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Possible Role of Reserpine in Post-Prostatectomy Hemorrhage
Vol. 107, January
THE JOURNAL OF UROLOGY
Copyright © 1972 by The Williams & Wilkins Co.
Printed in U.S.A
POSSIBLE ROLE OF RESERPINE IN POST-PROSTATECTOMY HEMORRHAGE DENNIS J. CARD
AND
MARTIN SCHIFF, JR.
From the Department of Surgery, Section of Urology, Yale University School of Medicine, New Haven, Connecticut
Reserpine and similar derivatives frequently are used in the management of hypertension. The development of more potent synthetic antihypertensive agents has not altered the indications for the use of reserpine compounds. It was customary to discontinue the administration of reserpine in patients 2 to 3 weeks prior to elective operation to diminish the likelihood of hypotensive episodes during anesthesia.1 Recently, however, this practice has been discarded owing to the development of new anesthetic agents and pressor substances, which can now be used safely to counteract pharmacologically induced hypotension should it occur during operation. Consequently, increasing numbers of patients are now continuing to take reserpine and similar antihypertensive agents until the time of operation. Seven patients being treated with reserpine for essential hypertension underwent elective prostatectomy for benign hyperplasia at the Yale-New Haven Medical Center between July 1968 and June 1969. The operative or immediate postoperative course was complicated by excessive bleeding in 5 patients. These cases are described herein to draw attention to this serious problem which appears likely to occur in patients taking reserpine. CASE REPORTS
Case 1. B. F., 446216, a 64-year-old white man, had been treated for hypertension with reserpine for l year. He underwent transurethral resection of the prostate with removal of 25 gm. tissue. Moderately severe bleeding occurred throughout the resection and postoperatively. It was partially controlled by tamponade with Foley catheter. Hematocrit fell from 47 to 34 per cent despite administration of 2 units of whole blood. Estimated blood loss was 3,000 cc. Case 2. I-I. T., Al 9053, a 67-year-old white man, had been treated with reserpine for several years for essential hypertension. He underwent suprapubic prostatectomy during which there was continuous, uncontrollable bleeding from the entire prostatic fossa. He was given 3,500 cc whole blood to replace a blood loss of approximately 3,000 cc. The prostatic fossa was packed, with satisfactory control of bleeding. Case 3. S. S., 736347, a 60-year-old white man, had a history of hypertension which had been treated with reserpine for 6 years. He underwent a suprapubic prostatectomy and immediately following the enucleation severe hemorrhage occurred from the entire prostatic fossa which could only be
Ejfects of reserpine therapy on the incidence of severe bleeding associated with prostatectomy Reserpine
No Reserpine
Nu.
Bleeding
No.
Bleeding
TUR
3
3
67
Open
4
2
58
0 3
125
Total
controlled with packing. Estimated blood loss was 4,000 cc and 9 units of whole blood were administered. Case 4. K. F., 477450, a 58-year-old white man, had been treated with reserpine for hypertension for 5 years. Transurethral resection of the prostate was performed and, although the procedure appeared uncomplicated, persistent bleeding began in the recovery room which was not controlled by traction on the urethral catheter or continuous irrigation with saline. The patient was returned to the operating room and the entire prostatic fossa was found to be bleeding. This was controlled eventually extensive fulguration. There was a total blood loss of approximately 3,000 cc. Case 5. W. W., 044052748, a 55-year-old white man, had been treated with reserpine for several years with satisfactory control of hypertension. A transurethral resection of the prostate was performed with removal of approximately 20 gm. tissue. During the resection, severe bleeding from the entire fossa began which was only partially controlled by extensive fulguration and traction on the urethral catheter. The patient received 3 units of whole blood during the operative procedure and an additional 3 units of fresh whole blood in the recovery room. However, bleeding continued and suprapubic cystotomy and packing of the prostatic fossa were required. Total blood loss was estimated at 4,000 cc. DISCUSSION
Five of 7 patients who had been treated with reserpine for essential hypertension up until the time of elective prostatectomy for benign hyperplasia experienced excessive bleeding during or following the operation. The average estimated blood loss was approximately 3,500 cc, a marked increase from what is usually experienced. 2 During the same interval 125 patients who had not been treated with reserp)ne underwent similar procedures, and unusual bleedmg occurred in only 3 instances (see table).
Accepted for publication January 22, 1971. 1 Minuck, M.: Reaction to drugs during surgery and anaesthesia. Canad. Med. Ass. J., 82: 1008, 1960.
2 Goldman, E. J. and Samellas, W.: Blood loss during prostatectomy. J. Urol., 86: 637, 1961.
97
98
CARD AND SCHIFF
It should be noted that a number of patients in this latter group were also hypertensive and several were under treatment with other antihypertensive agents. There were no abnormalities of clotting time, prothrombin time, partial thromboplastin time or platelet count in any of the 5 patients who bled. Neither was fibrinolytic activity detected in any of them. Reserpine is a semisynthetic antihypertensive agent, derived from one of the 20 alkaloids of the climbing plant Rauwolfia serpentina. Administration of the drug causes a gradual decline in blood pressure within several days. There is a general decrease in sympathetic tone with bradycardia, decreased cardiac output and peripheral vasodilatation. The decrease in sympathetic tone is due to depletion of norepinephrine from sympathetic postganglionic nerve endings. Experimentally, reserpine has been shown to deplete blood vessels, heart, brain and adrenal medulla of their catecholamine stores. 8 , 4 We have been unable to find mention in Brodie, B. B.: Selective release of norepinephrine and serotonin by reserpine-like compounds. Dis. Nerv. Syst., 21(3): suppl. p. 107, 1960. 4 Orlans, F. B., Finger, K. F. and Brodie, B. B.: Pharmacological consequences of the selective release 3
the literature of any coagulopathy associated with reserpine therapy. Reserpine affects cardiovascular reflexes only minimally or not at all. 5 However, it has been demonstrated to be comparable to guanethidine in depressing reflex constriction of the veins. 6 It is postulated that this aspect of the action of reserpine is responsible for the increased bleeding which occurred with prostatectomy in this group of patients. SUMMARY
Five of 7 patients who were taking reserpine at the time of prostatectomy bled excessively either during or following operation. Patients not treated with reserpine had a low incidence of hemorrhage. Reserpine acts in part by depleting catecholamine stores and suppressing peripheral reflex venoconstriction. It is possible that this mechanism may render patients treated with reserpine more susceptible to post-prostatectomy hemorrhage. of peripheral norepinephrine by syrosingopine (Su 3118). J. Pharmacol. Exp. Ther., 128: 131, 1960. 5 Burn, J. H.: Reserpine and vascular tone. Brit. J. Anaesth., 30: 351, 1958. 6 Gaffney, T. E., Bryant, W. M. and Braunwald, E.: Effects of reserpine and guanethidine on venous reflexes. Circ. Res., 11: 889, 1962.
THE JOURNAL OF UROLOGY
Copyright © 1972 by The Williams & Wilkins Co.
Printed in U.S.A
POSSIBLE ROLE OF RESERPINE IN POST-PROSTATECTOMY HEMORRHAGE DENNIS J. CARD
AND
MARTIN SCHIFF, JR.
From the Department of Surgery, Section of Urology, Yale University School of Medicine, New Haven, Connecticut
Reserpine and similar derivatives frequently are used in the management of hypertension. The development of more potent synthetic antihypertensive agents has not altered the indications for the use of reserpine compounds. It was customary to discontinue the administration of reserpine in patients 2 to 3 weeks prior to elective operation to diminish the likelihood of hypotensive episodes during anesthesia.1 Recently, however, this practice has been discarded owing to the development of new anesthetic agents and pressor substances, which can now be used safely to counteract pharmacologically induced hypotension should it occur during operation. Consequently, increasing numbers of patients are now continuing to take reserpine and similar antihypertensive agents until the time of operation. Seven patients being treated with reserpine for essential hypertension underwent elective prostatectomy for benign hyperplasia at the Yale-New Haven Medical Center between July 1968 and June 1969. The operative or immediate postoperative course was complicated by excessive bleeding in 5 patients. These cases are described herein to draw attention to this serious problem which appears likely to occur in patients taking reserpine. CASE REPORTS
Case 1. B. F., 446216, a 64-year-old white man, had been treated for hypertension with reserpine for l year. He underwent transurethral resection of the prostate with removal of 25 gm. tissue. Moderately severe bleeding occurred throughout the resection and postoperatively. It was partially controlled by tamponade with Foley catheter. Hematocrit fell from 47 to 34 per cent despite administration of 2 units of whole blood. Estimated blood loss was 3,000 cc. Case 2. I-I. T., Al 9053, a 67-year-old white man, had been treated with reserpine for several years for essential hypertension. He underwent suprapubic prostatectomy during which there was continuous, uncontrollable bleeding from the entire prostatic fossa. He was given 3,500 cc whole blood to replace a blood loss of approximately 3,000 cc. The prostatic fossa was packed, with satisfactory control of bleeding. Case 3. S. S., 736347, a 60-year-old white man, had a history of hypertension which had been treated with reserpine for 6 years. He underwent a suprapubic prostatectomy and immediately following the enucleation severe hemorrhage occurred from the entire prostatic fossa which could only be
Ejfects of reserpine therapy on the incidence of severe bleeding associated with prostatectomy Reserpine
No Reserpine
Nu.
Bleeding
No.
Bleeding
TUR
3
3
67
Open
4
2
58
0 3
125
Total
controlled with packing. Estimated blood loss was 4,000 cc and 9 units of whole blood were administered. Case 4. K. F., 477450, a 58-year-old white man, had been treated with reserpine for hypertension for 5 years. Transurethral resection of the prostate was performed and, although the procedure appeared uncomplicated, persistent bleeding began in the recovery room which was not controlled by traction on the urethral catheter or continuous irrigation with saline. The patient was returned to the operating room and the entire prostatic fossa was found to be bleeding. This was controlled eventually extensive fulguration. There was a total blood loss of approximately 3,000 cc. Case 5. W. W., 044052748, a 55-year-old white man, had been treated with reserpine for several years with satisfactory control of hypertension. A transurethral resection of the prostate was performed with removal of approximately 20 gm. tissue. During the resection, severe bleeding from the entire fossa began which was only partially controlled by extensive fulguration and traction on the urethral catheter. The patient received 3 units of whole blood during the operative procedure and an additional 3 units of fresh whole blood in the recovery room. However, bleeding continued and suprapubic cystotomy and packing of the prostatic fossa were required. Total blood loss was estimated at 4,000 cc. DISCUSSION
Five of 7 patients who had been treated with reserpine for essential hypertension up until the time of elective prostatectomy for benign hyperplasia experienced excessive bleeding during or following the operation. The average estimated blood loss was approximately 3,500 cc, a marked increase from what is usually experienced. 2 During the same interval 125 patients who had not been treated with reserp)ne underwent similar procedures, and unusual bleedmg occurred in only 3 instances (see table).
Accepted for publication January 22, 1971. 1 Minuck, M.: Reaction to drugs during surgery and anaesthesia. Canad. Med. Ass. J., 82: 1008, 1960.
2 Goldman, E. J. and Samellas, W.: Blood loss during prostatectomy. J. Urol., 86: 637, 1961.
97
98
CARD AND SCHIFF
It should be noted that a number of patients in this latter group were also hypertensive and several were under treatment with other antihypertensive agents. There were no abnormalities of clotting time, prothrombin time, partial thromboplastin time or platelet count in any of the 5 patients who bled. Neither was fibrinolytic activity detected in any of them. Reserpine is a semisynthetic antihypertensive agent, derived from one of the 20 alkaloids of the climbing plant Rauwolfia serpentina. Administration of the drug causes a gradual decline in blood pressure within several days. There is a general decrease in sympathetic tone with bradycardia, decreased cardiac output and peripheral vasodilatation. The decrease in sympathetic tone is due to depletion of norepinephrine from sympathetic postganglionic nerve endings. Experimentally, reserpine has been shown to deplete blood vessels, heart, brain and adrenal medulla of their catecholamine stores. 8 , 4 We have been unable to find mention in Brodie, B. B.: Selective release of norepinephrine and serotonin by reserpine-like compounds. Dis. Nerv. Syst., 21(3): suppl. p. 107, 1960. 4 Orlans, F. B., Finger, K. F. and Brodie, B. B.: Pharmacological consequences of the selective release 3
the literature of any coagulopathy associated with reserpine therapy. Reserpine affects cardiovascular reflexes only minimally or not at all. 5 However, it has been demonstrated to be comparable to guanethidine in depressing reflex constriction of the veins. 6 It is postulated that this aspect of the action of reserpine is responsible for the increased bleeding which occurred with prostatectomy in this group of patients. SUMMARY
Five of 7 patients who were taking reserpine at the time of prostatectomy bled excessively either during or following operation. Patients not treated with reserpine had a low incidence of hemorrhage. Reserpine acts in part by depleting catecholamine stores and suppressing peripheral reflex venoconstriction. It is possible that this mechanism may render patients treated with reserpine more susceptible to post-prostatectomy hemorrhage. of peripheral norepinephrine by syrosingopine (Su 3118). J. Pharmacol. Exp. Ther., 128: 131, 1960. 5 Burn, J. H.: Reserpine and vascular tone. Brit. J. Anaesth., 30: 351, 1958. 6 Gaffney, T. E., Bryant, W. M. and Braunwald, E.: Effects of reserpine and guanethidine on venous reflexes. Circ. Res., 11: 889, 1962.