Rhabdomyolysis Review


Pathologic condition in which necrosis of skeletal muscle occurs secondary to injury causing leaking of constituents into plasma.   Myoglobin, creatnine kinase (CK) are the primary constituents.


Can be divided into traumatic and atraumatic.  Most common causes are ETOH abuse, compression, seizures, and drug abuse.  Other causes are direct trauma, hypothermia, infection, metabolic abnormalities (dka, hypokalemia, hypophosphatemia), and gangrene.  Many drugs have been linked to rhabdo, but the most important class is the statins.  Genetic muscle metabolism abnormalities can also predispose to rhabdo.




Pressor agents can also cause mild rhabdomyolysis


Because substance abuse and compression injury are such common causes, inquire about drug use, alcohol use, binge drinking, and immobilization.


The final common pathway of these causes is a significant increase in intracellular free ionized calcium.  Increased calcium results either from direct injury to the muscle cell membrane or from insufficient energy supply to the muscle.


CK at least 5 times normal, but since peak levels may not be seen immediately, the cut-off for diagnosis is usually 3x normal.   (Mb should be less than 5% of it)  Peak levels are reached in 24-36 hours and then fall by ~40% a day.


Myoglobin, on the other hand, is cleared from the plasma very rapidly (1/2 life of 1-3 hours).  If myoglobinuria is present, fairly specific, but its absence is not helpful.


Hepatic dysfunction with liver enzyme increase, hyperbillirubinemia, and elevated PT.

DIC can also ensue.

Potassium, phosphorous, organic acids, and purines released from the muscle cells can cause hyperkalemia, hyperphosphatemia, metabolic acidosis, and hyperuricemia.  Hypocalcemia can be seen secondary to the hyperphosphatemia.   If the patient has acute renal failure as a result of the rhabdo, it will usually result in an increased creatnine without a proportional rise in BUN.  This is b/c of direct release of creatnine from the damaged muscle cells.


Compartment syndrome can be a cause or a serious complication of rhabdo.  Compartment syndrome that occurs late in the course is due to large fluid volume uptake by damaged tissue.


The most serious complication is acute renal failure.  The nephrotoxicity of myoglobin is dependant on hypovolemia, dehydration, and aciduria.


In crush injuries, give 1 liter bolus of NS followed by 1/2 normal at 200-700 cc/hr to achieve urine flow rates of 200-300 cc/hr.

In non-traumatic causes, 250 cc/hr of NS for 1 liter then switch to 1/2 NS at the rates above.


Mannitol can be given with intermittent boluses of 12.5-25 grams or add 10 gm to each liter of IVF.


Lasix does not help.


Alkalinize the urine to at least 6.5

Give 100 meq bolus then add 1-2 amps to each subsequent liter of fluids.


Crappy retrospective article showed no benefit to Mannitol or Bicarb (J Trauma Volume 56(6) June 2004)


Prophylaxis of acute renal failure in patients with rhabdomyolysis. Ren Fail. 1997 Mar;19(2):283-8. Homsi E, Barreiro MF, Orlando JM, Higa EM. Patients that develop rhabdomyolysis of different causes are at high risk of acute renal failure. Efforts to minimize this risk include volume repletion, treatment with mannitol, and urinary alkalinization as soon as possible after muscle injury. This is a retrospective analysis (from January 1, 1992, to December 31, 1995) of therapeutic response to prophylactic treatment in patients with rhabdomyolysis admitted to an intensive care unit (ICU). The diagnosis of rhabdomyolysis was based on creatinine kinase (CK) level (> 500 Ui/L) and the criteria for prophylaxis were: time elapsed between muscle injury to ICU admission < 48 h and serum creatinine < 3 mg/dL. Fifteen patients were treated with the association of saline, mannitol, and sodium bicarbonate (S + M + B group) and 9 patients received only saline (S group). Serum creatinine at admission was similar in both groups: 1.6 +/- 0.6 mg/dL in the S + M + B group and 1.5 +/- 0.6 mg/dL in the S group (p > 0.05). Maximum serum CK measured was 3351 +/- 1693 IU/L in the S + M + B group and 1747 +/- 2345 IU/L in the S group (p < 0.05). However the measurement of CK was earlier in S + M + B patients (1.7 vs 2.7 days after rhabdomyolysis). APACHE II scores were 16.9 +/- 7.4 and 13.4 +/- 4.9 in the S + M + MB and S groups, respectively (p > 0.05). *Despite the treatment protocol the serum levels of creatinine had similar behavior and reached normal levels in all patients in 2 or 3 days. *The saline infusion during the first 60 h on the ICU was 206 mL/h in the S group and 204 mL/h in S + M + B (p > 0.05). Mannitol dose was 56 g/day, and bicarbonate 225 mEq/day during 4.7 days. *Our data show that progression to established renal failure can be totally avoided with prophylactic treatment, and that once appropriate saline expansion is provided, the association of mannitol and bicarbonate seems to be unnecessary. * or Preventing renal failure in patients with rhabdomyolysis: do bicarbonate and mannitol make a difference? *Brown CV, Rhee P, Chan L, Evans K, Demetriades D, Velmahos GC: ** *J Trauma. 2004 Jun;56(6):1191-6. CONCLUSION: Abnormal CK levels are common among critically injured patients, and a CK level greater than 5,000 U/L is associated with RF. Bicarbonate/Mannitol does not prevent RF, dialysis, or mortality in patients with creatine kinase levels greater than 5,000 U/L. T*he standard of administering Bicarbonate/Mannitol to patients with post-traumatic rhabdomyolysis should be reevaluated.*

Start CVVH when Myoglobin is > 10,000


50% with ck>5000 will develop ARF

increased ldh and ast as well

causes profound intravascular depletion

myoglobin binds tamm-horsfal protein, cast formation is enhanced in acidic environments

lipid peroxidation

renal vasoconstrictors

blockage of NO renal vasodilation

(intens care med 2001;27:803)

The American Journal of Emergency Medicine Volume 24, Issue 4 , July 2006, Pages 509-510 This Document SummaryPlus Full Text + Links ·Full Size Images PDF (70 K) External Links Actions Cited By Save as Citation Alert E-mail Article Export Citation doi:10.1016/j.ajem.2006.03.020 Copyright © 2006 Elsevier Inc. All rights reserved. Correspondence Where does troponin I derive from in rhabdomyolysis? Josef Finsterer MDa, and Claudia Stöllberger MDb aNeurological Department Krankenanstalt Rudolfstiftung, A-1030 Vienna, Austria b2nd Medical Department, Krankenanstalt Rudolfstiftung, A-1030 Vienna, Austria Available online 17 June 2006. Referred to by: Reply to the Letter from Finsterer and Stöllberger, The American Journal of Emergency Medicine, Volume 24, Issue 4, July 2006, Pages 510-511 Siu Fai Lia, Jennifer Zapataa and Elizabeth Tillema SummaryPlus | Full Text + Links | PDF (52 K) Article Outline References With interest we read the article by Li et al on 109 patients with rhabdomyolysis among whom 55 (50%) also had elevated cardiac troponin I (cTnI). Of the 55, 32 were assessed as true positives, 18 as false positives, and 5 as indeterminate. Cocaine abuse, renal insufficiency, and myoglobinuria were excluded as causes of false-positive cTnI [1]. The report raises the following questions and concerns. The definition of rhabdomyolysis solely as creatine kinase (CK) elevation of more than 1000 U/L is insufficient. A more comprehensive definition of rhabdomyolysis requires the presence of tetraparesis, CK elevation more than 10 times the upper reference limit, myoglobinuria, hyperkaliemia, and coagulopathy [2]. According to this definition, the number of patients with rhabdomyolysis is presumably less than indicated. It is also of interest to know the cause of CK elevation in the included patients. It is well known that normal values of CK are dependent on the total muscle mass. Thus, they are usually different between women and men in most laboratories. The reference values applied in the present investigation, however, were unisexual. Why? How long did the patients stay at the ED? How long was the average follow-up duration? How many patients died during hospitalization? How many of the patients with true-positive and false-positive cTnI elevation had a myocardial infarction? How many of these patients underwent coronary angiography? The present study relied on the assumption that cTnI is solely released during myocardial ischemia. However, cTnI may also increase during myocardial damage from inflammation, intoxication, malignancy, or degeneration. This is why in addition to segmental or global wall motion abnormalities, features such as left ventricular hypertrabeculation/noncompaction, abnormal myocardial texture, left ventricular wall thickening, or reduced fractional shortening, diastolic dysfunction, or dilated cardiac cavities should be assessed on echocardiography. On electrocardiography, abnormalities other than signs of myocardial ischemia, such as left ventricular hypertrophy, expressed as various QRS indices, should be included in the evaluation. Some of the included patients might have presented with transient left ventricular dysfunction, also known as Takotsubo phenomenon, which is accompanied by CK elevation and can be precipitated by rhabdomyolysis [3]. Rhabdomyolysis may cause stress and thus myocardial damage with cTnI elevation. Because cTnI is as sensitive as cTnT in detecting myocardial necrosis caused by ischemia [4], it would be interesting to know whether cTnT was also determined and whether the frequency of false positives was as high as for cTnI. Cardiac troponin I may also be positive in malignancy with cardiac amyloidosis [5], pheochromocytoma [6], carcinoid syndrome [7], generalized seizures [8], stroke, shock, or massive pulmonary embolism [9]. Why were the 55 patients with positive cTnI not evaluated for causes of false-positive cTnI other than cocaine abuse, renal insufficiency, or myoglobinuria? Interestingly, there is a strong preponderance of male patients in the study population (male/female ratio, 3:1). Is this because myocardial infarction is more prevalent in men than in women or because of the higher muscle mass in men than in women? Was the male preponderance also present in the subgroup of the false positives? The absent correlation between peak cTnI and CK is not surprising as it was calculated for all 55 patients with positive cTnI. Consequently, it includes also the false positives in whom elevated CK most likely derives from a tissue other than the myocardium. The lower part of Table 1 is misleading. It appears impossible that 61 patients had myoglobinuria in the truly positive group, which consisted of 32 patients. This also holds true for more than 18 patients with cocaine abuse, myoglobinuria, renal failure, electrocardiogram abnormalities, and abnormal echocardiography in the false-negative group. It would be interesting to investigate the false positives prospectively by a neurologist to find out whether these patients had a neuromuscular problem or not. Determination of urine myoglobin is not sufficient to rule out neuromuscular disorder as many patients with elevated CK and muscle disease may have normal urine myoglobin. Was myoglobinuria more prevalent among patients with renal insufficiency or with normal renal function? In addition to the limitations already raised by the authors, we want to emphasize that a more thorough search for causes of false-positive cTnI has to be carried out than just looking for myoglobinuria, renal insufficiency, or cocaine abuse. Particularly, neuromuscular disorder, malignancy, Takotsubo phenomenon, cardiac amyloidosis, carcinoid syndrome, pheochromocytoma, shock, stroke, pulmonary embolism, or epilepsy cannot be definitively ruled out as causes of elevated cTnI by the methods applied. References [1] S.F. Li, J. Zapata and E. Tillem, The prevalence of false-positive cardiac troponin I in ED patients with rhabdomyolysis, Am J Emerg Med 23 (2005), pp. 860–863. SummaryPlus | Full Text + Links | PDF (98 K) | Abstract + References in Scopus | Cited By in Scopus [2] G. Melli, V. Chaudhry and D.R. Cornblath, Rhabdomyolysis: an evaluation of 475 hospitalized patients, Medicine (Baltimore) 84 (2005), pp. 377–385. Abstract-MEDLINE | Abstract-Elsevier BIOBASE | Abstract-EMBASE | Full Text via CrossRef | Abstract + References in Scopus | Cited By in Scopus [3] M. Kawabata, I. Kubo, K. Suzuki, T. Terai, T. Iwama and M. Isobe, ‘Tako-Tsubo cardiomyopathy’ associated with syndrome malin: reversible left ventricular dysfunction, Circ J 67 (2003), pp. 721–724. Abstract-MEDLINE | Abstract-EMBASE | Abstract + References in Scopus | Cited By in Scopus [4] J.S. Alpert, K. Thygesen, E. Antman and J.P. Bassand, Myocardial infarction redefined—a consensus document of The Joint European Society of Cardiology/American College of Cardiology Committee for the redefinition of myocardial infarction, J Am Coll Cardiol 36 (2000), pp. 959–969. Abstract-MEDLINE | Abstract-EMBASE | Abstract-Elsevier BIOBASE | Abstract + References in Scopus | Cited By in Scopus [5] A. Zabernigg, R. Schranzhofer, A. Kreczy and K. Gattringer, Continuously elevated cardiac troponin I in two patients with multiple myeloma and fatal cardiac amyloidosis, Ann Oncol 14 (2003), p. 1791. Abstract-MEDLINE | Abstract-Elsevier BIOBASE | Full Text via CrossRef | Abstract + References in Scopus | Cited By in Scopus [6] F. Casazza, A. Capozi, B. Conconi and E. Schiaffino, Acute myocardial damage from a pheochromocytoma, Ital Heart J 1 (2000) (Suppl 5), pp. 686–689. Abstract-EMBASE | Abstract-MEDLINE | Abstract + References in Scopus | Cited By in Scopus [7] W.G. Meijer, J.C. Swaanenburg, D. van Veldhuisen, I.P. Kema, P.H. Willemse and E.G. de Vries, Troponin I, troponin T, and creatine kinase–MB mass in patients with the carcinoid syndrome with and without heart failure, Clin Chem 45 (1999), pp. 2296–2297. Abstract-MEDLINE | Abstract-EMBASE | Abstract-Elsevier BIOBASE | Abstract + References in Scopus | Cited By in Scopus [8] A. Brobbey and K. Ravakhah, Elevated serum cardiac troponin I level in a patient after a grand mal seizure and with no evidence of cardiac disease, Am J Med Sci 328 (2004), pp. 189–191. Abstract-MEDLINE | Abstract-EMBASE | Full Text via CrossRef | Abstract + References in Scopus | Cited By in Scopus [9] A. Jeremias and C.M. Gibson, Narrative review: alternative causes for elevated cardiac troponin levels when acute coronary syndromes are excluded, Ann Intern Med 142 (2005), pp. 786–791. Abstract-EMBASE | Abstract-MEDLINE | Abstract + References in Scopus | Cited By in Scopus

Rhabdomyolysis and “False Positive” Troponin Elevation Cardiac troponin I (cTnI) is considered the most specific marker of cardiac muscle injury (1). Emergency Physicians commonly encounter patients with acute rhabdomyolysis who demonstrate marked CPK elevations. In such patients it is not unusual to find elevations of cTnI and the question arises as to whether the troponin elevation is due to acute coronary damage or is a “false positive” resulting from the rhabdomyolysis. In fact numerous studies demonstrate that the range of false-positive cTnI elevation in the setting of rhabdomyolysis ranges from 11% to 35% (the range is a result of different study methodologies, different assays, and different upper reference limits for cTnI) (1-4). The false positives may represent minor cardiac injuries that are undetected by EKG and echocardiography, or they may represent an underlying problem with cTnI assays. Troponin assays are immunoassays, and like all antibody assays, cross-reactions may occur, particularly in patients with rhabdomyolysis in whom the skeletal forms of troponin I are elevated (1,10). Of note, the false-positive elevations in cTnI are not affected by cocaine use, impaired renal function, or myoglobinuria (1). References: (1) Li SF, et al. The prevalence of false-positive cardiac troponin I in ED patients with rhabdomyolysis Am J Emerg Med 2005;23: 860-3. (2) Lavoinne A, Hue G Serum cardiac troponins I and T in early posttraumatic rhabdomyolysis Clin Chem 1998;44:667–668. (3) Punukollu G, et al. Elevated serum cardiac troponin I in rhabdomyolysis Int J Cardiol 2004;96:35–40. (4) Lofberg M, et al. Cardiac troponins in severe rhabdomyolysis Clin Chem 1996;42:1120–1121. (5) Simpson JA, et al. Differential detection of skeletal troponin I isoforms in serum of a patient with rhabdomyolysis: markers of muscle injury? Clin Chem 2002;48:1112–1114.


Comparison of Ringers and NS (Emerg Med J 2007;24:276)




High Permeability dialysis membrane allows effective removal of myoglobin (Crit Care Med 2011;38:184)

allows elimination of molecules up to 30 kDa



|      |      |

Back to top