An evaluation of Anti-Diuretic Hormone in intravenous urography “sniff urography”

( /i11, R a d i o L (1970) 21, 157-162

AN

EVALUATION

OF

ANTI-DIURETIC HORMONE UROGRAPHY "SNIFF UROGRAPHY"

IN

INTRAVENOUS

G. T. BENNESS

From the Department of Surgery, University of Sydney, Australia An appreciation of the factors controlling the radiopacity of the urine during intravenous urography has followed the careful study of the hydration of the patient and the dose and nature of the contrast agent. The value of preliminary dehydration has been confirmed. The suspicion that it was not always effective, led to an evaluation of the use of Lypressin (Anti-Diuretic Hormone) in urography. It is found that A.D.H. increases the urinary concentration of the contrast medium and therefore improves the quality of the pyelogram. This improvement is most marked when there has been limited dehydration. METHOD IN order to define the onset of the action of Lypressin (A.D.H.) in man, 4 volunteers had serial collections of urine before and after sniffing the agent. The collections were made after preliminary dehydration for varying periods. The studies all commenced at 9.00 a.m. and the control collection was for 30 minutes. After sniffing the A.D.H., urine samples were collected at 10, 20, 40 and 60 minutes if possible. Estimations of the urinary flow rate, osmolality, sodium and potassium concentrations were made. The urinary solute load and sodium and potassium loads were calculated. A matched series of urographic studies on prison volunteers, (Benness, 1970) was extended to examine the influence of A.D.H. in urography. The method of collecting samples of blood and urine, the timing of the radiographs, and the measurements performed have been previously described (Benness, 1970). The preparation for the examination varied from dehydration for 16 hours to no preparation at all. As previously described, a urine sample was collected on arrival (U. 1) and 2 more samples were collected over the 1-hour pre-injection period (U.2. and U.3). When A.D.H. was administered, it was given at the time of collection of the second urine sample (U.2). With the patient seated, 20 I.U. of A.D.H. were sniffed into the nose. On all occasions, Sodium Diatrizoate was injected intravenously in the 200-330 mg. I/kg. dose range.

RESULTS The effects of sniffing 20 I.U. of A.D.H. are illustrated in Fig. 1. Preparation consisted of a normal diet including breakfast (hydrated) or 11 hours fasting (dehydrated). The A.D.H. produced a E

157

reduction in the urinary flow rate, and an increase in the urinary osmolality. Calculation of the urinary solute load and the sodium and potassium loads also showed a decrease. The greatest changes in flow rate and osmolality were present in the second collection after sniffing the A.D.H. (10-20 mins.). In the 8 studies on the 4 volunteers, there was always an increase in the urinary osmolality after A.D.H., but the increase diminished as the preA.D.H. osmolality rose, Table 1. With limited dehydration the urinary osmolality increased by as much as 283 m0/kg. The maximum osmolality was nearly always observed in the second urine collection. The calculations showed that sniffing A.D.H. produced a definite reduction in the urinary solute load and sodium load and usually a small reduction in the potassium load. These findings suggested that the A.D.H. should be administered 10-20 minutes before the contrast agent injection. For the matched series it was convenient to do this after the collection of the second pre-injection sample (U.2). In 1 series of matched studies where the preliminary dehydration varied and A.D.H. was given, the results are summarised in Table 2. In the hydrated study there was no effective fluid restriction, while in the dehydrated studies no fluid was permitted for the previous 16 hours. In spite of similar instructions, the preliminary measurements showed considerable variation in the urinary flow rate and osmolality. The urinary osmolality and urinary flow rate were inversely related and calculation of the urinary solute load showed that the measurements were reliable. Administration of A.D.H. 17 rains, before the contrast medium injection produced a higher urinary

158

CLINICAL RADIOLOGY

;AD,. U FLOW~0 l RATE |0

mVmin

b ,b io

4o

12.00[ TOTAL [ 08MOLALITY800 t

-m% ,OOf

1200 U.SOLUTE 800 LOAD ,)u-~/'min 400

--o-

range of hydration and dehydration (Table 3). Moderate dehydration (663 m0/kg.) and A.D.H, produced a tJrinary contrast concentration approaching that obtained with excelIent dehydration (101l m0/kg.). Also good dehydration (769 m0,' kg,) combined with A.D.H. and a reduction in the 6'o contrast dose (200 mg.t/kg.) produced a urinary contrast concentration again very similar to that produced by excellent dehydration. The influence of A.D.H. and dehydration can also be seen in the radiography. The 3 minute radiographs of series on the patient in Table 3 are presented in Fig. 2. The top row shows the dramatic influence of preliminary hydration and dehydration. The bottom row shows the influence of moderate dehydration with A.D.H., and the possibility of contrast dose reduction with dehydration and A.D.H. In Fig. 3 the 25 minute radiographs of the same patient series are illustrated.

-o

U.No.+. 30o LOAD

")u'Eq/~nin

200 I00 i

4-

U.K. LOAD

2ool

.,~E~//min I°° I ©

HYDRATED 0 DERVDRATED

FzG, 1 Patieat 'G'. Effect of sniffing 20 units A.D.H. hydrated and dehydrated, (U.Na.--Urinesodium)_ (U.K.~Urinepotassium).

osmolality after the contrast injection and an appropriately higher urinary contrast concentration than in a similarly dehydrated study without A.D.H. The plasma contrast levels and urinary contrast loads were similar for these studies. The only variables were the patient preparation and A.D.H. In another matched series, there was a wider

DISCUSSION Lypressin (Sandoz) is a synthetic preparation (Lysine-8-Vasopressin), identical with the naturally occurring anti-diuretic hormone (A.D.H.) found in some animals particularly the pig and hippopotamus. If the lysine is replaced by arginine, Arginine8-Vasopressin, the form present in man is produced. The pharmacology of the 2 forms is identical. Miles et al. (1954), and Wood (1967), have compared the maximum urinary concentrations following dehydration with that after Pitressin and after Lypressin. More than 24 hours dehydration was necessary to achieve the maximum urinary concentration, and the synthetic A.D.H. was almost as effective as the endogenous A.D.H. produced by dehydration. Wood showed that the maximum urinary concentration after sniffing A.D.H. was generally obtained in the first 2 hours. The exact time and nature of the onset of the action of A.D.H. was studied in the present experiment in 4 volunteers and the results are shown in Fig. 1 and Table 1. These show that A.D.H. always increased the urinary osmolality even after 10-15 hours fasting and dehydration, and that the maximum effect was usually obtained 10-20 minutes after sniffing the agent. Wood recommended a dose of 40 I.U. for maximum effect on hydrated subjects. Since our subjects were partly dehydrated, only 20 I.U. were given. It is apparent that A.D.H. will generally improve the urinary concentration, but it is particularly effective when prior dehydration is limited. Dependence of urinary contrast concentration on dehydration has been shown by measurement

ANTI-DIURETIC

HORMONE

IN

INTRAVENOUS

UROGRAPHY

159

TABI E I MAXIMUM INCREASE IN URINARY OSMOLALITY AND llS TINIE OF COLLECTION AFTER SNIFFING

20 UNITS A . D . H . (4 PArIENTS: 8 S~t't)~ES) Urinary osmolality m0kg. : preADH Max postADH increase

Subject

G.

562 573 644 813 916 941 1006 1041

•

IG'.. I.'

845 750 778 916 1048 963 1124 1088

J

:

M a x i m u n n, U. o s m o l a l i t y at 0 - 10 - 20 40 - 6 0 r a i n s .

283 177 134 103 132 22 118 47

v~ V/ V

TABLE 2 PATIENT ' H ' . URINARY OSMOLALITY AND CONTRAST CONCENTRATION IN 4 STUDIES, WITH VARIABLE PREPARATION AND CONSTANT DOSE OF CONTRAST MEDIUM. CONTROL~LAST OF 3 PRE-INIECTION URINE COLLECTIONS. U 4 , U5, U 6 , U7~POST-INIECTION URINE COLLECTIONS. U. o s m o l a l i t y m 0 / k g . U. c o n t r a s t c o n c . m g . / m l . 'H'

Hydrated

330

Dehydrated + ADH

330

Dehydrated

330

Control

U. 4

U. 5

U. 6

U, 7

162

175 15

445 57

397 36

257 15

613

432 45

549 85

569 68

604 55

696

376 22

518 76

569 66

605 63 631 30

Dehydrated

TABLE PATIENT ' W ' .

3

URINARY OSMOLALITY AND CONTRAST CONCENTRATION IN 4 STUDIES W I T H VARIABLE PREPARATION AND DOSE

U. o s m o l a l i ~ m 0 / k g . U. c o n t r a s t c o n c , rng./ml. 'W'

mD g .oI /skeg .

- C o- n t r o l

I Hydrated

Dehydrated?

Dehydrated + ADH

300

Dehydrated* + ADH

200

* Good dehydration ~" Excellent d e h y d r a t i o n

298

188 13

10~7-1 --

799 148

663 --

652 107

T

775 85

~

300 - - - 300

U. 7 564 129

I

635 127

834 189

583 83 860 169

170

793 165

831 157

191

821 179

829 121

160

CLINICAL

RADIOLOGY

FIG. 2 PATIENT 'W'. 3 rain. radiographs of 4 studies in same patient, h--Hydrated, 300 mgI/kg. ~--Dehydrated 16 hrs., 300 mgI/kg, c--Dehydrated 12 hrs. + A . D . H . 300 mgI/kg. D--Dehydrated 12 hrs. ÷A.D.H., 200 mgI/kg.

(Keates, 1954; Scott Dunbar et al., 1960; and Benness, 1967 and 1968), but there is considerable variation between the published results of dehydration in routine practice and in controlled series. Sherwood et aI. (1968), in a U.K. series reported a mean pre-injection urinary osmolarity of 650 m0/kg. (12 patients) after dehydration from 10 p.m. on the day before the examination. An Australian series reported by Benness et aI. (1965), showed a mean pre-injection urinary osmolality of 770 m0/kg. (89 patients) after dehydration for 12 hours.

Scott Dunbar's Canadian volunteers had a preinjection osmolarity of 823 m0/1 when hydrated and 1040 m0/1 when dehydrated for 15 hours (21 subjects). These hydrated volunteers had a more concentrated urine than the average dehydrated Australian and U.K. hospital patient. It became apparent in the course of the present study with volunteers, that they were more co-operative than the routine patients and that preparation instructions were followed more closely. Clearly the duration of dehydration is most important in the

ANTI-DIURETIC

HORMONE

IN INTRAVENOUS

UROGRAPHY

161

Fro. 3 Patient ' W ' . 25 min. r a d i o g r a p h s o f same 4 studies as in Fig. 2.

preparation for urography, but patient co-operation, climate and perhaps heating are also important. In this series (Table 2) with each increase in the pre-injection urinary osmolality there was an appropriately higher urinary osmolality after the contrast injection, and this produced a greater concentration of the contrast agent. The combination of A.D.H. with moderate dehydration produced a definitely higher urinary osmolality and contrast concentration, than slightly more dehydration but without A.D.H. Similar improvement is noted in

Table 3 when the urinary contrast concentration following moderate dehydration and A.D.H. approaches that after excellent dehydration. Moderate dehydration reinforced with A.D.H. may even permit some reduction in the dose of the contrast agent. These changes can be seen in the radiographs and it is most interesting to note the higher initial urinary radio-opacity (U.4) achieved with either A.D.H. or excellent dehydration. Similar radiographic results have been reported by Wald et al. (1944), and Bream (1944). Both used Pitressin but

162

C L I N I C A L RADIOLOGY

the observations were n o t associated with physical measurements and the technique was never widely adopted. Recent developments in u r o g r a p h i c techniques have a d v o c a t e d larger doses o f contrast agent a n d less emphasis on dehydration, Schencker (1964, 1966) a n d Glanville et al. (1966). W h i l e a larger dose o f hypertonic c o n t r a s t agent m i g h t elevate the p l a s m a osmolality a n d stimulate A . D . H . release in a h y d r a t e d subject, for the reasons shown b y W e s t et al. (1955), this will n o t p r o d u c e as c o n c e n t r a t e d a urine as excellent dehydration, or m o d e r a t e d e h y d r a t i o n re-inforced b y A . D . H . P r e l i m i n a r y d e h y d r a t i o n for u r o g r a p h y on patients with i m p a i r e d renal function has frequently been avoided. Severe renal d a m a g e will p r o d u c e a p o o r l y c o n c e n t r a t e d urine u n d e r m o s t circumstances, b u t u r o g r a p h y on patients with slight functional i m p a i r m e n t w o u l d be i m p r o v e d b y d e h y d r a t i o n . W h e r e d e h y d r a t i o n is undesirable, A . D . H . with its r a p i d action has a definite a p p l i c a t i o n in increasing the u r i n a r y concentration. S i m i l a r l y its p o t e n t i a l value in urgent studies can be appreciated. CONCLUSION Progress in our u n d e r s t a n d i n g o f the factors influencing the quality o f the intravenous u r o g r a m has d r a w n attention to the dose a n d n a t u r e o f the c o n t r a s t agent. The final c o n c e n t r a t i o n o f the agent in the urine is d e p e n d e n t on the t u b u l a r concentrating m e c h a n i s m a n d this is p a r t i c u l a r l y d e h y d r a t i o n dependent. I f d e h y d r a t i o n is limited, the c o n c e n t r a t i o n can be increased b y using Lypressin (A.D.H.), a n d the quality o f the u r o g r a m will be i m p r o v e d . Aeknowledgement.--This work was dependent on the cooperation of the Prisons Department of New South Wales and the technical assistance of Miss M. Glazer. Radio-

graphic assistance from Royal Prince Alfred Hospital, the supply of Lypressin from Sandoz Pharmaceuticals and Hypaque from Sterling Pharmaceuticals was greatly appreciated. REFERENCES BENNESS, G. T., BULLEN, A. & B~mr~R, A. (1965). Double Dose Urography--Renal Function Test. Journal of the College of Radiologists of Australasia, 9, 234-245. BE~ESS, G. T. (1967). Urographic Excretion Study-Dehydration and Dose. Australasian Radiology, 11, 261-264. BENNESS,G. T. (1968). Urographic Excretion Study-Contrast Agents. Australasian Radiology, 12, 245-251. BENNESS, G. T. (1970). Urographic Contrast Agents--an evaluation in man. Clinical Radiology, in the press. BREAM,C. A. (1957). The clinical use of Pitressin in excretory urography. American Journal of Roentgenology, 78, 343-347. GLANVILLE, J. N. & HERLINGER,H. (1966). Normal Hydration Urography. Clinical Radiology, 17, 230. I~ATES, P. G. (1953). Improving the intravenous pyelogram: an experimental study. British Journal of Urology, 25, 366-370. MILES, B. E., PATON, A. • DE WARDENER, H. E. (1954). Maximum urine concentration. British Medical Journal, 2, 901-905. SCHENCKER,B. (1964). Drip Infusion Urography. Radiology, 83, 12-21. ScrrENCKER, B. (1966). Further experience with Drip Infusion Urography. Radiology, 87, 304-308. SCOTT-DtYNBAR,J., MACEWAN,D. W. & HE~ERT, F. (1960). The use of Dehydration in Intravenous Pyelography--an experimental study. American Journal of Roentgenology, 84, 813-836. SHERWOOD,T., DOYLE, F. H., BRECKENRIDGE,A., DOLLERY, C. T. & STEINER,R. E. (1968). Value of fluid deprivation in large dose urography. Lancet, 2, 754-755. WEST, C. D., TRAEGER,J. & KAPLAN,S. A. (1955). A comparison of the relative effectiveness of hydropoenia and of Pitressin in producing a concentrated urine. Journal of Clinical Investigation, 34, 887-898. WALD, M. H. & GALLOWAY,A. F. (1967). Pituitrin for concentrating Diodrast in excretory urography. Radiology, 43, 358-363. WOOD, T. J. (1967). The Use of a lysine vasopressin spray in the urine concentration test. Medical Journal of Australia, 54, 735-738.