Australas Radio1 1990; 34: 137-141

Low Dose Intravenous Urography: Results and Technique Modifications DR R.J. KEENAN, M.B.ChB dist. (NZ) Radiology Regktrar Department of Radiology Auckland, New Zealand DR A. LIST, M.B.Ch.B., F.R.A.C.R. (NZ) Uroradiologist Department of Radiology Auckland, New Zealand DR C. KENGSAKUL, M.D. (Thailand) Radiology Registrar Department of Radiology Auckland, New Zealand

ABSTRACT 100 consecutive patients routinely referred for intravenous urography were examined using low doses of the low osmolar contrast medium Iohexol (Omnipaque 350mgUml). Their dosage schedule was based on the physiological parameters of age, sex, body weight and renal function. Comparison with a control group using standard contrast doses revealed a 42% reduction in contrast could be used, and still produce diagnostic studies. Nephrographic quality was reduced in the low dose group requiring technique modification, in particular a delayed film sequence. Further reductions in contrast use are envisaged in patients over the age of 40 years.

METHODS One hundred and fifty consecutive inpatients and outpatients routinely referred for intravenous urography comprised our study group. This population was essentially non-selected with only trauma examinations being excluded. The total population was divided into three contrast groups which were not statistically different (p>0.05) with respect to age, sex, body weight or renal function (Table 1).

INTRODUCTION The benefits of the new low osmolar contrast media (LOCM) available for intravenous radiological studies are well documented (McClennan 1987). In particular, improved patient tolerance, acceptance and safety have resulted in their widespread routine use (Palmer 1988, Aakhus et a1 1980). These agents are however, significantly more expensive than conventional agents by a factor of five or six (Goldman and Eyes 1988, Evens 1987). This major limitation prompted our group to investigate a technique of low dose intravenous urography using the 3:l ratio non-ionic monomer, Iohexol (0mnipaque:Nycomed-Winthrop). We aimed to develop an optimum dosage schedule based on the physiological parameters of age, sex, body weight and renal function. Modifications to the radiographic sequence of the urogram were also examined in order to improve study quality. A schedule was sought which would minimise contrast dose and cost without sacrificing diagnostic quality but still be applicable to a standard radiologic practice.

Group

TABLE I PATIENT RAW DATA Group11

50

50

53

70.1

52 56 44 68.6

23 46.5 23 1 0.66

40.4 214 0.6 1

Patients Numbers Age

(w)

Sex: Male (%) Female (96) Weight (kg) Renal Impairment (5%) Contrast Volume (ml) Contrast Dose (mgvkg) Contrast Dcse (mYkg)

54 46

14

GroupnI 50 46

60 40 15.7 29 70.2

350 1.M)

(Contrast Medium: Iohexol 35OmgUml)

Groups I and I1 were studied prospectively using our experimental low dose schedule (Figure 1). Maximum and minimum doses were set at 7 and 35 grams (20 and l W Iohexol 35OmgUml) of Iodine respectively. Group 111 was a retrospective control group given a standard dose of contrast medium according to individual body size (Table 2). TABLE 2 STANDARD DOSE SCHEDULE

c: 50 > 50 Key words: Intravenous Urography, low dose Low Osmolar Contrast Media Economics, Medical

Group1

Normal

Intemediirte

L%F

50

50 70

100

50

50

(mi Iohexol 35OmgYml)

Address for correspondence: Dr R.J. Keenan Radiology Registrar Department of Radiology Auckland Hospital Auckland, New &land AustralasianRadiology, Vol. X X H K No. 2, May, 1990

Submitted for publication: 6th October, 1989 Accepted for publieation: 8th December, I989

I37

K.J. KEENAN eT al TABLE 5 EXPERIMENTAL DOSE SCHEDULE

500 i

I

400

15

300

100

0

20

40 60 Age in years

80

FIGURE 1 - Experimental Dose Schedule Graph of t k cxpcrimcntal wntrast dosc schedule used in Groups I and 11.

Radiographic film sequences were divided into two protocols. The standard protocol was used for Groups I and I11 and was the routine sequence in this institution prior to beginning this study. The modified protocol which included Serial films between four and six minutes was instituted in Group I1 (Table 3). TABLE 3 RADIOGRAPHIC SEQUENCES

2 4 5

6 8 15

Preliminary Coned Renal

Preliminary Coned Renal +/Tomography -

-

Plain Full Length Coned Renal +/Compression

25

105 (7 (age)-175) 350

(Contrast Medium: Iohexol 350mgVml)

200

0

Gontrast Dose CmgUkg)

Patknt Age &TS)

Full Length +I- Release Coned Bladder

The contrast medium dose was calculated for those in the experimental group according to age and weight measured prior to the examination. Abdominal compression was used routinely on all patients able to tolerate it. Radiographs were taken according to the sequences already described. Each set of films was reviewed using a four point scale to grade the quality of nephrograms, nephrotomograms, pyelograms, ureters and bladder (1 =Excellent 2 =Satisfactory 3 =Poor 4 =Inadequate). Right and left tracts were judged separately. An overall assessment of each study was made as to its diagnostic effect.

RESULB Contrast Dose Schedule: (Group I and 111) The mean contrast dose given to patients in Group I was 23OmgVkg (SD= 90) compared to 350mgVkg (SD=96) in the control Group 111. All examinations carried out were judged as being of diagnostic quality, with none requiring a repeat study. Nephrographic quality was statistically worse in the experimental low dose group when compared to the control (P>O.OS). This was particularly significant on the right (p>O.OI). The use of nephrotomography however eliminated this disparity bilaterally (p>O.OI) (Figure 2).

Renal Tomography Renal Tomography Renal Tomography Plain Full Length Coned Renal +/Compression Full Length +I- Release Coned Bladder

30 v)

c l=

a,

The first stage of our study compared Groups I and I11 in order to assess the effect of the low dose regimen on urographic quality, whilst the second stage compared Groups I1 and 111 to determine the effect of varying film sequences (Table 4).

'F.

TABLE 4 CONTRAST GROUP COMPARISON

3

Gw,

I I1 111

ProspWivc Prmpxtive Retrospective

20-

0 L

a,

10-

z

Dape

Film Sequence

Experimental Exgcrimental Control

Standard Modified Standard

Patients were not dehydrated, fluid restricted or given a bowel preparation. Following preliminary abdominal films, contrast medium was injected manually into an antecubital vein. Injection time was less than one minute. All patients received Iohexol (Omnipaque) 35Omg/ml. 138

(d

CL

O ! 0

1

2

*

3

1

4

5

Quality Grade FIGURE 2 - Nephrogram Quality Comparison of the nephrographic quality between Group 1 and Group 111. A Group I11 Nephrogram OGroup I Right Nephrogram .Group I Left Nephrogram 0Group I Right Nephrotomogram Group 1 Left Nephrotomogram

Australasian Radiology, Vol. XXXN,No. 2 , May, 1990

LOW DOSE INTRAVENOUS UROGRAPHY No difference could be demonstrated during the subsequent phases of the urogram (p>O.OI) (Figure 3). When patients with renal impairment in Groups I and 111were compared independently, no significant difference was detected in any phase including the nephrogram (p>O.Ol). Renal impairment was defined as a urea and creatinine measurement greater than the mean plus two standard deviations. . I -

0 L

a,

2

10

3

z

O! 0

1

10 20 Time of best Nephrogram (rnins)

FIGURE 4 - Time of Optimum Nephrogram Comparison of the optimum nephrogram timing between Group I1 and GrouD 111.

0

1

2 3 Quality Grade

4

5

FIGURE 3 - Pyelogram Quality Comparison of pyelogram quality between Group I and Group 111. 0Group I Right F‘yelogram 0 Group I Left Pyelogram 0Group I11 Right Pyelogram Group I11 Left Pyelogram

20 cn + !=

(I) ..+-

(d

a

5 10L

Radiographic Sequence: (Group I1 and 111) Only the timing of the most optimal radiograph in each urographic phase was recorded for our evaluation. Significant differences were noted between the conventional and modified sequences in both nephrogram and pyelogram phases. Timing of the best nephrogram was delayed in the experimental Group I1 to approximately 3-4 minutes with a rapid deterioration beyond 5 minutes (Figure 4). Similarly the peak pyelosam visualisation occured later than in the control group, at about 5-15 minutes. It was also apparent that the time range of peak visualisation was extended (Figure 5). No significant differences between Groups I1 and 111 was found in ureter or bladder phases. cost

The average volume of contrast administered to the one hundred patients assigned to the experimental dose regime was 43ml compared to the control group which received 70ml. This represents a cost saving of 39% in contrast used. An overall cost saving of 33% was achieved when extra film costs were considered. These however would not normally be incurred during usual clinical practice.

Australasian Radiology, Vol.XXXW,No.2 , May, I 9 9 0

(I)

I)

E

3

Z

o! 0

’ . ’ 20 30

-

1

.

I

40 50 Time of best Pyelogram (mins) 10

FIGURE 5 - Time of Optimum F‘yelogram Comparison of the optimum pyelogram timing between Group11 and Group 111. 0 Group 111 Group 11

DISCUSSION The nephrogram consists of a vascular phase in the first few seconcis which is short-lived, and not therefore clinically important (Talner 1972). The clinically significant or “immediate” nephrogram, is the direct result of filtered contrast medium (CM) in the extravascular extracellular space and more specifically the proximal convoluted tubule. Nephrographic quality is mainly dependent on the immediate plasma concentration of CM (Dawson 1984). This peak occurs during the first 5 minutes (Taenzer 1987) and is determined by the rate of injection, volume of distribution and total dose of Iodine/ kg. In the clinical context with rapid “boIus” administration of CM, the latter is most cwcial (Dawson 1988).

139

K.I. KEENAN et a1 LCXM are a l m t entirely excreted by glomerular filtration with no significant degree of renal tubular absorption or secretion f l a e m r 1987, Katezberg 1988). opacification of the collecting system was in the p t attributed to urinary concentration of CM ( S h e r w d er al 1968).Subsequent research has demonstrated that opacification is mainly dependent on the total amount of CM excreted and therefore the filtered load of iodinated CM (Dure-Smither a2 1971). This is the product of glomerular filtration rate (GFR) and plasma concentration of CM. Rend function is therefore most important in determining the quality of the pyelogram and subsequent u r e graphic phases but is of relatively less importance in affecting the nephrogram phase. A number of physiological parameters formed the basis for our protclcol design. Dehydration was not included in patient preparation due to its lack of reliability. There is also experimental evidence in animals that it produces a significant fall in GFR thus theoretically diminishing visualisation of the collecting system, another negative feature (Katezberg 1988). Abdominal compression was incorporated into our study protocol as it has been shown conclusively to overwme the main disadvantage of the LOCM in producing less osmotic diuresis and subsequently less distension of the collecting systems (Dawson er al 1984, Taenzer 1987, Dawson er a1 1983, Sjoberg er a2 1980). The actual experimental dose schedule was based on the age-relatd renal function curve investigated by a number of groups (Figure6) (Granerus and Aurell 1981, Rutland 1983). This demonstrates a near plateau between 10 and 40 years, followed by a rapid decrease from 40 to 75 years with another plateau in the elderly group beyond 75 years.

I

2

(0

-Pp

300: 200

m

Y rn

a

3

100

-

. -- .

C



-mm Z

o 10

-

20

Age in Years

30

40

50

60

70

80

FlGURE 6 - Age-GFR Curve Single Kidney Uptake Rate of DTPA and MDP by normal kidneys plottcd as a function of age in years. The units are Ilm and the values have bem multiplied by a million for ease of presentation.

The rate at which an individual kidney takes up DTPA is proportional to thc GFR. Uptake rats may be used to cakubte individual renal GFR when appropriate scaling factors are used. (RepiiRtd with pemricslonf i : Rutland M. Glomerular Filtration Rate without H d Sampling. Nucl. Med. Commun. 1983: 4 :425-433)

The ageGFR curve defines significant renal impairment with increasing age despite often normal blood urea and creatinine measurements which are relatively insensitive. Increasing age alone is therefore an indication for increasing the amount of contrast given. Our dose sched140

ule approximates a reciprocal function to the ageGFR curve. This theoretically aimed to compensate for the r a p idly reducing filtered load of iodinated CM in patients over the age of 50. Our baseline LOCM dose was derived from recent investigators having experience with Iohexol doses as low as 9omgVkg (Bjork and Zachrisson 1986, Bjork and Zachrisson 1986) or standard doses of 17.5 grams (Dawson et a/ 1984). These groups noted difficulty however in the obese and those with renal impairment. Contrary to previous beliefs, no sex difference in GFR has been found after correction for body surface area. In view of this we felt justified in using the same protocol for both males and females. The use of a body-weight related regime allows the most rational use of contrast media. This is inherent in the close relationship between body weight, volume of distribution and plasma Iodine concentration on urographic quality. Set standard doses delivered to our control group produces a very wide scatter. Despite a 42% reduction in contrast use in our experimental group no significant loss in diagnostic quality was observed. The use of lower doses of CM did however result in a significant reduction in nephrographic quality, as might be anticipated, by the lower peak plasma concentration of CM. This was overcome by routine use of nephrotomography and delaying the nephrogram films until 3-5 minutes rather than the traditional “immediate” film. This delay in the optimum nephrogram has been found before (Levorstad et al 1982). The delay has been attributed to a reduced volume of distribution (10%) for the newer agents resulting in higher effective peak plasma levels up to 5 minutes post injection. This is because larger molecules of LOCM are less osmotically active than conventional agents and result in less movement of intracellular water into the extracellularcompartment (Dawson 1988). The effect of reduced dose in reducing plasma Iodine concentration reduces the filtered load of CM into the collecting system hence theoretically impairing visualisation. No signifcant effect was demonstrated in this study. This is presumably due to our use of compression routinely which provides adequate distension despite the reduced diuresis induced by a lesser osmotic load present when dose is reduced. Another factor noted was our delay in the timing of the pyelogram and ureteric films to 5-15 minutes. This effect seems related to the longer time required to filter an adequate threshhold total amount of CM into the collecting system when plasma CM concentration is lower. Comparison of the experimental low dose group in two parts, those under 40 years and those over 40 years, indicates significantly better quality nephrograms in the older age group (pM.01). No difference was demonstrated in the other urographic phases. In view of this, we believe that further CM savings can be attained in the over 40 years age group. Reducing the maximum dose in these patients to approximately 2OOmgl/kg is theoretically possible. This dosage protocol would in fact more closely parallel the age-GFR curve already mentioned. Further investigation of such a modified protocol is anticipated. In summary, we have presented an effective low dose technique for intravenous urography, using the newer low osmolar contrast medium Iohexol, which is easily applicable to everyday radiological practice and provides considerable eost savings. Diagnostic efficacy is unaffected.

Australasian Radiology, Vol.XXXN,No. 2 , May, 1990

LOW DOSE INTRAVENOUS UROGRAPHY ACKNOWLEDGEMENTS Our thanks to Janet Hornbuckle, medical student, University of Sheffield for her help in the research for this manuscript.

REFERENCES Aakhus T., Sommerfelt S.C., Stormorken H., Dahlstrom K., Tolerance and Excretion of lohexol after Intravenous Injection in Healthy Volunteers: Preliminary Report. Acta. Radiol. Suppl. 1980; 362 : 131-134. Bjork L., Zachnwn B.F. Low Dose Urography. A clinical comparison of three low osmolar (ratio 3) contrast medii.Acta. Radiol. Diagn 1986; 27 : 557-559. Bjork L. Zachrisson B.F. Low Dose Urography with a Low Osmolar Contrast Medium. Acta. Radiol. Diagn 1986; 27 : 111-113. Dawson P. A New Look at Intravenous Urography. Australas Radiol 1988; 32 : 309-312. Dawson P., Heron C., Marshall J. Intravenous Urography with Low Osmolality Contrast Agents: Theoretical Considerations and Clinical Findings. Clin. Radiol. 1984; 35 : 173-175. Dawson P., Grainger R.G., Pitfield J. The New Lowusmolar Contrast Media: A Simple Guide. Clin. Radiol. 1983; 34 : 221-226. DureSmith P., Simenhoff M., Zimskind P.D., Kdroff M. The Bolus Effect in Excretory Urography. Radiology 1971; 101 : 29-34. Evens R.G. Economic Impact of Low Osmolality Contrast Agents on Radiology Procedures and Departments. Radiology 1987; 162 : 267-268.

Ausfralasian Radiology, Val.XmW, No. 2, May, 1990

Goldman M., Eyes B.E. Letter: Low Osmokr Contrast Media. Clin. Radml. 1988; 39 : 101. Granerus G., AureE M.Referenct values for 51 Cr-EDTA ckarance as a measure of glomerukr filtration rate. Scand. J. Clin. Lab. Invest. 1981; 41 : 611616. Katezberg R.W. New and Old Contrast Agents: Physiology and N e p b toxicity. Urol. Radiol. 1988; 10 : 6-11. Levorstad K., Kolenstrcdt A., Sommerfelt S., Zachrissen B., Jagcnburgc et ul. Tolerability and diagnostic usefulness of Iohexol in Urography. An open multicentre clinical trial. Acta. Radiol. Diagn. 1982; 23 : 4914%. McClennan B.L. Low Osmolality Contrast Media: pn#niSa and Prem ises. Radiology 1987; 162 : 1-8. Palmer F. The RACR Survey of Intravenous Contrast Media Reactions: Final Report. Austrahs Radml. 1988; 32 : 426-428. Rutland M.D. Glomeruhr Filtration Rate without Blood Sampling. Nucl. Med. Commun. 1983; 4 : 425433. Sherwood T., Brcckenbridge C.T., Dollery C.T., Doyle F.H.. Steiner R.E. Intravenous Urography and Renal Function. Clin. Radiol. 1968; 19 : 2%302. Sjoberg S, Almen T., Golman K. Excretion of Urographjc Contrast M a d i 1: Iohoxel and other media during free urine flow in tbc rabbit. Acta. Radi01. Suppl. 1980; 3 6 2 93-98. T a e m r V. Optimum b g e in Urography. In: Felix R., Fischer H.W., Kormano M., Paulin S, De Schepper A,, Skalpe LO., Speck U., Wolf K.J.,eds.Contrast Media from the Past to the Future: Symposium Bcrlin 27 March 1987. Stuttgart; New Yo& Thieme V e r b 1987. pp 123-135. Talner L.B. Urcgraphic Contrast Media in Uremia.Physiology and Pharmambgy. Radiol. Clin. North Am. 1972; 3 : 421432.

Low dose intravenous urography: results and technique modifications.

100 consecutive patients routinely referred for intravenous urography were examined using low doses of the low osmolar contrast medium Iohexol (Omnipa...
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