mg/dl) concentrations occurred 1 day after myelography, compared with base-line concentrations (6.15 and 1.24 mg/dl, respectively) and with concentrations from controls. Immunoglobulin M and IgA concentrations also were increased in some of these samples. However, immediately after myelography (3 hours after treatment) CSF albumin and IgG concentrations were comparable with those of controls, and these values returned to base line within 5 days of myelography and remained so for 30 days. A high correlation between albumin and IgG concentrations of individual CSF samples indicated the likelihood that leakage across the blood-CSF barrier was the origin of the increased values. A transient increase in CSF leukocytes, consisting of mononuclear cells and neutrophils, was also noticed 1 day after treatment but not at other times and not in controls. Nonsuppurative, predominately histiocytic meningitis of decreasing intensity was noticed in dogs euthanatized at 1 or 5 days, but not in dogs euthanatized at 10, 20, or 30 days after treatment. The meningeal cells stained intensely with periodic acid-Schiff stain and intracellular contrast medium was ultrastructurally apparent in phagolysosomes. Control dogs killed after 30 days did not have these changes. The intrathecal administration of metrizamide resulted in transient leakage of serum components into CSF and an accompanying transient meningitis.     

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.