ORIGINAL CONTRIBUTION urinalysis, reliability
Reliability of a Urine Dipstick in Emergency Department Patients We conducted a study to examine whether a negative Chemstrip 9 ®result for leukocyte esterase and nitrite would reliably exclude an abnormal microscopic examination of the urine of emergency department patients. Three hundred urine specimens were subjected to Chemstrip 9® evaluations and full microscopic examinations in the microscopy laboratory. As the microscopy laboratory examination identified lower WBC and bacteria counts, increasing numbers of false-negative urine dipsticks results occurred. The results of our study reveal that the nitrite and leukocyte esterase assays miss significant microscopic findings with corresponding clinical pathology, with the nitrite examination being the less sensitive of the two tests. Based on our results, we believe it would not be prudent to use the Chemstrip 9® dipstick in the ED to exclude the presence of WBC - and bacteria in the urine. [Propp DA, Weber D, Ciesla ML: Reliability of a urine dipstick in emergency department patients. Ann Emerg Med May 1989;18:560-563.] INTRODUCTION Performing microscopic examinations on the urine of emergency department patients can be costly and time consuming. Many authors have evaluated the use of multiagent urine dipsticks to screen patients for the purpose of excluding a microscopic examination of the urine. Unfortunately, none of these studies were done with ED patients. Therefore, we designed a double-blinded prospective study with two purposes in mind: to see if a normal Chemstrip 9 ® (Boehringer Manheim Diagnostics, Inc, Indianapolis, Indiana) for leukocyte esterase and nitrites would reliably exclude the presence of an abnormal microscopic urinalysis for bacteria and WBC in ED patients and to identify the clinical conditions that were present when the Chemstrip 9 ® was falsely negative.
Douglas A Propp, MD, FACEP*t Deborah Weber, MD*t Mary Lou Ciesla, RN* Park Ridge, Illinois From the Division of Emergency Medicine, Lutheran General Hospital, Park Ridge, Illinois;* University of Illinois Affiliated Hospitals Emergency Medicine Residency Program.t Received for publication August 8, 1988. Revision received November 14, 1988. Accepted for publication February 2, 1989. Address for reprints: Douglas A Propp, MD, FACER Division of Emergency Medicine, Lutheran General Hospital, 1775 Dempster Street, Park Ridge, Illinois 60068.
METHODS Three hundred urinalyses ordered from ED patients were studied prospectively. Assumptions of both the false-negative and the true-positive rates of urine dipstick evaluations were obtained from the literature} -4 Including urine specimens from 300 patients guaranteed a confidence interval of 95%.s Our study was performed in a residency-affiliated suburban teaching hospital ED with 39,000 patient visits a year. When a urinalysis was ordered, an aliquot of urine was kept in the ED for the purpose of performing a Chemstrip 9 ® examination while another portion was submitted to the clinical microscopy laboratory. I n the ED, a medical student, resident, or attending physician immediately performed a visual Chemstrip 9 ® examination on the urine specimen. The reading of the reagent strip was performed before any knowledge of the ultimate results obtained in the microscopy laboratory. The clinician noted the patient's name, medical record number, reason for obtaining the urinalysis, how it was obtained, and w h e t h e r a w o m a n was m e n s t r u a t i n g concurrently. The patient's current medications were also included on the data collection sheet. A full urinalysis was performed in the clinical microscopy laboratory by a trained technician within one hour of the time of collection of the urine. The analysis was performed on a Clinitek 200 machine using Multistix ®
18:5 May 1989
Annals of Emergency Medicine
560/117
URINE DIPSTICK Propp, Weber & Ciesla
10SG (Ames Division, Miles Laboratories, Elkhart, Indiana) after the color and turbidity of the urine were noted. This evaluation identified the specific gravity, leukocyte esterase, nitrite, urobilinogen, bilirubin, protein, pH, blood, ketones, and glucose. Once the a u t o m a t e d m u l t i r e a g e n t strip analysis was performed, all samples were centrifuged for five minutes at 2,000 rpm and examined microscopically. The microscopic examination identified the presence of epithelial cells, mucous, crystals, casts, red blood cells, white blood cells, bacteria, yeast, artifacts, and fat. The technician performing this complete urinalysis was blinded as to the results obtained by the clinician in the ED. The data collection sheets from both the ED and the clinical microscopy laboratory were reviewed and the results compared. All charts of patients having a negative ED Chemstrip 9 ® for leukocyte esterase or nitrites and a positive clinical microscopy urinalysis were reviewed.
RESULTS Three hundred three urine specimens were included in our study. If the ED Chemstrip 9 ® evaluation was anything but negative for leukocyte esterase or nitrite, it was considered a positive result. Three urine samples were excluded from the study due to inability to read the Chemstrip 9 ® results because of the presence of interfering pigmentation, f r o m e i t h e r gross blood or phenazopyridine (pyridium). One h u n d r e d n i n e t y - o n e urine specimens (64%) were obtained to look for WBC to confirm a urinary tract infection. Fifty-two urinalyses (17%) were ordered to evaluate patients for the presence of urolithiasis. Nineteen of the urinalyses (6.3%) were obtained as part of routine admission. Sixteen (5.3%) were ordered as part of the workup for abdominal pain. Eleven (3.7%) were obtained to exclude the presence of RBC in trauma victims. Eleven (3.7%) urinalyses were obtained for other reasons (Table 1). Examination of the leukocyte esterase results reveals that when more than 50 WBC were present on microscopy, none were missed by the ED Chemstrip 9 ® (sensitivity, 100%). Of the 21 patients with 21 to 50 WBC identified by microscopy, two would 118/561
TABLE 1. Reasons for obtaining urinalyses
Looking for WBC to rule out urinary tract infection Looking for RBC to rule out a stone Routine admission laboratory workup Evaluation of abdominal pain Looking for RBC in trauma victims Evaluation of diabetic patients Evaluation of hypertensive patients Looking for proteinuria Evaluation of hydration status Evaluation of purpuric patient Total
No.
%
191 52 19 16 11 3 3 2 2 1 300
64 17 6.3 5.3 3.7 1 1 0.7 0.7 0.3
TABLE 2. Clinical microscopy results - l e u k o c y t e esterase White Blood Cells > 50 Leukocyte Esterase Results True ( + ) False ( - )
Sensitivity (%)
22 0 1O0
21-50
19 2 90
13-20
6 4 60
6-12
10 13 44
TABLE 3. Clinical microscopy results - nitrite
Nitrite Results True ( + ) False ( - ) Sensitivity (%)
have been missed (sensitivity, 90%). Of the ten patients with 13 to 20 WBC, four were falsely negative in the ED (sensitivity, 60%). When the laboratory identified six to 12 WBC, 13 would have been missed by the Chemstrip 9 ® e x a m i n a t i o n (sensitivity, 44%) (Table 2). Examination of the nitrite results reveals that w h e n the laboratory identified a large amount of bacteria on microscopy, seven Chemstrip 9s ® were falsely negative (sensitivity, 73%). When the laboratory identified Annals of Emergency Medicine
Large Bacteria
Moderate Bacteria
19 7 73
5 9 46
a moderate amount of bacteria, nine C h e m s t r i p 9s ® w e r e m i s s e d by the examination (sensitivity, 46%) (Table 3). In comparing the Chemstrip 9 ® with the automated Multistix ® done in the microscopy laboratory, differences were noted. Of the total of 19 false-negative ED leukocyte esterase chemstrips, only eight were identified as negative by the automated screener (Table 4). Of the 16 falsely negative ED nitrite Chemstrips ®, t5 were also identified as negative by 18:5 May 1989
TABLE 4. Clinical m i c r o s c o p y results - false-negatives White Blood Cells
ED False-Negative Chemstrip 9 ® Microscopy Laboratory FalseNegative Multistix®
21 - 50
13 - 20
6 - 12
2
4
13
0
1
7
TABLE 5. Clinical m i c r o s c o p y results - false-negatives
ED False-Negative Chemstrip 9 ® Microscopy Laboratory FalseNegative Multistix®
the automated screener (Table 5). Of the 19 falsely negative urine dipsticks for leukocyte esterase, 11 patients u l t i m a t e l y had positive urine cultures, reflecting infection. Two patients had a viral syndrome, two had ureteral calculi, and one each had a partial bowel obstruction, cerebrovascular accident, diabetes out of control, and mittelschmerz. Of the 16 falsely negative ED urine dipsticks for nitrites, ten patients had culture-proven urinary tract infections. One each had renal insufficiency, a r e c u r r e n t m e n i n g i o m a , abdominal pain, vasculitis, appendicitis, and renal colic. DISCUSSION The urinalysis is a commonly ordered test for patients evaluated in the ED setting. Most are obtained with the specific intent of confirming the presence of bacteria, WBC, or blood. Occasionally, urinalyses are done as a screening test to increase the database in evaluating challenging cases. In addition, urinalyses are commonly ordered for patients who are ultimately hospitalized for reasons unrelated to acute urinary tract disease. 6 As xhe issues of time delay and cost involved in obtaining a complete urinalysis in the hospital laboratory are both realistic concerns, a quick, inexpensive, sensitive screening test not requiring technical expertise would be ideal.7, s 18:5 May 1989
Large Bacteria
Moderate Bacteria
7
9
6
9
Some authors have studied the value of screening urine specimens before complete microscopic evaluations.9, lo However, none were performed in an ED where both the prevalence of disease and the indications for ordering the test are unique. Several authors have questioned the reliability of a screening test to exclude the performance of a complete microscopic evaluation.11,12 However, these studies were not performed exclusively on emergency patients and used a different reagent strip than was chosen for this study. W h e r e a s t h e r e have been o t h e r studies supporting the use of a urine dipstick screening before a complete urinalysis, these studies lack direct application to ED patients because of the inclusion criteria used in their studies.I, 13-tz The study by Sewell et al was performed on all patients in a Veterans A d m i n i s t r a t i o n hospital who had urine specimens submitted for cultureJ z Another study was limited by inadequate descriptions of their patient selection process for purposes of adequate comparison. 2 Still another preferentially evaluated only pediatric patients38 The Chemstrip 9 ® was chosen because it was considered the most accurate urine dipstick available at the time the study was performed)2, ~s In addition, the selection of only ED patients for inclusion in the study is unique to the medical literature. The Annals of Emergency Medicine
results were considered reliable as the emergency physician and the clinical m i c r o s c o p y t e c h n o l o g i s t were unaware of each other's results. Because this study evaluated the use of a screening test to exclude a full microscol~ic ,urinalysis on patients who had a negative screen, only the false-negative results were of concern. The true-positive and true-negative patient results were reliably identified. Furthermore, the false-positive results of the screening test were considered acceptable because these individuals would have received a full microscopic urinalysis even if the dipstick examination had not been performed. The false-negative urine dipsticks were of primary concern. Because the manufacturer states that the test for leukocyte esterase should be sensitive to 10 WBC/high power field (hpf), our microscopic results were examined to a level equal to or above 6 to 12 WBC. The results reveal that although none of the 22 patients with more than 50 WBC/hpf were missed, there were increasing numbers of false-negatives as we approached the 10 WBC/hpf level. At 6 to 12 WBC/hpf, 56% of the results were falsely negative. Although a direct correlation between a nitrite level and b~cteriuria is not available, the nitrite dipstick proved even less reliable than the leukocyte esterase. Sixty-four percent of patients with moderate bacteriuria on microscopy had a falsely negative dipstick. This might not be surprising as the nitrite examination only identifies coagulase-splitting bacteria. There were no particular medications that the patients had been taking that interfered with the test results other than the previously mentioned pyridium. Although ascorbic acid has been recognized as interfering with the nitrite test, unless one of our patients acknowledged taking vitamins, ascorbic acid consumption was not noted on the data collection sheet by the physician. The automated urine dipstick performed in the microscopy laboratory would have correctly identified 58% (11 of 19) of the falsely negative ED leukocyte esterase dipsticks. The microscopy laboratory's results for the automated nitrite examination were not nearly as impressive. Only 6% (one of 16) of the falsely negative ED 562/119
URINE DIPSTICK Propp, Weber & Ciesla
nitrite dipsticks would have been correctly identified in the microscopy laboratory by their automated method. F i f t y - e i g h t p e r c e n t (11 of 19) of t h e patients who had a falsely negative leukocyte esterase in the ED ultimately had positive urine cultures with a presenting complaint directly r e f e r a b l e to a u r i n a r y t r a c t i n f e c t i o n . S i x t y - t w o p e r c e n t ( t e n of 16) of t h e falsely negative ED urine dipsticks for n i t r i t e h a d p o s i t i v e u r i n e c u l t u r e s w i t h p r o b l e m s r e f e r a b l e to a u r i n a r y tract infection. A l t h o u g h i t m i g h t h a v e b e e n ideal to c o m p a r e t h e u r i n e d i p s t i c k r e s u l t s w i t h a gold s t a n d a r d of u r i n e c u l t u r e s o n all p a t i e n t s , t h i s w o u l d n o t h a v e simulated true emergency medical p r a c t i c e . D u e to t h e n e e d to i n s t i t u t e t h e r a p y for m a n y p a t i e n t s b e f o r e t h e urine culture results are available, t h e u r i n a l y s i s r e s u l t s are h e a v i l y relied on for decisions regarding the likelihood of infection. Therefore, the microscopy laboratory's results f o r t h e p r e s e n c e of l e u k o c y t e s a n d b a c t e r i a i n t h e u r i n e w e r e u s e d as t h e gold s t a n d a r d . CONCLUSION Our findings indicate that in the ED s e t t i n g s i g n i f i c a n t n u m b e r s of p o s i tive urinalyses for leukocytes and bacteria were missed by using the
120/563
Chemstrip 9 ® examination. Though the automated urine dipstick in the m i c r o s c o p y l a b o r a t o r y w a s m o r e sensitive, i t s t i l l w a s n o t foolproof. Alt h o u g h i t is t e m p t i n g t o u s e t h e C h e m s t r i p 9 ® i n t h e E D b e c a u s e of it,~ speed, ease, a n d c o s t savings, o u r study demonstrates that there are i m p r e s s i v e gaps i n i t s r e l i a b i l i t y .
T h e a u t h o r s recognize t h e c o o p e r a t i o n and assistance of the L u t h e r a n General Medical Group, Sue Hall, M T (AMT), T Okuno, MD, E Chen, PhD, and Shirley Swanson in completing this study.
REFERENCES 1. Mariani AJ, Luangphinith S, Loo S, et al: Dipstick chemical urinalysis: An accurate costeffective screening test. J U r o t 1984;132:64-66. 2. Benham L, O'Kell RT: Urinalysis: Minimizing microscopy (letter). C l i n C h e m 1982; 28:1722. 3. Kusumi RK, Glover PJ, Kunin CM: Rapid detection of pyuria by leukocyte esterase activity. JAMA 1981;245:1653-i655. 4. Kiel DE Moskowitz MA: The urinalysis: A critical appraisal. M e d Clin North A m 1987; 71:607-624. 5. Boag JW: Number of patients required in a clinical trial. Br J Radiol 1971;44:122-125. 6. Schumann GB, Greenberg NF: Usefulness of macroscopic urinalysis as a screening procedure. A m J C1in PathoI 1979;71:452-456.
Annals of Emergency Medicine
7. Campbell TL: Routine urinalysis: Is the dipstick enough? (letter). JAMA 1985;254:1723. 8. Zilva JF: Is the unselective biochemical urine testing cost effective? Br M e d J 1985;291: 323-325. 9. Kiechle FL, Karcher RE, Epstein E: Routine microscopic examination of the urine sediment revisited (letter/. A r c h P a t h o i L a b M e d 1984;108:855. 10. Gillenwater JY: Detection of urinary leukocytes by Chemstrip-L. J Urol 1981;125:383. ll. Szwed J, Schaust C: The importance of microscopic examination of the urinary sediment. A m J Med Technology 1982;48:141-143. 12. Wenk RE, Dutta D, Rudert J, et ah Sediment microscopy, nitrituria and leukocyte esterasuria as predictors of significant bacteriuria. J Clin Lab A u t o m a t i o n 1982;2:117-121. i3. Valenstein PN, Koepke JA: Unnecessary microscopy in routine urinalysis. A m J Clin Pathol 1984;82:444-448. 14. Loo 8YT, Scottolini AG, Luangphinith MT, et ah Performance of a urine-screening protocol. A m J Clin Pathol 1986;85:479-484. 15. Shaw ST, Poon SY, Wong ET: Routine urinalysis: Is the dipstick enough? JAMA 1985; 253:1596-1600. 16. 8mailey DL, Bryan JA: Comparative evaluation of biochemical and microscopic urinalysis. A m J Med Technology April 1983;49:237-239. 17. Sewell DL, Burt SP, Gabhert NJ, et ah Evaluation of the Chemstrip 9 as a screening test for urinalysis and urine culture in men. A m J Clin Pathoi 1985;83:740-743. 18. Hamoudi AC, Bubis SC, Thompson C: Can the cost savings of eliminating urine microscopy in biochemically negative urines be extended to the pediatric population? A m J Clin Pathoi 1986;86:658-660.
18:5 May 1989