Bleeding and bleeding-related complications remain common after bipolar transurethral resection of the prostate (TURP) for benign prostatic hyperplasia. This may possibly lead to prolonged postoperative irrigation, catheterisation and hospital stay. The objective of this trial was to evaluate the effect of high-dose tranexamic acid (TXA) on perioperative blood loss in patients treated with bipolar TURP for prostate sizes between 30 and 80 grams.

We conducted a single-center, prospective, double-blind randomised controlled trial. 80 patients were screened for inclusion between March 2020 and January 2023. After exclusion, 65 patients were randomised in two comparable groups. The TXA group (31 patients) received a TXA intravenous loading dose of 10 mg/kg over 30 minutes before induction, followed by a maintenance dose of 5 mg/kg/h over 12 hours. The placebo group (34 patients) received an equal dose of saline infusion. We measured age, weight, preoperative prostate size, anticoagulant use, 5-alpha reductase inhibitor use, preoperative urinary tract infection, American Society of Anesthesiologists (ASA)-score, difference in pre- and 24h-postoperative hemoglobin and hematocrit levels, operative time, resected adenoma weight, duration of postoperative irrigation, total amount of postoperative irrigation fluid, indwelling catheter time, duration of hospital stay, blood transfusion rate and 4-week complication rate.

Baseline characteristics are presented in table 1. The two groups were comparable regarding age, weight, prostate volume, aspirin use, 5-ARI use, preoperative urinary tract infection and ASA-score. Table 2 shows our outcome measurements. Decrease in hemoglobin level, measured as difference between 24h-postoperative and preoperative level, was statistically significant (p = 0,04) in favour of TXA group with 1 mg/dl versus 1,6 mg/dl in the placebo group. Decrease in hematocrit level was also less in the TXA group, 3,09% versus 4,5% in the placebo group. However this did not reach statistical significance. No blood transfusion was observed in both groups. TXA group showed significantly shorter duration of irrigation (24,3h versus 37,9h), less irrigation fluid (10,7l versus 18,5l), shorter catheterisation time (40,8h versus 53,7h) and shorter hospital stay (46,9h versus 59,2h). No statistically significant difference was noted regarding operative time and weight of resected adenoma. Complication rate was similar in both groups (22,6% versus 29,4%). In the TXA group, 2 cases had a postoperative clot retention due to hematuria both needing reintervention, whilst in the placebo group 4 cases suffered from a clot retention of which one needed reintervention. Three cases of the placebo group had a postoperative urinary tract infection. One case, in the TXA group, suffered from a postoperative deep venous thrombosis of the lower extremity, successfully treated with anticoagulant therapy. Severity of complications, determined by Clavien Dindo score, was not significantly different between the two groups.

BPH is the most common cause for LUTS in the aging male population. TURP remains the reference standard for surgical treatment of BPH, especially for prostate sizes between 30 and 80 grams. (1) Bleeding related complications are the most common type after TURP with an incidence of 1-7%. (2) Recent meta-analyses also found promising results for TXA use in prostate surgery but stipulated the need for more trials to establish these findings in well designed trials. (3) Our present study was designed to evaluate the clinically relevant impact of TXA use in bipolar TURP by measuring hemoglobin loss, transfusion rate, irrigation fluid, operative time, complication rate and hospital stay. We did so with a sufficient powered sample size and clinical relevant patient population with a prostate size between 30 and 80 grams. 
The primary endpoints of our trial were hemoglobin loss and transfusion rate. Regarding the first, we found that hemoglobin difference between 24h-postoperative and preoperative level was significantly less in the TXA group when compared to placebo group. Other studies in the past often estimated blood loss through hemoglobin measurement in irrigation fluid as primary endpoint. This is a less clinically relevant endpoint and sensitive for errors. In our opinion hemoglobin reduction is more reliable. No blood transfusion was carried out in our population, so no conclusion could be made regarding this endpoint. 
Indirect but relevant consequences of blood loss in the perioperative setting of TURP are duration and amount of postoperative irrigation fluid, catheterisation time and hospital stay. These parameters are the secondary endpoints of our study. We found that the duration and amount of postoperative irrigation was significantly less in the TXA group (24,4h and 10,7 L, respectively), as compared to placebo (37,9h and 18,5 L, respectively). As a result also catheterisation time (40,8h versus 53,7h) and hospital stay (46,9h versus 59,2h) were significant different and in favour of TXA use. Although secondary endpoints, these outcomes are clinically relevant, especially as earlier decatheterisation and discharge are important for patients and caregivers, not only because of patients’ satisfaction but also in its cost-effectiveness. The overall difference of more than 12 hours regarding discharge in favour of TXA use, might suggest that in a large group of patients the hospital admission could be shortened with one day, leading to a great cost saving. In our center the mean cost for TXA administration is estimated around 10 euros for the patient and 120 euros for the hospital/insurance. In comparison, the mean estimated cost for one extra admission day amounts 30 euros for the patient and 840 euros for the hospital/insurance.  
Regarding complication rate, we found no statistically significant difference between our two groups, with 22,6% and 29,4% (TXA versus placebo group). The main complication was urinary retention without hematuria in 7 patients: 4 (12,9%) versus 3 (8,8%) respectively. Urinary retention however is generally attributed to primary detrusor failure and has little to do with perioperative amount of blood loss. Clot retention on the other hand does correlate with postoperative bleeding and was also seen in our study: clot retention with (6,5% versus 2,9% respectively) or without (0% versus 8,8% respectively) the need for reintervention. 
One of the main hesitations of TXA use is the concern with the risk of thromboembolic events (TEE). Despite this concern, the literature shows that TXA use in patients undergoing major surgery does not increase the risk for TEE. 
Despite its limitation due to the monocentric design, our study is one of the first being able to make firm conclusions on the use of high dose TXA in bipolar TURP by using clinical relevant endpoints in a sufficient powered and well-designed trial.

This trial confirms the benefit of high-dose TXA in bipolar TURP in reducing perioperative hemoglobin loss, resulting in less postoperative irrigation fluid, shorter postoperative irrigation and catheterisation time and earlier discharge, without increasing the risk of TXA related TEE. No conclusions could be made on blood transfusion rates.

Gravas S., Cornu J.N., Gacci, M, Gratzke C. et al. EAU guideline: Management of Non-neurogenic Male LUTS. ISBN 978-94-92671-16-5. EAU Guidelines Office, Arnhem, the Netherlands, 2022.
Rassweiler J, Teber D, Kuntz R, Hofmann R. Complications of transurethral resection of the prostate (TURP)--incidence, management, and prevention. European urology 2006;50:969-79; discussion 80.
Longo M., Cavalheiro B., et al. Systematic review and meta-analyses of tranexamic acid use for bleeding reduction in prostate surgery. J Clin An. 48 (2018): 32-38.