American Journal of Emergency Medicine 32 (2014) 260–262

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American Journal of Emergency Medicine

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Brief Report

Urinalysis is an inadequate screen for rhabdomyolysis☆,☆☆

Sameir A. Alhadi, MD ⁎, Rawnica Ruegner, MD, Brandy Snowden, MPH, Gregory W. Hendey, MD
UCSF Fresno Department of Emergency Medicine, Fresno, CA

a r t i c l e i n f o a b s t r a c t

Article history: Study Objectives: Hematuria by urine dipstick with absent red blood cells (RBCs) on microscopy is indicative of
Received 18 July 2013 rhabdomyolysis. We determined the sensitivity of this classic urinalysis (UA) finding in the diagnosis
Received in revised form 11 October 2013 of rhabdomyolysis.
Accepted 26 October 2013 Methods: We conducted a retrospective electronic medical record review of patients with a primary or
secondary diagnosis of rhabdomyolysis with a creatine phosphokinase (CPK) greater than 1000 IU/L and a UA
within the first 24 hours. Data were collected using a standardized data form, and a blinded panel of 3
emergency medicine physicians reviewed selected cases. Sensitivity and 95% confidence intervals (CIs) were
calculated for detection of rhabdomyolysis by UA.
Results: During the study period, 1796 patients were diagnosed with rhabdomyolysis, of whom 228 met
inclusion criteria. The mean peak CPK was 27 509 IU/L. One hundred ninety-five (86%) had a urine dip-
positive for blood. However, only 94 patients (41%) had a positive urine dip and negative microscopic
hematuria, resulting in a sensitivity of 41% (95% CI, 35%-47%). In a subset of 66 patients (29%) with more
severe rhabdomyolysis (initial CPK, ≥ 10 000 IU/L; mean CPK, 53 365 IU/L), UA had a sensitivity of 55% (95% CI,
43%-67%). Broadening the definition of negative microscopy from 0 to 3 RBCs to less than 10 RBCs only
increased the sensitivity to 79% (95% CI, 73%-83%).
Conclusions: The combination of a positive urine dip for blood and negative microscopy is an insensitive test
for rhabdomyolysis, and the absence of this finding should not be used to exclude the diagnosis.
© 2014 Elsevier Inc. All rights reserved.

1. Introduction
Rhabdomyolysis is a clinical syndrome that is defined by the
breakdown of striated skeletal muscle resulting from injury. Bywaters
and Beall [1] initially described it in 1941 as a syndrome related to
severe trauma and crush injuries. The etiology of rhabdomyolysis has
since been expanded to include other more commonly encountered
exposures such as drugs and toxins, intense physical exertion,
infections, hyperthermia, muscle ischemia, and hereditary muscle
enzyme defects [2-4]. The damaged muscle cell membranes and
sarcolemma allow for the leakage of intracellular constituents and
cause an influx of calcium into the cell. This results in the expulsion of
creatine phosphokinase (CPK), lactic dehydrogenase, potassium,
aldolase, uric acid, glutamic oxaloacetic transaminase, and myoglobin
into the extracellular fluid. Myoglobin is a heme-containing monomer
that is excreted into the renal tubules and causes the classic reddish-
brown or tea-colored urine common in patients with rhabdomyolysis
[5,6]. Myoglobin levels begin to rise in serum 2 hours after the initial
injury and must reach a renal threshold before it is detectable in the
urine [6].
It is critical to diagnose rhabdomyolysis early to initiate treatment
aimed at preventing acute kidney injury [7]. The traditional screening
test for rhabdomyolysis is the urinalysis (UA). The presence of blood
on a qualitative urine dipstick test while red blood cells (RBCs) are
absent on microscopy is suggestive of myoglobinuria and thus
rhabdomyolysis [5]. This reaction is formed by the orthotoluidine on
the urine dip test strip and the heme molecule found in both
myoglobin and hemoglobin [6]. Despite these classic teachings, the
sensitivity of the UA as a screening test for the detection of
rhabdomyolysis in the emergency department (ED) has not been
well established.
The objective of this study was to determine the sensitivity of UA
as a screening test for the detection of rhabdomyolysis in the ED.
2. Methods
2.1. Study design, setting, and selection of patients

☆ The abstract was presented at the SAEM and the Western SAEM Conference in
2010.
☆☆ No external or outside financial interest contributed to this study.
⁎ Corresponding author. Department of Emergency Medicine, UCSF Fresno Medical
Education Program, Fresno, CA 93701. Tel.: +1 559 499 6440; fax: +1 559 499 6441.
E-mail address: salhadi@fresno.ucsf.edu (S.A. Alhadi).
We conducted a retrospective electronic medical record review at
a university-affiliated, level 1 trauma center with an emergency
medicine residency program. The study was approved by the
Community Regional Medical Center Institutional Review Board.
Patients selected for the study included all those with a primary or

0735-6757/$ – see front matter © 2014 Elsevier Inc. All rights reserved.
http://dx.doi.org/10.1016/j.ajem.2013.10.045
 S.A. Alhadi et al. / American Journal of Emergency Medicine 32 (2014) 260–262
secondary admission or discharge diagnosis of rhabdomyolysis as
determined by the International Classification of Diseases, Ninth
Revision. Patients enrolled were selected from September 1, 2003, to
December 31, 2008, using the available electronic medical record.
Data were obtained by trained abstractors using a standardized
form to record demographic information, laboratory values, treat-
ment, and disposition.
2.2. Data collection
For study inclusion, we required a UA and serum CPK within 24
hours of presentation to the ED. We defined rhabdomyolysis as a CPK
greater than 1000 IU/L in the ED or during the subsequent
hospitalization, along with a diagnosis of rhabdomyolysis as deter-
mined by a blinded expert review. Cases were reviewed by a panel of
3 board-certified emergency physicians, blinded for the purpose of
the study, to determine whether rhabdomyolysis was present or
absent. The expert reviewers were instructed to review the medical
record of cases with CPK greater than 1000 IU/L, looking at peak and
trend of CPK measurement, renal function, hospital disposition,
consultations, and any other information and to consider whether
the treating physician diagnosed and treated the patient for
rhabdomyolysis. If 2 of 3 reviewers concluded that rhabdomyolysis
was present, the case was included for study purposes.
We defined a UA as “positive” for the detection of rhabdomyolysis
if the dipstick test for blood was positive in any way (trace, 1 +, 2 +, or
3 +) and microscopy was negative (≤3 RBCs), according to our
clinical laboratory definition. Acute kidney injury or changes in renal
function were defined by using the International Classification of
Diseases, Ninth Revision, diagnosis of acute renal failure.
2.3. Analysis
We entered the study data into a password-protected spreadsheet
(Microsoft Excel 2007, Redmond, WA). We then calculated the
sensitivity and 95% confidence intervals (CIs) for the initial ED UA
for the detection of rhabdomyolysis. Because many rhabdomyolysis
cases by our definition would be mild and of little clinical
consequence, we also analyzed the subgroup of patients with
presumably more severe rhabdomyolysis, with an initial CPK greater
than 10 000 IU/L.
3. Results
The medical record search revealed 1796 cases with an admission
or discharge diagnosis of rhabdomyolysis. Most, however, had a
remote history of rhabdomyolysis, rather than an acute episode or had
a minimal elevation of CPK. Of 1796 cases, 290 had a CPK greater than
1000 IU/L at some point during the hospitalization, and the remainder
were excluded (Fig.). Thirty-nine additional cases were excluded by
the expert panel review, and 23 were excluded for not having a UA
done within 24 hours of presentation. Thus, 228 patients met the
inclusion criteria and comprised the study population (Fig.).
Fig. Breakdown of patients diagnosed with rhabdomyolysis. *Study criteria included medical record diagnosis of rhabdomyolysis, CPK greater than 1000, expert panel chart review
consistent with rhabdomyolysis, and UA performed within 24 hours of admission.
261
The mean age was 46 years (range, 15-102); 79% were male, and
21% were female (Table 1). The most common presumed causes of
rhabdomyolysis included recent illicit drug use, seizures, and sepsis,
although approximately half were idiopathic (Table 1). All the
patients included in the study were hospitalized, and their overall
mortality was 18%. Sixteen (7%) were diagnosed with acute kidney
injury or required hemodialysis.
The mean initial CPK was 17 371 IU/L (range, 56-278 000 IU/L), and
mean peak CPK was 27 509 IU/L (range, 1166-404 700 IU/L) (Table 2).
Of the 228 patients, 195 (86%) included in the study had a UA dipstick
positive for blood. However, only 94 (41%) had both UA dipstick
positive for blood and negative microscopy (Table 1). The sensitivity
of the initial UA for rhabdomyolysis within the first 24 hours of
presentation was 41% (95% CI, 35%-47%).
A subset of 66 patients with more severe rhabdomyolysis, defined
as an initial CPK greater than 10 000 IU/L (mean CPK, 53 365 IU/L),
were found to have a UA sensitivity of 55% (95% CI, 43%-67%). If we
further broadened the definition of negative urine microscopy to less
than 10 RBCs (instead of b 3 RBCs), the resulting sensitivity increased
to 79% (95% CI, 73%-83%).
4. Discussion
According to our definitions, we found that, in contrast to the
classic teaching, the initial UA was not a sensitive screening test for
the detection of rhabdomyolysis. Even when we changed the
conditions of the search to maximize the sensitivity of the UA by
examining the subgroup of more severe rhabdomyolysis and using a
more liberal definition of “negative” urine microscopy, the screening
UA would have missed more than 20% of the cases.
Given that rhabdomyolysis is an inexact syndrome with a wide
clinical spectrum, we defined cases for this study using both a
threshold CPK and an expert panel review of the clinical settings. We
chose a threshold CPK greater than 1000 IU/L, but because there is
no well-accepted definition, our choice was arbitrary. Likewise, our
panel of expert reviewers had no clear evidence-based guidelines to
assist in the determination of which patients, in fact, had
rhabdomyolysis. An important purpose of our expert panel review
was to eliminate cases that had a small, transient elevation of CPK
with no clinical consequence. By allowing the reviewers access to
the UA results, our study was vulnerable to incorporation bias.
However, the most likely effect of this bias would be to falsely inflate
the sensitivity of the UA, causing us to overestimate its value. Thus,
there is no effect on our conclusion that the UA is an inadequate
screening test for rhabdomyolysis.
Almost 10% of the cases were excluded because a UA was not
obtained within 24 hours of admission. It is unclear whether this
introduced significant bias into our study. One could surmise that the
cases were so severely dehydrated or anuric that urine could not be
obtained or that they were so clinically mild that the elevated CPK was
thought irrelevant. However, the 23 excluded cases were actually
quite similar to the remainder of the study population, with a mean
peak CPK of 29 812 IU/L and mortality of 21%, so it seems unlikely that
262 S.A. Alhadi et al. / American Journal of Emergency Medicine 32 (2014) 260–262

Table 1 Table 2
Characteristics of study population Creatine phosphokinase data

Study population (N = 228) CPK mean CPK range

Age (y), mean (range) 46 (15-102) Initial 17 371 56-278 000

Sex Peak 27 509 1166-404 700
Male 180 (79%) Discharge 2823 26-115 510
Female 48 (21%)
Causes
Unknown 99 (43%)
Illicit drug use 66 (29%)
Seizures 27 (12%)
not tested. Even a case leading to acute kidney injury requiring
Sepsis 25 (11%) dialysis would have been missed by our design if CPK was not tested.
Trauma 9 (4%) Our study was also limited by the lack of consensus regarding the
Heat illness 2 (1%) definition of rhabdomyolysis. We sought to overcome this limitation
Acute kidney injury 16 (7%)
by carefully combining laboratory and clinical parameters and the
Mortality 41 (18%)
Urinalysis use of an expert review panel, but the process was inexact. It is likely
Dipstick positive, micro negative that we missed some cases of rhabdomyolysis or included others
Dip 3+ blood, (−) RBCa 51 (22%) that did not actually have rhabdomyolysis, which may reflect the
Dip 1-2+ blood, (−) RBC 34 (15%) fact that the definition of rhabdomyolysis in clinical practice is
Dip trace blood, (−) RBC 9 (4%)
Subtotal 94 (41%)
somewhat arbitrary.
Dipstick positive, micro positive In conclusion, we found that the classic combination of a positive
Dip 3+ blood, (+) RBC 62 (27%) urine dipstick for blood without RBCs on urine microscopy was an
Dip 1-2+ blood, (+) RBC 33 (14.5%) insensitive screening test for rhabdomyolysis in the ED. It should be
Dip trace blood, (+) RBC 6 (3%)
stressed that rhabdomyolysis is a syndrome with a wide spectrum of
Subtotal 101 (44%)
Dipstick negative clinical presentations and the UA alone should not be used to exclude
Dip (−) blood, (+) RBC 1 (0.5%) the diagnosis when it is suspected.
Dip (-) blood, (−) RBC 32 (14%)
Subtotal 33 (14.5%)
Total 228 (100%)
a
(−) RBC: 0-3 RBCs per high-power field detected on urine microscopy.

their exclusion significantly changed our results. Even if the UA had
been positive in all 23 excluded cases, the sensitivity would only
increase from 41% to 47%.
Although we found that the classically described UA findings were
not a good screening test for rhabdomyolysis, most (86%) did have a
positive urine dip test. Our results suggest that, if there is clinical
suspicion for rhabdomyolysis, a positive urine dip test alone warrants
further testing for rhabdomyolysis with one or serial CPK levels.
It is important to note some limitations. Our study was a
retrospective chart review from a single institution, with missing
data elements in some cases. It is also possible that some cases were
missed altogether if rhabdomyolysis was not suspected and CPK was
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