Lumbar myelography with iohexol and metrizamide: a comparative multicenter prospective study

Diagnostic quality of radiographs and adverse reactions associated with the use of metrizamide and iohexol as contrast agents in lumbar myelography were compared in a prospective randomized double blind study in 350 patients at seven centers. The contrast media were administered in comparable volumes at a concentration of 180 mg I per ml. Overall quality of radiographic visualization was graded good or excellent in 95% of 175 metrizamide studies and in 98% of 175 iohexol studies. Ninety-three patients examined using metrizamide (53%) and 130 patients examined using iohexol (74%) experienced no discomfort during or after myelography. Postmyelographic headache was associated with 38% of metrizamide examinations and 21% of iohexol examinations. Nausea and vomiting were also more common with metrizamide. Five patients examined using metrizamide (3%) experienced transient confusion and disorientation following lumbar myelography. No such reactions were observed following iohexol myelography.     

Iohexol versus metrizamide for cervical myelography: double-blind trial

Cervical myelography was performed by lateral C1-C2 puncture in 60 patients. Thirty patients received iohexol (an investigational aqueous contrast agent) and 30 received metrizamide in order to provide a prospective, randomized, double-blind trial comparing these contrast media. The two media produced radiographs of equal quality. Contrast-related morbidity was suffered by four patients (13%) in the iohexol group and by 11 patients (37%) in the metrizamide group. These features indicate that iohexol is superior to metrizamide as a contrast agent for cervical myelography.     

Iohexol vs. metrizamide: study of efficacy and morbidity in cervical myelography

A double-blind study was conducted in 60 patients undergoing either cervical or more complete myelography via C1-C2 puncture. Patients received either iohexol or metrizamide at a 300 mg l/ml concentration. The contrast media were equally efficacious in the production of high-quality radiographs and CT scans. However, the incidence of adverse reactions differed markedly. Of patients receiving metrizamide, 68% had some type of adverse reaction, whereas only 26% receiving iohexol had symptoms. The incidence of headache (metrizamide, 34%; iohexol, 26%) was not statistically different, but the quality of the headache differed: half of the metrizamide headaches were moderate or severe, whereas all iohexol headaches were mild. Nausea (31%) and vomiting (28%) were common with metrizamide but unusual (3% nausea) with iohexol. Of the metrizamide patients, 21% had overt psychologic changes that did not occur in the iohexol group.     

Central nervous system reactions to cervical myelography

In a double blind prospective study of side effects to cervical myelography 38 patients were evaluated with neurologic examination, electroencephalography (EEG), brainstem evoked response (BER), somatosensory evoked responses (SSER), and continuous reaction times prior to and at 6 h and 24 h after myelography with either metrizamide or iohexol. A difference in the incidence of side effects (for example headache, dizziness, nausea, and neck pain) to the two different contrast media indicated that the inconveniences related to myelography were not only due to the spinal puncture. A contrast medium effect on the central nervous system varying from one agent to another was present. A high frequency of EEG deteriorations among patients with adverse clinical reactions and on only discrete affection upon BER indicated the reaction to be located to the cerebral cortex. Weakened tendon reflexes and reduced strength in the upper extremities were probably caused by blockade in the motor roots as SSER were normal indicating no affection of the sensory pathways. This hypothesis is in agreement with the fact that the patients were in the prone position in the first phase of the investigation causing the highest concentration of contrast medium around the motor roots and the anterior part of the spinal cord. Difference in metabolic effect may explain differences in side effects of metrizamide and iohexol.     

Myelography with a dimeric (iodixanol) and a monomeric (iohexol) contrast medium: a clinical multicentre comparative study

The purpose of this study was to evaluate and compare the radiographic efficacy and safety of iodixanol (Visipaque; 270 and 320 mg I/ml) and iohexol (Omnipaque; 300 mg I/ml) in myelography. The study was randomized, double-blind and comparative including 398 patients from five European university clinics. The radiographic visualisation was evaluated as poor, good or excellent. Adverse events were recorded by interviewing the patients after the myelography, and each patient was given a questionnaire to be returned after 1 week. In cervical myelography with cervical puncture more films with excellent quality was obtained after iodixanol 320 mgI/ml compared with iohexol 300 mgI/ml (p = 0.009). Also in lumbar myelography iodixanol 320 mgI/ml compared favourably with iohexol 300 mgI/ml (p = 0.006). The most frequent adverse event was headache, which occurred in 5–35 % of patients during the first 24 h and in 19–61 % within the first 7 days, depending on the centre. There was no difference in frequency and severity of the adverse effects between the contrast media. Received 13 March 1997; Revision received 29 December 1997; Accepted 5 January 1997     

Iohexol versus metrizamide for lumbar myelography: double-blind trial

Lumbar myelography was performed in 50 patients; 25 received iohexol (an investigational aqueous contrast agent) and 25 received metrizamide. The two media produced radiographs of equal quality. However, iohexol is stable in solution, while metrizamide is not. Further, markedly less morbidity resulted from iohexol. These features indicate that iohexol may be superior to metrizamide as a contrast agent for lumbar myelography.     

Cognitive and affective changes after myelography: a comparison of metrizamide and iohexol

A battery of brief cognitive tests and a mood scale were administered to 42 patients before and after cervical myelography with either metrizamide (20 patients) or iohexol (22 patients). The patients receiving metrizamide experienced a deterioration in mood after myelography and a relatively greater decline in cognitive test performance than did those receiving iohexol. These two side effects tended to occur together in the metrizamide group, suggesting a common underlying cause; but there was no correlation between changes in mood and cognitive function after myelography with iohexol. These results suggest that metrizamide has a greater neurotoxic effect than iohexol.     

Risk of seizures after myelography: comparison of iohexol and metrizamide

A parallel, double-blind, randomized study comparing iohexol and metrizamide--both 180 mg l/ml--in lumbar myelography was carried out in 60 consecutive patients. Eight to 15 ml of contrast medium were administered with the upper level at the middle thoracic column. A detailed neurologic examination was performed before and 24 hr after myelography. EEG recordings--evaluated visually and with fast Fourier transformation analysis--and somatosensory evoked responses were registered before, 6 hr after, and 24 hr after myelography. All patients were observed for adverse reactions for 24-48 hr. Iohexol did not produce any epileptiform activity but epileptiform activity was detected in five patients receiving metrizamide. Iohexol produced significantly less frequent and less severe EEG changes than did metrizamide both at visual evaluation (p less than .0025) and at fast Fourier transformation analysis (p less than .04). No significant changes occurred in the early components of the somatosensory evoked potentials after either contrast medium. Iohexol caused significantly (p less than .002) less frequent and less severe adverse reactions than did metrizamide. The neurologic examination revealed no changes of clinical importance with either contrast agent.     

C1-C2 myelography with iohexol and metrizamide: comparative study

Comparison of metrizamide and iohexol contrast media for myelography performed via lateral C1-C2 puncture in a total of 64 patients demonstrated superiority of iohexol with respect to the incidence of postprocedure adverse reactions. There was no significant difference between the two media in quality of radiographic demonstration in the cervical region. Patients in whom posterior fossa positive-contrast radiographic examinations were performed at the same time as myelography, using either water-soluble agent, did not demonstrate any increased incidence of side effects over those having myelography alone.     

Metrizamide compared with iohexol for cervical myelography: a double-blind study

A double-blind comparative study of iohexol and metrizamide for use in cervical myelography through lumbar puncture was carried out in a group of 30 patients. No difference was found in the quality of radiographic examinations of the cervical or lumbar regions nor in the postmyelographic computed tomographic examinations of the cervical spine. The overall incidence of side effects was significantly higher in the metrizamide group (93.4%) than in the iohexol group (40%) (p = 0.002). The differences in incidence of nausea (53% in the metrizamide group compared with 13% in the iohexol group) and vomiting (46.6% with metrizamide, 6.6% with iohexol) were also significant (p = 0.02). Pyramidal signs and seizures occurred only after metrizamide myelography.     

The effect of intrathecal iohexol on visual evoked response latency: a comparison including incidence of headache with iopamidol and metrizamide in myeloradiculography

Fifty consecutive unselected patients referred for myeloradiculography and examined by the same radiologist, when facilities for measuring the visual evoked response were available, are considered. The effect on the visual evoked response of the examination and the incidence of headache following the use of iohexol as the contrast medium are compared with those after the use of iopamidol and metrizamide reported in a previous study. A total of 400 cases examined with iopamidol and 200 cases examined with iohexol are reviewed with regard to the incidence of headache. Whereas iopamidol and, to a greater extent metrizamide, were found to cause significant lengthening of the visual evoked response latency 20 hours after the radiological examination, iohexol did not. Furthermore there was no significant difference in the 20 hour reading following the use of iohexol compared with the original control group of patients who underwent lumbar puncture alone. There was a lower incidence and severity of headache following the use of iohexol than with iopamidol and a markedly reduced incidence compared with metrizamide. Iohexol is considered less neurotoxic than iopamidol which had previously superceded metrizamide as the contrast medium used for myeloradiculography in the Royal Surrey County Hospital. Volumes of up to 14 ml of iohexol 300 mg I/ml have been used for lumbar radiculography and for total myelography and up to 10 ml for direct lateral cervical puncture. In 350 cases examined to date with iohexol the only serious sequel was a case of chemical meningitis following the lumbar injection of 10 ml of the 300 mg I/ml solution for a cervical examination. The patient made an uneventful recovery.     

Ambulatory myelography using iohexol (Omnipaque): methods and results

Outpatient myelography with iohexol (Omnipaque) was performed in 150 patients. Side effects were noted in 28 patients (19%), with only 3 (2%) major complaints. It concerned 2 patients with severe and prolonged headache and one patient with seizures. Side effects were not more frequent in outpatient myelography than in reported series of hospitalized patients. The frequency of side effects was significantly lower with the use of iohexol than in comparable studies with metrizamide. Headache was the most frequent side effect, followed by an increase or exacerbation of ischiatiform pain, nausea and vomiting. Side effects were slightly more frequent in cervical myelography than in lumbar myelography and were not related to underlying pathology. It is concluded that outpatient myelography is feasable for as far as iohexol is used and patient surveillance is carefully organized.     

Clinical experience with iopamidol for myelography

Within 20 months 145 ascending thoracocervical myelographies and 155 lumbar myelographies with the nonionic water-soluble contrast medium iopamidol were performed. The iodine concentration given was 250 mg I/ml or 200 mg I/ml respectively. The total iodine never exceeded 2.5 g (8-10 ml). Image quality was assessed in terms of diagnostic value having experience of more than 1,000 myelographies using metrizamide. Picture quality was similar to metrizamide of equal iodine concentration. In 35 patients electroencephalography (EEG) was recorded before and after myelography with iopamidol 250. No changes that could be referred to the contrast medium were seen. There were no adverse reactions to lumbar myelography other than those following the lumbar puncture. In thoracocervical myelography mild and transient side effects occurred in 41 (28.3%). The most common were headache (41 cases), nausea (12), radicular pain (10), and dizziness (five). General seizures and psychopathologic symptoms were not observed.     

Iohexol lumbar myelography: clinical study

Forty-three patients underwent lumbar myelography with the new, nonionic contrast medium iohexol. Multiple laboratory examinations, neurologic examinations, and electrocardiograms showed no significant alterations after intrathecal injection of the contrast agent. Mild electroencephalographic changes were seen in one patient. Nineteen adverse reactions occurred in 13 patients; only one of them was considered severe. No patient experienced a seizure, auditory or visual hallucination, or similar neuropsychologic reaction. This is a distinct improvement over the side effects described for previous water-soluble contrast agents. The adverse reactions occurring with iohexol myelography are fewer in number and less severe than with metrizamide myelography, and radiographic visualization obtained with iohexol is equal to that obtained with metrizamide. With iohexol, it appears that the most disturbing and disabling neuropsychologic reactions have been reduced to an acceptable minimum.     

Iohexol and metrizamide in lumbar myelography. Comparison of side effects

In routine lumbar myelography carried out in 100 patients iohexol (n = 50) produced side effects in fewer patients (p less than 0.03), especially meningeal and cerebral (p less than 0.03), and among these a lower rate of headache (p less than 0.07), than did metrizamide. The overall frequency of afflicted patients (50% after iohexol and 72% after metrizamide) was high, mainly because of deliberate inclusion of patients with a high risk of side effects in the investigation. The side effects recorded up to six hours after the administration of the contrast medium were less frequent when using iohexol. If severe side effects are present at 24 hours or appear thereafter, as occurred in a few of the present patients after iohexol, surgical treatment or discharge of the patient is in some cases unnecessarily delayed.     

Iohexol in paediatric myelography

Summary Iohexol was introduced by lumbar puncture in a series of 148 consecutive children aged between 5 days and 16 years referred for myelography; no patient was excluded. Initially, iohexol 180 mgI/ml was used in dosage proportional to body weight varying between 5 ml and 15 ml. During the later part of the trial concentration of iodine was increased to 240 mg/ml for cases in which the dorsal region was of particular interest (69 patients) and to 300 mg/ml for 8 cervical studies. The total dose ranged up to 4.8 g and varied between 0.03 g and 0.51 gI/kg body weight. In all patients, neurological examinations were performed before and at 24 h and observations for adverse reactions continued over a period of 48 h. The contrast medium was run up to the foramen magnum or basal cisterns in 128 patients and to the upper dorsal region in the other 20. In the first 62 patients vital studies were performed over the period of the myelogram and for 24 h following, and an additional limited neurological examination was made at 6 h, and in the first 26 cases of the series EEG's were done before and at 24 h after the myelogram. Minor variations in pulse rate and blood pressure were observed but these were not of sufficient magnitude to be of clinical significance. In 7 patients there was minor, generally slow wave abnormality on the EEG taken after the procedure, but no spike or epileptogenic activity was obserse reactions. Focal increase in neurological signs, associated with backache and probably related to the mechaniccs of lumbar puncture and myelography, occurred in 3 tumour patients; otherwise no change in neurological condition was observed in any case. Minor reactions were observed in 24 other patients (16.2%); vomiting 14 (9.5%), headache 8 (5.7%), backache 6 (4.1%), stomache ache 2 (1.5%), mild pyrexia 3 (2.0%). The incidence and severity of these reactions was considerably less than with metrizamide myelography and all resolved within 2 days of the iohexol injection. In conclusion, iohexol has significant advantages over previously used non-ionic contrast media and is suitable for paediatric myelography.     

Myelography with iohexol (Omnipaque): review of 300 cases

The side effects of iohexol were evaluated in the 300 patients who had nonemergency myelography over a 9 month period. No patients studied with myelography were excluded from the iohexol trial. Age range was 14-86 years. Introduction was by lumbar puncture in 206 patients and by lateral C1-C2 injection in 94. Side effects, including discomfort, were denied by 81.3% of the patients. The other 18.7% had adverse reactions, the most common being headache, reported by 11% of the total population studied. Image quality was judged unsatisfactory in 8.1% of cervical myelograms and in 2.6% of lumbar myelograms. With lumbar injection, cervical myelograms were judged to be inadequate in 13.5%; with cervical injection, lumbar myelograms were inadequate in 25%. Iohexol caused significantly fewer side effects in the 300 patients than would have been expected with metrizamide. The low cost and ease of use are additional factors that favor iohexol as the contrast agent of choice for myelography.     

A double-blind, prospective, randomized, multicenter group comparison study of iopromide 240 vs iohexol 240 in myelography

The aim of this study was to evaluate the safety and efficacy of iopromide 240 mgI/ml in comparison with iohexol 240 mgI/ml in myelography. A total of 421 patients in seven centers and four countries received an average of 11.9 ml of either iopromide 240 (278 patients) or iohexol 240 (143 patients) for X-ray and/or CT myelography in a randomized (2:1), prospective, double-blind study. All patients were followed up 3–4 h after the procedure, and 327 patients remained hospitalized for 24 h. In 82 patients an EEG was recorded prior to as well as 3–4 h and 24 h after myelography. Physical examinations, including measurement of vital signs, were performed in all patients at these time points. The results were subject to statistical analysis with the primary variable being the incidence of adverse events. Both contrast media (CM) were equally effective in terms of opacification. The rating for opacity was “good” or “excellent” in 88 % for both CM. Four patients (iopromide group: n = 3; iohexol group: n = 1) had transient EEG changes but did not show clinical symptomatology. The overall rate of patients experiencing any adverse event (AE) was 16.9 % for iopromide 240 and 14.0 % for iohexol 240. Equivalence testing was inconclusive; however, the results indicated equivalence. The rate for AEs considered as study-drug related was slightly lower with iopromide 240 than with iohexol 240 (7.2 vs 7.7 %, respectively). Neither unknown nor unexpected AEs known for myelographic X-ray CM nor serious adverse events were observed. Iopromide 240 and iohexol 240 are equally safe and effective and can be recommended for myelography. Received: 19 August 1998; Revision received: 26 November 1998; Accepted: 4 February 1999     

High-dose iohexol myelography

Lumbar myelography was performed with high volumes of iohexol (15-24 ml) at a concentration of 180 mgI/ml (average dose, 20 ml) in 48 patients. In 44 patients receiving more than the currently recommended upper dose limit of 17 ml, the frequency of headache (41%), nausea (14%), and vomiting (9%) was comparable to results for routine-dose lumbar metrizamide myelography. Overall, adverse reactions were more frequent, particularly at the highest dose levels, than reported for conventional-dose iohexol myelography. However, there were no occurrences of neuropsychiatric disorder, encephalopathy, or seizure. High-dose technique allows superior visualization of upper lumbar and conus detail and may be advantageous in patients with large subarachnoid spaces and in multi-level examinations. This study supports the results of previous trials that suggested the relative safety of iohexol as a contrast agent and extends those observations to a higher dose range. Because of the increased rate of adverse reactions at the highest dose levels (despite the absence of major adverse reactions), iohexol should continue to be used conservatively, with doses carefully tailored to each examination.     

Functional cervical myelography with iohexol

Summary Thirty patients underwent functional cervical myelography, i.e. radiographs in the lateral view were obtained in extension as well as in flexion of the neck. Sagittal tomography was performed in both positions. Widening of the subarachnoid space and decreased sagittal diameter of the spinal cord due to shortening were demonstrated in the lateral view in flexion. In some cases with advanced narrowing or spinal block in extension, such widening in flexion resulted in better diagnostic images by providing passage of the contrast medium caudally. Although iohexol (Omnipaque, Nyegaard & Co., Oslo) was regularly forced into the posterior cranial fossa by the movements, the frequency of side effects was approximately the same as in our former trials with iohexol in conventional cervical myelography. EEG changes occurred in two patients (7%). A sitting position for 3–4 min after the examination followed by an elevated head end of the bed was probably important for preventing side effects from the contrast medium. Specific questioning revealed twice as many subjective side effects as reported after general questions alone.