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Low dose low osmolar intravenous urography
Clinical Radiology (1987) 38, 403-405
Low Dose Low Osmolar Intravenous Urography B. E. EYES, M. G O L D M A N , T. E. NIXON, J. S C A L L Y and A. B R O W N
Departments of Radiology, Walton and Fazakerley Hospitals, Liverpool
A prospective double blind randomised trial using 25 ml of Hexabrix 320 (ioxaglate, May and Baker), Niopam 370 (iopamidol, Merck) or Omnipaque 350 (iohexol, Nycomed) intravenous urography was carried out. The results showed no perceptible difference in the diagnostic quality of urograms with each of the media. An additional 25 ml of contrast medium was required by 4% of patients in order to obtain a satisfactory examination. We recommend that a dose of 25 ml of low-osmolar medium be used for all patients with the excePtion of the obese, those taking diuretics or those who have renal impairment.
The introduction of low osmolar contrast agents with increased cost and reduced incidence of adverse reactions has prompted a reassessment of the standard dose of contrast media which has evolved over many years (Grainger, 1986). The low osmolar contrast agents produce a greater urinary concentration of iodine for a given dose than the ionic media due to the reduced osmotic diuresis (Dalla Palma et al., 1982). It should therefore be possible to reduce the iodine dosage whilst maintaining a satisfactory urinary concentration. This paper reports a prospective double-blind trial comparing an equal volume (25 ml) dose of Hexabrix 320 (ioxaglate, May and Baker), Niopam 370 (iopamidol, Merck) and Omnipaque 350 (iohexol, Nycomed). The equal volume dose was preferred to an equal iodine dose as it was felt that the results could more easily be translated to routine clinical practice. We have attempted to show that 25 ml of any of the low osmolar agents can produce a diagnostically acceptable intravenous urogram. If this reduced dosage becomes generally accepted then considerable financial savings would accrue. What is more, it might then be possible to give all patients the low osmolar agents and not restrict them to high risk categories.
PATIENTS AND M E T H O D
One hundred and fifty patients aged 18-65 who were to undergo intravenous urography were randomly allocated by computer to receive 25 ml of Hexabrix 320, Niopam 370 or Omnipaque 350. Patients with known urinary tract abnormalities, renal failure or diabetes were excluded from the trial. Obese patients and those taking diuretics were also excluded. The patients had nothing to eat or drink for 12 h prior to the procedure. Bowel preparation was not given. Prior to the investigation each patient's weight was recorded and a blood sample was taken for urea and creatinine estimation. If the blood urea was later found to be elevated then the patient was rejected from the
trial. Twenty five ml of the allocated contrast material were injected as rapidly as possible. The cannula was left in the vein following the injection. The following radiographs were taken: 1 Control full length abdomen; 2 Three minute film coned to the renal area. Abdominal compression was then applied; 3 Seven minute film coned to the renal area. The need for tomography was assessed at this stage by one of the Senior Registrars. The technical quality of the film was also assessed at this point and if it was considered not to be of diagnostic quality a further 25 ml of the allocated contrast material were injected; 4 Ten minute film coned to the renal area; 5 Twenty minute full length film after release of compression; 6 Full bladder film; 7 Bladder film after micturition. Any side effects during the examination were noted. The diagnostic quality of the urograms was assessed later by two or us (B.E. and M . G . ) , neither of whom knew which medium had been used in each case. The visualisation of the nephrograms, pyelograms, ureters and bladder was graded from one to four (1 = v e r y poor; 2 = p o o r ; 3 = g o o d ; 4=exceUent).
RESULTS Hexabrix Group - 50 Patients
One patient experienced a mild urticarial reaction. Detail of the pelvicalyceal system was thought to be insufficient in two cases and these both received a further 25 ml of Hexabrix. T o m o g r a p h y was deemed necessary in 20 cases due to Overlying bowel content obscuring detail. Niopam Group - 50 Patients
No reactions were noted in this group. An additional dose of contrast medium was required in three cases due to insufficient detail. Thirteen patients required tomography. Omnipaque Group - 50 Patients
One patient required an additional dose of contrast medium. Tomography was required in 24 cases. No reactions were noted in this group. Statistical analysis showed no significant differences between the mean visualisation scores at each stage of the urogram for each of the media. Ranking (Table 1) of the various phases of the urogram showed minor differences between the three media. Niopam appeared best in the nephrogram phase
404 Table
CLINICAL R A D I O L O G Y
1 - Rank
Hexabrix Niopam Omnipaque
scores
Nephrogram
Pyelogram
Ureters
Bladder
Total
2 3 1
1 2 3
1.5 1.5 3
1 3 2
5.5 9.5 9.0
and in the demonstration of the bladder. O m n i p a q u e was ranked highest in the pyelographic and ureteric phases, but lowest in the n e o p h r o g r a m phase. Although Hexabrix did not attain the best position at any level, its overall results were satisfactory. Total rank scores gave N i o p a m 9.5 and O m n i p a q u e 9.0, both better than Hexabrix with 5.5. The results show marginal differences between the two non-ionic contrast agents (Niopam and Omnipaque) but they failed to reach statistical significance at any level.
DISCUSSION The introduction of low osmolality contrast media has increased the safety of intravascular contrast agents particularly for those patients in the 'at risk' categories. It has recently been demonstrated that this benefit is probably also enjoyed by the general population. A 2.1% incidence of reactions was recorded for O m n i p a q u e during intravenous urography (Schrott, 1986) compared with an 8.5% incidence (Ansell, 1970) and 4.8% (Shehadi, 1975) for conventional media, although as yet there has been no large-scale controlled trial. The low osmolar agents achieve a higher urinary iodine concentration for a given dose of iodine because of the reduced osmotic diuresis, it was originally thought by Dawson et al. (1983) that this benefit might be outweighed by significantly less pelvicalyceal distension. However, Dawson et al. (1984) did not find any evidence of this when efficient abdominal compression was applied. It is important therefore to reassess the optimal amount of contrast agent that is required to produce acceptable diagnostic information as costs have been considerably increased by the new media. Acceptable diagnostic quality is difficult to define. In the context of this study it is probably easier to define those patients whose examinations did not reach 'acceptable quality' (4% of cases). They were rejected because a particular phase of the urogram was visualised poorly, e.g. low density, poorly defined nephrograms, or inadequately filled, poorly opacified pelvicalyceal systems. These patients received a further 25 ml dose of the allocated agent and an acceptable urogram was then obtained. In the remaining 96% of patients each phase of the urogram was delineated satisfactorily with good pelvicalyceal filling and well defined nephrograms. It may be argued that with only 25 ml something may be missed that would be visible with 50 ml. We think this is unlikely given the quality of the urograms produced. We suggest that 25 ml is the optimum dose of the new media because of their different biochemical and physical properties. The density of the nephrogram produced by the lower dose will obviously be less than with conventional higher doses as the nephrographic density is directly proportional to the administered dose of iodine
(Talner, 1972). H o w e v e r , in our study the nephrograms produced were of sufficient clarity to demonstrate the renal outlines. We also believe that with the introduction of ultrasound scanning the very 'bright' nephrograms previously required to exclude space occupying lesions are no longer necessary. In dubious cases an ultrasound scan could be done during the course of the urogram. As a consequence of the reduced diuresis the bladder did not achieve the same degree of distension as is usual with the high dose of conventional media. It may be necessary to take the bladder films later to allow filling. T o m o g r a p h y was required in 40% of the cases, an incidence which was unchanged from previous usage. T o m o g r a p h y involved a single thick cut through the kidneys. The m a j o r indication for tomography was overlying bowel content and gas. No increased costs or increased radiation dosage would be incurred by the adoption of the low dose regime. This study has demonstrated that the 25 ml dose produces satisfactory results in most cases. Not all patients will be suitable for this low dose, e.g. those in renal failure and those in whom compression cannot be applied. It has been our experience since adopting the guidelines suggested by Grainger (1984) for the use of low osmolar agents that a large proportion of our patients fell into one or other of the 'at risk' categories. Hence there has been a considerable increase in the expenditure on contrast media. As it has now been demonstrated that low osmolar agents probably produce fewer reactions in the general population (Schrott et al., 1986) as well as in the 'at risk' groups then the pressure to use the new media exclusively is considerable. The adoption of the lower dose regime would considerably reduce the financial burden of such a change. The study has demonstrated that half (25 ml) of the standard 50 ml contrast dose will produce subjectively acceptable urograms in 96% of the patients studied. There are minor differences between the three low osmolar agents but none reached statistical significance. We r e c o m m e n d that 25 ml should become the accepted standard dose of low osmolar contrast agent for intravenous urography. Acknowledgements. We are grateful to Mr D. Copc, Superintendent Radiographer at Walton Hospital, for his assistance in collating the data, and to Mr J. Hart and his colleagues of E. Merck Ltd, for their helpful advice and statistical analysisof the results. We thank Mrs Ann Cookson for typing the manuscript and her patience, also to Mrs P. Hinde for her radiographic excellence.
REFERENCES
Ansell, G (1970). Adverse reactions to contrast agents. Scope of the problem. Investigative Radiology, 5, 374-384. Dalla Palma, L, Rossi, M, Stacul, F & Agostine, R (1982). Iop,amidol in urography: a comparison between ionic and non-ionic contrast media in patients with normal and impaired renal function. Urologic Radiology, 4, l-3. Dawson, P, Grainger, RG & Pitfield, J (1983). The new low osmolar contrast media: a simple guide. Clinical Radiology, 34, 221-226. Dawson, P, Heron C & Marshall, J (1984). Intravenous urography with low-osmolalitycontrast agents: theoretical considerations and clinical findings. Clinical Radiology, 35, 173-175. Grainger, RG (1984). The clinical and financial implications of the
J
LOW DOSE LOW OSMOLAR IV UROGRAPHY iow-osmolar radiological contrast media. Clinical Radiology, 35, 251. Grainger, RG (1986). The optimum concentration of contrast medium for aortography and femoral arteriography: a comparison of Hexabrix 320 and Hexabrix 250. Clinical Radiology, 37, 281-284. Schrott, KM, Behrends, B, Clauss, W, Kaufmann, J & Lehnert, J
405
(1986). Iohexol in excretory urography. Fortschritte der Medizin, 104, 153-156. Shehadi, W (1975). Adverse reactions to intravascularly administered contrast media. American Journal of Roentgenology, 124,145-152. Talner, LB (1972). Urographic contrast media in uraemia. Radiologic Clinics of North America, 10, 421-432.
Low Dose Low Osmolar Intravenous Urography B. E. EYES, M. G O L D M A N , T. E. NIXON, J. S C A L L Y and A. B R O W N
Departments of Radiology, Walton and Fazakerley Hospitals, Liverpool
A prospective double blind randomised trial using 25 ml of Hexabrix 320 (ioxaglate, May and Baker), Niopam 370 (iopamidol, Merck) or Omnipaque 350 (iohexol, Nycomed) intravenous urography was carried out. The results showed no perceptible difference in the diagnostic quality of urograms with each of the media. An additional 25 ml of contrast medium was required by 4% of patients in order to obtain a satisfactory examination. We recommend that a dose of 25 ml of low-osmolar medium be used for all patients with the excePtion of the obese, those taking diuretics or those who have renal impairment.
The introduction of low osmolar contrast agents with increased cost and reduced incidence of adverse reactions has prompted a reassessment of the standard dose of contrast media which has evolved over many years (Grainger, 1986). The low osmolar contrast agents produce a greater urinary concentration of iodine for a given dose than the ionic media due to the reduced osmotic diuresis (Dalla Palma et al., 1982). It should therefore be possible to reduce the iodine dosage whilst maintaining a satisfactory urinary concentration. This paper reports a prospective double-blind trial comparing an equal volume (25 ml) dose of Hexabrix 320 (ioxaglate, May and Baker), Niopam 370 (iopamidol, Merck) and Omnipaque 350 (iohexol, Nycomed). The equal volume dose was preferred to an equal iodine dose as it was felt that the results could more easily be translated to routine clinical practice. We have attempted to show that 25 ml of any of the low osmolar agents can produce a diagnostically acceptable intravenous urogram. If this reduced dosage becomes generally accepted then considerable financial savings would accrue. What is more, it might then be possible to give all patients the low osmolar agents and not restrict them to high risk categories.
PATIENTS AND M E T H O D
One hundred and fifty patients aged 18-65 who were to undergo intravenous urography were randomly allocated by computer to receive 25 ml of Hexabrix 320, Niopam 370 or Omnipaque 350. Patients with known urinary tract abnormalities, renal failure or diabetes were excluded from the trial. Obese patients and those taking diuretics were also excluded. The patients had nothing to eat or drink for 12 h prior to the procedure. Bowel preparation was not given. Prior to the investigation each patient's weight was recorded and a blood sample was taken for urea and creatinine estimation. If the blood urea was later found to be elevated then the patient was rejected from the
trial. Twenty five ml of the allocated contrast material were injected as rapidly as possible. The cannula was left in the vein following the injection. The following radiographs were taken: 1 Control full length abdomen; 2 Three minute film coned to the renal area. Abdominal compression was then applied; 3 Seven minute film coned to the renal area. The need for tomography was assessed at this stage by one of the Senior Registrars. The technical quality of the film was also assessed at this point and if it was considered not to be of diagnostic quality a further 25 ml of the allocated contrast material were injected; 4 Ten minute film coned to the renal area; 5 Twenty minute full length film after release of compression; 6 Full bladder film; 7 Bladder film after micturition. Any side effects during the examination were noted. The diagnostic quality of the urograms was assessed later by two or us (B.E. and M . G . ) , neither of whom knew which medium had been used in each case. The visualisation of the nephrograms, pyelograms, ureters and bladder was graded from one to four (1 = v e r y poor; 2 = p o o r ; 3 = g o o d ; 4=exceUent).
RESULTS Hexabrix Group - 50 Patients
One patient experienced a mild urticarial reaction. Detail of the pelvicalyceal system was thought to be insufficient in two cases and these both received a further 25 ml of Hexabrix. T o m o g r a p h y was deemed necessary in 20 cases due to Overlying bowel content obscuring detail. Niopam Group - 50 Patients
No reactions were noted in this group. An additional dose of contrast medium was required in three cases due to insufficient detail. Thirteen patients required tomography. Omnipaque Group - 50 Patients
One patient required an additional dose of contrast medium. Tomography was required in 24 cases. No reactions were noted in this group. Statistical analysis showed no significant differences between the mean visualisation scores at each stage of the urogram for each of the media. Ranking (Table 1) of the various phases of the urogram showed minor differences between the three media. Niopam appeared best in the nephrogram phase
404 Table
CLINICAL R A D I O L O G Y
1 - Rank
Hexabrix Niopam Omnipaque
scores
Nephrogram
Pyelogram
Ureters
Bladder
Total
2 3 1
1 2 3
1.5 1.5 3
1 3 2
5.5 9.5 9.0
and in the demonstration of the bladder. O m n i p a q u e was ranked highest in the pyelographic and ureteric phases, but lowest in the n e o p h r o g r a m phase. Although Hexabrix did not attain the best position at any level, its overall results were satisfactory. Total rank scores gave N i o p a m 9.5 and O m n i p a q u e 9.0, both better than Hexabrix with 5.5. The results show marginal differences between the two non-ionic contrast agents (Niopam and Omnipaque) but they failed to reach statistical significance at any level.
DISCUSSION The introduction of low osmolality contrast media has increased the safety of intravascular contrast agents particularly for those patients in the 'at risk' categories. It has recently been demonstrated that this benefit is probably also enjoyed by the general population. A 2.1% incidence of reactions was recorded for O m n i p a q u e during intravenous urography (Schrott, 1986) compared with an 8.5% incidence (Ansell, 1970) and 4.8% (Shehadi, 1975) for conventional media, although as yet there has been no large-scale controlled trial. The low osmolar agents achieve a higher urinary iodine concentration for a given dose of iodine because of the reduced osmotic diuresis, it was originally thought by Dawson et al. (1983) that this benefit might be outweighed by significantly less pelvicalyceal distension. However, Dawson et al. (1984) did not find any evidence of this when efficient abdominal compression was applied. It is important therefore to reassess the optimal amount of contrast agent that is required to produce acceptable diagnostic information as costs have been considerably increased by the new media. Acceptable diagnostic quality is difficult to define. In the context of this study it is probably easier to define those patients whose examinations did not reach 'acceptable quality' (4% of cases). They were rejected because a particular phase of the urogram was visualised poorly, e.g. low density, poorly defined nephrograms, or inadequately filled, poorly opacified pelvicalyceal systems. These patients received a further 25 ml dose of the allocated agent and an acceptable urogram was then obtained. In the remaining 96% of patients each phase of the urogram was delineated satisfactorily with good pelvicalyceal filling and well defined nephrograms. It may be argued that with only 25 ml something may be missed that would be visible with 50 ml. We think this is unlikely given the quality of the urograms produced. We suggest that 25 ml is the optimum dose of the new media because of their different biochemical and physical properties. The density of the nephrogram produced by the lower dose will obviously be less than with conventional higher doses as the nephrographic density is directly proportional to the administered dose of iodine
(Talner, 1972). H o w e v e r , in our study the nephrograms produced were of sufficient clarity to demonstrate the renal outlines. We also believe that with the introduction of ultrasound scanning the very 'bright' nephrograms previously required to exclude space occupying lesions are no longer necessary. In dubious cases an ultrasound scan could be done during the course of the urogram. As a consequence of the reduced diuresis the bladder did not achieve the same degree of distension as is usual with the high dose of conventional media. It may be necessary to take the bladder films later to allow filling. T o m o g r a p h y was required in 40% of the cases, an incidence which was unchanged from previous usage. T o m o g r a p h y involved a single thick cut through the kidneys. The m a j o r indication for tomography was overlying bowel content and gas. No increased costs or increased radiation dosage would be incurred by the adoption of the low dose regime. This study has demonstrated that the 25 ml dose produces satisfactory results in most cases. Not all patients will be suitable for this low dose, e.g. those in renal failure and those in whom compression cannot be applied. It has been our experience since adopting the guidelines suggested by Grainger (1984) for the use of low osmolar agents that a large proportion of our patients fell into one or other of the 'at risk' categories. Hence there has been a considerable increase in the expenditure on contrast media. As it has now been demonstrated that low osmolar agents probably produce fewer reactions in the general population (Schrott et al., 1986) as well as in the 'at risk' groups then the pressure to use the new media exclusively is considerable. The adoption of the lower dose regime would considerably reduce the financial burden of such a change. The study has demonstrated that half (25 ml) of the standard 50 ml contrast dose will produce subjectively acceptable urograms in 96% of the patients studied. There are minor differences between the three low osmolar agents but none reached statistical significance. We r e c o m m e n d that 25 ml should become the accepted standard dose of low osmolar contrast agent for intravenous urography. Acknowledgements. We are grateful to Mr D. Copc, Superintendent Radiographer at Walton Hospital, for his assistance in collating the data, and to Mr J. Hart and his colleagues of E. Merck Ltd, for their helpful advice and statistical analysisof the results. We thank Mrs Ann Cookson for typing the manuscript and her patience, also to Mrs P. Hinde for her radiographic excellence.
REFERENCES
Ansell, G (1970). Adverse reactions to contrast agents. Scope of the problem. Investigative Radiology, 5, 374-384. Dalla Palma, L, Rossi, M, Stacul, F & Agostine, R (1982). Iop,amidol in urography: a comparison between ionic and non-ionic contrast media in patients with normal and impaired renal function. Urologic Radiology, 4, l-3. Dawson, P, Grainger, RG & Pitfield, J (1983). The new low osmolar contrast media: a simple guide. Clinical Radiology, 34, 221-226. Dawson, P, Heron C & Marshall, J (1984). Intravenous urography with low-osmolalitycontrast agents: theoretical considerations and clinical findings. Clinical Radiology, 35, 173-175. Grainger, RG (1984). The clinical and financial implications of the
J
LOW DOSE LOW OSMOLAR IV UROGRAPHY iow-osmolar radiological contrast media. Clinical Radiology, 35, 251. Grainger, RG (1986). The optimum concentration of contrast medium for aortography and femoral arteriography: a comparison of Hexabrix 320 and Hexabrix 250. Clinical Radiology, 37, 281-284. Schrott, KM, Behrends, B, Clauss, W, Kaufmann, J & Lehnert, J
405
(1986). Iohexol in excretory urography. Fortschritte der Medizin, 104, 153-156. Shehadi, W (1975). Adverse reactions to intravascularly administered contrast media. American Journal of Roentgenology, 124,145-152. Talner, LB (1972). Urographic contrast media in uraemia. Radiologic Clinics of North America, 10, 421-432.