From the Department of Emergency Medicine (Wang TL, Lin CM, Ma HP, Chang H), Shin-Kong Wu Ho-Su Memorial Hospital
Correspondence to Dr. Tzogn-Luen Wang, Department of Emergency Medicine, Shin-Kong Wu Ho-Su Memorial Hospital, 95 Wen Chang Road, Taipei, Taiwan. E-mail M002183@ms.skh.org.tw
 

Rhabdomyolysis with renal failure is one of the most serious complications of crushing injury.¹ Rhabdomyolysis was first described in the victims of crush injury in Sicilian earthquake in Messina in 1908 and those in World War I.¹ From then on, the problem of crushing injury with subsequent rhabdomyolysis and acute renal failure became an important issue in any kind of disasters. It therein deserves investigation how to detect early the renal involvement in crushing injury under the circumstances of disasters or mass casualties.
Rhabdomyolysis is defined as the breakdown of muscle fibers with leakage of potentially toxic cellular contents into the systemic circulation. The clinical presentation is often subtle. Preliminary diagnosis of rhabdomyolysis requires a high index of suspicion whereas definitive diagnosis is made by laboratory evaluation. Besides elevation of serum cardiac enzymes such as creatine kinase can provide evidence of rhabdomyolysis, a urine dipstick test for blood has positive results in the presence of hemoglobin or myoglobin. Although the urine dipstick test for blood that has positive findings in the absence of red blood cells suggests myoglobinuria, it provides poor differential power in clinical situations. We therein designed the following prospective investigation to study a urine rapid test specific for myoglobin to determine its role in diagnosis of renal involvement in crushing injury.

The consecutive patients presenting with crushing injury and a serum creatine kinase (CK) of >5000 IU/L from 1999 to 2001 have been enrolled as study population. Patients with chronic renal failure, acute myocardial infarction, or any chronic illness with a short life expectancy were excluded from the study. The patients or their relatives gave the informed consent, and the Ethical Committee of our institute approved the study protocol. Twenty healthy controls (12 men and 8 women; mean age 36+8 years) underwent the same protocol as comparisons.

All of the subjects underwent routine blood examinations such as complete blood cell count, prothrombin time, activated partial thromboplastin time, and biochemistry tests (including renal function test, liver function tests and electrolytes). In addition, serum CK and its isoenzyme CK-MB, serum and urine myoglobin were also measured. A urine rapid myoglobin test was also performed as comparisons. All of the victims with crushing injury accepted standard medical and surgical treatment as indicated. They also underwent forced alkaline diuresis to maintain urine output to 150 mL/hr and a urinary pH of >7.0. Intravenous furosemide was given as indicated. None of the patients received mannitol and none were dialyzed. Significant muscle compartment syndrome was detected in five patients, but the situation resolved without surgical intervention.
A Foley catheter was inserted for urine collection, and an intra-arterial cannula was inserted for hemodynamic monitoring and blood sampling. The urine was collected in fractions of 6 hrs, the volumes were measured, and aliquots were taken for analyses. Blood samples were taken at the study baseline and at 6-hr intervals. All the analyses from the sera were made from unfrozen samples. Urinary samples were alkalinized in vitro to pH 8.5-9.0 to improve the stability of myoglobin and stored at -70? until thawed and analyzed on a single occasion.
Serum myoglobin concentration was determined with an immunoturbidimetric assay on a Hitachi 917 automatic analyzer (Hitachi Medical, Tokyo, Japan) immediately. Myoglobin has been shown to be stable in serum for at least 1 month when stored at 2-8? . The reference range for serum myoglobin in our laboratory is <3.8 nmol/L for men and <3.2 nmol/L for women. For urinary myoglobin, the reference value is <1.0 nmol/L for both sexes.
Creatinine clearance was calculated by using the following equation: creatinine clearance = creatinine_urine x urine flow (mL/min)/ creatinine_serum. The reference values for creatinine clearance are age dependent. In our patient population, the lowest limit of reference ranges varies from 55 mL/min to 90 mL/min. The myoglobin clearance was calculated similarly, using myoglobin concentrations in serum and urine. The clearance values were calculated for every 6-hr interval, using the measured volume of urine during this time period. The mean value of serum concentrations at the starting and end point of the interval was used in calculations.
Rapid urine myoglobin test was performed by a commercially available one-step immunochromatography kit (The Myoglobin Insta Test, Cortez Diagnostics Inc., CA, USA). The presence of myoglobin at level 100 ng/ml or higher can be detected in 5 minutes.

Fifty-four consecutive patients were enrolled in the study. The mean age was 37+10 years. Thirty-eight (69%) of them were men and 16 (31%) women. The involved areas were upper extremities (n=32, 60%), lower extremity (n=18, n=33%) and abdomen (n=4, 7%). Among them, 4 had symptoms and signs of shock and all of them were abdominal crushing injury.
We firstly compared the evolution of creatinine clearance and the presence of urine myoglobin by rapid urine myoglobin test. If the renal involvement was defined as the creatinine clearance decline more than 10% of the baseline values and/or the creatine clearance being lower than 50 mL/min, the rate of renal involvement was about 56% (30 out of 54 patients). Urine myoglobin was present in 29 of these 30 victims (97%) with renal involvement and 2 of 24 patients (8%) without it by the rapid urine myoglobin test. The sensitivity and specificity of rapid urine myoglobin test were thus 94% and 86%, respectively.
Figure illustrates the correlation of urine myoglobin levels in the presence or absence of positive rapid urine myoglobin test. The cut-off value of positive rapid urine myoglobin test was around 50 nmol/L by the ROC analysis with the sensitivity of 98% [95% CI 92-100%] and the specificity 86% [95% CI 80-92%].

This study revealed that a rapid urine test specific for myoglobin can provide a rapid and reliable examination for early diagnosis of acute renal failure in those with crushing injury.
As disaster medicine progressed, it has become an important issue to prevent the victims of devastating disaster from rhabdomyolysis and acute renal failure. The number of ARF patients is influenced largely by local circumstances, such as the severity of the shock, the size of the disaster area, the quality of the buildings, the time needed for extrication, the triage and identification procedures, and the availability of local rescue teams and medical facilities. However, the lack of immediate reliable diagnostic tools in the disaster circumstances may also be one of the contributing factors. Acute renal failure develops in 30-40% of patients with rhabdomyolysis. Possible mechanisms include precipitation of myoglobin and uric acid crystals within renal tubules, decreased glomerular perfusion, and the nephrotoxic effect of ferrihemate.^1-4 Some investigations suggested that predictors for the development of renal failure include peak CK more than 6000 IU/L, dehydration (hematocrit >50, serum sodium >150 mEq/L, orthostasis, pulmonary wedge pressure <5 mm Hg, urinary fractional excretion of sodium <1%), sepsis, hyperkalemia or hyperphosphatemia, and hypoalbuminemia.^5-17 Most of the conditions can be met in the victims of disasters. Our study provided a simple test for detection of urine myoglobin that has been proven to be highly associated with the occurrence of acute renal failure.
Increased likelihood of mass casualty incidents and high public expectations for an appropriate and timely response mandate careful and complete planning. Mass casualty planning requires thorough knowledge of adjacent service capacities and response times.^18,19 Planning must account for the fact that traditional transport and communications system will break down. Field personnel must be specifically trained in mass casualty triage and stabilization because austere field conditions change management strategies. However, in the viewpoints of DMAT, rapid and reliable diagnostic tools or kits may provide invaluable benefit in subsequent management for some specific situations. Rapid diagnostic kits such as bioterrorism kits or chemical kits may be examples. Early detection and prevention of acute renal failure for those with crushing injury and high risk of renal involvement is another important issue. Mobility, easy performance, and power-independence are important considerations in laboratory setting in the mass casualty scenes. The rapid urine test can fulfill these criteria.
The major limitation in this study is the limited cases. A large-scale prospective study may be needed to confirm the result. Another limitation is that most of our participants were checked urine via a Foley catheter collection which may prevent from contamination with blood or other tissue fluid. In a real disaster field, most of the victims can not be treated like this. The possible contamination may be another interfering factor for correct diagnosis.
In conclusion, our data provide preliminary experience about the application of a rapid urine myoglobin test in early detection of myoglobinuria. We expect the utilization of such a tool can provide help in the real disaster fields.