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Indomethacin in the Treatment of Ureteral Colic: Is Fluid Restriction Necessary?
0022-534 7/86/1362-0390$02.00/0 Vol. 136, August Printed in U.S.A.
THE JOURNAL OF UROLOGY
Copyright © 1986 by The Williams & Wilkins Co.
INDOMETHACIN IN THE TREATMENT OF URETERAL COLIC: IS FLUID RESTRICTION NECESSARY? TOM-HARALD EDNA, FREDRIK HESSELBERG AND BORGER LOE From the Department of Surgery, Innherred Hospital, Levanger, Norway
ABSTRACT
The effect of fluid load on pain was estimated in 60 patients with acute ureteral colic treated with 50 mg. intravenous indomethacin. One group received 3 1. fluid intravenously, while in another group all fluids were withheld for 6 hours. Pain was assessed with a visual analogue scale. No intergroup difference in regard to pain was found after 1, 3 and 6 hours of observation. vant difference and 3) the estimated standard deviation was 10 units.
Acute ureteral colic is a common urological emergency. The many factors that influence the pain or spontaneous passage of ureteral stones still are not understood. Different views are held concerning the consequences of fluid intake during the acute episode. 1- 4 In a previous study on acute ureteral colic we could find no difference in pain between a volume loaded group of patients and a group given no fluid at all 6 hours after injection of meperidine. 5 Prostaglandin synthesis inhibitors are believed to relieve the pain of acute ureteral obstruction owing to a decrease in glomerular capillary pressure and urinary excretion, leading to a decrease in renal pelvic pressure and, thus, to reduced tension in the renal pelvic wall. Clinical studies have shown the usefulness of prostaglandin synthesis inhibitors during acute attacks of renal colic. 6- 11 On the basis of animal experiments fluid restriction has been advocated to obtain relief of pain when indomethacin was used. 6 We evaluated the effect of fluid load on acute pain in patients with ureteral stones treated with indomethacin.
RESULTS
The 60 patients studied are listed according to sex, duration of the last attack of pain and diameter of the stone in table 1. Both treatment groups were well matched in regard to these parameters. The location of the stone in the upper, middle and lower part of the ureter was equal in both groups. The effect of treatment on pain as measured on the visual analogue scale is summarized in table 2. Two patients in each group required additional analgesics (meperidine) before the end of 6 hours. These patients were given the score of 50 after 6 hours. There was no significant intergroup difference con cerning initial pain, or pain after 1, 3 or 6 hours of observation. This finding also holds true in patients with pain durations of less than 6 hours when treatment was begun. The fate of the ureteral stones is shown in table 3. DISCUSSION
PATIENTS AND METHODS
We studied all patients who were hospitalized between June 1982 and February 1985 with acute pain owing to ureteral stones. The diagnosis was confirmed by excretory urography. Patients with signs of congestive heart failure, pregnancy, active peptic ulcer, asthmatic bronchitis or adverse reactions to nonsteroidal anti-inflammatory drugs were excluded from the study. All of the patients were given 50 mg. indomethacin slowly by intravenous injection and they were allocated randomly into 2 treatment groups: group 1 patients were allowed no fluids for 6 hours and group 2 patients received 2 l. 5 per cent glucose solution and 1 l. Ringer's acetate solution intravenously during 6 hours. Meperidine was given if pain recurred. Pain was measured according to a visual analogue scale12 before indomethacin was given, and then after 1, 3 and 6 hours. No pain was graded as O and the worst imaginable pain was graded as 50. . For statistical analysis the Wilcoxon 2-sample, 2-tailed test was used, corrected for ties and based on the normal distribution. The selected significance level was 0.05. A total sample of 60 patients was calculated to be necessary to detect a medically relevant difference between the 2 groups. With 60 patients the power of the test would be 0.97 if the least relevant difference in pain was 10, on a scale of O to 50. The power would be 0.80 if the least relevant difference was chosen to be 7. 13 The following 3 assumptions were made: 1) the pain could be graded on a continuous scale of O to 50, 2) a difference of 7 to 10 units between the treatment groups was the smallest medically releAccepted for publication March 24, 1986.
Ureteral colic is believed to be caused by rapid distension of the ureter, renal pelvis and renal capsule above an obstructing ureteral stone. 14 The first hours of ureteral obstruction are characterized by an increase in renal pelvic and tubular pressure, and increased renal blood flow and glomerular capillary pressure. 15- 1s Urine flow decreases progressively as ureteral pressure increases. 17 The period of pressure increase lasts only a few hours and thereafter the pressure decreases. 19- 22 The initial vasodilatation is followed by a vasoconstriction with a decrease in perfusion. In the contralateral kidney there is a slow compensatory increase in blood flow and glomerular filtration rate. 23• 24 An increase in renal pelvic pressure stimulates the kidney synthesis of prostaglandins. Prostaglandins mediate renal vasodilatation and increased blood flow. 6 • 21 Indomethacin is a strong prostaglandin synthesis inhibitor that reduces the renal pelvic pressure above an obstructed ureter. Infusion of saline · after the administration of indomethacin counteracts the presTABLE
1. Distribution of patients with acute ureteral colic according to sex, duration of the last attack of pain and stone diameter Group 1No Fluid Intake
Women Men Median age (range) Median duration of pain (hrs.) at hospitalization (range) Median mm. stone diameter (range)
390
7
7
23 50 (17-85) 4.5 (1-34) 3
Group 2-High Fluid Intake
(1.5-7.5)
23 47 (27-69) 5 (0.5-26) 3 (1-15)
391 TABLE 2. Pain score in patients with acute ureteral stone colic treated with indomethacin Before Treatment
Hrs. After Treatment 3
1
Highest value 3rd quartile Median 1st quartile Lowest value P value
6
Group 2
Group 1 50 38 32 26 14
Group 1
Group 2
Group 1
Group 2
Group 1
Group 2
30 10
30
36 20 0 0 0
36 7 0 0 0
50 10 0
50 4 0 0
50 40 36 27 7
11 7
3 0 0
0
0 0.35
0.39
0.68
0
0
0
0.94
Group 1-no fluid intake. Group 2-high fluid intake.
TABLE 3. Fate of the ureteral stone Group 1No Fluid Intake Stone removed surgically Stone manipulated cystoscopically Stone expelled spontaneously Pt. lost to followup Totals
Group 2-High Fluid Intake
4
2
0
2
26
23
0
3
30
30
within wide ranges, there is relatively little effect on the kidney function. 34 Our study seems to indicate that the amount of fluid intake after treatment has no practical influence on the degree of pain in patients with acute ureteral colic treated with indomethacin, at any rate not after 1, 3 or 6 hours, nor did the results suggest that fluid intake influences the likelihood of spontaneous excretion of the stone. REFERENCES
sure decrease induced indomethacin in anesthetized pigs and rats. 25 · 26 Patients completely relieved of ureteral colic after infusion of indomethacin have higher levels of antidiuretic hormone in plasma before the infusion than patients with incomplete relief 27 • 28 This finding indicates that the state of hydration before treatment may influence the pain-reducing capacity of indomethacin. Our study shows that this is not necessarily so when hydration is secondary to the infusion of indomethacin. The explanation for this finding may be multifactorial and some possible factors are discussed, The prostaglandins have been detected in almost every tissue and body fluid, and they produce a remarkably broad spectrum of effects that embraces almost every biological function. 29 Therefore, indomethacin may produce its effect on ureteral colic through the action on many organs, such as the ureter, kidney, and peripheral and central nervous systems. Prostaglandin Es and prostaglandin I2 are known to sensitize the afferent nerve endings to the effect of chemical or mechanical stimuli. 30 Pain from the renal capsule, pelvis and ureter is mediated the plexus of the renal nerves to the sympathetic celiac 5 v.u 5 u~,u. Norepinephrine is a sympathetic neurotransmitter. effect of indomethacin in man has been a decrease levels. 31 on musculature from the renal and ureter have shown that prevent the spontaneous musculature A decrease in renal musculature may be an important contributing factor to the pain-relieving effect of indomethacin, 32 Indomethacin might have a favorable effect on the renal pressure in awake humans who are fluid loaded, even if the opposite occurred in animal experiments. The antiphlogistic effect of indomethacin on the edematous ureteral wall around the stone is favorable but hardly can explain the immediate relief of pain. 14 Almost all of the excess fluid given to group 2 probably was filtered in the contralateral kidney. Indomethacin would not oppose this effect. Prostaglandin-inhibiting drugs have no effect on renal blood flow or glomerular filtration rate in normal, nonanesthetized animals. When the renin-angiotensin system is activated, either by anesthesia or a low sodium diet, prostaglandin inhibition then causes a decrease in renal blood flow. 33 In nonanesthetized, normal humans it appears that whether one diminishes or augments endogenous prostaglandins, even
1. Holmlund, D.: Uretarstenssjukdomen. In: Uretarsten. Giiteborg: Akademiforlaget, p. 22, 1972.
2. Drach, G. W.: Urinary lithiasis. In: Campbell's Urology, 4th ed. Edited by J. H. Harrison, R. F. Gittes, A. D. Perlmutter, T. A. Stamey and P. C. Walsh. Philadelphia: W. B. Saunders Co., vol. 1, sect. VI, chapt. 22, pp. 779-820, 1978. 3. Morishima, M. S. and Ghaed, N.: Glucagon and diuresis in the treatment of meteral calculi. Radiology, 129: 807, 1978. 4. Algood, C. B., Sood, N., Fairchild, T. and Mayo, M. E.: Experimental study of ureteral calculus disease: effects of calculus size, obstruction and hydration. J. Urol., 130: 999, 1983. 5. Edna, T.-H. and Hesselberg, F.: Acute ureteral colic and fluid intake. Scand. J. Urol. NephroL, 17: 175, 1983. 6. Sjodin, J.-G.: Effects of intravenous indomethacin during acute ureteral obstruction. Scand. J. Urol. Nephrol., suppl. 66, p. 1, 1981. 7. Lundstam, S. 0. A., Leissner, K.-H., Wahlander,
L.A.
and Kral,
J. G.: Prostaglandin-synthetase inhibition with diclofenac sodium in treatment of renal colic: comparison with use of a narcotic analgesic. Lancet, l: 1096, 1982. 8. Flannigan, G. M., Clifford, R. P. C., Carver, R. A., Yule, A. G., Madden, N. P. and Towler, J.M.: Indomethacin-an alternative to pethidine in ureteric colic. Brit. J. Urol., 55: 6, 1983. 9. Uden, P., Rentzhog, L. and Berger, T.: A comparative study on the analgesic effects of indomethacin and hydromorphinechlorideatropine in acute ureteral-stone pain. Acta Chir. Scand., 149: 497, 1983,
10. Sjodin, J.-G.: Clinical experience of indomethacin in pain from uretera! stone. Scand. J. Urol. Nephrol., suppl. 75, 35, 1983. 11. Persson, N. H., Bergqvist, D., Melander, A. and f,P,r1P1·tio1t. B.: Comparison of a narcotic (oxicone) and a non-narcotic antiinflammatory analgesic (indoprofen) in the treatment of renal colic. Acta Chir. Scand., 151: 105, 1985. 12. Scott, J. and Huskisson, E. C.: Graphic representation of pain. Pain, 2: 175, 1976. 13. Altman, D. G.: Statistics and ethics in medical research. HI-how large a sample? Brit. Med. J., 281: 1336, 1980. 14. Holmlund, D. and Sjodin, J.-G.: Treatment of ureteral colic with intravenous indomethacin. J. Urol., 120: 676, 1978. 15. Wahlberg, J.: The renal response to ureteral obstruction. Scand. J. UroL Nephrol., suppl. 73, p. 1, 1983. 16. Navar, L. G. and Baer, P. G.: Renal autoregulatory and glomerular filtration responses to graded ureteral obstruction. Nephron, 7: 301, 1970. 17. Wilson, D.R.: Pathophysiology of obstructive nephropathy. Kidney Int., 18: 281, 1980. 18. Moody, T. E., Vaughan, E. D., Jr. and Gillenwater, J. Y.: Relationship between renal blood flow and ureteral pressure during 18
hours of total unilateral ureteral occlusion. Implications for changing sites of increased renal resistance. Invest. UroL, 13:
392
EDNA, HESSELBERG AND LOE
246, 1975. 19. Djurhuus, J. C.: Peristaltic activity of the upper urinary tract in obstruction. Prog. Clin. Biol. Res., 78: 393, 1981. 20. Biancani, P. and Weiss, R. M.: Effects of obstruction on the ureter. Prog. Clin. Biol. Res., 78: 405, 1981. 21. Allen, J. T., Vaughan, E. D., Jr. and Gillenwater, J. Y.: The effect of indomethacin on renal blood flow and ureteral pressure in unilateral ureteral obstruction in awake dogs. Invest. Urol., 15: 324, 1978. 22. Provoost, A. P. and Molenaar, J.C.: Nierenfunktion wiihrend und nach einseitiger Ureterobstruktion bei der Ratte. Urologe A, 19: 8, 1980. 23. Vaughan, E. D., Jr., Sorenson, E. J. and Gillenwater, J. Y.: The renal hemodynamic response to chronic unilateral complete ureteral occlusion. Invest. Urol., 8: 78, 1970. 24. Schelfhout, W., Simons, M., Oosterlinck, W. and De Sy, W. A.: Evaluation of 99 mTc-dimercaptosuccinic acid renal uptake as an index of individual kidney function after acute ureteral obstruction and desobstruction. An experimental study in rats. Eur. Urol., 9: 221, 1983. 25. Sjodin, J.-G. and Holmlund, D. E. W.: Effects of saline load, roentgen contrast medium and indomethacin on diuresis and pelvic pressure in the acute obstructed kidney. Brit. J. Urol., 54: 446, 1982. 26. Sjodin, J. G., Wahlberg, J. and Persson, A. E. G.: The effect of indomethacin on glomerular capillary pressure and pelvic pres-
sure during ureteral obstruction. J. Urol., 127: 1017, 1982. 27. Grenabo, L., Aurell, M., Delin, K., Holmlund, D. and Sjodin, J. G.: Antidiuretic hormone levels and the effect of indomethacin on ureteral colic. J. Urol., 129: 941, 1983. 28. Grenabo, L. and Holmlund, D.: The significance of fluid restriction in indomethacin treatment of pain from ureteral stone. Scand. J. Urol. Nephrol., suppl. 75, p. 39, 1983. 29. Moncada, S., Flower, R. J. and Vane, J. R.: Prostaglandins, prostacyclin, and thromboxane A2. In: The Pharmacological Basis of Therapeutics, 6th ed. Edited by A. G. Gilman, L. S. Goodman and A. Gilman. New York: Macmillan Publishing Co., chapt. 28, pp. 668-681, 1980. 30. Ferreira, S. H., Moncada, S. and Vane, J. R.: Prostaglandins and signs and symptoms of inflammation. In: Prostaglandin Synthetase Inhibitors: Their Effects on Physiological Functions and Pathological States. Edited by H.J. Robinson and J. R. Vane. New York: Raven Press, part Ill, pp. 175-187, 1974. 31. Gullner, H. G.: Prostaglandin actions on the adrenergic nervous system. Klin. Wochenschr., 61: 533, 1983. 32. Lundstam, S.: Cited in Colleen, S., Hellsten, S., Pompeius, R. and Wadstrom, L. B.: Nordic cooperation in urologic research and developmental work. Nord. Med., 99: 43, 1984. 33. Ferris, T. F.: Prostaglandins and the kidney. Amer. J. Nephrol., 3: 139, 1983. 34. Lifschitz, M. D.: Renal effects of nonsteroidal anti-inflammatory agents. J. Lab. Clin. Med., 102: 313, 1983.
THE JOURNAL OF UROLOGY
Copyright © 1986 by The Williams & Wilkins Co.
INDOMETHACIN IN THE TREATMENT OF URETERAL COLIC: IS FLUID RESTRICTION NECESSARY? TOM-HARALD EDNA, FREDRIK HESSELBERG AND BORGER LOE From the Department of Surgery, Innherred Hospital, Levanger, Norway
ABSTRACT
The effect of fluid load on pain was estimated in 60 patients with acute ureteral colic treated with 50 mg. intravenous indomethacin. One group received 3 1. fluid intravenously, while in another group all fluids were withheld for 6 hours. Pain was assessed with a visual analogue scale. No intergroup difference in regard to pain was found after 1, 3 and 6 hours of observation. vant difference and 3) the estimated standard deviation was 10 units.
Acute ureteral colic is a common urological emergency. The many factors that influence the pain or spontaneous passage of ureteral stones still are not understood. Different views are held concerning the consequences of fluid intake during the acute episode. 1- 4 In a previous study on acute ureteral colic we could find no difference in pain between a volume loaded group of patients and a group given no fluid at all 6 hours after injection of meperidine. 5 Prostaglandin synthesis inhibitors are believed to relieve the pain of acute ureteral obstruction owing to a decrease in glomerular capillary pressure and urinary excretion, leading to a decrease in renal pelvic pressure and, thus, to reduced tension in the renal pelvic wall. Clinical studies have shown the usefulness of prostaglandin synthesis inhibitors during acute attacks of renal colic. 6- 11 On the basis of animal experiments fluid restriction has been advocated to obtain relief of pain when indomethacin was used. 6 We evaluated the effect of fluid load on acute pain in patients with ureteral stones treated with indomethacin.
RESULTS
The 60 patients studied are listed according to sex, duration of the last attack of pain and diameter of the stone in table 1. Both treatment groups were well matched in regard to these parameters. The location of the stone in the upper, middle and lower part of the ureter was equal in both groups. The effect of treatment on pain as measured on the visual analogue scale is summarized in table 2. Two patients in each group required additional analgesics (meperidine) before the end of 6 hours. These patients were given the score of 50 after 6 hours. There was no significant intergroup difference con cerning initial pain, or pain after 1, 3 or 6 hours of observation. This finding also holds true in patients with pain durations of less than 6 hours when treatment was begun. The fate of the ureteral stones is shown in table 3. DISCUSSION
PATIENTS AND METHODS
We studied all patients who were hospitalized between June 1982 and February 1985 with acute pain owing to ureteral stones. The diagnosis was confirmed by excretory urography. Patients with signs of congestive heart failure, pregnancy, active peptic ulcer, asthmatic bronchitis or adverse reactions to nonsteroidal anti-inflammatory drugs were excluded from the study. All of the patients were given 50 mg. indomethacin slowly by intravenous injection and they were allocated randomly into 2 treatment groups: group 1 patients were allowed no fluids for 6 hours and group 2 patients received 2 l. 5 per cent glucose solution and 1 l. Ringer's acetate solution intravenously during 6 hours. Meperidine was given if pain recurred. Pain was measured according to a visual analogue scale12 before indomethacin was given, and then after 1, 3 and 6 hours. No pain was graded as O and the worst imaginable pain was graded as 50. . For statistical analysis the Wilcoxon 2-sample, 2-tailed test was used, corrected for ties and based on the normal distribution. The selected significance level was 0.05. A total sample of 60 patients was calculated to be necessary to detect a medically relevant difference between the 2 groups. With 60 patients the power of the test would be 0.97 if the least relevant difference in pain was 10, on a scale of O to 50. The power would be 0.80 if the least relevant difference was chosen to be 7. 13 The following 3 assumptions were made: 1) the pain could be graded on a continuous scale of O to 50, 2) a difference of 7 to 10 units between the treatment groups was the smallest medically releAccepted for publication March 24, 1986.
Ureteral colic is believed to be caused by rapid distension of the ureter, renal pelvis and renal capsule above an obstructing ureteral stone. 14 The first hours of ureteral obstruction are characterized by an increase in renal pelvic and tubular pressure, and increased renal blood flow and glomerular capillary pressure. 15- 1s Urine flow decreases progressively as ureteral pressure increases. 17 The period of pressure increase lasts only a few hours and thereafter the pressure decreases. 19- 22 The initial vasodilatation is followed by a vasoconstriction with a decrease in perfusion. In the contralateral kidney there is a slow compensatory increase in blood flow and glomerular filtration rate. 23• 24 An increase in renal pelvic pressure stimulates the kidney synthesis of prostaglandins. Prostaglandins mediate renal vasodilatation and increased blood flow. 6 • 21 Indomethacin is a strong prostaglandin synthesis inhibitor that reduces the renal pelvic pressure above an obstructed ureter. Infusion of saline · after the administration of indomethacin counteracts the presTABLE
1. Distribution of patients with acute ureteral colic according to sex, duration of the last attack of pain and stone diameter Group 1No Fluid Intake
Women Men Median age (range) Median duration of pain (hrs.) at hospitalization (range) Median mm. stone diameter (range)
390
7
7
23 50 (17-85) 4.5 (1-34) 3
Group 2-High Fluid Intake
(1.5-7.5)
23 47 (27-69) 5 (0.5-26) 3 (1-15)
391 TABLE 2. Pain score in patients with acute ureteral stone colic treated with indomethacin Before Treatment
Hrs. After Treatment 3
1
Highest value 3rd quartile Median 1st quartile Lowest value P value
6
Group 2
Group 1 50 38 32 26 14
Group 1
Group 2
Group 1
Group 2
Group 1
Group 2
30 10
30
36 20 0 0 0
36 7 0 0 0
50 10 0
50 4 0 0
50 40 36 27 7
11 7
3 0 0
0
0 0.35
0.39
0.68
0
0
0
0.94
Group 1-no fluid intake. Group 2-high fluid intake.
TABLE 3. Fate of the ureteral stone Group 1No Fluid Intake Stone removed surgically Stone manipulated cystoscopically Stone expelled spontaneously Pt. lost to followup Totals
Group 2-High Fluid Intake
4
2
0
2
26
23
0
3
30
30
within wide ranges, there is relatively little effect on the kidney function. 34 Our study seems to indicate that the amount of fluid intake after treatment has no practical influence on the degree of pain in patients with acute ureteral colic treated with indomethacin, at any rate not after 1, 3 or 6 hours, nor did the results suggest that fluid intake influences the likelihood of spontaneous excretion of the stone. REFERENCES
sure decrease induced indomethacin in anesthetized pigs and rats. 25 · 26 Patients completely relieved of ureteral colic after infusion of indomethacin have higher levels of antidiuretic hormone in plasma before the infusion than patients with incomplete relief 27 • 28 This finding indicates that the state of hydration before treatment may influence the pain-reducing capacity of indomethacin. Our study shows that this is not necessarily so when hydration is secondary to the infusion of indomethacin. The explanation for this finding may be multifactorial and some possible factors are discussed, The prostaglandins have been detected in almost every tissue and body fluid, and they produce a remarkably broad spectrum of effects that embraces almost every biological function. 29 Therefore, indomethacin may produce its effect on ureteral colic through the action on many organs, such as the ureter, kidney, and peripheral and central nervous systems. Prostaglandin Es and prostaglandin I2 are known to sensitize the afferent nerve endings to the effect of chemical or mechanical stimuli. 30 Pain from the renal capsule, pelvis and ureter is mediated the plexus of the renal nerves to the sympathetic celiac 5 v.u 5 u~,u. Norepinephrine is a sympathetic neurotransmitter. effect of indomethacin in man has been a decrease levels. 31 on musculature from the renal and ureter have shown that prevent the spontaneous musculature A decrease in renal musculature may be an important contributing factor to the pain-relieving effect of indomethacin, 32 Indomethacin might have a favorable effect on the renal pressure in awake humans who are fluid loaded, even if the opposite occurred in animal experiments. The antiphlogistic effect of indomethacin on the edematous ureteral wall around the stone is favorable but hardly can explain the immediate relief of pain. 14 Almost all of the excess fluid given to group 2 probably was filtered in the contralateral kidney. Indomethacin would not oppose this effect. Prostaglandin-inhibiting drugs have no effect on renal blood flow or glomerular filtration rate in normal, nonanesthetized animals. When the renin-angiotensin system is activated, either by anesthesia or a low sodium diet, prostaglandin inhibition then causes a decrease in renal blood flow. 33 In nonanesthetized, normal humans it appears that whether one diminishes or augments endogenous prostaglandins, even
1. Holmlund, D.: Uretarstenssjukdomen. In: Uretarsten. Giiteborg: Akademiforlaget, p. 22, 1972.
2. Drach, G. W.: Urinary lithiasis. In: Campbell's Urology, 4th ed. Edited by J. H. Harrison, R. F. Gittes, A. D. Perlmutter, T. A. Stamey and P. C. Walsh. Philadelphia: W. B. Saunders Co., vol. 1, sect. VI, chapt. 22, pp. 779-820, 1978. 3. Morishima, M. S. and Ghaed, N.: Glucagon and diuresis in the treatment of meteral calculi. Radiology, 129: 807, 1978. 4. Algood, C. B., Sood, N., Fairchild, T. and Mayo, M. E.: Experimental study of ureteral calculus disease: effects of calculus size, obstruction and hydration. J. Urol., 130: 999, 1983. 5. Edna, T.-H. and Hesselberg, F.: Acute ureteral colic and fluid intake. Scand. J. Urol. NephroL, 17: 175, 1983. 6. Sjodin, J.-G.: Effects of intravenous indomethacin during acute ureteral obstruction. Scand. J. Urol. Nephrol., suppl. 66, p. 1, 1981. 7. Lundstam, S. 0. A., Leissner, K.-H., Wahlander,
L.A.
and Kral,
J. G.: Prostaglandin-synthetase inhibition with diclofenac sodium in treatment of renal colic: comparison with use of a narcotic analgesic. Lancet, l: 1096, 1982. 8. Flannigan, G. M., Clifford, R. P. C., Carver, R. A., Yule, A. G., Madden, N. P. and Towler, J.M.: Indomethacin-an alternative to pethidine in ureteric colic. Brit. J. Urol., 55: 6, 1983. 9. Uden, P., Rentzhog, L. and Berger, T.: A comparative study on the analgesic effects of indomethacin and hydromorphinechlorideatropine in acute ureteral-stone pain. Acta Chir. Scand., 149: 497, 1983,
10. Sjodin, J.-G.: Clinical experience of indomethacin in pain from uretera! stone. Scand. J. Urol. Nephrol., suppl. 75, 35, 1983. 11. Persson, N. H., Bergqvist, D., Melander, A. and f,P,r1P1·tio1t. B.: Comparison of a narcotic (oxicone) and a non-narcotic antiinflammatory analgesic (indoprofen) in the treatment of renal colic. Acta Chir. Scand., 151: 105, 1985. 12. Scott, J. and Huskisson, E. C.: Graphic representation of pain. Pain, 2: 175, 1976. 13. Altman, D. G.: Statistics and ethics in medical research. HI-how large a sample? Brit. Med. J., 281: 1336, 1980. 14. Holmlund, D. and Sjodin, J.-G.: Treatment of ureteral colic with intravenous indomethacin. J. Urol., 120: 676, 1978. 15. Wahlberg, J.: The renal response to ureteral obstruction. Scand. J. UroL Nephrol., suppl. 73, p. 1, 1983. 16. Navar, L. G. and Baer, P. G.: Renal autoregulatory and glomerular filtration responses to graded ureteral obstruction. Nephron, 7: 301, 1970. 17. Wilson, D.R.: Pathophysiology of obstructive nephropathy. Kidney Int., 18: 281, 1980. 18. Moody, T. E., Vaughan, E. D., Jr. and Gillenwater, J. Y.: Relationship between renal blood flow and ureteral pressure during 18
hours of total unilateral ureteral occlusion. Implications for changing sites of increased renal resistance. Invest. UroL, 13:
392
EDNA, HESSELBERG AND LOE
246, 1975. 19. Djurhuus, J. C.: Peristaltic activity of the upper urinary tract in obstruction. Prog. Clin. Biol. Res., 78: 393, 1981. 20. Biancani, P. and Weiss, R. M.: Effects of obstruction on the ureter. Prog. Clin. Biol. Res., 78: 405, 1981. 21. Allen, J. T., Vaughan, E. D., Jr. and Gillenwater, J. Y.: The effect of indomethacin on renal blood flow and ureteral pressure in unilateral ureteral obstruction in awake dogs. Invest. Urol., 15: 324, 1978. 22. Provoost, A. P. and Molenaar, J.C.: Nierenfunktion wiihrend und nach einseitiger Ureterobstruktion bei der Ratte. Urologe A, 19: 8, 1980. 23. Vaughan, E. D., Jr., Sorenson, E. J. and Gillenwater, J. Y.: The renal hemodynamic response to chronic unilateral complete ureteral occlusion. Invest. Urol., 8: 78, 1970. 24. Schelfhout, W., Simons, M., Oosterlinck, W. and De Sy, W. A.: Evaluation of 99 mTc-dimercaptosuccinic acid renal uptake as an index of individual kidney function after acute ureteral obstruction and desobstruction. An experimental study in rats. Eur. Urol., 9: 221, 1983. 25. Sjodin, J.-G. and Holmlund, D. E. W.: Effects of saline load, roentgen contrast medium and indomethacin on diuresis and pelvic pressure in the acute obstructed kidney. Brit. J. Urol., 54: 446, 1982. 26. Sjodin, J. G., Wahlberg, J. and Persson, A. E. G.: The effect of indomethacin on glomerular capillary pressure and pelvic pres-
sure during ureteral obstruction. J. Urol., 127: 1017, 1982. 27. Grenabo, L., Aurell, M., Delin, K., Holmlund, D. and Sjodin, J. G.: Antidiuretic hormone levels and the effect of indomethacin on ureteral colic. J. Urol., 129: 941, 1983. 28. Grenabo, L. and Holmlund, D.: The significance of fluid restriction in indomethacin treatment of pain from ureteral stone. Scand. J. Urol. Nephrol., suppl. 75, p. 39, 1983. 29. Moncada, S., Flower, R. J. and Vane, J. R.: Prostaglandins, prostacyclin, and thromboxane A2. In: The Pharmacological Basis of Therapeutics, 6th ed. Edited by A. G. Gilman, L. S. Goodman and A. Gilman. New York: Macmillan Publishing Co., chapt. 28, pp. 668-681, 1980. 30. Ferreira, S. H., Moncada, S. and Vane, J. R.: Prostaglandins and signs and symptoms of inflammation. In: Prostaglandin Synthetase Inhibitors: Their Effects on Physiological Functions and Pathological States. Edited by H.J. Robinson and J. R. Vane. New York: Raven Press, part Ill, pp. 175-187, 1974. 31. Gullner, H. G.: Prostaglandin actions on the adrenergic nervous system. Klin. Wochenschr., 61: 533, 1983. 32. Lundstam, S.: Cited in Colleen, S., Hellsten, S., Pompeius, R. and Wadstrom, L. B.: Nordic cooperation in urologic research and developmental work. Nord. Med., 99: 43, 1984. 33. Ferris, T. F.: Prostaglandins and the kidney. Amer. J. Nephrol., 3: 139, 1983. 34. Lifschitz, M. D.: Renal effects of nonsteroidal anti-inflammatory agents. J. Lab. Clin. Med., 102: 313, 1983.