EMERGENCY DRAINAGE FOR UROSEPSIS ASSOCIATED WITH UPPER URINARY TRACT CALCULI

0022-5347/05/1732-0458/0 THE JOURNAL OF UROLOGY® Copyright © 2005 by AMERICAN UROLOGICAL ASSOCIATION

Vol. 173, 458 – 462, February 2005 Printed in U.S.A.

DOI: 10.1097/01.ju.0000150512.40102.bb

Infection/Inflammation EMERGENCY DRAINAGE FOR UROSEPSIS ASSOCIATED WITH UPPER URINARY TRACT CALCULI KOJI YOSHIMURA,* NORIAKI UTSUNOMIYA, KENTARO ICHIOKA, NOBUFUMI UEDA, YOSHIYUKI MATSUI AND AKITO TERAI From the Department of Urology, Kurashiki Central Hospital, Kuashiki, Japan

ABSTRACT

Purpose: We examined the characteristics of patients with urosepsis associated with upper urinary tract calculi requiring emergency drainage. Materials and Methods: From January 1994 to December 2003, 424 patients were admitted to our urological department a total of 473 times for treatment of upper urinary tract calculi, of whom 53 required a total of 59 emergency drainage procedures for urosepsis. We summarized the characteristics of these patients and events, and determined risk factors for emergency drainage using logistic regression analysis. Results: In 14 events (24%) intensive management, such as the use of vasopressors and anticoagulants, was performed. Transient thrombocytopenia less than 100,000/mm3 occurred in 18 events (31%). Hyperbilirubinemia occurred in 8 of 38 events (16%) without prior antibiotic therapy. One patient (2%) died of urosepsis. Patients with calculi who underwent emergency drainage required a longer hospital stay than those without emergency drainage (25.2 vs 14.8 days, p ⬍0.001). Of the variables analyzed poor performance status (Karnofsky performance status 70% or less, OR 2.9, p ⫽ 0.003), age 75 years or older (OR 2.1, p ⫽ 0.038) and female sex (OR 1.8, p ⫽ 0.046) were risk factors on multivariate analysis. Conclusions: Our findings suggest that the frequency of emergency drainage in elderly patients with poor performance status has increased in recent years, at least in our rural area of Japan. Preventing calculous formation and urinary tract infection in individuals with poor performance status will be of considerable importance in the future. KEY WORDS: urinary tract, calculi, drainage, Karnofsky performance status, emergency treatment

Although urolitiasis is one of the most common urological diseases, it can be lethal if urinary tract infection associated with obstructive uropathy due to upper urinary tract calculi results in bacteremia and sepsis.1 The term sepsis is defined as systemic inflammatory response to infection and systemic inflammatory response syndrome (SIRS) includes 2 or more of 1) fever greater than 38C or less than 36C, 2) an increased heart rate of greater than 90 beats per minute, 3) tachypnea, as manifested by a respiratory rate greater than 20 breaths per minute or hyperventilation, as indicated by a partial CO2 pressure of less than 32 mm Hg and 4) an alteration in the white blood cell count, such as a count greater than 12,000/mm3 or less than 4,000/mm3, or more than 10% immature neutrophils.2– 4 Since SIRS should be managed rapidly and appropriately, urosepsis (urological infection with SIRS) associated with obstructive uropathy frequently requires drainage. However, to our knowledge no studies have assessed the clinical characteristics and risk factors of urosepsis associated with upper urinary tract calculi. In this retrospective study we identified the clinical characteristics of patients undergoing emergency drainage as well as those of events of emergency drainage for urosepsis associated with upper urinary tract calculi. We also describe risk factors for emergency

drainage by comparison with other patients hospitalized for the treatment of upper urinary calculi.

PATIENTS AND METHODS

We reviewed the records of patients who required hospitalization at our urological department from January 1994 to December 2003 for the treatment of upper urinary calculi and associated conditions. Of the patients those who met certain criteria were enrolled in this study, namely 1) the definition of SIRS, as noted, 2) positive urine culture (greater than 105 cfu/ml),5 no antibiotic therapy just prior to consultation at our urological department, 3) positive urine culture (greater than 102 cfu/ml)6 or pyuria, defined as 10 or more leukocytes per high power field in the centrifuged specimen with flank pain,7 some antibiotic therapy just prior to consultation at our department and 4) an absent clinical focus of infection other than the urinary tract. In male patients digital rectal examination and palpation of the epididymis were performed to rule out acute prostatitis and acute epididymitis. The distribution of the date of emergency drainage, type of drainage, number of interventions for urinary tract calculi after initial drainage, interval from the initiation of symptoms to drainage and hospital stay were analyzed. We also assessed how many medical physicians, general physicians and specialists at departments other than urology examined patients prior to consultation with us and whether these physicians provided

Submitted for publication March 30, 2004. * Correspondence: Kurashiki Central Hospital, 1-1-1 Miwa, Kurashiki, Okayama, Japan (telephone: 81-86-422-0210; FAX: 8186-421-3424; e-mail: [email protected]). 458

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antibiotics. Peak C-reactive protein (CRP), the peak blood leukocyte count and the blood thrombocyte count nadir were assessed. In an attempt to determine the rate of hepatic damage by urosepsis we examined serum total bilirubin. Serum aspartate 2-oxoglutarate aminotransferase, alanine 2-oxoglutarate aminotransferase, ␥-glutamyltranspeptidase and alkaline phosphatase were also examined. Events with prior antibiotic therapy were excluded from this analysis because of the possibility of drug induced liver damage. Types of uropathogens and the calculous composition were examined. How many events required intensive management, including the use of vasopressors, anticoagulants and ␥ globulin, was also assessed. By comparison with other patients hospitalized for the treatment of upper urinary tract calculi during this decade (inpatient population) we investigated risk factors for emergency drainage for urosepsis associated with upper urinary tract calculi. The candidate risk factors we selected were patient age (75 years or older vs younger), sex, history of urolithiasis, history of acute pyelonephritis, immunosuppressant use, diabetes mellitus comorbidity, retirement home residence and performance status (Karnofsky performance status8 80% or more vs 70% or less). The chi-square test, unpaired Student’s t test and logistic regression model were used for statistical analysis with p ⬍0.05 considered statistically significant. RESULTS

A total of 424 patients with upper urinary tract calculi were hospitalized a total of 473 times. Of the patients 84 were treated with emergency drainage (percutaneous nephrostomy or ureteral stenting) a total of 91 times. The reasons for this procedure were not only SIRS from urosepsis, but also relief of intolerable pain, renal failure due to bilateral ureteral obstruction and other. Febrile upper urinary tract infection was identified in a total of 68 events in 62 patients. Five of these events with mild systemic inflammation did not meet SIRS criteria. Another event included evidence of SIRS and acute arthritis, in addition to urosepsis. The remaining 3 events met SIRS criteria with possible urosepsis but we did not perform urine culture examination. A total of 59 events in 53 patients met inclusion criteria and were included in the main analysis. Emergency drainage was performed 1 to 4 times in 50, 1, 1 and 1 patients, respectively. Of the 59 events 35 (59%) were managed by ureteral stent insertion and the remaining 24 (41%) were managed by percutaneous nephrostomy. Table 1 lists the characteristics of patients experiencing the 59 events with emergency drainage as well as the other 414 events. Of the 473 cases 190 (40%) and 39 (8%) showed a history of urolithiasis and acute pyelonephritis, respectively. Of the patients 64 (14%) had diabetes mellitus, 9 (2%) received immunosuppressants and 14 (3%) lived in a retirement home. Performance status in 67

cases (14%) was 70% or less. Patients undergoing emergency drainage required significantly more interventions and a longer hospital stay. Of the 59 events 21 (36%) were associated with antibiotic therapy prior to consultation at our urological department and 14 (24%) required intensive medication, including the administration of oxygen, vasopressors, anticoagulants and Igs, blood transfusion (red blood cells and platelets) and intensive care unit management. Table 2 shows data on these 59 events. One or more general physicians and/or specialists at other departments examined patients in 43 events (73%). Thrombocytopenia less than 100,000/mm3 was observed in 18 cases (31%) and the thrombocytopenia nadir occurred 0 to 3 days after drainage (average ⫾ SEM 1.3 ⫾ 1.1 days). Hyperbilirubinemia of 1.2 mg.dl or higher occurred in 6 of 38 cases (16%) without prior antibiotics. At least 1 of the 5 markers (bilirubin, aspartate 2-oxoglutarate aminotransferase, alanine 2-oxoglutarate aminotransferase, ␥-glutamyltranspeptidase and alkaline phosphatase) showed transient abnormality in 20 cases (53%). All 6 cases of hyperbilirubinemia were accompanied by at least 1 abnormal level of the other 4 enzymes. Two or more of the 5 markers showed abnormal values in 13 events (34%). One patient died of urosepsis despite intensive care. Patients undergoing ureteral stenting had more rapid progression of inflammation and more severe thrombocytopenia than those undergoing nephrostomy. However, the former patients were younger and recovered earlier than the latter. Although the distribution of stone locations did not differ between these 2 groups, stones were larger in the nephrostomy group than in the ureteral stent group (9.7 vs 2.6 mm, p ⫽ 0.006). The group without prior antibiotics experienced marginally but not significantly more severe thrombocytopenia than the group with prior antibiotics. Peak CRP and peak blood leukocyte count, and the rate of requiring intensive management did not differ between these 2 groups. Not surprisingly peak and nadir data on CRP, the blood leukocyte count and the blood platelet count were worse in patients requiring intensive care than those without it. Patients requiring intensive care were significantly older and had marginally poorer performance status than those not requiring it. The distribution of calculous composition was not remarkable. Calcium phosphate and calcium oxalate were the most frequent components of calculi, followed by magnesium ammonium phosphate. Escherichia coli was the most frequent uropathogen. Multiple uropathogens were recognized in 9 of 38 cases (24%) without and in 6 of 21 (29%) with prior antibiotics. None of the 38 events without prior antibiotics and 3 of the 21 with prior antibiotics were associated with Candida albicans. Table 3 shows analyses of risk factors for emergency drain-

TABLE 1. Patient characteristics, interventions and hospitalization No. Pts Mean age ⫾ SEM No. sex: Male Female Mean No. interventions/hospitalization ⫾ SEM No. intervention type: Drainage Shockwave lithotripsy Transurethral lithotripsy Percutaneous nephrolithrotripsy Other No. hospitalization date: 1994–1998 1999–2003 Mean hospital stay ⫾ SEM (days)

No Drainage (414)

Drainage (59)

58.3 ⫾ 15.7

62.6 ⫾ 17.0

0.052 (unpaired t test)

p Value

246 168 1.8 ⫾ 1.4

24 35 2.5 ⫾ 1.4

0.010 (chi-square test)

49 312 189 159 21

60 40 30 13 5

180 234 14.8 ⫾ 40.3

13 46 25.2 ⫾ 21.6

⬍0.001 (unpaired t test)

⬍0.001 (chi-square test) ⬍0.001 (unpaired t test)

Mean age ⫾ SEM No. men/women Mean days from symptom initiation to drainage ⫾ SEM* Physicians prior to urological consultation:* Mean No. ⫾ SEM No. 0 No. 1 No. 2 or more No. prior antibiotics (days):* 1⬃7 8⬃30 31⬃ Mean CRP peak ⫾ SEM White blood count (1,000/mm3): Mean peak No. greater than 12.0 No. 12.0 or less Thrombocyte count (10,000/mm3): Mean nadir ⫾ SEM No. less than 10.0 No. 10.0 or greater No. hyperbilirubinemia (1.2 mg/dl or greater): Yes No No. intensive management: Yes No Mean hospital stay ⫾ SEM (days) * Before hospitalization.

No. Pts

Ureteral Stent 35 59.5 ⫾ 17.4 12/23 2.6 ⫾ 2.5 0.9 ⫾ 0.7 6 14 4 4 3 1 19.4 ⫾ 6.7 17.0 ⫾ 9.8 14 10 19.4 ⫾ 11.9 6 18 1 13 7 28 36.3 ⫾ 27.4

Total Emergency Drainage Events 59 62.6 ⫾ 17.0 24/35 5.5 ⫾ 10.7 1.0 ⫾ 0.7 16 30 13 14 3 4 20.0 ⫾ 7.7 18.0 ⫾ 9.6 40 19 15.8 ⫾ 10.2 18 41

Not analyzed Not analyzed 14 45 25.2 ⫾ 21.6

7 17 17.6 ⫾ 11.9

5 19

13.4 ⫾ 8.2 12 23

18.7 ⫾ 9.5 26 9

10 0 0 20.5 ⫾ 8.3

1.0 ⫾ 0.8 10 16 9

24 67.3 ⫾ 15.7 12/12 9.7 ⫾ 15.7

Percutaneous Nephrostomy

⬍0.001

0.62

Not analyzed

0.014 0.64

0.25 0.32

0.30

Not analyzed

0.34

0.042 0.34 0.006

p Value

8 30 20.5 ⫾ 15.9

6 32

14.4 ⫾ 9.9 15 23

18.2 ⫾ 9.9 24 14

0 0 0 20.4 ⫾ 8.1

0.7 ⫾ 0.7 16 18 4

38 60.8 ⫾ 16.3 17/21 2.6 ⫾ 2.9

No

6 15 33.8 ⫾ 27.7

Not analyzed Not analyzed

18.5 ⫾ 10.5 3 18

17.7 ⫾ 9.2 16 5

14 3 1 19.4 ⫾ 6.9

1.5 ⫾ 0.6 0 12 9

21 65.9 ⫾ 18.1 7/14 10.7 ⫾ 16.4

Yes

Prior Antibiotics

TABLE 2. Patients with emergency drainage

0.011

0.74

Not analyzed

0.07 0.09

0.44 0.46

0.32

Not analyzed

⬍0.001

0.14 0.56 0.002

p Value

0 45 24.2 ⫾ 18.5

4 28

18.8 ⫾ 9.5 6 39

15.9 ⫾ 7.7 26 19

10 1 1 19.2 ⫾ 7.9

0.9 ⫾ 0.8 15 21 9

14 0 28.6 ⫾ 30.0

2 4

6.4 ⫾ 6.0 12 2

24.8 ⫾ 11.9 14 0

4 2 0 22.7 ⫾ 6.1

1.2 ⫾ 0.6 1 9 4

14 77.3 ⫾ 10.0 4/10 2.7 ⫾ 2.7

Yes

0.26

Not analyzed

⬍0.001 ⬍0.001

⬍0.001 0.009

0.066

Not analyzed

0.077

⬍0.001 0.46 0.14

p Value

Intensive Medication

45 58.1 ⫾ 16.2 20/25 6.3 ⫾ 12.0

No

Unpaired t

Chi-square

Unpaired t Chi-square

Unpaired t Chi-square

Unpaired t

Unpaired t

Unpaired t Chi-square Unpaired t

Statistical Test

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EMERGENCY DRAINAGE FOR UROSEPSIS TABLE 3. Emergency drainage risk factors

Age (75 yrs or older vs 74 yrs or younger) Sex (female vs male) History of urolithiasis (yes vs no) History of acute pyelonephritis (yes vs no) Diabetes mellitus comorbidity (yes vs no) Immunosuppression (yes vs no) Retirement home residence (yes vs no) Performance status (70% or less vs 80% or more)

Univariate p Values

p Value

Multivariate OR

95% CI

0.001 0.010 0.628 0.369 0.215 0.979 0.973 ⬍0.001

0.038 0.046 Not used Not used Not used Not used Not used 0.003

2.1 1.8 Not used Not used Not used Not used Not used 2.9

1.1–4.0 1.0–3.2 Not used Not used Not used Not used Not used 1.5–5.6

age for urosepsis in inpatients who underwent treatment for upper urinary tract calculi. Performance status, patient age and sex were independent risk factors. DISCUSSION

SIRS is believed to arise indirectly from the response of the host to an acute, life threatening challenge to systemic homeostasis.9 Although plasma concentrations of many types of cytokines, such as tumor necrosis factor-␣, and interleukin (IL)-1␤, IL-6 and IL-8, are frequently increased in sepsis, it is currently unclear how an abnormal stress response arises.10 This syndrome, especially severe forms of it such as severe sepsis and septic shock, requires intensive care. Since acute obstructive uropathy due to upper urinary tract calculi raises intrarenal pelvic pressure and theoretically decreases the delivery of drugs administered to the kidney, SIRS due to upper urinary tract infection associated with upper urinary tract calculi should frequently require drainage for treatment. While 59 of our 473 patients with lithiasis met our criteria for urosepsis, some others required emergency drainage clinically. Since we do not routinely perform blood gas analysis, still more patients might have met the criteria. Our study revealed that patients undergoing emergency drainage required more treatment interventions and a longer hospital stay than other patients with lithiasis. These findings are not surprising because it takes time for patients to recover from systemic inflammatory status after drainage and undergo treatment for calculi. While our patients with emergency drainage stayed in the hospital 10 days longer than other patients with lithiasis, the degree of difference must differ among countries according to the insurance system. A mean of 1 medical physician, general physician or specialist at a department other than urology examined patients prior to consultation at our department and in 21 of 59 events (36%) some antibiotic therapy had already been given before consultation. There were no marked differences between patients with and those without prior antibiotics except in the number of examinations by physicians prior to consultation with us and the interval from symptom initiation to drainage. This finding combined with the difference in the interval suggests that patients without prior antibiotics tended to have rapid progression of systemic inflammation but it does not imply the efficacy of antibiotic monotherapy for urological infection combined with obstructive uropathy. Ureteral stenting and percutaneous nephrostomy were similarly effective for decreasing systemic inflammation with minor complications. Thrombocytopenia status and stone size may be responsible for determining which procedure is better. While blood thrombocytes have important roles in antimicrobial host defense, megakaryocytopoiesis is inhibited and platelet turnover increases after acute infection with viruses or bacteria.11 Thus, blood thrombocytopenia is included in the determination of the severity of multiple organ dysfunction.12, 13 Approximately 30% of our patients experienced thrombocytopenia. Hyperbilirubinemia suggesting transient hepatic damage was observed in 16% of events and abnormal levels of at least 2 of the 5 liver markers occurred in 34% of

patients. This finding indicates that transient liver damage was common in patients with urosepsis. Although the liver produces inflammatory mediators, it also becomes a target organ for the effects of inflammatory mediators.14 Our analysis of risk factors for emergency drainage was performed by comparison with all patients who required hospitalization for the treatment of upper urinary tract calculi, while most patients with urolithiasis at our department were treated conservatively without hospitalization or with shock wave lithotripsy. This analysis revealed that performance status, age and sex were risk factors for emergency drainage. A history of urolithiasis and diabetes mellitus comorbidity were not associated with emergency drainage. Poor performance status, as represented by spinal cord injury, is a well-known risk factor for renal calculi.15, 16 Our study revealed that poor performance status was also a strong risk factor for urosepsis associated with upper urinary tract calculi. Furthermore, older age and poor performance status were also associated with intensive care. Currently Japan has the longest average life span in the world.17 The World Health Report 2003 indicated that in our country the average life span of men was 78.4 years and that of women was 85.3 years, and these spans have gradually increased.18 This tendency is considered somewhat common in developed countries. Thus, our findings suggest that the number of patients requiring emergency drainage will increase in the future in developed countries. Since these patients require many interventions and a long hospital stay, the increase in the number of them is quite problematic. The prevention of urolithiasis and urinary tract infection in elderly individuals and those with poor performance status will be of considerable importance in the future. REFERENCES

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13. Marshall, J. C., Cook, D. J., Christou, N. V., Bernard, G. R., Sprung, C. L. and Sibbald, W. J.: Multiple organ dysfunction score: a reliable descriptor of a complex clinical outcome. Crit Care Med, 23: 1638, 1995 14. Ferreira, F. L., Bota, D. P., Bross, A., Melot, C. and Vincent, J. L.: Serial evaluation of the SOFA score to predict outcome in critically ill patients. JAMA, 286: 1754, 2001 15. Szabo, G., Romics, L., Jr. and Frendl, G.: Liver in sepsis and systemic inflammatory response syndrome. Clin Liver Dis, 6: 1045, 2002 16. Comarr, A. E., Kawaichi, G. K. and Bors, E.: Renal calculosis of patients with traumatic cord lesions. J Urol, 87: 447, 1962 17. Kracht, H. and Bruscher, H. K.: Formation of staghorn calculi and their surgical implications in paraplegics and tetraplegics. Paraplegia, 12: 98, 1974 18. World Health Report 2003. Washington, D.C.: World Health Organization, 2004