Percutaneous nephrolithotomy in patients with incidental encountered purulent urine at initial puncture

We are reporting the 39 patients’ outcomes who underwent percutaneous nephrolithotomy and purulent urine encountered at the initial steps of surgery. Of 873 patients who underwent PCNL, 48 had purulent fluid during the initial puncture. After excluding those at risk for infection, we studied 39 patients’ preoperative and postoperative variables-including postoperative day (POD) 1, 3, 5 fevers. In group 1, 21 patients had a nephrostomy tube placed, and PCNL was postponed. In group 2, 18 patients had successful stone removal in the first session. All surgeries were successful, with no septic events during follow-up. No significant differences in preoperative variables were found. 14% and 22% of patients in groups 1 and 2 had infected fluid (p = 0.470). Four patients in group 1 (19%) and seven patients in group 2 (38.9%) had a high fever (≥ 38 C) on POD1 (p = 0.171), and 1 (5%) in group 1 and 3 (17%) in group 2 had high fever on POD 3 (p = 0.22). No patients remained with high fever on POD5. Mild sepsis was diagnosed in 9.5% of group 1 and 16% of group 2 (p = 0.820), and hospitalization time differed significantly (p < 0.001). Stone size and operation time were correlated with postoperative fever, and prolonged hospital stays were associated with positive blood cultures and postponed procedures. PCNL with proper technique and antibiotics can lead to quicker recovery and reduced hospitalization time in selected patients with pus in their pelvicalyceal system.


Introduction
Percutaneous Nephrolithotomy (PCNL) is the first-line recommended surgical procedure for treating large and complex kidney stones [1] and has a success rate of over 90% due to improved technology and surgical skill, leading to fewer complications [2].However, Clavien > 2 complications still occur in around 9% of the cases, and postoperative sepsis is one of the most detrimental [3].It has been reported that the risk of developing fever following PCNL is 10.4-18.9% and will lead to septic shock in 0.3-4.7% of the patients, with an 80% chance of death [4,5].
Predicting which patients are at risk is paramount.In the absence of preoperative infection signs and obtaining sterile urine, proceeding PCNL with antibiotic prophylaxis and placing a nephrostomy tube or double j stent in a septic patient is the best practical approach [6] .However, despite basic precautions, there is a chance that septicemia can occur [7,8].Many studies showed further possible determining factors on postoperative septic complications such as preoperative infected urine, operation time, amount of irrigation fluid used, intra-renal hydrostatic pressure, stones culture positivity, and postoperative nephrostomy tube or a stent in place [9][10][11].
In some circumstances, however, surgeons could need second though about some patients who need to undergo PCNL and have some inexplicit risk factors, such as incidentally detected purulent fluid during surgery while having sterile urine culture and no signs of infection.This is not an uncommon condition, and growing evidence shows that not all patients with purulent fluid in the pelvicalyceal system 107 Page 2 of 7 are infected; fewer than half of the patients had organisms on purulent fluid, and proceeding with PCNL in these patients is a feasible option [5,[12][13][14][15][16].
In this situation, surgeons should take a patient-centered, balanced approach considering all possible risk factors, even if the patients have one, to avoid overtreatment when preventing possible infection complications.Nevertheless, the insufficient number of studies in these fields warrants further investigation, and we need more evidence to make a definite recommendation for clinical practice.
Since 2015, we have been performing PCNL on certain well-selected patients who unexpectedly have pus in their PCS during surgery.Therefore, we analyzed and reported our findings to contribute to the existing research in this area.

Patients and methods
We performed 873 PCNL surgeries for renal stone patients from 2015 to 2023.48 cases had purulent fluid despite no signs of infection preoperatively.We investigated these cases retrospectively with medical ethics committee approval.
Patients with complex/total staghorn stones, acute impacted UPJ stones, thick and heavy foul pus in aspirated urine, aged over 65, and uncontrolled diabetes were excluded from the study.The remaining 39 patients' documents were evaluated (Tables 1, 2).A stone-free status was defined as having less than 4 mm stones, and transfusion rates were also recorded.In 21 patients (group 1), the procedure was postponed until the collecting system became clear by placing a nephrostomy tube, and the patients were hospitalized during this time.In 18 patients (group 2), the PCNL procedures were performed in the same sitting.1 gr ceftriaxone IV was given 1 h before the operation to all patients as empirical antibiotic treatment.Routine PCNL informed consent was taken before the operation from the patients; however, after the process, all patients were fully informed about the procedures they had been undertaking.All aspirated purulent fluid samples were sent to the laboratory for culture, and the anesthesia team was informed about the possibility of a septic state.Groups were formed by randomly selecting patients.
All operations were performed under general anesthesia and in a prone position following a 6 French open-ended ureteral catheter insertion into the collecting system in the lithotomy position.Percutaneous renal accesses were performed by the same surgeon with an 18-gauge puncture needle under fluoroscopy guidance into the desired calyx.In the PCNL continued group, all fluid is drained out after 30 f Amplatz sheath placement, and the collecting system is gently irrigated directly under low pressure without a nephoscope.The height of the irrigation bags is set at 2 feet above the level of the kidney to ensure working under lower pressure.The stones were fragmented by a pneumatic lithotripter and extracted by forceps.If there are limitations to the irrigation flow around the nephroscope, like renal tissue collapse or incomplete placement of the nephroscopy sheath in the collecting system, efforts were made to adjust the sheath position to ensure the sheath tip was entirely within the collecting system.All operations were completed under low pressure throughout the procedure.After the process, a 14 f nephrostomy tube was placed for all the patients.Plain X-ray and ultrasound were the preferred method for determining residual stones within the hospitalization time to determine stone-free status.Postoperative nephrostomy tubes were removed when there was no blood or pus in the drainage of both groups and removal times were similar in both groups [2-4 days].
Postoperative vitals were closely monitored and recorded eight times a day.Fevers (> 38 C) occurred in the first 24 h after the PCNL was defined as a POD1 fever.Empirical antibiotic treatment was changed to meropenem 1 gr 3 × 1 IV for the patients who had experienced POD1 fever, and blood and urine samples were drawn for these patients, and the treatments continued until three symptom-free days were achieved.According to the drug sensitivity test results, the treatment was changed if necessary.POD1, 3, 5 fevers and the CRP and WBC levels were also analyzed.Postoperative nephrostomy urine samples were only taken from the patients who had a positive aspirated fluid culture in group 1 before the PCNL procedure.

Statistical analyses
Data were analyzed using IBM SPSS statistic date editor (Statistical Package for the Social Sciences, version 21.0, SPSS Inc, and Chicago, Ill, USA).The Kolmogorov-Smirnov and Shapiro-Wilks test to compare the two groups, the student t-test, the Mann-Whitney U test, and the proportions Z tests were used to evaluate normality.Also, the linear regression model was performed to evaluate the factors affecting the duration of hospital stay and POD high fever.P values less than 0.05 were regarded as significant.

Results
All patients' preoperative urine culture results were negative.There were 25 men (64%) and 14 women (36%) in the study.There were no statistical differences in preoperative variables between the groups (p > .05).The mean operation time was 54.1 min for Group 1 and 53.3 min for Group 2 (Table 1).A stone-free status was 86% in Group 1 and 94% in Group 2. Blood transfusion was required in 2 and 1 patients in groups 1 and 2, respectively.PCS aspirates were only positive in 5 samples in total (17%); two E coli, one Proteus mirabilis in group 1(14%), three E coli, and one for Klebsiella in group 2 (22%) (p = 0.470) (Table 2).Among the 11 blood cultures samples taken from feverish patients, two were positive in group 1 and three in group 2; the predominantly grown organism was ESBL + E Coli in three samples and K pneumonia in one.There was inconsistency between blood and aspirate culture positivity, as only 1 out of 5 blood culture-positive patients had positive aspirate culture; for others, aspirate cultures were negative.Postoperative Urine cultures were only positive in 4 out of 5 blood culture-positive patients, and grown organisms were the same.Postoperative nephrostomy urine samples were taken from the positive aspirate, and all samples returned negative after three days of targeted antibiotic treatment.
Although there were initial statistical differences in fevers between the groups on POD 1 (p = 0171) and POD3 (p = 0.01), these differences were no longer present by POD 5 after appropriate management (p = 0.4).Patients in groups 1 and 2 had high fevers on POD1 (19% and 38.9%, respectively) and POD3 (5% and 17%, respectively).However, by POD5, no patients had a high fever.The difference in fever rates between the two groups was insignificant on either day.
According to clinical and laboratory findings, two patients in group 1 (9,5%) and 3 in group 2 (16%) were diagnosed with SIRS and mild sepsis on POD1 (p = 0.82).No patients developed severe sepsis and required intensive care unit transfer during the hospital stay.Of the five patients who developed mild sepsis in POD1, three had an operation time of ≥ 65 min, while the mean operation time was 53.7 min in the study, three had a stone size of 35 mm, and two had 22 and 26 m.However, linear regression models of pre and perioperative factors did not provide sufficient predictive power on sepsis.
There was a statistical difference between the two groups regarding hospitalization time (p < 0.001).The mean length of hospital stay was 9.1 days for Group 1 and 6.8 days for Group 2. One patient in group 2 needed a prolonged hospital stay (18 days) due to antibiotic changes (meropenem to amikacin).In group 1, nephrostomy tube clearance times were 2-7 days before the PCNL operation.

Discussion
Aspirating purulent fluid during PCNL surgery in asymptomatic patients raises concern for the risk of post-PCNL infection.The preferred method is to stop the procedure, drain pus via a nephrostomy tube, complete a course of antibiotics, and resume the operation [18].On the other hand, studies have challenged the practice of stopping PCNL for patients with purulent fluid in the PCS, since not all are infected and fewer than half have organisms on the fluid.Continuing PCNL may be an option [5,[12][13][14][15][16].
In this circumstance, categorizing patients based on their post-PCNL infection risk level as outlined in the literature can help understand the balance between over-treatment and infection risk.
Hosseini et al. [15] found no significant differences in infectious complication rates between patients with immediate or delayed PCNL, with 45 patients included.Huang et al. demonstrated that one-stage mini PCNL using by suction lithotripsy sheat for calculous pyonephrosis reduced the length of hospital stay and treatment costs while ensuring patient safety [16].A study conducted by Etemadian et al. [13], found no significant difference in postoperative fever rates between immediate and delayed PCNL in patients whose purulent urine was aspirated from the renal pelvis.Hospitalization duration was correlated with postoperative positive blood and urine cultures and fever.According to a study by Aron et al. [12] delaying PCNL did not affect sepsis incidence and risk factors for sepsis include recent febrile UTI, mild WBC elevation, thick pus, single tube/ tract, delayed second tract insertion, and operating time over 90 min., irrespective of the option chosen.Similarly, We did not find significant differences (p = 0.171) between the groups regarding POD1 fever ≥ 38 and sepsis and postoperative blood culture positivity (p < 0.001) and delayed procedure (group 1) (p < 0.001) were the main factors on longer hospitalization time.
A positive urine culture is the established risk factor for post-PCNL sepsis.[1,2,9,[19][20][21][22]. Patients with sterile urine culture have a lower chance of developing postoperative fever (17%) compared to those with preoperative bacteriuria (50%), according to a study by Gonen et al. [21].Bacteriuria in bladder urine culture predicts postoperative fever over 38.5 °C, according to CROES data analyzed through univariate and multivariate methods [2].On the other hand, the bacterial condition of the renal pelvis is another extensively researched preoperative risk factor [18,20].Based on this evidence, we studied patients with clear preoperative urine cultures; all obtained PCS urine samples were analyzed, and a prophylactic antibiotic was administered accordingly.
In our study, five out of 39 urine samples from the renal pelvis showed positive results for bacteria.Only one patient in the PCNL group experienced sepsis on the first postoperative day.Four out of the five patients with sepsis had negative renal pelvis cultures.Our study found gram-negative bacteria, including ESBL + E Coli and K pneumonia, to be the leading cause of sepsis, while Margel et al. [20] found Gram-positive organisms as the leading cause in patients with negative preoperative cultures.
In the study of Rivera et al. [3] staghorn calculi remained significantly associated with fever/SIRS/sepsis (OR 3.41; p = 0.01), and Gutierrez et al. showed that [22] staghorn calculus, preoperative nephrostomy, lower patient age, and diabetes all increased the risk of postoperative fever.In the case of significant stones borden, some authors recommend multiple tract placements to drain all pus from PKS obstructed by large stones [12].To prioritize patient safety, we excluded those with uncontrolled diabetes and staghorn calculus.We used debulking stone techniques to drain hole PKS, reducing tissue damage and septic event risk in cases with large stones instead of multiple tract.Our study reveals that patients with high fever have larger stones on average (33.4 mm) than those with normal fever (25.4 mm).Previous studies have supported this connection, recommending preventive measures for this group [9].
Prolonged operation time may increase the risk of septic shock.Wang and Chen's studies reveal that post-PCNL SIRS patients experienced longer operative times, with over 90 and 132 min, respectively [23,24].The risk of postoperative fever can be decreased if the critical values of 102 min and 23 L are not exceeded [25].Accordingly, we found that patients with high POD fever took 67.73 min for procedures, while for others it was 48.25 min on average.
Various studies have linked postoperative sepsis to intrapelvic pressure during PCNL.According to the study of Zhong et al. [26] patients whose intrapelvic pressure of 30 mmHg or higher for over 30 s were more prone to have a postoperative fever According to a study by Traxel et al. using a 30Fr nephroscope sheath is usually sufficient for maintaining adequate irrigation drainage and keeping the intrapelvic pressure below 20 mm and keeping the sheath to the collecting system can significantly decrease intrapelvic pressure when pressure increases [27].Recently, the use of suction in percutaneous nephrolithotomy (PCNL) has sparked interest in the one-stage management of infected kidneys through this approach [16].We kept the pressure low using the mentioned techniques, even though we could not measure the intrapelvic pressure.In this concept, it can be advised to perform surgery in a supine position, and a larger nephrostomy tube can be placed postoperatively to make the drainage easier.
It was found that fewer than half of the patients had organisms present in their kidney pus cultures [12,13].This suggests that antibiotics may have effectively sterilized the area or that there was sterile inflammation due to crystalline or amorphous calculi debris.In our series, we found similar results.17% of the pus collected from the kidney was positive, and only one out of five sepsis patients had positive aspirate cultures.
Despite limitations like a small sample size and a retrospective design, our findings can still be valuable for current research.However, conducting extensive prospective studies with larger sample sizes is necessary to make a clinical decision.

Conclusions
Without well-designed prospective clinical trials, surgeons likely postpone PCNL surgery when encountering incidental purulent fluid during the initial access.However, if they proceed for any reason, selecting appropriate patients based on the potential risk factors and working under low pressure along with full antibiotic coverage is highly recommended.Patients may experience a shorter hospital stay and quicker recovery from their stones using this approach.

Table 1
Preoperative and postoperative information of the patients BMI body mass index, CRP Serum C-reactive protein, WBC white blood cells, Hb Hemoglobin

Table 2
Postoperative variables of the patients PCNL Percutaneous nephrolithotripsy, POD Postoperative day, CRP Serum C-reactive protein, WBC white blood cells, Hb Hemoglobulin

Table 3
Linear regression model for prediction of hospitalization time (R 2 = 0.542)