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Keywords:

  • contrast radiography;
  • diagnostic imaging;
  • spinal cord

Abstract

  1. Top of page
  2. Abstract
  3. Introduction
  4. Materials and Methods
  5. Results
  6. Discussion
  7. Acknowledgements
  8. Footnotes
  9. References

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.


Introduction

  1. Top of page
  2. Abstract
  3. Introduction
  4. Materials and Methods
  5. Results
  6. Discussion
  7. Acknowledgements
  8. Footnotes
  9. References

Myelography is the most common diagnostic imaging method used in veterinary practice to determine the location and extent of spinal cord disease.1 It is an invasive method of contrast radiography involving injection of contrast medium into the spinal subarachnoid space under general anesthesia. Possible complications of the procedure include neurologic signs ranging from muscle fasciculations to generalized seizures, exacerbation of the patient's neurologic condition, and vomiting.2 The incidence of seizures depends on lesion location,3,4 severity of neurologic deficit,5 type of myelography (location, contrast medium, volume, concentration, and number of injections of contrast medium),3,5–8 as well as type and duration of anesthesia.7 Age, sex, and weight can also influence the incidence of seizures.4

Iopamidol and iomeprol are nonionic contrast media that have a relatively low risk of adverse effects.2,8 They can be safely used in dogs even at higher concentrations.9 Iopamidol was shown to have minimal neurotoxicologic effects on the leptomeninges.10 Iomeprol is stated to be nonepileptogenic, and its acute toxicity is comparable to that of iopamidol.11–14 Nonionic contrast media may be used at higher concentrations in dogs to obtain better myelograms.15 The use of contrast media with a higher iodine concentration enhances the quality of the image of spinal cord contours; however, this is limited by a higher risk of adverse effects induced by hyperosmolarity.6,7

The ideal contrast medium would be radiopaque, nontoxic, miscible with cerebrospinal fluid (CSF), isotonic, and pharmacologically inert.15 Iopamidol and iomeprol are iodine-based, nonionic and water-soluble compounds with a low osmolality. These agents are not metabolized and are secreted unchanged through the kidneys.12,14 Commercial preparations are available at various iodine concentrations (iopamidol 200, 300, and 400 mg iodine/mL; iomeprol 150, 200, 250, 300, and 400 mg iodine/mL). Some authors7,16 consider 300 mg iodine/mL an ideal concentration, in terms of balancing the quality of a myelogram with the risk of possible adverse effects. Widmer and Blevins9 reported that the most suitable concentration of iodine was 200 mg iodine/mL. Fatone et al15 reported better contrast imaging of the spinal cord (without a significant increase in adverse effects) after injection of a contrast agent at concentrations of 350–370 mg iodine/mL.

The risk of seizures after myelography is reduced further, by proper anesthesia.17 The anesthetic protocol should minimize the risk of seizures and other possible complications (changes in respiratory and heart rate, cardiac arrhythmias) after subarachnoid application of contrast medium. Close attention should be paid to appropriate perioperative pain management and adequate spontaneous ventilation.6,18–23

The aims of this study were (1) to compare the incidence of seizures as a complication of myelography in dogs with compressive lesions of the spinal cord caused by intervertebral disk disease (IVDD) following the use iopamidol and iomeprol; and (2) to assess whether the incidence of seizures differed between the 2 agents when severity of neurologic deficits, location of cord compression, duration of anesthesia, site of myelogram, volume of contrast, and concentration of contrast were evaluated.

Materials and Methods

  1. Top of page
  2. Abstract
  3. Introduction
  4. Materials and Methods
  5. Results
  6. Discussion
  7. Acknowledgements
  8. Footnotes
  9. References

The medical records of our clinic were reviewed to find dogs that were presented between January 2000 and December 2002 with signs of neurologic deficit. The inclusion criteria for the study were a diagnosis of IVDD combined with surgical treatment. Patients with history of seizures, organ dysfunctions, general neurologic disorders, or mild degree of neurologic deficit were excluded. Preoperative workup included complete physical and neurologic exam, and hematology and serum biochemistry profile. Neurologic deficits were scored on a scale of I–III (cervical spinal cord lesions) and I–IV (thoracolumbar spinal cord lesions) according to severity.5

After the neurologic examination, all dogs underwent general anesthesia, survey radiography, and myelography. Patients were premedicated with medetomidinea (0.02 mg/kg, IV) and buprenorphineb (0.01 mg/kg, IV) and anesthesia was induced with propofolc (1 mg/kg, IV) and maintainedd by inhalation of isofluranee in 100% oxygen.

Based on the clinical lesion localization, cranial, caudal, or combined cranial and caudal myelography were performed using standard techniques.17,24 Percutaneous puncture was performed using a 22-Ga spinal needle.f Before injection of the contrast agent, a sample of CSF was obtained for cytologic and biochemical analysis.24 Needle placement within the subarachnoid space was confirmed either clinically by visualization of CSF backflow into the needle hub or by fluoroscopy after injection of a small volume of contrast medium.

Before injection, the contrast medium was preheated to 38°C and then injected very slowly over 2 minutes. After the procedure, the patients were placed on an inclined mat to facilitate flow of contrast to the site of the lesion.24

Lateral, ventrodorsal, and 2 oblique (45°) ventrodorsal radiographs were taken of the spinal segment of interest, to determine the location and character of the spinal lesions.24 Ventral slot decompression and removal of extruded disk fragments from the extradural space8 were performed in patients with cervical spinal lesions. Thoracolumbar lesions were managed by hemilaminectomy.8,25,26 Myelography and surgical procedures were performed under standard conditions (lege artis) by 2 specialists. All patients were monitored for the occurrence of seizures for 24 hours after myelography.

Seizures were defined as episodes characterized by presence of any of the following: excessive salivation, chewing movements, rigid extension of the limbs, clonic limb activity or paddling, uncontrollable jerking of the head and trunk, or urinary or fecal incontinence.4

Statistical methods

Iopamidol and iomeprol were compared for incidence of seizures using the χ2-test. Groups with low incidence were compared by Fisher's exact test. Multivariate analyses were performed for the following variables: location of spinal compression, severity of neurologic deficits, myelography site, concentration, and volume of contrast medium, and duration of anesthesia. These were compared between dogs that did and did not develop seizures. Significance was set at P<0.05.

Results

  1. Top of page
  2. Abstract
  3. Introduction
  4. Materials and Methods
  5. Results
  6. Discussion
  7. Acknowledgements
  8. Footnotes
  9. References

Over the study period from January 2000 to December 2002, 556 dogs with neurologic deficits were presented to the clinic, and of these 161 dogs met the inclusion criteria for the study. Of the 161 dogs studied, 94 were male and 67 were female. Twenty-three breeds were represented. The median age was 7.2 years (range, 1.5–12 y); median weight was 10.65 kg (range, 2.6–44). Eighteen of 161 patients (11%) had motor deficits of the thoracic limbs and 143 of 161 (89%) had deficits of the pelvic limbs. All patients from our study group had intervertebral disk protrusion/extrusion located in the cervical or thoracolumbar spinal cord area. The preoperative laboratory findings were not clinically significant in any of the dogs. Surgery was performed immediately following myelography in dogs with thoracolumbar compression, and at a later stage in dogs with cervical compression.

Anesthesia was uneventful in all cases and vital functions were monitoredg throughout. During anesthesia and in the recovery phase, lactated Ringer's solution was administered at a rate of 10 mL/kg/h. Duration of anesthesia from administration of contrast medium to recovery ranged from 40 to 120 minutes (mean 93 min).

Thirty-one of 161 dogs (19%) were subjected to cranial myelography, 125 of 161 (78%) to caudal myelography, and 5 of 161 (3%) to combined cranial and caudal myelography.

The CSF protein was elevated in 33 of 161 patients (20%). There were no pathologic changes on cytologic analysis of CSF in any patient.

Iopamidolh was injected at concentrations of 200 or 300 mg iodine/mL and iomeproli at 250 or 300 mg iodine/mL. Volumes ranged from 0.2 to 0.54 mL/kg. Seventy-four dogs received iopamidol for myelography and 87 received iomeprol. Twenty of 161 dogs (23%) received 0.2–0.3 mL/kg of contrast medium, 102 of 161 (63%) dogs received 0.3–0.5 mL/kg, and 39 of 161 (24%) dogs received >0.5 mL/kg (Table 1).

Table 1.   Incidence of seizures in relation to the myelography technique and the type and volume of contrast medium administered
Contrast agentVolume (mL/kg)Cranial myelographyCaudal myelographyCranial and caudal myelography
SeizuresNo seizuresTotalSeizuresNo seizuresTotalSeizuresNo seizuresTotal
Iopamidol0.2–0.3022088000
0.3–0.523552934101
>0.510151722011
Iomeprol0.2–0.3347022011
0.3–0.52121444347011
>0.502201212011

Eighteen of 161 dogs (11%) had cervical spinal lesions and 143 of 161 (89%) had thoracolumbar lesions. The 143 dogs with thoracolumbar lesions had surgery immediately after the myelogram. Surgery was not performed immediately in the dogs with cervical lesions, which were allowed to recover from anesthesia after the myelogram.

Seizures occurred in 23 of 161 dogs (14%). Four of the 18 (22%) dogs with cervical lesions seizured, compared with 19 of 143 (13%) of those with thoracolumbar lesions (Figure 1). There was no significant difference overall between iopamidol (seizures in 14 of 74 dogs; 19%) and iomeprol (seizures in 9 of 87 dogs; 10%), when factors other than myelography type and location of spinal cord compression lesion were considered (P>0.05) (Figure 1).

image

Figure 1.  Incidence of seizures between groups according to the type of the contrast medium, the location of its administration, and localization of lesion.

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However, statistically significant differences were found between the contrast agents when dogs were grouped according to localization of the lesion and severity of the neurologic deficit. Paraplegic dogs with compression lesions in the thoracolumbar area had a significantly higher incidence of seizures after iopamidol compared with iomeprol: 12 of 51 dogs (24%) versus 5 of 55 dogs (9%), respectively (P=0.04) (Figure 2).

image

Figure 2.  Incidence of seizures between groups according to the type of contrast medium, the location of compression, and the degree of neurologic deficit. *Significantly higher incidence of seizures (P=0.04) with the use of iopamidol in dogs with degree IV neurologic deficits as compared with iomeprol.

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In paraplegic dogs that received iopamidol, there was a higher incidence of seizures (P=0.04) after caudal myelography (12/51 [24%]), especially at the higher concentration of iodine (iopamidol 300 mg iodine/mL) (7/29 [24%]) (P=0.01) (Figure 3).

image

Figure 3.  Incidence of seizures in dogs with thoracolumbar lesions between groups administered differing concentrations of iodine. *Significantly higher incidence of seizures (P=0.01) with use of iopamidol (300 mg iodine/mL) compared with the same concentration of iomeprol.

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If compression was located in the cervical area, no significant difference was found between iopamidol (2/6 [33%]) and iomeprol (2/12 [17%]) (Figure 1).

In paraplegic patients with duration of anesthesia longer than 90 minutes (106 patients), there was a significantly higher incidence of seizures after iopamidol (12/51 [24%]) than iomeprol (5/55 [9%]) (P=0.04) (Figure 4). Significant differences were not detected based on volume of contrast medium, age, sex, or weight of dogs.

image

Figure 4.  Incidence of seizures in dogs with thoracolumbar lesions according to the type of contrast medium and duration of anesthesia (>90 min). *Significantly higher incidence of seizures (P=0.04) with use of iopamidol in comparison with iomeprol.

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Discussion

  1. Top of page
  2. Abstract
  3. Introduction
  4. Materials and Methods
  5. Results
  6. Discussion
  7. Acknowledgements
  8. Footnotes
  9. References

This retrospective study identified a significantly higher incidence of seizures after subarachnoid iopamidol injection in paraplegic dogs with thoracolumbar lesions that had been subjected to caudal myelography and had longer duration of anesthesia.

In this group of patients there was also a significantly higher incidence of seizures after the use of iopamidol at a concentration of 300 mg iodine/mL. The higher incidence of seizures in these patients could be explained by the fact that during caudal myelography the contrast material proceeds cranially. Both, volume of contrast medium injected and disturbed CSF flow due to the compressive lesion, can result in increased intracranial pressure.3,27

These findings might also be the result of slower excretion of iopamidol from the subarachnoid space compared with iomeprol.12,13,28 In addition, dogs with paraplegia are prone to dehydration as they usually cannot urinate spontaneously and may drink smaller amounts. This could lead to slower elimination of contrast media from the subarachnoid space and increased incidence of seizures.11,17 We strove to eliminate this factor by fluid therapy (based on the clinical signs of hydratation status).29

The higher incidence of seizures after injection of iopamidol at the higher iodine concentration could be also explained by the negative effect of hyperosmolarity. Because the same anesthetic protocol was used in all patients, the difference in incidence of seizures with the longer duration of anesthesia was probably also related to faster elimination of iomeprol than iopamidol from the subarachnoid space.12 This finding is consistent with the fact that no significant difference was found between the incidence of seizures after iopamidol versus iomeprol in patients with a shorter duration of anesthesia. These patients had lesions in the cervical area of the spinal cord, which in itself increases risk of seizures.4 In addition, where cranial myelography was used the surgery did not immediately follow the myelogram, and the duration of anesthesia was shorter than in patients with thoracolumbar disk extrusion.

The incidence of seizures was quite low and there were no significant differences between contrast media for patients with lesions in the cervical spine. These results correspond with studies performed in dogs4,8,30 (frequency of seizures varies between 11% and 75%) and men.13 Careful and slow injection of contrast medium into the cerebellomedullary cistern may help explain the low incidence of seizures. Control radiographic views showed that contrast medium did not enter the cerebral ventricles. After application of contrast medium, the patient's head was elevated to reduce the risk of contrast medium flowing cranially.17

The absence of a statistically significant difference when comparing the overall incidence of seizures after application of different volumes of iopamidol and iomeprol was probably due to the low osmolality, water-solubility, high neurotolerability, and low toxicity of both media.2,10,11 It is interesting to note that there was a higher incidence of seizures after injection of smaller volumes of iomeprol (up to 0.3 mL/kg, maximum 12 mL total volume) into the cerebellomedullary cistern in dogs with paraplegia, compared with higher volumes. However, this was not statistically significant compared with the same dose of iopamidol. This may be explained by the increased risk of seizure activity after cranial myelography due to impaired caudal drainage of CSF in animals with severe compression lesions, or an increase of intracranial pressure, or both.3,4,17 Our findings are in agreement with those of a retrospective study of iohexol myelography in 182 dogs where the dose of contrast medium was not correlated with seizure activity.4

In contrast to the study of Barone et al,4 that reported a higher incidence of seizures in dogs weighing >20 kg, we did not find a statistically significant influence of body weight on the incidence of seizures after iopamidol or iomeprol myelography. This could be due to the low number of dogs weighing >20 kg (5 of 161) in our study.

Our study has several limitations. In some groups there were low number of patients, making meaningful statistical comparison difficult or impossible to evaluate. We did not compare incidence of seizures in animals with preexisting seizure disorders, which is an area for future study.

In conclusion, although small, the present study shows that the overall incidence of seizures was similar for iopamidol and iomeprol. However, statistically significant differences were found in paraplegic dogs with IVDD localized to the thoracolumbar spinal cord area, in which there was a higher incidence of seizures after caudal myelography with the use of iopamidol and a longer duration of anesthesia. The results suggest that in this patient group, it is preferable to perform myelography by administering iomeprol via the L5-L6 intervertebral space rather than iopamidol, in order to minimize the risk of seizures.

From a clinical point of view, it is important to note that both iopamidol and iomeprol are relatively safe for myelography in dogs with IVDD. The overall incidence of seizures was quite low. Therefore, both contrast media are suitable for myelography in dogs.

Acknowledgements

  1. Top of page
  2. Abstract
  3. Introduction
  4. Materials and Methods
  5. Results
  6. Discussion
  7. Acknowledgements
  8. Footnotes
  9. References

The authors thank Susan B. Robbins, Katarina Brezna, Vladimir Jekl, Radka, and Zdenek Andysik for technical support.

Footnotes

  1. Top of page
  2. Abstract
  3. Introduction
  4. Materials and Methods
  5. Results
  6. Discussion
  7. Acknowledgements
  8. Footnotes
  9. References

aDomitor, Orion Corporation, Espoo, Finland.

bTemgesic, Reckitt and Colman Prod. Ltd, Hull, UK.

cPropofol 1%, Fresenius Kabi, Graz, Austria.

dAnemat N8, Chirana, Stara Tura, Slovak Republic.

eForane, Aesica Queenborough Ltd, Queenborough, UK.

fSpinocan, B.Braun, S.A., Sao Goncalo, Brazil.

gDatex Cardiocap II, Datex-Ohmeda, Helsinki, Finland.

hIopamiro, Bracco S.p.A., Milano, Italy.

iIomeron, Bracco S.p.A.

References

  1. Top of page
  2. Abstract
  3. Introduction
  4. Materials and Methods
  5. Results
  6. Discussion
  7. Acknowledgements
  8. Footnotes
  9. References
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