Definition of Rhabdomyolysis
Rhabdomyolysis is defined as a clinical and laboratory syndrome resulting from skeletal muscle injury with release of intracellular muscle contents—including creatine kinase, myoglobin, electrolytes, and other toxic substances—into the circulation. 1, 2, 3
Core Diagnostic Criteria
The diagnosis of rhabdomyolysis fundamentally depends on three key elements:
- Elevated creatine kinase (CK) levels greater than 5 times the upper limit of normal, which serves as the primary laboratory marker 4
- Clinical symptoms of muscle injury, including muscle pain, weakness, or soreness 5, 1
- Evidence of myoglobinuria, manifested as red-to-brown colored urine that tests positive for blood on urinalysis without red blood cells present 6, 1
Severity Spectrum
The clinical presentation exists on a broad spectrum:
- Mild disease may present with asymptomatic elevations of muscle enzymes without systemic complications 1, 7, 3
- Moderate disease involves symptomatic muscle injury with CK elevations but preserved renal function 8
- Severe disease progresses to life-threatening complications including acute kidney injury, severe electrolyte abnormalities (particularly hyperkalemia), metabolic acidosis, compartment syndrome, and disseminated intravascular coagulation 5, 2, 4, 3
Pathophysiologic Mechanism
The underlying pathophysiology involves:
- Muscle cell breakdown (myonecrosis) as the common final pathway, regardless of etiology 2, 3
- Release of intracellular contents including potassium, calcium, phosphate, uric acid, creatinine kinase, and myoglobin into the bloodstream 4, 3
- Myoglobin-induced renal tubular obstruction and toxicity, which represents the most serious systemic complication and can lead to acute kidney injury requiring dialysis 5, 9, 8
Critical Diagnostic Threshold
While CK elevation >5 times the upper limit of normal is the standard diagnostic criterion 4, severe rhabdomyolysis warranting aggressive intervention is typically defined by:
- CK levels >15,000 IU/L, which indicates severe disease requiring >6L/day fluid resuscitation 6
- CK levels of 3,000-5,000 IU/L are considered abnormal and associated with increased acute kidney injury risk in clinical populations 6
Common Diagnostic Pitfall
A critical caveat is that CK levels do not peak immediately but rather between 24-120 hours after the muscle injury, depending on the mechanism 6. This delayed peak due to lymphatic clearance of the large CK molecule (82 kDa) means that initial CK levels may be misleadingly low, and repeat measurement at 24 hours is essential if clinical suspicion remains high 6.