The Edge: Rhabdomyolysis—Signs, Symptoms, and Management

The Edge is a monthly blog series developed by EMS World and FlightBridgeED that features top EMS medical directors exploring the intricacies of critical care in EMS practice. In this installment FlightBridgeED Vice President of Business Operations Ashley Bauer, MSN, MBA, APRN, discusses rhabdomyolysis.

A healthy 31-year-old male calls 9-1-1 when he is unable to fully bend his legs upon awakening. He complains of aching muscles, especially in his legs; fatigue; and notices his urine is darker than usual. 

The patient says he went to a cycling class two days ago, was fatigued afterward, and noticed some pain in his anterior thighs. Yesterday he was sore but could go about his daily activities. Last night his pain increased, and he took ibuprofen without relief. 

He denies abdominal pain, flank pain, dysuria, nausea, vomiting, diarrhea, back pain, recent illness, or fever. Aside from the dark urine and muscle pain, he has no other complaints. He does not take any regular home medications and denies any significant medical or surgical history. He says he’s just now getting back into working out after taking several months off. He has never been a smoker and denies alcohol or substance use. 

On examination you note tenderness to palpation over bilateral lower extremities, with thighs more tender than lower legs, but no abdominal tenderness. You find no obvious soft-tissue edema or ecchymosis. His vitals are BP 132/82, HR 74, RR 16 and unlabored, temperature 98.3ºF, and SpO₂ 99% on room air. He cannot bear weight to ambulate and cannot fully extend his lower extremities. You suspect rhabdomyolysis and initiate a liter of NS bolus. You also obtain an EKG en route that shows normal sinus rhythm with no other acute findings. 

Rhabdomyolysis

Rhabdomyolysis occurs when intracellular contents are released into the circulation after damage to skeletal muscles. This leads to systemic effects; acute kidney injury (AKI) is the most common. In more severe cases it can also lead to electrolyte disturbances, disseminated intravascular coagulation (DIC), and cardiac instability. Symptoms are typically weakness, myalgias, and dark-colored urine secondary to myoglobinuria. 

The pathophysiology behind rhabdomyolysis can be complex but essentially involves myocyte (muscle cell) death and the release of contents from within the cell. Normal myocytes are regulated by ion pumps that maintain concentration gradients across the cell membrane, with sodium and calcium levels lower inside the cell than out and potassium higher inside the cell. Adenosine triphosphate (ATP) is required for these pumps to work effectively and muscle contraction to occur. If ATP is reduced or there is a disruption to the pumps, it causes cellular injury, allowing excess calcium and sodium to enter the cell. The excess of intracellular calcium is devastating to cells and causes excessive muscle contractions.¹ This causes a further decline in ATP and leads to destruction of the cell membrane, allowing more calcium to accumulate, eventually leading to muscle cell death.

When the cell dies it releases the intracellular contents (potassium, calcium, sodium, creatine kinase, and myoglobin) into the extracellular space. Uric acid and myoglobin released from ruptured cells accumulate and lead to tubular necrosis, a form of AKI.²

Excess potassium and calcium are released with cell death and can also lead to clinical symptoms. Hyperkalemia can cause weakness and cardiac disturbances. Hypercalcemia can lead to muscle weakness, vomiting, acute kidney injury, and bradycardia. Creatine kinase (CK), aspartate transaminase (AST), and lactate dehydrogenase (LDH) are also released with muscle cell death.² DIC can be a severe complication secondary to activation of the coagulation pathways from myocyte destruction.

Causes and Presentation

The causes of rhabdomyolysis are often divided into exertional and nonexertional. In the adult population we often see rhabdomyolysis with overexertion/exercise, immobility, or intoxication. Certain medications, such as propofol, quetiapine (Seroquel), and statins, have been associated with its development. 

Also consider rhabdomyolysis in the setting of local muscle damage, especially with crush injuries. However, in the pediatric population, a vast majority of cases are nonexertional, often secondary to viral infections. Less common in children are inherited syndromes and exercise-induced cases. The most common viruses responsible for rhabdomyolysis development in the pediatric population are influenza, Epstein-Barr, and cytomegalovirus. Group A beta-hemolytic streptococci, a bacterial infection, has also been reported in cases. Common inherited disorders include inborn errors of metabolism, inflammatory myopathies, congenital myopathies, and muscular dystrophies. 

Exercise-induced rhabdomyolysis is more often seen in the teenage population. When dealing with the older pediatric population, also consider intoxications such as alcohol, marijuana, heroin, cocaine, LSD, ecstasy, and amphetamines as a cause for rhabdomyolysis. 

The classic presentation of rhabdomyolysis includes muscle weakness, myalgias, and brown (tea-colored) urine. However, the presence of all three “classic” symptoms is uncommon. Many patients may complain of nonspecific symptoms, including nausea, vomiting, tachycardia, swelling, palpitations, oliguria, and anuria. Most patients complain of muscle pain or weakness. 

The pediatric population will often present with myalgias only, and parents may note recent viral illness symptoms. When obtaining a thorough history from the patient and parent, always ask about recent infections. It is also important to consider excessive exercise and fasting, especially in the older female pediatric population.

Diagnostics

The initial workup should include a complete blood count (CBC), comprehensive metabolic panel (CMP), urinalysis with microscopic examination, and serum CK level. If leukocytosis is present on the CBC, consider an infectious process occurring. The CMP will help evaluate any electrolyte abnormalities and assess overall kidney function. Electrolyte disturbances may include hyponatremia, hypo- or hypercalcemia, hyperkalemia, hyperuricemia, hyperphosphatemia, and metabolic acidosis.

There are no definitive criteria for the diagnosis of rhabdomyolysis; however, most clinicians utilize the elevated CK or myoglobin, because it seems the most sensitive marker for muscle breakdown. It is often easiest to use five times the upper limit of normal for the CK level as positive for a diagnosis of rhabdomyolysis (~1,000 IU/L). This is typically true for both adult and pediatric populations. The CK level starts rising about 2–12 hours after the insult occurs, peaks 24–72 hours later, and declines over the next 5–10 days. 

In contrast, the serum myoglobin level is less sensitive than CK for diagnosing rhabdomyolysis. Myoglobin rises sooner than CK but has a shorter half-life, leading to more rapid clearance. Because elevations rapidly return to normal, myoglobin is not often used to diagnose rhabdomyolysis. 

The classic tea-brown urine results from myoglobin. Although most urine dipsticks do not directly test for myoglobin, its presence can be inferred from large amounts of blood without red blood cells. The absence of myoglobin in the urine should not be used to exclude rhabdomyolysis—it has high specificity but poor sensitivity. Use it in this setting to help confirm your suspicions. There may be elevated aminotransferases (AST and ALT). This is likely secondary to intramuscular release and not always due to liver damage, although that should be considered. 

Management

Once you have diagnosed rhabdomyolysis, focus on treatment of the underlying problem, treatment of the current situation, and prevention of secondary complications. If the rhabdomyolysis is from hyperthermia, actively cool the patient as quickly as possible. Stop any offending medications immediately. Antibiotics should be initiated for active infections. If compartment syndrome is suspected, an emergent fasciotomy should be performed in the operating room. 

The initial treatment goal should be to prevent AKI and preserve kidney function. The best way to accomplish this is administration of IV fluids. IV fluids within the first six hours after muscle injury have been shown to decrease AKI risk. 

While there is consensus that fluids should be administered, there is less agreement about the best type, rate, or duration. This is true for both pediatric and adult populations. Normal saline (NS) still seems to be the most commonly used fluid for rhabdomyolysis. A study comparing the use of NS and lactated Ringer’s demonstrated no difference in CK or serum potassium levels or the development of AKI.¹ However, while NS may be used, excessive volumes can lead to iatrogenic hyperchloremic metabolic acidosis and slower myoglobin clearance.

The rate of IV fluid administration tends to vary as well. Initially, in the adult population, 1.5 liters an hour is the recommendation. However, using a target urine output (UO) of 200–300 mL/hr in adults until serum CK levels begin to decrease is a better marker of adequate fluid resuscitation. Titrate IV fluids to achieve the desired UO. In the pediatric population a 20-mL/kg bolus is administered initially, followed by a maintenance rate that is twice the normal rate. UO for the pediatric patient should be approximately 3–4 times the adult rate or 3–4 mL/kg/hr until the serum CK levels begin to decrease. Adjust IV fluids depending on the UO or overall fluid balance. Monitor for and avoid overhydration.

Rhabdomyolysis is associated with decreased urine pH, which can lead to a decrease in myoglobin excretion. Sodium bicarbonate is often added to alkalinize the urine and help get rid of excess myoglobin to prevent AKI. However, no randomized controlled trials demonstrate the benefit of sodium bicarb compared to aggressive IV fluid administration alone.³ It may still be used in the setting of severe acidosis (urine pH less than 6.5), but remember sodium bicarb in larger doses can worsen hypocalcemia, so use caution in patients who are already hypocalcemic. 

Mannitol has also been used in the past as an osmotic diuretic. Like sodium bicarb, there are no good RCTs demonstrating a benefit in the use of mannitol compared to IV fluids alone.³ Avoid nephrotoxic medications, such as nonsteroidal anti-inflammatory drugs, in these patients. Address any electrolyte disturbances as warranted. If hypocalcemia is present, avoid using calcium chloride or gluconate unless the patient is symptomatic or severely hyperkalemic. Supplementing calcium can lead to further muscle damage and rebound hypercalcemia.¹ Overall, management should focus on using IV fluids to achieve the desired UO. Routine use of sodium bicarb, mannitol, and furosemide is no longer recommended based on the present literature.

Case Conclusion

Upon arrival in the ED, your patient has the following abnormalities noted on his labs: AST 1,235 U/L (normal 8–35), ALT 180 U/L (normal 10–80), and total CK 78,493 IU/L (normal 35–250). Urinalysis reveals red discoloration with 2+ protein, 3+ occult blood, 1+ bilirubin, urine casts, and granular casts present, but no urine RBCs. Your initial suspicion of rhabdomyolysis is confirmed. 

Your patient continues to receive IV fluids and is ultimately admitted for continued fluids and trending of his CK. His UO is maintained at approximately 200 mL/hr, and he does not develop AKI during his stay. He is released on day four with normal renal function and advised on a gradual return to exercise. His CK normalizes over the next two weeks. 

References

1. 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 Mar; 37(3): 518–23. 

2. Szugye HS. Pediatric Rhabdomyolysis. Pediatr Rev, 2020 Jun; 41(6): 265–75. 

3. Marik PE. Evidence-Based Critical Care, 3rd ed. Springer, 2018. 

Ashley Bauer, MSN, MBA, APRN, FNP-C, CFRN, C-NPT, TCRN, is vice president of business operations for FlightBridgeED. She is an advanced-practice RN in the ED. She began as an ER nurse, transitioned to flight nurse, and is currently a nurse practitioner.