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Electroresection of the Prostate in Patients Treated with Heparin
0022-5347 /80/1242-0221$02.00/0 Vol. 124, August
THE JOURNAL OF UROLOGY
Copyright © 1980 by The Williams & Wilkins Co.
Printed in U.S.A.
ELECTRORESECTION OF THE PROSTATE IN PATIENTS TREATED WITH HEP ARIN R. TSCHOLL, W. STRAUB
AND
E. ZINGG
From the Urological and Medical Departments, University of Bern, Inselspital, Bern, Switzerland
ABSTRACT
A compari~~n was ~ade of blood lo~s under controlled heparinization and that occurring under norm~ cond1t10ns durmg electroresect10n of the prostate. Mean blood loss in patients treated with heparm amounted to 429.4 ± 524.8 ml. and in the control group it was 391.8 ± 451.4 ml. The diff~rence is. not signific~nt. T~erefore, a transurethral operation does not require interruption of anticoagulation therapy m card10vascu.lar patients. Transurethral resection of the prostate in patients under effective anticoagulation therapy is performed rarely, since it is considered dangerous. Patients with bladder obstruction from prostatic disease who are under anticoagulation therapy usually are treated by an indwelling catheter. If the latter is not accepted by the patient and the prostate must be resected anticoagulation therapy usually is interrupted, 1 replaced by low dose subcutaneous heparin2 or reduced to an ineffective level. However, the risk of transurethral resection of the prostate in patients under effective anticoagulation therapy has never been assessed. Our investigation was done to determine whether controlled anticoagulation therapy will enhance operative blood loss compared to blood loss occurring under normal conditions. This question becomes important for patients with prostatic hyperplasia who 1) have alloplastic heart valves, 2) have been subjected to prior endarterectomy or 3) are subject to recurrent deep venous thrombosis with pulmonary embolism. MATERIAL AND METHOD
The prospective study is based upon 23 consecutive strictly randomized individuals with obstructive prostatic hyperplasia (see table). The patients were alternatively put into the anticoagulation therapy or control group. Patients with a contraindication to anticoagulation (arterial hypertension with diastolic pressure > 105 mm. Hg, nephrolithiasis, renal insufficiency or ulcers in the gastrointestinal tract) were not included in the study. Anticoagulation was achieved with heparin. Patients in the anticoagulation group received 5,000 IU heparin intravenously 15 hours preoperatively, followed by an infusion containing 15,000 IU /1. 0.9 per cent sodium chloride. The rate of infusion was controlled by a pump. Based upon the measurement of the thrombin dotting time after 3 and 12 hours the infusion rate was adjusted individually so that at the onset of the operation the patients were at least in a state of anticoagulation characterized by 1) thrombin clotting time I-no clotting and 2) thrombin clotting time Il-8 to 20 seconds. The thrombin clotting time corresponds to a clotting time of 0.2 ml. citrated plasma after adding 0.1 ml. of a thrombin solution. To measure thrombin dotting times I and II a solution of2.5 and 10 National Institutes of Health-Units thrombin, respectively, per ml. is used. The technique of prostatic resection was identical in each group. Operative blood loss was computed according to the principle of clearance: 3 the volume of irrigating fluid times the concentration of hemoglobin in irrigating fluid is divided by the concentration of hemoglobin in blood. The concentration of Accepted for publication August 24, 1979.
221
Results of anticoagulation Control Group, 11 Pts.
Heparin Group, 12 Pts. Case No. 1 3 5 7 9 11 13 15 17 19 21 23
Mean± standard deviation Correlation
Wt. of Adenoma (gm.)
Operative Blood Loss
15 45 65 20 5 20 25 50 35 40 40
67.6 491.4 1,489.1 80.3 14.9 64.8 192.0 389.7 201.2 116.6 556.4 1,488.6
30.8 ± 17.9*
429.4 ± 524.St
(ml.)
10
r
=
Case No. 2 4 6 8 10
12 14 16 18 20 22
Wt. of Adenoma
Operative Blood Loss
(gm.)
(ml.)
10 30 10 25 20 20 45 65 60
75.2 218.9 188.7 219.1 74.6 162.6 603.4 1,523.0 860.0 19.0 364.9
10
35 30.0 ± 19.5*
391.8 ± 451.41
r = 0.92
0.76
* Significance of difference 0.9< p <1.0. t Significance of difference 0.8< p <0.9.
hemoglobin in the fluid was measured by the methemoglobin 4 and the differential-spectrophotometrical methods. 5 Mean blood loss was calculated in each group of patients and the values were compared by Student's t test. RESULTS
Blood loss increased with the increased weight of the resected prostatic adenoma, whether or not heparin was given. Correla-tion between blood loss and weight of the resected tissue in the heparin and the control groups was 0.76 and 0.92 ml., respectively. Mean weight of the resected adenoma was 30.8 ± 17.9 gm. in patients treated with heparin and 30 ± 19.5 gm. in the control group. The difference was not significant (0.9< p <1.0). Mean blood loss amounted to 429.4 ± 524.8 ml. in patients treated with heparin and 391.8 ± 451.4 ml. in the contirol group. The difference was not significant (0.8< p <0.9). Three patients were included in this statistical comparison although they had at the time of the operation a much higher degree of anticoagulation than was defined initially, their thrombin clotting time II not being measurable because there was no clotting at all. These 3 patients were subjected to the resection since early in the study we already had the impression that anticoagulation therapy did not create any additional difficulty during the resection. Resection of a 40, 25 and 65 gm. adenoma in these patients led to an operative blood loss of 1,488, 192 and 1,489 ml., respectively. The resections were concluded with the bleeding being well controlled.
222
TSCHOLL, STRAUB AND ZINGG
DISCUSSION
Patients anticoagulated with heparin can be subjected to transurethral resection of the prostate without any additional danger owing to the anticoagulation. All patients were at least under an effect of heparin used in the postoperative period after implantation of alloplastic heart valves, while 3 patients were anticoagulated to an extent used in the treatment of deep venous thrombosis and pulmonary embolism. The quantity of heparin necessary to achieve this defined degree of anticoagulation varied strongly from 1 patient to another, and was between 7,000 and 26,000 IU. This amount is at least equivalent to the quantity given in low dose heparin prophylaxis that effectively protects against postoperative thrombosis and that consists of 2 subcutaneous injections of 5,000 IU heparin daily, whereby a temporary concentration of heparin in the plasma of 0.12 ± 0.11 IU/ml. is created 4 hours after the injection. 6 With the quantity of heparin given to our patients there is by definition no clotting of the plasma if the conventional thrombin clotting time I is used, whereas the thrombin clotting time II measured by means of a solution of 10 National Institutes of Health-Units per ml. is doubled. This corresponds to a lengthening of the partial thromboplastin time by about a third. Under low dose heparin prophylaxis such values can be found in just a few patients, in some only temporarily 2 to 4 hours after the subcutaneous application and in most patients never. 6' 7 If heparinization exceeds the defined limit the blood loss will increase but without making the operative procedure more difficult. The only consequence in the management of the patient is that a correspondingly larger quantity of blood must be given to offset the greater amount of blood lost. Our results indicate that patients under controlled anticoagulation with heparin do not bleed more than normal individuals during transurethral resection of the prostate. Neither the endoscopic visibility nor the precise cauterization of the opened blood vessels nor the postoperative course is influenced in any way by the anticoagulation. This experience has practical clinical importance. Patients with alloplastic heart valves should not have indwelling urethral
catheters because it might become the starting point of a hematogenous infection of the implanted valves. For such patients anticoagulated with crystalline warfarin sodium Mulcahy and associates recommend that anticoagulation be stopped 48 hours before the prostatic resection and resumed 48 hours afterwards. 1 However, we were able to demonstrate that it is unnecessary to run the risk of valvular thrombosis by interrupting anticoagulation therapy. Based on our experience to date we suggest to discontinue the crystalline warfarin sodium 1 or 2 days preoperatively while giving heparin so that the anticoagulation is never interrupted. The warfarin can be resumed 2 days after the transurethral operation and heparin is stopped as soon as the former is effective. The number of patients with alloplastic heart valves and those anticoagulated for other reasons who have vesical obstruction from prostatic disease will most likely increase. Thus, the clinical relevance of prostatic resection in patients under anticoagulation therapy will increase in the coming years. REFERENCES
1. Mulcahy, J. J., Brandenburg, R. 0., Pluth, J. R. and Greene, L. F.: Transurethral prostatic resection in patients with prosthetic cardiac valves. J. Urol., 113: 642, 1975. · 2. Allen, N. H., Jenkins, J. D. and Smart, C. J.: Surgical haemorrhage in patients given subcutaneous heparin as prophylaxis against thromboembolism. Brit. Med. J., 9: 1326, 1978. 3. Hartung, R., Mauermayer, W., Beck, F. and Green, G.: Die kontrollierte TUR: eine neue Messmethode zur Bestimmung des intraoperativen Blutverlustes bei der TUR. Urologe A, 15: 254, 1976. 4. Richterich, R. and Colombo, J. P.: Klinische Chemie. Basel: S. Karger, p. 437, 1978. 5. Levere, R. D., Swerdlow, F. and Garavoy, M. R.: Measurement of human plasma hemoglobin by difference spectrophotometry. J. Lab. Clin. Med., 77: 168, 1971. 6. Pitney, W. R. and Dean, S.: Plasma heparin concentrations during subcutaneous heparin therapy. Aust. New Zeal. J. Med., 6: 454, 1976. 7. Wessler, S. and Yin, E. T.: Theory and practice of minidose heparin in surgical patients. A status report. Circulation, 47: 671, 1973.
THE JOURNAL OF UROLOGY
Copyright © 1980 by The Williams & Wilkins Co.
Printed in U.S.A.
ELECTRORESECTION OF THE PROSTATE IN PATIENTS TREATED WITH HEP ARIN R. TSCHOLL, W. STRAUB
AND
E. ZINGG
From the Urological and Medical Departments, University of Bern, Inselspital, Bern, Switzerland
ABSTRACT
A compari~~n was ~ade of blood lo~s under controlled heparinization and that occurring under norm~ cond1t10ns durmg electroresect10n of the prostate. Mean blood loss in patients treated with heparm amounted to 429.4 ± 524.8 ml. and in the control group it was 391.8 ± 451.4 ml. The diff~rence is. not signific~nt. T~erefore, a transurethral operation does not require interruption of anticoagulation therapy m card10vascu.lar patients. Transurethral resection of the prostate in patients under effective anticoagulation therapy is performed rarely, since it is considered dangerous. Patients with bladder obstruction from prostatic disease who are under anticoagulation therapy usually are treated by an indwelling catheter. If the latter is not accepted by the patient and the prostate must be resected anticoagulation therapy usually is interrupted, 1 replaced by low dose subcutaneous heparin2 or reduced to an ineffective level. However, the risk of transurethral resection of the prostate in patients under effective anticoagulation therapy has never been assessed. Our investigation was done to determine whether controlled anticoagulation therapy will enhance operative blood loss compared to blood loss occurring under normal conditions. This question becomes important for patients with prostatic hyperplasia who 1) have alloplastic heart valves, 2) have been subjected to prior endarterectomy or 3) are subject to recurrent deep venous thrombosis with pulmonary embolism. MATERIAL AND METHOD
The prospective study is based upon 23 consecutive strictly randomized individuals with obstructive prostatic hyperplasia (see table). The patients were alternatively put into the anticoagulation therapy or control group. Patients with a contraindication to anticoagulation (arterial hypertension with diastolic pressure > 105 mm. Hg, nephrolithiasis, renal insufficiency or ulcers in the gastrointestinal tract) were not included in the study. Anticoagulation was achieved with heparin. Patients in the anticoagulation group received 5,000 IU heparin intravenously 15 hours preoperatively, followed by an infusion containing 15,000 IU /1. 0.9 per cent sodium chloride. The rate of infusion was controlled by a pump. Based upon the measurement of the thrombin dotting time after 3 and 12 hours the infusion rate was adjusted individually so that at the onset of the operation the patients were at least in a state of anticoagulation characterized by 1) thrombin clotting time I-no clotting and 2) thrombin clotting time Il-8 to 20 seconds. The thrombin clotting time corresponds to a clotting time of 0.2 ml. citrated plasma after adding 0.1 ml. of a thrombin solution. To measure thrombin dotting times I and II a solution of2.5 and 10 National Institutes of Health-Units thrombin, respectively, per ml. is used. The technique of prostatic resection was identical in each group. Operative blood loss was computed according to the principle of clearance: 3 the volume of irrigating fluid times the concentration of hemoglobin in irrigating fluid is divided by the concentration of hemoglobin in blood. The concentration of Accepted for publication August 24, 1979.
221
Results of anticoagulation Control Group, 11 Pts.
Heparin Group, 12 Pts. Case No. 1 3 5 7 9 11 13 15 17 19 21 23
Mean± standard deviation Correlation
Wt. of Adenoma (gm.)
Operative Blood Loss
15 45 65 20 5 20 25 50 35 40 40
67.6 491.4 1,489.1 80.3 14.9 64.8 192.0 389.7 201.2 116.6 556.4 1,488.6
30.8 ± 17.9*
429.4 ± 524.St
(ml.)
10
r
=
Case No. 2 4 6 8 10
12 14 16 18 20 22
Wt. of Adenoma
Operative Blood Loss
(gm.)
(ml.)
10 30 10 25 20 20 45 65 60
75.2 218.9 188.7 219.1 74.6 162.6 603.4 1,523.0 860.0 19.0 364.9
10
35 30.0 ± 19.5*
391.8 ± 451.41
r = 0.92
0.76
* Significance of difference 0.9< p <1.0. t Significance of difference 0.8< p <0.9.
hemoglobin in the fluid was measured by the methemoglobin 4 and the differential-spectrophotometrical methods. 5 Mean blood loss was calculated in each group of patients and the values were compared by Student's t test. RESULTS
Blood loss increased with the increased weight of the resected prostatic adenoma, whether or not heparin was given. Correla-tion between blood loss and weight of the resected tissue in the heparin and the control groups was 0.76 and 0.92 ml., respectively. Mean weight of the resected adenoma was 30.8 ± 17.9 gm. in patients treated with heparin and 30 ± 19.5 gm. in the control group. The difference was not significant (0.9< p <1.0). Mean blood loss amounted to 429.4 ± 524.8 ml. in patients treated with heparin and 391.8 ± 451.4 ml. in the contirol group. The difference was not significant (0.8< p <0.9). Three patients were included in this statistical comparison although they had at the time of the operation a much higher degree of anticoagulation than was defined initially, their thrombin clotting time II not being measurable because there was no clotting at all. These 3 patients were subjected to the resection since early in the study we already had the impression that anticoagulation therapy did not create any additional difficulty during the resection. Resection of a 40, 25 and 65 gm. adenoma in these patients led to an operative blood loss of 1,488, 192 and 1,489 ml., respectively. The resections were concluded with the bleeding being well controlled.
222
TSCHOLL, STRAUB AND ZINGG
DISCUSSION
Patients anticoagulated with heparin can be subjected to transurethral resection of the prostate without any additional danger owing to the anticoagulation. All patients were at least under an effect of heparin used in the postoperative period after implantation of alloplastic heart valves, while 3 patients were anticoagulated to an extent used in the treatment of deep venous thrombosis and pulmonary embolism. The quantity of heparin necessary to achieve this defined degree of anticoagulation varied strongly from 1 patient to another, and was between 7,000 and 26,000 IU. This amount is at least equivalent to the quantity given in low dose heparin prophylaxis that effectively protects against postoperative thrombosis and that consists of 2 subcutaneous injections of 5,000 IU heparin daily, whereby a temporary concentration of heparin in the plasma of 0.12 ± 0.11 IU/ml. is created 4 hours after the injection. 6 With the quantity of heparin given to our patients there is by definition no clotting of the plasma if the conventional thrombin clotting time I is used, whereas the thrombin clotting time II measured by means of a solution of 10 National Institutes of Health-Units per ml. is doubled. This corresponds to a lengthening of the partial thromboplastin time by about a third. Under low dose heparin prophylaxis such values can be found in just a few patients, in some only temporarily 2 to 4 hours after the subcutaneous application and in most patients never. 6' 7 If heparinization exceeds the defined limit the blood loss will increase but without making the operative procedure more difficult. The only consequence in the management of the patient is that a correspondingly larger quantity of blood must be given to offset the greater amount of blood lost. Our results indicate that patients under controlled anticoagulation with heparin do not bleed more than normal individuals during transurethral resection of the prostate. Neither the endoscopic visibility nor the precise cauterization of the opened blood vessels nor the postoperative course is influenced in any way by the anticoagulation. This experience has practical clinical importance. Patients with alloplastic heart valves should not have indwelling urethral
catheters because it might become the starting point of a hematogenous infection of the implanted valves. For such patients anticoagulated with crystalline warfarin sodium Mulcahy and associates recommend that anticoagulation be stopped 48 hours before the prostatic resection and resumed 48 hours afterwards. 1 However, we were able to demonstrate that it is unnecessary to run the risk of valvular thrombosis by interrupting anticoagulation therapy. Based on our experience to date we suggest to discontinue the crystalline warfarin sodium 1 or 2 days preoperatively while giving heparin so that the anticoagulation is never interrupted. The warfarin can be resumed 2 days after the transurethral operation and heparin is stopped as soon as the former is effective. The number of patients with alloplastic heart valves and those anticoagulated for other reasons who have vesical obstruction from prostatic disease will most likely increase. Thus, the clinical relevance of prostatic resection in patients under anticoagulation therapy will increase in the coming years. REFERENCES
1. Mulcahy, J. J., Brandenburg, R. 0., Pluth, J. R. and Greene, L. F.: Transurethral prostatic resection in patients with prosthetic cardiac valves. J. Urol., 113: 642, 1975. · 2. Allen, N. H., Jenkins, J. D. and Smart, C. J.: Surgical haemorrhage in patients given subcutaneous heparin as prophylaxis against thromboembolism. Brit. Med. J., 9: 1326, 1978. 3. Hartung, R., Mauermayer, W., Beck, F. and Green, G.: Die kontrollierte TUR: eine neue Messmethode zur Bestimmung des intraoperativen Blutverlustes bei der TUR. Urologe A, 15: 254, 1976. 4. Richterich, R. and Colombo, J. P.: Klinische Chemie. Basel: S. Karger, p. 437, 1978. 5. Levere, R. D., Swerdlow, F. and Garavoy, M. R.: Measurement of human plasma hemoglobin by difference spectrophotometry. J. Lab. Clin. Med., 77: 168, 1971. 6. Pitney, W. R. and Dean, S.: Plasma heparin concentrations during subcutaneous heparin therapy. Aust. New Zeal. J. Med., 6: 454, 1976. 7. Wessler, S. and Yin, E. T.: Theory and practice of minidose heparin in surgical patients. A status report. Circulation, 47: 671, 1973.