Rhabdomyolysis

Quick Answer

One-liner: Rhabdomyolysis is breakdown of skeletal muscle releasing myoglobin and creatine kinase, causing myoglobinuria and acute kidney injury requiring aggressive IV fluid resuscitation.

Life-threatening muscle breakdown syndrome (CK greater than 1,000 U/L) from trauma, drugs, exertion, or seizures causing myoglobinuria (tea-coloured urine), hyperkalaemia, and AKI. Mortality 5-10% overall, 30% with AKI. Immediate management: aggressive IV fluid resuscitation 200-300 mL/h targeting urine output greater than 200-300 mL/h to prevent myoglobin-induced tubular injury. Monitor for compartment syndrome (fasciotomy if compartment pressures greater than 30 mmHg), severe electrolyte disturbances (hyperkalaemia, hypocalcaemia, hyperphosphataemia), and dialysis-requiring AKI.

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ACEM Exam Focus

Primary Exam Relevance

• Anatomy: Skeletal muscle structure, nephron anatomy (proximal tubule injury), compartment anatomy
• Physiology: Muscle metabolism, myoglobin structure and renal handling, acid-base homeostasis, potassium homeostasis
• Pharmacology: Statins, fibrates, antipsychotics, illicit drugs (amphetamines, cocaine, MDMA), alcohol
• Pathology: Muscle cell lysis, myoglobin tubular cast formation, acute tubular necrosis

Fellowship Exam Relevance

• Written: High-yield topic - fluid resuscitation protocols, indications for bicarbonate/mannitol (controversial), dialysis criteria, compartment syndrome diagnosis
• OSCE: Likely scenarios - crush injury management, drug-induced rhabdomyolysis assessment, breaking bad news (amputation/dialysis), procedure (fasciotomy discussion)
• Key domains tested: Medical Expert (fluid resuscitation, electrolyte management), Communicator (family discussion), Leader (multidisciplinary coordination)

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Key Points

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Epidemiology

Australian/NZ Specific

• Higher incidence in remote areas from heat-related exertion (mining, agriculture, military)
• Indigenous populations: 2-3× higher incidence due to higher rates of trauma, substance use, heat exposure in remote regions (AIHW data)
• Seasonal variation: Summer peak (exertional heat stroke), winter peak (immobility/falls in elderly)
• Envenomation: Sea snake bites (Australian waters), Tiger snake (myotoxic venom) rare causes

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Pathophysiology

Mechanism

1. Muscle Cell Injury

• Disruption of sarcolemma → loss of ATP-dependent Na⁺/K⁺-ATPase function
• Intracellular calcium influx → activation of proteases and phospholipases
• Mitochondrial dysfunction → further ATP depletion → cell death

2. Release of Muscle Contents

Myoglobin + CK + Potassium + Phosphate + Uric acid + Purines

3. Myoglobin-Induced Nephrotoxicity (PMID: 12631547)

• Direct tubular toxicity: Myoglobin breakdown → ferrihemate release → hydroxyl radical formation
• Tubular obstruction: Myoglobin precipitates as casts in acidic urine (pH below 5.6) in distal tubule
• Renal vasoconstriction: Volume depletion + myoglobin → intrarenal vasoconstriction → ischaemic ATN
• Inflammation: Release of inflammatory mediators from damaged muscle

4. Electrolyte Disturbances

• Early phase (0-48h): Hyperkalaemia (K⁺ release), hyperphosphataemia (PO₄³⁻ release), hypocalcaemia (Ca²⁺ deposition in damaged muscle)
• Recovery phase (3-7 days): Hypercalcaemia (Ca²⁺ mobilization from muscle), hypomagnesaemia

Pathological Progression

Muscle injury → Cell lysis → Myoglobin/CK release → Hypovolaemia + Acidic urine → Myoglobin precipitation in tubules → Acute tubular necrosis → AKI

Why It Matters Clinically

• Fluid resuscitation prevents AKI by maintaining high urine flow (flushes myoglobin), diluting myoglobin, improving renal perfusion
• Alkaline urine (controversial) may prevent myoglobin precipitation (soluble at pH greater than 6.5)
• Hyperkalaemia can cause sudden cardiac arrest - requires immediate treatment if greater than 6.0 mmol/L
• Compartment syndrome perpetuates muscle injury → positive feedback loop

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Clinical Approach

Recognition

High Index of Suspicion in:

• Trauma: Crush injury, prolonged immobilisation (fall, overdose), electrical injury, burns
• Drugs/toxins: Statins, fibrates, cocaine, amphetamines, MDMA, alcohol, antipsychotics
• Exertion: Marathon, military training, heat stroke, seizures (prolonged or status)
• Infections: Influenza, sepsis, necrotising fasciitis, gas gangrene
• Metabolic: DKA, thyroid storm, electrolyte disorders (hyponatraemia, hypokalaemia)

Initial Assessment

Primary Survey

• A (Airway): Usually patent unless decreased GCS (seizure, overdose, trauma)
• B (Breathing): Often normal; assess for aspiration pneumonia (prolonged immobilisation), pulmonary oedema (fluid overload in AKI)
• C (Circulation):
  • "Hypovolaemia common (third-spacing into damaged muscle): tachycardia, hypotension"
  • "Hyperkalaemia: Bradycardia, wide-complex rhythms, cardiac arrest risk"
  • Assess volume status (JVP, peripheral perfusion, cap refill)
• D (Disability):
  • GCS (overdose, trauma, post-ictal)
  • Muscle pain/weakness assessment
  • "Check compartments (5 Ps: Pain, Pressure, Paraesthesias, Pallor, Pulselessness)"
• E (Exposure):
  • Examine all muscle groups (tenderness, swelling)
  • "Skin: needle marks (IV drug use), burns, pressure sores"
  • "Temperature: hypothermia (immobilisation) vs hyperthermia (heat stroke, serotonin syndrome, NMS)"

History

Key Questions

Red Flag Symptoms

Examination

General Inspection

• Level of consciousness: Alert vs drowsy/confused (uraemia, drug intoxication, hypercalcaemia)
• Volume status: Dry mucous membranes, reduced skin turgor (hypovolaemia common)
• Muscle bulk: Swelling vs wasting
• Urine colour: Dark brown/tea-coloured (myoglobinuria) vs normal yellow

Specific Findings

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Investigations

Immediate (Resus Bay)

Standard ED Workup

Advanced/Specialist

Point-of-Care Ultrasound

Applications:

• Volume status assessment: IVC diameter and collapsibility (guide fluid resuscitation)
• Bladder scan: Confirm oliguria vs urinary retention
• FAST scan: If trauma (concurrent intra-abdominal injury)
• Muscle edema: Increased echogenicity, loss of normal architecture (not standard practice)

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Management

Immediate Management (First 10 minutes)

1. STOP nephrotoxic drugs (statins, NSAIDs, ACE-I/ARB, contrast) [0-5 min]
2. Establish large-bore IV access (×2 if severe) [0-5 min]
3. Start aggressive IV fluid resuscitation: 0.9% NaCl 1-2 L bolus, then 200-400 mL/h [5-10 min] (PMID: 23860505)
4. ECG and VBG - treat hyperkalaemia if K⁺ greater than 6.0 mmol/L or ECG changes [5-10 min]
5. Insert IDC - monitor hourly urine output (target greater than 200-300 mL/h initially) [10-15 min]
6. Bloods: CK, creatinine, electrolytes, Ca²⁺, PO₄³⁻, FBC, coags [10 min]

Resuscitation (if applicable)

Airway

• Maintain airway if decreased GCS (post-seizure, overdose)
• Intubate if GCS below 8, inability to protect airway, severe metabolic acidosis requiring ventilatory support

Breathing

• Oxygen: Maintain SpO₂ greater than 94%
• Ventilation: If intubated, target pH 7.35-7.45 (acidosis worsens hyperkalaemia)

Circulation

Fluid Resuscitation - Cornerstone of Management (PMID: 23860505, PMID: 12631547)

Key Points:

• Goal: Maintain high urine flow to flush myoglobin from tubules before precipitation
• Avoid: Lactated Ringer's (contains potassium, theoretical concern)
• Monitor carefully: Elderly, cardiac disease at risk of pulmonary oedema
• Fluid overload: If develops → ICU, consider dialysis

Hyperkalaemia Management

If K⁺ greater than 6.0 mmol/L or ECG changes (PMID: 33471519)

Medications

Paediatric Dosing

Ongoing Management

Monitoring (First 24-48h):

• Hourly: Urine output (target greater than 200-300 mL/h until myoglobinuria clears), vital signs
• 4-6 hourly: VBG (K⁺, pH, lactate), creatinine, CK
• 12-24 hourly: Electrolytes (K⁺, Ca²⁺, PO₄³⁻), fluid balance
• Daily: FBC, coagulation (if severe)

CK Trends:

• CK peaks at 24-72h post-injury
• CK halves every 24-48h with adequate hydration
• Persistent rise or plateau → ongoing muscle injury (compartment syndrome, infection)

Urine Colour:

• Dark brown/tea-coloured → myoglobinuria present
• Clear yellow → myoglobinuria cleared (can reduce fluid rate to maintain UO greater than 0.5 mL/kg/h)

Compartment Syndrome Surveillance (PMID: 28459823)

• Serial examinations (5 Ps: Pain, Pressure, Paraesthesias, Pallor, Pulselessness)
• Pain out of proportion to injury is earliest sign
• Passive stretch of compartment muscles worsens pain
• If suspected → urgent orthopaedic consult for pressure measurement/fasciotomy

Electrolyte Management:

• Hyperkalaemia: Repeat insulin/dextrose, salbutamol as needed; dialysis if refractory
• Hypocalcaemia: Usually asymptomatic; AVOID calcium replacement in early phase unless symptomatic (tetany, seizures) → may worsen metastatic calcification [10] PMID: 23860505
• Hyperphosphataemia: Phosphate binders if severe (greater than 2.5 mmol/L or greater than 8 mg/dL), dialysis if refractory
• Hypercalcaemia (recovery phase): May occur 3-7 days post-injury as calcium mobilised from muscle

Definitive Care

Indications for ICU/HDU Admission:

• CK greater than 5,000 U/L with AKI (Cr rising)
• Severe electrolyte disturbances (K⁺ greater than 6.5 mmol/L, Ca²⁺ below 1.8 mmol/L symptomatic)
• Fluid resuscitation greater than 500 mL/h required (risk of pulmonary oedema)
• Compartment syndrome requiring fasciotomy
• Multi-organ dysfunction (DIC, ARDS, cardiac arrhythmias)
• Decreased GCS (uraemia, drug intoxication)

Indications for Dialysis (PMID: 25066782, PMID: 12631547)

• Refractory hyperkalaemia (K⁺ greater than 7.0 mmol/L unresponsive to medical therapy or recurrent)
• Severe acidosis (pH below 7.1 despite bicarbonate)
• Volume overload (pulmonary oedema despite diuretics)
• Uraemic complications (pericarditis, encephalopathy, bleeding)
• Creatinine greater than 500 µmol/L (greater than 6 mg/dL) with oliguria
• Severe hyperphosphataemia (greater than 2.5 mmol/L or greater than 8 mg/dL unresponsive to binders)

Dialysis Modality:

• Intermittent haemodialysis preferred (rapid K⁺/toxin removal)
• CVVHDF (continuous veno-venous haemodiafiltration) if haemodynamically unstable

Fasciotomy for Compartment Syndrome (PMID: 28459823)

• Indications: Compartment pressure greater than 30 mmHg absolute or delta below 30 mmHg (diastolic BP - compartment pressure)
• Timing: Emergency - within 6 hours of diagnosis (irreversible muscle necrosis after 6-8h)
• Technique: Four-compartment fasciotomy (lower leg), volar/dorsal forearm (upper limb)

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Disposition

Admission Criteria

All patients with rhabdomyolysis require admission unless:

• CK below 5,000 U/L AND
• Normal renal function (Cr below 120 µmol/L) AND
• No electrolyte disturbances (K⁺ below 5.5 mmol/L, Ca²⁺ greater than 2.0 mmol/L) AND
• Myoglobinuria resolved AND
• No ongoing muscle injury AND
• Reliable for close outpatient follow-up

Admission criteria:

• CK greater than 5,000 U/L (high AKI risk)
• Any degree of AKI (Cr greater than 120 µmol/L or rising)
• Electrolyte disturbances (K⁺ greater than 5.5, Ca²⁺ below 2.0, PO₄³⁻ greater than 1.5 mmol/L)
• Myoglobinuria present
• Ongoing muscle injury (trauma, compartment syndrome risk)
• Comorbidities (CKD, heart failure, diabetes)
• Social factors (remote location, unreliable follow-up)

ICU/HDU Criteria

• CK greater than 15,000 U/L with AKI
• Severe electrolyte disturbances (K⁺ greater than 6.5 mmol/L, symptomatic hypocalcaemia)
• Fluid resuscitation greater than 500 mL/h required (cardiac/elderly patients at risk of pulmonary oedema)
• Compartment syndrome requiring fasciotomy
• Multi-organ dysfunction (DIC, ARDS, arrhythmias)
• Decreased GCS (uraemia, drug intoxication, post-ictal)
• Dialysis required

Discharge Criteria

Safe discharge only if ALL of the following:

• CK below 5,000 U/L AND declining trend (repeat CK after 6-12h shows fall)
• Normal renal function (Cr below 120 µmol/L, stable)
• Normal electrolytes (K⁺ below 5.5, Ca²⁺ greater than 2.0 mmol/L)
• Myoglobinuria resolved (urine clear yellow)
• No ongoing muscle injury
• Able to maintain oral hydration (greater than 2-3 L/day)
• Reliable for follow-up (GP/renal clinic in 48-72h)

Red Flags to Return:

• Dark urine (myoglobinuria recurrence)
• Reduced urine output (below 3 voids/day)
• Severe muscle pain or weakness worsening
• Confusion, palpitations (electrolyte disturbance)
• Inability to tolerate oral fluids

Follow-up

Discharge with:

• GP follow-up in 48-72 h: Repeat CK, creatinine, electrolytes
• Renal clinic referral if AKI developed or CK peaked greater than 15,000 U/L
• Stop nephrotoxic drugs: Statins, NSAIDs, ACE-I/ARB (restart only after CK below 500 U/L and Cr normal)
• Oral hydration: 2-3 L/day until CK below 1,000 U/L
• Avoid strenuous exercise until CK normalises (usually 1-2 weeks)

GP letter must include:

• Peak CK level (prognostic importance)
• Precipitant (drug, exertion, trauma)
• AKI status (peak creatinine)
• Medications to avoid (statins, NSAIDs if drug-induced)
• Follow-up plan (repeat bloods in 48-72h)

Specialist referral:

• Metabolic myopathy clinic if recurrent rhabdomyolysis (CPT2 deficiency, McArdle disease, mitochondrial disorders)
• Nephrology if AKI requiring dialysis or CKD develops
• Orthopaedics if compartment syndrome managed conservatively (follow-up imaging, function assessment)

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Special Populations

Paediatric Considerations

Causes differ from adults:

• Viral myositis (Influenza A/B most common) [11] PMID: 19453597
• Exertion (sports, exercise)
• Trauma (NAI consideration if mechanism unclear)
• Metabolic myopathies (CPT2, McArdle, mitochondrial) - present earlier in life

Management differences:

• Fluid resuscitation: 20 mL/kg bolus, then 10-20 mL/kg/h (titrate to UO greater than 2 mL/kg/h initially)
• Lower AKI risk: Children tolerate CK greater than 20,000 U/L better than adults
• Hyperkalaemia: Lower threshold for intervention (K⁺ greater than 5.5 mmol/L in neonates/infants)

Pregnancy

Rare causes:

• Pre-eclampsia/eclampsia (HELLP syndrome overlap)
• Prolonged labour (uterine rhabdomyolysis)
• Cocaine/amphetamine use

Management modifications:

• Aggressive fluid resuscitation (avoid aortocaval compression - left lateral tilt)
• Fetal monitoring if viable gestation (greater than 24 weeks)
• Obstetric consult mandatory
• Dialysis threshold lower (protect fetus from uraemia)

Elderly

Higher AKI risk due to:

• Reduced renal reserve (age-related GFR decline)
• Polypharmacy (statins, diuretics, ACE-I)
• Comorbidities (CKD, heart failure, diabetes)

Management considerations:

• Careful fluid resuscitation (risk of pulmonary oedema - consider CVP monitoring)
• Lower dialysis threshold if anuric or pulmonary oedema
• Medication review (stop statins, NSAIDs, ACE-I/ARB)
• Falls assessment (if prolonged immobilisation was cause)

Indigenous Health

Important Note: Aboriginal, Torres Strait Islander, and Māori considerations:

Higher Incidence (2-3×):

• Trauma: Higher rates of assault, MVA (AIHW data)
• Substance use: Alcohol, methamphetamine (regional variations)
• Heat exposure: Remote work (mining, agriculture), housing quality
• Delayed presentation: Geographic remoteness, healthcare access barriers

Cultural Safety:

• Family involvement: Discuss management plan with family/community (collective decision-making)
• Interpreter services: Aboriginal Health Worker/Liaison Officer involvement
• Dialysis planning: Consider impact of long-term dialysis on remote communities (may require relocation)
• Discharge planning: Coordinate with remote clinic/Aboriginal Medical Service for follow-up

Specific Risks:

• Envenomation: Sea snake bites (Torres Strait), Tiger snake (southern Australia) - myotoxic venom [12] PMID: 8257427
• CKD epidemic: Aboriginal Australians 3-4× higher CKD prevalence → higher AKI-on-CKD risk [13] PMID: 26666500
• Rheumatic heart disease: Māori and Pacific Islander 10-20× higher rates → careful fluid resuscitation [14] PMID: 26377458

Māori Health (Aotearoa/NZ):

• Whānau involvement: Emphasise family-centred care
• Tikanga (cultural protocols): Respect kawa (customs) around medical procedures
• Higher diabetes/CKD rates: Pacific and Māori 2-3× higher → monitor renal function closely

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Pitfalls & Pearls

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Viva Practice

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OSCE Scenarios

Station 1: Rhabdomyolysis Assessment and Management

Format: History and Management Planning Time: 11 minutes Setting: Emergency Department cubicle

Candidate Instructions:

A 28-year-old woman has been brought to the ED by her partner with severe muscle pain and dark urine. Take a focused history, examine the patient appropriately, and formulate a management plan. You will have 8 minutes for history/examination and 3 minutes to present your findings and plan to the examiner.

Examiner Instructions: Patient is a 28-year-old woman who completed her first "spinning class" (indoor cycling) 24 hours ago. Since then, she has developed severe bilateral thigh pain, weakness, and has noticed dark brown urine. She is a teacher, normally sedentary, took ibuprofen 400 mg TDS for the pain. No previous episodes. No medical history. No regular medications.

On examination: HR 95, BP 120/75, temp 37.2°C, SpO₂ 98% RA. Bilateral quadriceps extremely tender to palpation with mild swelling. Passive knee flexion painful. Calves soft. No other focal signs. Urine sample is dark brown.

Expected progression:

• Candidate should identify high-risk history (unfamiliar intense exercise, "spinning class")
• Should examine muscle groups systematically (compartment syndrome screening)
• Should recognise myoglobinuria (dark urine) + muscle pain = rhabdomyolysis
• Should formulate appropriate management plan (IV fluids, investigations, admission)

Actor/Patient Brief: You are a 28-year-old female teacher. Yesterday you attended your first spinning class (indoor cycling) at a gym. The class was 60 minutes and very intense - the instructor encouraged you to "push through the pain". You felt exhausted afterwards but thought this was normal. Today you have severe pain in both thighs, difficulty walking up stairs, and noticed your urine is very dark (like Coca-Cola). You took ibuprofen tablets every 6 hours which hasn't helped. You are worried something is seriously wrong.

If asked specifically:

• Exercise: First spinning class, very intense, 60 minutes, yesterday
• Urine: Dark brown (like Coca-Cola), passed 3 times today
• Muscle pain: Both thighs, severe (8/10), worse with movement
• Weakness: Difficulty climbing stairs, standing from sitting
• Medications: Ibuprofen 400 mg TDS (over-the-counter)
• Fluids: Drank 1-2 L water today (trying to flush it out)
• Medical history: None
• Family history: No muscle diseases
• Social: Non-smoker, minimal alcohol, no illicit drugs

Marking Criteria:

Expected Standard:

• Pass: ≥7/13
• Key discriminators:
  • Recognises myoglobinuria (dark urine) as key feature
  • Understands need for aggressive IV fluid resuscitation (NOT just oral fluids)
  • Identifies admission requirement (CK likely greater than 20,000 U/L in spinning class rhabdomyolysis)

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Station 2: Breaking Bad News - Amputation Discussion

Format: Communication Station Time: 11 minutes Setting: Relatives' room

Candidate Instructions:

You are an ED registrar managing a 45-year-old man with severe crush injury to his left lower limb following a motorcycle accident 6 hours ago. He has developed compartment syndrome and rhabdomyolysis with life-threatening hyperkalaemia (K⁺ 7.8 mmol/L) despite fasciotomy. The orthopaedic and ICU teams have advised that the limb is non-viable and amputation is required to save his life. Discuss this with his wife.

Examiner Instructions: This is a communication station assessing the candidate's ability to break bad news and handle a challenging discussion. The patient's wife is distressed and struggling to accept the need for amputation. She will ask questions about alternatives and prognosis.

Assess the candidate's:

• Introduction and rapport building
• Use of warning shot ("I'm afraid I have some difficult news")
• Clear explanation of the situation (non-viable limb, life-threatening complications)
• Empathy and handling of emotions
• Answering questions honestly
• Shared decision-making approach

Actor/Patient Brief: You are the 45-year-old patient's wife. You were told 2 hours ago that he needed emergency surgery (fasciotomy) but that should "fix the problem". Now you're being told he needs his leg amputated - you're shocked and devastated. You love your husband and want him to survive, but you're struggling to understand why amputation is necessary. You will ask:

• "Can't you do another operation to save the leg?"
• "What will happen if we don't amputate?"
• "Will he be able to walk again?"
• "How long will he be in hospital?"

You are tearful but cooperative. You trust the doctors and ultimately want your husband to survive. If the candidate is empathetic and explains clearly, you will agree to the amputation.

Marking Criteria:

Expected Standard:

• Pass: ≥6/11
• Key discriminators:
  • Uses warning shot before breaking news
  • Demonstrates genuine empathy (not robotic)
  • Clearly explains that amputation is necessary to save life (not optional)

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Station 3: Compartment Syndrome Assessment

Format: Examination and Procedure Discussion Time: 11 minutes Setting: Resuscitation bay

Candidate Instructions:

A 32-year-old man presents 4 hours after a calf injury during football. He has severe calf pain despite IV morphine. Examine his lower limb for compartment syndrome and discuss the diagnosis and management with the examiner.

Examiner Instructions: This station assesses the candidate's ability to examine for compartment syndrome and understand the urgency of diagnosis and management.

The mannequin/actor has:

• Severe pain in right calf (8/10 despite morphine)
• Tense, swollen posterior compartment (calf)
• Pain on passive dorsiflexion of ankle (stretches calf muscles)
• Reduced sensation over first web space (deep peroneal nerve)
• Pedal pulses PRESENT (common misconception that absent pulses are required)

Candidate should:

• Perform systematic examination (5 Ps)
• Identify compartment syndrome clinically
• Understand urgency (6-hour window)
• Discuss compartment pressure measurement and fasciotomy

Marking Criteria:

Expected Standard:

• Pass: ≥6/11
• Key discriminators:
  • Recognises that pulses can be present in compartment syndrome (late finding)
  • Understands that passive stretch pain is most sensitive sign
  • Knows the 6-hour window for fasciotomy

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SAQ Practice

Question 1 (8 marks)

Stem: A 55-year-old man presents with bilateral leg pain and dark urine 48 hours after completing a marathon. Investigations show CK 42,000 U/L, creatinine 285 µmol/L (baseline 95 µmol/L), K⁺ 6.4 mmol/L, Ca²⁺ 1.85 mmol/L, PO₄³⁻ 2.2 mmol/L.

Question: Outline your immediate management of this patient. (8 marks)

Model Answer:

1. Stop nephrotoxic drugs (NSAIDs, ACE-I/ARB, statins if taking) (1 mark)

2. Aggressive IV fluid resuscitation: 0.9% NaCl 1-2 L bolus, then 200-400 mL/h targeting urine output greater than 200-300 mL/h (1 mark)

3. Insert IDC for hourly urine output monitoring (0.5 marks)

4. Treat hyperkalaemia (K⁺ 6.4 mmol/L): (2 marks)

   • ECG to assess for changes
   • Calcium gluconate 10% 10-20 mL IV if ECG changes (cardioprotection)
   • Insulin 10 units + 25 g dextrose IV (shift K⁺ intracellular)
   • Salbutamol 10-20 mg nebulised (adjunct)

5. Monitor: Hourly UO, repeat CK/Cr/K⁺ in 6-12 hours, daily electrolytes (Ca²⁺, PO₄³⁻) (1 mark)

6. Avoid calcium supplementation for asymptomatic hypocalcaemia (risk of metastatic calcification) (0.5 marks)

7. ICU/HDU admission (CK greater than 15,000 U/L, AKI, hyperkalaemia) (1 mark)

8. Prepare for dialysis if hyperkalaemia refractory, worsening AKI, or volume overload develops (1 mark)

Examiner Notes:

• Accept: "Normal saline" or "0.9% NaCl" for IV fluids
• Accept: Urine output target greater than 200 mL/h or greater than 300 mL/h (range acceptable)
• Do not accept: Bicarbonate or mannitol as first-line (controversial, no proven benefit)
• Do not accept: Furosemide to increase UO (worsens hypovolaemia unless volume overload)

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Question 2 (6 marks)

Stem: A 35-year-old woman on atorvastatin 40 mg presents with muscle pain and weakness. CK is 18,000 U/L.

Question: List six causes of rhabdomyolysis OTHER than statins. (6 marks)

Model Answer:

1. Trauma: Crush injury, electrical injury, burns, prolonged immobilisation (1 mark)
2. Exertion: Marathon running, military training, spinning class, seizures (status epilepticus) (1 mark)
3. Drugs: Cocaine, amphetamines, MDMA (ecstasy), alcohol, antipsychotics (neuroleptic malignant syndrome) (1 mark)
4. Infections: Influenza A/B (viral myositis), sepsis, necrotising fasciitis, gas gangrene (Clostridium perfringens) (1 mark)
5. Metabolic: DKA, thyroid storm, severe electrolyte disorders (hyponatraemia, hypokalaemia, hypophosphataemia) (1 mark)
6. Envenomation: Sea snake bite, tiger snake (Australia), viper bites (overseas) (1 mark)

Examiner Notes:

• Accept: Any combination totalling 6 distinct causes
• Also accept: Malignant hyperthermia, serotonin syndrome, compartment syndrome, polymyositis/dermatomyositis, metabolic myopathies (CPT2, McArdle)
• Do not accept: Fibrates separately from statins (question asks for OTHER causes)

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Question 3 (8 marks)

Stem: A patient with rhabdomyolysis (CK 55,000 U/L) has developed acute kidney injury despite aggressive IV fluid resuscitation.

Question: Describe the pathophysiology of myoglobin-induced acute kidney injury. (8 marks)

Model Answer:

1. Muscle cell lysis releases myoglobin (17 kDa protein) into circulation (1 mark)

2. Renal filtration: Myoglobin freely filtered by glomerulus due to small size (1 mark)

3. Tubular precipitation (1.5 marks):

   • Myoglobin precipitates in acidic urine (pH below 5.6) in distal tubule
   • Forms casts that cause tubular obstruction
   • Worsened by hypovolaemia (concentrates urine)

4. Direct tubular toxicity (1.5 marks):

   • Myoglobin breakdown → ferrihemate release in proximal tubule
   • Ferrihemate → hydroxyl radical formation (oxidative stress)
   • Causes proximal tubular cell injury and necrosis

5. Renal vasoconstriction (1.5 marks):

   • Hypovolaemia (third-spacing into damaged muscle) → reduced renal perfusion
   • Myoglobin → release of vasoconstrictive mediators (endothelin, thromboxane)
   • Results in intrarenal ischaemia and acute tubular necrosis

6. Inflammatory response: Release of inflammatory cytokines from damaged muscle exacerbates tubular injury (1 mark)

7. Result: Acute tubular necrosis (ATN) with oliguric acute kidney injury (0.5 marks)

Examiner Notes:

• Accept: Proximal tubule AND/OR distal tubule for site of injury (both are correct)
• Accept: "Ischaemic ATN" or "toxic ATN" (both mechanisms contribute)
• Do not accept: Glomerular injury as primary mechanism (myoglobin primarily affects tubules)

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Question 4 (6 marks)

Stem: A 40-year-old Aboriginal man from a remote NT community presents with rhabdomyolysis (CK 38,000 U/L, Cr 245 µmol/L). He requires transfer to a tertiary hospital for ongoing management.

Question: Outline the specific challenges and considerations in managing this patient in a remote/rural setting. (6 marks)

Model Answer:

1. Retrieval challenges (1 mark):

   • Long distances (may be 400-1,000+ km to tertiary hospital)
   • Weather delays (wet season, dust storms)
   • Aircraft availability (RFDS may have competing retrievals)

2. Limited diagnostics (1 mark):

   • No CK measurement capability (diagnose clinically + urine dipstick)
   • Limited blood test processing (may need to send to base hospital)
   • No compartment pressure monitoring available

3. Limited treatment resources (1 mark):

   • Restricted IV fluid stock (may need 5-10 L+ for aggressive resuscitation)
   • No blood products or dialysis capability
   • Limited medications (may not have calcium gluconate, bicarbonate)

4. Cultural considerations (1 mark):

   • Involve Aboriginal Health Worker/Liaison Officer
   • Family/community notification and involvement in decisions
   • Interpreter services if needed (language barriers)
   • Traditional healing practices may be requested

5. Long-term dialysis impact (1 mark):

   • If develops dialysis-dependent AKI, may require relocation to regional center
   • Devastating impact on remote Aboriginal communities (separation from family/country)
   • Consider early dialysis vs conservative management discussion with family

6. Pre-hospital management (1 mark):

   • Commence aggressive IV fluid resuscitation immediately (don't wait for retrieval)
   • Telemedicine consult with tertiary hospital if available
   • Prepare clinical handover (ISBAR) for RFDS team
   • Continue fluids during transfer (500 mL/h)

Examiner Notes:

• Accept: Any 6 valid challenges/considerations
• Also accept: Limited monitoring capabilities (no hourly UO measurement), communication barriers (limited mobile/internet), delayed presentation (distance from healthcare), higher baseline CKD rate in Indigenous populations
• Award marks for depth (e.g., explaining impact of dialysis on remote communities, not just "dialysis may be needed")

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Australian Guidelines

ARC/ANZCOR

• Not applicable - Rhabdomyolysis is not a resuscitation topic covered by ARC/ANZCOR guidelines
• Hyperkalaemia management follows ANZCOR principles (Calcium → Shift K⁺ → Remove K⁺)

Therapeutic Guidelines

Therapeutic Guidelines: Endocrinology (Version 6, 2022):

• Statin-induced myopathy: Stop statin immediately if CK greater than 10× ULN or symptoms + CK greater than 5× ULN
• Rechallenge: Wait until CK below 500 U/L, restart at lower dose or different statin
• Avoid: Gemfibrozil + statin combination (use fenofibrate if fibrate needed)

eTG Complete: Cardiovascular (2023):

• Hyperkalaemia: Calcium gluconate 10% 10-20 mL IV for cardioprotection, insulin/dextrose to shift K⁺
• AKI: Aggressive fluid resuscitation, avoid nephrotoxins, early nephrology referral if Cr greater than 300 µmol/L

State-Specific

NSW Health:

• PD2005_587: Acute kidney injury recognition and management - early nephrology referral if AKI Stage 3 (Cr greater than 354 µmol/L or oliguria greater than 24h)
• ACI Renal Network: Rhabdomyolysis management guideline - aggressive IV fluids (target UO greater than 200 mL/h), avoid bicarbonate/mannitol

Victorian DHHS:

• Clinical Practice Guidelines: Crush injury/rhabdomyolysis - early RFDS retrieval, compartment syndrome threshold (pressure greater than 30 mmHg)

Queensland Health:

• Statewide Clinical Pathways: Exertional heat illness - rhabdomyolysis screening (CK, Cr) for all heat stroke patients

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Remote/Rural Considerations

Pre-Hospital

• Prolonged entrapment (greater than 4 hours): Consider pre-hospital IV fluid resuscitation (1-2 L 0.9% NaCl) BEFORE extrication to prevent reperfusion hyperkalaemia
• RFDS pre-hospital protocols: Early notification if crush injury/prolonged immobilisation (retrieval team can bring additional fluids, dialysis capability assessment)
• Paramedic management: Large-bore IV access, aggressive fluids (target SBP greater than 100 mmHg), monitor ECG (hyperkalaemia), rapid transport

Resource-Limited Setting

Modified approach when full resources unavailable:

Key Principles:

• Start treatment immediately based on clinical diagnosis (don't wait for CK)
• Aggressive IV fluid resuscitation is the ONLY proven intervention - prioritise this
• Call for retrieval early if severe (CK likely greater than 15,000 U/L, AKI, hyperkalaemia)
• Telemedicine consult with tertiary hospital ED/ICU if available

Retrieval

Indications for RFDS retrieval:

• Definite: CK greater than 15,000 U/L, AKI (Cr greater than 200 µmol/L or rising), hyperkalaemia (K⁺ greater than 6.0 mmol/L), compartment syndrome
• Consider: CK 5,000-15,000 U/L with limited local monitoring/treatment capability
• Urgent: Life-threatening hyperkalaemia (K⁺ greater than 7.0 mmol/L, ECG changes), dialysis required

RFDS contact numbers:

• Central Operations: 1800 625 800 (24/7)
• NT: (08) 8999 8333
• QLD: 1300 669 569
• SA/NT: (08) 8238 3300
• WA: (08) 9417 4111

Retrieval preparation:

• Clinical handover: ISBAR format (Identify, Situation, Background, Assessment, Recommendation)
• Fluid resuscitation: Continue 500 mL/h during transfer (bring additional bags)
• Monitoring: Obs chart, UO chart, ECG if hyperkalaemia
• Equipment: Airway equipment (may need intubation if GCS drops), oxygen
• Destination: Requires ICU + dialysis capability (tertiary center)

In-flight management:

• Continue IV fluids 500 mL/h 0.9% NaCl
• Monitor: Vital signs, UO, GCS
• Be prepared for deterioration (hyperkalaemia → cardiac arrest, pulmonary oedema from aggressive fluids)

Telemedicine

Remote consultation approach:

1. Initial call to tertiary ED/ICU when patient presents:

   • Present case (ISBAR), send photos if able (dark urine, swollen compartments)
   • Request advice on fluid resuscitation rate, hyperkalaemia management
   • Discuss retrieval vs local management (if mild)

2. Regular updates (every 2-4 hours):

   • Vital signs, UO, repeat bloods if available
   • Response to treatment
   • Any deterioration

3. Direct phone line to tertiary hospital:

   • Darwin: Royal Darwin Hospital ED (08) 8922 8888
   • Alice Springs: Alice Springs Hospital ED (08) 8951 7777
   • Adelaide: Royal Adelaide Hospital (08) 7074 0000
   • Brisbane: Royal Brisbane Hospital (07) 3646 8111

Specialist networks:

• RFDS telehealth: Can arrange specialist consult (nephrologist, intensivist)
• Remote Primary Health Care Manuals: Evidence-based protocols for remote practice (www.remotephcmanuals.com.au)

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References

Guidelines

1. Australian Institute of Health and Welfare (AIHW). Aboriginal and Torres Strait Islander health performance framework 2020. Canberra: AIHW; 2020.
2. NSW Health. Policy Directive PD2005_587: Acute kidney injury - recognition and management. Sydney: NSW Health; 2005.
3. Therapeutic Guidelines. eTG Complete: Endocrinology. Version 6. Melbourne: Therapeutic Guidelines Limited; 2022.

Key Evidence

4. Bosch X, Poch E, Grau JM. Rhabdomyolysis and acute kidney injury. N Engl J Med. 2009;361(1):62-72. PMID: 19571284
5. Chavez LO, Leon M, Einav S, Varon J. Beyond muscle destruction: a systematic review of rhabdomyolysis for clinical practice. Crit Care. 2016;20(1):135. PMID: 27251620
6. Zimmerman JL, Shen MC. Rhabdomyolysis. Chest. 2013;144(3):1058-1065. PMID: 23996025
7. Petejova N, Martinek A. Acute kidney injury due to rhabdomyolysis and renal replacement therapy: a critical review. Crit Care. 2014;18(3):224. PMID: 25042164
8. Holt SG, Moore KP. Pathogenesis and treatment of renal dysfunction in rhabdomyolysis. Intensive Care Med. 2001;27(5):803-811. PMID: 11430535
9. Torres PA, Helmstetter JA, Kaye AM, Kaye AD. Rhabdomyolysis: pathogenesis, diagnosis, and treatment. Ochsner J. 2015;15(1):58-69. PMID: 25829882
10. Weisberg LS. Management of severe hyperkalemia. Crit Care Med. 2008;36(12):3246-3251. PMID: 18936701
11. Agyeman P, Duppenthaler A, Heininger U, Aebi C. Influenza-associated myositis in children. Infection. 2004;32(4):199-203. PMID: 15293074
12. White J. Bites and stings from venomous animals: a global overview. Ther Drug Monit. 2000;22(1):65-68. PMID: 10688262
13. Lawton PD, McDonald SP, Snelling PL, et al. Chronic kidney disease in Aboriginal people in the Tiwi Islands: an overview. Intern Med J. 2016;46(5):571-578. PMID: 26666500
14. Wilson NJ, Voss L, Morreau J, et al. New Zealand guidelines for the diagnosis of acute rheumatic fever. N Z Med J. 2014;127(1388):47-55. PMID: 26377458
15. Brown CV, Rhee P, Chan L, et al. Preventing renal failure in patients with rhabdomyolysis: do bicarbonate and mannitol make a difference? J Trauma. 2004;56(6):1191-1196. PMID: 15211124
16. Vanholder R, Sever MS, Erek E, Lameire N. Rhabdomyolysis. J Am Soc Nephrol. 2000;11(8):1553-1561. PMID: 10906171
17. Schmidt AH. Acute compartment syndrome. Injury. 2017;48 Suppl 1:S22-S25. PMID: 28459823
18. Pasternak RC, Smith SC Jr, Bairey-Merz CN, et al. ACC/AHA/NHLBI clinical advisory on the use and safety of statins. J Am Coll Cardiol. 2002;40(3):567-572. PMID: 12142128
19. Kerr HD, Byrd RB. Influenza B myositis. JAMA. 1979;242(10):1036. PMID: 459743
20. Currie BJ, Sutherland SK, Hudson BJ, Kemp GA. An epidemiological study of sea snake bites in the Australasian region. Med J Aust. 1991;154(4):266-269. PMID: 1987791
21. Adnet P, Lestavel P, Krivosic-Horber R. Neuroleptic malignant syndrome. Br J Anaesth. 2000;85(1):129-135. PMID: 10928000
22. Scharman EJ, Troutman WG. Prevention of kidney injury following rhabdomyolysis: a systematic review. Ann Pharmacother. 2013;47(1):90-105. PMID: 23324509
23. Huerta-Alardín AL, Varon J, Marik PE. Bench-to-bedside review: Rhabdomyolysis -- an overview for clinicians. Crit Care. 2005;9(2):158-169. PMID: 15774072
24. Prueksaritanont T, Tang C, Qiu Y, et al. Effects of fibrates on metabolism of statins in human hepatocytes. Drug Metab Dispos. 2002;30(11):1280-1287. PMID: 12386136
25. Better OS, Rubinstein I, Winaver JM, Knochel JP. Mannitol therapy revisited (1940-1997). Kidney Int. 1997;52(4):886-894. PMID: 9328926
26. Nelson DA, Deuster PA, Carter R 3rd, et al. Sickle cell trait, rhabdomyolysis, and mortality among U.S. Army soldiers. N Engl J Med. 2016;375(5):435-442. PMID: 27518661
27. Brogan M, Ledesma R, Coffino A, Chandra-Strobos N. Freehand-weight-induced rhabdomyolysis. Ann Intern Med. 1998;128(8):686. PMID: 9537947

Systematic Reviews

28. Melli G, Chaudhry V, Cornblath DR. Rhabdomyolysis: an evaluation of 475 hospitalized patients. Medicine (Baltimore). 2005;84(6):377-385. PMID: 16267412
29. Fernández WG, Hung O, Bruno GR, et al. Factors predictive of acute renal failure and need for hemodialysis among ED patients with rhabdomyolysis. Am J Emerg Med. 2005;23(1):1-7. PMID: 15672330
30. Safari S, Yousefifard M, Hashemi B, et al. The value of serum creatine kinase in predicting the risk of rhabdomyolysis-induced acute kidney injury: a systematic review and meta-analysis. Medicine (Baltimore). 2016;95(17):e3280. PMID: 27124009

Landmark Studies

31. Ward MM. Factors predictive of acute renal failure in rhabdomyolysis. Arch Intern Med. 1988;148(7):1553-1557. PMID: 3382301
32. Mikkelsen TS, Toft P. Prognostic value, kinetics and effect of CVVHDF on serum of the myoglobin and creatine kinase in critically ill patients with rhabdomyolysis. Acta Anaesthesiol Scand. 2005;49(6):859-864. PMID: 15954972
33. 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. PMID: 15213274
34. Knochel JP. Mechanisms of rhabdomyolysis. Curr Opin Rheumatol. 1993;5(6):725-731. PMID: 8117532

Additional Evidence

35. Gabow PA, Kaehny WD, Kelleher SP. The spectrum of rhabdomyolysis. Medicine (Baltimore). 1982;61(3):141-152. PMID: 7078398
36. Slater MS, Mullins RJ. Rhabdomyolysis and myoglobinuric renal failure in trauma and surgical patients: a review. J Am Coll Surg. 1998;186(6):693-716. PMID: 9632159
37. Veenstra J, Smit WM, Krediet RT, Arisz L. Relationship between elevated creatine phosphokinase and the clinical spectrum of rhabdomyolysis. Nephrol Dial Transplant. 1994;9(6):637-641. PMID: 7970093
38. Abassi Z, Hoffman A, Better OS. Acute renal failure complicating muscle crush injury. Semin Nephrol. 1998;18(5):558-565. PMID: 9754604

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Summary Metrics:

• Lines: 1,591
• Citations: 38 PubMed references
• Viva Scenarios: 4 (with model answers)
• OSCE Stations: 3 (with marking criteria)
• SAQ Questions: 4 (with model answers)
• Indigenous Health: Comprehensive coverage (Aboriginal, Torres Strait Islander, Māori)
• Remote/Rural: Extensive RFDS, retrieval, resource-limited considerations