Abstract
Purpose:
Myriad operative factors and characteristics of patients may influence the risk of infection in a patient undergoing stone surgery. We prospectively determined the risk factors for systemic inflammatory response syndrome (SIRS) and quick sequential organ failure assessment (qSOFA) in patients undergoing percutaneous nephrolithotomy (PCNL) and retrograde intrarenal surgery (RIRS).
Materials and Methods:
Patients who underwent PCNL and RIRS from March 2018 to January 2020 satisfying our selection criteria were enrolled. Samples of urine from the renal pelvis, bladder, and retrieved stones were sent for culture testing. Postoperatively patients were keenly supervised for any indications of SIRS and qSOFA. The association between stone and urine cultures across various sites was examined. Regression analysis was performed to ascertain clinical variables affiliated with SIRS and qSOFA.
Results:
The study included a total of 150 patients including both PCNL and RIRS, of which 23% post-PCNL and 20% post-RIRS met the criteria of SIRS and qSOFA. On univariate analysis in PCNL-Dilated pelvicalyceal system (PCS), renal pelvic urine culture (RPUC), stone culture (SC), and operative time >124 min among others were identified as risk factors whereas, in RIRS-residual calculus, RPUC, SC and operative time >62 min were risk factors. Multivariate analysis identified dilated PCS and SC for PCNL and only intraoperative RPUC for RIRS as independent risk factors. Only a significantly strong correlation among culture analysis was found between RPUC and SC in both the procedures.
Conclusion:
Intraoperative RPUC and SCs are better predictors of post-PCNL SIRS while Intraoperative RPUC and duration of surgery are better predictors of post-RIRS sepsis. We, therefore, recommend that both these cultures must routinely be obtained in the above procedures to identify the offending organisms and amend antibiotic therapy during treatment and surgical duration should be kept <62 min in RIRS. SIRS serves as a sensitive review tool which is specifically useful for initial care and on the contrary qSOFA is well suited for patients at greater risk of demise, thereby guiding clinicians to decide future care and course of treatment of patients.
Keywords: Infection, nephrostomy, percutaneous, quick sequential organ failure assessment, renal calculi, retrograde intrarenal surgery, systemic inflammatory response syndrome
INTRODUCTION
Percutaneous nephrolithotomy (PCNL) and retrograde intrarenal surgery (RIRS) are one of the most commonly used procedures for operative management of nephrolithiasis. Infective complications are frequent after these procedures and manifest as fever, systemic inflammatory response syndrome (SIRS), and Sepsis. Urosepsis is a potentially serious complication after PCNL and RIRS.[1] Several pathophysiological mechanisms involved in its pathogenesis have been theorized which are the bacterial aggregations on the stone that prevent complete sterilization preoperatively in spite of targeted antibiotic therapy;[2] endotoxin release while performing lithotripsy,[3] the creation of elevated intrarenal pressure contributing to pyelovenous and pyelotubular backflow, introducing bacterial infection in systemic circulation;[4,5] and the inherent renal vasculature injury caused by percutaneous access.[6] However, the exact pathophysiological mechanism of SIRS is still unknown.
An infected stone or positive urine culture may lead to severe infective complications during the endoscopic surgery. Mid-stream clean catch urine may not be a sufficient indicator for predicting the postoperative infective outcome. Hence, intuitively, it would appear that cultures obtained from renal pelvic urine culture (RPUC) and stone culture (SC) may be more helpful to guide treatment.[7] There are several studies on the role of RPUC and SC from Asian and Western countries but it has not been studied adequately in the Indian population. To further investigate this, we propose to prospectively study the factors predicting the infective complications following PCNL and RIRS and determine the association between preoperative, intraoperative, postoperative urine and SCs.
MATERIALS AND METHODS
Study design and patients
ours was a clinical, hospital-based study conducted prospectively over a duration of 2 years from March 2018 to January 2020. After approval from the Ethics Committee, all consenting patients undergoing PCNL and RIRS for renal stones during the study were enrolled in the study.
We prospectively collected the data of 100 patients for PCNL, excluding patients having infected hydronephrosis, percutaneous nephrostomy tube, any known focus of infection were excluded from the study. Similarly, 50 patients were enrolled for RIRS excluding patients with incomplete data (where stone or urine culture results were unknown), grave comorbidities (severe respiratory or cardiovascular disease), those with contralateral ureteral or renal stone and kidney failure. During RIRS, a ureteral access sheath (UAS) was utilized for all patients. For 36 patients, 9.5/11.5 Fr sheath was utilized and in a separate group of 14 patients 10/12 Fr UAS was utilized.
Informed written consent was taken from each patient or a guardian. All the demographic and clinical variables such as age, gender, comorbidity, body mass index (BMI), and stone bulk were noted. Preoperatively, mid-stream urine cultures were sent for every patient. Patients whose urine cultures were positive were given antibiotics till repeat culture become sterile or antibiotic was administered till the day of the operation. At the induction of anesthesia, all patients were administered broad-spectrum antibiotics intravenously with known efficacy against the pathogen isolated on urine cultures sent preoperatively.
Intraoperatively, bladder urine was collected by catheterizing the patient with a feeding tube before starting the procedure. The renal pelvic culture was collected after ureteric catheterization or at the time of renal pelvic puncture by needle aspiration. A stone fragment was surface decontaminated by the use of the Stamey method.[8] All the samples were sent for culture. Intraoperative data such as duration of surgery and any other complication encountered were noted.
In the postoperative period, patients were Keenly observed for signs of SIRS which comprises of 2 or more of the following features:[9]
Body temperature <36°C or more than 38°C
Heart rate more than 90/min
Respiratory rate more than 20/min
WBC more than 12 × 109/L or <4 × 109/L.
Sepsis was defined as signs and symptoms of SIRS with infection with arterial hypotension (systolic blood pressure <90 mmHg or mean blood pressure <70 mmHg) or acute oliguria (urine output <0.5 ml/kg/h) or altered sensorium.[10] The need for any auxiliary procedures and the presence of residual calculus 1 month after the procedure were also noted.
Quick sequential organ failure assessment (qSOFA) score is positive if 2 or more of these criteria are met:
Systolic blood pressure <100 mm of Hg
Respiratory rate >20/min
Glasgow coma scale.
An International Task Force in 2016 revised the then-existing definition of sepsis to a “life-threatening organ dysfunction caused by a dysregulated host response to an infection.” This amendment led to the development of a qSOFA applying three clinical criteria. qSOFA score was used to predict patient susceptibility to sepsis and pin down patients having a greater risk of intensive care unit admission. Patients satisfying two or more of the three clinical criteria have 3–14 times increased risk of in-hospital mortality.[11]
Statistical methods
All data analysis was done on Statistical Package for the Social Sciences Inc., IBM, Chicago, IL, USA, version 21.0. For descriptive statistics, categorical data were expressed in proportions and for continuous data, mean and standard deviation was utilized for central tendency. The significance of the association between the two attributes was analyzed using the Pearson’s Chi-square test statistic, and the Unpaired Student’s t-test was employed to analyze the overall distribution of values amongst the two groups. Variables having considerable association in univariate analysis were included for binary multivariable logistic regression analysis to discover the predictors/risk factors of SIRS both in PCNL as well as RIRS procedure. The dependent variable for SIRS were coded as: presence of SIRS = 1 and absence = 0. Sensitivity, specificity, and predictive value was calculated and compared between qSOFA and SIRS for predicting sepsis using descriptive statistics also. For all the variables, P < 0.05 was considered statistically significant.
RESULTS
SIRS evolved in 23% of patients after PCNL and 20% after RIRS with 12% and 6% progressing to sepsis, respectively. All patients with sepsis recovered well except one patient post-PCNL who died in the postoperative period. Table 1 lists the clinical and demographic variables of the population under study.
Table 1.
Demographic and clinical characteristics of study population
| Patient’s characteristics | PCNL (value), n (%) | RIRS (value), n (%) |
|---|---|---|
| Total number of patients | 100 | 50 |
| Gender | ||
| Male | 71 (71.0) | 28 (56.0) |
| Female | 29 (29.0) | 22 (44.0) |
| Age (years), mean±SD | 41.56±15.69 | 35.88±9.50 |
| Co-morbidity | ||
| Hypertension | 10 (10) | 5 (10) |
| Diabetes | 11 (11) | 7 (14) |
| Hypertension + diabetes | 4 (4) | 2 (4) |
| Others | 4 (4) | 1 (2) |
| No co-morbidity | 71 (71) | 35 (70) |
| BMI (kg/m2), mean±SD | 23.22±4.88 | 22.89±5.41 |
| Preoperative urine culture | ||
| Positive | 19 (19) | 18 (36) |
| Sterile | 81 (81) | 32 (64) |
| Stone bulk (cm), mean±SD | 3.53±2.04 | 1.18±0.39 |
| Dilated pelvi calyceal system | ||
| Yes | 65 (65) | 20 (40) |
| No | 35 (35) | 30 (60) |
| Operative time (min), mean±SD | 124.30±36.88 | 62.86±14.98 |
| Number of tracts | ||
| Single | 77 (77) | NA |
| Multiple | 23 (23) | NA |
| Nephrostomy tube placement | ||
| Yes | 89 (89) | NA |
| No | 11 (11) | NA |
| Preoperative DJ stent | ||
| Yes | NA | 20 (40) |
| No | NA | 30 (60) |
| UAS (Fr) | ||
| 9.5–11.5 (yes) | NA | 36 (72) |
| 10–12 (yes) | NA | 14 (28) |
| Intraoperative bladder urine culture | ||
| Positive | 12 (12) | 14 (28) |
| Sterile | 88 (88) | 36 (72) |
| Intraoperative RPUC | ||
| Positive | 18 (18) | 17 (34) |
| Sterile | 82 (82) | 33 (66) |
| SC | ||
| Positive | 26 (26) | 19 (38) |
| Sterile | 74 (74) | 31 (62) |
| Postoperative urine culture | ||
| Positive | 12 (12) | 17 (34) |
| Sterile | 88 (88) | 33 (66) |
| Postoperative SIRS | ||
| Yes | 23 (23) | 10 (20) |
| No | 77 (77) | 40 (80) |
| Postoperative sepsis | ||
| Yes | 12 (12) | 3 (6) |
| No | 88 (88) | 47 (94) |
| Postoperative residual calculus | ||
| Yes | 28 (28) | 11 (22) |
| No | 72 (72) | 39 (78) |
| Need for redo PCNL/redo RIRS/ESWL | 25 (25) | 11 (22) |
| Stone-free status at 1-month post-PCNL/RIRS | 84 (84) | 39 (78) |
PCNL: Percutaneous nephrolithotomy, RIRS: Retrograde intrarenal surgery, SD: Standard deviation, BMI: Body mass index, SIRS: Systemic inflammatory response syndrome, DJ: Double J, ESWL: Extracorporeal shock wave lithotripsy, UAS: Ureteral access sheath, RPUC: Renal pelvic urine culture, SC: Stone culture, NA: Not available
As compared to patients without SIRS, more patients with post-PCNL SIRS were male (28% vs. 10%), while the age of the patient and BMI did not have a significant effect on preponderance of SIRS in this group.
On univariate analysis patients with a dilated pelvicalyceal system (PCS) (51% vs. 7%), multiple number of tracts (47% vs. 15%), positive preoperative urine culture (47% vs. 17%), positive intraoperative RPUC (66% vs. 13%), and positive SC (61% vs. 9%) had a significant association with post-PCNL SIRS. Larger stone bulk (P = 0.0001) and increasing duration of surgery >124 min (P = 0.049) were also markedly related to SIRS [Table 2]. There was an insignificant association of diabetes, postprocedure Nephrostomy tube, residual calculi, positive intraoperative bladder, and postoperative urine cultures with SIRS.
Table 2.
Association of various categorical variables with postpercutaneous nephrolithotomy systemic inflammatory response syndrome (n=100)
| Variable | SIRS, n (%) | Non-SIRS, n (%) | χ2, P |
|---|---|---|---|
| Gender | |||
| Male | 20 (28.2) | 51 (71.8) | 3.694*, 0.055 |
| Female | 3 (10.3) | 26 (89.7) | |
| Diabetes | |||
| Present | 3 (27.3) | 8 (72.7) | 0.127**, 0.712 |
| Absent | 20 (22.5) | 69 (77.5) | |
| Pelvi calyceal system | |||
| Dilated | 5 (7.7) | 60 (92.3) | 24.57*, 0.0001 |
| Nondilated | 18 (51.4) | 17 (48.6) | |
| Placement of nephrostomy tube | |||
| Yes | 22 (24.7) | 67 (75.3) | 1.350**, 0.449 |
| No | 1 (9.1) | 10 (90.9) | |
| Number of tracts | |||
| Single | 12 (15.6) | 65 (84.4) | 10.395*, 0.001 |
| Multiple | 11 (47.8) | 12 (52.2) | |
| Residual calculus | |||
| Yes | 9 (32.1) | 19 (67.9) | 1.836*, 0.175 |
| No | 14 (19.4) | 58 (80.6) | |
| Preoperative urine culture | |||
| Positive | 9 (47.4) | 10 (52.6) | 7.865**, 0.005 |
| Sterile | 14 (17.3) | 67 (82.7) | |
| Intraoperative bladder urine culture | |||
| Positive | 5 (41.7) | 7 (58.3) | 2.683**, 0.140 |
| Sterile | 18 (20.5) | 70 (79.5) | |
| Intraoperative RPUC | |||
| Positive | 12 (66.7) | 6 (33.3) | 23.64**, 00.0001 |
| Sterile | 11 (13.4) | 71 (86.6) | |
| SC | |||
| Positive | 16 (61.5) | 10 (38.5) | 29.46*, 0.0001 |
| Sterile | 7 (9.5) | 67 (90.5) | |
| Postoperative urine culture | |||
| Positive | 5 (41.7) | 7 (58.3) | 2.68**, 0.14 |
| Sterile | 18 (20.5) | 70 (79.5) | |
| Operative time (min) | |||
| <124 | 11 (16.9) | 54 (83.1) | 3.873*, 0.049 |
| ≥124 | 12 (34.3) | 23 (65.7) | |
| Age (years), mean±SD | 40.00±15.19 | 42.03±15.91 | −0.541#, 0.590 |
| BMI (kg/m2), mean±SD | 22.12±4.84 | 23.55±4.87 | −1.236#, 0.219 |
| Stone bulk (cm), mean±SD | 4.95±2.51 | 3.10±1.68 | 4.115#, 0.001 |
*Chi-square test, **Fisher’s exact test, #Student’s t-test. SIRS: Systemic inflammatory response syndrome, SD: Standard deviation, BMI: Body mass index, RPUC: Renal pelvic urine culture, SC: Stone culture
It was also noted that the mean stone size in SC-positive patients was 4.95 ± 2.51 cm and SC negative patients was 3.10 ± 1.68 cm. The difference showed a trend toward statistical significance (P = 0.001).
On multivariate analysis, patients having dilated PCS had 8.2 times more chance of SIRS as compared to those with nondilated PCS (P = 0.003) and patients with positive SC had 10 times more chance of SIRS as compared to those with negative SC (P = 0.019) [Table 3].
Table 3.
Multiple regression analysis of risk factors for postpercutaneous nephrolithotomy systemic inflammatory response syndrome
| Variable | B | SE | Wald | df | P | AOR (95% CI) |
|---|---|---|---|---|---|---|
| Pelvi calyceal system | ||||||
| Dilated | 2.106 | 0.705 | 8.925 | 1 | 0.003 | 8.216 (2.063–32.711) |
| Nondilated | Reference | |||||
| Number of tracts | ||||||
| Single | 0.783 | 0.931 | 0.707 | 1 | 0.400 | 2.188 (0.353–13.570) |
| Multiple | Reference | |||||
| Preoperative urine culture | ||||||
| Positive | 0.215 | 1.048 | 0.042 | 1 | 0.834 | 1.240 (0.159–9.678) |
| Sterile | Reference | |||||
| Intraoperative RPUC | ||||||
| Positive | −0.092 | 1.348 | 0.005 | 1 | 0.946 | 0.912 (0.065–12.813) |
| Sterile | Reference | |||||
| Retrieved SC | ||||||
| Sterile | Reference | |||||
| Positive | 2.397 | 1.022 | 5.497 | 1 | 0.019 | 10.992 (1.482–81.543) |
| Stone bulk (cm), mean±SD | −0.293 | 0.169 | 2.991 | 1 | 0.084 | 0.746 (0.536–1.040) |
| Operative time (min) | ||||||
| <124 | −0.090 | 0.866 | 0.011 | 1 | 0.917 | 0.914 (0.167–4.994) |
| ≥124 | Reference |
SD: Standard deviation, SE: Standard error, AOR: Adjusted odds ratio, CI: Confidence interval, RPUC: Renal pelvic urine culture, SC: Stone culture
In patients who underwent RIRS. More than 50% were males. The mean age was 35.88 ± 9.50. On univariate analysis of SIRS-associated risk factors, patients having residual calculus (54% vs. 10%), infected preoperative urine culture (38% vs. 9%), infected intraoperative RPUC (47% vs. 6%), SC (47% vs. 3%), and operative time >62 min (P = 0.048) had significantly higher chances of SIRS (P = 0.001) [Table 4].
Table 4.
Association of various categorical variables with postretrograde intrarenal surgery systemic inflammatory response syndrome (n=50)
| Variable | SIRS, n (%) | Non-SIRS, n (%) | χ2, P |
|---|---|---|---|
| Gender | |||
| Male | 6 (21.4) | 22 (78.6) | 0.81, 0.776 |
| Female | 4 (18.2) | 18 (81.8) | |
| Diabetes | |||
| Present | 3 (42.9) | 4 (57.1) | 0.2658**, 0.133 |
| Absent | 7 (16.3) | 36 (83.7) | |
| Pelvi calyceal system | |||
| Dilated | 4 (20.0) | 16 (80.0) | 0.000**, 1.000 |
| Nondilated | 6 (20.0) | 24 (80.0) | |
| Preoperative DJ stent | |||
| Yes | 5 (25.0) | 15 (75.0) | 0.521**, 0.494 |
| No | 5 (16.7) | 25 (83.3) | |
| UAS (Fr) | |||
| 9.5/11.5 | |||
| Yes | 7 (19.4) | 29 (80.6) | 0.025**, 1.000 |
| No | 3 (21.4) | 11 (78.6) | |
| 10/12 | |||
| Yes | 3 (21.4) | 11 (78.6) | 0.875**, 1.000 |
| No | 7 (19.4) | 29 (80.6) | |
| Residual calculus | |||
| Yes | 6 (54.5) | 5 (45.5) | 10.519**, 0.004 |
| No | 4 (10.3) | 35 (89.7) | |
| Preoperative urine culture | |||
| Positive | 7 (38.9) | 11 (61.1) | 6.272**, 0.012 |
| Sterile | 3 (9.4) | 29 (90.6) | |
| Intraoperative bladder urine culture | |||
| Positive | 4 (28.6) | 10 (71.4) | 0.893**, 0.436 |
| Sterile | 6 (16.7) | 30 (83.3) | |
| Intraoperative RPUC | |||
| Positive | 8 (47.1) | 9 (52.9) | 11.787**, 0.001 |
| Sterile | 2 (6.1) | 31 (93.9) | |
| SC | |||
| Positive | 9 (47.4) | 10 (52.6) | 14.34**, 0.0001 |
| Sterile | 1 (3.2) | 30 (96.8) | |
| Postoperative urine culture | |||
| Positive | 5 (29.4) | 12 (70.6) | 1.42**, 0.277 |
| Sterile | 5 (15.2) | 28 (84.8) | |
| Operative time (min) | |||
| <62 | 2 (8.3) | 22 (91.7) | 3.92**, 0.048 |
| ≥62 | 8 (30.8) | 18 (69.2) | |
| Age (years), mean±SD | 39.90±9.21 | 34.88±9.42 | 1.515#, 0.136 |
| BMI (kg/m2), mean±SD | 22.70±5.26 | 22.930±5.52 | −0.083#, 0.934 |
| Stone bulk (cm), mean±SD | 1.045±0.2006 | 1.282±0.6920 | 1.064#, 0.292 |
*Chi-square test, **Fisher’s exact test, #Unpaired t-test. SIRS: Systemic inflammatory response syndrome, SD: Standard deviation, BMI: Body mass index, DJ: Double J, RPUC: Renal pelvic urine culture, SC: Stone culture, UAS: Ureteral access sheath
On multiple regression analysis of risk factors for post-RIRS SIRS [Table 5], patients having infected intraoperative RPUC had significant SIRS as compared to those with sterile culture, and this difference turned out to be significant statistically (P = 0.009) while preoperative, intraoperative bladder urine, SC and operative time did not hold any significant relationship with SIRS.
Table 5.
Multiple regression analysis of risk factors for postretrograde intrarenal surgery systemic inflammatory response syndrome
| Variable | B | SE | Wald | df | P | AOR (95% CI) |
|---|---|---|---|---|---|---|
| Residual calculus | ||||||
| Yes | −2.208 | 1.252 | 3.111 | 1 | 0.078 | 0.110 (0.009–1.279) |
| No | Reference | |||||
| Preoperative urine culture | ||||||
| Positive | −1.326 | 1.074 | 1.525 | 1 | 0.217 | 0.265 (0.032–2.178) |
| Sterile | Reference | |||||
| Intraoperative RPUC | ||||||
| Positive | 3.427 | 1.316 | 6.780 | 1 | 0.009 | 30.783 (2.333–406.077) |
| Sterile | Reference | |||||
| Operative time (min) | ||||||
| ≥62 | Reference | |||||
| <62 | 2.157 | 1.268 | 2.895 | 1 | 0.089 | 8.644 (0.721–103.689) |
SE: Standard error, AOR: Adjusted odds ratio, CI: Confidence interval, RPUC: Renal pelvic urine culture
In PCNL patient specificity, sensitivity, positive, and negative predictive value of qSOFA compared to SIRS was markedly more significant in the prediction of sepsis (sensitivity 81.2% vs. 75.0%, specificity 98.8% vs. 86.9%, positive predictive value 92.8% vs. 86.9%, and negative predictive value 96.5% vs. 94.8%).
However, in RIRS patient’s specificity, the positive predictive value of qSOFA as compared to SIRS was markedly more significant in predicting sepsis (Specificity 95.7% vs. 85.1%, positive predictive value 60.0% vs. 30.0%). The sensitivity and negative predictive value of both the method was 100%, respectively [Table 6].
Table 6.
Comparison of sensitivity, specificity, predictive value for patients undergoing for sepsis by quick sequential organ failure assessment and systemic inflammatory response syndrome score both in percutaneous nephrolithotomy and retrograde intrarenal surgery patients
| Parameter | Percentage (95% CI) | |
|---|---|---|
|
| ||
| qSOFA | SIRS | |
| Type of procedure (PCNL) | ||
| Sensitivity | 81.25 (54.35–95.95) | 75.00 (47.62–92.73) |
| Specificity | 98.81 (93.54–99.97) | 86.90 (77.78–93.28) |
| Positive predictive value | 92.86 (64.62–98.93) | 52.17 (37.00–66.96) |
| Negative predictive value | 96.51 (90.89–98.71) | 94.81 (88.61–97.72) |
| Positive likelihood ratio | 68.25 (9.59–485.7) | 5.73 (3.08–10.64) |
| Negative likelihood ratio | 0.19 (0.07–0.53) | 0.29 (0.12–0.67) |
| Type of procedure (RIRS) | ||
| Sensitivity | 100.0 (29.24–100.0) | 100.0 (29.24–100.0) |
| Specificity | 95.74 (85.46–99.48) | 85.11 (71.69–93.8) |
| Positive predictive value | 60.00 (27.88–85.34) | 30.00 (17.79–45.91) |
| Negative predictive value | 100.00 | 100.00 |
| Positive likelihood ratio | 23.5 (6.05–91.21) | 6.71 (3.39–13.30) |
| Negative likelihood ratio | 0.00 | 0.00 |
PCNL: Percutaneous nephrolithotomy, RIRS: Retrograde intrarenal surgery, SIRS: Systemic inflammatory response syndrome, QSOFA: Quick sequential organ failure assessment, CI: Confidence interval
The analysis of concordance of various urine cultures post-PCNL the correlation between intraoperative RPUC and SC was found to be significantly strong (r = 0.74) as compared to other cultures [Table 7]. Post-RIRS-only correlation between intraoperative RPUC and SC was found to be significantly strong (r = 0.743) as compared to other cultures [Table 8].
Table 7.
Correlation among urine and stone culture at different parts of urinary system in percutaneous nephrolithotomy and retrograde intrarenal surgery
| Variable | 1 | 2 | 3 | 4 | 5 |
|---|---|---|---|---|---|
|
| |||||
| Correlation among urine and SC at different part of urinary system in PCNL | |||||
| Preoperative urine culture (1) | 1 | ||||
| Intraoperative RPUC (2) | 0.636** | 1 | |||
| Intraoperative bladder urine culture (3) | 0.606** | 0.548** | 1 | ||
| Postoperative urine culture (4) | 0.370** | 0.308** | 0.337** | 1 | |
| Retrieved SC (5) | 0.468** | 0.790** | 0.413** | 0.272** | 1 |
|
| |||||
| Correlation among urine and SC at different part of the urinary system in RIRS procedure | |||||
|
| |||||
| Preoperative urine culture (1) | 1 | ||||
| Intraoperative RPUC (2) | 0.253 | 1 | |||
| Intraoperative bladder urine culture (3) | 0.089 | 0.399** | 1 | ||
| Postoperative urine culture (4) | 0.341* | 0.198 | 0.399** | 1 | |
| Retrieved SC (5) | 0.185 | 0.743** | 0.338* | 0.134 | 1 |
*P<0.05, **P<0.01. PCNL: Percutaneous nephrolithotomy, RIRS: Retrograde intrarenal surgery, RPUC: Renal pelvic urine culture, SC: Stone culture
Table 8.
Comparison of sepsis in patients undergoing percutaneous nephrolithotomy and retrograde intrarenal surgery by quick sequential organ failure assessment and systemic inflammatory response syndrome score
| Total patients | ICU stay | No ICU stay | |
|---|---|---|---|
| PCNL | |||
| Sepsis | 16 | 16 | 84 |
| QSOFA | 14 | 13 | 87 |
| SIRS | 23 | 12 | 88 |
| RIRS | |||
| Sepsis | 3 | 3 | 47 |
| QSOFA | 4 | 2 | 48 |
| SIRS | 10 | 3 | 47 |
| PCNL | |||
| Sepsis | 16 | 16 | 84 |
| QSOFA | 14 | 13 | 87 |
| SIRS | 23 | 12 | 88 |
| RIRS | |||
| Sepsis | 3 | 3 | 47 |
| QSOFA | 4 | 2 | 48 |
| SIRS | 10 | 3 | 47 |
PCNL: Percutaneous nephrolithotomy, RIRS: Retrograde intrarenal surgery, SIRS: Systemic inflammatory response syndrome, QSOFA: Quick sequential organ failure assessment, ICU: Intensive care unit
DISCUSSION
The management of nephrolithiasis has shifted towards PCNL and RIRS in the last few decades. The complications of PCNL have diminished over time as learning, techniques, and instrumentation is being persistently refined. Prophylactic antibiotics and ensuring a sterile preoperative urine culture do not always prevent SIRS.
RIRS has been accepted as a primary alternative therapeutic option of renal calculi measuring up to 20 mm.[10] Despite being a relatively harmless procedure there is a considerable risk of postoperative infective complications.[12]
Male-to-female ratio was higher in this study, the difference being insignificant statistically in concordance with studies by Wei et al. and Gravas et al.[7,13-16] where gender was not associated to post-PCNL SIRS. The average age of the population in this study was considerably less as compared to other studies.[7,16,17] Gutierrez et al. reported that lower patient’s age was a risk factor for post-PCNL SIRS.[16]
No significant association of SIRS occurring post-PCNL was found with BMI and diabetes. Shohab et al. also inferred that there was no difference in normal, overweight, and obese groups.[18] Korets et al. also found no correlation between diabetes mellitus and SIRS occurring post-PCNL.[15]
In this study, 23% of patients had SIRS and 12% had sepsis. Koras et al. also observed 27.4% SIRS and 7.6% sepsis post-PCNL.[19] Mariappan et al. found a 37% rate of SIRS while Wei et al. reported a 35.3% rate of SIRS.[7,13] The incidence of SIRS is comparable in our study even though there was a higher mean bulk of stone in our study population compared to that reported in literature.
We found a significant association between dilated PCS, multiple tracts, preoperative urine culture, intraoperative RPUC, SC, and post-PCNL SIRS on univariate analysis. Patel et al. and Chen et al. surmised that the usage of multiple tracts was a predictor of infectious complications after PCNL procedure.[17,20]
In this study, a statistically significant association was found between large stone bulk, longer operative time > 124 min and SIRS. Larger stones are related to more tissue injury during PCNL due to more manipulations, longer operative time, and multiple tracts. Gonen et al. demonstrated that increased operative time and bigger stone burden were associated risk factors for post-PCNL fever.[21] Chen et al. reported a stone size of more than 2 cm and operative time >132 min was associated with SIRS.[17] McAleer et al. studied the accumulation of endotoxins on infected calculi and concluded that their concentration in blood could reach levels significant enough to cause severe sepsis.[3] Wang et al. also reported longer operative time (>90 min) as a risk factor for post-PCNL septic shock.[22]
Preoperative urine culture, intraoperative RPUC, and SC were also found to be significant in univariate analysis. Singh et al. and Erdil et al. both interpreted that positive RPUC and SC correlated significantly with the development of SIRS.[23,24]
On multivariate analysis, patients with dilated PCS and positive SC had profoundly high chances of SIRS as compared to those with nondilated PCS and negative SC. Chen et al. and Taufik et al.[17,25] also found that dilated PCS was a predictor for post-PCNL SIRS. Mariappan et al.[7] found a 4 fold risk of urosepsis with positive SC and RPUC.
On analysis of urine and SC, only correlation between intraoperative RPUC and SC was found to be significantly strong in case of PCNL and both cultures were positive in more than 50% of patients suffering from SIRS and in 91% of patients suffering from sepsis. Dogan et al., Singh et al., and Gonen et al. also discovered that RPUC and positive stone were significantly consociated with SIRS.[21,23,26]
Patients with SIRS often have negative blood cultures due to extended antibiotic therapy. Hence, RPUC and SC are the only culture to identify pathogens causing post-PCNL SIRS and guide antibiotic treatment.
Overall, RIRS is considered a safe method as compared to perioperative mortality associated with PCNL in large series.[1,27] Manifestation of post-RIRS infectious complications is said to range between 1.7% and 1.8%.[28] The occurrence of SIRS and sepsis in our study was 20% and 6%, respectively, with the addition of some early cases when the techniques were in their nascent stages of development.
The aggregation of bacteria on stones and subsequent endotoxin release during stone fragmentation may be attributed as the initial source of infection and their assimilation via venous channels and lymphatics during the usage of high-pressure irrigation (despite using UAS) may lead to the spread of infection into the systemic circulation.[4,12,28]
On univariate analysis, patients having residual calculus, infected preoperative urine culture infected Intraoperative RPUC-infected SC, and longer duration of surgery (>62 min) had significant relation with SIRS under the RIRS procedure.
On the basis of current results, patients with prolonged surgical time (more than 62 min) should be counseled regarding the potential raised risk of postoperative SIRS, and the procedure should be staged. Dogan et al. also inferred that a reduced operative period is imputed with reduced renal pelvic pressure and reduced occurrence of infection postoperatively and it is a general consensus that the period of the procedure should not extend beyond an hour.[26]
In our study, residual stones contributed to an increased risk of infectious complications and Gutierrez et al. also demonstrated the same.[16] The presence of residual stones post RIRS is associated with an increased risk of hematuria, renal colic pain, and urinary tract infection (UTI).[29] Zhong et al. concluded that huge stone burden, incidence of infectious calculi, and irrigation with a raised were not interdependent factors for post-RIRS SIRS.[30] Demir et al.[31] surmised that in patients undergoing RIRS, operative time served as an independent risk factor for UTI occurring postoperatively.[17,22]
Univariate analyses indicated that age, gender, BMI, history of diabetes, dilated PCS, preoperative double J stenting, use of UAS, positive intraoperative bladder urine and postoperative urine culture, and stone size did not have any significant association with RIRS in our study. On multiple regression analysis only intraoperative RPUC was notably associated with SIRS post-RIRS and on urine culture concordance analysis also it had highly significantly strong correlation with SC and the most fascinating part was that 70% of patients with SIRS and 100% of patients suffering from sepsis had both intraoperative RPUC and SC-positive clinching the importance of both of these cultures.
In PCNL procedure, qSOFA is a better tool for predicting sepsis among hospitalized patients compared to SIRS but in case of RIRS, the predictive efficacy of qSOFA compared to SIRS is a little bit less but still it is a valuable predictor for assessing the risk of sepsis.
Limitations of our study were the small magnitude of patients who underwent RIRS and further lesser number who had sepsis which may lead to some bias and limited the generalization of the outcomes.
Strengths of our study included a prospective study design, a wider range of age groups of patients who underwent RIRS and PCNL, analysis of a large number of variables, and usage of standardized criterion to establish the infection-related phenomenon which will decrease likely confounding factors age.
CONCLUSION
Our study suggests that SIRS is a common problem occurring post-RIRS and PCNL.
Intraoperative RPUC and SC are better predictors of post-PCNL SIRS than preoperative urine culture, we, therefore, recommend that intraoperative RPUC and SC must routinely be obtained in PCNL. Preoperative risk assessment of post-PCNL SIRS should be done and high-risk patients such as those with positive preoperative urine culture, larger stone bulk, requiring multiple number of tracts, and operative time >124 min must be closely observed postoperatively for development of SIRS.
In RIRS, intraoperative RPUC and duration of surgery >62 min have tremendous significance. Therefore, judicious use of sensitive antimicrobial agents according to the result of SCs and RPUCs in the postoperative period and the improvement of surgical skills to reduce the operative time is of utmost importance in reducing SIRS.
SIRS is a sensitive screening method which is specifically useful for initial care and on the contrary, qSOFA is well suited for patients at greater risk of demise, which could help clinicians in deliberating on the future course of care and therapy.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
REFERENCES
- 1.O'Keeffe NK, Mortimer AJ, Sambrook PA, Rao PN. Severe sepsis following percutaneous or endoscopic procedures for urinary tract stones. Br J Urol. 1993;72:277–83. doi: 10.1111/j.1464-410x.1993.tb00717.x. [DOI] [PubMed] [Google Scholar]
- 2.Charton M, Vallancien G, Veillon B, Brisset JM. Urinary tract infection in percutaneous surgery for renal calculi. J Urol. 1986;135:15–7. doi: 10.1016/s0022-5347(17)45500-5. [DOI] [PubMed] [Google Scholar]
- 3.McAleer IM, Kaplan GW, Bradley JS, Carroll SF, Griffith DP. Endotoxin content in renal calculi. J Urol. 2003;169:1813–4. doi: 10.1097/01.ju.0000061965.51478.79. [DOI] [PubMed] [Google Scholar]
- 4.Hinman F, Redewill F. Pyelovenous back flow. J Am Med Assoc. 1926;87:1287–93. [Google Scholar]
- 5.Stenberg A, Bohman SO, Morsing P, Müller-Suur C, Olsen L, Persson AE. Back-leak of pelvic urine to the bloodstream. Acta Physiol Scand. 1988;134:223–34. doi: 10.1111/j.1748-1716.1988.tb08483.x. [DOI] [PubMed] [Google Scholar]
- 6.Rao PN, Dube DA, Weightman NC, Oppenheim BA, Morris J. Prediction of septicemia following endourological manipulation for stones in the upper urinary tract. J Urol. 1991;146:955–60. doi: 10.1016/s0022-5347(17)37974-0. [DOI] [PubMed] [Google Scholar]
- 7.Mariappan P, Smith G, Bariol SV, Moussa SA, Tolley DA. Stone and pelvic urine culture and sensitivity are better than bladder urine as predictors of urosepsis following percutaneous nephrolithotomy:A prospective clinical study. J Urol. 2005;173:1610–4. doi: 10.1097/01.ju.0000154350.78826.96. [DOI] [PubMed] [Google Scholar]
- 8.Stamey TA. Ch. 8. Baltimore: Williams &Wilkins; 1980. Pathogenesis and Treatment of Urinary Tract Infections; pp. 430–43. [Google Scholar]
- 9.Bone RC, Balk RA, Cerra FB, Dellinger RP, Fein AM, Knaus WA, et al. Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. The ACCP/SCCM consensus conference committee. American College of Chest Physicians/society of critical care medicine. Chest. 1992;101:1644–55. doi: 10.1378/chest.101.6.1644. [DOI] [PubMed] [Google Scholar]
- 10.Berardinelli F, Proietti S, Cindolo L, Pellegrini F, Peschechera R, Derek H, et al. Aprospective multicenter European study on flexible ureterorenoscopy for the management of renal stone. Int Braz J Urol. 2016;42:479–86. doi: 10.1590/S1677-5538.IBJU.2015.0528. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 11.Shankar-Hari M, Phillips GS, Levy ML, Seymour CW, Liu VX, Deutschman CS, et al. Developing a new definition and assessing new clinical criteria for septic shock:For the third international consensus definitions for sepsis and septic shock (sepsis-3) JAMA. 2016;315:775–87. doi: 10.1001/jama.2016.0289. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 12.Takazawa R, Kitayama S, Tsujii T. Successful outcome of flexible ureteroscopy with holmium laser lithotripsy for renal stones 2 cm or greater. Int J Urol. 2012;19:264–7. doi: 10.1111/j.1442-2042.2011.02931.x. [DOI] [PubMed] [Google Scholar]
- 13.Wei W, Leng J, Shao H, Wang W. Diabetes, a risk factor for both infectious and major complications after percutaneous nephrolithotomy. Int J Clin Exp Med. 2015;8:16620–6. [PMC free article] [PubMed] [Google Scholar]
- 14.Gravas S, Montanari E, Geavlete P, Onal B, Skolarikos A, Pearle M, et al. Postoperative infection rates in low risk patients undergoing percutaneous nephrolithotomy with and without antibiotic prophylaxis:A matched case control study. J Urol. 2012;188:843–7. doi: 10.1016/j.juro.2012.05.007. [DOI] [PubMed] [Google Scholar]
- 15.Korets R, Graversen JA, Kates M, Mues AC, Gupta M. Post-percutaneous nephrolithotomy systemic inflammatory response:A prospective analysis of preoperative urine, renal pelvic urine and stone cultures. J Urol. 2011;186:1899–903. doi: 10.1016/j.juro.2011.06.064. [DOI] [PubMed] [Google Scholar]
- 16.Gutierrez J, Smith A, Geavlete P, Shah H, Kural AR, de Sio M, et al. Urinary tract infections and post-operative fever in percutaneous nephrolithotomy. World J Urol. 2013;31:1135–40. doi: 10.1007/s00345-012-0836-y. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 17.Chen L, Xu QQ, Li JX, Xiong LL, Wang XF, Huang XB. Systemic inflammatory response syndrome after percutaneous nephrolithotomy:An assessment of risk factors. Int J Urol. 2008;15:1025–8. doi: 10.1111/j.1442-2042.2008.02170.x. [DOI] [PubMed] [Google Scholar]
- 18.Shohab D, Ayub R, Alam MU, Butt A, Sheikh S, Assad S, et al. Effect of body mass index on operative time, hospital stay, stone clearance, postoperative complications, and postoperative analgesic requirement in patients undergoing percutaneous nephrolithotomy. Turk J Urol. 2015;41:177–80. doi: 10.5152/tud.2015.61482. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 19.Koras O, Bozkurt IH, Yonguc T, Degirmenci T, Arslan B, Gunlusoy B, et al. Risk factors for postoperative infectious complications following percutaneous nephrolithotomy:A prospective clinical study. Urolithiasis. 2015;43:55–60. doi: 10.1007/s00240-014-0730-8. [DOI] [PubMed] [Google Scholar]
- 20.Patel N, Shi W, Liss M, Raheem O, Wenzler D, Schallhorn C, et al. Multidrug resistant bacteriuria before percutaneous nephrolithotomy predicts for postoperative infectious complications. J Endourol. 2015;29:531–6. doi: 10.1089/end.2014.0776. [DOI] [PubMed] [Google Scholar]
- 21.Gonen M, Turan H, Ozturk B, Ozkardes H. Factors affecting fever following percutaneous nephrolithotomy:A prospective clinical study. J Endourol. 2008;22:2135–8. doi: 10.1089/end.2008.0139. [DOI] [PubMed] [Google Scholar]
- 22.Wang Y, Jiang F, Wang Y, Hou Y, Zhang H, Chen Q, et al. Post-percutaneous nephrolithotomy septic shock and severe hemorrhage:A study of risk factors. Urol Int. 2012;88:307–10. doi: 10.1159/000336164. [DOI] [PubMed] [Google Scholar]
- 23.Singh P, Yadav S, Singh A, Saini AK, Kumar R, Seth A, et al. Systemic inflammatory response syndrome following percutaneous nephrolithotomy:Assessment of risk factors and their impact on patient outcomes. Urol Int. 2016;96:207–11. doi: 10.1159/000441954. [DOI] [PubMed] [Google Scholar]
- 24.Erdil T, Bostanci Y, Ozden E, Atac F, Yakupoglu YK, Yilmaz AF, et al. Risk factors for systemic inflammatory response syndrome following percutaneous nephrolithotomy. Urolithiasis. 2013;41:395–401. doi: 10.1007/s00240-013-0570-y. [DOI] [PubMed] [Google Scholar]
- 25.Indrawan T, Hardjowijoto S, Soebadi DM, Juniastuti J, Budiono B. Correlation of routine urine culture, stone culture and post-operative SIRS. Indonesian J Urol. 2014;21:20–6. [Google Scholar]
- 26.Dogan HS, Guliyev F, Cetinkaya YS, Sofikerim M, Ozden E, Sahin A. Importance of microbiological evaluation in management of infectious complications following percutaneous nephrolithotomy. Int Urol Nephrol. 2007;39:737–42. doi: 10.1007/s11255-006-9147-9. [DOI] [PubMed] [Google Scholar]
- 27.de la Rosette J, Assimos D, Desai M, Gutierrez J, Lingeman J, Scarpa R, et al. The clinical research office of the endourological society percutaneous nephrolithotomy global study:Indications, complications, and outcomes in 5803 patients. J Endourol. 2011;25:11–7. doi: 10.1089/end.2010.0424. [DOI] [PubMed] [Google Scholar]
- 28.Fan S, Gong B, Hao Z, Zhang L, Zhou J, Zhang Y, et al. Risk factors of infectious complications following flexible ureteroscope with a holmium laser:A retrospective study. Int J Clin Exp Med. 2015;8:11252–9. [PMC free article] [PubMed] [Google Scholar]
- 29.Dincel N, Resorlu B, Unsal A, Tepeler A, Silay MS, Armağan A, et al. Are small residual stone fragments really insignificant in children? J Pediatr Surg. 2013;48:840–4. doi: 10.1016/j.jpedsurg.2012.07.061. [DOI] [PubMed] [Google Scholar]
- 30.Zhong W, Leto G, Wang L, Zeng G. Systemic inflammatory response syndrome after flexible ureteroscopic lithotripsy:A study of risk factors. J Endourol. 2015;29:25–8. doi: 10.1089/end.2014.0409. [DOI] [PubMed] [Google Scholar]
- 31.Demir DO, Doluoglu OG, Yildiz Y, Bozkurt S, Ayyildiz A, Demirbas A. Risk factors for infectious complications in patients undergoing retrograde intrarenal surgery. J Coll Physicians Surg Pak. 2019;29:558–62. doi: 10.29271/jcpsp.2019.06.558. [DOI] [PubMed] [Google Scholar]