1. Overview and Definitions

Rhabdomyolysis is defined by skeletal muscle breakdown with release of intracellular constituents—creatine kinase (CK), myoglobin, and electrolytes—into the circulation. Early recognition relies on biochemical criteria and clinical signs.

Diagnostic Criteria:

• Serum CK >5× upper limit of normal (ULN) or >1,000 IU/L
• Myoglobinuria: urine dipstick positive for blood without red blood cells
• Dark (“tea-colored”) urine and oliguria in the appropriate clinical context

2. Epidemiology and Incidence

In ICU populations, rhabdomyolysis incidence varies by patient cohort—highest in trauma, burn, and severe sepsis. Elevated biomarkers correlate with AKI rates and mortality.

ICU Incidence Data:

• Trauma with crush injuries or prolonged immobilization: 20–40%
• Burn patients (≥20% total body surface area): 10–30%
• Severe sepsis/septic shock: 5–15%

Outcome Metrics:

• AKI develops in 13–50% of rhabdomyolysis cases
• Mortality ranges 3%–20%, driven by AKI severity and need for renal replacement therapy

High-Risk Cohorts:

• Statin users, especially with CYP450 inhibitors
• Illicit drug or heavy alcohol users
• Underlying metabolic myopathies or genetic enzyme defects

3. Pathophysiology

Mechanical, ischemic, or toxic insults disrupt the sarcolemma, triggering calcium overload, protease activation, and release of myocyte contents.

A. Mechanisms of Muscle Injury

• Mechanical: crush, blunt trauma, compartment syndrome
• Ischemic: vascular compromise, prolonged pressure
• Toxic: statins, illicit drugs, infections, electrolyte disturbances

B. Intracellular Content Release

• Myoglobin (17.5 kDa): filtered at glomerulus, nephrotoxic at high concentrations
• Creatine kinase: sensitive marker of muscle injury
• Electrolytes: K⁺, PO₄³⁻, uric acid → risk of hyperkalemia, hyperphosphatemia

C. Myoglobin-Mediated Renal Injury

• Tubular obstruction: myoglobin–Tamm–Horsfall protein casts in acidic urine
• Oxidative stress: free radicals damage tubular epithelium
• Vasoconstriction: nitric oxide scavenging and vasoactive mediators reduce renal blood flow

4. Influence of Chronic Comorbidities

Pre-existing CKD, diabetes, and metabolic syndrome compromise renal reserve and magnify muscle and renal injury in rhabdomyolysis.

Chronic Kidney Disease

• Reduced nephron mass impairs myoglobin clearance
• Baseline CK elevations may confound new injury detection

Diabetes and Metabolic Syndrome

• Microvascular disease and hyperglycemia enhance oxidative injury
• Impaired muscle perfusion increases ischemic vulnerability

Medication-Related Factors

• Statins (HMG-CoA reductase inhibitors): dose-dependent myopathy risk
• Interacting agents (e.g., macrolides, azoles) and renal impairment raise rhabdomyolysis risk

5. Social Determinants of Health

Socioeconomic status, health literacy, and system barriers influence recognition, presentation timing, and outcomes in rhabdomyolysis.

Medication Access & Adherence

• Cost or formulary restrictions → nonadherence, abrupt discontinuation

Health Literacy

• Low literacy delays recognition of muscle pain and dark urine

Systemic Barriers

• Insurance status and rural location delay ICU presentation

Mitigation Strategies

• Pharmacist-led education on symptom recognition and medication safety
• Community outreach to high-risk groups; telehealth follow-up