Rhabdomyolysis in the ICU

Quick Answer

Rhabdomyolysis is a life-threatening syndrome of skeletal muscle breakdown releasing intracellular contents (myoglobin, creatine kinase, potassium, phosphate) into the circulation. It affects 2.1-2.5 per 100,000 population annually and causes 7-10% of all acute kidney injury (AKI) cases.

Key Clinical Features:

• Classic triad: muscle pain, weakness, dark ("tea-coloured") urine (present in <10% of cases)
• Markedly elevated creatine kinase (CK) >5× upper limit of normal (>1,000 U/L)
• Myoglobinuria causing pigmenturia
• Electrolyte disturbances: hyperkalaemia, hyperphosphataemia, hypocalcaemia (early), hypercalcaemia (late)

Emergency Management:

1. Aggressive IV crystalloid resuscitation: Target urine output 200-300 mL/hr (3 mL/kg/hr)
2. Monitor and treat hyperkalaemia: ECG, cardiac monitoring, calcium gluconate, insulin-dextrose
3. Assess for compartment syndrome: Urgent fasciotomy if compartment pressure >30 mmHg or within 30 mmHg of diastolic pressure
4. Consider early RRT: Refractory hyperkalaemia, severe acidosis, fluid overload, uraemic complications

ICU Mortality: 5-10% overall; 20-50% if requiring RRT

Must-Know Facts:

• CK level correlates with AKI risk: >5,000 U/L → 19% AKI risk; >15,000 U/L → 50% AKI risk
• Myoglobin is directly nephrotoxic via tubular obstruction, oxidative stress, and vasoconstriction
• Urinary alkalinization remains controversial with no RCT evidence of benefit
• Hypocalcaemia in acute phase should NOT be corrected unless symptomatic (prevents rebound hypercalcaemia)
• Early RRT is indicated for refractory electrolyte disturbances, not empirically for myoglobin removal

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CICM Exam Focus

What Examiners Expect

Second Part Written (SAQ):

Common SAQ stems:

• "A 35-year-old male is brought to ED after being found collapsed at home for unknown duration. CK is 85,000 U/L, K+ 7.2 mmol/L. Outline your immediate management."
• "Discuss the pathophysiology of myoglobin-induced acute kidney injury."
• "A marathon runner presents with muscle cramps and dark urine. CK 45,000 U/L, creatinine 320 μmol/L. Describe your management approach and indications for renal replacement therapy."
• "Compare and contrast the evidence for urinary alkalinization in rhabdomyolysis."
• "A patient with crush injury from a building collapse has compartment syndrome of the left leg. Describe the pathophysiology and management."

Expected depth:

• Pathophysiology of myoglobin nephrotoxicity (three mechanisms)
• Evidence base for fluid resuscitation (crystalloid volume and targets)
• Controversy around urinary alkalinization (lack of RCT evidence)
• RRT timing and modality (continuous vs intermittent)
• Electrolyte management (hyperkalaemia, hypocalcaemia)
• Compartment syndrome recognition and fasciotomy timing
• Aetiology categories with Australian-specific causes

Second Part Hot Case:

Typical presentations:

• Post-crush injury trauma patient Day 2 with oliguric AKI on CRRT
• Drug-induced rhabdomyolysis (recreational drugs, statins) with multi-organ dysfunction
• Exertional rhabdomyolysis in military/athlete with severe hyperkalaemia
• Neuroleptic malignant syndrome or serotonin syndrome with rhabdomyolysis

Examiners assess:

• Systematic A-E examination with focus on volume status
• Recognition of compartment syndrome (examine limbs)
• Review of fluid balance charts and urine output trends
• Understanding of RRT prescription and anticoagulation
• Management prioritization (hyperkalaemia before AKI)
• Communication with surgical team regarding fasciotomy

Second Part Viva:

Expected discussion areas:

• Pathophysiology of pigment nephropathy
• Comparison of trauma vs non-trauma causes
• Fluid resuscitation targets and evidence
• Urinary alkalinization controversy
• RRT timing - emergency indications vs prophylactic
• Compartment syndrome assessment and surgical timing
• Crush syndrome and field management
• Australian remote/rural considerations

Examiner expectations:

• Safe, consultant-level decision-making
• Evidence-based practice with appropriate uncertainty (no RCTs for alkalinization)
• Understanding of Australian context (mining accidents, sports injuries)
• Indigenous health considerations

Common Mistakes

• Failing to recognise that CK may continue to rise for 24-72 hours after injury
• Treating asymptomatic hypocalcaemia (risks rebound hypercalcaemia in recovery phase)
• Over-reliance on urinary alkalinization without evidence of benefit
• Delayed recognition of compartment syndrome
• Inadequate fluid resuscitation (target 200-300 mL/hr urine output, not 0.5 mL/kg/hr)
• Not considering exertional or drug-induced causes in young healthy patients
• Forgetting to check for DIC (consumptive coagulopathy in severe cases)

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Key Points

Must-Know Facts

1. Definition: Rhabdomyolysis is defined as skeletal muscle injury with release of intracellular contents. Diagnosed by CK >5× ULN (typically >1,000 U/L), with peak CK correlating with AKI risk (PMID: 15547292).

2. AKI Incidence: 10-50% of rhabdomyolysis patients develop AKI. Risk increases with CK >5,000 U/L (19% AKI), CK >15,000 U/L (50% AKI), CK >40,000 U/L (>75% AKI) (PMID: 24089526).

3. Myoglobin Nephrotoxicity: Three mechanisms - (1) tubular obstruction from myoglobin-Tamm-Horsfall casts, (2) oxidative stress from iron-mediated free radical generation, (3) renal vasoconstriction from nitric oxide scavenging (PMID: 10793162).

4. Fluid Resuscitation: Aggressive crystalloid (balanced preferred) targeting urine output 200-300 mL/hr (3 mL/kg/hr). Early resuscitation (<6 hours from injury) reduces AKI risk from 40% to 4% (PMID: 421543).

5. Urinary Alkalinization: Controversial - theoretical benefit (prevents myoglobin precipitation, reduces ferryl myoglobin toxicity) but NO RCT evidence. May cause hypocalcaemia and fluid overload. Not routinely recommended by KDIGO (PMID: 23527829).

6. Hyperkalaemia Management: Life-threatening; treat immediately with calcium gluconate (membrane stabilisation), insulin-dextrose, and consider early RRT. K+ may rise 2-3 mmol/L in first 24 hours from massive muscle necrosis (PMID: 23535634).

7. Hypocalcaemia Paradox: Early hypocalcaemia (calcium sequestration in necrotic muscle) should NOT be treated unless symptomatic (seizures, tetany, QT prolongation). Aggressive calcium replacement causes rebound hypercalcaemia during recovery phase (PMID: 26070960).

8. Compartment Syndrome: Suspect if severe pain disproportionate to injury, pain on passive stretch, tense swelling, paraesthesias. Measure compartment pressure - fasciotomy if >30 mmHg or delta pressure (diastolic - compartment pressure) <30 mmHg. 6-hour window to prevent irreversible injury (PMID: 26200932).

9. RRT Indications: Standard KDIGO indications (AEIOU) - refractory hyperkalaemia, severe metabolic acidosis, fluid overload, uraemic complications. No evidence for prophylactic RRT to "clear myoglobin" (PMID: 22303527).

10. Prognosis: Overall mortality 5-10%. With AKI requiring RRT: 20-50% mortality. McMahon score >6 predicts 52% risk of death or RRT (PMID: 15547292).

Memory Aids

CRUSH Mnemonic for Causes:

• C: Compression (trauma, prolonged immobilization, coma)
• R: Recreational drugs (cocaine, amphetamines, MDMA)
• U: Underlying metabolic (hypothyroidism, diabetic ketoacidosis)
• S: Strenuous exertion (marathon, military training, seizures)
• H: Hyperthermia (NMS, serotonin syndrome, malignant hyperthermia, heat stroke)

MYOGLOBIN Mnemonic for Complications:

• M: Metabolic acidosis
• Y: Hyperkalaemia (elevated K+)
• O: Oliguria/AKI
• G: Coagulopathy (DIC)
• L: Liver dysfunction
• O: Cardiac arrhythmias
• B: Bleeding (DIC)
• I: Inflammation (SIRS)
• N: Neurological (from electrolytes)

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Epidemiology

Definition

Rhabdomyolysis is defined as acute skeletal muscle necrosis with release of intracellular muscle contents into the circulation. The diagnosis requires:

1. Clinical suspicion based on history and examination
2. Elevated creatine kinase (CK) >5× upper limit of normal (typically >1,000 U/L)
3. Myoglobinuria may cause dark urine (though myoglobin is rapidly cleared)

Severity Classification (based on CK level and outcomes):

Incidence

Rhabdomyolysis affects 2.1-2.5 per 100,000 population annually in developed countries. The true incidence is likely underestimated due to mild cases not requiring hospitalisation (PMID: 24089526).

ICU-specific data:

• Accounts for 7-10% of all AKI cases in ICU
• 10-50% of rhabdomyolysis patients develop AKI
• 5-15% of patients with rhabdomyolysis-induced AKI require RRT

Australian/NZ Data:

• Higher rates in mining communities (crush injuries)
• Sports-related exertional rhabdomyolysis common in military and elite athletes
• Recreational drug-associated cases increasing in urban centres
• Remote and rural areas face delayed presentation and treatment challenges

Mortality

Short-term outcomes:

• Overall mortality: 5-10%
• With AKI not requiring RRT: 10-20%
• With AKI requiring RRT: 20-50%
• Crush syndrome with multi-organ failure: 30-50%

Long-term outcomes:

• Recovery of renal function: 70-80% (if survive acute phase)
• Progression to CKD: 10-20%
• ESRD requiring long-term dialysis: 2-5%
• Recurrent rhabdomyolysis: 5-10% (higher in genetic causes)

Risk Factors

Patient factors:

• Chronic kidney disease (reduced renal reserve)
• Diabetes mellitus (autonomic dysfunction, metabolic derangement)
• Hypothyroidism (impaired muscle energy metabolism)
• Genetic myopathies (McArdle disease, CPT-II deficiency)
• Elderly (reduced muscle mass but prolonged immobilization risk)
• Dehydration/hypovolaemia

Exposure factors:

• Prolonged immobilization (>4 hours)
• Statin therapy (especially high-dose or with interacting drugs)
• Recreational drugs (cocaine, amphetamines, MDMA)
• Antipsychotics (NMS risk)
• Serotonergic drugs (serotonin syndrome)
• Extreme exercise (marathon, military training)

High-Risk Populations

Aboriginal and Torres Strait Islander peoples:

• Higher rates of diabetes, CKD, and cardiovascular disease increasing AKI susceptibility
• Remote communities face delayed access to healthcare
• Mining and manual labour occupations increase trauma risk
• Cultural considerations in family involvement and decision-making
• Aboriginal Health Workers (AHWs) and Aboriginal Liaison Officers (ALOs) should be involved

Māori:

• Similar health disparities with higher CKD and diabetes prevalence
• Whānau involvement in decision-making is essential
• Access challenges in rural New Zealand
• Māori Health Workers facilitate culturally safe care

Remote/rural populations:

• Mining industry crush injuries (common in outback Australia)
• Delayed presentation due to distance from healthcare facilities
• RFDS/retrieval medicine considerations
• Limited access to dialysis services

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Applied Basic Sciences

Anatomy

Skeletal Muscle Structure:

Skeletal muscle comprises 40% of body mass (approximately 30 kg in 75 kg adult). Each muscle fibre is a multinucleated cell (myocyte) containing:

• Sarcolemma: Cell membrane containing Na+/K+-ATPase, Ca²⁺ channels
• Sarcoplasmic reticulum: Calcium storage (Ca²⁺-ATPase pumps)
• Mitochondria: High density (25% of cell volume) for ATP production
• Myofibrils: Contractile apparatus (actin, myosin)
• Cytoplasm (sarcoplasm): Contains myoglobin (oxygen storage), potassium, phosphate, CK

Relevant ICU Anatomy:

Compartments of the Lower Limb (for compartment syndrome assessment):

Leg (4 compartments):

1. Anterior: Tibialis anterior, EHL, EDL - deep peroneal nerve
2. Lateral: Peroneus longus/brevis - superficial peroneal nerve
3. Superficial posterior: Gastrocnemius, soleus - sural nerve
4. Deep posterior: Tibialis posterior, FDL, FHL - tibial nerve

Thigh (3 compartments):

1. Anterior: Quadriceps - femoral nerve
2. Medial: Adductors - obturator nerve
3. Posterior: Hamstrings - sciatic nerve

Forearm (3 compartments):

1. Anterior (superficial and deep): Flexors
2. Posterior: Extensors
3. Mobile wad: Brachioradialis, ECRL, ECRB

Physiology

Normal Muscle Physiology:

Intracellular vs Extracellular Concentrations:

Myoglobin Physiology:

• Molecular weight: 17,800 Da (freely filtered at glomerulus)
• Function: Oxygen storage and transport within muscle
• Structure: Single polypeptide chain with heme group (iron-containing)
• Normal plasma level: <90 ng/mL
• Concentration in muscle: 2-5 mg/g wet weight
• Total body myoglobin: 60-150 g in average adult

Creatine Kinase (CK):

• Isoenzymes: CK-MM (skeletal muscle, 95% of total), CK-MB (cardiac), CK-BB (brain)
• Normal plasma: <200 U/L
• Half-life: 36-48 hours (peak CK at 24-72 hours post-injury)
• CK release indicates sarcolemmal membrane damage

Pathophysiology

Mechanisms of Muscle Cell Death:

1. ATP Depletion:

• Ischaemia, hypoxia, or metabolic crisis depletes ATP
• Na⁺/K⁺-ATPase failure → intracellular Na⁺ and water accumulation → cell swelling
• Ca²⁺-ATPase failure → intracellular Ca²⁺ overload → activates proteases and lipases
• Mitochondrial dysfunction → further ATP depletion (vicious cycle)

2. Calcium Overload:

• Sustained muscle contraction (seizures, NMS) depletes ATP
• Intracellular Ca²⁺ rises from 0.0001 to 0.1-1 mmol/L
• Activates calpains (cysteine proteases) → cytoskeletal degradation
• Activates phospholipase A₂ → membrane phospholipid breakdown
• Mitochondrial calcium uptake → opens permeability transition pore → cell death

3. Oxidative Stress:

• Reperfusion following ischaemia generates reactive oxygen species (ROS)
• Xanthine oxidase activation, neutrophil infiltration
• Lipid peroxidation and membrane damage

Myoglobin Nephrotoxicity (Three Mechanisms):

Mechanism 1: Tubular Obstruction (PMID: 10793162)

• Myoglobin precipitates with Tamm-Horsfall protein (uromodulin) in tubular lumen
• Cast formation enhanced by acidic urine (pH <5.6)
• Casts obstruct tubular flow → increased intratubular pressure
• Reduced GFR and oliguria

Mechanism 2: Oxidative Injury (PMID: 15766528)

• Myoglobin contains heme iron (Fe²⁺)
• In acidic conditions, iron oxidised to Fe³⁺ (metmyoglobin)
• Further oxidation to Fe⁴⁺ (ferryl myoglobin) - highly reactive
• Generates hydroxyl radicals via Fenton reaction: Fe²⁺ + H₂O₂ → Fe³⁺ + OH• + OH⁻
• Lipid peroxidation damages proximal tubular cells
• F₂-isoprostanes and malondialdehyde elevated in rhabdomyolysis AKI

Mechanism 3: Renal Vasoconstriction (PMID: 18094678)

• Myoglobin scavenges nitric oxide (NO) → reduces vasodilation
• Endothelin-1 release → vasoconstriction
• Isoprostanes (from lipid peroxidation) → vasoconstriction
• Reduced renal blood flow, especially outer medulla
• Exacerbated by hypovolaemia (third-spacing into injured muscle)

Systemic Effects of Rhabdomyolysis:

Hyperkalaemia:

• Massive K⁺ release from necrotic muscle (150 mmol/L intracellular)
• Can rise 2-3 mmol/L in 24 hours
• Exacerbated by acidosis (H⁺/K⁺ exchange), renal failure
• Life-threatening arrhythmias (peaked T waves, widened QRS, sine wave)

Hypocalcaemia (Early):

• Calcium sequestration in necrotic muscle (calcium-phosphate precipitation)
• Hyperphosphataemia (100 mmol/L intracellular release)
• Cellular Ca²⁺ influx into damaged myocytes
• Usually asymptomatic; treat only if symptomatic

Hypercalcaemia (Late, Recovery Phase):

• Mobilisation of calcium from necrotic muscle during resolution
• Occurs in 20-30% of patients during recovery
• May cause polyuria, confusion, arrhythmias
• Exacerbated if calcium was given during acute phase

Hyperphosphataemia:

• Released from muscle (100 mmol/L intracellular)
• Contributes to hypocalcaemia (calcium-phosphate precipitation)
• Exacerbates AKI if calcium-phosphate product >70

Metabolic Acidosis:

• Lactic acid from anaerobic muscle metabolism
• Uric acid, phosphoric acid, sulfuric acid release
• High anion gap metabolic acidosis
• Worsens myoglobin precipitation in tubules

Disseminated Intravascular Coagulation (DIC):

• Occurs in 5-10% of severe cases
• Thromboplastin release from necrotic muscle
• Consumptive coagulopathy
• May complicate fasciotomy procedures

Pharmacology

Drugs Causing Rhabdomyolysis:

Statins (PMID: 12079710):

• Mechanism: Impaired isoprenoid synthesis → reduced CoQ10 → mitochondrial dysfunction
• Risk factors: High-dose therapy, CYP3A4 inhibitors, renal impairment, hypothyroidism
• Incidence: 0.01-0.1% for severe rhabdomyolysis; myopathy 1-5%
• Management: Stop statin immediately; rechallenge with alternative statin after recovery

Recreational Drugs:

Antipsychotics (Neuroleptic Malignant Syndrome):

• Mechanism: Dopamine D₂ receptor blockade → hypothalamic dysfunction, muscle rigidity
• Clinical: Hyperthermia, lead-pipe rigidity, autonomic instability, altered consciousness
• CK: Often >10,000-100,000 U/L
• Treatment: Stop offending drug, dantrolene 1-2.5 mg/kg IV, bromocriptine, supportive care

Serotonergic Drugs (Serotonin Syndrome):

• Mechanism: Serotonin excess → hyperthermia, muscle hyperactivity
• Clinical: Hyperthermia, hyperreflexia, clonus, agitation, diaphoresis
• Differentiation from NMS: Rapid onset, hyperreflexia/clonus (vs rigidity), mydriasis
• Treatment: Stop serotonergic drugs, cyproheptadine 12 mg then 2 mg q2h, supportive care

Key ICU Drugs for Rhabdomyolysis Treatment:

Crystalloid Fluids:

• Balanced crystalloids preferred: Hartmann's, Plasmalyte
• Rationale: Normal saline may exacerbate hyperchloraemic acidosis
• Dosing: 1-2 L boluses initially, then 200-500 mL/hr to target UO 200-300 mL/hr
• Monitoring: Volume status, electrolytes, lactate

Sodium Bicarbonate (if used for urinary alkalinization):

• Mechanism: Increases urine pH, may reduce myoglobin precipitation
• Dosing: 150 mmol NaHCO₃ in 1L 5% dextrose at 150-200 mL/hr
• Target: Urine pH >6.5 (controversial)
• Risks: Hypokalaemia, ionised hypocalcaemia, volume overload, hypernatraemia
• Evidence: No RCT evidence of benefit; not recommended routinely

Mannitol (limited role):

• Mechanism: Osmotic diuresis, free radical scavenger, reduced intratubular myoglobin
• Dosing: 0.5-1 g/kg bolus, max 200 g/day
• Contraindications: Anuric AKI (risk of hyperosmolar state)
• Evidence: No RCT evidence; may be harmful in established AKI

Pathology

Histopathology of Muscle:

• Myocyte swelling and fragmentation
• Loss of cross-striations
• Hypercontraction bands
• Inflammatory cell infiltration
• Myocyte necrosis with pale eosinophilic cytoplasm

Renal Histopathology (Pigment Nephropathy):

• Myoglobin casts in distal tubules (brown/red-brown on H&E)
• Acute tubular necrosis in proximal tubules
• Tubular epithelial cell sloughing
• Interstitial oedema
• Relatively preserved glomeruli (distinguishes from glomerulonephritis)

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Aetiology

Classification by Mechanism

Traumatic Causes:

Crush Syndrome (PMID: 26070960):

• Prolonged compression (earthquakes, building collapse, MVA)
• Classic scenario: victim trapped for hours, rescued, then deteriorates
• "Smiling death"
• patient appears well initially, develops hyperkalaemia, arrhythmias
• Reperfusion releases K⁺, myoglobin, acids into circulation
• Field management: IV fluids BEFORE extrication if possible
• Australian context: mining accidents, farm accidents

Other Trauma:

• High-voltage electrical injury (direct muscle damage)
• Burns (thermal injury to muscle)
• Lightning strike
• Blast injury

Exertional Causes:

Exertional Rhabdomyolysis (PMID: 27003213):

• Intense exercise beyond usual conditioning
• Military training, marathon, CrossFit
• High ambient temperature, humidity
• Dehydration
• Novel or eccentric exercise
• Genetic susceptibility (sickle cell trait, CPT-II deficiency)

Seizures:

• Prolonged generalised tonic-clonic seizures
• Status epilepticus
• Repeated seizures

Drug-Induced:

Prescribed Medications:

• Statins (especially simvastatin, atorvastatin) ± interacting drugs
• Fibrates (gemfibrozil - do not combine with statins)
• Colchicine (especially with CKD)
• Zidovudine (mitochondrial toxicity)
• Ciclosporin, tacrolimus
• Propofol (propofol infusion syndrome - PMID: 23989012)

Recreational Drugs:

• Cocaine, amphetamines, MDMA, heroin, synthetic cannabinoids
• Alcohol (direct toxicity, immobilization)

Toxins:

• Snake envenomation (Australian brown snake, tiger snake - phospholipase A₂)
• Spider envenomation (funnel-web myotoxicity)
• Wasp/bee stings (massive envenomation)
• Carbon monoxide (tissue hypoxia)
• Organophosphates (cholinergic crisis, fasciculations)

Metabolic and Endocrine:

• Hypokalaemia (severe <2.5 mmol/L - impaired glycogenolysis)
• Hypophosphataemia (severe <0.3 mmol/L)
• Hypo/hypernatraemia (severe)
• Diabetic ketoacidosis (osmotic stress, hypokalaemia)
• Hyperosmolar hyperglycaemic state
• Hypothyroidism (myxoedema myopathy)
• Thyrotoxic crisis

Hyperthermia Syndromes:

Infection:

• Viral myositis (influenza A/B, Coxsackie, EBV, HIV)
• Bacterial (Legionella, Streptococcus, Staphylococcus, Salmonella)
• Parasitic (trichinosis)
• Sepsis (systemic inflammation)

Ischaemic:

• Arterial occlusion (embolism, thrombosis)
• Compartment syndrome (any cause)
• Prolonged surgery with limb compression
• Vascular surgery with cross-clamping

Genetic Myopathies (consider if recurrent):

• McArdle disease (myophosphorylase deficiency)
• Carnitine palmitoyltransferase II (CPT-II) deficiency
• Phosphofructokinase deficiency
• Malignant hyperthermia susceptibility (RYR1 mutations)

Immobilization:

• Coma/overdose (prolonged unconsciousness)
• Post-operative (positioning)
• Stroke/spinal cord injury
• Restraint (physical or chemical)

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Clinical Presentation

ICU Admission Scenarios

Scenario 1: Crush Injury (Trauma)

A 45-year-old mine worker is extricated after being trapped by a rock fall for 6 hours. Initially appears well with leg pain but becomes hypotensive and develops peaked T waves on ECG within 2 hours of rescue.

• History: Prolonged compression, rapid deterioration post-extrication
• Examination: Tense, swollen legs, weak pulses, hypotensive, tachycardic
• Severity: Severe crush syndrome with hyperkalaemia

Scenario 2: Drug-Induced (MDMA at Music Festival)

A 22-year-old is brought to ED after collapsing at a music festival. Temperature 40.2°C, agitated, diaphoretic, with rigid muscles and dark urine.

• History: MDMA ingestion, dancing for hours, minimal hydration
• Examination: Hyperthermia, tachycardia, hypertension, dilated pupils, hyperreflexia
• Severity: Severe serotonin syndrome/drug-induced rhabdomyolysis

Scenario 3: Exertional (Marathon Runner)

A 35-year-old completes their first marathon on a hot day. Presents 12 hours later with muscle cramps, weakness, and tea-coloured urine.

• History: Novel intense exercise, hot environment, dehydration
• Examination: Diffuse muscle tenderness, normal temperature, oliguria
• Severity: Moderate exertional rhabdomyolysis

Scenario 4: Prolonged Immobilization (Overdose)

A 55-year-old found unconscious at home for unknown duration. Empty medication bottles nearby. Develops swollen, tense right arm with pain on passive finger extension.

• History: Overdose (benzodiazepines, opioids), prolonged positioning
• Examination: Right forearm compartment syndrome, responsive to naloxone
• Severity: Moderate-severe with compartment syndrome

Symptoms and Signs

History:

• Chief complaint: Muscle pain (50-75%), weakness (50%), dark urine (30-50%)
• Classic triad: Present in only <10% of cases
• Associated symptoms: Malaise, fever, nausea/vomiting, confusion
• Time course: Acute (trauma, drugs) or subacute (exertional, metabolic)
• Specific triggers: Recent exercise, drug use, trauma, surgery, immobilization

Red Flag History:

• Prolonged immobilization or entrapment
• New medications (statins, antipsychotics)
• Recreational drug use
• Recent intense/novel exercise
• Family history of rhabdomyolysis or malignant hyperthermia
• Features suggesting NMS or serotonin syndrome

Examination:

A - Airway:

• Usually patent
• May be compromised if GCS reduced (overdose, metabolic encephalopathy)

B - Breathing:

• Tachypnoea (compensating for metabolic acidosis)
• Kussmaul breathing if severe acidosis
• May develop pulmonary oedema (fluid overload from resuscitation)

C - Circulation:

• Hypovolaemia (third-spacing into injured muscle)
• Tachycardia
• Hypotension (fluid loss, vasoplegia from inflammation)
• Cardiac arrhythmias (hyperkalaemia - peaked T, wide QRS, sine wave)

D - Disability:

• Altered consciousness (electrolyte disturbances, uraemia)
• Seizures (hypocalcaemia)
• Weakness (muscle injury, electrolyte disturbances)

E - Exposure:

• Muscle tenderness: Diffuse or localised
• Swelling: Affected muscle groups
• Compartment syndrome signs: Tense, shiny skin; pain on passive stretch; paraesthesias; paralysis (late)
• Skin changes: Blistering over pressure areas
• Temperature: Elevated in NMS, serotonin syndrome, heat stroke
• Urine: Dark "tea-coloured" or "cola-coloured" (myoglobinuria)

Severity Scoring

McMahon Score (PMID: 15547292):

Predicts risk of death or need for RRT in rhabdomyolysis:

Interpretation:

• Score ≤5: Low risk (3% death/RRT)
• Score 6-10: Moderate risk (14% death/RRT)
• Score >10: High risk (52% death/RRT)

General ICU Scores:

• APACHE II: Correlates with mortality
• SOFA: Tracks organ failure
• KDIGO AKI staging: Grades AKI severity

Differential Diagnosis

1. Acute Myocardial Infarction: CK-MB elevated (but <6% of total CK), troponin positive, ECG changes, chest pain. Differentiate by CK isoform analysis, troponin, clinical context.

2. Myocarditis: Troponin elevated, ECG changes, echo abnormalities, often viral prodrome. CK elevation typically less marked.

3. Inflammatory Myopathies: Dermatomyositis, polymyositis. Subacute, proximal weakness, skin changes, auto-antibodies (anti-Jo-1).

4. Hypothyroid Myopathy: Chronic weakness, raised CK (usually <5,000 U/L), low T4/high TSH.

5. McArdle Disease: Exercise intolerance, second-wind phenomenon, recurrent episodes.

6. Acute Kidney Injury (other causes): Prerenal, intrinsic, or postrenal AKI without elevated CK.

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Investigations

Laboratory Investigations

Bedside Tests:

Arterial Blood Gas (typical findings):

• pH: 7.20-7.35 (metabolic acidosis)
• PaCO2: 25-35 mmHg (respiratory compensation)
• PaO2: Usually normal unless pulmonary oedema/ARDS
• HCO3: 12-20 mmol/L (low)
• Lactate: 2-10 mmol/L (elevated)
• Base Excess: -5 to -15 mmol/L
• Potassium: Often 5.5-8+ mmol/L (high)
• Ionised Calcium: Often low (<1.0 mmol/L)
• Interpretation: High anion gap metabolic acidosis with hyperkalaemia

Urine Dipstick:

• Blood: Positive (but no RBCs on microscopy - myoglobin cross-reacts)
• Colour: Brown/tea-coloured
• pH: Often acidic (<6.0)
• Specific gravity: Concentrated if hypovolaemic

Blood Tests:

Serial CK Monitoring:

• Peak CK typically occurs 24-72 hours post-injury
• CK half-life approximately 36-48 hours
• Declining CK indicates resolving muscle injury
• Persistently rising CK suggests ongoing damage (compartment syndrome, re-injury)

Urine Tests:

• Urine myoglobin: Elevated (but rapidly cleared, may be negative)
• Urine microscopy: Few or no RBCs despite positive dipstick ("discordance")
• Urine sodium: <20 mmol/L (prerenal physiology if hypovolaemic)
• Fractional excretion of sodium: May be low initially

Imaging

Chest X-Ray:

• Rule out pulmonary oedema from aggressive fluid resuscitation
• May identify ARDS in severe cases

Ultrasound:

• Renal ultrasound: Normal sized kidneys, no obstruction (excludes postrenal cause)
• Muscle ultrasound: May show muscle oedema, hyperechogenicity
• Cardiac echo: If hypotensive (assess for cardiomyopathy in NMS/drug toxicity)

CT Scan:

• Generally not required for diagnosis
• CT extremity: May show muscle swelling, fat stranding in compartment syndrome
• May be indicated if diagnostic uncertainty

MRI:

• STIR sequences show oedema in affected muscles
• Rarely needed acutely; may help identify extent of involvement

Compartment Pressure Measurement:

• Indications: Clinical suspicion of compartment syndrome, unconscious patient
• Technique: Needle or catheter-based measurement
• Normal: <10 mmHg
• Concerning: >30 mmHg OR delta pressure (diastolic BP - compartment pressure) <30 mmHg
• Action threshold: Urgent fasciotomy indicated

Physiological Monitoring

Non-Invasive Monitoring:

• Continuous ECG: Monitor for hyperkalaemia changes (peaked T, prolonged PR, wide QRS, sine wave)
• SpO2: Target >94%
• NIBP: Target MAP >65 mmHg
• Temperature: Continuous if hyperthermia suspected
• Urine output: Hourly (target 200-300 mL/hr or 3 mL/kg/hr)

Invasive Monitoring:

• Arterial line: For haemodynamic monitoring and serial ABGs
• Central venous access: For vasopressors if needed, RRT if anticipated
• Urinary catheter: Essential for accurate urine output monitoring

Organ-Specific Monitoring:

• Urine output: Target 200-300 mL/hr (higher than standard ICU targets)
• Urine pH: If using alkalinization (target >6.5)
• Cardiac rhythm: Continuous ECG for arrhythmias
• Limb checks: Regular assessment for compartment syndrome

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ICU Management

Initial Resuscitation (First Hour)

A - Airway:

• Assessment: Usually patent unless GCS reduced
• Intervention: Intubate if GCS ≤8, unable to protect airway, severe hyperkalaemia with arrhythmias
• Avoid succinylcholine: May cause acute hyperkalaemia (use rocuronium)

B - Breathing:

• Oxygen therapy: Target SpO2 >94%
• Ventilatory support: If intubated, lung-protective ventilation
• Monitor for pulmonary oedema from aggressive fluid resuscitation

C - Circulation:

Immediate Hyperkalaemia Management (K+ >6.5 mmol/L or ECG changes):

1. Calcium gluconate 10%: 10 mL (2.2 mmol) IV over 5 minutes

   • Stabilises cardiac membrane (onset 1-3 min, duration 30-60 min)
   • Repeat in 5 min if ECG changes persist

2. Insulin-Dextrose: 10 units soluble insulin + 50 mL 50% dextrose IV

   • Shifts K+ intracellularly (onset 15-30 min, peak 30-60 min)
   • Monitor glucose hourly for 6 hours

3. Salbutamol: 10-20 mg nebulised (caution if tachyarrhythmia)

   • Shifts K+ intracellularly (onset 30 min)

4. Sodium bicarbonate: 50-100 mmol if concurrent severe acidosis

   • Limited efficacy for K+ shifting; avoid if hypocalcaemic

5. Renal replacement therapy: If refractory or K+ >7.0 mmol/L

Fluid Resuscitation:

• Type: Balanced crystalloid (Hartmann's, Plasmalyte) preferred over 0.9% saline
• Initial: 1-2 L bolus if hypovolaemic
• Ongoing: 200-500 mL/hr to achieve target urine output
• Target urine output: 200-300 mL/hr (3 mL/kg/hr) - HIGHER than standard ICU targets (PMID: 421543)
• Rationale: Dilute tubular myoglobin, maintain renal perfusion
• Monitor: Central venous pressure, lung auscultation, fluid balance

D - Disability:

• GCS monitoring: Every 1-2 hours initially
• Treat seizures: Benzodiazepines (avoid phenytoin if hypocalcaemic)
• Sedation: If ventilated, target RASS 0 to -2
• Glucose control: Target 6-10 mmol/L

E - Exposure:

• Temperature: Active cooling if hyperthermia (NMS, serotonin syndrome, heat stroke)
• Limb examination: Assess all four limbs for compartment syndrome
• Remove cause: Stop offending drugs, treat underlying infection

Definitive Management (First 24-48 Hours)

Aggressive Fluid Resuscitation:

• Ongoing rate: Titrate to urine output 200-300 mL/hr
• Typical requirement: 6-12 L in first 24 hours (individualise)
• Caution: Risk of pulmonary oedema, especially if anuric
• Endpoint reassessment: Reduce rate once CK declining and urine output established
• Evidence: Brown et al. (PMID: 15547292) - early resuscitation reduces AKI from 40% to 4%

Urinary Alkalinization (CONTROVERSIAL):

Theoretical rationale:

• Urine pH >6.5 reduces myoglobin-Tamm-Horsfall precipitation
• Alkaline pH reduces ferryl myoglobin toxicity
• May reduce cast formation

Evidence:

• No randomised controlled trials demonstrating benefit
• Observational studies inconsistent (PMID: 23527829)
• KDIGO does not recommend routine use
• European Working Party (2014) suggests "may be considered" (weak recommendation)

If using alkalinization:

• Solution: 150 mmol NaHCO₃ in 1L 5% dextrose
• Rate: 150-200 mL/hr
• Target urine pH: >6.5
• Monitoring: Serum pH, potassium, ionised calcium
• Risks: Hypokalaemia, hypocalcaemia precipitation, volume overload, hypernatraemia
• Stop if: Serum pH >7.50, severe hypokalaemia, hypocalcaemia

Current Australian Practice: Variable - many units use crystalloid alone without bicarbonate

Electrolyte Management:

Hyperkalaemia:

• Continue monitoring every 2-4 hours
• Repeat calcium/insulin-dextrose as needed
• Early RRT if refractory (K+ >6.5 despite medical therapy)

Hypocalcaemia:

• DO NOT TREAT unless symptomatic (tetany, seizures, prolonged QTc with arrhythmia)
• Asymptomatic hypocalcaemia (even iCa <0.8 mmol/L) should be observed
• Reason: Calcium given in acute phase is deposited in necrotic muscle and mobilised during recovery → rebound hypercalcaemia (20-30% of patients) (PMID: 26070960)

Hyperphosphataemia:

• Usually self-limiting with adequate fluid resuscitation
• Phosphate binders (aluminium hydroxide, calcium carbonate) rarely needed
• Consider RRT if severe (PO4 >3.0 mmol/L with symptoms)

Hyperuricaemia:

• Usually managed with fluids
• Allopurinol may be considered (controversial)

Compartment Syndrome Management

Recognition:

• Clinical: Pain disproportionate to injury, pain on passive stretch, tense compartments, paraesthesias
• Pressure measurement: >30 mmHg absolute OR delta pressure <30 mmHg
• Time-sensitive: Irreversible muscle damage after 6-8 hours

Management:

• Surgical consultation: Immediate orthopaedic/general surgery referral
• Fasciotomy: Within 6 hours of symptom onset
• Technique: Four-compartment fasciotomy for lower leg
• Post-operative: Leave wounds open, delayed primary closure or skin grafting

Australian Context:

• Remote locations may delay fasciotomy
• RFDS/retrieval considerations
• Telemedicine consultation with orthopaedics

Renal Replacement Therapy

Indications (Standard KDIGO criteria - AEIOU):

• A: Refractory metabolic Acidosis (pH <7.1)
• E: Refractory Electrolyte abnormality (K+ >6.5 mmol/L despite medical therapy)
• I: Ingestion/toxin requiring dialytic removal (rare in rhabdomyolysis per se)
• O: Refractory fluid Overload
• U: Uraemic complications (encephalopathy, pericarditis, bleeding)

NOT an indication:

• Prophylactic RRT to "clear myoglobin"
• no evidence of benefit (PMID: 22303527)
• High CK alone without other indications

Modality:

• CRRT (CVVHDF): Preferred in haemodynamically unstable patients
• IHD: Appropriate if haemodynamically stable
• No survival difference: Between CRRT and IHD (PMID: 19812446)

Prescription:

• Effluent dose: 20-25 mL/kg/hr (higher doses not beneficial - RENAL trial)
• Anticoagulation: Regional citrate anticoagulation preferred
• Vascular access: Internal jugular preferred (right IJ first choice)

Myoglobin Removal:

• Myoglobin MW 17.8 kDa - cleared by high-flux dialysis and haemodiafiltration
• High-cutoff membranes (50-60 kDa) may enhance removal
• No RCT evidence that myoglobin-targeted RRT improves outcomes (PMID: 31284991)

Specific Cause Management

Neuroleptic Malignant Syndrome:

• Stop antipsychotic/antiemetic
• Dantrolene 1-2.5 mg/kg IV every 10 min (max 10 mg/kg)
• Bromocriptine 2.5-5 mg PO/NG TDS
• Aggressive cooling
• Intensive care admission

Serotonin Syndrome:

• Stop serotonergic agents
• Cyproheptadine 12 mg loading then 2 mg every 2 hours (max 32 mg/day)
• Benzodiazepines for agitation
• Active cooling if hyperthermia
• Avoid dantrolene (not effective)

Malignant Hyperthermia:

• Stop triggering agent (volatiles, succinylcholine)
• Dantrolene 2.5 mg/kg IV bolus, repeat q5min up to 10 mg/kg
• Active cooling
• Hyperventilate with 100% O2
• Contact Australian Malignant Hyperthermia Register

Snake Envenomation (Australian context):

• Pressure immobilisation bandage
• Antivenom (polyvalent if species unknown)
• Supportive care, RRT if required
• Contact Poisons Information Centre 13 11 26

Australian-Specific Protocols

ANZICS-CORE Recommendations:

• Follow KDIGO AKI guidelines for RRT initiation
• No specific Australian guideline for rhabdomyolysis management
• Regional citrate anticoagulation recommended for CRRT

Therapeutic Guidelines Australia:

• Aggressive IV crystalloid for rhabdomyolysis-induced AKI
• Avoid nephrotoxins
• RRT for standard indications

State-Based Considerations:

• NSW: Critical Care Transport for severe cases, ECMO retrieval if cardiogenic shock
• Victoria: Adult Retrieval Victoria (ARV) coordination
• Queensland: RSQ/RACQ LifeFlight for remote retrievals
• Western Australia: RFDS for mining-related crush injuries
• RFDS: Pre-hospital IV fluids, manage hyperkalaemia, direct to tertiary centre

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Monitoring and Complications

ICU-Specific Monitoring

Daily Parameters:

• Vital signs: Hourly initially, then 2-4 hourly
• Fluid balance: Strict I/O charting, daily weights
• Urine output: Hourly, target 200-300 mL/hr during active resuscitation
• CK: Every 6-12 hours until peak identified, then daily until <5,000 U/L
• Electrolytes: Every 4-6 hours initially (K+, Ca2+, PO4, Mg2+), then twice daily
• Creatinine/urea: Every 6-12 hours initially, then daily
• ABG: As clinically indicated (acidosis monitoring)
• Coagulation: Daily if severe; more frequent if DIC suspected

Trend Monitoring:

• Serial CK: Peak usually 24-72 hours, then declines
• Creatinine trajectory: May continue to rise for 3-5 days
• Potassium: May require repeated measurements q2-4h if labile
• Lactate clearance: Suggests improving perfusion

Safety Monitoring:

• ECG: Continuous cardiac monitoring
• Limb checks: Every 2-4 hours for compartment syndrome

Complications

Early Complications (First 24-48 hours):

Hyperkalaemia:

• Incidence: 40-70% of severe rhabdomyolysis
• Risk factors: High CK, AKI, acidosis, trauma
• Presentation: ECG changes (peaked T, wide QRS), arrhythmias, weakness
• Prevention: Aggressive fluid resuscitation, early RRT if refractory
• Management: Calcium, insulin-dextrose, salbutamol, RRT

Compartment Syndrome:

• Incidence: 10-20% of crush injuries
• Risk factors: Prolonged compression, reperfusion, fasciotomy delay
• Presentation: Pain, tense compartment, pain on passive stretch
• Prevention: High index of suspicion, early pressure measurement
• Management: Urgent fasciotomy within 6 hours

Cardiac Arrhythmias:

• Incidence: 5-15%
• Causes: Hyperkalaemia, hypocalcaemia, acidosis
• Prevention: Electrolyte management, ECG monitoring
• Management: Standard ACLS, treat underlying electrolyte disturbance

Metabolic Acidosis:

• Incidence: 50-80%
• Mechanism: Lactic acid, uric acid, phosphoric acid release
• Management: Fluid resuscitation, RRT if severe

Late Complications (Beyond 48 hours):

Acute Kidney Injury:

• Incidence: 10-50% (higher with CK >15,000 U/L)
• Timing: Typically develops 24-72 hours after muscle injury
• Prognosis: 70-80% recover renal function; 20-30% require RRT

Hypercalcaemia (Recovery Phase):

• Incidence: 20-30%
• Timing: Days to weeks after acute injury
• Mechanism: Mobilisation of calcium from necrotic muscle
• Prevention: Avoid calcium replacement in acute phase unless symptomatic
• Management: Saline diuresis, bisphosphonates if severe

Disseminated Intravascular Coagulation (DIC):

• Incidence: 5-10%
• Risk factors: Severe rhabdomyolysis, sepsis, massive tissue injury
• Diagnosis: Prolonged PT/APTT, low fibrinogen, elevated D-dimer, low platelets
• Management: Treat underlying cause, blood products as needed

ICU-Acquired Weakness:

• Incidence: Variable (more common if prolonged ICU stay)
• Risk factors: Severity, duration of critical illness, corticosteroids
• Prevention: Early mobilization, avoid prolonged paralysis
• Management: Rehabilitation, physiotherapy

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Prognosis and Outcome Measures

Mortality

Short-Term Outcomes:

• Overall mortality: 5-10%
• Mortality with AKI: 15-30%
• Mortality with AKI requiring RRT: 20-50%
• Mortality in crush syndrome with MOF: 30-50%

Long-Term Outcomes:

• 1-year mortality: 15-25% (reflecting underlying comorbidities)
• Recovery of renal function: 70-80% if survive acute phase
• Progression to CKD: 10-20%
• ESRD requiring long-term dialysis: 2-5%

Morbidity

Functional Recovery:

• Return to baseline muscle function: 80-90% at 6 months
• Residual weakness: 10-20%
• Recurrent rhabdomyolysis: 5-10% (higher in genetic myopathies)

ICU Survivorship:

• Post-Intensive Care Syndrome (PICS): 20-40%
• Physical weakness: 10-30%
• Cognitive impairment: 10-20%
• Psychological sequelae: 20-30%

Prognostic Factors

Good Prognostic Factors:

• Young age
• Single aetiology
• Early presentation and treatment
• Low initial creatinine
• Preserved urine output
• CK <15,000 U/L
• No compartment syndrome

Poor Prognostic Factors:

• Advanced age
• Pre-existing CKD
• CK >40,000 U/L
• Initial creatinine >221 μmol/L
• Hypocalcaemia <1.88 mmol/L
• Hyperphosphataemia >1.29 mmol/L
• Metabolic acidosis HCO3 <19 mmol/L
• Delayed presentation (>6 hours)
• Compartment syndrome requiring fasciotomy
• Multi-organ dysfunction

McMahon Score for Prognostication

The McMahon score (PMID: 15547292) predicts death or need for RRT:

• Score ≤5: Low risk (3% outcome)
• Score 6-10: Moderate risk (14% outcome)
• Score >10: High risk (52% outcome)

Australian/NZ Outcome Data

• Limited published data specific to Australian ICU population
• ANZICS APD does not specifically track rhabdomyolysis outcomes
• Mining-related crush injuries have higher mortality due to delayed access
• Indigenous populations may have worse outcomes due to higher comorbidity burden and delayed presentation

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SAQ Practice Questions

SAQ 1: Crush Injury Rhabdomyolysis

Time Allocation: 10 minutes
Total Marks: 20

Stem:

A 52-year-old male construction worker is extricated after being trapped under collapsed scaffolding for 5 hours. He is brought to the ED by ambulance. Pre-hospital he received 1L normal saline.

Past Medical History: Type 2 diabetes, hypertension

Medications: Metformin, perindopril

Observations on arrival:

• HR: 120 bpm
• BP: 85/50 mmHg
• RR: 28/min
• SpO2: 96% on 6L O2
• Temperature: 36.5°C
• GCS: 15

Examination: Both lower limbs swollen, tense, and tender. Weak pulses palpable. Right leg appears worse with pain on passive ankle dorsiflexion.

Investigations:

ABG (FiO2 0.28):

• pH: 7.22
• PaCO2: 28 mmHg
• PaO2: 88 mmHg
• HCO3: 11 mmol/L
• Lactate: 6.5 mmol/L
• K+: 7.4 mmol/L
• iCa: 0.92 mmol/L

Bloods:

• CK: 95,000 U/L
• Creatinine: 285 μmol/L
• Urea: 18 mmol/L
• Phosphate: 2.8 mmol/L

ECG: Sinus tachycardia, peaked T waves, PR interval 220ms

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Question 1.1 (8 marks)

List your immediate management priorities in the first 30 minutes.

Question 1.2 (6 marks)

Describe the pathophysiology of myoglobin-induced acute kidney injury (give three mechanisms).

Question 1.3 (6 marks)

What are the indications for renal replacement therapy in this patient, and what modality would you choose?

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Model Answer

Question 1.1 (8 marks total)

Immediate management priorities:

A - Airway (0.5 marks)

• Assess and maintain patent airway
• Likely intact given GCS 15

B - Breathing (0.5 marks)

• Supplemental oxygen to maintain SpO2 >94%
• Monitor for respiratory distress (acidosis compensation)

C - Circulation - Hyperkalaemia (3 marks)

• Cardiac protection: Calcium gluconate 10% 10mL IV over 5 minutes (membrane stabilisation)
• Potassium shifting: Insulin 10 units + 50mL 50% dextrose IV
• Potassium shifting: Salbutamol 10-20mg nebulised
• Continuous ECG monitoring
• Prepare for emergency RRT if refractory

C - Circulation - Fluid Resuscitation (2 marks)

• Aggressive IV crystalloid (balanced preferred - Hartmann's/Plasmalyte)
• Initial 1-2L bolus
• Target urine output 200-300 mL/hr (3 mL/kg/hr)
• Insert urinary catheter for accurate monitoring
• Arterial line and central venous access

D - Disability (0.5 marks)

• Monitor GCS, glucose management
• Withhold metformin (AKI, lactic acidosis risk)

E - Exposure (1.5 marks)

• Urgent assessment for compartment syndrome
• Measure compartment pressures in right leg
• Emergency orthopaedic/surgical consultation for likely fasciotomy
• Right leg - pain on passive dorsiflexion suggests anterior compartment involvement

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Question 1.2 (6 marks total)

Three mechanisms of myoglobin-induced AKI:

Mechanism 1: Tubular Obstruction (2 marks)

• Myoglobin precipitates with Tamm-Horsfall protein (uromodulin) in tubular lumen
• Cast formation is enhanced in acidic urine (pH <5.6)
• Casts obstruct tubular flow, increasing intratubular pressure
• Results in reduced GFR and oliguria

Mechanism 2: Oxidative Injury (2 marks)

• Myoglobin contains heme iron (Fe2+)
• In acidic conditions, iron is oxidised to Fe3+ (metmyoglobin) then Fe4+ (ferryl myoglobin)
• Ferryl myoglobin generates hydroxyl radicals via Fenton reaction
• Lipid peroxidation causes proximal tubular cell damage

Mechanism 3: Renal Vasoconstriction (2 marks)

• Myoglobin scavenges nitric oxide → reduced vasodilation
• Endothelin-1 release → vasoconstriction
• Isoprostanes from lipid peroxidation → vasoconstriction
• Reduced renal blood flow, especially in outer medulla
• Exacerbated by hypovolaemia (fluid sequestration in injured muscle)

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Question 1.3 (6 marks total)

Current indications for RRT (3 marks):

In this patient, RRT is indicated for:

1. Refractory hyperkalaemia (K+ 7.4 mmol/L with ECG changes)

   • If not responsive to medical therapy (calcium, insulin-dextrose) within 30-60 minutes

2. Severe metabolic acidosis (pH 7.22, HCO3 11 mmol/L)

   • Contributing to hyperkalaemia and cardiac instability

3. Anticipate fluid overload with aggressive resuscitation requirements

NOT an indication: High CK level alone or to "clear myoglobin" (no evidence of benefit)

Modality choice (3 marks):

CRRT (CVVHDF) is preferred for this patient:

1. Haemodynamic instability (BP 85/50) - continuous therapy better tolerated
2. More gradual electrolyte and fluid shifts
3. Allows concurrent aggressive IV fluid resuscitation for muscle perfusion
4. No evidence of improved myoglobin clearance with any modality

Prescription:

• Effluent dose: 25 mL/kg/hr
• Regional citrate anticoagulation preferred
• Vascular access: Right internal jugular preferred

---

Common Mistakes:

• Not treating hyperkalaemia as first priority
• Forgetting compartment syndrome assessment
• Giving calcium for asymptomatic hypocalcaemia
• Starting RRT based on CK level rather than standard indications
• Using normal saline (may worsen hyperchloraemic acidosis)

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SAQ 2: Exertional Rhabdomyolysis with Renal Failure

Time Allocation: 10 minutes
Total Marks: 20

Stem:

A 28-year-old male army recruit presents to the ED 18 hours after completing a 20km forced march in hot conditions (35°C ambient temperature). He reports severe muscle cramps and has noticed his urine is "dark brown".

Past Medical History: Nil significant. Family history of uncle who "couldn't exercise properly".

Medications: Pre-workout supplements, creatine

Observations:

• HR: 95 bpm
• BP: 115/70 mmHg
• RR: 18/min
• SpO2: 98% on room air
• Temperature: 37.8°C
• GCS: 15

Examination: Diffuse muscle tenderness in thighs and calves. No compartment syndrome signs.

Investigations:

ABG:

• pH: 7.34
• HCO3: 22 mmol/L
• Lactate: 2.1 mmol/L
• K+: 5.6 mmol/L

Bloods:

• CK: 65,000 U/L
• Creatinine: 245 μmol/L (baseline unknown)
• Calcium: 2.0 mmol/L (iCa 0.95 mmol/L)
• Phosphate: 1.8 mmol/L

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Question 2.1 (6 marks)

Outline your fluid resuscitation strategy, including the controversy around urinary alkalinization.

Question 2.2 (8 marks)

List six causes of exertional rhabdomyolysis and describe three risk factors for severe disease.

Question 2.3 (6 marks)

The patient's uncle had a similar episode. What genetic conditions predispose to recurrent rhabdomyolysis, and how would you investigate?

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Model Answer

Question 2.1 (6 marks total)

Fluid Resuscitation Strategy (4 marks):

Fluid type: Balanced crystalloid (Hartmann's, Plasmalyte) preferred

• Avoids hyperchloraemic acidosis from normal saline
• No evidence that colloids are superior

Rate and targets:

• Initial bolus: 1-2L if hypovolaemic
• Ongoing: 200-500 mL/hr to achieve target urine output
• Target urine output: 200-300 mL/hr (3 mL/kg/hr)
• This is HIGHER than standard ICU target of 0.5 mL/kg/hr
• Early aggressive resuscitation (<6 hours) reduces AKI incidence from 40% to 4%

Monitoring:

• Hourly urine output via catheter
• Regular electrolytes (K+, Ca2+, PO4)
• Serial CK (expect peak at 24-72 hours)
• Clinical assessment for fluid overload

Urinary Alkalinization Controversy (2 marks):

Theoretical rationale:

• Urine pH >6.5 reduces myoglobin precipitation (casts form in acidic urine)
• Alkaline pH reduces ferryl myoglobin toxicity
• May prevent cast formation with Tamm-Horsfall protein

Evidence against routine use:

• No randomised controlled trials demonstrating benefit
• Observational studies show inconsistent results
• KDIGO does not recommend routine alkalinization
• European guidelines give weak recommendation "may be considered"

Risks of alkalinization:

• Hypokalaemia (shifts K+ intracellularly)
• Worsening ionised hypocalcaemia (alkalosis reduces free calcium)
• Fluid overload and hypernatraemia
• Difficult to achieve target urine pH

Current practice: Variable. Many Australian ICUs use aggressive crystalloid alone without bicarbonate, given lack of evidence.

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Question 2.2 (8 marks total)

Six Causes of Exertional Rhabdomyolysis (3 marks - 0.5 each):

1. Intense exercise beyond usual conditioning (marathon, CrossFit, military training)
2. High ambient temperature and humidity (heat stress)
3. Dehydration (reduced muscle perfusion)
4. Novel or eccentric exercise (running downhill, unaccustomed resistance training)
5. Stimulant use (pre-workout supplements, caffeine, amphetamines)
6. Underlying genetic myopathy (McArdle disease, CPT-II deficiency)
7. Sickle cell trait (exertional sickling)
8. Viral illness (recent URTI may predispose)

Three Risk Factors for Severe Disease (5 marks):

1. Genetic myopathy (1.5 marks)

   • McArdle disease, CPT-II deficiency
   • Impaired muscle energy metabolism
   • Recurrent episodes with relatively modest exercise
   • Family history suggestive (as in this case)

2. Sickle cell trait (1.5 marks)

   • Exertional sickling causes microvascular occlusion
   • Higher risk in heat, altitude, dehydration
   • May cause sudden collapse and death
   • More common in athletes of African descent

3. Environmental factors (2 marks)

   • High ambient temperature (>25°C)
   • High humidity (impairs heat dissipation)
   • Dehydration (reduced muscle blood flow, concentrated myoglobin)
   • Lack of acclimatisation
   • Previous heat illness

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Question 2.3 (6 marks total)

Genetic Conditions Predisposing to Recurrent Rhabdomyolysis (3 marks):

1. McArdle Disease (Glycogen Storage Disease Type V)
   • Myophosphorylase deficiency
   • Cannot break down glycogen during exercise
   • "Second wind phenomenon"

• feel better after 10-15 minutes
  • Elevated CK even at rest

2. Carnitine Palmitoyltransferase II (CPT-II) Deficiency

   • Most common inherited myopathy causing rhabdomyolysis
   • Impaired long-chain fatty acid oxidation
   • Triggered by prolonged exercise, fasting, infection
   • Often normal CK between episodes

3. Malignant Hyperthermia Susceptibility

   • RYR1 or CACNA1S mutations
   • Triggered by volatile anaesthetics, succinylcholine
   • Family history of anaesthetic complications

4. Phosphofructokinase Deficiency (Tarui Disease)

5. Phosphoglycerate Kinase Deficiency

6. Myoadenylate Deaminase Deficiency

Investigation Approach (3 marks):

Initial workup:

• Detailed family history (exercise intolerance, anaesthetic problems)
• CK level between episodes (persistently elevated in some myopathies)
• Ischaemic forearm exercise test (no lactate rise in McArdle disease)

Specific testing:

• Genetic testing: Targeted panels for metabolic myopathies (PYGM for McArdle, CPT2 for CPT-II)
• Muscle biopsy: Enzyme activity assays, histochemistry
• Acylcarnitine profile: Elevated in CPT-II deficiency

Referral: Neuromuscular specialist/metabolic genetics service

Counselling:

• Implications for military career
• Exercise modification
• Family screening
• Anaesthetic precautions (if MH susceptibility)

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Viva Scenarios

Viva Scenario 1: Pathophysiology and Fluid Management

Stem:

"A 40-year-old man is admitted to ICU after being found unconscious in his apartment for estimated 18 hours following an opioid overdose. He has bilateral swollen lower limbs, CK 120,000 U/L, creatinine 380 μmol/L, K+ 6.8 mmol/L. You are the ICU registrar."

Duration: 12 minutes (2 min reading + 10 min discussion)

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Opening Question:

"What are your immediate concerns about this patient?"

Expected Answer (2-3 minutes):

This patient has severe rhabdomyolysis from prolonged immobilization with:

1. Life-threatening hyperkalaemia (K+ 6.8 mmol/L)

   • Immediate risk of cardiac arrhythmia
   • Requires urgent treatment before progressing

2. Established acute kidney injury

   • Creatinine 380 μmol/L
   • Myoglobin nephrotoxicity contributing
   • Will worsen hyperkalaemia

3. Possible compartment syndrome

   • Bilateral swollen limbs after prolonged compression
   • Requires urgent assessment - limbs, pulses, compartment pressures
   • Time-critical for fasciotomy if present (6-hour window)

4. Underlying overdose

   • May need naloxone if still sedated
   • Risk of aspiration, respiratory depression

5. Volume depletion

   • Third-spacing into injured muscle
   • Needs aggressive resuscitation

---

Follow-up Question 1 (2-3 minutes):

"Describe the pathophysiology of muscle cell death in this patient."

Expected Answer:

Mechanism of muscle death from compression:

1. Ischaemia during compression

   • Vascular occlusion and reduced oxygen delivery
   • ATP depletion (Na+/K+-ATPase and Ca2+-ATPase failure)
   • Intracellular sodium and water accumulation → cell swelling
   • Intracellular calcium overload → activates proteases (calpains), lipases

2. Reperfusion injury

   • Upon release of compression, blood flow returns
   • Reactive oxygen species generation
   • Inflammatory cell infiltration (neutrophils)
   • Paradoxical worsening of injury

3. Release of intracellular contents

   • Potassium (150 mmol/L intracellular → extracellular)
   • Myoglobin (2-5 mg/g muscle, 60-150g total body)
   • Phosphate, uric acid, organic acids
   • Creatine kinase (diagnostic marker)

This explains the "smiling death" phenomenon - patients appear well initially but deteriorate after extrication due to sudden release of potassium and acids.

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Follow-up Question 2 (2-3 minutes):

"What is the evidence for urinary alkalinization?"

Expected Answer:

Theoretical rationale:

• Myoglobin precipitates with Tamm-Horsfall protein in acidic urine (pH <5.6)
• Alkaline urine may reduce cast formation
• Alkaline pH reduces ferryl myoglobin (Fe4+) toxicity
• Historical observational studies suggested benefit

Current evidence:

• No randomised controlled trials comparing alkalinization vs crystalloid alone
• Retrospective studies show inconsistent results
• Brown et al. 2004 - large observational study showed volume resuscitation was the key factor, not alkalinization
• Several studies show no additional benefit beyond adequate fluid resuscitation

Guideline recommendations:

• KDIGO: Does not recommend routine urinary alkalinization
• European Working Party 2014: Weak recommendation ("may be considered")
• Australian practice: Variable - many units use crystalloid alone

Practical concerns with alkalinization:

• Difficult to achieve target urine pH >6.5
• Hypokalaemia (shifts K+ intracellularly)
• Worsening ionised hypocalcaemia
• Fluid overload, hypernatraemia

My approach: I would prioritise aggressive crystalloid resuscitation targeting urine output 200-300 mL/hr. I would not routinely add bicarbonate unless there is severe metabolic acidosis (pH <7.1) as a primary indication.

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Follow-up Question 3 (2-3 minutes):

"When would you initiate renal replacement therapy?"

Expected Answer:

Standard KDIGO indications (AEIOU mnemonic):

1. A - Acidosis: Refractory metabolic acidosis (pH <7.1) despite medical therapy
2. E - Electrolytes: Refractory hyperkalaemia (K+ >6.5 mmol/L) despite medical therapy
3. I - Ingestion: Dialysable toxin (not applicable here specifically)
4. O - Overload: Refractory fluid overload (especially if limiting resuscitation)
5. U - Uraemia: Uraemic complications (encephalopathy, pericarditis, bleeding)

In this patient:

• K+ 6.8 mmol/L - approaching threshold
• If refractory to calcium, insulin-dextrose, salbutamol → urgent RRT
• Established AKI (creatinine 380) → lower threshold for RRT

What is NOT an indication:

• High CK level alone
• "Prophylactic" RRT to clear myoglobin
• No evidence that RRT targeting myoglobin removal improves outcomes

Modality choice:

• CRRT preferred if haemodynamically unstable
• Allows concurrent aggressive fluid resuscitation
• High-flux or high-cutoff membranes may enhance myoglobin removal but no proven outcome benefit

Timing evidence:

• AKIKI and STARRT-AKI trials in general AKI population
• No specific trials in rhabdomyolysis
• Trend towards waiting for absolute indications rather than prophylactic initiation

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Examiner's Expected Level:

Pass:

• Recognises hyperkalaemia as immediate life-threatening emergency
• Systematic approach to resuscitation
• Understands pathophysiology of myoglobin nephrotoxicity
• Knows evidence base for alkalinization is weak
• Uses standard RRT indications, not empiric myoglobin clearance

Fail:

• Misses hyperkalaemia urgency
• Cannot explain mechanisms of muscle damage
• Over-relies on alkalinization or mannitol
• Initiates RRT based on CK level alone

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Viva Scenario 2: Compartment Syndrome and Indigenous Health

Stem:

"A 38-year-old Aboriginal man from a remote community in the Northern Territory is transferred via RFDS after a quad-bike rollover accident 12 hours ago. He was trapped under the vehicle for 4 hours before discovery. He has a swollen, tense right thigh and calf. CK is 85,000 U/L. His family have arrived and are distressed."

Duration: 12 minutes (2 min reading + 10 min discussion)

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Opening Question:

"What are the clinical features of compartment syndrome and how would you assess this patient?"

Expected Answer:

Clinical Features of Compartment Syndrome (5 P's - but unreliable):

1. Pain - out of proportion to injury, not relieved by analgesia
2. Pain on passive stretch - most reliable early sign
   • Leg anterior compartment: pain on passive plantarflexion
   • Leg posterior compartment: pain on passive dorsiflexion
3. Pressure - tense, firm compartment on palpation
4. Paraesthesias - nerve ischaemia (relatively late)
5. Pulselessness - very late sign (compartment pressure rarely exceeds systolic)
6. Paralysis - late, indicates irreversible damage

Assessment in this patient:

Clinical examination:

• Palpate all four compartments of the right leg
• Assess anterior, lateral, superficial posterior, deep posterior
• Check thigh compartments as well
• Pain on passive stretch testing
• Pulses (but presence doesn't exclude compartment syndrome)
• Neurological assessment (sensation, motor function)

Pressure measurement (essential in obtunded/uncertain cases):

• Normal: <10 mmHg
• Concerning: >30 mmHg absolute
• Critical: Delta pressure (diastolic - compartment pressure) <30 mmHg
• Indicates need for fasciotomy

This patient has been trapped 4 hours, transferred over 12 hours - very high risk of established compartment syndrome with muscle necrosis. Urgent surgical consultation essential.

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Follow-up Question 1 (2-3 minutes):

"What are the surgical considerations, and what complications might occur post-fasciotomy?"

Expected Answer:

Surgical Considerations:

Timing:

• Fasciotomy should occur within 6-8 hours of symptom onset
• After 6-8 hours, irreversible muscle necrosis occurs
• This patient: 16+ hours since injury - some muscle may be non-viable

Technique (lower leg):

• Four-compartment fasciotomy via two incisions
• Lateral incision: anterior and lateral compartments
• Medial incision: superficial and deep posterior compartments
• Skin and fascia incised full length of compartment
• Wounds left open

Post-fasciotomy complications:

1. Ongoing muscle necrosis - release may be too late
2. Bleeding - especially if coagulopathic (DIC)
3. Infection - open wounds, contaminated environment
4. Reperfusion syndrome - hyperkalaemia, acidosis may worsen
5. Need for debridement - non-viable muscle removal
6. Skin coverage - delayed primary closure or skin grafting
7. Chronic pain, contractures, weakness
8. Amputation - if extensive necrosis

Australian context:

• Remote location - delayed fasciotomy
• Transfer time considerations
• May need to return for staged procedures

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Follow-up Question 2 (2-3 minutes):

"How would you approach communication with this patient's family, considering cultural factors?"

Expected Answer:

Indigenous Health Considerations:

Cultural Safety Principles:

1. Involve Aboriginal Health Worker (AHW) or Aboriginal Liaison Officer (ALO)

   • Cultural broker and interpreter
   • Understands community dynamics
   • Can explain medical concepts in culturally appropriate way

2. Kinship and Family

   • Large family groups may wish to be involved
   • Respect for Elders in decision-making
   • May need to wait for key family members to arrive
   • "Sorry business" may affect family availability

3. Communication Style

   • Allow time for discussion (don't rush)
   • Avoid direct eye contact if culturally inappropriate
   • Use plain language, avoid medical jargon
   • Check understanding frequently
   • Be aware of "gratuitous concurrence" (agreeing to avoid conflict)

4. Spiritual and Cultural Beliefs

   • Illness may have spiritual significance
   • Traditional healers may be involved
   • Respect for cultural practices around body, surgery
   • Concerns about blood transfusion, surgery, amputation

Practical Approach for This Case:

• Request AHW/ALO attendance urgently
• Find quiet, private space for family meeting
• Allow family time to assemble
• Explain situation clearly: serious leg injury, may need surgery, risk of complications
• Allow questions and discussion
• Document discussion and family involvement
• Ensure interpreter if English not first language
• Be prepared for different decision-making processes

Health System Considerations:

• Remote community - family may have limited resources to stay
• Accommodation support for family
• Social work involvement
• Plan for eventual transfer back to community
• Follow-up arrangements

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Follow-up Question 3 (2 minutes):

"What are the challenges of managing rhabdomyolysis in remote and rural Australia?"

Expected Answer:

Remote/Rural Challenges:

1. Delayed presentation

   • Distance from healthcare facilities
   • Limited access to transport
   • May present late with established AKI

2. Delayed definitive care

   • Fasciotomy may not be available locally
   • RFDS/retrieval required
   • Transfer times 4-12+ hours

3. Pre-hospital care limitations

   • Limited IV fluids in remote settings
   • May not have IV access established
   • Hyperkalaemia may not be detected or treated

4. Dialysis access

   • RRT only available in major centres
   • Remote patients must be transferred
   • May be hundreds of kilometres away

5. Higher burden of disease

   • Aboriginal and Torres Strait Islander populations
   • Higher rates of diabetes, CKD
   • Reduced renal reserve, worse outcomes

6. Aeromedical considerations

   • Altitude effects on gas expansion
   • Limited space for interventions
   • Need stable patient for transfer

Solutions:

• Telemedicine consultation with intensivists
• Pre-hospital protocols (early IV fluids, ECG monitoring)
• Hub-and-spoke dialysis networks
• Cultural liaison and support
• RFDS/retrieval training for remote staff

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Indigenous Health Considerations

Aboriginal and Torres Strait Islander Peoples

Health Disparities:

• 2-3× higher rates of diabetes mellitus
• 2-3× higher rates of chronic kidney disease
• Higher rates of end-stage renal disease
• Younger age at presentation with complications
• Higher cardiovascular disease burden

Risk Factors for Rhabdomyolysis:

• Mining and heavy industry employment (crush injuries)
• Remote location with delayed access to care
• Higher rates of alcohol use disorder (immobilization)
• Reduced baseline renal reserve

Cultural Considerations:

• Involve Aboriginal Health Workers (AHWs) and Aboriginal Liaison Officers (ALOs)
• Extended family involvement in decision-making
• Respect for Elders and cultural authority
• Allow time for family meetings and discussion
• "Sorry business" (funerals, mourning) may affect family availability
• Consider language barriers and need for interpreters
• Traditional beliefs about illness and treatment
• Concerns about surgery, blood products, organ donation

Practical Steps:

1. Ask about cultural needs on admission
2. Request AHW/ALO involvement early
3. Ensure family accommodation support
4. Document cultural considerations in notes
5. Plan for culturally safe follow-up care
6. Consider need for return to country during recovery

Māori Health (New Zealand)

Health Disparities:

• 2-2.5× higher rates of diabetes
• Higher rates of CKD and cardiovascular disease
• Younger age at renal replacement therapy

Cultural Considerations:

• Whānau (extended family) involvement essential
• Tikanga Māori (customs and protocols) should be respected
• Manaakitanga (hospitality, care for others)
• Kaumātua (elders) may be key decision-makers
• Māori Health Workers facilitate culturally safe care
• Consider karakia (prayers) and cultural practices