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.     

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.     

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.     

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.     

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.     

Neurotoxicologic effects of the nonionic contrast agent iopamidol on the leptomeninges of the dog

The effect of iopamidol on the leptomeninges was tested and compared with that of metrizamide and normal saline solution in 18 dogs. Pathologic and clinical effects were evaluated at 24 hours and 14 days after cisternal injection of iopamidol, metrizamide, or normal saline solution. Pathologic changes were evaluated by microscopic examination of serial CSF samples and of sections of brain and spinal cord with the leptomeninges intact. Clinical changes were subjectively evaluated. Electromyograms and EEG were performed on each dog after physical and neurologic examination. There were no changes seen in neurologic status, electromyogram, or EEG in any of the dogs immediately after subarachnoid injection nor at 24 hours or 14 days later. Pathologic changes were limited to mild, moderate, or severe patchy hemorrhagic leptomeningitis seen at 24 hours after iopamidol or metrizamide was injected. The severity of changes were judged to be similar with both these agents. The CSF analysis and histologic evaluation of brain and spinal cord sections revealed a neutrophilic response to iopamidol and a mononuclear response to metrizamide. These findings indicate that iopamidol has minimal neurotoxicologic effect on the leptomeninges and therefore has merit as a myelographic agent.     

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 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.     

STANDING MYELOGRAPHY IN SIX ADULT HORSES

Standing myelography was conducted in six neurologically normal adult horses. Myelograms were performed without general anesthesia or tranquilization. Four horses were premedicated orally with 2.2 milligrams/kilogram (mg/kg) of phenobarbital 16 hours and 4 hours prior to myelography to raise their seizure threshold. One-hundred milliters (ml) of cerebral spinal fluid (CSF) was withdrawn from the lumbosacral space prior to injection. Approximately 100 ml of technical grade metrizamide * was injected into the subarachnoid space via a lumbosacral tap. After injection the horse's head was lowered for approximately 10 minutes to facilitate cranial movement of the metrizamide. Lateral cervical radiographs were taken in a standing position. Filling of the subarachnoid space in the cranial cervical region was good to excellent in five horses. In one horse there was poor definition of the cranial cervical region. There was good to excellent filling of the subaranoid space in the caudal cervical region in all six horses. Reactions to metrizamide injection varied. The most severe reaction was generalized seizure.     

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%).     

Oxytocin Content of the Cerebrospinal Fluid of Dogs and Its Relationship to Pain Induced by Spinal Cord Compression

Objectives —To determine whether oxytocin exists in the cerebrospinal fluid (CSF) of dogs and whether the amount of oxytocin in the CSF of dogs with neck or back pain caused by spinal cord compression is significantly different than that in the CSF of clinically normal dogs.
Study Design —Prospective controlled study.
Animal Population —A total of 15 purpose-bred beagles and 17 client-owned dogs.
Methods —CSF was collected by needle puncture of the cerebellar medullary cistern after induction of general anesthesia. Oxytocin levels within the samples were determined through radioimmunoassay.
Results —Dogs with spinal cord compression had significantly more oxytocin in their CSF than the clinically normal dogs (13.76 ± 2.0 pg/mL and 3.61 ± 0.63 pg/mL, respectively; P < .0001). Dogs with chronic signs (>7 days) had significantly more oxytocin in their CSF than dogs with acute signs (<7 days) (21.60 ± 0.86 pg/mL and 6.80 ± 0.81 pg/mL, respectively; P < .0001). Both acutely and chronically affected dogs had significantly more oxytocin in their CSF than the controls ( P < .005 and P < .0001 respectively).
Conclusions —Dogs with neck and back pain caused by spinal cord compression have significantly more oxytocin in their CSF than clinically normal dogs. Dogs with chronic clinical signs have significantly more oxytocin in their CSF than dogs with acute clinical signs.
Clinical Relevance —In humans, intrathecal injection of oxytocin is effective in treating low back pain for up to 5 hours. Intrathecal oxytocin may be a logical choice for perioperative analgesia in dogs undergoing myelography because the intrathecal space is accessed for injection of contrast agent.     

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.     

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.     

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.     

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.     

Phagocytosis and erythrocyte antibody-rosette formation by three populations of mononuclear phagocytes obtained from dogs treated with glucocorticoids

The effect of systemic administration of glucocorticoids was evaluated on 3 populations of macrophages obtained from healthy dogs. Phagocytic and Fc-receptor activities were determined for mononuclear phagocytes from blood and pulmonary and peritoneal lavage fluids. Samples were collected from 12 dogs before treatment and again on the same dogs after glucocorticoid administration. Thirty or more days were allowed between treatment periods. Twelve hours after combined prednisolone sodium succinate and dexamethasone sodium phosphate administration, the percentage of phagocytosing cells decreased for blood monocytes and increased for pulmonary macrophages. The percentage of pulmonary macrophages positive for erythrocyte antibody-rosette formation (Fc-receptor activity) increased. After 7 days of oral administration of prednisone, the percentage of phagocytosing peritoneal macrophages increased, whereas the percentage of blood monocytes with Fc-receptor activity increased. Results indicate that significant (P less than 0.05) changes in macrophage function occur after systemic administration of the glucocorticoid doses used in this study. Also, the effect of systemic administration of glucocorticoids on mononuclear phagocytes varies, depending on the specific cell location.     

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.     

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.     

Serum biochemical indicators of hepatobiliary function in dogs following prolonged anaesthesia with sevoflurane or isoflurane

Objective To investigate the changes in serum enzymes considered as biochemical indicators of hepatobiliary function in dogs following 5 hours of anaesthesia with isoflurane (ISO) or sevoflurane (SEVO). Study design Experimental randomized crossover study, with intervals of at least 15 days between successive treatments. Animals Eight healthy adult mongrel dogs, four male, four female, weight 13.6–21.6 kg. Methods Treatments consisted of anaesthesia with ISO or SEVO at 1 or 1.5 minimum alveolar concentration (MAC) delivered in oxygen. MAC was taken as 1.39% for ISO and 2.36% for SEVO. Anaesthesia was induced by mask then, after endotracheal intubation, maintained according to the treatment protocol using a small animal circle system. Cardiopulmonary monitoring was carried out. Venous blood samples, obtained by needle puncture, were taken at 24 hours and 2, 7 and 14 days post anaesthesia. Serum concentrations of total protein, aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase, (LDH), alkaline phosphatase (ALP), gamma‐glutamyltransferese and total bilirubin were measured. Changes with time and with treatment were compared by Friedman analysis, Wilcoxon Signed test and Kruskal‐Wallis test as relevant. p‐ value < 0.05 was considered significant. Results Compared to base‐line values, at 24 hours post‐anaesthesia there were significant increases in AST, ALT, ALP and LDH following one or more of the treatments, but by 2 days residual changes were not significant. At 24 hours, AST for treatment 1.5 MAC ISO was higher than 1 MAC ISO (p < 0.002), and LDH higher for 1.5 MAC SEVO than 1 MAC SEVO. Conclusion and clinical relevance Both ISO and SEVO, at concentrations used for clinical anaesthesia, produce transient moderate effects on some hepatobiliary enzyme concentrations in dogs.