Rhabdomyolysis: Evidence-Based Management
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Rhabdomyolysis: Evidence-Based Management in the Emergency Department

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About This Issue

Rhabdomyolysis is a life-threatening disease process in which muscle cell breakdown results in the release of intracellular contents. There can be downstream consequences of this process for all organ systems, most notably the renal system. Because prompt intervention is required to prevent adverse outcomes, clinicians should consider rhabdomyolysis in the differential for a broad range of clinical presentations. Treatment must address the inciting etiology in addition to treating the rhabdomyolysis itself with administration of IV crystalloid fluids.

Which etiologies and clinical presentations should prompt a high level of suspicion for rhabdomyolysis?

Is there a potential benefit to initiating IV fluid administration in the prehospital setting?

What is the CK level cutoff for the diagnosis of rhabdomyolysis, and what level is concerning for kidney injury? Which other diagnostic tests should be ordered to evaluate for possible downstream complications?

What is the best IV fluid for treatment of rhabdomyolysis? Is the addition of mannitol, a loop diuretic, or sodium bicarbonate recommended?

At what rate and volume should IV fluids be administered? Which patients may be at risk of complications associated with aggressive fluid resuscitation?

When is renal replacement therapy indicated?

What is the role of genetic predisposition in rhabdomyolysis?

Do all patients with rhabdomyolysis require admission?

Table of Contents
  1. Abstract
  2. Case Presentations
  3. Introduction
  4. Critical Appraisal of the Literature
  5. Etiology and Pathophysiology
  6. Differential Diagnosis
  7. Prehospital Care
  8. Emergency Department Evaluation
    1. History
    2. Physical Examination
  9. Diagnostic Studies
  10. Treatment
    1. Intravenous Fluids
      1. Fluid Resuscitation
      2. Choice of Intravenous Fluids
    2. Mannitol and Loop Diuretics
    3. Renal Replacement Therapy
  11. Special Circumstances
    1. Pediatric Patients
    2. Genetic Predisposition
    3. Human Immunodeficiency Virus
  12. Controversies and Cutting Edge
  13. Disposition
  14. Summary
  15. Time- and Cost-Effective Strategies
  16. Risk Management Pitfalls for Rhabdomyolysis
  17. Case Conclusions
  18. Clinical Pathway for Emergency Department Management of Rhabdomyolysis
  19. Tables and Figures
    1. Table 1. Differential of the Causes of Rhabdomyolysis
    2. Figure 1. The Healthy Myocyte
    3. Figure 2. The Myocyte During Normal Muscle Contraction
    4. Figure 3. The Myocyte When Ion Chemicals Are Injured or the Cell is Depleted of Adenosine Triphosphate
  20. References

Abstract

Rhabdomyolysis is a life-threatening pathological process that must be treated as early as possible to avoid potentially life-threatening sequelae. Much of the evidence that informs the management of rhabdomyolysis is retrospective research, often reported from mass disasters, and many practices that have been implemented as standard treatment are based on small studies published more than 30 years ago. This issue reviews the current literature on rhabdomyolysis and provides recommendations for each phase of care, from the prehospital setting through disposition. The evidence is examined regarding the variety of therapies that are used to manage rhabdomyolysis, the potential for recognizing a genetic predisposition for the condition, and therapeutic recommendations that improve patient outcomes.

Case Presentations

A 25-year-old man is brought to the ED in police custody. The police officer states that the man was found running in the street, screaming incoherently, and attacking passersby. The man is in 4-point hard restraints and is severely agitated, thrashing on the EMS gurney and yelling profanities. He is tachycardic but his other vital signs are normal. In order to safely transfer him to the hospital gurney, he is given 4 mg of midazolam IM and 20 mg of ziprasidone IM, after which he is sedated. You order laboratory studies, including a total CK level, and start 1 L of IV crystalloid fluids. A urine toxicology screen returns positive for methamphetamines. His CK level is 6000 U/L and the CMP is notable for a new AKI with a creatinine level of 2.0 mg/dL. You wonder how much fluid he should receive, and whether you should initiate any other medical interventions, such as alkalinization of the urine, loop diuretics, or mannitol . . .

A 40-year-old woman presents to the ED as a trauma activation following a rollover motor vehicle accident. She had been pinned under a vehicle and extrication took 40 minutes. She is tachycardic on arrival, but her vital signs are otherwise normal. She is alert, oriented, and protecting her airway, but has gross deformity of both of her thighs. Due to concern for possible crush syndrome, you order laboratory studies including CK levels, and administer 1 L of IV crystalloid fluids prior to sending her to the radiology department. Imaging reveals bilateral femur fractures. Her laboratory test results include a CK level of 40,000 U/L, a CMP notable for a new AKI with a creatinine level of 3.0 mg/dL, and a K+ level of 6.2 mEq/L. She is producing urine but it is dark. You consider reaching out to the on-call nephrologist about starting dialysis . . .

A 16-year-old girl presents to the ED with severe pain in both of her thighs after completing her first-ever spinning class today. Her vital signs are normal. On examination, her thighs are swollen, weak, and tender to palpation. Her laboratory test results are notable for a CK level of 1700 U/L and a creatinine level of 1.1 mg/dL. She asks if she will have to be admitted to the hospital, and you wonder whether she can be discharged safely . . .

Introduction

Rhabdomyolysis is a complex disease process in which the breakdown of muscle cells leads to the release of intracellular contents, including myoglobin, creatine kinase (CK), and electrolytes. An excess of these contents in the extracellular space exerts toxic effects, resulting in a clinical syndrome that most notably affects the renal system, but has consequences on all organ systems. Rhabdomyolysis has a broad spectrum of clinical presentations. Data on the incidence of rhabdomyolysis are limited, primarily because of variability in the populations studied, but also due in part to a lack of prospective epidemiological studies and standardized definitions, along with a failure to diagnose and report milder cases. A 1994 study found a 0.074% incidence of rhabdomyolysis over a 7-year period among patients at a large university hospital.1 Conversely, a 2004 study that included routine CK screening for all trauma patients in the intensive care unit over a 5-year period found that rhabdomyolysis was present in 85% of the patients.2

Emergency clinicians should routinely consider rhabdomyolysis in the differential diagnosis of a number of presentations. With a range of possible etiologies, from infectious to iatrogenic to traumatic, as well as a range of symptom presentations, rhabdomyolysis can both resemble and exist as a consequence of many other disease processes. Rhabdomyolysis is a disease process in which mitigation of the devastating downstream effects depends on immediate intervention, ideally before the patient arrives to the emergency department (ED). Though the overall incidence of rhabdomyolysis is low in comparison to other disease processes that are routinely managed in the ED, the stakes for timely medical management are too high to dismiss.

There have been few prospective studies or randomized controlled trials to establish a gold standard for the treatment of rhabdomyolysis, and evidence for treatment modalities tends to be sourced from retrospective studies. To some extent, treatment is driven by dogma and tradition.3 A substantial portion of the research upon which clinicians base their management of rhabdomyolysis was published prior to 2000. This creates a somewhat mixed and outdated picture, with no formalized guidelines on standard of care.

This issue of Emergency Medicine Practice reviews the literature on the management of rhabdomyolysis and provides a set of evidence-based recommendations for managing this disease process, while steering away from treatments based on individual anecdote or institutional tradition.

Critical Appraisal of the Literature

A literature search was performed on MEDLINE®, The Cochrane Database of Systematic Reviews, and the Database of Abstracts of Reviews of Effects. The term rhabdomyolysis emergency was searched in MEDLINE®. Citations were limited to English-language references from 2010 to 2020, with article types of controlled study, evidence-based medicine, major clinical study, meta-analysis, multicenter study, practice guideline, prospective study, randomized control trial, and retrospective study. This search produced 134 results, 23 of which were relevant. The term rhabdomyolysis was searched in the Cochrane Database of Systematic Reviews, producing 9 results, 1 of which was relevant. The term rhabdomyolysis emergency was searched in the Database of Abstracts of Reviews of Effects. Citations were limited to English-language references from 2010 to 2020, with an article type of peer-reviewed journals. This search produced 65 results, 20 of which were relevant. Finally, the bibliographies of the identified relevant articles were searched for other relevant sources, limited to peer-reviewed, English-language references from 1994 to 2020. This search produced an additional 37 studies. A total of 51 references were selected for inclusion in this review.

Based on standardized data quality scales, the bulk of the references fall within the categories of Level 3 to Level 5 evidence. The majority of references are retrospective studies, case series, or case reports; just 16 of the relevant references are randomized controlled trials or meta-analyses. The review identified by the Cochrane database search discloses that the quality of the meta-analysis was poor due to suboptimal methodology in the source studies. There are several possible reasons for this paucity of high-quality data. Individual, institution-based practices for the management of rhabdomyolysis may have produced acceptable patient outcomes in general, so further research into this topic is viewed as a low priority. Alternatively, while rhabdomyolysis is more common in specific subsets of patients (eg, critically ill trauma patients), it is seen less consistently in the ED overall, leading to only a handful of prospective studies with few participants, even in studies conducted over the course of several years. The incidence of rhabdomyolysis increases sharply during episodes of major mass disaster (particularly earthquakes), so the data collected in the setting of such disasters comprise the most robust source of information available on the topic. Unfortunately, by virtue of the chaotic and unanticipated nature of these incidents, careful design and implementation of high-quality prospective studies are not feasible, leaving a large body of literature drawn primarily from retrospective chart review. Bearing these limitations in mind, we have compiled an updated set of recommendations for the management of rhabdomyolysis based on the highest-quality data available. Recommendations for which evidence is scant are noted as such.

Risk Management Pitfalls for Rhabdomyolysis

3. “I resuscitated my rhabdomyolysis patient with NS.”

We recommend the of use LR for fluid resuscitation rather than NS. While there has been some debate over this issue, the literature suggests that LR is excellent for maintenance of the appropriate alkaline urine pH, while large volumes of NS may cause iatrogenic hyperchloremic metabolic acidosis.

6. “My rhabdomyolysis patient has a 20G IV catheter. That should be sufficient access for his fluids.”

Because patients with rhabdomyolysis require resuscitation with large volumes of fluid, a single small-bore IV catheter is unlikely to be sufficient to meet the urine output goals. A large-bore IV catheter with fluids running wide open is superior. Depending on the severity of the patient’s rhabdomyolysis, multiple points of access may be considered in order to run fluids simultaneously.

8. “This is my patient’s second documented visit for rhabdomyolysis, but since the inciting etiology was clear in both cases, there’s no need to suspect a genetic disorder.”

The recent literature has demonstrated that underlying genetic predisposition to rhabdomyolysis is much more common than was previously assumed. Recurrent episodes of rhabdomyolysis are suggestive of a genetic predisposition, and a clear inciting cause does not rule out underlying genetic predisposition, as rhabdomyolysis is frequently multifactorial. While genetic testing will not be performed in the ED, it is worth discussing it with the patient so that outpatient testing can be considered in consultation with a primary care provider.

Tables and Figures

Table 1. Differential of the Causes of Rhabdomyolysis

References

Evidence-based medicine requires a critical appraisal of the literature based upon study methodology and number of subjects. Not all references are equally robust. The findings of a large, prospective, randomized, and blinded trial should carry more weight than a case report.

To help the reader judge the strength of each reference, pertinent information about the study, such as the type of study and the number of patients in the study is included in bold type following the references, where available. The most informative references cited in this paper, as determined by the authors, are highlighted.

  1. Veenstra J, Smit WM, Krediet RT, et al. Relationship between elevated creatine phosphokinase and the clinical spectrum of rhabdomyolysis. Nephrol Dial Transplant. 1994;9(6):637-641. (Retrospective chart review; 93 patients) DOI: 10.1093/ndt/9.6.637
  2. Brown CV, Rhee P, Chan L, et al. Preventing renal failure in patients with rhabdomyolysis: do bicarbonate and mannitol make a difference? J Trauma. 2004;56(6):1191-1196. (Retrospective chart review; 2083 patients) DOI: 10.1097/01.ta.0000130761.78627.10
  3. Long B, Koyfman A, Gottlieb M. An evidence-based narrative review of the emergency department evaluation and management of rhabdomyolysis. Am J Emerg Med. 2019;37(3):518-523. (Review)
  4. Al-Ismaili Z, Piccioni M, Zappitelli M. Rhabdomyolysis: pathogenesis of renal injury and management. Pediatr Nephrol. 2011;26(10):1781-1788. (Review)
  5. Bosch X, Poch E, Grau JM. Rhabdomyolysis and acute kidney injury. N Engl J Med. 2009;361(1):62-72. (Review)
  6. Okubo K, Kurosawa M, Kamiya M, et al. Macrophage extracellular trap formation promoted by platelet activation is a key mediator of rhabdomyolysis-induced acute kidney injury. Nat Med. 2018;24(2):232-238. (Randomized control study; rats)
  7. Melli G, Chaudhry V, Cornblath DR. Rhabdomyolysis: an evaluation of 475 hospitalized patients. Medicine (Baltimore). 2005;84(6):377-385. (Retrospective chart review; 475 patients)
  8. United States Food and Drug Administration. FDA Drug Safety Communication: New restrictions, contraindications, and dose limitations for Zocor (simvastatin) to reduce the risk of muscle injury. Available at: https://www.fda.gov/drugs/drug-safety-and-availability/fda-drug-safety-communication-new-restrictions-contraindications-and-dose-limitations-zocor. Accessed November 10, 2020. (Incidence report and consensus statement)
  9. Jankovic’ SR, Stosic’ JJ, Vucinic’ S, et al. Causes of rhabdomyolysis in acute poisonings. Vojnosanit Pregl. 2013;70(11):1039-1045. (Retrospective chart review; 656 patients)
  10. Knafl EG, Hughes JA, Dimeski G, et al. Rhabdomyolysis: patterns, circumstances, and outcomes of patients presenting to the emergency department. Ochsner J. 2018;18(3):215-221. (Retrospective chart review; 1957 patients)
  11. Gunal AI, Celiker H, Dogukan A, et al. Early and vigorous fluid resuscitation prevents acute renal failure in the crush victims of catastrophic earthquakes. J Am Soc Nephrol. 2004;15(7):1862-1867. (Retrospective chart review; 16 patients)
  12. Shimazu T, Yoshioka T, Nakata Y, et al. Fluid resuscitation and systemic complications in crush syndrome: 14 Hanshin-Awaji earthquake patients. J Trauma. 1997;42(4):641-646. (Retrospective chart review; 14 cases)
  13. Iraj N, Saeed S, Mostafa H, et al. Prophylactic fluid therapy in crushed victims of Bam earthquake. Am J Emerg Med. 2011;29(7):738-742. (Retrospective chart review)
  14. Alavi-Moghaddam M, Safari S, Najafi I, et al. Accuracy of urine dipstick in the detection of patients at risk for crush-induced rhabdomyolysis and acute kidney injury. Eur J Emerg Med. 2012;19(5):329-332. (Retrospective chart review; 1821 patients)
  15. de Meijer AR, Fikkers BG, de Keijzer MH, et al. Serum creatine kinase as predictor of clinical course in rhabdomyolysis: a 5-year intensive care survey. Intensive Care Med. 2003;29(7):1121-1125. (Retrospective chart review; 26 patients) DOI: 10.1007/s00134-003-1800-5
  16. Safari S, Yousefifard M, Hashemi B, et al. The value of serum creatine kinase in predicting the risk of rhabdomyolysis-induced acute kidney injury: a systematic review and meta-analysis. Clin Exp Nephrol. 2016;20(2):153-161. (Meta-analysis; 18 studies)
  17. Hollander-Rodriguez JC, Calvert JF, Jr. Hyperkalemia. Am Fam Physician. 2006;73(2):283-290. (Review)
  18. Chen CY, Lin YR, Zhao LL, et al. Clinical spectrum of rhabdomyolysis presented to pediatric emergency department. BMC Pediatr. 2013;13:134. (Retrospective chart review; 37 patients) DOI: 10.1186/1471-2431-13-134
  19. Brogan M, Ledesma R, Coffino A, et al. Freebie rhabdomyolysis: a public health concern. Spin class-induced rhabdomyolysis. Am J Med. 2017;130(4):484-487. (Case report; 3 cases)
  20. Wik L, Patterson JM, Oswald AE. Exertional paraspinal muscle rhabdomyolysis and compartment syndrome: a cause of back pain not to be missed. Clin Rheumatol. 2010;29(7):803-805. (Case report)
  21. Vanbrabant P, Moke L, Meersseman W, et al. Excruciating low back pain after strenuous exertion: beware of lumbar paraspinal compartment syndrome. J Emerg Med. 2015;49(5):641-643. (Case report)
  22. Huerta-Alardín AL, Varon J, Marik PE. Bench-to-bedside review: rhabdomyolysis -- an overview for clinicians. Crit Care. 2005;9(2):158-169. (Review)
  23. Parzych L, Jo J, Diwan A, et al. “Found down” compartment syndrome: experience from the front lines of the opioid epidemic. J Bone Joint Surg Am. 2019;101(17):1569-1574. (Retrospective chart review; 30 participants)
  24. Isoardi KZ, Ayles SF, Harris K, et al. Methamphetamine presentations to an emergency department: management and complications. Emerg Med Australas. 2019;31(4):593-599. (Retrospective chart review; 378 cases)
  25. Pasternak RC, Smith SC, Jr., Bairey-Merz CN, et al. ACC/AHA/NHLBI clinical advisory on the use and safety of statins. Stroke. 2002;33(9):2337-2341. (Consensus statement)
  26. Mikkelsen TS, Toft P. Prognostic value, kinetics and effect of CVVHDF on serum of the myoglobin and creatine kinase in critically ill patients with rhabdomyolysis. Acta Anaesthesiol Scand. 2005;49(6):859-864. (Prospective and retrospective cohort study; 47 patients) DOI: 10.1111/j.1399-6576.2005.00577.x
  27. Jaffe AS, Vasile VC, Milone M, et al. Diseased skeletal muscle: a noncardiac source of increased circulating concentrations of cardiac troponin T. J Am Coll Cardiol. 2011;58(17):1819-1824. (Retrospective chart review; 16 patients)
  28. Li SF, Zapata J, Tillem E. The prevalence of false-positive cardiac troponin I in ED patients with rhabdomyolysis. Am J Emerg Med. 2005;23(7):860-863. (Retrospective cohort study; 109 patients)
  29. Petejova N, Martinek A. Acute kidney injury due to rhabdomyolysis and renal replacement therapy: a critical review. Crit Care. 2014;18(3):224. (Review)
  30. Weibrecht K, Dayno M, Darling C, et al. Liver aminotransferases are elevated with rhabdomyolysis in the absence of significant liver injury. J Med Toxicol. 2010;6(3):294-300. (Retrospective chart review; 215 cases)
  31. Schmidt AH, Bosse MJ, Frey KP, et al. Predicting acute compartment syndrome (PACS): the role of continuous monitoring. J Orthop Trauma. 2017;31 Suppl 1:S40-S47. (Prospective observational study; 191 patients)
  32. Scharman EJ, Troutman WG. Prevention of kidney injury following rhabdomyolysis: a systematic review. Ann Pharmacother. 2013;47(1):90-105. (Meta-analysis; 27 studies)
  33. Cho YS, Lim H, Kim SH. Comparison of lactated Ringer’s solution and 0.9% saline in the treatment of rhabdomyolysis induced by doxylamine intoxication. Emerg Med J. 2007;24(4):276-280. (Randomized controlled trial; 28 patients) DOI: 10.1136/emj.2006.043265
  34. Holt S, Moore K. Pathogenesis of renal failure in rhabdomyolysis: the role of myoglobin. Exp Nephrol. 2000;8(2):72-76. (Review)
  35. Homsi E, Barreiro MF, Orlando JM, et al. Prophylaxis of acute renal failure in patients with rhabdomyolysis. Ren Fail. 1997;19(2):283-288. (Retrospective chart review; 15 patients)
  36. Bragadottir G, Redfors B, Ricksten SE. Mannitol increases renal blood flow and maintains filtration fraction and oxygenation in postoperative acute kidney injury: a prospective interventional study. Crit Care. 2012;16(4):R159. (Randomized controlled trial; 11 patients)
  37. Mehta RL, Pascual MT, Soroko S, et al. Diuretics, mortality, and nonrecovery of renal function in acute renal failure. JAMA. 2002;288(20):2547-2553. (Retrospective chart review, 552 patients) DOI: 10.1001/jama.288.20.2547
  38. Zeng X, Zhang L, Wu T, et al. Continuous renal replacement therapy (CRRT) for rhabdomyolysis. Cochrane Database Syst Rev. 2014(6):CD008566. (Meta-analysis; 3 studies, 101 participants)
  39. Perreault S, Birca A, Piper D, et al. Transient creatine phosphokinase elevations in children: a single-center experience. J Pediatr. 2011;159(4):682-685. (Retrospective study; 130 patients)
  40. Sanadgol H, Najafi I, Rajabi Vahid M, et al. Fluid therapy in pediatric victims of the 2003 Bam, Iran earthquake. Prehosp Disaster Med. 2009;24(5):448-452. (Retrospective chart review; 31 patients)
  41. Nelson DA, Deuster PA, Kurina LM. Sickle cell trait and rhabdomyolysis among U.S. Army soldiers. N Engl J Med. 2016;375(17):1696. (Retrospective chart review; 47,944 patients)
  42. Scalco RS, Gardiner AR, Pitceathly RD, et al. Rhabdomyolysis: a genetic perspective. Orphanet J Rare Dis. 2015;10:51. (Review)
  43. Slobogean BL, Reilly CW, Alvarez CM. Recurrent viral-induced compartment syndrome. Pediatr Emerg Care. 2011;27(7):660-662. (Case report)
  44. Vivante A, Ityel H, Pode-Shakked B, et al. Exome sequencing in Jewish and Arab patients with rhabdomyolysis reveals single-gene etiology in 43% of cases. Pediatr Nephrol. 2017;32(12):2273-2282. (Cohort study; 21 patients)
  45. Thomas J, Crowhurst T. Exertional heat stroke, rhabdomyolysis and susceptibility to malignant hyperthermia. Intern Med J. 2013;43(9):1035-1038. (Case report)
  46. Delo D, Brett AS, Postic B. Primary HIV infection presenting with acute rhabdomyolysis. Am J Med Sci. 2006;332(1):46-47. (Case report)
  47. Gagnon J, Katner H, Core SB, et al. Rhabdomyolysis as presenting feature of acute HIV-1 seroconversion in a pediatric patient. Am J Emerg Med. 2016;34(4):760.e3-760.e5. (Case report)
  48. Nassar A, Talbot R, Grant A, et al. Rapid diagnosis of rhabdomyolysis with point-of-care ultrasound. West J Emerg Med. 2016;17(6):801-804. (Case report)
  49. Su BH, Qiu L, Fu P, et al. Ultrasonic appearance of rhabdomyolysis in patients with crush injury in the Wenchuan earthquake. Chin Med J (Engl). 2009;122(16):1872-1876. (Case report)
  50. Manis T, George-Varghese B, Kashani J. Rhabdomyolysis - go big or go home. Am J Emerg Med. 2019;37(12):2194-2196. (Retrospective chart review; 115 patients) DOI: 10.1016/j.ajem.2019.03.024
  51. Delaney K, Vohra R. Prediction of safe discharge of emergency department patients with acute rhabdomyolysis. Crit Care. 2004;8(Suppl 1):P154. (Retrospective chart review; 144 patients)
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Publication Information
Authors

Gi Xiang Lee, MD; David K. Duong, MD, MS, FACEP

Peer Reviewed By

Ryan Knight, MD; Ram A. Parekh, MD

Publication Date

December 1, 2020

CME Expiration Date

December 2, 2023

CME Credits

4 AMA PRA Category 1 Credits™, 4 ACEP Category I Credits, 4 AAFP Prescribed Credits, 4 AOA Category 2-A or 2-B Credits.

Pub Med ID: 33211443

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