Question 1

a)

Causes (2 marks; 0.5 marks per cause. No additional marks for multiple causes under same heading. Examples of medications/infections etc. required for marks.)

1.    Trauma - Crush injury, electrocution, extensive burns, compartment syndrome
2.    Exertional - Prolonged exertion, refractory seizures, severe agitation
3.    Medications - corticosteroids, statins, antipsychotics, neuroleptics
4.    Toxins - methanol, ethylene glycol, barbiturates, amphetamine, MDMA, CO poisoning, cyanide, snake, spider envenomation
5.    Body temperature changes - Heat stroke, malignant hyperthermia, malignant neuroleptic syndrome, hypothermia
6.    Infections - Influenza A and B, coxsackievirus, Epstein–Barr virus, primary HIV, legionella
7.    Rarer causes – electrolyte disturbances (hypoPO4, K, Ca, Na), endocrine (HONK etc.)
 

b)

Review history to identify risk factors or causes. .History of pre-existing renal injury or conditions that might predispose to acute kidney injury or conditions that might predispose to it.

History of Trauma, seizures, immobility, drug exposure, muscle pain, dark coloured urine,

Clinical examination/assessment: Muscle compartment swelling, tenderness, weakness, fever, myoglobinuria, peripheral perfusion

Laboratory Tests

Elevated CK

Renal dysfunction Cr – elevated; urea:Cr ratio may be decreased

electrolyte abnormalities (hyperkalemia, hypocalcemia, hyperphosphataemia, hyperuricemia, lactic acidosis). Elevated AG – due to phosphates and organic acids released from muscle

Further investigations will depend on need to further identify underlying cause e.g. urine drug screen, blood alcohol, glucose, TFTs etc

c)

Management (5 marks)

Stop further skeletal muscle damage

Interventions will vary depending on cause; e.g. discontinuation of medications, control agitation, treat infection, correct metabolic abnormalities, cool or warm, surgery etc

Rapidly identify life or limb-threatening complications

If compartment syndrome needs orthopaedic consultation – monitor pressures +/- decompressive fasciotomy

Treat any significant electrolyte abnormalities, e.g. hyperkalaemia or hypocalcaemia Prevent acute renal failure

Early and aggressive volume resuscitation with 0.9% N/saline. Dilutes nephrotoxins and promotes renal tubule flow. Urinary alkalization, forced mannitol diuresis and frusemide have been described; (candidates were not given marks for mentioning these or penalised for omitting them)

Renal replacement therapy: for usual traditional indications (hyperkalaemia, metabolic acidosis, volume overload and uraemia). Not advocated for myoglobin removal

Examiners Comments:

Candidates are reminded to read the question carefully; some answers included investigations such as CT scans and exploratory surgery, which are not “laboratory tests”.

Well answered overall.

Discussion

a)

Though the question asked for only five causes, this table was compiled so as to accommodate a range of wacky differentials. It is pleasing to see the examiners tip their hand- they specify that only five classes of causes would yield full marks, i.e. one would score poorly if one just gave five different kinds of embolic phenomena. 

Causes of Rhabdomyolysis

Vascular causes	Embolic phenomena Vascular insufficiency
Infectious causes	Bacterial causes S.pyogenes or C.perfringens infections Necrotising fasciitis Viral causes: Influenza A and B HIV Cioxsackie virus Epstein-Barr virus Echovirus Cytomegalovirus Adenovirus Herpes simplex Parainfluenza Varicella zoster
Neoplastic causes	Paraneoplastic cause of autoimmune myositis
Drug-related causes	Antipsychotics (neuroleptic-malignant syndrome) SSRIs (serotonin syndrome) Statins Alcohol Cocaine MDMA Volatile anaesthetics (malignant hyperthermia) Propofol infusion syndrome Imatinib, sunatinib (tyrosine kinase inhibitors) Daptomycin (Hohenegger, 2012) Envenomation by spiders, hornets, bees and snakes
Idiopathic causes	Extreme exertion, eg. strenuous exercise Seizures
Congenital causes	Congenital abnormalities of glycogenesis, lipid metabolism, mitochondrial disorders, and G6PD deficiency
Autoimmune causes	Myositis and dermatomyositis
Traumatic causes	Crush injury Prolonged immobilisation, eg. for prolonged surgery as in Question 5 from the first paper of 2017 Heat stroke Hypothermia (eg. frostbite) Compartment syndrome Trauma to arteries supplying the extremities
Endocrine causes	HONK DKA Hypokalemia

b)

"History and clinical examination, and what specific laboratory investigations" allocates only 10% of the mark to each aspect, which means one cannot afford to dwell too long on this answer.

• Historical features: Trauma, seizures, immobility, drug exposure
• Symptoms:- muscle pain, decreased mobility, weakness, tea-coloured urine
• Signs: Muscle compartment swelling, tenderness, weakness, fever
• Biochemistry: Elevated CK, AST, LDH, urinary myoglobin; renal dysfunction and electrolyte abnormalities (particularly hyperkalemia, hypocalcemia, hyperphosphataemia, hyperuricemia, lactic acidosis). DIC may also result.

c)

• Commence IV fluids within 6 hours - as early as possible
• Aim for a urine output greater than 300ml/hr
• Manage or prevent compartment syndrome (invasive compartment pressure monitoring or fasciotomy)
• Use of sodium bicarbonate is only indicated to correct systemic acidosis. There is no evidence for any benefit in rhabdomyolysis-induced AKI except for some uncontrolled case series, which does not stop people from recommending it anyway. It appears in the 2010 college answer, which pre-dates this 2013 meta-analysis. The savvy trainee seeking to remain in the good books with examiners who use forced alkaline diuresis will want to mention this therapy in their answer, with the caveat that it is may not be helpful, but is also probably not harmful.
• Free radical scavengers have been recommended historically, without much evidence to support their use (allopurinol, pentoxifylline)
• Avoid replacing calcium: it may exacerbate muscle injury (Chatzizisis et al, in 2008, believed that it would "intensify the accumulation of calcium in the muscular tissue and consequently reinforce the mechanism of rhabdomyolysis")
• Use of mannitol is only indicated if urine output >300ml/hr cannot be maintained 
• Dialysis may be commenced to improve the removal of myoglobin, if a high-permeability membrane filter is available. Even if it is not, standard CVVHDF seems to decrease the risk of renal injury.