Blood loss predictive factors and transfusion practice during percutaneous nephrolithotomy of kidney stones: a prospective study

Objectives Bleeding is the most common complication of percutaneous nephrolithotomy (PCNL). Injudicious transfusion is frequently performed in current practice, even though it is not always needed. This study aimed to identify the predictive factors of blood loss in the PCNL procedure and evaluate the perioperative transfusion practice. Methods A prospective study of PCNL was randomly performed by two consultants of endo-urology at our institution. The inclusion criteria were adults with kidney pelvic stones >20 mm or stone in inferior calyx >10 mm or staghorn stone. Those with coagulopathy, under anti-coagulant treatment or open conversion were excluded. A full blood count was taken at baseline and during 12, 24, 36, 72-hours post-operatively. Factors such as stone burden, sex, body surface area, shifting of hematocrit level and amount of blood transfused were analyzed statistically using line regression to identify the predictive factors of total blood loss (TBL). Results Eighty-five patients were enrolled in this study. Mean TBL was 560.92 ± 428.43 mL for both endo-urology surgeons. Stone burden was the most influential factor for TBL (p=0.037). Our results revealed that TBL (mL) = -153.379 + 0.229 × stone burden (mm2) + 0.203 x baseline serum hematocrit (%); thus considerably predicted the need for blood transfusion. A total of 87.1% patients did not receive perioperative transfusion, 3.5% received intra-operative transfusion, 7.1% received post-operative transfusion, 23% had both intra and post-operative transfusion, resulting in a cross-matched transfusion ratio of 7.72. Mean perioperative blood transfused was 356.00 ± 145.88 mL.

Kidney stones prove to be a common affliction in many countries worldwide because of high incidence and prevalence. In America, kidney stone incidence was found in 116 out of 100,000 individuals 1 . A higher incidence was discovered in the German population aged 14 years and older, amounting to 720 out of 100,000 individuals 2 . An excessively high number of cases was found in Asian countries, namely, 114.3 per 100,000 in Japan, while Iranian urolithiasis incidence was assessed at 145.1 in 2005 3 . A global increase in kidney stone cases was determined in individuals of all ages, sex, and races 4 . In our institution we have, to date, treated an increasing number of kidney stone patients, from 182 in 1997 to 847 in 2002 5 .
Percutaneous nephrolithotomy (PCNL) is a urological minimallyinvasive procedure to extract kidney stones by means of percutaneous access 6 . Nowadays, PCNL is widely accepted to treat those complex kidney stone cases that are hard in consistency, of a large size, infected, obstructed with anatomical abnormalities, generally cases that could not be treated by other modalities 7 . In European guidelines, PCNL is favoured as the treatment of choice for calyx and pelvic stones >20 mm 28 . For stones >20 mm, PCNL demonstrated a stone-free rate up to 78-95% 9 . There has been a decrease in open surgery number in our institution during 2001-2009, whereby the PCNL procedure has become more frequent 10 .
One of the most bothersome complications of PCNL is hemorrhage. Direct access to the pelvicalyceal system and intrarenal manipulation during PCNL procedures cause injury to the renal vasculature, particularly to the segmental and interlobar arteries. The renalcollecting system is rich in vascularization, covering 20% of the total cardiac output, and often results in hemorrhage during PCNL 11 . The high percentage of blood loss and the necessity of transfusion often results in the erroneous management of hemorrhage during the PCNL procedure.
It has been reported that 1-11% of patients who underwent PCNL required blood transfusion; a higher transfusion rate, 2-53% was determined in the staghorn cases 11 . Previous studies describe many hemorrhage risk factors during PCNL, such as, age 12 , pre-operative urinary tract infections 12 , large stones (exceeding 1250 mm 2 ) 13 , staghorn calculi 13,14 , multiple access 11,13,14 , diabetes mellitus 11,13,15 , prolonged surgery time 11-13 and stone composition 13 . Other risk factors have been postulated: i.e. stone location, pre-operative hemoglobin, hydronephrosis grade, renal parenchymal thickness, however, to date, have not yet been proven. Many of the hemorrhage cases during PCNL could be managed conservatively, however, 0.8% patients required a more invasive procedure to deal with the bleeding 14 .
To date there are no specific data available to determine the blood transfusion requirement during PCNL procedures. In our institution, blood units are requested pre-operatively according to clinical estimation. However, this does not always concede to the intra-operative blood loss. This study was aimed at predicting the amount of blood loss during PCNL by identifying the pre-operative factors that could possibly lead to a lower morbidity rate.

Materials and methods
The present study includes patients who underwent percutaneous nephrolithotomy procedure in our hospital from October 2012 to October 2013. Adult patients (≥18 years old) with pelvic stones >20 mm, inferior calyx stones >10 mm or staghorn stones who agreed to enroll by written informed consent were included in this study. Those with coagulopathy, under anti-coagulant treatment or conversion to open procedure were excluded.
Patients were admitted the day prior to procedure. Stone burden was assessed pre-operatively by multiplying sum of length and width by means of imaging. The PCNL was randomly performed under spinal anesthesia by two endo-urology consultants. The patient was placed in prone position, access gained to pelvicalyceal system with fluoroscopic guidance, followed by dilatation using a metal and fascia dilator before application of sheath. The number and location of punctures were decided intra-operatively, based on pelvicalyceal system. We used pneumatic lithotripsy to break the stone which was subsequently extracted by forceps or grasper. The procedure was completed when the patient was stone-free and any arising complications alleviated.
Full blood counts were taken prior to procedure and thereafter at 12, 24, 36, 72-hours post-operatively. Total blood loss was calculated considering body surface area, sex-adjusted estimated blood volume, initial hematocrit level and 72-hour post-operative hematocrit level. Study protocol has been approved by the Ethical Committee, Faculty of Medicine, Universitas Indonesia (No.89/ H2.F1/ETIK/2013).
We compiled a chart 15,16 to assess total blood loss (TBL) to include sex, body surface area, shifting of hematocrit level and amount of blood transfused, as shown in Table 1.
Bivariate analysis was done by correlating numerical variables with total blood loss, and associating categorical variables with perioperative blood transfusion amount. Those with significancy of <0.25 were further analyzed with multivariate analysis of linier and logistic regression.

Results
A total of 85 PCNL procedures were performed on 85 patients (46 males, 39 females) who completed this study, thus gave statistical power of 0.8. The average age was 50.96 ± 11.87 years. Most of the patients complained of flank pain at initial presentation ( Table 2). Staghorn calculi were found in 50.6% patients.
The mean hematocrit drop was 5.20 ± 3.36%. Average total blood loss was 560.92 ± 428.43 mL with median 511.46 (95% CI: 0.00-1974.84) mL. There were two cases with pelvicalyceal laceration, one with massive hemorrhage (perioperative blood loss 1974.84 mL). There was no significant difference of total blood loss between the cases performed by the two PCNL surgeons (p>0.05).
Stepwise multivariate regression analysis which included variables with p-value < 0.25 (Table 3) showed that stone burden was the Defined as blood volume transfused deficit less than 15.0% of total blood loss (mL) Over-transfusion 18 Defined as blood volume transfused excess greater than 15.0% of total blood loss (mL) Abbreviations: RBC = red blood cell, BW = body weight most influential predictor of blood loss (p=0.037). Meanwhile operative time was found not associated (p-value >0.05) with blood loss. We assessed total blood loss (in mL) as -153.379 + 0.229 × stone burden (mm 2 ) + 0.203 × serum hematocrit baseline (%). This means it is predicted that a kidney stone patient with 1000 mm 2 stone burden and baseline hematocrit 40% will have 83.74 mL blood loss during PCNL procedure perioperative.
The average amount of blood units 435.29 ± 114.13 mL was crossmatched for each procedure pre-operatively (Table 4). Nevertheless, 87.1% of patients did not receive blood transfusion perioperatively, thus yielding the blood transfusion rate as 12.9%. Blood transfusion was required by 3.5% patients intra-operatively, 7.1% postoperatively and 2.3% both intra and post-operatively. In total, the cross-matched transfusion ratio was 7.72. The average amount of blood transfused during PCNL procedure: 356.00 ± 145.88 mL. The raw data of the bivariate analysis between related factors and total blood loss are provided. The raw data for 'Blood transfusion practice' are provided.

Discussion
In this study we did not use conventional, visual estimated blood loss to determine hemorrhage due to high bias factors, subjectivity, persistence of dilution effect and poor accuracy 19-23 . Laboratory parameters in our study were recorded until 72-hours postoperatively, in order to minimize intravenous hydration and retroperitoneal fluid absorption effects. We used the hematocrit level as the main parameter to determine blood loss rather than hemoglobin to avoid hemodilution effect 15,24 ; Furthermore, the hematocrit level positively correlated with the total blood volume 25 . It has been reported that also a center in Turkey applies a blood transfusion policy that depends on the hematocrit level (transfusion was indicated when hematocrit level was less than 30%) 14 .
Stone burden was the most influential predictive factor for blood loss during the PCNL procedure in this study, similar to other studies performed. A multivariate analysis showed that complete and partial staghorn calculi were associated with a greater blood loss than with the calyx stones 14 . Other studies concluded that larger stone burdens 11 or staghorn calculi 26 required a greater amount of unit blood transfused during the PCNL procedure compared to the smaller stones. Greater hematocrit level changes in staghorn calculi were found during PCNL, while further multivariate tests concluded that staghorn calculi were associated with a greater amount of blood loss (OR 1.92) and a greater decrease in the hemoglobin level compared to non-staghorn cases 13 . Prolonged and excessive intra-renal maneuver performed for large stone burdens was assumed to increase incidence of injury to renal vasculature 11 .
Our transfusion rate was similar to the one reported in a retrospective study from Pakistan showing an overall blood transfusion rate of 14.2% with one angioembolization performed to control hemorrhage 26 . In our study, all cases presenting with massive hemorrhage could be managed conservatively. Lower blood transfusion rates were reported in two other studies from Pakistan, one study from United Kingdom and one study from the United States; these differences occurred due to the younger age group 27 , supine position used 28 and balloon dilatation 29,30 . A higher transfusion rate (23.8%) compared to our result was shown in a retrospective analysis. An aggressive approach by torqueing the rigid nephroscope to maximize stone clearance at one stage was explained. 14 A precise estimation of surgical blood loss is essential in order to avoid excessive usage of blood units. Most of the previous studies emphasize the estimated blood loss rather than the objective prediction. Our calculation of total blood loss included perioperative factors: the patient's blood volume (based on sex, body weight and height), the number of red cell units transfused, the hematocrit changes, and the amount of hemodilution. To our knowledge, this is the first study that has applied a mathematical approach to predict blood loss during PCNL procedures. We did not include hydronephrosis grading, parenchymal thickness and stone composition to analyze the predictive factors of blood loss, due to the possible limitations relating to our study.

Conclusions
Stone burden was the most influential PCNL blood loss predictive factor in our institution. We estimated that the amount of blood requested and cross-matched for PCNL is much greater than the actual blood loss. Our principle was proposed as a guidance to reduce any unnecessary costs and excessive requirements of blood units.

Consent
Written informed consent to participate in the study and publish clinical data was obtained by the patients.

Data availability
F1000Research: Dataset 1. Raw data for

Competing interests
No competing interests were disclosed.

Grant information
Cipto Mangunkusumo Hospital Operational Research Grant 2013 funded this research.
The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
underestimates calculated blood loss during radical retropubic prostatectomy.

Introduction
No specific comments.

Material and Methods
Were all patients included in this study consecutively? How was stone burden assessed by means of imaging? Was it measured from CT-scan, plain film, or IVP? How was a hematocrit level measured? Was it from a full blood draw or just fingertip needle sticks crude measurement? What was an algorithm of decision for perioperative blood transfusion in this study? Did the authors make a judgement based on a "specific" cutoff point of the most recent blood count (at 12, 24, 36, and 72 hours after PCNL) or make a decision subjectively? There should be a systematic methodology in this issue because it significantly affected transfusion rate and volume.

Results
How many patients were excluded from this study because of a conversion to open procedure? Were they converted from profound intraoperative bleeding? What were a mean BMI of patients, and distribution of hydronephrosis in this series? The authors have mentioned in the Introduction that they were risk factors for blood transfusion flowing PCNL.
What was a distribution of renal access (upper/middle/lower/multi-tract) in this study? Did number of renal access tract affect blood loss or transfusion rate? In a multivariate analysis of variables and blood loss, was stone burden (p = 0.037) the only one factor that remained statistically significant? This data was not shown in Table 3. What were other variables included in the multivariate analysis and why did the authors include operative time (p > 0.05) in this model?

Discussion
The authors mentioned a hematocrit cut-point of 30% from a Turkish study. Did the authors use the same cut-point for transfusion in this study? Transfusion rate in this series was relatively high (12.9%) and the authors have demonstrated a significant correlation between stone burden and blood loss. Could this high transfusion rate cause by a larger stone burden? This data (mean stone burden) was not shown in the manuscript. What is a clinical benefit of the mathematical equation to predict blood loss preoperatively? Could we use it to obviate blood request in some patients?

Miscellaneous
In Table 2, it may be more understandable to order presenting symptoms by percentages. In Dataset 1, why did the authors perform PCNL in some stones of 5 mm size. Is it more reasonable to treat them with ESWL or flexible ureteroscopy.
I have read this submission. I believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above.
No competing interests were disclosed. Competing Interests: 30