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The role of preoperative dutasteride in reducing bleeding during transurethral resection of the prostate: A systematic review and meta-analysis of randomized controlled trials
Kloping YP, Yogiswara N, Azmi Y
Asian journal of urology. 2022;9(1):18-26
Abstract
OBJECTIVE Bleeding is one of the most common complications of transurethral resection of the prostate (TURP). Several previous studies reported that administering dutasteride before surgery could reduce perioperative bleeding. We aimed to evaluate the efficacy of preoperative dutasteride treatment in benign prostatic hyperplasia patients undergoing TURP by performing a meta-analysis of relevant randomized controlled trials (RCTs). METHODS A comprehensive literature search was performed through the electronic databases including Medline, Cochrane Library, Google Scholar, and ClinicalTrial.gov in October 2020. RCTs evaluating the role of dutasteride for TURP were screened using the eligibility criteria and the quality of RCTs was assessed using the Cochrane Risk of Bias Tool. The heterogeneity was assessed using I (2) statistic. The measured outcomes were hemoglobin (Hb) levels, perioperative blood loss, blood transfusion, microvessel density (MVD), and operation time. Data were pooled as mean difference (MD) and odds ratio (OR). RESULTS A total of 11 RCTs consisting of 627 samples from the treatment group and 615 samples from the placebo group were analyzed. Patients that received dutasteride had less reduction in Hb levels (MD -1.10, 95% confidence interval [CI] -1.39 to -0.81, p<0.00001). Dutasteride also significantly reduced the operation time (MD -1.79, 95% CI -2.97 to -0.61, p=0.003) and transfusion rate after surgery (OR 0.34, 95% CI 0.15 to 0.77, p=0.009) compared to the control group. However, the MVD (MD -3.60, 95% CI -8.04 to 0.84, p=0.11) and perioperative blood loss in dutasteride administration for less than 4 weeks (MD 46.90, 95% CI -144.60 to 238.41, p=0.63) and more than 4 weeks (MD -190.13, 95% CI -378.05 to -2.21, p=0.05) differences were insignificant. CONCLUSION Preoperative administration of dutasteride is able to reduce bleeding during TURP, as indicated by less reduction in Hb level, lower transfusion rate, and less operation time.
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2.
Effect of preoperative finasteride on perioperative blood loss during transurethral resection of the prostate and on microvessel density in patients with benign prostatic hyperplasia: An open label randomized controlled trial
Dutt UK, Kumar S, Dorairajan LN, Badhe BA, Manikandan R, Singh S
Urology annals. 2021;13(3):199-204
Abstract
OBJECTIVE Transurethral resection of the prostate (TURP) is a common procedure for the treatment of benign prostatic hyperplasia (BPH). Previous studies on the effect of 5-alpha reductase inhibitors on perioperative blood loss in TURP and microvessel density (MVD) in the prostate are equivocal. We evaluated whether pretreatment with finasteride for 2 weeks before surgery can reduce perioperative blood loss in TURP and MVD in the prostate. MATERIALS AND METHODS Sixty-eight patients of BPH planned for TURP were randomized into two groups. The study group comprising 34 patients was treated with finasteride (5 mg/day) for 2 weeks and the placebo group comprising 34 patients received placebo for 2 weeks, before TURP. Blood loss was measured in terms of a reduction in the blood hemoglobin (Hb) and hematocrit (HCT) levels between preoperative values and 24 h after surgery. MVD was measured in the resected prostate tissue stained with anti-CD31 monoclonal antibody. RESULTS The reduction of Hb and HCT in the finasteride group was significantly lower than the reduction in the placebo group (P < 0.05). The artery (P = 0.005), vein (P = 0.05), and gland (P = 0.008) densities were significantly less in the finasteride group than in the placebo group. There was no significant correlation between blood loss and MVD. CONCLUSIONS Our study suggests a clear advantage of the preoperative use of finasteride for 2 weeks by reducing the perioperative blood loss in TURP in patients with BPH. While there is a significant reduction in MVD in the prostate on treatment with finasteride, it is not clear that this is the mechanism of reduction in blood loss in TURP.
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3.
Surgical blood loss during holmium laser enucleation of the prostate (HoLEP) is not affected by short-term pretreatment with dutasteride: a double-blind placebo-controlled trial on prostate vascularity
Busetto GM, Del Giudice F, Maggi M, Antonini G, D'Agostino D, Romagnoli D, Del Rosso A, Giampaoli M, Corsi P, Palmer K, et al
Aging (Albany NY). 2020;12
Abstract
Five alpha-reductase inhibitors (5ARIs) are able to reduce prostate volume and are a useful treatment for reducing perioperative bleeding during prostate surgery. Holmium laser enucleation of the prostate (HoLEP) is an effective surgical technique for the definitive cure of benign prostate enlargement.We investigated whether pretreatment with dutasteride before HoLEP could reduce intraoperative bleeding. A total of 402 patients were included in this double-blind placebo-controlled trial to receive daily 0.5 mg of dutasteride or placebo over 8 weeks before HoLEP. Vascular endothelial growth factor (VEGF) and microvascular density (MVD) were evaluated. Analysis was also stratified according to prostate volume (<70 mL vs ≥70 mL).Hemoglobin and hematocrit values before and after surgery were not statistically different between the two groups. MVD and VEGF index in smaller prostates were 23.35+/-1.96 and 4.06+/-0.76 in the treatment group and 19.04+/-0.96 and 2.55+/-0.55 in placebo (p<0.05); in patients with larger prostates MVD and VEGF were 26.83+/-2.812 and 8.54+/-1.18 in the treatment group and 20.76+/-0.79 and 3.21+/-0.54 in placebo (p<0.05).Vascularization of the prostate was affected by 5ARIs therapy. HoLEP is less burdened in perioperative bleeding and for this reason we did not find any difference in hemoglobin/hematocrit values pre- and post- surgery.
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4.
Holmium laser enucleation of the prostate in benign prostate hyperplasia patients with or without oral antithrombotic drugs: a meta-analysis
Zheng, X., Peng, L., Cao, D., Han, X., Xu, H., Yang, L., Ai, J., Wei, Q.
International Urology and Nephrology. 2019;51(12):2127-2136
Abstract
BACKGROUND The continuous intake of antithrombotic drugs during holmium laser enucleation of the prostate (HoLEP) remains nonconsensual. We aim to pool those controversial evidence and provide practical guidance of oral antithrombotics on HoLEP for benign prostate hyperplasia (BPH). METHOD PubMed, Embase and CENTRAL database were systematically searched up to June 2019 for trials on patients with and without oral antithrombotics undergoing HoLEP. Number of events and mean value with standard deviation were, respectively, extracted for dichotomous and continuous parameters. Subgroup analyses of anticoagulation and antiplatelet were also performed. All statistical analyses were conducted with Review Manager v.5.3 software. Newcastle-Ottawa Scale (NOS) was used to assess the quality of selected trials. RESULT Nine studies with 5528 patients were eventually selected, and patients included were generally older than 65 years. It revealed that the non-antithrombotic group had a lower rate of blood transfusion (OR 0.21, 95% CI 0.10-0.45, P < 0.0001), bladder tamponade (OR 0.30, 95% CI 0.13-0.69, P = 0.004) and acute urine retention (OR 0.52, 95% CI 0.30-0.89, P = 0.02). Operation time was also shorter (MD - 10.31, 95% CI - 12.76 to - 7.85, P < 0.00001) in the non-antithrombotic group, but the heterogeneity was considerable (I(2) = 75%). Subgroup analyses were generally consistent with the primary analysis except the non-anticoagulation and anticoagulation group having similar operation time (MD 6.66, 95% CI - 7.15 to 20.48, P = 0.34). CONCLUSION The current study confirmed that continuous intake of antithrombotic drugs could significantly increase the risk of bleeding and blood transfusion, bladder tamponade and acute urine retention.
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5.
Transurethral resection of prostate and bleeding: a prospective randomized, double blind, placebo controlled trial to see efficacy of short term use of Finasteride and Dutasteride on operative blood loss and prostatic micro-vessel density
Bansal A, Arora A
Journal of Endourology. 2017
Abstract
OBJECTIVE To evaluate the effects of short term use of finasteride and dutasteride on the amount of intraoperative blood loss and microvessel density (MVD) of prostatic stromal and suburethral tissues in the patients with benign prostatic hyperplasia (BPH) prior to transurethral resection of prostate (TURP). METHODS The study involved 450 male patients who planned to have TURP and were prospectively randomized into 3 groups (150 patients each). Group 1 received placebo, group 2 received finasteride 5 mg/day and group 3 received dutasteride 0.5 mg/day for 4 weeks before the operation. The total blood loss, requirement of blood, and prostatic stromal and suburethral tissues MVDs were recorded for each patient and compared among the 3 groups. RESULTS There were significantly less mean blood loss, blood loss/time, total blood loss/weight of resected tissue in the finasteride and dutasteride group than in the placebo group. Prostatic and suburethral MVDs were significantly greater in the placebo group. Blood transfusion was required in 9.3%, 2.7%, and 2% of the patients, respectively (p=0.004). However, no significant statistical differences were found between the finasteride and dutasteride groups for any of these variables (p >0.05). The mean operating time, weight of resected prostate tissue group, and the amount of irrigation fluid showed no significant differences among the 3 groups. CONCLUSION Short-term pretreatment with finasteride and dutasteride has similar efficacy and significantly reduces perioperative bleeding during TURP and has minimal negative impact on sexual function. According to our findings, a 4 weeks' prior administration of 5-ARIs may reduce operative blood loss and prostatic MVD in TURP, thus potentially decreasing blood loss- related complications and the requirement of blood transfusion.
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Effect of Preoperative Finasteride on the Volume or Length Density of Prostate Vessels, Intraoperative, Postoperative Blood Loss during and after Monopolar Transurethral Resection of Prostate: A Dose Escalation Randomized Clinical Trial Using Stereolog Methods
Aminsharifi, A., Salehi, A., Noorafshan, A., Aminsharifi, A., Alnajar, K.
Urology Journal. 2016;13(1):2562-8
Abstract
PURPOSE To evaluate the effects of two preoperative treatment courses with Finasteride on intraoperative and postoperative bleeding complications and prostate blood vessel characteristics in men who underwent transurethral resection of prostate (TURP) using monopolar energy. MATERIALS AND METHODS Men scheduled for TURP were randomized into group 1 (control n = 25, no medication), group 2 and 3 (n = 20 in each, 5 mg Finasteride daily for 2 and 4 weeks before TURP; respectively). Hematocrit level in the irrigation fluid, weight of the resected prostate chips, decreases in blood hemoglobin (Hb) level 6 and 24 hours after the operation together with volume and length density of prostate vessels using stereological methods were compared. RESULTS The three groups were matched regarding preoperative demographic data, resection time and weight of the resected tissue. Men who received preoperative Finasteride (groups 2 and 3) had significantly lower hematocrit levels in irrigation fluid than control group (control, 0.59 ± 0.85, group 2, 0.25 ± 0.4, group 3, 0.175 ± 0.16; P = .028; Power = .80). However, no statistically significant difference was found in hematocrit level in irrigation fluid between groups 2 and 3 (0.25 ± 0.4 vs. 0.175 ± 0.16, 95% confidence interval (CI) = -0.28-0.42; P = .68). These values were independent of the weight of the resected tissue and resection time. There were no significant differences between the three groups in the decrease in Hb 6 hours (P = .58) and 24 hours after TURP (P = .65). The stereological and histological characteristics of blood vessels in suburethral prostate tissue were similar in all three groups. CONCLUSION A 2-week preoperative course of daily Finasteride seems sufficient to significantly reduce intraoperative blood loss; this effect was independent of the weight of the resected tissue and resection time. Neither the 2-week nor the 4-week presurgical Finasteride regimen could significantly decrease postoperative blood loss, and neither regimen induced significant changes in characteristics of prostate tissue blood vessels.
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Effects of parecoxib on analgesia benefit and blood loss following open prostatectomy: a multicentre randomized trial
Dirkmann, D., Groeben, H., Farhan, H., Stahl, D. L., Eikermann, M.
BMC anesthesiology. 2015;15:31
Abstract
BACKGROUND This multi-centre, prospective, randomized, double-blind, placebo-controlled study was designed to test the hypotheses that parecoxib improves patients' postoperative analgesia without increasing surgical blood loss following radical open prostatectomy. METHODS 105 patients (64 ± 7 years old) were randomized to receive either parecoxib or placebo with concurrent morphine patient controlled analgesia. Cumulative opioid consumption (primary objective) and the overall benefit of analgesia score (OBAS), the modified brief pain inventory short form (m-BPI-sf), the opioid-related symptom distress scale (OR-SDS), and perioperative blood loss (secondary objectives) were assessed. RESULTS In each group 48 patients received the study medication for 48 hours postoperatively. Parecoxib significantly reduced cumulative opioid consumption by 24% (43 ± 24.1 mg versus 57 ± 28 mg, mean ± SD, p=0.02), translating into improved benefit of analgesia (OBAS: 2(0/4) versus 3(1/5.25), p=0.01), pain severity (m-BPI-sf: 1(1/2) versus 2(2/3), p < 0.01) and pain interference (m-BPI-sf: 1(0/1) versus 1(1/3), p=0.001), as well as reduced opioid-related side effects (OR-SDS score: 0.3(0.075/0.51) versus 0.4(0.2/0.83), p=0.03). Blood loss was significantly higher at 24 hours following surgery in the parecoxib group (4.3 g⋅dL(-1) (3.6/4.9) versus (3.2 g⋅dL(-1) (2.4/4.95), p=0.02). CONCLUSIONS Following major abdominal surgery, parecoxib significantly improves patients' perceived analgesia. Parecoxib may however increase perioperative blood loss. Further trials are needed to evaluate the effects of selective cyclooxygenase-2 inhibitors on blood loss. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT00346268.
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Intraoperative continuous norepinephrine infusion combined with restrictive deferred hydration significantly reduces the need for blood transfusion in patients undergoing open radical cystectomy: results of a prospective randomised trial
Wuethrich PY, Studer UE, Thalmann GN, Burkhard FC
European Urology. 2014;66((2)):352-60.
Abstract
BACKGROUND Open radical cystectomy (ORC) is associated with substantial blood loss and a high incidence of perioperative blood transfusions. Strategies to reduce blood loss and blood transfusion are warranted. OBJECTIVE To determine whether continuous norepinephrine administration combined with intraoperative restrictive hydration with Ringer's maleate solution can reduce blood loss and the need for blood transfusion. DESIGN, SETTING, AND PARTICIPANTS This was a double-blind, randomised, parallel-group, single-centre trial including 166 consecutive patients undergoing ORC with urinary diversion (UD). Exclusion criteria were severe hepatic or renal dysfunction, congestive heart failure, and contraindications to epidural analgesia. INTERVENTION Patients were randomly allocated to continuous norepinephrine administration starting with 2mug/kg per hour combined with 1ml/kg per hour until the bladder was removed, then to 3ml/kg per hour of Ringer's maleate solution (norepinephrine/low-volume group) or 6ml/kg per hour of Ringer's maleate solution throughout surgery (control group). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS Intraoperative blood loss and the percentage of patients requiring blood transfusions perioperatively were assessed. Data were analysed using nonparametric statistical models. RESULTS AND LIMITATIONS Total median blood loss was 800ml (range: 300-1700) in the norepinephrine/low-volume group versus 1200ml (range: 400-2800) in the control group (p<0.0001). In the norepinephrine/low-volume group, 27 of 83 patients (33%) required an average of 1.8 U (+0.8) of packed red blood cells (PRBCs). In the control group, 50 of 83 patients (60%) required an average of 2.9 U (+2.1) of PRBCs during hospitalisation (relative risk: 0.54; 95% confidence interval [CI], 0.38-0.77; p=0.0006). The absolute reduction in transfusion rate throughout hospitalisation was 28% (95% CI, 12-45). In this study, surgery was performed by three high-volume surgeons using a standardised technique, so whether these significant results are reproducible in other centres needs to be shown. CONCLUSIONS Continuous norepinephrine administration combined with restrictive hydration significantly reduces intraoperative blood loss, the rate of blood transfusions, and the number of PRBC units required per patient undergoing ORC with UD. Copyright 2013 European Association of Urology. Published by Elsevier B.V. All rights reserved. ES 1873-7560 DI S0302-2838(13)00874-9