Rhabdomyolysis 

🔹 Introduction

Rhabdomyolysis is a clinical and biochemical syndrome resulting from skeletal muscle breakdown with the release of intracellular contents—notably myoglobin, creatine kinase (CK), potassium, phosphate, uric acid, and other proteins—into the circulation.
This can lead to acute kidney injury (AKI), electrolyte disturbances, disseminated intravascular coagulation (DIC), and metabolic derangements.

🔹 Pathophysiology

1. Muscle Cell Injury
• Muscle fibers (myocytes) are disrupted by mechanical, metabolic, or toxic insults.
• Sarcolemma integrity is lost → massive release of intracellular contents into plasma.

2. Key Intracellular Components Released

• Myoglobin → nephrotoxic, causes tubular obstruction and oxidative damage.
• Creatine kinase (CK) → diagnostic marker.
• Potassium → hyperkalemia → arrhythmias.
• Phosphate → hyperphosphatemia → hypocalcemia (due to calcium phosphate precipitation).
• Uric acid → tubular precipitation.

3. Renal Injury Mechanisms

• Tubular obstruction by myoglobin casts (esp. acidic urine).
• Direct cytotoxicity of myoglobin to tubular epithelial cells.
• Renal vasoconstriction → ischemic injury (via nitric oxide scavenging, endothelin release).

4. Acidic urine enhances myoglobin precipitation, worsening nephrotoxicity.

🔹 Etiology (Mnemonic: 5 M’s)

1️⃣ Mechanical / Traumatic

• Crush injuries (earthquake victims, accidents)
• Prolonged immobilization, coma, seizures, surgery under tight tourniquets

2️⃣ Metabolic / Exertional

• Strenuous exercise (marathon, military training)
• Heat stroke
• Seizures, delirium tremens

3️⃣ Medication / Toxin-induced

• Statins (esp. with CYP inhibitors, fibrates)
• Alcohol, cocaine, amphetamines, MDMA
• Carbon monoxide, cyanide, snake venoms
• Antipsychotics (neuroleptic malignant syndrome)
• Malignant hyperthermia (succinylcholine, halothane)
• Propofol infusion syndrome

4️⃣ Metabolic / Electrolyte Disorders

• Hypokalemia, hypophosphatemia, hypocalcemia
• Diabetic ketoacidosis

5️⃣ Miscellaneous / Infectious

• Viral (influenza, HIV, COVID-19)
• Bacterial toxins (Clostridium perfringens)
• Autoimmune myositis, polymyositis, dermatomyositis

🔹 Clinical Features

Early

• Muscle pain, tenderness, swelling
• Weakness
• Dark or cola-colored urine (myoglobinuria)

Systemic Features

• Fever, tachycardia
• Confusion, agitation
• Hypovolemia (fluid sequestration into injured muscles)
• Electrolyte abnormalities:
• Hyperkalemia → arrhythmias
• Hypocalcemia (early phase)
• Hyperphosphatemia
• Hyperuricemia
• Metabolic acidosis

Late

• Acute kidney injury (AKI) — oliguria, azotemia
• DIC
• Compartment syndrome (in severe muscle swelling)

🔹 Diagnosis

 Laboratory Findings

 Imaging (if needed)

• MRI or CT may show swollen, edematous muscles.
• Used to detect compartment syndrome or underlying cause (trauma).

🔹 Diagnostic Criteria

No universal criteria, but CK > 1000 U/L (or >5× ULN) in presence of compatible history/symptoms is highly suggestive.
Myoglobinuria supports diagnosis but is not mandatory.

🔹 Complications

🔹 Management

1️⃣ Initial Resuscitation

• Airway, breathing, circulation (ABC)
• Remove the cause (e.g., stop statin, treat seizure, cool hyperthermia)
• Aggressive fluid resuscitation is cornerstone

2️⃣ Fluid Therapy

• Goal: Maintain urine output ≥200–300 mL/h
• Preferred fluid: Isotonic saline (avoid lactate-containing fluids early)
• Typical regimen:
• 1–2 L NS in first 2 h, then 500 mL/h
• Adjust to urine output and hemodynamics
• Continue until CK < 1000 IU/L and urine clears.

3️⃣ Urine Alkalinization

• Rationale: Prevent myoglobin precipitation and free radical injury
• Regimen: Add 50–100 mEq sodium bicarbonate to 1 L D5W
• Target urine pH >6.5, serum pH <7.5
• Only after ensuring adequate urine output.

4️⃣ Mannitol (optional)

• Osmotic diuretic → enhances urine flow, decreases edema
• Use only if urine output >20 mL/h and no AKI
• Avoid in oliguria or established AKI.

5️⃣ Electrolyte Correction

• Hyperkalemia: Calcium gluconate, insulin + glucose, β₂-agonists, dialysis if refractory
• Hypocalcemia: Correct only if symptomatic (tetany, arrhythmia)
• Hyperphosphatemia / Hyperuricemia: Treat as per standard protocols

6️⃣ Renal Replacement Therapy (RRT)

• Indications same as AKI:
• Refractory hyperkalemia
• Severe acidosis
• Volume overload
• Uremic complications
• Hemodialysis preferred; myoglobin removal limited but helps metabolic control.

7️⃣ Compartment Syndrome

• Early recognition, measure compartment pressures.
• Fasciotomy if pressure >30 mmHg.

🔹 Prevention (for High-Risk Patients)

• Early hydration during crush injury or major trauma
• Avoid nephrotoxins (NSAIDs, contrast)
• Monitor CK in patients on statins or propofol infusion
• Treat heat stroke, seizures promptly

🔹 Prognosis

• Mortality ≈ 5–10%, mainly due to AKI and electrolyte derangements.
• Favorable outcome with early diagnosis and hydration.
• Poor prognosis with CK >50,000 IU/L, delayed resuscitation, or multi-organ failure.

🔹 Special Scenarios

 # Crush Syndrome

• Severe rhabdomyolysis from trauma/compression.
• “Reperfusion injury” after extrication causes sudden release of toxins → shock, hyperkalemia, AKI.
• Prevention: Early IV saline before limb release.

# Malignant Hyperthermia / NMS

• Myotoxic states with similar biochemistry.
• Treat underlying disorder (Dantrolene in MH, bromocriptine in NMS).

# Propofol Infusion Syndrome

• Seen with prolonged high-dose infusions (>4 mg/kg/h).
• Features: Rhabdomyolysis, metabolic acidosis, cardiac failure.
• Stop propofol immediately.

🔹 Key Points

• Most sensitive lab marker: CK (not myoglobin)
• Earliest urine finding: Heme-positive, RBC-negative dipstick
• Major cause of mortality: AKI, hyperkalemia
• Avoid: Diuretics before establishing good urine output
• Urine alkalinization helps only if adequate diuresis

 References

• Harrison’s Principles of Internal Medicine, 21st ed.
• UpToDate: “Clinical features and diagnosis of rhabdomyolysis”
• KDIGO AKI Guidelines (2023 Update)
• NEJM 2022;386:100–111 — Rhabdomyolysis: Pathogenesis, Diagnosis, and Treatment