Clinical Outcomes After Ureteroscopic Lithotripsy in Patients Who Initially Presented with Urosepsis: Matched Pair Comparison with Elective Ureteroscopy

Abstract

Background and Purpose:

The outcomes of ureteroscopy (URS) after urgent decompression and antibiotics for patients who initially present with urosepsis because of obstructive urolithiasis have not been previously evaluated. The aim of this study was to compare the outcomes and complications of URS in patients with a recent history of sepsis with those without sepsis.

Methods:

The study included 138 patients who underwent URS for stone removal from January 2004 to September 2011 at a university medical center. A matched-pair analysis was performed using three parameters (age, sex, and race) to compare outcomes and complications between 69 patients who had sepsis vs a matched cohort who did not have sepsis before URS.

Results:

The study included 138 patients, 88 (64%) females and 50 (36%) males with a median age of 57.5 years (range 18–88 years). Patients with previous sepsis had similar patient characteristics and stone-free rates (81% vs 77%) compared with patients without previous sepsis (P>0.05). Patients with previous sepsis, however, had a significantly higher complications rate (20% vs 7%), longer hospital length of stay (LOS), and longer courses of postoperative antibiotics after URS (P<0.05). Sepsis developed postoperatively in two patients with diabetes (one with and one without previous sepsis), and postoperative fever developed in five patients with previous sepsis.

Conclusions:

URS after decompression for urolithiasis-related sepsis has similar success but higher complication rates, greater LOS, and longer course of postoperative antibiotics. This is important in counseling patients who present for definitive URS after urgent decompression for urolithiasis-related sepsis.

Introduction

Urosepsis is defined as sepsis caused by a urogenital tract infection. Urosepsis in adults accounts for approximately 25% of all sepsis cases.¹ Severe sepsis and septic shock is a critical condition, with a reported mortality rate ranging from 20% to 40%.^1,2 Urosepsis is mainly caused by urinary obstruction, with urolithiasis being the most common cause.^1,2 An early diagnosis is imperative for better clinical outcome. Emergent decompression of the collecting system is the standard of care for the initial management of urosepsis from obstructive urolithiasis. Both retrograde internal ureteral stent placement and percutaneous nephrostomy (PCN) drainage appear equally effective.^3

–6

After adequate decompression of the collecting system and proper treatment with antibiotics, definitive management of the stone is needed. Patients with ureteral stones or smaller intrarenal stone burden are likely to be amenable to definitive treatment with ureteroscopy (URS). There have been a number of reports in the literature demonstrating the high success rates and low complication rates of patients undergoing URS for treatment of stones.^5,7

–10 The outcomes of URS after urgent decompression and an appropriate course of antibiotics for patients who initially present with urosepsis from obstructive urolithiasis have not been previously evaluated, however. The aim of this study is to compare the outcomes and complications of URS in patients who initially presented with sepsis in comparison with those who had elective URS without a history of sepsis.

Methods

After obtaining Institutional Review Board approval, we performed a retrospective review of 854 patients who underwent URS at our University Hospital from January 2004 to September 2011, using Current Procedural Terminology code 52353. We used a combination search approach to screen patients who initially presented with obstructive urolithiasis-related sepsis. Adult patients with an International Classification of Diseases (ICD)-9 diagnostic codes for urolithiasis (592.1, 592.0, and 592.9) were first identified and then cross-referenced for a diagnostic code for infection (995.91, 599.0, 590, and 780.6). This pool of patients was then filtered for concomitant procedural codes for either ureteral stent placement (52332, 59.8) or PCN (50390, 50392, 74425, 74475, 55.03, and 55.92).

Patients who had obstructive urolithiasis based on CT diagnosis and sepsis identified by systemic inflammatory response syndrome defined by presence of ≥2 of the features mentioned in Table 1 were included and were age- and sex-matched with similar patients who did not present with sepsis. We identified 69 patients who presented initially with obstructive urolithiasis-related sepsis and were treated with urgent decompression and antibiotics followed by definitive URS.

Table 1.

Features of Systemic Inflammatory Response

Temperature	<36°C or >38°C
Heart rate	>90 beats/minute
Respiratory rate	>20 breaths/minute
White blood cells	>12,000 or <4000 cells/mm³
Immature band forms	≥10%

Matched-pair analysis was performed to compare outcomes and complications between these 69 patients who had sepsis at initial presentation vs a matched 69 patients who presented for elective URS and did not have a history of a septic episode. Stone characteristics such as stone size, number, and location were not included in the matching criteria because this would have limited the number of patients included in the study. The impact of stone characteristics on clinical outcomes and complication rates, however, were evaluated in univariable and multivariable models. The matching was specified 1:1 using three patients' characteristics (age, sex, and race), and the closest match was chosen from patients who had URS without previous sepsis. The matching was performed using the R software v2.13 (The R Foundation for Statistical Computing, Vienna, Austria) with the MatchIt library.

Primary outcomes included stone-free and complications rates. The stone-free rate was defined as the absence of any residual stones or fragments of any size on postoperative imaging performed 4 to 8 weeks after URS. Patients were evaluated 4 to 8 weeks after URS by kidneys, ureters, and bladder (KUB) radiography and tomography and renal ultrasonography or intravenous urography (IVU) or CT based on the discretion of the treating urologist. Postoperative complications were recorded and graded according to the Clavien system.¹¹ Secondary outcomes included hospital length of stay (LOS), postoperative admission to the intensive care unit (ICU), duration of postoperative antibiotics, and duration of postoperative internal ureteral stent.

Comparative outcomes between the treatment groups were assessed using a chi-square or Fisher exact test for categorical variables, and a Mann-Whitney U test for continuous variables. Multivariable linear regression model was used to evaluate independent predictors for residual fragments or complications. Statistical analysis was performed using SPSS version 21 (SPSS, Chicago, IL) with level of significance set at 0.05.

Results

Patient characteristics

The study included 138 adult patients who underwent URS for stone removal from January 2004 to September 2011–88 (64%) females and 50 (36%) males with a median age of 57.5 years (range 18–88 years). Table 2 describes patient and stone characteristics in those with and without previous sepsis. The stone size was larger in patients with previous sepsis with median stone diameter 8 mm (interquartile range [IQR] 5.5–11.5) compared with 6 mm (IQR 3–9) in patients without previous sepsis. Pretreatment stone diameter >5 mm was found in 52 (75.4%) patients with initial sepsis vs 39 (56.5%) patients without previous sepsis.

Table 2.

Patient and Treatment Characteristics

	No sepsis, n (%)	Sepsis, n (%)	P value
Age, years (median, IQR)	58 (47–67)	57 (44–66)	0.545
Sex, female/male	42/27 (61/39)	46/23 (67/33)	0.479
Body mass index (median, IQR)	28 (25–34)	27.5 (24–33)	0.455
Diabetes	13 (19)	18 (26)	0.308
Stone size, mm (median and IQR)	6 (3–9)	8 (5.5–11.5)	0.008
Stone side, right/left	40/28 (58/42)	33/36 (48/52)	0.233
Stone location
Kidney	27 (39)	19 (28)	0.225
Ureter	36 (52)	39 (56)
Kidney and ureter	6 (9)	11 (16)
Stone number
Single	49 (71)	48 (70)	0.852
Multiple	20 (29)	21 (30)

IQR=interquartile range.

Outcomes

Patients who presented with sepsis were treated initially with decompression (63 with internal ureteral stents and 6 with PCN) and antibiotics. Intravenous (IV) antibiotics were used for a median period of 2 days (range 1–11 days) followed by oral antibiotics for 1 to 3 weeks after initial decompression. Of these 69 patients who presented with initial sepsis, 22 (32%) had to be admitted to the ICU for a mean 1.3 days (range 1–11 days), and 3 (4.3%) patients needed vasopressors. Patients were treated definitively by URS after a median duration of 32 days after initial presentation with sepsis and decompression of obstructive urolithiasis (range 5–126 days).

Patients were evaluated 4 to 8 weeks after URS by KUB radiography and tomography and renal ultrasonography (61 patients; 44%) or IVU (48 patients; 35%) or noncontrast CT (29 patients; 21%) based on the discretion of the treating urologist, with no significant difference between modality of follow-up imaging in sepsis and elective groups (p>0.05). Table 3 describes the clinical outcomes including stone-free rates, complications, hospital LOS, postoperative admission to the ICU, duration of antibiotics use, and duration of stent after URS. Patients with previous sepsis had similar stone-free rates (81% vs 77%) compared with patients without previous sepsis (P>0.05). Table 4 describes the stone-free rates in relation to stone characteristics.

Table 3.

Clinical Outcomes

	No sepsis n (%)	Sepsis n (%)	P value
Stone-free rate	53/69 (77)	56/69 (81)	0.531
Overall complications	5/69 (7)	14/69 (20)	0.007
High-grade complications	3/69 (4)	5/69 (7)	0.466
Hospital length of stay, days (mean and range)	0.6 (0–4)	2.5 (0–33)	<0.001
Postoperative admission to ICU	0	2 (3)	0.154
Duration for antibiotics, days (mean and range)	0.4 (0–20)	1.7 (0–29)	0.023
Duration of stent, days (mean and range)	7.4 (2–67)	9.8 (1–76)	0.149

ICU=intensive care unit.

Table 4.

Stone-Free Rates Stratified by Stone Characteristics

	Stone-free rates
Stone characteristics	All patients	P value	No sepsis	P value	Sepsis	P value
Size
≤10 mm	79	0.891	76	0.692	82	.772
>10 mm	80		83		79
Multiplicity
Single	84.5	0.014	79	0.493	90	0.007
Multiple	66		85		62
Location
Ureter	80		75		85
Kidney	85	0.076	81.5	0.689	89.5
Kidney and ureter	59		67		54.5	0.044

In patients who presented initially with sepsis, the stone-free rates dropped significantly from 90% in patients with single stones to 62% in patients with multiple stones (P=0.007) and from >85% in patients who had stones either in the kidney or ureter to 54.5% in patients with stones located in both kidney and ureter (P=0.044). These differences were not significant in patients who underwent elective URS with no previous sepsis (P>0.05). The stone size did not have a significant impact on stone-free rates in both groups (P>0.05).

Patients with previous sepsis had significantly higher complications rate (20% vs 7%, P=0.007), longer LOS, and longer courses of postoperative antibiotics (P<0.05). Sepsis developed postoperatively in two patients with diabetes (one with and one without previous sepsis), and postoperative fever developed in five patients with previous sepsis. Table 5 describes the complications and their Clavien grading. Patients with previous sepsis had significantly higher overall complications; however, there was no statistically significant difference between high-grade complications in patients with and without previous sepsis (7% vs 4%, P=0.466).

Table 5.

Complications Stratified by Clavien Grade

Grade	Description	No sepsis (%)	Sepsis (%)
I	Fever	0	5 (7.2)
	Ureteral injury	0	1 (1.4)
II	Hematuria	1 (1.4)	0
	Atrial fibrillation	1 (1.4)	2 (2.8)
	Others	0	1 (1.4)
III	Hematuria	0	1 (1.4)
	Ureteral perforation/urinoma	1 (1.4)	1 (1.4)
	Migrated ureteral stent	0	1 (1.4)
	Reoperation for residual stones	1 (1.4)	1 (1.4)
IV	Sepsis	1 (1.4)	1 (1.4)

In multivariable models, location, size, multiplicity of the stones and initial presentation with sepsis were not independent predictors of developing complications or having residual stones after URS.

Discussion

URS can be used to treat most patients with renal and ureteral stones without specific contraindications. URS outcomes have been well reported in the literature.^5,7

–10 The outcomes of URS after urgent decompression for patients who initially present with urosepsis from obstructive urolithiasis have not been well studied, however. In this study, URS after decompression for urolithiasis-related sepsis had similar stone-free but higher overall complication rates. The stone-free rate for patients with previous sepsis was 81% and was not significantly different from those patients without previous sepsis. Stone-free rates after URS were reported between 78% and 98% for management of ureteral stones depending on stone location, size, multiplicity, as well as definition of stone-free status.^5,7,9

In our study, stone-free rates were significantly lower in patients with multiple stones and stones located in both the kidney and ureter, particularly in patients with previous sepsis (Table 4). The relatively small number of patients included in this study precluded detection of independent predictors of leaving residual fragments or having complications related to URS. We could not find an association between pretreatment stone diameter or sepsis with stone-free rates after URS.

A recent study included 667 URS to evaluate the predictors of residual fragments >2 mm on postoperative CT. Pretreatment stone size, stone location, the presence of multiple stones, longer operative time, and exclusive use of flexible URS were associated with presence of residual fragments in follow-up CT. In a multivariable model, however, only pretreatment stone diameter was independently associated with residual fragments after URS. Of note, the stone-free rate after URS for ureteral stones was 78% vs 49% for kidney stones; 65% for stones located in the kidney or ureter alone vs 50% for stones located in both the kidney and ureter. Moreover, the stone-free rate dropped from 80% for stones ≤5 mm vs 44% for stones 6 to 10 mm, and from 69% for single stones vs 49% for multiple stones.¹⁰

A recent study from Japan¹² addressed the safety and efficacy of URS after management of obstructive pyelonephritis. The study compared 48 URS to 40 shockwave lithotripsy (SWL) cases. The study found that URS had a higher success rate of 98% compared with SWL at 67.5%, P<0.001. In that study, however, only ureteral stones were assessed, and the authors did not define the criteria for determining the stone-free rate. They evaluated patients with KUB radiography and renal ultrasonography 1 or 2 days after URS or SWL.¹²

URS for management of stones is generally a safe modality associated with a low rate of complications (<0 %).^5,9 The overall complication rate was higher in patients with previous sepsis (20%) than in those without previous sepsis (7%). High-grade complications, however, were not significantly different and were within a reasonable range (7% in patients with previous sepsis vs 4% in patients without sepsis). The Japanese study¹² mentioned earlier also evaluated complications of URS in patients without pyelonephritis (10%) compared with patients with initial obstructive pyelonephritis (12%). They reported fever or urosepsis in 8% of patients with obstructive pyelonephritis vs 6% in patients with no obstructive pyelonephritis beforeURS.¹² Similar to our study, these authors found higher complications rates in patients with pyelonephritis before URS.

Irrigation during URS increases renal pelvic pressure, potentially causing intrarenal, pyelovenous, and pyelolymphatic backflow.¹³ Therefore, there is a concern that URS might induce urosepsis by causing absorption of infected urine. To avoid postoperative sepsis, urinary tract infections should be treated adequately by proper antibiotics. In addition, the use of a ureteral access sheath might be effective in reducing renal pelvic pressure.¹⁴

The incidence of sepsis after URS was not higher in patients with previous sepsis in our study; however, postoperative fever was higher. Our results showed that postoperative fever developed after URS in five (7.2%) patients in the sepsis group. Similarly, fever was the most frequent postoperative complication (1.8%) in a recent study from The Clinical Research Office of the Endourological Society URS Global Study in 11,855 URS patients performed between 2010 and 2012 from 114 centers around the world.⁹ The higher incidence of fever might explain the longer LOS and longer courses of postoperative antibiotics (P<0.05) in the sepsis group in our study, particularly with no fever reported in patients without previous sepsis. We had only two patients with diabetes in whom sepsis developed postoperatively—one with and one without previous sepsis—with overall 1.4% incidence of sepsis in our study, compared with 2% to 4% in the literature.^5,7

Similar to the relatively low incidence of sepsis, we had very few minor ureteral injuries in the present study. Reviewing complications, we had three (2.1%) patients with ureteral injury; two (1.4%) of them had ureteral perforation, 1 in each group. These patients were treated with ureteral stent placement for 2 weeks, with no adverse consequences during follow-up. Ureteral injuries were reported between 3% and 6% in nephrolithiasis guidelines and contemporary reviews.^5,7 Overall ureteral perforation rates <2% have been described in previous studies.^7,8

Patients with febrile infection and obstruction should be treated with emergent decompression and an appropriate course of antibiotics before definitive endourologic stone intervention. Optimal duration of antibiotic administration and appropriate waiting time before definitive URS, however, remain to be determined. In the present study, patients who presented with sepsis were treated initially with decompression, and IV antibiotics were used for a median period of 2 days (up to 11 days) followed by oral antibiotics for 1 to 3 weeks.

Patients were treated definitively by URS after a median period of 32 days from initial decompression of sepsis (range 5–126 days). This is relatively longer than similar studies that reported average duration from urgent drainage to URS was approximately 2 weeks.^12,15 Interestingly, it has been reported that URS can be safely performed even before sepsis has been resolved.¹⁶ Yet, it is our routine practice to wait for at least 2 weeks after initial decompression to perform definitive URS, and we do not advocate performing definitive URS before resolution of the fever.

The waiting time between the initial decompression and definitive URS can be affected by multiple factors including severity of initial presentation, clinical response to treatment with decompression and antibiotics, surgeon availability, and patient choice. We did not find any association between duration from initial decompression to definitive URS and complications or success rates. Therefore, further study might be needed to determine optimal timing of URS for patients with sepsis with obstructing stones.

We routinely use a single perioperative prophylactic dose of antibiotics in patients without a history of UTI or sepsis. A preoperative course of antibiotics is used in patients with symptomatic and/or culture-proven UTI. Our current practice does not include hospital admission or use of postoperative antibiotics after routine URS. URS is usually performed as an outpatient procedure in our center. Our results from this matched pair analysis have demonstrated that patients with previous urosepsis, however, are more likely to be admitted and may need postoperative use of antibiotics compared with those undergoing elective URS.

There were inherent limitations to the present study. This was a retrospective study and as such might have been subject to bias. It included a relatively small number of patients, which precluded the production of clinically meaningful multivariable models addressing independent predictors of treatment outcomes, particularly with the relative small number of events (residual fragments or complications). We were not able to include stone characteristics such as stone size and location in the matching criteria, because these parameters would have further limited the number of patients included in the study. Stone characteristics were evaluated, however, in multivariable models that did not demonstrate a significant impact on clinical outcomes or complication rates. Finally, we were not able to study the differences in outcomes based on the type of infecting organism in patients with previous sepsis.

We believe that our study is novel and provides important clinical information for counseling a selected group of patients with a specific and serious clinical scenario that was not well studied before. Matched-pair analysis enables comparison of URS in patients with previous sepsis with a similar group of patients treated with URS for stone disease but without previous sepsis comparing “like-for-like” cases, compensating for the relatively low number that can be found in any single center. Our results may improve patient counseling after decompression for obstructive urolithiasis-related sepsis and before definitive stone removal. Early diagnosis and emergent decompression of urosepsis related to obstructive urolithiasis is imperative for improved clinical outcomes.

Conclusions

Patients who present initially with urosepsis from obstructive urolithiasis and are treated with urgent decompression and antibiotics should be counseled about the following treatment outcomes before definitive URS is performed: In comparison with elective URS, these persons may have similar stone-free but higher overall complication rates, greater LOS, and a longer course of postoperative antibiotics. The multiplicity of stones and presence of stones in both the ureter and kidney might be associated with lower stone-free rates. High-grade complications and the incidence of sepsis are not higher after definitive URS.

Disclosure Statement

No competing financial interests exist.

Footnotes

Abbreviations Used

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