Rhabdomyolysis: Evidence-Based Management in the Emergency Department

Table of Contents

 

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?

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

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.

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