Paired Comparison of Iopamidol and Iopromide in Hepatic Arteriography1

J Korean Radiol Soc 2003;48:141-145

Paired Comparison of Iopamidol and Iopromide in Hepatic Arteriography1 Young Ho Choi, M.D.2, Jin Wook Chung, M.D., Guk Myung Choi, M.D., Chang Jin Yoon, M.D., Keon Ha Kim, M.D., Seung Gyu Moon, M.D., Hyo-cheol Kim, M.D., Jae Hyung Park, M.D.

Purpose: To compare the clinical efficacy of iopamidol 370 and iopromide 370, as used in hepatic arteriography, in terms of their safety, patient tolerance, and image quality. Materials and Methods: Between February and April 2001, 30 patients (M:F=27:3; mean age, 57 years) with hepatocellular carcinoma underwent hepatic angiography in which iopamidol 370 was used for transcatheter arterial chemoembolization (TAE). Sensations of heat or pain following contrast injection, a patient’s distress or discomfort levels, and any side effects of the contrast media were monitored, and afterwards patients were asked whether they were aware of any differences between iopamidol 370 and iopromide 370, which had been used in hepatic angiography for previous TAE prior to February 2001. Three experienced independent radiologists assessed the diagnostic efficacy of the contrast media in terms of overall image quality, which was statistically analysed using Wilcoxon’s signed ranks test. Results: No patient experienced sensations of heat or pain during angiography, or showed any objective distress or discomfort, though two suffered mild nausea during angiography with iopamidol 370. None was aware of any difference between iopromide 370 and iopamidol 370. In terms of overall image quality, the diagnostic efficacy of contrast media in all patients was‘ good’to‘ excellent’, with no significant difference between iopromide 370 and iopamidol 370 (p>0.05). Conclusion: In hepatic arteriography, the clinical efficacy of iopamidol 370 is comparable with that of another nonionic contrast medium, iopromide 370, in terms of safety, tolerance, and image quality. Iopamidol 370 is thus a useful alternative medium.

Index words : Contrast media, efficacy study Contrast media, comparative studies Contrast media, angiography

The development of contrast media for angiography creased tolerance and good radio-opacity. Since the first has always been directed toward substances with in- nonionic contrast agent was developed in 1969 to over- come the limitations of ionic contrast media that caused 1Department of Radiology, Seoul National University College of Medicine and the Institute of Radiation Medicine, SNUMRC more intense sensations of heat and pain, and cardiac 2 Department of Radiology, Boramae Municipal Hospital toxicity due to high osmolarity (1, 2), ongoing efforts Received March 7, 2002 ; Accepted September 24, 2002 Address reprint requests to : Jin Wook Chung, M.D., Department of have been made to develop media with fewer side ef- Radiology, Seoul National University College of Medicine and the Institute of Radiation Medicine, SNUMRC fects. 28, Yongon-dong, Chongno-gu, Seoul 110-744, Korea. Iopamidol is one of the most widely used nonionic Tel. 82-2-760-2584 Fax. 82-2-743-6385 E-mail: [email protected] contrast media with low osmolarity. To date, many clin- ─ 141 ─ Young Ho Choi, et al : Paired Comparison of Iopamidol and Iopromide in Hepatic Arteri ography ical studies involving its use in aortography (3, 4), pe- unstable or pregnant; had moderate to severe cardiac, ripheral angiography (5-7), cardiac angiography (8- hepatic, or renal failure; suffered from paraproteinemia, 10), cerebral angiography (11, 12), and visceral arteriog- multiple myeloma, thrombocytopenia, or sickle cell raphy (13) have been performed, but to our knowledge, anaemia; had an allergic or hypersensitive condition for none have examined its use in hepatic arteriography. In which a drug had been prescribed; or had received any conjunction with Dong Kook Pharmaceuticals, we other contrast medium within the previous 48 hours, therefore conducted the present investigation. were excluded from the study. In this study, the clinical efficacy of two nonionic contrast media, iopamidol 370 (PamirayⓇ; Dong Kook, Procedures Seoul, Korea) and iopromide 370 (Ultravist(r); Shering, Before chemoembolization, patients underwent an- Seoul, Korea) was compared in terms of safety, patient giography to determine the location and extent of the tu- tolerance, and image quality (Fig. 1). Iopromide 370 is mor. Local anesthesia with 1% lidocaine was performed one of the nonionic contrast media most widely used in prior to femoral arterial puncture for insertion of an ar- angiographic procedures such as abdominal aortogra- terial sheath. A 5-Fr RH catheter (Cook, Bloomington, phy and visceral arteriography, and its osmolarity and U.S.) was inserted into the aorta and its branches under viscosity are similar to those of iopamidol 370 (Table 1). fluoroscopic guidance, and angiography of the celiac In our study, the two media were used serially during trunk was performed. The amount of contrast medium transcatheter arterial chemoembolizations (TAE) under- used ranged from 42 to 48 mL and the injection rate was gone by each of the patients involved. 7 to 8 mL/second. If it was suspected that an aberrant hepatic artery originated from the superior mesenteric Materials and Methods artery, this was examined angiographically after the injection of contrast media at a rate of 6-8 mL/second. Patients Using a 3-Fr microcatheter, if necessary, selective an- Between February and April 2001, 30 patients [M:F = giography of the right or left hepatic, or inferior phrenic 27:3; age, 40-74 (mean, 57) years] in whom hepatocel- artery was performed to determine the exact location of lular carcinoma had been diagnosed prior to February 2001 underwent TAE once using iopamidol 370 after Table 1. written consent to its use had been obtained. Prior to Iopamidol 370 Iopromide 370 February 2001, TAE was performed at least once, using Iodine concentration (mg/mL) 370 370 iopromide 370. Osmolarity (mOsm/kg H2O) 796 780 All patients except one (Patient 28) were in relatively Molecular weight 770 791 good general condition. Any one who were medically Viscocity at 37°C (centipoises) 9.5 9.5

A B Fig. 1. Molecular structure of iopamidol and iopromide. Iopamidol (A) and iopromide (B) have a tri-iodinated benzene ring and three highly hydrophilic side chains. They are stable in solution. ─ 142 ─ J Korean Radiol Soc 2003;48:141-145

the tumor and to clarify the site of its feeding artery. The side effects for at least 24 hours after the completion of amount of contrast media used ranged from 3 to 14 mL, procedures. injected at 0.5-2 mL/second according to the size of the After the conclusion of angiography, patients were vessel. asked whether they were aware of any differences be- The respective amounts of iopromide 370 and iopami- tween iopamidol 370 and iopromide 370, which had dol 370 used were 42-105 (mean, 70.2) and 42-105 been used in hepatic angiography before February 2001. (mean, 68.6) mL, with no statistically significant differ- The safety of iopromide 370 was analysed on the basis ence between the mean volumes. of the answers and the patients’medical records. Angiographic images were obtained using a Siemens Image quality was assessed by three experienced inde- Polytron S-Plus DSA System in conjunction with a pendent radiologists blinded to a patient’s identity and Siemens Angiostar Table equipped with a 13-inch inten- clinical profile and to the contrast media used. In addi- sifier. tion, each was unware of the other radiologists’assessment. Using original images, the diagnostic efficacy of Safety and Efficacy Analysis contrast media in terms of overall image quality was as- During hepatic angiography performed using iopami- sessed according to a five-point scale, as follows: 1, poor dol 370 between February and April 2001, patients were opacification; 2, insufficient opacification; 3, sufficient told that sensations of heat or pain might occur after opacification; 4, good opacification; 5, excellent opacifi- contrast injection, and were asked to grade these sensa- cation.“ Poor”indicated that image quality did not per- tions after the whole procedure as ‘none’, ‘mild’, mit diagnosis, and“ excellent”that vessel detail was visi- ‘moderate’or‘ severe’. Investigators used a four-point ble. For statistical analysis of image quality, Wilcoxon’s scale, as follows, to assess the degree of a patient’s dis- signed ranks test was used. Two-sided probability (p) tress or discomfort: 0, no evidence of distress; 1, slight values of <0.05 were considered statistically significant. movement and/or vocal complaint; 2, moderate move- The reproducibility of the three observers’assessment ment and/or vocal complaint; 3, forcible movement of image quality was assigned a ĸ (kappa) value. and/or loud cries. Side effects during the procedures were determined Results by direct questioning and observation. The severity of any side effect was graded as‘ none’,‘ mild’(disappear- No patient experienced sensations of heat or pain during spontaneously, or no need for therapy),‘ moderate’ ing angiography with either iopromide 370 or iopamidol (necessitating therapy but responding immediately) or 370, or showed any objective distress or discomfort. ‘severe’(alarming or life-threatening, responding poor- Two patients complained that the use of iopamidol 370 ly or slowly to therapy). All patients were monitored for led to mild nausea, though none were aware of any dif-

A B Fig. 2. Image quality of hepatic angiography. Two hepatic angiograms were evaluated as“ good opacification”(A) and“ exellent opacification”(B) by all three radiologists. ─ 143 ─ Young Ho Choi, et al : Paired Comparison of Iopamidol and Iopromide in Hepatic Arteri ography ferences between the two media. were collected from just 30 patients, which may have With regard to the reproducibility of observors’as- induced bias. To determine whether iopamidol and oth- sessment of image quality, ĸ values of 0.58, 0.74, and er contrast media, including iopromide, exert different 0.64 was assigned to observers 1 and 2, 1 and 3, and 2 effects because of differences in their formulation or and 3, respectively. Thus, interobserver agreement was physicochemical characteristics, studies involving more good. The diagnostic efficacy of contrast media in terms subjects are thus required. of overall image quality was‘ good’to‘ excellent’in all Second, the safety of iopromide, including possible patients, with no significant difference between iopro- side effects, was evaluated prospectively on the basis of mide 370 and iopamidol 370 (p=0.257, 0.763, and 0.102 the patients’recollections and hospital records, and this in observer 1, 2, and 3, respectively) (Fig. 2). may have induced bias. However, investigation of the safety of iopromide showed at least equal or better re- Discussion sults than that of iopamidol, and conclusions may thus be reasonably drawn from our data. Nonionic intravenously or intra-arterially adminis- In conclusion, the clinical efficacy of iopamidol 370, as tered contrast media have been proven to be better tol- used in hepatic arteriography, is comparable to that of erated and safer than commonly used ionic media with iopromide 370 in terms of safety, patient tolerance, and high osmolarity (1, 2). Thus, larger amount of nonionic diagnostic efficacy. In diagnostic angiography, including contrast media can be used with relative safety in high- hepatic arteriography, iopamidol is thus a useful alterna- risk patients. Since first becoming available, this type tive to other nonionic contrast media. has thus become established as most suitable for most applications. References In high-concentration aqueous solution, iopamidol is chemically similar to other nonionic contrast media, io- 1. Grainger RG. Intravascular contrast media. Br J Radiol 1982;55:1- 18 promide and iohexol, in terms of its low osmolarity, low 2. Katayama H, Yamaguchi K, Kozuka T, Takashima T, Seez P, viscosity, and low capacity for protein binding. Matsuura K. Adverse reactions to ionic and nonionic contrast me- Iopromide has a slight advantage over iopamidol in dia. A report from the Japanese Committee on the Safety of terms of osmolarity and protein binding, though in this Contrast Media. Radiology 1990;175:621-628 3. Whitehouse GH, Snowdon SL. An assessment of iopamidol, a non- study, no differences in safety, patient tolerance or im- ionic contrast medium, in aorto-femoral angiography. Clin Radiol age quality were noted. 1982;33:231-234 Extensive research in Europe and North America (3- 4. Verow P, Nossen JO, Sheppick A, Kjaersgaard P. A comparison of 13) has demonstrated the safety, diagnostic quality, and iodixanol with iopamidol in aorto-femoral angiography. Br J Radiol 1995;68:973-978 improved patient tolerance of the nonionic contrast me- 5. Simmons MJ, Waite DW, Galland RB, Torrie EPH. Double blind dia, iopamidol, relative to ionic contrast media, in pe- comparison of iomeprol 350 and iopamidol 340 in intravenous dig- ripheral arteriography, cardiac angiography, myelogra- ital subtraction angiography for peripheral vascular disease. Clin phy, urography, cerebral angiography, abdominal aor- Radiol 1992;45:338-339 6. Dacoronias D, Minguzzi P, Ugolotti U, Dettori AG. Iomeprol vs tography, and visceral arteriography. However, no iopamidol in intraarterial peripheral digital subtraction angiogra- equivalent study has provided a paired comparison of phy. Angiology 1992;43:734-740 these contrast media for hepatic arteriography. In this 7. Ugolotti U, Larini P, Marcato C, Cusmano F, Puccianti F. Peripheral arteriography with a new nonionic agent: comparison study, we have determined whether there is any differ- of iomeprol with iopamidol. Eur J Radiol 1994;18 Suppl 1:S77-S82 ence between the two nonionic contrast media, iopami- 8. Wisneski JA, Gertz EW, Dahlgren M, Muslin A. Comparison of dol and iopromide, as used in hepatic arteriography. low osmolality ionic (ioxaglate) versus nonionic (iopamidol) con- We found that iopamidol was equivalent to iopromide trast media in cardiac angiography. Am J Cardiol 1989;63:489-495 9. Beltramello A, Piovan E, Rosta L. Double-blind comparison of in terms of the sensations of heat or pain, or distress or safety and efficacy of iomeprol and iopamidol in carotid digital discomfort induced; side effects; and diagnostic efficacy. subtraction angiography. Eur J Radiol 1994;18 Suppl 1:S67-S72 Both media proved to be safe and well tolerated, provid- 10. Fattori R, Piva R, Schicchi F, et al. Iomeprol and iopamidol in car- ing good radiographic quality without untoward side ef- diac angiography: a randomized, double-blind, parallel-group comparison. Eur J Radiol 1994;18 Suppl 1:S61-S66 fects. The one side effect reported by two patients was 11. Bird CR, Drayer BP, Velaj R, et al. Safety of contrast media in cere- mild nausea during angiography with iopamidol. bral angiography: iopamidol vs. methylglucamine iothalamate. Our study suffered certain limitations. First, our data AJNR Am J Neuroradiol 1984;5:801-803 ─ 144 ─ J Korean Radiol Soc 2003;48:141-145

12. Pelz DM, Fox AJ, Vinuela F, Lylyk P. A comparison of iopamidol of the safety, tolerance, and diagnostic efficacy of iopromide as and iohexol in cerebral angiography. AJNR Am J Neuroradiol 1988; compared with iopamidol and iohexol in patients requiring aortog- 9:1163-1166 raphy and visceral angiography. Invest Radiol 1994;29 Suppl 1:S98- 13. Faykus MH Jr, Cope C, Athanasoulis C, et al. Double-blind study S101

대한방사선의학회지 2003;48:141-145

간동맥 조영술에서 Iopamidol과 Iopromide의 임상적 유용성의 비교1

1서울대학교 의과대학 방사선과학교실, 서울대학교 의학연구원 방사선의학연구소 2시립보라매병원 방사선과

최영호2·정진욱·최국명·윤창진·김건하·문승규·김효철·박재형

목적: 간동맥 조영술에서 iopamidol 370의 임상적 유용성을 평가하였다. 이러한 평가는 조영제 사용시 안전성, 환자 의 용인도, 획득한 영상의 질의 관점에서 iopromide 370과 비교를 통해 이루어졌다. 대상과 방법: 2001년 2월에서 2001년 4월까지 30명의 간암환자(평균나이 57세, 남녀비 27:3)가 간동맥 색전술을 위해 iopamidol 370을 사용하여 간동맥 조영술을 시행받았다. 이때 환자가 느끼는 열감 또는 통증, 불편감, 조영제 의 부작용을 관찰하였다. 혈관조영술 후 환자에게 iopamidol 370이 2001년 2월 이전에 간동맥 색전술을 위해 시행 한 간동맥 조영술시 사용된 iopromide 370과 비교해서 환자가 느끼는 열감 또는 통증, 조영제의 부작용의 관점에서 어떠한 차이가 있었는지 알아보았다. 또한 3명의 방사선전문의가 영상획득시 사용된 조영제의 진단적 유용성을 평 가하였다. 이의 통계적 분석을 위해 Wilcoxon signed ranks test를 사용하였다. 결과: 대상환자 모두 혈관조영술시 열감 또는 통증을 경험하지 않았고 객관적인 불편감을 보이지 않았다. 두 명의 환 자가 iopamidol 370을 사용한 조영술시 경도의 오심을 경험하였다. 대상환자 모두 두 조영제간의 차이를 느끼지 못 하였다. 영상획득시 사용된 조영제의 진단적 유용성은 모든 경우에‘좋음’‘아주 좋음’이었고 통계적으로 두 조영제 간의 차이는 보이지 않았다(p>0.05). 결론: 간동맥 조영술에서 iopamidol 370의 임상적 유용성은 조영제 사용시 안전성, 환자의 용인도, 획득한 영상의 질 의 관점에서 다른 비이온성 조영제 iopromide 370에 비견할만하다. 그러므로 iopamidol 370은 다른 비이온성 조영 제를 대신하여 간동맥 조영술에 사용될 수 있다.

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