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lopamidol vs. Metrizamide Myelography: Clinical Comparison of Side Effects

Claudio Trevisan,1 Cristina Malaguti, Manuela Manfredini, and Donatella Tampieri

One hundred myelographies with iopamidol and 100 with occipital injecti on (8% ). The amount of contrast medium adm inIS­ metrizamide were performed in order to compare the side effects tered was 8-20 ml (average, 10 ml), usually with an iodine concC' n­ of the two contrast media after injection into the spinal subarach­ trati on of 300 mg / ml. Most of the 200 patients (1 23 men , 67 noid space. All patients were observed for a follow-up period of women) were 40- 60 years of age (range, 17-63). In order to aVCJ id at least 4 days. The most frequently observed side effect, head­ technical differences, illl myelographies were performed by the ache, was more common, of longer duration, and more severe same operator. Patients were observed for a follow-up period 01 at with the use of metrizamide than with iopamidol. Only neck pain least 4 days by the same physician, except those who presen ted was more common with iopamidol. More severe side effects more severe symptoms and were followed until all symptoms such as meningeal irritation, psychoorganic syndrome, and epi­ ceased. leptic seizures occurred only with metrizamide. The results seem to indicate a lower neurotoxicity and better patient tolerance for iopamidol than for metrizamide. Results

Fifty-four patients studied with iopamidol and 29 with metrizamide Many publications have dealt with the adverse side effects of had no adverse side effects. The remaining 117 patients had nne metrizamide injected into the spinal subarachnoid space [1 -15]. or more postexamination symptoms, of which headache was most Among these side effects, headache is the most frequent, occurring frequently observed (table 1). The incidence and severity of head­ in 10.5%-64% of subjects [2, 4-8, 11 , 12]. According to some ache in relation to the spinal region examined are shown in ta bl" 2. authors, headache is directly related to the contrast medium [2, 5, Headache in myelographies with metrizamide was more freq u8nt, 12], while others attribute it to the lumbar puncture [16]. Other of longer duration, and more severe than that observed after in;ec­ reactions, such as nausea, vomiting, leg or neck pain, and worsen­ tion of iopamidol. Regardless of the contrast agent, severe hE'a d­ ing of preexisting symptoms, vary in intensity and duration [2, 3, 5- ache occurred more frequently in patients who underwent myelo­ 8, 11 , 12]. Meningeal irritation, hyperpyrexia, mental confu sion , graphic study of two or more vertebral levels. There was no si gn ifi­ arachnoiditis, epileptic seizures, psychoorganic syndrome, and cant relation between the incidence and severity of headache ~ nd spinal epilepsy are reported less frequently [1 , 3, 5, 8-11, 14, the total dose of iodine (table 3). 15]. All these side effects are probably directly related to the action All other side effects except neck pain occurred mu ch ",are of the contrast medium on the central nervous system. frequently with metrizamide than with iopamidol (table 1). Th e most A few papers have reported the adverse side effects of iopamidol, severe reactions were observed with metrizamide. A patient e>a m­ ined for lumbar and sciatic pain experienced meningeal irritat ion a new non ionic contrast medium. It appears that the symptoms after metrizamide injection (total iodine dose, 3 g). An other pati ent observed with the use of this agent are the same as th ose seen with other contrast media, but distinctly less severe and less frequent had a grand mal seizure 2 hr after suboccipital injecti on of metri­ [17, 18]. We know of only one report comparing the side effects of zamide (total iodine dose, 2.5 g). When the same patient underwent iopamidol myelography via lumbar puncture (iodine dose, 4.5 g) a metrizamide and iopamidol [1 9]. Its au th ors ascribe the higher few days later, no adverse effects were observed. Finally, si x cases frequency of headache after iopamidol myelography to the faster reabsorption rate of this agent. The present study compares the had a reaction pattern simil ar to the psychoorganic syndro me respective side effects of metrizamide and iopamidol in a large described by other authors. In one case the syndrome consistr' d of sleep difficulties with oneirism throughout the night after IUI'lbar seri es of myelographies. myelographic examin ati on (iodine dose, 3 g). The other fi ve edses experienced mental confusion lasting a maximum of 3 days. This Subjects and Methods symptom always arose immediately after the myelography, wlich was conducted for examination of the lumbar region in two C-lses One hundred myelographies with metrizamide and 100 with and the whole spine in three. All five patients had received 'lore iopamidol were studied. Most (58%) of the examinations were than 3 g of iodin e and two had a total dose of 4.5 g. In one of I'lese sacculoradiculographies, followed by myelographies of the entire two, the onset of symptoms was extremely acute and closely re aled spinal column (23%) and cervical myelographies (19%). Lumbar to leakage of the contrast medium into th e c ranial cavity as a I~ S UIt punctu re was used for th e injecti on of the contrast media in most of technical error. El ectroencephalographic readings obtaine(' dur­ cases (79.5%), followed by upper laterocervical (1 2.5%) and sub- ing the fi rst few hours after myelography performed in th e I deral

I All authors: Servizio di Neurorad iolog ia. Ospedale Bellaria. Via Altura 3. Bolog na, Italy. Address rep rint requests to C. Trevisan. AJNR 4:306-308, May / June 1983 0195-6108/ 83 / 0403-0306 $00.00 © Ameri can Roen tgen Ray Society AJ NR:4, May/ June 1983 NEW CONTRAST AGENTS 307

TABLE 1: Type and Incidence of Side Effects after lopamidol medium injected and the extent or region of the spine examined. vs. Metrizamide Myelography This observation is supported by the large number of patients who showed no side effects after iopamidol myelography: 54, in contrast Contrast Agent to 29 among those who had received metrizamide. Even headache, Side Effecl lopamidol Metrizamide th e most common side effect reported in both groups, was more (n ~ 100) (n ~ 100 ) freq uently observed , of longer duration, and more severe after Headache 29 43 metrizam ide (43%) than after iopamidol (29%). Similar differences Nausea and vomiting 10 22 between th e two groups were observed in reported frequency of Worsening of preexisting symptoms 6 15 the less common symptoms such as nausea, vomiting, leg pain and Leg pain ...... 6 8 worsening of preexisting symptoms, with the single excepti on of Neck pain 8 3 neck pain, which occurred more frequently after injection of iopam­ Lumbar pain 7 Psychoorganic syndrome 6 idol. At present, we can offer no plausible explanation for this. The Dizz iness 4 5 most remarkable result seems to be th e absence of the so-call ed Fever ...... 1 3 psychoorganic syndrome as a reaction to iopamidol, although this Change in blood pressure 1 3 syndrome was observed in six cases after injection of metrizamide. Meningism ...... Moreover, one patient in the metrizamide group experi enced men­ Epile ptic seizures ingeal irritation and one had a grand mal seizure. In these two cases, however, we had ad ministered doses of contrast medium slightly higher th an those recommended in the literature [20 , 21). On the other hand, slightly higher amounts of iopamidol were well TABLE 2: Incidence and Severity of Headache According to tolerated and always produced images of excell ent quality. Contrast Agent and Investigated Region

No. (% ) wilh Headache Contrast Agent: Vertebral Reg ion Investigated REFERENCES Mild Moderate Severe Totals lopamidol (n = 100): 1. Schmidt RC. Mental disorders after myelography with metri­ Cervical only (n = 21) 2 (9) 1 (5) 3 (14) zamide and other water-soluble contrast media. Neuroradiol­ Lum bar only (n = 54) 16 (30) 4 (7) 20 (37) ogy 1980; 1 9 : 1 53-1 57 Two or more regions (n 2. Sykes RH, Wasenaar W, Clark P. Incidence of adverse effects = 25) 4 (16) 3 (12) 7 (28) followin g metrizamide myelography in nonambulatory and am­ Metrizamide (n = 1 00): bulatory patients. Radiology 1981 ;138: 625-627 Cervical only (n = 17) 1 (6) 6 (35) 1 (6) 8 (47) Lumbar only (n = 62) 10(16) 6 (10) 9 (14) 25 (40) 3. Legre J , Lavieille J, Debaene A, Tapias PL, Vaillant J. Preven­ Two or more regions (n tion des accidents de la myelographie cervicale a I'amipaque. = 21) 4 (19) 3 (14) 3 (14) 10 (47) J Neuroradio/1 981 ;8 : 353- 361 4 . Rolfe EB , Maguire PD. Th e incidence of headache following various techniques of metrizamide myelography. Br J Radiol 1980; 53: 840-844 TABLE 3: Incidence and Severity of Headache According to 5 . Gelmers HJ . Adverse side effects of metrizamide in myelogra­ Contrast Agent and Total Dose of Iodine phy. Neuroradiology 1979; 18: 11 9-1 24 6. Baker RA , Hillman BJ , MacLennan JE, Strand RD , Kaufman Severity of Headache Tolal SM. Sequelae of metrizamide myelography in 200 examina­ Contrast Agent: Total No. (% ) Dose of Iodine (g) Wilh ti ons. AJR 1978; 130: 499-502 Mild Moderate Severe Headache 7. Manelfe C, Treil J, Bonafe A. Myelographie cervicale au metri­ lopamidol (n = 100): zamide par voie laterale en C1-C2. Nouv Presse Med 2.5 (n = 12) 3 (25) 2 (17) 5 (42) 1978;7: 657 -661 2. 5-3.5 (n = 53) 9 (17) 4 (7) 1 (2) 14 (26) 8. Eld evik OP, Nakken KO, Haugton VM. The effect of dehydra­ 3.5 (n = 35) 8 (23) 2 (6) 10 (29) tion on th e side effects of metrizamide myelography. Radiology Metrizamide (n = 1978;129:715-71 6 100): 9. Ahlgren P. Amipaque myelography without late adhesive arach­ 2.5 (n = 28) 1 (4) 4 (14) 8 (29) 3 (11) noid changes. Neuroradiology 1978;14 : 231 - 233 2. 5-3.5 (n = 56) 9 (16) 6 (11) 11 (19) 26 (46) 10. Hansen EB, Fahrenkrug A, Praestholm J. Late meningeal ef­ 3.5 (n = 16) 3 (18.7) 3 (18.7) 3 (18.7) 9 (56) fects of myelographic contrast media with special reference to Note. -Percentages are given in parentheses. metrizamide. BrJ Radio/ 1978;5 1 :321-327 11. Sackett JF, Strother CM , Quaglieri CE, Javid MJ, Levin AB, Duff TA. Metrizamide. Analysis of clinical application in 2 15 patients. Radiology 1977; 123: 779-782 decubi tus position showed slow-wave activity on the side the patient 12. Skalpe 10, Amundsen I. Thoracic and cervi cal myelography lay on during the examination. This slow-wave activity became with metrizamide. Radiology 1975; 116: 1 01 -1 06 difiu se in the hours that followed , and electroencephalograms re­ 13. Praestholm J, Moller S. Cardiovascular reactions to myelog­ mai ned abnormal for over 5 days. raphy with water-soluble contrast media. Neuroradiology 1977;1 3: 195-199 Disc ussion 14. Eldevik OP, Haugton VM . Ri sk factors in complications of aqueous myelog raphy. Radiology 1978;128: 415-416 The results seem to indicate a better patient tolerance for iopam­ 15. Lee BC , Gomez DG , Popts DG , Pavese AM . Subacute reacti ons idol th an for metrizamide, independent of the amount of contrast to intrathecal Amipaque (metrizamide), Conray and Dimer X: a 308 NEW CONTRAST AGENTS AJNR:4, May / June 1983

stru ctural and ultrastructural stu dy. Neuroradiology uble contrast medium for neuroradiology. Neuroradiology 1981 ;20: 229-233 1980;19 : 119-1 31 16. Tourtell ote WW, Haerer AF, Heller GL, Somers GE. Post-lum­ 20. Hacker H, Vonofakos O. Kraniale CT -Untersuchnungen nach bar puncture headache. Springfield, IL: Thomas, 1964 lumbaler myelographie mit Amipaque. In : Frommhold W, 17. Belloni G, Bonaldi G, Maschini L, Quilici N. Cervical myelog­ Hacker H, Schmitt HE, Vogelsang H, eds. Amipaque workshop raphy with iopamidol. Neuroradiology 1981 ;21 : 97 -99 Amsterdam: Excerpta Medica, 1978: 1 2-15 18 . Carell a A, Federico F, Oi Cuonzo F, Vinjau E, Lamberti P. 2 1. Schmidt RC. Probleme der Myelographie mit Metrizamid (A ml­ Adverse side-effects of metrizamide and iopamidol in myelog­ paque) bei altern en Patienten. In : Frommhold W, Hacker H, raphy. Neuroradiology 1982;22: 247-249 Schmitt HE, Vogelsang H, eds. Amipaque workshop. Amster­ 19. Hamm er N, Lackner W. lopamidol, a new non-ionic hydrosol- dam: Excerpta Med ica, 1978: 20-23