Blood Loss Comparison During Transurethral Resection of Prostate and High Power GreenLight ™ Laser Therapy Using Isotopic Measure of Red Blood Cells Volume

Abstract

Background:

Transurethral resection of the prostate (TURP) remains the gold standard in the operative management of symptomatic benign prostatic hyperplasia (BPH). The main morbidity of TURP is bleeding, which leads to clot retention and blood transfusion. Newer techniques have appeared, and photovaporization of the prostate (PVP) with the GreenLight™ laser has been developed to reduce the morbidity of bladder outflow surgery. Isotopic measurements of total red cell volume and total blood volume (BV) are a recommended reference technique to evaluate bleeding occurring during endoscopic ablation of the prostate. Here, we compare blood loss during PVP and TURP using an isotopic method.

Methods:

Eighteen patients underwent PVP, and 20 patients underwent a TURP for symptomatic BPH by one surgeon. The two groups were comparable in demographic data; however, prostate volume was significantly higher in the PVP group. BV was measured pre- and postoperatively using the isotope technique.

Results:

The total BV was measured to have increased by 362 mL in PVP group compared with a loss of 315 mL in TURP group (p=0.001). The difference in total red cell volume increased by 148 mL in PVP group compared with a loss of 216 mL in TURP group (p=0.005).

Conclusions:

Using the isotope method, we have shown a significant difference in postoperative blood loss between TURP and PVP. Our study is the first to use an isotopic method to measure the blood loss during PVP. This technique needs further standardization before being introduced into routine clinical practice.

Background

T ransurethral resection of the prostate (TURP) represents the gold standard in the operative management of symptomatic benign prostatic hyperplasia (BPH). The main morbidity of TURP remains bleeding, which leads to clot retention and blood transfusion, and glycerine irrigant absorption, which can lead to TURP syndrome.¹ Photovaporization of the prostate (PVP) with the GreenLight™ laser is an effective procedure that has been developed to reduce the peri-operative morbidity of bladder outflow surgery.^2,3 PVP provides the advantages of good hemostasis, elimination of the risk of TUR syndrome due to irrigation with normal saline, and a shortened recovery time.

Traditionally, bleeding during surgery is estimated by the measurement of blood loss in drains, swabs, and suction or by comparing pre and postoperative serum hemoglobin. Measuring the blood loss during TURP is challenging, because blood is mixed with glyceine irrigation. The difference between preoperative and postoperative hemoglobin is consequently used to evaluate the bleeding occurring during endoscopic ablation of the prostate.⁴ These measurements have been criticized, and isotopic measurement of total red cells volume and total blood volume (BV) is a more precise method of evaluation and is recognized as a reference technique.^5,6 This radio isotopic method has been established for many years⁷ and is well validated with regular revisions from the International Committee for Standardization in Hematology (ICSH), describing the techniques for measurement^8
–10 and their accurate interpretation.^11,12 This method has been designated as the ICSH-selected method on the basis of its reliability, reproducibility, and ease of operation in routine clinical use. This article is the first to describe the use of this technique being in a urological setting to compare bleeding during TURP and PVP. Our hypothesis is that blood loss is significantly less in PVP than in TURP. In this study, we compared TURP with PVP in terms of blood loss by using the radio isotopic method.

Methods

Study population

Male patients requiring bladder outflow surgery, either a TURP or PVP, who had no contraindications to isotopic measurement, were enrolled consecutively in the study. None of the patients had a hematological pathology. In our center, PVP was indicated for patients with prostates larger than 70 mL or with mandatory antiplatelet treatment (aspirin or clopidogrel). Patients gave informed consent to enter the study, which had been approved by the local ethics committee.

Preoperative evaluation included medical history, American Society of Anesthesia (ASA) score, prostate-specific antigen (PSA), digital rectal examination (DRE), transrectal ultrasonography, uroflowmetry, postvoid residual urine volume evaluation, and routine blood analysis. Quality of life was estimated using a standard questionnaire.

An ASA score of 2 or less was required for enrolment. Patients with an abnormal PSA or a DRE suggesting a prostatic malignancy were excluded from the study. Patients with an indwelling catheter as a result acute urinary retention were not enrolled. Patients receiving ongoing oral anticoagulation (e.g., Warfarin) were excluded, but patients with ongoing thrombocyte aggregation inhibitors were asked not to discontinue their treatment before PVP and were eligible for the study.

PVP and TURP were performed by the same surgeon under spinal anesthesia. PVP was performed with a 120 watt GreenLight-HPS™ laser (American Medical Systems) using a technique already described through a 23F continuous flow cystoscope.¹³ Hemoglobin and hematocrit were measured by the same laboratory the day before surgery and at postoperative day 1.

Clinical outcomes were recorded after a mean period of 1 month and included maximum flow rate, postvoid residual volume, International Prostate Symptom Score (IPSS) score, and quality of life score (8th question of the IPSS).

Isotopic techniques

The red cell volume of every patient was measured the day before and 48 hours after the surgical procedure. The plasma compartment was not measured, as it is necessary to inject human serum albumin (blood product) for the labeling, thus increasing the cost and complexity of the measurement. The total mass of blood was calculated by means of the red cell volume and the hematocrit value. Ten milliliters of venous blood from each patient were withdrawn, and the red cells were labeled with a specific amount (proved the exact amount) of ⁵¹chromium (⁵¹Cr)(sodium chromate). The labeled red cells were then re-injected intravenously, and a further venous blood sample was drawn 30 minutes after injection, thus allowing for distribution of ⁵¹chromium-labeled cells throughout the circulation. The total radioactive activity in the blood sample was estimated. Venous hematocrit was corrected to obtain the somatic hematocrit. The ⁵¹Cr activities used for the labeling before and postsurgery were different (0.5 MBq preoperative and 1.9 MBq postoperative) to provide the lowest possible residual activity in the blood at the time of the second measurement. A blood sample was withdrawn, and the residual ⁵¹Cr activity was counted just before the postoperative isotope investigation. The next samples were then corrected by subtracting this value from the current level.

Statistical analysis

All data were statistically analyzed with the Fisher exact test and the Student t test and are presented as mean±standard deviation of the mean (SD). p-value of <0.05 was considered statistically significant. Statistical analysis was performed using the SPSS 10.1 software (SPSS Inc.).

Results

A total of 38 patients were enrolled in the study: 18 patients underwent PVP, and 20 patients underwent a TURP between January 2007 and April 2008 (Table 1). Patient age, quality of life score, and preoperative peak urinary flow rate were comparable between the groups. Forty-four percent of the patient in the PVP group were on aspirin or clopidrogel versus 15% in the TURP group (p=0.001). Initial IPSS score was significantly lower and the prostate volume higher in the PVP group. Clinical outcomes at a mean follow-up of 1 month are summarized in Table 2. Patients who underwent TURP generally required postoperative irrigation for 24 hour, whereas no irrigation was necessary after PVP. No patients with PVP required conversion to TURP due to technical problems. Serum electrolyte imbalance was not seen in any of the patients. All catheters were removed the first postoperative day after PVP and at day 2 or 3 for TURP. No recatheterization was necessary, and all the patients were catheter free when they left the hospital. Both groups had a significant improvement over baseline in maximum flow rate, postvoid residual urine, and IPSS. No transfusion was necessary in either of the groups. Median hospital stay was 1 day for PVP and 3 days for TURP. Mild pain during micturition appeared in 44% and 55% of patients 1 month after TURP and PVP, respectively (p=0.4). The mean energy delivered during PVP was 256,850 J, which corresponded to 5600 J/mL of tissue removed.

Table 1.

Baseline Characteristics of Patients Included in the Study

	PVP	TURP	p-value
Number of patients	18	20
Mean age (CI)	68 (12)	72 (5)	0.17
IPSS	17.1 (4.9)	21.4 (5.4)	0.037
Peak urinary flow rate (Q max), mL/s	8.9 (5.3)	9.3 (3.9)	0.81
Prostate volume, g	74.5	41.6	0.003
Aspirin or clopidogrel	8	3	0.001

p-values are significant (p<0.05).

TURP=transurethral resection of the prostate; PVP=photovaporization of the prostate; IPSS=International Prostate Symptom Score; CI=confidence interval.

Table 2.

Clinical Outcome at a Mean Outcome of 1 month

	PVP	TURP	p-value
Maximum flow rate, mL/s	10.1 (5.1)	12.3 (5.2)	0.23
Postoperative Postvoid residual volume, mL	98 (83)	102 (80)	0.88
Quality of life (Qol) score (IPSS)	4.6	4.4	0.34
Median Day at discharge [range]	1[1–3]	3[1–7]	<0.0001

p-values are significant (p<0.05).

Blood loss is summarized in Table 3. The postoperative hemoglobin was significantly lower after PVP (13.2 g/dL) than after TURP (14.3 g/dL) (p=0.003). Preoperatively isotopic measurements were not different between groups; however, post-operative total red cell volume was significantly higher after PVP than after TURP (p=0.022).

Table 3.

Blood Loss Estimated by Conventional and Isotopic Measurements

	PVP	TURP	p-value
Standard measurements
Hemoglobin preoperative, g/dL	14.3	14.7	0.414
Hemoglobin postoperative, g/dL	13.2	14.3	0.003
Isotopic measurements
Preoperative
Veinous hematocrit	43.8	42.6	0.494
Total red cell volume, mL	2092	1958	0.465
Total blood volume, mL	5177	5152	0.948
Postoperative
Veinous hematocrit	43.5	40.3	0.052
Total red cell volume	2240	1756	0.022
Total blood volume, mL	5545	4773	0.076
Difference between postoperative and preoperative
Hemoglobin	−1.02±0.84	−0.61±0.85	0.207
Total red cell	148±319	−216±322	0.005
Total blood volume	362±834	−315±545	<0.001

p-values are significant (p<0.05).

The measured total BV increased by 362 mL in the PVP group compared with a decrease of 315 mL in the TURP group (p=0.01). The measured total red cell volume increased by 148 mL in the PVP group compared with a loss of 216 mL in the TURP group (p=0.005).

Comparing total red cell volume per gram of prostate removed, 3.2 mL of red cell volume was added per gram of prostate after PVP compared with a decrease of 14.7 mL after TURP.

Discussion

Despite TURP remaining the classical technique for bladder outflow surgery, this procedure is still associated with a blood transfusion rate of 2% to 7%.¹ Surgical treatments have been developed to decrease perioperative complications. Different classes of laser have been used for surgical treatment of BPH, but initial results were disappointing.¹ Power has gradually been increased and provides more encouraging results. One randomized study confirmed that short-term functional results were similar to TURP.¹⁴ The major advantage of PVP for bladder outflow surgery is its hemostatic properties, but a few methods are available to accurately evaluate blood loss. About 120 watt laser vaporization has been performed with similar results and permitted safe procedures on larger glands.¹⁵ Monopolar TURP has been compared with bipolar TURP using the standard methods for measuring blood loss.¹⁶ This study did not show any difference in the reduction in postoperative hemoglobin between the two groups. One study showed a major difference in blood loss after TURP using the radionuclide method.^6,17 In this study, the authors assumed that blood loss during TURP was 500 mL, which is larger than previously reported amounts showing that the radionuclide method has a higher sensitivity than standard hemoglobin estimations. However, this method is slightly more expansive than standard methods (110 Euros).

Measurement of red cell mass is a well-established method that has been used for many years and has been selected by the ICSH as the reference method for estimating blood loss. The recommended techniques are standardized,⁸ easy to reproduce, and very accurate. The residual activity present before the second measurements had no influence, because this residual activity was subtracted from the activity of the other samples. The postoperative mean total BV and red cell mass in PVP group increased a little (+7%) and by a similar amount for both parameters, probably related to the operative context and blood regeneration. Blood regeneration between two samples for radionuclide measurement may explain the gain of red cell volume shown by this method. This contrasts with a postoperative decrease in the TURP group, which was moderate for total BV (−7%) and slightly higher for red cell mass (−10%), thus suggestive of increased bleeding. The other hypothesis is that spleen contractions due to the procedure may mobilize red cells which emphasize the difference between the two procedures.

Others have used different methods for measuring bleeding during TURP. Nadler and colleagues estimated BV taking into account sex, body mass, and height.¹⁸ Blood loss has been estimated using a complex formula.¹⁹ This method is not sensitive and does not take into account the variability of BV and volume substitution before and after surgery. Transfusions occurred in 2.5 per cent of patients who underwent a TURP.¹ Since transfusion is rare during PVP, transfusion rate is unsuitable for comparing blood loss during TURP or PVP. In our study, we found no difference in loss of hemoglobin or transfusion rate between groups, but blood loss was significantly higher after TURP than after PVP using the radionuclide method.

Our population was not matched, as there were larger prostates in the PVP group. PVP has been used for large prostates of greater than 70 mL in size.²⁰ In this study, short-term results were promising, even though the percentage reduction in prostate volume was significantly higher after TURP (64.1% vs. 43.3%). For PVP, one study compared small and high volume of BPH and showed a trend toward a larger hemoglobin reduction in the large prostate group.²¹ This result was not significant. Our method for evaluating blood loss could be used to compare open prostatectomy and PVP for prostates >100 mL in volume. In this study, five prostates were greater than 100 mL, and there was no difference between blood loss in patients with glands more or <100 mL as evaluated with isotopic methods (p=0.4).

Resected tissue weight is difficult to be evaluated after PVP. We compared postoperative with preoperative DRE to measure the tissue removed during PVP. Other studies have used trans-rectal ultrasound to evaluate prostatic volume after PVP and have confirmed that the prostatic volume continues to decrease for several months with a 28% tissue reduction at 6 months and 53% at 1 year.²² Chen and al showed that 50% of initial tissue had been resected at 16 weeks after TURP using ultrasound measurements.²³ Our results suggest that tissue removed during PVP was higher than after TURP, but these results need to be confirmed with comparative ultrasounds that are planned to be performed after 1 year of follow-up. Nevertheless, we delivered more energy to the prostate than previous studies that treated large prostates. Rajbabu et al. delivered 1400 J/mL of prostate but used the 80-W powered GreenLight laser.²⁴ Unfortunately, no data are available to compare with 120-W users.

The GreenLight laser is commonly used for its vaporization effect on prostate tissue. The procedure is safe and may be an effective treatment even in patients receiving anticoagulants or antiagregants.²⁵ GreenLight laser has been used for treating patients receiving thrombocyte aggregation inhibitors.^20,26 Since then, we have used this technique on patients with ongoing treatment without stopping it and have found no increase in bleeding. Our study population had a larger number of patients on thrombocyte aggregation inhibitors (aspirin or clopidogrel) in the PVP group (44%) than in the TURP group (15%). This difference emphasizes our results, as our PVP group had more risk of bleeding. Since less blood loss occurred after PVP than TURP, we can conclude that this technique is safe in these patients who are at a high risk. Additionally we did not find any difference of blood loss between patients on antiagregants and those not on antiagregants.

Our study is the first to use such a precise procedure to measure the blood loss during PVP. Although this study is not randomized, the differences should have favored TURP over PVP as the latter group's prostates were bigger and more patients had ongoing aggregation inhibitors. Our results consistently showed that more bleeding occurred after TURP than after PVP. Additionally, our study showed that hemoglobin is not so relevant to evaluate blood loss and that isotopic measurements are more sensitive.

Conclusions

PVP is an acceptable alternative to TURP for treating large prostate glands. Patients taking antiplatelet drugs (aspirin or clopidogrel) can be treated without stopping these medications by PVP. The red cell mass measurements using sodium radiochromate (Cr-51) is a reference method and may measure blood loss during surgery. This easy method is accurate and sensitive enough to be used to compare bleedings in different procedures. We have, thus, shown that patients lost more blood after TURP than after PVP. We can then hypothesize that PVP reduces per and postoperative bleeding in comparison to TURP.

Footnotes

Disclosure Statement

Dr. Franck Bruyère received speaker honoraria from American Medical Systems (AMS). The other authors did not receive any financial incentives associated with the publication of this article.

Authors' Contributions

Study concept and design: Bruyere, Valat.

Acquisition of data: Brichart, Valat, Bruyere.

Analysis and interpretation of data: Bruyere, Huglo.

Drafting of the manuscript: Bruyere, Challacombe.

Statistical analysis: Bruyere, Brichart.

Obtaining funding: None.

Administrative, technical, material support, ethical aspect: Haillot.

Supervision: Bruyere.

Abbreviations Used

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