What is the recommended management for rhabdomyolysis?

Management of Rhabdomyolysis

Immediate Fluid Resuscitation

Aggressive intravenous fluid resuscitation is the single most critical intervention for rhabdomyolysis and must be initiated immediately upon diagnosis to prevent acute kidney injury and death. 1, 2, 3

Fluid Administration Protocol

• Initiate isotonic saline (0.9% NaCl) immediately at the scene of injury or upon diagnosis, as delayed treatment significantly increases the risk of acute kidney injury and mortality 1, 2, 3

• Target urine output of 300 mL/hour to facilitate myoglobin clearance and prevent renal tubular obstruction 2, 4

• For severe rhabdomyolysis (CK >15,000 IU/L), administer >6L of fluid per day; for moderate cases (CK 5,000-15,000 IU/L), use 3-6L per day 1, 2

• In extensive rhabdomyolysis, volumes of ≥12L daily may be required to stabilize circulation, mobilize edema fluids sequestered in injured muscles, and protect against nephrotoxic effects of myoglobinemia 3

• Monitor closely for fluid overload, particularly in patients with cardiac or renal compromise, though young carefully monitored individuals typically tolerate large positive fluid balance well 2, 3

Evidence Supporting Aggressive Fluid Resuscitation

The Eastern Association for the Surgery of Trauma meta-analysis demonstrated that aggressive intravenous fluid resuscitation decreased both the incidence of acute renal failure and need for dialysis in patients with rhabdomyolysis 5. Historical data from muscle crush syndrome shows mortality reduction from nearly 100% to <20% over 70 years through early vigorous fluid resuscitation 3.

Electrolyte Monitoring and Management

Critical Electrolyte Surveillance

• Monitor potassium levels every 6-12 hours in severe cases, as hyperkalemia can precipitate life-threatening cardiac arrhythmias and pulseless electrical activity 1, 2

• Perform repeated bioassessment including plasma myoglobin, CK, and potassium measurements throughout the acute phase 1, 2

• Check complete electrolyte panels including calcium, phosphorus, and magnesium, as hypocalcemia and hyperphosphatemia commonly occur 1, 2

• Assess for metabolic acidosis via arterial blood gas, which frequently develops in severe rhabdomyolysis 1, 2

Electrolyte Correction

• Correct significant electrolyte abnormalities promptly, particularly life-threatening hyperkalemia 1, 2

• Maintain urine pH at approximately 6.5 if possible through adequate hydration 2

Medications to Avoid and Discontinue

Immediate Discontinuation Required

• Immediately discontinue all causative medications and supplements, including statins, creatine monohydrate, red yeast rice, wormwood oil, licorice, and Hydroxycut 1, 6, 2

• Cease the specific physical activity that triggered the rhabdomyolysis episode 6, 2

• Avoid succinylcholine in perioperative settings, as it can exacerbate rhabdomyolysis 1

Nephrotoxic Agents to Avoid

• Avoid all NSAIDs (ibuprofen, ketoprofen, diclofenac, naproxen, mefenamic acid) due to their gastrointestinal and renal toxicity in patients already at high risk for acute kidney injury 1

• Withdraw all nephrotoxic medications to prevent re-injury 6

Bicarbonate and Mannitol: Not Recommended

Neither bicarbonate nor mannitol administration should be routinely used in rhabdomyolysis management. 5

• The Eastern Association for the Surgery of Trauma conditionally recommends against treatment with bicarbonate or mannitol, as neither improved the incidence of acute renal failure or need for dialysis in meta-analysis 5

• Once appropriate saline expansion is provided, the association of mannitol and bicarbonate appears unnecessary, as demonstrated in prospective studies where progression to established renal failure was avoided with saline alone 7

This represents a critical divergence from older practices, with the most recent and highest quality evidence (2022 meta-analysis) clearly showing no benefit 5.

Pain Management

First-Line Analgesic

• Use acetaminophen 500-1000 mg as the preferred initial analgesic, with onset of action in 15-30 minutes and maximum daily dose of 4-6 grams 1

• Acetaminophen avoids nephrotoxic effects that are particularly problematic in rhabdomyolysis patients at high risk for acute kidney injury 1

Severe Pain Management

• Reserve opioids for severe muscle pain unresponsive to acetaminophen 1

• Use oral morphine 20-40 mg for opioid-naive patients with moderate to severe pain 1

• In patients with established acute kidney injury (eGFR <30 ml/min), use fentanyl or buprenorphine as the safest opioid choices 1

• Provide round-the-clock dosing with rescue doses (10-15% of total daily dose) for breakthrough pain, titrating rapidly while monitoring for side effects 1

Compartment Syndrome Surveillance

Early Recognition Critical

• Maintain high suspicion for compartment syndrome, which can both cause and complicate rhabdomyolysis 1, 2

• Early signs include pain, tension, paresthesia, and paresis; late signs include pulselessness and pallor, which often indicate irreversible damage 1, 2

Surgical Intervention Thresholds

• Perform early fasciotomy for established compartment syndrome 1, 2

• Consider fasciotomy when compartment pressure exceeds 30 mmHg or when differential pressure (diastolic BP – compartment pressure) is <30 mmHg 1, 2

Renal Replacement Therapy

Indications for RRT

• Initiate RRT if CK remains persistently elevated despite 4 days of adequate hydration, as this indicates severe rhabdomyolysis with significant risk of irreversible kidney damage 2

• Consider RRT for refractory hyperkalemia, severe metabolic acidosis, or progressive acute kidney injury 2

• Early initiation of RRT is associated with improved outcomes in severe cases 2

Diuretic Challenge

• After ensuring adequate volume expansion, a diuretic challenge with furosemide may help assess kidney function in select cases 2

• Response to diuretics may predict successful recovery of kidney function 2

Laboratory Workup

Initial Essential Tests

• Creatine kinase (CK) level - diagnosis requires elevation of at least 10 times the upper limit of normal, though severe disease may reach 100,000 IU/L 8

• Complete metabolic panel including creatinine, BUN, electrolytes (particularly potassium, calcium, phosphorus, magnesium) 1, 2

• Urinalysis - look for brown color, cloudiness, and positive for blood without RBCs indicating myoglobinuria 1

• Complete blood count with differential to evaluate for infection or systemic processes 1

• Liver function tests (AST, ALT, alkaline phosphatase) to assess for transaminitis from muscle enzyme release 1

• Arterial blood gas to assess for metabolic acidosis 1, 2

Additional Testing Based on Clinical Context

• Cardiac assessment including ECG and cardiac troponin in patients with severe rhabdomyolysis to rule out cardiac involvement 1

• Coagulation studies to evaluate for disseminated intravascular coagulation 1

Etiology-Specific Testing for Recurrent Cases

• For recurrent rhabdomyolysis, history of exercise intolerance, or family history of neuromuscular disorders, perform genetic testing 1, 8

• RYR1 and CACNA1S gene sequencing for malignant hyperthermia susceptibility, particularly in exertional rhabdomyolysis or heat illness 1

• CPT2, PYGM, ACADM, AMPD1, and VLCAD gene testing for metabolic myopathies causing recurrent rhabdomyolysis 1

• SLCO1B1 gene mutations increase risk of statin-induced rhabdomyolysis 1

Timing Considerations for Trauma Cases

• In traumatic rhabdomyolysis, CK levels peak 24-120 hours after the event due to lymphatic clearance mechanisms 1

• Repeat CK measurement at 24 hours post-fall if clinical suspicion remains high, as impact trauma can drastically increase CK without reflecting true muscle breakdown 1

Discharge Planning and Follow-Up

Immediate Post-Discharge Monitoring

• Schedule laboratory evaluation within 3-7 days after discharge to assess kidney recovery, including creatinine, BUN, and electrolyte panels 6

• Continue weekly monitoring of creatinine values if kidney function has not fully normalized 6

• Arrange continued follow-up with a nephrologist, particularly for patients with more severe kidney injury, pre-existing chronic kidney disease, diabetes, or proteinuria 6

Medication Adjustments

• Adjust all renally excreted medications based on current kidney function 6

• Do not resume causative medications or supplements, as this increases risk of recurrent episodes 6

Activity Recommendations

• Maintain adequate oral hydration to support continued myoglobin clearance 6

• Return to normal activities in a graded fashion, avoiding sudden increases in exercise intensity or duration 6

Special Considerations for Dialysis-Dependent Patients

• Inform chronic dialysis facility to utilize a personalized approach maximizing renal recovery 6

• Avoid excessive fluid removal and hypotension during dialysis sessions, as these can cause re-injury and reduce likelihood of recovery 6

• Perform weekly assessment of pre-dialysis serum creatinine and regular evaluation of residual kidney function using 24-hour urine collections 6

Common Pitfalls to Avoid

• Delaying fluid resuscitation is the most critical error, associated with higher risk of acute kidney injury and worse outcomes 1, 2, 3

• Inadequate fluid volume (using <6L/day in severe cases with CK >15,000 IU/L) may fail to prevent renal complications 1, 2

• Failure to monitor and correct hyperkalemia can lead to pulseless electrical activity and cardiac arrest 1, 2

• Missing compartment syndrome, particularly in traumatic or severe exertional cases, results in irreversible muscle and nerve damage 1, 2

• Using bicarbonate or mannitol routinely, which lacks evidence for benefit and may cause harm 5

• Delaying follow-up laboratory assessment beyond 7 days, which can miss early signs of kidney function deterioration 6