Urol Radiol 12:56-60 (1990)
Urologic Radiology © Springer-VerlagNew York Inc. 1990
Ioversol for Intravenous Urography: A Comparison Study Alan J. Kaufman,1 Raoul Concepcion, 2 Fred K. Kirchner, Jr., 2 W. Scott McDougal, 2 and Alan C. Winfield 1 Departments of ~Radiology& Radiological Sciences and 2Urology,Vanderbilt University School of Medicine, Nashville, Tennessee, USA
Abstract. A new nonionic, low-osmolar iodinated contrast media, ioversol, was compared with another low-osmolar, nonionic contrast media, iohexol, in 80 patients undergoing intravenous urography. There were 40 patients in each contrast group. Patients were assessed for changes in vital signs, patient tolerance (heat and pain), and other adverse effects. Double-blind evaluation was also performed for comparison o f the urogram image quality. There were no severe, life-threatening reactions for either contrast group. Ten patients (25%) receiving ioversol and seven (17.5%) receiving iohexol perceived body heat related to the injection o f contrast material. Two patients (5%) in each group experienced mild nausea. Two patients (5%) o f the ioversol group noted unpleasant taste, and two patients (5%) o f the iohexol group complained o f headache. Vital signs remained stable without significant change in both groups, and image quality was considered equivalent. T h e results indicate that the two contrast agents are equivalent in image quality, safety, and incidence o f adverse effects. Key words: Ioversol -- Intravenous urography -Intravenous contrast agents -- Nonionic contrast material -- Low osmolar iodinated contrast.
T h e introduction and use oflow-osmolality contrast media (LOCM) have generated great interest and
Address reprint requests to: Alan J. Kaufman, M.D., Department
of Radiology & Radiological Sciences, Vanderbilt University Medical Center, Nashville, TN 37232-2675, USA
research in the medical c o m m u n i t y . These relatively new agents are being c o m p a r e d to the conventional high-osmolality contrast media ( H O C M ) with respect to urographic image quality, patient tolerance, and adverse reactions including anaphylaxis [ 1-10]. It is generally agreed that L O C M provoke fewer and less severe adverse and undesirable reactions. T h e y are, however, substantially more expensive than the conventional H O C M , a factor which has initiated great concern as it relates to skyrocketing medical costs and "cost-effectiveness." The goal o f this double-blind study was to evaluate two nonionic contrast agents: the newer ioversol-240 (Optiray, Mallinckrodt, St. Louis, MO, USA) and iohexol-300 (Omnipaque, W i n t h r o p Laboratories, New York, NY, USA) by comparing image quality, patient tolerance, vital signs, and adverse reactions. Both agents are low-osmolality, nonionic triiodinated benzoic acid derivatives with a difference in a side chain (Fig. 1). T h e r e is an additional hydroxyl group in ioversol and thus it is m o r e hydrophilic. Ioversol has recently been c o m p a r e d to conventional ionic agents for peripheral, abdominal, and coronary angiography, as well as left ventriculography [11, 12]. This study compares two nonionic L O C M for intravenous urography.
Materials and Methods Eighty adult outpatients without known renal function impairment and with serum creatinine levels of less than 2.0 mg/dl underwent intravenous urograms at Vanderbilt University Medical Center. The patients were randomly and equally divided into two groups of 40. Group I received 75 ml ioversol-240 (18 g iodine). Group II received iohexol-300. Of those receiving iohexol, 32 patients were administered 60 ml (18 g iodine), while eight patients received only 50 ml (15 g iodine).
A.J. Kaufman et al.: Ioversol for Intravenous Urography
H OH O c/N,v, OH H
OH
0 A
OH
H OH OC/N 0H
H3ctC' N),
H OH J c/N-,, OH
'o' B HO Fig. 1. Chemical structure of (A) ioversol and (B) iohexol: triiodinated benzene rings in nonionic form.
This comparison study was conducted in a randomized, double-blind fashion so that the physician injecting the contrast agent did not take part in the evaluation of side effects, the quality of the urogram, nor in the acquisition of vital signs. The patients, consisting of 44 males and 36 females, ranged in age from 18-86 (mean, 45.3; median, 43). Informed consent, as established by the Institutional Review Board, was obtained for all patients prior to the injection. Entrance criteria were established and adhered to such that patients: (a) did not have a known history of sensitivity to iodinated contrast material; (b) could not be pregnant or nursing; (c) had not received contrast media within 24 h or oral cholecystography contrast agents in the last 7 days; and (d) had no history of diabetes, asthma, pheochromocytoma, sickle-cell disease, multiple myeloma, or significant renal disease. Serum cre° atinine was obtained on all patients within 2 weeks prior to urography. Vitalsigns (systolic blood pressure, diastolic blood pressure, pulse rate and respiratory rate) were monitored just prior to injection, and at 5, 30, and 60 min postintravenous injection of contrast. The patient tolerance was monitored by asking the patient to assess body heat and pain at or near the injection site occurring with or just after the intravenous injection by giving a discomfort score: none, mild, moderate, or severe. In addition, all adverse reactions were noted, described, timed, and graded in severity (mild, moderate, or severe). Mild reactions required no therapy, moderate reactions were graded such that appropriate therapy was administered, and severe reactions required hospitalization. The quality of the urogram was judged by one experienced radiologist by separately grading the density of contrast within
57 Table 1, A summary of demographic data Ioversol-240
Iohexol-300
Number of patients
40
40
Sex Men Women
22 18
22 18
Age range (years) Mean age (years)
20.9-76.8 45.3
19.0-86.9 45.3
Weight range (kg) Mean weight (kg)
46.8-110 70.7
43.6-116.8 78.8
Height range (cm) Mean height (cm)
149.9-185.4 169.5
152.4-188 171.1
parenchyma, calyces, pelvis, and ureter for each kidney, as well as the urinary bladder and general overall quality. The opacification was scored as none (no radiographic opacification), poor (inadequate for diagnostic evaluation), adequate (sufficient for diagnostic evaluation), and excellent (the radiographic opacification such that diagnostic information was easily perceived and the anatomic detail readily seen).
Data Analysis Standard parametric and nonparametric statistical procedures as implemented in the Statistical Analysis System (SAS, Mallinckrodt, Inc., St. Louis, MO, USA) were used to compare drug groups with respective responses. Fischer's exact probability test, as implemented in the SAS procedure FREQ, was used to compare the drug groups with respect to the proportion of patients who are white, proportion of patients for whom the quality of visualization was considered excellent, proportion for whom the procedure was considered diagnostic, proportion of patients having clinically significant changes in vital signs, proportion of patients having one or more adverse reactions, and proportion of patients for whom the drug was evaluated as safe to use. Wilcoxon's twosample test (normal approximation with continuity correction of 0.5) as implemented in the SAS procedure NPARIWAY was used to compare the drug groups with respect to average scores in the patients' assessment of heat and pain using the following code: 0 = none; 1 = mild; 2 = moderate; and 3 = severe. The Wilcoxon two-sample test was also used to compare the drug groups with respect to average change in vital sign parameters from baseline.
Results T h e d e m o g r a p h i c d a t a is s u m m a r i z e d i n T a b l e 1. Vital signs ( s y s t o l i c a n d d i a s t o l i c b l o o d p r e s s u r e , p u l s e rate, a n d r e s p i r a t o r y rate) d i d n o t s i g n i f i c a n t l y change after intravenous contrast administration in a n y o f t h e 80 p a t i e n t s . The analysis of patient tolerance (perception and a s s e s s m e n t ) o f h e a t a n d p a i n is d e t a i l e d i n T a b l e 2. None of the patients perceived pain in either contrast group. Ten of 40 patients (25%) in the ioversol group and seven of 40 patients (17.5%) in the ioh e x o l g r o u p p e r c e i v e d b o d y h e a t r e l a t e d to t h e i n -
58
A.J. Kaufman et al.: Ioversol for Intravenous Urography
jection o f contrast material. O f the eight patients in the iohexol group who inadvertently received only 50 ml (l 5 g iodine), none experienced heat or pain. N o n e o f the patients studied d e v e l o p e d urticaria, b r o n c h o s p a s m , or angioneurotic edema. T h e r e were no major, life-threatening reactions in either contrast group. O f the 40 patients receiving ioversol, two (5%) experienced nausea a n d two (5%) experienced an unpleasant taste. Similar results were seen in the iohexol group with two (5%) experiencing nausea and two (5%) c o m p l a i n i n g o f headache. All o f these side effects subsided spontaneously within 2 m i n postinjection. Evaluation o f image quality revealed no significant difference between either contrast agent. T a b l e 3 details the c o m p a r a t i v e results o f patients 1-65. T w e n t y - f o u r o f 33 u r o g r a m s (72.7%) scored "excellent" and eight o f 33 u r o g r a m s (24.2%) scored " a d e q u a t e " with ioversol, while 25 o f 32 u r o g r a m s (78%) were considered excellent and six o f 32 (18.75%) were " a d e q u a t e " with iohexol.
Table 2. A summary of data relative to heat as assessed by the
patient
Drug group
None
Mild
UnMod specerate Severe ified Total
Ioversol-240 Iohexol-300
30 33
8 6
2 1
0 0
0 0
40 40
Table 4 c o m p a r e s the results o f all 80 patients, including the eight iohexol patients who inadvertently received 50 ml instead o f the 60 m l (18 g iodine), which was specified in this protocol. F o r this population, 30 o f 40 patients (75%) receiving ioversol h a d "excellent" results and 27 o f 40 (67.5%) receiving iohexol scored "excellent." O f the eight patients receiving only 15 g iodine in iohexol, only two were d e e m e d "excellent" a n d six " a d e q u a t e . " In s u m m a r y , the results o f this study indicate that in c o m p a r i n g vital signs, adverse effects, and imaging quality, there is no significant difference between these two nonionic contrast agents. Discussion
Although the pathogenesis o f adverse contrast reactions is complex and multi-faceted, it does a p p e a r that m e c h a n i s m s associated with h y p e r o s m o l a l i t y play a part in objective and subjective undesirable effects [ 13-16]. W h e n c o m p a r i n g the urographic diagnostic i m age quality o f L O C M nonionics a n d the H O C M ionics, the nonionics h a v e been reported to be equivalent [ 17] or superior [2-4, 6, 7]. C o n t r o v e r s y still exists concerning the extent and cause o f n e p h rotoxicity o f the various types o f contrast agents, with the m o s t recent data suggesting that L O C M and H O C M h a v e an equally nephrotoxic effect [18, 19]. This study c o m p a r e s the urographic diagnostic
Table 3. Frequency distributions of patients according to quality of procedure excluding patients numbered 66 through 80
Ioversol-240
Iohexol-300
Region of interest
Excellent Adequate Poor
None
Total
Excellent Adequate Poor
None
Total
Right kidney Parenchyma Calyces Pelvis Ureter
26 26 26 23
6 6 6 9
1 1 1 1
0 0 0 0
33 33 33 33
26 28 29 27
5 3 2 3
1 1 1 2
0 0 0 0
32 32 32 32
Left kidney Parenchyma Calyces Pelvis Ureter
26 26 26 23
6 6 6 8
1 1 1 2
0 0 0 0
33 33 33 33
25 27 28 27
5 3 2 3
1 1 1 1
1 1 1 1
32 32 32 32
Bladder Overall quality
26 24
6 8
1 1
0 0
33 33
25 25
6 6
1 1
0 0
32 32
Ioversol-240
Overall diagnostic utility
Iohexol-300
Diagnostic
Nondiagnostic Total
Diagnostic
Nondiagnostic Total
32
1a
32
0
33
32
a In this 73-year-old male patient, there has been long-term renovascular disease with hypertension and resultant nephrosclerosis.
59
A.J. Kaufman et al.: Ioversol for Intravenous Urography Table 4. Frequency distributions of patients according to quality of procedure Ioversol-240
Iohexol-300
Region of interest
Excellent Adequate Poor
None
Total
Excellent Adequate Poor
None
Total
Right kidney Parenchyma Calyces Pelvis Ureter
32 32 32 29
7 7 7 10
1 1 1 1
0 0 0 0
40 40 40 40
28 30 31 29
10 8 7 8
2 2 2 3
0 0 0 0
40 40 40 40
Left kidney Parenchyma Calyces Pelvis Ureter
32 32 32 29
7 7 7 9
1 1 1 2
0 0 0 0
40 40 40 40
27 29 30 29
11 9 8 9
1 1 1 1
1 1 1 1
40 40 40 40
Bladder Overall quality
32 30
7 9
1 1
0 0
40 40
27 27
12 12
1 1
0 0
40 40
Ioversol-240
Overall diagnostic utility
Iohexol-300
Diagnostic
Nondiagnostic Total
Diagnostic
Nondiagnostic Total
39
1
40
0
image quality, adverse reactions, vital signs, and patient tolerance of two nonionic, low-osmolality contrast agents. The results reveal that both ioversol and iohexol are equivalent in regard to the aforementioned parameters. Much of the current debate in the medical community concerns itself with the cost and "cost-effectiveness" of these low-osmolality, nonionic contrast agents [20-23]. Unfortunately, the definition and analysis of the term "cost-effectiveness" vary greatly. The notion of cost effectiveness is indeed important and worthy of consideration as are moral, ethical, and legal issues, and, of course, patient safety. Currently, the commonly used nonionics are reported to produce fewer adverse reactions than the ionic HOCM [1-10, 13-16]. As stated by Dr. Ronaid G. Grainger of the United Kingdom, "The second generation, low-osmolar media are, therefore, to be preferred to conventional media for most purposes, arterial or intravenous injection. The only problem is one of expense as they cost four to six times the price of conventional media" [24]. This current study comparing the two nonionics reveals that quite adequate and even excellent image quality can be obtained with only 18 g iodine. Perhaps the high costs could be reduced by diminishing the doses being administered, while fostering patient safety and comfort without sacrificing quality. Studies comparing smaller amounts of LOCM to large amounts of H O C M would be beneficial in substantiating our initial observations.
40
40
Acknowledgments. We thank Tom Ebers for his expert editorial assistance, Linda Pennington for her secretarial aid, and Mallinckrodt, Inc. for contrast material, funding, and statistical analysis. This work was supported in part by Mallinckrodt, Inc.
References 1. Bettmann MA: Angiographic contrast agents: conventional and new media compared. A JR 139:787-794, 1982 2. Winfield AC, Dray ILl, Kirchner FK Jr, Muhletaler CA, Price RR: Iohexol for excretory urography: a comparative study. A JR 41:571-573, 1983 3. Rankin RN, Hong Tai Eng FW: Iohexol vs. diatrizoate: a comparative study in intravenous urography. Invest Radiol 20 (suppl):S112-S114, 1985 4. Spataro RF, Katzberg RW, Fischer HW, McMannis MJ: High-dose clinical urography with the low-osmolality contrast agent Hexabrix: comparison with a conventional contrast agent. Radiology 161:9-14, 1987 5. Dahlstrom K, Shaw DD, Clauss W, Andrew E, Karl S: Summary of U.S. and European intravascular experience with iohexol based on the clinical trial program. Invest Radio120 (suppO:S117-S121, 1985 6. Cochran ST, Ballard JW, Katzberg RW, Barbaric ZL, Spataro R, Iwamoto K, Lee J J: Evaluation of iopamidol and diatrizoate in excretory urography: a double-blind clinical study. A JR 115:523-527, 1988 7. Jacobsson BF, Jorulf H, Kalantar MS, Narasimham DL: Nonionic versus ionic contrast media in intravenous urography: clinical trial in 1,000 consecutive patients. Radiology 167:601-605, 1988 8. Kinnison ML, Powe NR, Steinberg EP: Results of randomized controlled trials of low- versus high-osmolality contrast media. Radiology 70:381-389, 1989 9. Powe NR, Kinnison ML, Steinberg EP: Quality assessment
60
10.
1 I.
12.
13.
14. 15.
16.
A.J. Kaufman et al.: Ioversol for Intravenous Urography of randomized control trials of contrast media. Radiology 170:377-380, 1989 McClennan BL, Heiken JP, Lee JKT, James MA: Computed body tomography with a new nonionic contrast agent: comparison of ioversol with sodium meglumine diatrizoate. Invest Radio124 (suppl):S35-S38, 1989 Grassi CJ, Bettmann MA, Finkelstein J, Reagan K: Ioversol: double-blind study of a new low osmolar contrast agent for peripheral and visceral arteriography. Invest Radio124:133137, 1989 Reagan K, Bettmann MA, Finkelstein J, Ganz P, Grassi CJ: Double-blind study of a new nonionic contrast agent for cardiac angiography. Radiology 167:409-413, 1988 Dawson P: Chemotoxicity of contrast media and clinical adverse effects: a review. Invest Radiol 20(suppl):S84-S9 l, 1985 Laerum F: Injurious effects of contrast media on human vascular endothelium. Invest Radio120(suppl):S98-S99, 1985 Salem DN, Findlay SR, Isner JM, Konstam MA, Cohen PF: Comparison of histamine release effects of ionic and nonionic radiographic contrast media. Am J Med 80:382-384, 1986 Dray R J, Winfield AC, Muhletaler CA, Kirchner FK Jr:
17.
18.
19.
20. 21. 22.
23. 24.
Advantages of non-ionic contrast agents in adult urography. Urology 24:297-299, 1984 Stake G, Smevik B: Iohexol and metrizamide for urography in infants and children. Invest Radiol 20(suppl):S115-S116, 1985 Golman K, Admen T: Contrast media-induced nephrotoxicity: survey and present state. Invest Radio120(suppl):S92$97, 1985 Schwab SJ, Hlatky MA, Pieper KS, Davidson CJ, Morris KG, Skelton TN, Bashore TM: Contrast nephrotoxicity: a randomized controlled trial of a nonionic and an ionic radiographic contrast agent. NEnglJMed 320:149-153, 1989 Reuter SR: The use of conventional vs low-osmolar contrast agents: a legal analysis. A JR 151:529-531, 1988 White RI Jr, Halden WJ Jr: Liquid gold: low-osmolality contrast media. Radiology 159:559-560, 1986 Evens RG: Economic impact oflow-osmolality contrast agents on radiology procedures and departments. Radiology 162: 267-268, 1987 McClennan BL: Low-osmolality contrast media: premises and promises. Radiology 162:1-8, 1987 Grainger RG: The clinical and financial implications of the low-osmolar radiological contrast media (correspondence). Clin Radio135:251-252, 1984
Urologic Radiology © Springer-VerlagNew York Inc. 1990
Ioversol for Intravenous Urography: A Comparison Study Alan J. Kaufman,1 Raoul Concepcion, 2 Fred K. Kirchner, Jr., 2 W. Scott McDougal, 2 and Alan C. Winfield 1 Departments of ~Radiology& Radiological Sciences and 2Urology,Vanderbilt University School of Medicine, Nashville, Tennessee, USA
Abstract. A new nonionic, low-osmolar iodinated contrast media, ioversol, was compared with another low-osmolar, nonionic contrast media, iohexol, in 80 patients undergoing intravenous urography. There were 40 patients in each contrast group. Patients were assessed for changes in vital signs, patient tolerance (heat and pain), and other adverse effects. Double-blind evaluation was also performed for comparison o f the urogram image quality. There were no severe, life-threatening reactions for either contrast group. Ten patients (25%) receiving ioversol and seven (17.5%) receiving iohexol perceived body heat related to the injection o f contrast material. Two patients (5%) in each group experienced mild nausea. Two patients (5%) o f the ioversol group noted unpleasant taste, and two patients (5%) o f the iohexol group complained o f headache. Vital signs remained stable without significant change in both groups, and image quality was considered equivalent. T h e results indicate that the two contrast agents are equivalent in image quality, safety, and incidence o f adverse effects. Key words: Ioversol -- Intravenous urography -Intravenous contrast agents -- Nonionic contrast material -- Low osmolar iodinated contrast.
T h e introduction and use oflow-osmolality contrast media (LOCM) have generated great interest and
Address reprint requests to: Alan J. Kaufman, M.D., Department
of Radiology & Radiological Sciences, Vanderbilt University Medical Center, Nashville, TN 37232-2675, USA
research in the medical c o m m u n i t y . These relatively new agents are being c o m p a r e d to the conventional high-osmolality contrast media ( H O C M ) with respect to urographic image quality, patient tolerance, and adverse reactions including anaphylaxis [ 1-10]. It is generally agreed that L O C M provoke fewer and less severe adverse and undesirable reactions. T h e y are, however, substantially more expensive than the conventional H O C M , a factor which has initiated great concern as it relates to skyrocketing medical costs and "cost-effectiveness." The goal o f this double-blind study was to evaluate two nonionic contrast agents: the newer ioversol-240 (Optiray, Mallinckrodt, St. Louis, MO, USA) and iohexol-300 (Omnipaque, W i n t h r o p Laboratories, New York, NY, USA) by comparing image quality, patient tolerance, vital signs, and adverse reactions. Both agents are low-osmolality, nonionic triiodinated benzoic acid derivatives with a difference in a side chain (Fig. 1). T h e r e is an additional hydroxyl group in ioversol and thus it is m o r e hydrophilic. Ioversol has recently been c o m p a r e d to conventional ionic agents for peripheral, abdominal, and coronary angiography, as well as left ventriculography [11, 12]. This study compares two nonionic L O C M for intravenous urography.
Materials and Methods Eighty adult outpatients without known renal function impairment and with serum creatinine levels of less than 2.0 mg/dl underwent intravenous urograms at Vanderbilt University Medical Center. The patients were randomly and equally divided into two groups of 40. Group I received 75 ml ioversol-240 (18 g iodine). Group II received iohexol-300. Of those receiving iohexol, 32 patients were administered 60 ml (18 g iodine), while eight patients received only 50 ml (15 g iodine).
A.J. Kaufman et al.: Ioversol for Intravenous Urography
H OH O c/N,v, OH H
OH
0 A
OH
H OH OC/N 0H
H3ctC' N),
H OH J c/N-,, OH
'o' B HO Fig. 1. Chemical structure of (A) ioversol and (B) iohexol: triiodinated benzene rings in nonionic form.
This comparison study was conducted in a randomized, double-blind fashion so that the physician injecting the contrast agent did not take part in the evaluation of side effects, the quality of the urogram, nor in the acquisition of vital signs. The patients, consisting of 44 males and 36 females, ranged in age from 18-86 (mean, 45.3; median, 43). Informed consent, as established by the Institutional Review Board, was obtained for all patients prior to the injection. Entrance criteria were established and adhered to such that patients: (a) did not have a known history of sensitivity to iodinated contrast material; (b) could not be pregnant or nursing; (c) had not received contrast media within 24 h or oral cholecystography contrast agents in the last 7 days; and (d) had no history of diabetes, asthma, pheochromocytoma, sickle-cell disease, multiple myeloma, or significant renal disease. Serum cre° atinine was obtained on all patients within 2 weeks prior to urography. Vitalsigns (systolic blood pressure, diastolic blood pressure, pulse rate and respiratory rate) were monitored just prior to injection, and at 5, 30, and 60 min postintravenous injection of contrast. The patient tolerance was monitored by asking the patient to assess body heat and pain at or near the injection site occurring with or just after the intravenous injection by giving a discomfort score: none, mild, moderate, or severe. In addition, all adverse reactions were noted, described, timed, and graded in severity (mild, moderate, or severe). Mild reactions required no therapy, moderate reactions were graded such that appropriate therapy was administered, and severe reactions required hospitalization. The quality of the urogram was judged by one experienced radiologist by separately grading the density of contrast within
57 Table 1, A summary of demographic data Ioversol-240
Iohexol-300
Number of patients
40
40
Sex Men Women
22 18
22 18
Age range (years) Mean age (years)
20.9-76.8 45.3
19.0-86.9 45.3
Weight range (kg) Mean weight (kg)
46.8-110 70.7
43.6-116.8 78.8
Height range (cm) Mean height (cm)
149.9-185.4 169.5
152.4-188 171.1
parenchyma, calyces, pelvis, and ureter for each kidney, as well as the urinary bladder and general overall quality. The opacification was scored as none (no radiographic opacification), poor (inadequate for diagnostic evaluation), adequate (sufficient for diagnostic evaluation), and excellent (the radiographic opacification such that diagnostic information was easily perceived and the anatomic detail readily seen).
Data Analysis Standard parametric and nonparametric statistical procedures as implemented in the Statistical Analysis System (SAS, Mallinckrodt, Inc., St. Louis, MO, USA) were used to compare drug groups with respective responses. Fischer's exact probability test, as implemented in the SAS procedure FREQ, was used to compare the drug groups with respect to the proportion of patients who are white, proportion of patients for whom the quality of visualization was considered excellent, proportion for whom the procedure was considered diagnostic, proportion of patients having clinically significant changes in vital signs, proportion of patients having one or more adverse reactions, and proportion of patients for whom the drug was evaluated as safe to use. Wilcoxon's twosample test (normal approximation with continuity correction of 0.5) as implemented in the SAS procedure NPARIWAY was used to compare the drug groups with respect to average scores in the patients' assessment of heat and pain using the following code: 0 = none; 1 = mild; 2 = moderate; and 3 = severe. The Wilcoxon two-sample test was also used to compare the drug groups with respect to average change in vital sign parameters from baseline.
Results T h e d e m o g r a p h i c d a t a is s u m m a r i z e d i n T a b l e 1. Vital signs ( s y s t o l i c a n d d i a s t o l i c b l o o d p r e s s u r e , p u l s e rate, a n d r e s p i r a t o r y rate) d i d n o t s i g n i f i c a n t l y change after intravenous contrast administration in a n y o f t h e 80 p a t i e n t s . The analysis of patient tolerance (perception and a s s e s s m e n t ) o f h e a t a n d p a i n is d e t a i l e d i n T a b l e 2. None of the patients perceived pain in either contrast group. Ten of 40 patients (25%) in the ioversol group and seven of 40 patients (17.5%) in the ioh e x o l g r o u p p e r c e i v e d b o d y h e a t r e l a t e d to t h e i n -
58
A.J. Kaufman et al.: Ioversol for Intravenous Urography
jection o f contrast material. O f the eight patients in the iohexol group who inadvertently received only 50 ml (l 5 g iodine), none experienced heat or pain. N o n e o f the patients studied d e v e l o p e d urticaria, b r o n c h o s p a s m , or angioneurotic edema. T h e r e were no major, life-threatening reactions in either contrast group. O f the 40 patients receiving ioversol, two (5%) experienced nausea a n d two (5%) experienced an unpleasant taste. Similar results were seen in the iohexol group with two (5%) experiencing nausea and two (5%) c o m p l a i n i n g o f headache. All o f these side effects subsided spontaneously within 2 m i n postinjection. Evaluation o f image quality revealed no significant difference between either contrast agent. T a b l e 3 details the c o m p a r a t i v e results o f patients 1-65. T w e n t y - f o u r o f 33 u r o g r a m s (72.7%) scored "excellent" and eight o f 33 u r o g r a m s (24.2%) scored " a d e q u a t e " with ioversol, while 25 o f 32 u r o g r a m s (78%) were considered excellent and six o f 32 (18.75%) were " a d e q u a t e " with iohexol.
Table 2. A summary of data relative to heat as assessed by the
patient
Drug group
None
Mild
UnMod specerate Severe ified Total
Ioversol-240 Iohexol-300
30 33
8 6
2 1
0 0
0 0
40 40
Table 4 c o m p a r e s the results o f all 80 patients, including the eight iohexol patients who inadvertently received 50 ml instead o f the 60 m l (18 g iodine), which was specified in this protocol. F o r this population, 30 o f 40 patients (75%) receiving ioversol h a d "excellent" results and 27 o f 40 (67.5%) receiving iohexol scored "excellent." O f the eight patients receiving only 15 g iodine in iohexol, only two were d e e m e d "excellent" a n d six " a d e q u a t e . " In s u m m a r y , the results o f this study indicate that in c o m p a r i n g vital signs, adverse effects, and imaging quality, there is no significant difference between these two nonionic contrast agents. Discussion
Although the pathogenesis o f adverse contrast reactions is complex and multi-faceted, it does a p p e a r that m e c h a n i s m s associated with h y p e r o s m o l a l i t y play a part in objective and subjective undesirable effects [ 13-16]. W h e n c o m p a r i n g the urographic diagnostic i m age quality o f L O C M nonionics a n d the H O C M ionics, the nonionics h a v e been reported to be equivalent [ 17] or superior [2-4, 6, 7]. C o n t r o v e r s y still exists concerning the extent and cause o f n e p h rotoxicity o f the various types o f contrast agents, with the m o s t recent data suggesting that L O C M and H O C M h a v e an equally nephrotoxic effect [18, 19]. This study c o m p a r e s the urographic diagnostic
Table 3. Frequency distributions of patients according to quality of procedure excluding patients numbered 66 through 80
Ioversol-240
Iohexol-300
Region of interest
Excellent Adequate Poor
None
Total
Excellent Adequate Poor
None
Total
Right kidney Parenchyma Calyces Pelvis Ureter
26 26 26 23
6 6 6 9
1 1 1 1
0 0 0 0
33 33 33 33
26 28 29 27
5 3 2 3
1 1 1 2
0 0 0 0
32 32 32 32
Left kidney Parenchyma Calyces Pelvis Ureter
26 26 26 23
6 6 6 8
1 1 1 2
0 0 0 0
33 33 33 33
25 27 28 27
5 3 2 3
1 1 1 1
1 1 1 1
32 32 32 32
Bladder Overall quality
26 24
6 8
1 1
0 0
33 33
25 25
6 6
1 1
0 0
32 32
Ioversol-240
Overall diagnostic utility
Iohexol-300
Diagnostic
Nondiagnostic Total
Diagnostic
Nondiagnostic Total
32
1a
32
0
33
32
a In this 73-year-old male patient, there has been long-term renovascular disease with hypertension and resultant nephrosclerosis.
59
A.J. Kaufman et al.: Ioversol for Intravenous Urography Table 4. Frequency distributions of patients according to quality of procedure Ioversol-240
Iohexol-300
Region of interest
Excellent Adequate Poor
None
Total
Excellent Adequate Poor
None
Total
Right kidney Parenchyma Calyces Pelvis Ureter
32 32 32 29
7 7 7 10
1 1 1 1
0 0 0 0
40 40 40 40
28 30 31 29
10 8 7 8
2 2 2 3
0 0 0 0
40 40 40 40
Left kidney Parenchyma Calyces Pelvis Ureter
32 32 32 29
7 7 7 9
1 1 1 2
0 0 0 0
40 40 40 40
27 29 30 29
11 9 8 9
1 1 1 1
1 1 1 1
40 40 40 40
Bladder Overall quality
32 30
7 9
1 1
0 0
40 40
27 27
12 12
1 1
0 0
40 40
Ioversol-240
Overall diagnostic utility
Iohexol-300
Diagnostic
Nondiagnostic Total
Diagnostic
Nondiagnostic Total
39
1
40
0
image quality, adverse reactions, vital signs, and patient tolerance of two nonionic, low-osmolality contrast agents. The results reveal that both ioversol and iohexol are equivalent in regard to the aforementioned parameters. Much of the current debate in the medical community concerns itself with the cost and "cost-effectiveness" of these low-osmolality, nonionic contrast agents [20-23]. Unfortunately, the definition and analysis of the term "cost-effectiveness" vary greatly. The notion of cost effectiveness is indeed important and worthy of consideration as are moral, ethical, and legal issues, and, of course, patient safety. Currently, the commonly used nonionics are reported to produce fewer adverse reactions than the ionic HOCM [1-10, 13-16]. As stated by Dr. Ronaid G. Grainger of the United Kingdom, "The second generation, low-osmolar media are, therefore, to be preferred to conventional media for most purposes, arterial or intravenous injection. The only problem is one of expense as they cost four to six times the price of conventional media" [24]. This current study comparing the two nonionics reveals that quite adequate and even excellent image quality can be obtained with only 18 g iodine. Perhaps the high costs could be reduced by diminishing the doses being administered, while fostering patient safety and comfort without sacrificing quality. Studies comparing smaller amounts of LOCM to large amounts of H O C M would be beneficial in substantiating our initial observations.
40
40
Acknowledgments. We thank Tom Ebers for his expert editorial assistance, Linda Pennington for her secretarial aid, and Mallinckrodt, Inc. for contrast material, funding, and statistical analysis. This work was supported in part by Mallinckrodt, Inc.
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Advantages of non-ionic contrast agents in adult urography. Urology 24:297-299, 1984 Stake G, Smevik B: Iohexol and metrizamide for urography in infants and children. Invest Radiol 20(suppl):S115-S116, 1985 Golman K, Admen T: Contrast media-induced nephrotoxicity: survey and present state. Invest Radio120(suppl):S92$97, 1985 Schwab SJ, Hlatky MA, Pieper KS, Davidson CJ, Morris KG, Skelton TN, Bashore TM: Contrast nephrotoxicity: a randomized controlled trial of a nonionic and an ionic radiographic contrast agent. NEnglJMed 320:149-153, 1989 Reuter SR: The use of conventional vs low-osmolar contrast agents: a legal analysis. A JR 151:529-531, 1988 White RI Jr, Halden WJ Jr: Liquid gold: low-osmolality contrast media. Radiology 159:559-560, 1986 Evens RG: Economic impact oflow-osmolality contrast agents on radiology procedures and departments. Radiology 162: 267-268, 1987 McClennan BL: Low-osmolality contrast media: premises and promises. Radiology 162:1-8, 1987 Grainger RG: The clinical and financial implications of the low-osmolar radiological contrast media (correspondence). Clin Radio135:251-252, 1984
