Perioperative Dutasteride for Hemorrhage Control in Bipolar TURP Under Anticoagulation.

This prospective double-blinded randomized study was conducted to assess the effect of two-week pretreatment with a 5-alpha reductase inhibitor (5-ARI) dutasteride 0.5 mg orally once daily on perioperative outcomes in patients with benign prostatic hyperplasia (BPH) undergoing bipolar transurethral resection of the prostate (TURP). The study will particularly evaluate its effect on intraoperative and postoperative bleeding, as well as the volume and duration of bladder irrigation required until clearance of postoperative hematuria.

The study population will consist of 44 male patients diagnosed with BPH, presenting predominantly with obstructive lower urinary tract symptoms and having an indication for surgical treatment. Patients with a prostate with a large prostate, more than 50 g. . All eligible participants will undergo bipolar TURP as the definitive surgical intervention and will be randomly assigned to the study groups according to the predefined study protocol.

Evaluation of the Patients All eligible patients scheduled for bipolar transurethral resection of the prostate (TURP) will undergo a comprehensive preoperative assessment before enrollment in the study. The assessment will include detailed history taking, complete physical examination, laboratory investigations, and appropriate evaluation of the prostate and lower urinary tract symptoms. The collected clinical and demographic data will be recorded in a standardized manner for subsequent comparison between the two study groups.

Inclusion Criteria

Patients will be eligible for participation in the study if they fulfill the following criteria:

• Male patients aged more than 50 years.

• Patients receiving anticoagulant therapy.

• Patients scheduled for bipolar TURP for benign prostatic hyperplasia.

• Patients with a large prostate measuring more than 50 g. Exclusion Criteria

Patients will be excluded from the study if any of the following criteria are present:

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• Concomitant urethral stricture.

• Previous prostatic surgical or endoscopic procedure.

• Known or suspected prostate cancer.

• High-risk cardiac condition.

• Severe hepatic impairment or significant liver disease.

• Severe renal impairment, including patients undergoing dialysis.

• Active urinary tract infection that has not been adequately treated before surgery.

Patient Assessment:

All individuals will be subjected to the following:

I. Preoperative Assessment:

A. Full history taking:

• Age.
• Personal history.
• Comorbidities.
• Medications (especially anticoagulants/antiplatelets)
• previous surgeries.
• Urinary symptoms.
• BPH-related complaints.
• Completion of the IPSS questionnaire.

B. Complete physical examination:

• General examination: - Blood pressure, temperature, heart rate (HR), and respiratory rate.

• Local examination: - Digital rectal examination. 43

C. Routine laboratory investigations:

- Complete blood cell (CBC).

• Coagulation profile.
• Liver and kidney function.
• Prostatic specific antigen (PSA).
• Urine analysis.

D. Radiological examination:

Pelvic-abdominal ultrasonography will be done to assess prostate volume, post-voiding residual urine, and any bladder pathology.

E. Preoperative preparations of anticoagulant drugs: The most common practice before TURP is to discontinue all oral AC or AP therapy for a few days (2 to 5 days) prior to surgery and to preoperatively bridge with heparin or low-molecular-weight heparin (LMWH) therapy.

II. Surgical Procedure: All patients will undergo bipolar TURP in the lithotomy position under spinal anesthesia, unless contraindicated, after administration of a prophylactic antibiotic 1 hour before surgery.

Bipolar TURP will be performed using isotonic 0.9% sodium chloride irrigation. Homeostasis will be achieved throughout, with immediate cauterization of arterial and venous bleeding. Resected adenoma chips will be removed using an Ellik evacuator. A 3-way Foley catheter will be inserted, and continuous bladder irrigation will be maintained for 24 hours, stopping once the effluent became clear. Operative time and weight of resected tissue will be recorded. Intraoperative blood loss will be evaluated in terms of reduction in serum hemoglobin (Hb) and hematocrit (Hct) levels, which will measured before, immediately after surgery. The catheter will be removed on the 5th postoperative day unless bleeding persists. Antibiotics and analgesics will be administered as needed.

III. Postoperative Assessment:

Hemoglobin and hematocrit levels will be measured at 24 hours postoperatively. Irrigation fluid volume and time, hospital stay, and indwelling catheter duration will 44 be documented. Antibiotics and analgesics will be prescribed as needed. Postoperative complications such as clot retention, severe hematuria, need for reoperation, and other general complications will be recorded and managed. Follow-up will be scheduled at postoperative day 5-8 and 1 month, including bladder ultrasonography for postvoid residual volume and completion of the IPSS questionnaire.

Patients' Characteristics and Randomization Patients fulfilling the eligibility criteria will be randomly assigned into two parallel groups in a 1:1 allocation ratio. Randomization will be performed using an online randomization program, and each participant will be assigned a study code. The allocation sequence will be concealed using opaque sealed envelopes until the appropriate time of group assignment.

Group I (Dutasteride group): Patients allocated to this group will receive dutasteride 0.5 mg orally once daily for two weeks before bipolar TURP and will continue the treatment for two weeks postoperatively.

Group II (Control group): Patients assigned to the control group will receive matching placebo capsules once daily for two weeks before surgery and for two weeks following bipolar TURP.

The use of a matching placebo together with concealed randomization will allow the study to maintain its double-blinded randomized design and minimize potential bias during assessment of the study outcomes.

Sample Size The sample size was calculated using G-Power© software version 3.1.7 (Institute of Experimental Psychology, Heinrich Heine University, Dusseldorf, Germany), based on a previously published paper to show that the hemoglobin (Hb) and hematocrit (Hct) levels are significantly different from the null hypothesis value of 0.5 using a T-test, with an α-level of 0.05, a power of 85%, and an effect size of 0.985. The sample size was 20 cases in each group and was increased to avoid missing data by 10% to be nearly the total size of 22 cases in each group.

45 Bipolar TURP Equipment and Operative Team All surgical procedures were performed under standardized operative conditions in both study groups using the same Karl Storz bipolar resectoscope connected to a video-assisted system. To minimize variation related to surgical technique, the procedures were carried out by a team of three well-trained surgeons with comparable levels of surgical experience.

The equipment used for bipolar prostate resection consisted of the following components:

1. A 4-mm autoclavable telescope with a 30° direction of view, providing adequate visualization of the operative field.

2. An active working element used to facilitate manipulation and resection of the prostatic tissue.

3. An inner sheath equipped with a standard obturator. 4. A 26-Fr outer sheath fitted with two rotatable stopcocks to facilitate irrigation and drainage during the procedure.

5. Karl Storz bipolar electrodes are used for resection and coagulation of the prostatic tissue.

Using the same equipment and maintaining comparable surgical expertise in both groups helped ensure that differences in postoperative outcomes were not attributable to variations in the operative setting or surgeon experience.

Procedure • All patients included in the study received prophylactic antibiotic therapy with a third-generation cephalosporin approximately one hour before the scheduled operation.

• The procedure was performed under either spinal anesthesia or combined spinal/epidural anesthesia, according to the anesthetic assessment.

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• Following induction of anesthesia, the patient was appropriately positioned in the lithotomy position, and standard surgical preparation and draping were performed.

• Normal saline was used as the irrigation solution throughout the procedure. The irrigation fluid was maintained at a height of approximately 60 cm above the level of the operating table, providing continuous irrigation and adequate visualization during the resection.

• The procedure was initially started with a careful pancystoscopic examination. This initial inspection was performed to assess the urethra and prostatic urethra, evaluate the overall size and configuration of the prostate and its lobes, and identify both ureteric orifices. The bladder was also systematically examined for associated pathological findings, including bladder stones, tumors, and diverticula. Identification of the relevant anatomical landmarks before resection was considered an essential step for safe completion of the procedure.

• Particular attention was initially directed toward identification of the verumontanum, which served as the distal limit of prostatic tissue resection.

• The sequence of prostate resection was determined according to the configuration and relative size of the prostatic lobes. In patients with a prominent or large median lobe, the median lobe was addressed first. Resection was initiated between the 5 and 7 o'clock positions, with progressive removal of the adenomatous tissue until the level of the surgical capsule was reached. Following adequate treatment of the median lobe, resection was continued on the lateral lobes and the ventral portions of the gland. The apical portion of the prostate was reserved for the final stage of resection.

• In patients in whom the two lateral lobes were considerably enlarged while the median lobe was relatively small, the resection strategy was modified accordingly. Resection was initially started at approximately the 1 o'clock position and continued toward the surgical capsule. The resection was then extended toward the area where the lateral lobe meets the median lobe. Attention was subsequently directed to the opposite side, beginning at approximately the 11 o'clock position, and the corresponding lateral lobe was resected in a similar manner. Once adequate resection of both lateral lobes down to the level of the prostatic capsule had been achieved, the median lobe was subsequently addressed.

• During the final stage, the apical prostatic tissue was carefully resected. Particular caution was exercised in this region to avoid injury to the external 48 urethral sphincter

, thereby minimizing the risk of postoperative urinary incontinence.

• After completion of the prostatic resection, the irrigation inflow was temporarily discontinued to reduce the pressure within the bladder. This facilitated identification of residual bleeding points within the prostatic fossa, which were subsequently managed by appropriate coagulation until satisfactory hemostasis was achieved.

• Following completion of hemostasis, the resected prostatic tissue fragments were removed from the bladder using a bladder Ellik evacuator.

• Complete evacuation of the resection chips was performed to prevent their retention within the bladder and to minimize potential postoperative complications, particularly clot or tissue-related urinary retention and recurrent urinary tract infection.

• At the conclusion of the procedure, a 24-Fr three-way urethral catheter was inserted and securely fixed.

• Continuous bladder irrigation with normal saline at a slow rate was then initiated. Irrigation was maintained postoperatively and adjusted according to the degree of hematuria, with the aim of obtaining clear or satisfactorily clear urine before discontinuation of irrigation.

Postoperative Assessment and Follow-up Postoperative clinical and laboratory parameters were systematically recorded for all patients. Hemoglobin and hematocrit levels were assessed at one hour and 24 hours after surgery and compared with the corresponding preoperative measurements to evaluate the postoperative change in blood parameters.

The collected tissue fragments were subsequently prepared and submitted for histopathological examination.

Postoperatively, the urethral catheter was maintained until the urine became grossly clear, allowing discontinuation of continuous bladder irrigation. Longer catheterization was considered only when clinically indicated, such as in cases of bladder perforation or other circumstances requiring prolonged urinary drainage.

Before hospital discharge, the following postoperative parameters were documented:

• Duration of postoperative catheterization.

• Length of postoperative hospital stay. 49

• Occurrence of postoperative clot retention.

• Any other postoperative complications. Following satisfactory postoperative recovery, patients were discharged with prescribed oral antibiotics, analgesics, and laxatives. They were instructed to avoid straining and strenuous physical activities during the early postoperative period.

After removal of the urethral catheter, the patient was observed until satisfactory spontaneous voiding was achieved. Post-voiding residual urine (PVR) was then assessed by ultrasonography to confirm adequate bladder emptying.

Follow-up

Postoperative follow-up visits were scheduled after surgery. During this visit, patients were assessed clinically and, when indicated, underwent:

• Urine analysis, when clinically required.

• Measurement of post-voiding residual urine volume by ultrasonography.

• Assessment of urinary continence.

• Reassessment of lower urinary tract symptoms using the International Prostate Symptom Score (IPSS).

This postoperative follow-up allowed assessment of the early recovery, urinary function, and symptomatic outcome following bipolar TURP