Risk factors of Systemic inflammatory response syndrome after minimally invasive percutaneous nephrolithotomy with a controlled irrigation pressure

doi:10.21203/rs.3.rs-4668323/v1

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Risk factors of Systemic inflammatory response syndrome after minimally invasive percutaneous nephrolithotomy with a controlled irrigation pressure

https://doi.org/10.21203/rs.3.rs-4668323/v1

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Objective

This study aims to identify the risk factors for systemic inflammatory response syndrome (SIRS) after minimally percutaneous nephrolithotomy (PCNL) with a controlled irrigation pressure and to find which patients undergoing PCNL are likely to develop SIRS under the pressure-controlled condition.

Methods

A total of 303 consecutive patients who underwent first-stage PCNL in our institute between July 2016 and June 2018 were retrospectively reviewed. All the procedures were performed with an 18F tract using an irrigation pump setting the irrigation fluid pressure at 110 mmHg and the flow rate of irrigation at 0.4L/min. SIRS and sepsis were recorded after PCNL. The demographic data, clinical features, and test results were analyzed.

Results

52 patients (17.2%) developed SIRS and only 3 patients (0.99%) further progressed to severe sepsis. The results of univariate analysis showed that the stone size, operative time, history of DM, the value of glycosylated hemoglobin, history of ipsilateral surgery, preoperative urine culture, Staghorn calculi, pelvic urine culture, stone culture, number of tracts, blood transfusion, and residual stones were found to have a significant correlation with post-PCNL SIRS (p < 0.05). In multivariate analysis, the stone size (OR = 3.743, p = 0.012), preoperative urine culture (OR = 2.526, p = 0.042), pelvic urine culture (OR = 13.523, p < 0.001), the number of access tract (OR = 8.945, p = 0.002), blood transfusion (OR = 26.308, p < 0.001) were identified as the independent risk factors for post-PCNL SIRS.

Conclusion

The stone size(>4cm²), positive preoperative urine culture, positive pelvic urine culture, multiple tracts, receipt of a blood transfusion are the independent risk factors for SIRS under the pressure-controlled condition. More attention should be paid when the PCNL patients have these risk factors.

Renal calculi

Minimally invasive percutaneous nephrolithotomy

Systemic inflammatory response syndrome

irrigation pressure

risk factors

Percutaneous nephrolithotomy(PCNL) is the standard treatment for the management of large upper urinary tract stones at many institutions[1]. Despite technological advances that have increased the safety of the procedure, one of the most common complications following the procedure is postoperative systemic inflammatory response syndrome(SIRS), the incidence of which is reported to range from 9.8 to 37%[1]. SIRS is not always infectious in aetiology, it can occur in patients who have undergone polytrauma, severe burns, or a major operation. When the presence of both SIRS and infection, the clinical syndrome is defined as sepsis. Albeit rare, about 0.25–4.7% of the post-PCNL patient’s further progress into severe sepsis and uroseptic shock, even multiorgan dysfunction syndrome (MODS), which is very life-threatening with high mortality of 50–66%.[2–4] Therefore, predicting which patients are at greatest risk, is of paramount importance.

Previous studies have reported that a variety of factors were found to increase the risk of post-PCNL SIRS and sepsis[5]. One of the important factors is intrapelvic pressure sustained during PCNL. Currently, there is no standard or consensus with respect to the optimal pressures needed for nephroscopy. It is greatly influenced by the type of endoscope, the size of sheath, intra-operative irrigation fluid pressure and flow rate of irrigation. However, most studies just define the type of endoscope and the size of tract, not the irrigation fluid pressure and the flow rate of irrigation. Furthermore, a number of studies do not differentiate between sepsis and SIRS according to the strict definitions. In this study, we identify the risk factors of SIRS after PCNL, which was performed with an 18F tract using an irrigation pump setting up a clearly-defined irrigation fluid pressure and flow rate of irrigation. Our intention is to find which patient undergoing PCNL is at risk of developing SIRS under the pressure-controlled condition in order to close monitoring, early diagnosis and intervention after the procedure.

A total of 303 consecutive patients who underwent first-stage PCNL at the Department of Urology, Third Affiliated Hospital of Sun Yat-sen University between July 2016 and June 2018 were retrospectively identified and their clinical data were reviewed. This study was approved by the Institutional Ethic Committee of Third Affiliated Hospital of Sun Yat-sen University. All participants provided written informed consent. Exclusion criteria included: patients with compromised renal function, tumors, hematopathy, immunosuppressive disease, horseshoe kidney, polycystic kidney, fever before surgery, and a heart rate greater than 90 beats/min before surgery.

The diagnosis was made by preoperative KUB, ultrasonography, intravenous urography (IVU) or computed tomography urography (CTU). Stone size was calculated as the maximum diameter×minimum diameter. For multiple stones, superficial area of all stones was taken separately and added. Staghorn calculi were defined as stones occupying the pelvis and two or more calyces. The grade of hydronephrosis was defined by the Onen grading system[6]. The mid-urine exam and preoperative midstream urine culture with drug sensitivity screen were done in all the patients. Patients with a positive urine culture were treated adequately with culture-specific antibiotics. If the patients had a history of diabetes mellitus, the value of glycosylated hemoglobin was determined. Above 7% was defined as an abnormal glycosylated hemoglobin.

The procedure was performed under general anesthesia in all the patients. All the patients received a single dose of prophylactic antibiotic at the induction of anaesthesia. Under anesthesia, the ipsilateral ureter was catheterized, then the patient was turned to be prone. The puncture was performed under ultrasonic guidance with an 18-gauge needle at the 11th intercostal space or 12th subcostal site. Once puncture needle was achieved into the pelvicalyceal of the kidney, urine from the pelvicalyceal system was collected for pelvic urine culture. The access tract was dilated with a fascial dilator, and an 18F Amplatz sheath was placed. The stones were fragmented by 550um Holmium: YAG laser (20-60W, Lumenis, USA) using an 8/9.8F rigid ureteroscope (Wolf, Germany). The intraoperative fluid perfusion was utilized with an irrigation pump (JRJ-111, JINGRUI, China) setting the irrigation fluid pressure at 110 mmHg and the flow rate of irrigation at 0.4L/min. The stone fragments were collected for culture. A 5-6Fr double-J stent and a 14-Fr nephrostomy tube were placed at the end of the procedure. After the procedure, the patient’s vital signs were closely monitored for 24 hours, and haematological and biochemical determination was checked immediately and the next morning. The procedures creating two or more tracts were regarded as multiple tracts of PCNL. The operative time was calculated from the initial puncture to placement of nephrostomy tube. The residual stones were determined based on KUB or a non-contrast CT if the treated stone was radiolucent one month after the procedure.

Postoperative SIRS and sepsis were defined according to the criteria established by EAU 2017 Guidelines on Urological Infections. Severe sepsis was termed in case of systolic blood pressure (BP) < 90 mmHg OR systolic BP drop > 40 mmHg[7]. The clinical characteristics including age, sex, body mass index (BMI), history of diabetes mellitus(DM), the value of glycosylated hemoglobin, history of ipsilateral surgery, preoperative urine culture, stone size, Staghorn calculi, degree of hydronephrosis, pelvic urine culture, stone culture, number of tracts, operative time, blood transfusion, and residual stones were recorded.

Statistics analysis

Statistical analysis was performed using the SPSS statistical software package (Version 20.0 for Windows, SPSS, Inc). Continuous variables were expressed as median (IQR) and were compared using the Wilcoxon rank sum test. Categorical variables were compared with the χ2 test. The continuous variables were divided into 2 groups according to the previous studies for further comparison[5]. Spearman correlation analysis was used to analyze the correlation between variables in different groups. Univariate and multivariable logistic regression analysis were used to identify the independent factors associated with the postoperative SIRS after PCNL. All plots were completed by the R software, version 4.3.2 (R Project for Statistical Computing).

The flowchart shows the study design and data collection process (Fig. 1). This retrospective study included 303 patients comprising 169 (55.8%) males and 134 (44.2%) females. The patients’ demographics and characteristics are showed in Table 1. The median of age and BMI was 51(42,60) years and 23.3(21.5, 25.7) kg/m2, respectively. 53 patients (17.5%) had a history of DM, and only 42 patients (13.9%) had an abnormal value of glycosylated hemoglobin. A history of ipsilateral surgery was presented in 41 patients (13.5%). The preoperative urine culture was positive in 57 patients (18.8%) compared to 22 patients (7.3%) with a positive pelvic urine culture and 31 patients (10.2%) with a positive stone culture. 122 patients (40.3%) had a stone size of more than 4 cm² and 98 patients (32.3%) presented a staghorn stone. The median operative time was 88 (68, 119) min and 75 patients (24.8%) with an operative time of more than 120 min. Multiple access tracts were used in only 18 patients (5.9%) and 17 patients (5.6%) required blood transfusion. Residual stones were observed in 21 patients (6.9%). We also visualized the density distribution for four continuous variables: age, BMI, stone size and operative time, based on the SIRS groups (Fig. 2). The density distribution of age (Panel A) showed that the SIRS group generally had a higher density in the 50–70 age range, while the non-SIRS group had a higher density in younger age ranges. For BMI (Panel B), the SIRS group tended to have higher BMI values compared to the non-SIRS group, which had a higher density in the lower BMI range. In terms of stone size (Panel C), both groups showed a higher concentration of smaller stone sizes, with the non-SIRS group having a higher density in this range. For operative time (Panel D), the SIRS group had a higher density in longer operative times, whereas the non-SIRS group had a higher density in shorter operative times.

Table 1

Demographic and clinical characteristics description
Variables	Total (n = 303)	Non-SIRS (n = 251)	SIRS (n = 52)	P value
Sex, n(%)
Male	169(55.8)	146(58.2)	23(44.2)	0.066
Female	134(44.2)	105(41.8)	29(55.8)
Age, years median (IQR)	51(42,60)	50(38,59)	55(47,62)	0.007
Age group, years, n(%)
< 60	227(74.9)	190(75.7)	37(71.2)	0.492
≥60	76(25.1)	61(24.3)	15(28.8)
BMI (kg/m²) median (IQR)	23.3(21.5,25.7)	23.2(21.3,25.4)	25.0(22.6,26.7)	0.005
BMI group (kg/m²), n(%)
<24	164(54.1)	142(56.6)	22(42.3)	0.060
≥24	139(45.9)	109(43.4)	30(57.7)
Stone size (cm²) median (IQR)	3.45(2.00,6.00)	3.00(1.76,5.32)	6.80(3.75,10.45)	< 0.001
Stone size group (cm²), n(%)
<4	181(59.7)	166(66.1)	15(28.8)	< 0.001
≥4	122(40.3)	85(33.9)	37(71.2)
Operative time (min) median (IQR)	88(68,119)	85(64,112)	106(86,137)	< 0.001
Operative time group (min), n(%)
<120	228(75.2)	198(78.9)	30(57.7)	0.001
≥120	75(24.8)	53(21.1)	22(42.3)
Diabetes, n(%)
No	250(82.5)	219(87.3)	31(59.6)	< 0.001
Yes	53(17.5)	32(12.7)	21(40.4)
Glycosylated hemoglobin, n(%)
Normal	261(86.1)	228(90.8)	33(63.5)	< 0.001
Abnormal	42(13.9)	23(9.2)	19(36.5)
History of ipsilateral surgery, n(%)
No	262(86.5)	228(90.8)	34(65.4)	< 0.001
Yes	41(13.5)	23(9.2)	18(34.6)
Preoperative urine culture, n(%)
Negative	246(81.2)	215(85.7)	31(59.6)	< 0.001
Positive	57(18.8)	36(14.3)	21(40.4)
Staghorn calculi, n(%)
No	205(67.7)	182(72.5)	23(44.2)	< 0.001
Yes	98(32.3)	69(27.5)	29(55.8)
Hydronephrosis, n(%)
0	19(6.3)	17(6.8)	2(3.8)	0.429
1	113(37.3)	93(37.1)	20(38.5)
2	20(6.6)	19(7.6)	1(1.9)
3	107(35.3)	87(34.7)	20(38.5)
4	44(14.5)	35(13.9)	9(17.3)
Pelvic urine culture, n(%)
Negative	281(92.7)	243(96.8)	38(73.1)	< 0.001
Positive	22(7.3)	8(3.2)	14(26.9)
Stone culture, n(%)
Negative	272(89.8)	236(94.0)	36(69.2)	< 0.001
Positive	31(10.2)	15(6.0)	16(30.8)
Number of tracts, n(%)
1	285(94.1)	241(96.0)	44(84.6)	0.002
2–3	18(5.9)	10(4.0)	8(15.4)
Blood transfusion, n(%)
No	286(94.4)	247(98.4)	39(75.0)	< 0.001
Yes	17(5.6)	4(1.6)	13(25.0)
Residual stones, n(%)
No	282(93.1)	237(94.4)	45(86.5)	0.042
Yes	21(6.9)	14(5.6)	7(13.5)
P value means the difference comparison between Non-SIRS and SIRS groups.

52 patients (17.2%) developed SIRS, and of these patients, 29 patients (55.8%) were female. Table 1 showed the factors studied in context to SIRS. The median age of SIRS group was older than non-SIRS group (50 VS 55, P = 0.007), but no significant difference on the percentage of patients with more than 60 years between two groups. Compared with non-SIRS group, the SIRS group had a higher median of BMI (23.2 VS 25, p = 0.005). A higher percentage of patients in the SIRS group had a history of DM and ipsilateral surgery than the non-SIRS group. Compared to the patients in non-SIRS group, patients in the SIRS group had significantly larger stone burdens (3.0 VS 6.8, p < 0.001) and longer operative time (85 VS 106, p < 0.001). A higher percentage of patients in the SIRS group was found to be positive in the preoperative urine culture, pelvic urine culture and stone culture. Similarly, a greater percentage of patients in the SIRS group required multiple access tracts and blood transfusion. The rate of residual stones in the SIRS group was a little higher than non-SIRS group (p = 0.042). There were no significant differences regarding the distribution of sex, age, BMI, and degree of hydronephrosis between these two groups (p > 0.05). Only 3 patients in the SIRS group further progressed to severe sepsis. Fortunately, all three patients were immediately transferred to the intensive care unit and responded to fluid resuscitation and antibiotics. There was no mortality. For the study of correlations between different variables, we conducted heatmaps of Spearman correlation analysis based on SIRS groups and sex groups, respectively (Fig. 3). Overall, the total patient group (Panel A) displayed notable positive and negative correlations among various clinical variables. The non-SIRS group (Panel B) and SIRS group (Panel C) showed different correlation patterns, with the SIRS group exhibiting stronger correlations between certain variables. Gender-specific panels (Panel D for males and Panel E for females) revealed differences in correlation patterns, indicating that some clinical variables correlate differently depending on the patient's sex.

Table 2 demonstrated the key risk factors for the development of SIRS after PCNL in the multivariable logistic analysis. The results showed that stone size (OR = 3.743, 95%CI = 1.333–10.458, p = 0.012), preoperative urine culture (OR = 2.526, 95%CI = 1.035–6.166, p = 0.042), pelvic urine culture (OR = 13.523, 95%CI = 3.756–48.687, p < 0.001), the number of access tract(OR = 8.945, 95%CI = 2.166–36.942, p = 0.002), blood transfusion (OR = 26.308, 95%CI = 5.937-116.573, p < 0.001) were independently correlated with postoperative SIRS after PCNL. It was worth mentioning that the risk for the development of SIRS was more than 10 times greater when the patients received a blood transfusion or had a positive pelvic urine culture compared with the patients with non-transfusion or negative pelvic urine culture.

Table 2

Factors associated with SIRS following minimally PCNL with a controlled irrigation pressure
Index		Univariate			Multivariate
Index	OR	95%CI	P value	OR	95%CI	P value
Sex	1.753	0.960–3.201	0.068
Age	1.263	0.649–2.457	0.492
BMI	1.776	0.971–3.250	0.062
Stone size	4.817	2.504–9.268	< 0.001	3.734	1.333–10.458	0.012
Operative time	2.740	1.462–5.134	0.002
Diabetes	4.636	2.380–9.030	< 0.001
GH	5.708	2.809–11.596	< 0.001
HIS	5.248	2.569–10.721	< 0.001
PUC	4.046	2.098–7.803	< 0.001	2.526	1.035–6.166	0.042
Staghorn calculi	3.326	1.801–6.142	< 0.001
Hydronephrosis	1.103	0.866–1.405	0.429
Pelvic urine culture	11.191	4.400-28.463	< 0.001	13.523	3.756–48.687	< 0.001
Stone culture	6.993	3.183–15.359	< 0.001
Number of tracts	4.382	1.639–11.718	0.003	8.945	2.166–36.942	0.002
Blood transfusion	20.583	6.386–66.348	< 0.001	26.308	5.937-116.573	< 0.001
Residual stones	2.633	1.007–6.899	0.048
GH, Glycosylated hemoglobin. HIS, History of ipsilateral surgery. PUC, Preoperative urine culture.

In China, a large number of PCNL were completed every year. With the advancement of imaging equipment and endourological instrumentation, the efficacy and safety of PCNL have been substantially improved. However, postoperative SIRS remains a challenging complication, which can longer hospital stay and require additional antibiotic treatment. In our study, the incidence rate of SIRS (17.2%) after PCNL was similar to the previous reports (9.8 to 37%). Probably, most patients with SIRS recover without sequelae after treatment, but some doctors ignore the underlying risks. Unfortunately, a small part of SIRS patients could progress to catastrophic severe sepsis. A Recent series identified an international cohort of > 5,000 patients who underwent PCNL and found that only two died of sepsis[8]. In this study, 3 out of 303 patients developed into severe sepsis, who were admitted to an intensive care unit and rescued successfully.

The pathophysiology of post-PCNL SIRS is multifactorial including infection, proinflammatory cytokines, ischemia-reperfusion injury, and response to the injury of kidney[9]. Though the exact mechanism of SIRS after PCNL is still obscure, two reasons can not be neglected. One reason is that the stones as a foreign body contribute to the escape of bacterial eradication by antibiotics and immune system[10]. The other one is that the minimally invasive nature of PCNL has the potential to create high intrarenal pressure, triggering the backflow of contaminated fluids into the systemic circulation, which may include bacteria, endotoxins and the inflammatory mediators, etc. Several investigators have correlated intrapelvic pressure with postoperative SIRS[11]. The intraoperative intrapelvic pressure was mainly affected by the type of endoscope, the size of access tract, the size of endoscope, irrigation fluid pressure, and flow rate of irrigation. Especially, many Chinese institutions preferred the 18F or 20F access tract compared with 24F or 26F access tract in America and Europe. In our study, all the procedures were performed with 18F access tract using an 8/9.8F rigid ureteroscope by an irrigation pump setting the irrigation fluid pressure at 110 mmHg and the flow rate of irrigation at 0.4L/min. We aimed to explore the risk factors of post-PCNL SIRS under controlled intrapelvic pressure.

Many investigators have examined the risk factors that increase the likelihood of post-PCNL SIRS. The risk factors for SIRS after PCNL differ among the studies. Gonzalez-Ramirez et al identified staghorn stones, body mass index < 18.5 kg/m², bleeding, and prolonged surgical time were associated with postoperative fever in a study of 280 cases[12]. Several studies suggested that female sex, DM, positive renal pelvic urine culture, operative time, stone size, stone culture, blood transfusion, residual stones, and hydronephrosis were the risk factors facilitating the development of SIRS after PCNL[13–15]. In the current study, the stone size, operative time, history of DM, the value of glycosylated hemoglobin, history of ipsilateral surgery, preoperative urine culture, Staghorn calculi, pelvic urine culture, stone culture, number of tracts, blood transfusion, and residual stones were found to have a significant correlation with post-PCNL SIRS. However, only the stone size, preoperative urine culture, pelvic urine culture, number of tracts, and blood transfusion were identified to be the independent risk factors for post-PCNL SIRS. This is probably attributed to the close relationship between risk factors.

Positive preoperative urine culture has been found to be a risk for postoperative fever and confirmed by several studies[15, 16]. A recent study demonstrated that the rate of postoperative SIRS in patients with positive preoperative urine culture was nearly twice than that with a sterile urine culture[17]. In this study, positive preoperative urine culture was demonstrated as an independent risk factor for SIRS after PCNL, which is consistent with the previous studies. However, preoperative urine culture often fails to grow stone-colonizing bacteria, and the discordance was reported to reach 25%[18]. In the current study, 5 cases were found that the type of bacteria in preoperative urine culture was different from that of stone culture. Therefore, some researchers suggested that positive pelvic urine and stone culture may be better predictors of post-PCNL sepsis than preoperative urine culture[19]. In this cohort of patients, 29 patients(9.6%) had a positive pelvic urine culture or stone culture but a negative preoperative urine culture. In the current study, we found that positive pelvic urine (OR = 13.523, 95%CI = 3.756–48.687) may be a stronger predictor than preoperative urine culture (OR = 3.743, 95%CI = 1.333–10.458).

Higher stone burden prolongs the operative time and increases propensity of bleeding while the intraoperative bleeding hampers vision resulting in lengthening the operative time, making it a vicious cycle. Moreover, staghorn stones may require multiple tracts and increase the probability of residual stones. In this study, stone size was an independent risk factor of post-PCNL SIRS, although the operative time and staghorn stones were significantly associated with postoperative SIRS but not an independent risk factor, which was comparative to findings of previous studies[20–21]. The requirement of blood transfusion for PCNL often occurrs in patients with intraoperative bleeding, which indicates a higher volume of fluid absorption and pyelosinus backflow[22]. Sometimes, a new tract was needed for a better operative field, which led to an increased risk of bleeding or transfusion. It has been reported that a higher rate of blood transfusion in patients was observed when multiple access tracts were used[23]. In the current study, blood transfusion was a strong independent risk factor of SIRS after PCNL, which has been reported in the previous study[24].

Moreover, we also used the Spearman correlation analysis to analyze the correlation among various clinical variables in total and different subgroups. Our study found that the correlation pattern of variables in total and different subgroups was different, suggesting that the correlation between variables may vary with gender, disease status or other conditions. Further elucidating the causes of these heterogeneities may help us to better understand the mechanism of post-PCNL SIRS and improve disease management.

There are some limitations to this study because of the small number of cases, the single-center study and the retrospective nature. Many important factors are required to be further investigated regarding their correlation with SIRS. The cause-and-effect relationship between the risk factors and post-PCNL SIRS also needs to be confirmed by a prospective and randomized study. Our results provide the warnings that contribute to the occurrence of SIRS after PCNL.

Our retrospective study demonstrates that the stone size(>4cm²), positive preoperative urine culture, positive pelvic urine culture, multiple tracts, and receipt of a blood transfusion are the independent risk factors for the development of SIRS after minimally PCNL under a controlled irrigation pressure. Special precautions and close monitoring should be recommended when the PCNL patients present these risk factors though very few patients develop into severe sepsis and uroseptic shock. Minimizing these risk factors may decrease the probability of post-PCNL SIRS.

Acknowledgments

Deepest appreciation to every participants and each member of the trial for their dedication and diligent work to medical research.

Author contributions

Senlin Lan: Conceptualization; data curation; formal analysis; methodology; visulization; writing–original draft; writing–review and editing. Bohao Liu: Conceptualization; data curation; formal analysis; methodology; visulization; writing–original draft; writing–review and editing. Siwei Xie: Formal analysis, data curation, writing–review and editing and visualization. Chunting Yang: Funding acquisition; investigation; project administration; resources; supervision; validation; writing–original draft.

All authors approve the final version of this manuscript to be published and agree to be accountable for all aspects of the work.

Funding information

This work was supported by National Natural Science Foundation of China NO. 82072831 (Yun Luo), Special Foundation for Young and Middle aged Medical Experts with Outstanding Contributions in Zhangzhou City (Senlin Lan) and Social Development Technology Key Project of Dongguan NO. 20211800905352 (Chunting Yang).

Compliance with ethical standards

Conflicts of interest

The authors declare no conflict of interest.

Research involving human/animal participants

This article does not contain any studies with animals performed by any of the authors.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional review board of the ten sites and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.

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No competing interests reported.

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05 Jul, 2024
Submission checks completed at journal
05 Jul, 2024
First submitted to journal
01 Jul, 2024

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Risk factors of Systemic inflammatory response syndrome after minimally invasive percutaneous nephrolithotomy with a controlled irrigation pressure

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Abstract

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Introduction

Patients and methods

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Results

Discussion

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Additional Declarations

Status:

Version 1