The Journal of Emergency Medicine, Vol. 49, No. 2, pp. 130–135, 2015 Copyright Ó 2015 Elsevier Inc. Printed in the USA. All rights reserved 0736-4679/$ - see front matter

http://dx.doi.org/10.1016/j.jemermed.2014.12.085

Original Contributions

RISK FACTORS ASSOCIATED WITH UROLOGIC INTERVENTION IN EMERGENCY DEPARTMENT PATIENTS WITH SUSPECTED RENAL COLIC Justin W. Yan, MD, MSC, FRCPC, Shelley L. McLeod, MSC, Marcia L. Edmonds, MD, FRCPC, MSC, Robert J. Sedran, MD, FRCPC, MSC, and Karl D. Theakston, MD, MSC Division of Emergency Medicine, Department of Medicine, The University of Western Ontario and Schulich School of Medicine and Dentistry, The University of Western Ontario, London, Ontario, Canada Reprint Address: Justin W. Yan, MD, MSC, FRCPC, Division of Emergency Medicine, Department of Medicine, The University of Western Ontario, Room E1-120, Westminster Tower, 800 Commissioners Road East, London, ON N6A 5W9, Canada

, Abstract—Background: Whereas most patients with urolithiasis pass their stones spontaneously and require only symptomatic management, a minority will require urologic intervention. Objective: Our primary objective was to confirm previously reported risk factors and to identify additional predictors of urologic intervention within 90 days, for emergency department (ED) patients with suspected renal colic. Methods: We conducted a prospective cohort study of adult patients presenting to one of two tertiary care EDs with suspected renal colic over a 20-month period. Multivariate logistic regression models determined predictor variables independently associated with urologic intervention. Results: Of the 565 patients included in the analysis, 220 (38.9%) patients had a ureteric stone visualized on diagnostic imaging. Eighty-four patients (14.9%) had urologic intervention within 90 days of their initial ED visit. Urinary nitrites (odds ratio [OR] 4.2, 95% confidence interval [CI] 1.3–13.6), stone size $ 5 mm (OR 4.2, 95% CI 2.4– 7.4), proximal ureteric stone (OR 3.1, 95% CI 1.5–6.4), age $ 50 years (OR 2.8, 95% CI 1.5–5.0), tachycardia at triage (OR 2.5, 95% CI 1.1–5.4), urinary leukocyte esterase (OR 2.3, 95% CI 1.2–4.5), abnormal serum white blood cells (OR 2.0, 95% CI 1.2–3.3), and history of renal colic (OR 1.8, 95% CI 1.1–3.1) were factors independently associated with urologic intervention within 90 days. Conclusions: Our study reports eight risk factors associated with urologic intervention within 90 days in patients presenting to the ED with renal colic. These risk factors should be considered when making management, prognostic, and disposition deci-

sions for patients with suspected urolithiasis. Elsevier Inc.

Ó 2015

, Keywords—urolithiasis; risk factors; urologic intervention; emergency medicine

INTRODUCTION Whereas most patients with urolithiasis pass their stones spontaneously and require only symptomatic management, a minority will require urologic intervention, such as extracorporeal shock wave lithotripsy, ureteric stenting, or open stone extraction (1–4). Several studies have attempted to identify predictors of urologic intervention (1,5,6). In a prospective study of 75 patients with ureterolithiasis, Miller and Kane found that increased stone size ($5 mm) was correlated with higher rates of urologic intervention (5). Another study, by Coll et al., reported an association between spontaneous stone passage and stone location as identified by computed tomography (CT) (1). This retrospective study of 172 patients found that rates of spontaneous passage were higher with progressively distal location of the calculus, whereas proximal stones were associated with increased need for urologic intervention. Additionally,

RECEIVED: 2 July 2014; FINAL SUBMISSION RECEIVED: 30 September 2014; ACCEPTED: 21 December 2014 130

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patients with larger stones were less likely to pass their stones spontaneously, confirming previous results reported by Miller and Kane (1,5). In a prospective cohort study by Papa et al., emergency department (ED) patients with renal colic were followed to identify predictors of urologic intervention (6). In addition to stone size and location, they found that pain score upon ED discharge was also associated with urologic intervention within 4 weeks after initial presentation. However, urologic intervention may be necessary if the calculus does not progress or spontaneously pass within 30 days (7). Additionally, complications may occur up to 3 months after the stone has been identified, suggesting that follow-up longer than 30 days may be necessary (8). Despite being a non-life-threatening illness, the burden of disease of renal colic is significant. Inadequate management of symptoms such as nausea, vomiting, or pain may affect patients beyond the duration of the initial ED visit. Delayed patient-important outcomes may include prolonged duration of analgesic use, missed days of school or work, and multiple repeat visits to a health care provider. The primary objective of our study was to confirm previously reported risk factors and identify additional predictors of urologic intervention within 90 days for patients who present to the ED with suspected renal colic. We also sought to determine the burden of disease with respect to delayed patient-important outcomes after patients were discharged from the ED. METHODS We conducted a prospective cohort study over a 20month period (Oct 2010 to June 2012) at an academic tertiary care center consisting of two EDs with a combined annual census of 140,000 visits. Our center is the major regional referral center for urologic intervention within London, Ontario, Canada, with a catchment area containing over three million patients. The study protocol was approved by the Health Sciences Research Ethics Board at The University of Western Ontario. All adult patients ($18 years) who presented to the ED with suspected renal colic were eligible to be enrolled. Triage nurses screened all patients with chief complaints of abdominal pain, flank pain, or hematuria to determine if they were eligible for study enrollment. Attending physicians screened patients when they were missed at triage. Eligibility was confirmed by the attending physician who also obtained informed written consent. Enrollment in the study did not alter the patients’ ED management. Trained research personnel extracted demographic and clinical parameters from paper and electronic charts using a standardized data collection tool. Patients were contacted by telephone 48–72 h and again 10–14 days af-

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ter their initial ED visit to determine use of analgesics, missed days of school or work, and repeat visits to a health care provider. If patients were unable to be contacted by telephone, questionnaires were mailed. A 90day electronic chart review was also conducted by research assistants to determine whether patients had repeat ED visits, outpatient urology visits, or urologic intervention. To estimate the sample size required for the multivariate regression model, we used the formula by Peduzzi et al. (1996), N = 10 k/p; where p is the estimated proportion of patients who require urologic intervention and k is the number of covariates (independent variables) to be included in the model (9). We expected to include 13 covariates in the multivariate model and estimated that 23% of patients would require urologic intervention, resulting in an estimated sample size of 565 patients. Data were entered directly into a study-specific Microsoft Excel database (Microsoft Corporation, Redmond, WA). Patient characteristics were summarized using descriptive statistics and 95% confidence intervals using standard equations. Data elements were chosen with the intent of evaluating variables for model inclusion based on what is known about the epidemiology of the disease process as well as hypothesized relationships between potential independent variables and urologic intervention. Univariate analysis of all potential patient risk factors were completed and clinically relevant variables with a p-value of 0.10 or less in the univariate analysis were considered for the multivariate models. Multivariate logistic regression models were used to determine predictor variables independently associated with urologic intervention. Likelihood ratio tests determined appropriate inclusion of variables in the multivariate logistic regression model. Backwards, stepwise multivariable logistic regression (Wald removal criterion of 0.1) was done to determine predictor variables independently associated with urologic intervention. The Hosmer–Lemeshow goodness-of-fit statistic measured how well the final model described the response variable. All analyses were performed using SPSS 21.0 (IBM Corporation, Somers, NY). RESULTS Over the 20-month study period, a total of 768 patients were screened by triage nurses for eligibility. Of those, 203 were excluded, leaving 565 patients in our final data analysis (Figure 1). Characteristics of these patients are summarized in Table 1. There were 1236 ED patient visits with a final diagnosis of urolithiasis over the study period. Of the 565 patients enrolled in our study, 438 (77.5%) had some form of diagnostic imaging completed in the ED. Of the 565

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Figure 1. Consort diagram of eligible and enrolled patients. RC = renal colic.

included study patients, 220 (38.9%) had a ureteric stone visualized on CT scan, ultrasound (US), or both, and 84 (14.9%) patients underwent urologic intervention within 90 days of their initial ED visit. The median stone size for patients who had urologic intervention was 7 (interquartile range [IQR] 5–10) mm. Variables considered in the logistic regression model are listed in Table 2. Presence of nitrites on Chemstrip (Roche Diagnostics, Indianapolis, IN) urinalysis (odds ratio [OR] 4.2, 95% confidence interval [CI] 1.3–13.6), ureteric stone size $ 5 mm on either CT scan or US (OR 4.2, 95% CI 2.4–7.4), proximal (above mid-ureter) ureteric stone (OR 3.1, 95% CI 1.5–6.4), age $ 50 years (OR 2.8, 95% CI 1.5–5.0), tachycardia at triage (OR 2.5, 95% CI 1.1–5.4), presence of leukocyte Table 1. Characteristics and Emergency Department Demographics of Study Patients Characteristic

n = 565

Male Mean (SD) age (years) Previous history of renal colic Previous history of urologic intervention for ureterolithiasis Previous history of hypertension Previous history of diabetes mellitus Median (IQR) pain score at triage Microscopic hematuria on urinalysis Median (IQR) creatinine (micromoles/L) CTAS 2 CTAS 3 CTAS 4 CTAS 5 Admitted from ED

355 (62.8%) 46.6 (14.4) 258 (45.7%) 59 (10.4%) 108 (19.1%) 38 (6.7%) 9 (7–10) 451 (79.8%) 79 (66–96) 251 (44.4%) 271 (48.0%) 40 (7.1%) 3 (0.5%) 15 (2.7%)

SD = standard deviation; IQR = interquartile range; CTAS = Canadian Triage and Acuity Scale; ED = emergency department.

esterase on Chemstrip urinalysis (OR 2.3, 95% CI 1.2– 4.5), abnormal serum white blood cells (OR 2.0, 95% CI 1.2–3.3), and history of renal colic (OR 1.8, 95% CI 1.1–3.1) were independently associated with urologic intervention within 90 days (Table 3). Of the 565 patients enrolled in our study, 539 (95.4%) were contacted at 48–72 h and again 10–14 days after their ED visit to determine analgesic use, missed days of school or work, and repeat visits to a health care provider. Fifteen (2.7%) patients were admitted. There were 143 (26.5%) patients who reported passing a stone spontaneously within 72 h, and 57 (10.6%) additional patients reported passing a stone spontaneously within 14 days. There were 421 (78.1%) patients who required analgesia for a median (IQR) duration of 4 (2–7) days, with 135 (25.0%) still requiring analgesia at 10– 14 days. Also, 266 (49.4%) patients missed school or work for a median (IQR) duration of 2 (1–3) days, and 255 (47.3%) reported seeing another physician within 10–14 days (Table 4). DISCUSSION The results of our study confirm two previously reported risk factors (stone size $ 5 mm on either CT scan or US and proximal ureteric stone). Furthermore, we identified six additional predictors (presence of nitrites on Chemstrip urinalysis, presence of leukocyte esterase on Chemstrip urinalysis, age $ 50 years, tachycardia at triage, abnormal serum white blood cells, and a history of renal colic) independently associated with urologic intervention within 90 days for suspected renal colic patients presenting to the ED. The presence of nitrites and leukocyte esterase on Chemstrip urinalysis are suggestive of urinary tract infection (UTI). Whereas most ureteric stones can be managed with pain control and symptomatic management, obstructing stones with a suspected UTI may require additional treatment. In these patients, it is often necessary to eradicate both the infection and the causative obstruction to avoid more severe complications such as permanent renal scarring, dysfunction, or urosepsis (10,11). Therefore, suspicion of UTI associated with urolithiasis, either clinically or confirmed with urinalysis or culture, may warrant prompt consultation for admission and urologic intervention. Age $ 50 years, abnormal serum white blood cells, and tachycardia (initial heart rate $ 100 beats/min) were also found to be predictive of urologic intervention within 90 days. It is possible that older patients with more comorbidities are at greater risk for serious complications of ureterolithiasis, lowering a surgeon’s threshold for intervention. Additionally, patients with an abnormal serum white blood cell count may have a more

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Table 2. Characteristics of Presenting Patients, Organized by whether They Had Urologic Intervention (n = 84) or not (n = 481)

Variable

Urologic Intervention n = 84 n (14.9%)

No Urologic Intervention n = 481 n (85.1%)

Total N = 565

Male Age > 50 years* CTAS 2 CTAS 3 CTAS 4 CTAS 5 Tachycardia at triage (HR $ 100 beats/min)* Triage pain score > 7.5 Discharge pain score > 5 Previous renal colic* Previous urologic intervention Hematuria on urinalysis Leukocyte esterase on urinalysis* Nitrites on urinalysis* Abnormal WBC on blood work* Elevated creatinine (male > 120 mmol/L; female > 100 mmol/L)* Presence of hydronephrosis* Abnormal ureteric jet* Presence of perinephric fluid* Any ureteric stone seen on imaging* Ureteric stone size $ 5 mm* Proximal location of stone*

56 (66.7%) 63 (75.0%) 41 (48.8%) 38 (45.2%) 4 (4.8%) 1 (1.2%) 14 (16.7%) 42 (50.0%) 23 (27.4%) 48 (57.1%) 6 (7.1%) 72 (85.7%) 24 (28.6%) 8 (9.5%) 45 (53.6%) 13 (15.5%) 38 (45.2%) 20 (23.8%) 8 (9.5%) 58 (69.0%) 45 (53.6%) 23 (27.4%)

299 (62.2%) 253 (52.6%) 210 (43.7%) 233 (48.4%) 36 (7.5%) 2 (0.4%) 46 (9.6%) 213 (44.3%) 118 (24.5%) 211 (43.9%) 53 (11.0%) 379 (78.8%) 64 (13.3%) 10 (2.1%) 185 (38.5%) 28 (5.8%) 130 (27.0%) 62 (12.9%) 21 (4.4%) 162 (33.7%) 89 (18.5%) 29 (6.0%)

355 316 251 271 40 3 60 255 141 259 59 451 88 18 230 41 168 82 29 220 134 52

CTAS = Canadian Triage Acuity Scale; HR = heart rate; WBC = white blood cells. * These variables were considered in the multivariate model.

concerning infectious or inflammatory reaction compared to patients with a normal white blood cell count, which may be helpful in identifying infected obstructed stones where urinary markers are erroneously absent. Finally, we found that tachycardia at triage was predictive of intervention and is a clinical sign that may be indicative of a more severe disease process. Although a history of renal colic was found to be predictive of urologic intervention in our analysis, previous urologic intervention was not found to be an independent risk factor. This may be due to varying opinions between Table 3. Variables Independently Associated with Urologic Intervention Within 90 Days as Determined by Multivariate Logistic Regression Model Predictor Variable

Adjusted 95% Confidence Odds Ratio Intervals

urologists regarding the necessity for intervention, and the threshold for managing urolithiasis surgically may be physician-specific at our center. Furthermore, several other variables that we expected might have been related to urologic intervention were not found to be independently associated in our analysis. These included results of blood work and imaging tests that were indicative of an obstructive process, including elevated creatinine, presence of hydronephrosis, perinephric fluid, or abnormal urinary jets. In contrast to the Papa et al. study, our findings did not show that discharge pain score was predictive of urologic intervention (6). The median pain score on discharge was

Table 4. Patients Who Reported Seeing Another Physician Within 10–14 Days after Their Initial ED Visit Physician Type

Presence of nitrites on Chemstrip urinalysis Stone size $ 5 mm on either CT scan or US Proximal (above mid-ureter) ureteric stone Age $ 50 years Tachycardia at triage Presence of leukocyte esterase on Chemstrip urinalysis Abnormal serum white blood cells History of renal colic

4.2

1.3, 13.6

4.2

2.4, 7.4

3.1

1.5, 6.4

2.8 2.5 2.3

1.5, 5.0 1.1, 5.4 1.2, 4.5

2.0 1.8

1.2, 3.3 1.1, 3.1

CT = computed tomography; US = ultrasound.

Family physician or walk-in clinic Urologist Another emergency physician Family physician or walk-in clinic and another emergency physician Urologist and another emergency physician Family physician or walk-in clinic and urologist Other physician Family physician and other physician Family physician or walk-in clinic and another emergency physician and urologist ED = emergency department.

n = 255 127 (49.8%) 80 (31.4%) 19 (7.5%) 8 (3.1%) 8 (3.1%) 5 (2.0%) 5 (2.0%) 2 (0.8%) 1 (0.4%)

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2 (IQR 1–5), compared to an initial median pain score at triage of 9 (IQR 7–10). This suggests that our patients are not being discharged until their pain is well managed in comparison to their presenting pain. Additionally, pain is a self-reported, subjective measure and is less predictive of disease severity or complications. Recently, in an attempt to identify patients with either a very high or a very low probability of having an uncomplicated ureterolithiasis, Moore et al. retrospectively derived and prospectively validated the STONE score, which reliably predicts the presence of an uncomplicated ureteral stone and lower likelihood of acutely important alternative findings (12). The presence of nausea or vomiting, microscopic hematuria, short pain duration, and being male and non-black were all found to be independent predictors of uncomplicated ureteral stones in adults with flank pain. Of the patients contacted 10–14 days after their ED visit to determine repeat visits to a health care provider, 255 (47.3%) reported seeing another physician within 2 weeks. Of these patients who saw another physician, 94 (36.9%) had follow-up with a urologist within 2 weeks. A retrospective study by Sterrett et al. enrolled 130 patients diagnosed with ureterolithiasis in the ED over a 2-year period (13). In that study, 116 (89.2%) patients were discharged by the emergency physician, 71 patients (61%) followed up with a urologist, 27 patients (23%) followed up with a primary care physician, 10 patients (9%) returned to the ED for their initial follow-up, and 8 patients (7%) had no further follow-up. Of the 44 patients with ureteral calculi $ 5 mm, 38 patients (86%) either received urologic consultation in the ED or followed up with a urologist as an outpatient (13). Limitations Our study was conducted at a single center consisting of two tertiary care EDs, and the results may not be generalizable to other settings. The threshold for ED urologic consultation and surgical intervention rates for renal colic vary by urologist and by region. The specific clinical indication for intervening was not captured as part of this study. Additionally, it is possible that some of the patients enrolled may have sought urologic consultation outside of our center’s catchment area. However, our institution is the major regional referral center within Southwestern Ontario for urologic intervention, resulting in a relatively closed medical system. Selection bias may have been a factor in our study. Eligibility for enrollment was based on a clinical suspicion of renal colic at triage. Although triage nurses and physicians were asked to consider all comers with any presenting complaint that could be related to urolithiasis, the majority of patients enrolled likely had a classic pre-

J. W. Yan et al.

sentation. Patients with more atypical signs and symptoms may not have been enrolled. Caution should be used if results from our study are extrapolated to a broader population of patients with more atypical symptoms. However, given that this was a prospective, pragmatic study, we do not believe that the external validity of our conclusion is compromised. CONCLUSIONS Our study identified eight variables independently associated with urologic intervention within 90 days of an initial ED visit for patients with suspected renal colic: presence of nitrites on Chemstrip urinalysis, presence of leukocyte esterase on Chemstrip urinalysis, stone size $ 5 mm, proximal location of stone on imaging, age $ 50 years, tachycardia at triage, abnormal white blood cells on blood work, and a previous history of renal colic. Patients with these risk factors have a higher likelihood of urologic intervention and should be considered for early urologic follow-up. Despite being a non-lifethreatening illness, the burden of disease of urolithiasis is significant. Adverse outcomes may affect patients and the health care system beyond what may be seen with an isolated ED visit. REFERENCES 1. Coll DM, Varanelli MJ, Smith RC. Relationship of spontaneous passage of ureteral calculi to stone size and location as revealed by unenhanced helical CT. AJR Am J Roentgenol 2002;178:101–3. 2. Hubner WA, Irby P, Stoller ML. Natural history and current concepts for the treatment of small ureteral calculi. Eur Urol 1993; 24:172–6. 3. Glowacki LS, Beecroft ML, Cook RJ, et al. The natural history of asymptomatic urolithiasis. J Urol 1992;147:319–21. 4. Riehle RA Jr, Fair WR, Vaughan ED Jr. Extracorporeal shock-wave lithotripsy for upper urinary tract calculi. JAMA 1986;255:2043–8. 5. Miller OF, Kane CJ. Time to stone passage for observed ureteral calculi: a guide for patient education. J Urol 1999;162:688–90. 6. Papa L, Stiell IG, Wells GA, et al. Predicting intervention in renal colic patients after emergency department evaluation. CJEM 2005;7:78–86. 7. Leventhal EK, Rozanski TA, Crain TW, et al. Indwelling urethral stents as definitive therapy for distal ureteric calculi. J Urol 1995; 153:34–6. 8. Tan AH, Al-Omar M, Watterson JD, et al. Results of shockwave lithotripsy for pediatric urolithiasis. J Endourol 2004;18:527–30. 9. Peduzzi P, Concato J, Kemper E, et al. A simulation study of the number of events per variable in logistic regression analysis. J Clin Epidemiol 1996;49:1373–9. 10. Preminger GM, Tiselius H, Assimos DG, et al. 2007 guideline for the management of ureteral calculi. Eur Urol 2007;52:1610–31. 11. Graham A, Luber S, Wolfson AB. Urolithiasis in the emergency department. Emerg Med Clin North Am 2011;29:519–38. 12. Moore CL, Bomann S, Daniels B, et al. Derivation and validation of a clinical prediction rule for uncomplicated ureteral stone—the STONE score: retrospective and prospective observational cohort studies. BMJ 2014;348:g2191. 13. Sterrett SP, Moore NW, Nakada SY. Emergency room follow-up trends in urolithiasis: single-center report. Urology 2009;73: 1195–8.

Urologic Intervention for Suspected Renal Colic in the ED

ARTICLE SUMMARY 1. Why is this topic important? Whereas most patients with urolithiasis pass their stones spontaneously and only require symptomatic management, a minority will require urologic intervention. Several studies have attempted to identify predictors of urologic intervention and found that increased stone size ($5 mm), proximal stones, and pain score upon emergency department (ED) discharge were associated with higher rates of extracorporeal shock wave lithotripsy, ureteric stenting, or open stone extraction. 2. What does this study attempt to show? The primary objective of this study was to confirm previously reported risk factors and identify additional predictors of urologic intervention within 90 days for patients who present to the ED with suspected renal colic. We also sought to determine the burden of disease with respect to delayed patient-important outcomes after patients were discharged from the ED. 3. What are the key findings? This study identified eight variables independently associated with urologic intervention within 90 days of an initial ED visit for patients with suspected renal colic: presence of nitrites and leukocyte esterase on Chemstrip urinalysis, stone size $ 5 mm, proximal location of stone on imaging, age $ 50 years, tachycardia at triage, abnormal white blood cells on blood work, and a previous history of renal colic. 4. How is patient care impacted? Patients with these risk factors have a higher likelihood of urologic intervention and should be considered for early urologic follow-up.

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Risk Factors Associated with Urologic Intervention in Emergency Department Patients with Suspected Renal Colic.

Whereas most patients with urolithiasis pass their stones spontaneously and require only symptomatic management, a minority will require urologic inte...
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