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2025 PACUPrep BCCCP Preparatory Course Rhabdomyolysis Rhabdomyolysis: Clinical Management and Pharmacotherapy

Lesson 18, Topic 2

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Rhabdomyolysis: Clinical Management and Pharmacotherapy

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Initial Diagnosis and Severity Stratification of Rhabdomyolysis

Objective

Apply diagnostic and classification criteria to assess a patient with rhabdomyolysis and guide initial management.

Learning Points

Recognize key clinical features: muscle pain, weakness, cramps, and dark urine.
Interpret laboratory tests (CK, myoglobin, renal function, electrolytes, urinalysis) for diagnosis and etiology.
Use AKI staging (RIFLE, AKIN, KDIGO) and the McMahon rhabdomyolysis score for risk stratification.

1. Clinical Manifestations

Rhabdomyolysis presents with a variable spectrum of symptoms, from mild myalgias to profound weakness and characteristic dark (“tea-colored”) urine. Early recognition of the clinical triad—muscle symptoms, swelling, and urine changes—is crucial for facilitating urgent evaluation and intervention.

Patient Symptoms

Myalgia, cramps, and stiffness: These symptoms are most common in large, proximal muscle groups such as the thighs, calves, and lower back.
Weakness: The degree of weakness can range from mild functional limitation to complete immobility, depending on the severity of muscle injury.

Physical Signs

Muscle swelling and tenderness: Affected muscles may be visibly swollen, firm, and tender to palpation.
Tense compartments: Severe swelling can lead to tense, fluid-filled muscle compartments, raising suspicion for compartment syndrome, a surgical emergency.
Range-of-motion limitation: Pain and swelling can significantly restrict movement of the affected limbs.

Urine Changes

Dark or cola-colored appearance: The classic description of urine in rhabdomyolysis is due to myoglobinuria.
Absence of color change: Importantly, urine may appear normal despite severe muscle injury, especially if the patient is well-hydrated.

Case Vignette

A 45-year-old marathon runner presents to the emergency department with severe bilateral leg pain and dark urine 24 hours after completing a 50 km race. On examination, his calves are swollen and exquisitely tender. Initial labs reveal a creatine kinase (CK) of 18,000 IU/L and a serum potassium of 6.2 mmol/L. Early, aggressive fluid resuscitation and continuous ECG monitoring are initiated immediately.

Clinical Pearls

Up to 50% of patients may have normal-colored urine despite significant myoglobinuria and muscle injury. Do not rule out rhabdomyolysis based on urine color alone.
Compartment syndrome is a clinical diagnosis, but compartment pressures should be measured urgently if swelling is severe, pain is out of proportion to the exam, or there are signs of neurovascular compromise.

2. Laboratory Evaluation

Serum creatine kinase (CK) is the cornerstone biomarker for diagnosing rhabdomyolysis. This is supported by evaluation of myoglobin, renal function indices, electrolytes, and urinalysis. Understanding the kinetics, diagnostic thresholds, and potential pitfalls of these tests is essential for accurate assessment.

Key Biomarkers

Creatine Kinase (CK): A level >5 times the upper limit of normal or an absolute value >1,000 IU/L confirms the diagnosis. CK levels begin to rise 2–12 hours after injury, peak at 24–72 hours, and then decline over several days. Pitfalls include falsely low levels in patients with delayed presentation, those undergoing renal replacement therapy (RRT), or those with low baseline muscle mass.
Serum Myoglobin: Rises very early after injury but is rapidly cleared by the kidneys within 1–6 hours. Its utility is limited by this short half-life and variable assay sensitivity.
Renal Function and Urine Output: Trends in BUN and creatinine (Cr) are critical for detecting acute kidney injury (AKI). Oliguria, defined as urine output <0.5 mL/kg/hr, is a key sign, though nonoliguric AKI can also occur.
Electrolytes: Hyperkalemia from cellular release is a life-threatening complication and should be monitored every 4–6 hours in severe cases. Hypocalcemia is common early due to calcium deposition in injured muscle, while hyperphosphatemia is also frequently seen. Rebound hypercalcemia can occur during the recovery phase.
Urinalysis: A urine dipstick that is positive for heme (blood) in the absence of red blood cells (RBCs) on microscopy strongly suggests myoglobinuria. The presence of granular (“muddy brown”) casts indicates acute tubular necrosis (ATN).

Clinical Pearls

While a peak CK >15,000–20,000 IU/L is correlated with a higher risk of AKI, there is no absolute CK value that reliably predicts renal failure. The overall clinical picture is more important.
A positive urine dipstick for blood without corresponding RBCs on microscopy has a high specificity for myoglobinuria and is a valuable, rapid screening tool.

3. Classification and Severity Scoring

Standardized criteria are used to stratify the risk of renal injury and other adverse outcomes. The KDIGO guidelines are the international standard for defining and staging AKI, while the McMahon score provides rhabdomyolysis-specific prognostication for AKI, the need for RRT, and mortality.

AKI Staging Systems

The RIFLE, AKIN, and KDIGO criteria are used to classify the severity of AKI based on changes in serum creatinine and urine output. KDIGO is the most current and widely accepted system.

Comparison of AKI Staging Criteria
Stage	RIFLE	AKIN	KDIGO (Preferred)
1 (Risk)	Cr ×1.5 OR UO <0.5 mL/kg/hr for 6h	Cr ↑ ≥0.3 mg/dL OR Cr ×1.5–2	Cr ↑ ≥0.3 mg/dL (in 48h) OR Cr ×1.5–1.9 (in 7d)
2 (Injury)	Cr ×2 OR UO <0.5 mL/kg/hr for 12h	Cr ×2–3	Cr ×2–2.9 from baseline
3 (Failure)	Cr ×3 OR UO <0.3 mL/kg/hr for 24h OR Anuria 12h	Cr ×3 OR Cr ≥4.0 mg/dL OR RRT initiation	Cr ×3 OR Cr ≥4.0 mg/dL OR RRT initiation
UO = Urine Output; Cr = Creatinine; RRT = Renal Replacement Therapy

McMahon Rhabdomyolysis Score

This validated risk score uses eight clinical and laboratory variables at presentation to predict the likelihood of developing severe AKI, requiring RRT, or in-hospital mortality. A score of ≥6 indicates high risk.

McMahon Score Calculation

Age, Sex

Etiology

Creatinine, Ca²⁺

CK, PO₄³⁻, HCO₃⁻

Calculate Score (0-10+)

Score <6: Low Risk

Score ≥6: High Risk

Figure 1: McMahon Rhabdomyolysis Score. This score integrates key patient data to stratify risk for AKI, need for RRT, and mortality, guiding the intensity of monitoring and therapy.

4. Integration into Initial Management

Severity stratification directly informs the intensity of fluid resuscitation, frequency of lab monitoring, and early identification of patients who may require RRT. Pharmacists play a critical role in ensuring appropriate monitoring, therapy adjustments, and multidisciplinary coordination.

Fluid Resuscitation

High-Risk Patients (McMahon ≥6 or KDIGO stage 2–3): Begin aggressive resuscitation with an isotonic crystalloid (e.g., Lactated Ringer’s or Plasma-Lyte) to target a urine output of 1–3 mL/kg/hr (approx. 100-200 mL/hr).
Therapeutic Goal: The primary goal is to maintain renal perfusion and flush out myoglobin casts. Adjust the fluid rate based on volume responsiveness, hemodynamic stability, and signs of volume overload.

Electrolyte Correction

Hyperkalemia: Treat urgently if potassium is >6 mmol/L or if there are associated ECG changes (peaked T waves, wide QRS). Management includes intravenous calcium gluconate for membrane stabilization, followed by insulin/glucose and beta-2 agonists to shift potassium intracellularly. Consider RRT for refractory or severe hyperkalemia.
Hypocalcemia: Treat only if the patient is symptomatic (e.g., tetany, seizures) or if hypocalcemia is severe (ionized calcium <1.9 mmol/L or total calcium <7.5 mg/dL), as over-correction can lead to rebound hypercalcemia during recovery.

Indications for Renal Replacement Therapy (RRT)

Early nephrology consultation is crucial for high-risk patients. The primary triggers for initiating RRT are the life-threatening complications of rhabdomyolysis-induced AKI:

Refractory hyperkalemia
Severe metabolic acidosis (pH < 7.1-7.2)
Symptomatic uremia (e.g., encephalopathy, pericarditis)
Significant volume overload unresponsive to diuretics

Role of the Pharmacist

Pharmacists are integral members of the care team. Key responsibilities include:

Recommending serial lab monitoring (e.g., CK, creatinine, electrolytes) every 6–12 hours during the acute phase.
Advising on dose adjustments for all renally cleared medications.
Preventing further kidney injury by identifying and discontinuing other nephrotoxic agents.
Leading the development and implementation of electrolyte management protocols and overseeing fluid balance.

References

Bosch X, Poch E, Grau JM. Rhabdomyolysis and acute kidney injury. N Engl J Med. 2009;361(1):62–72.
Kodadek L, Carmichael SP II, Seshadri A, et al. Rhabdomyolysis: clinical consensus document. Trauma Surg Acute Care Open. 2022;7:e000836.
Sauret JM, Marinides G, Wang GK. Rhabdomyolysis. Am Fam Physician. 2002;65(5):907–912.
Chavez LO, Leon M, Einav S, Varon J. Beyond muscle destruction: systematic review of rhabdomyolysis. Crit Care. 2016;20:135.
Simpson JP, Taylor A, Sudhan N, et al. Validation of the McMahon score in rhabdomyolysis. Eur J Anaesthesiol. 2016;33(12):906–912.
McMahon GM, Zeng X, Waikar SS. A risk prediction score for rhabdomyolysis-induced AKI. JAMA Intern Med. 2013;173(19):1821–1828.
KDIGO AKI Work Group. KDIGO clinical practice guideline for acute kidney injury. Kidney Int Suppl. 2012;2(1):1–138.
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.

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