The effect of DDAVP on intravenous urography - BIR Publications

1981, Britishjfournal of Radiology, 54,484-487

The effect of DDAVP on intravenous urography By *A. K. Dixon, M.A., M.R.C.P., F.R.C.R., Judith A. W. Webb, B.Sc, M.R.C.P., F.R.C.R., W. R. Cattell, M.D., F.R.C.P. and I. Kelsey Fry, D.M., F.R.C.P., F.R.C.R. Departments of Diagnostic Radiology and Nephrology, St. Bartholomew's Hospital, London EC1A 7BE (Received January 1981) ABSTRACT

The possible role of an antidiuretic hormone analogue, DDAVP (1 deamino-8-Z)-arginine vasopressin), in intravenous urography has been studied. The minimum effective dose of intravenous DDAVP in normal hydrated subjects was shown to be 2 ng/kg. During intravenous urography in fluid restricted subjects, a dose of 1 fig DDAVP was necessary to reduce significantly the urine flow rate after contrast medium injection. Although the mean pyelographic score after DDAVP was increased, the differences observed were not statistically significant. The possible reasons for this finding are discussed.

The radiodensity of the pyelogram obtained during intravenous urography depends on two principal factors—the concentration of contrast medium in the urine and the depth of contrast laden urine through which the X-ray beam passes. The depth of the collecting system depends on its volume, which in turn relates to the anatomy of the system, the rate of urine flow and. the effectiveness of the partial ureteric obstruction induced by abdominal compression bands. The concentration of contrast medium in the urine depends on the dose of contrast medium given and the degree to which the glomerular filtrate is concentrated as it passes along the renal tubule (Fry et al., 1967). Since the circulating level of endogenous antidiuretic hormone (ADH) is one of the factors facilitating water reabsorption in the distal renal tubule, it became standard practice to enhance this by fluid restriction of patients before intravenous urography. Some workers took this further by giving exogenous ADH—as pitressin (Wald and Galloway, 1944; Bream, 1957) or lysine vasopressin (Benness, 1970)—before urography. However, these agents have the disadvantage of vasopressor side-effects. The introduction of an ADH analogue, 1-deamino-8-Z)-arginine vasopressin (DDAVP) without pressor side-effects (Vavra et al., 1968; Edwards et al., 1973; Ward and Fraser, 1974) stimulated a study of the possible role of this agent in improving the quality of the intravenous urogram. DDAVP has a prolonged action, the duration of which relates to the dose given (Andersson et al., 1972). A prolonged antidiuretic effect could be un*Present address: University Department of Radiology, Addenbrooke's Hospital, Cambridge.

desirable in patients undergoing intravenous urography. Since the smallest effective dose was not known, a preliminary study in hydrated subjects was undertaken to determine both the minimum effective dose of DDAVP and its duration of action. Our investigations were then extended to determine the effect of three different doses of DDAVP, given before urography, on the contrast induced diuresis and on the quality of the pyelograms. Since we wished to investigate the possible role of DDAVP in normal urographic practice, we elected to study fluid restricted patients and to use abdominal compression bands during urography, although we recognized that both of these measures were likely to diminish the demonstrable effect of DDAVP. The study was approved by the St. Bartholomew's Hospital Ethical Committee and the informed consent of all subjects and patients was obtained. METHODS

1. Minimum effective dose ofDDA VP in hydrated subjects Based on animal studies (Vavra et al., 1968; Mulder, 1974, personal communication), a dose of DDAVP of 1-2 ng/kg was chosen. Well hydrated volunteers (urine osmolality < 200 mOsm/kg) were given either saline or DDAVP (Ferring) intravenously in a dose of 1 or 2 ng/kg, prepared by serial dilution. They were unaware of which injection they had received. No further fluid was drunk for two hours. Urine samples were obtained before the injection and at 30-minute intervals for two hours. A one litre water load was then given and serial urine collections continued for approximately two further hours. Urine flow rate and osmolality (Advanced Osmometer) were measured on all urine samples. Subjects were asked to record any adverse effects noted. 2. Effect of DDA VP on intravenous urogram Patients requiring intravenous urography for clinical management were studied. The following were excluded: those with elevated serum creatinine or known urinary tract abnormalities, children, patients on diuretics and those unable to tolerate abdominal compression. All patients were fluid restricted before intravenous urography: those who had

484

JUNE 1981

The effect of DDA VP on intravenous urography morning appointments were fluid restricted overnight and those with afternoon appointments had nothing after one cup of fluid at breakfast. Patients emptied their bladder on arrival in the department and again after 30 minutes (urine 1). If the urine flow rate in this period exceeded 0.6 ml/min it was considered that the quality of the intravenous urogram might be improved by DDAVP and these patients were selected for further study. Intravenous DDAVP or placebo (saline) was given according to a randomizing chart. The dose used initially was 200 ng DDAVP (Group A). Subsequently doses of 1 /u,g (Group B) and 4 /xg (Group C) were used. As the study was spread over more than a year, each dose schedule for DDAVP had its own control group to reduce possible seasonal variation in urine flow rates. Forty minutes after injection of DDAVP the patient again voided (urine 2). An intravenous line was then inserted. Blood was taken for serum creatinine estimation and contrast medium was injected in a dose of 325 mgl/kg (sodium iothalamate, Conray 325). The intravenous urogram was performed according to our standard practice, with exposures at 60-70 kV and ureteric compression applied from five to ten minutes after contrast injection. The patient again voided (urine 3) before the aftermicturition film was obtained at approximately 30 minutes. Patients who had received DDAVP were instructed not to drink more than 500 ml over the next three hours, and were asked to report any adverse effects. Urine flow rate and osmolality (Advanced Osmometer) were measured on all urine samples. Urinary creatinine concentration was measured in urine 1 and serum creatinine on the blood sample. From these the basal creatinine clearance was calculated. The intravenous urograms were reviewed and those with anatomical abnormalities were excluded. The ten-minute "compression" films were scored by two observers, who did not know whether saline or DDAVP had been given. The upper, middle and lower calyceal groups and pelvis of each kidney were scored by eye on a scale of 0-5—a modification of a previously described method (Fry et al., 1967). The mean of the two observers' scores was obtained, the possible maximum score being 40. Statistical analysis of the results was by Student's t test.

DDAVP DOSE o A •

2ng/kg (4 subjects) 1 ng/kg (5 subjects)

saline (5 subjects)

800 700 600 Mean Urine Osmolality (m OSm/kg)

500 400 300 200 100 0

0

30

60

90

120

150

180

210

TIME (mins)

FIG.1.

The effect of DDAVP on urine osmolality in hydrated subjects. TABLE I THE EFFECT OF DDAVP ON URINE OSMOLALITY IN HYDRATED SUBJECTS.

Time after DDAVP injection (minutes) 30

DDAVP 1 ng/kg versus saline NS DDAVP 2 ng/kg versus saline NS

60

90

120

150