Bishan Rajapakse – ED Registrar

Wollongong Hospital ED Reg teaching - 3/10/12

Rhabdomyolysis

Image courtesy of Dr Carl Oller https://vimeo.com/34408361

Rhabdomyolysis - Overview

Rhabdomyolysis in ACEM fellowship curriculum

Clinical Case – ‘teaser’ “Rhabdo facts”

Epidemiology, causes, pathophys &management

Clinical Cases – ‘pleaser’ Discussion Summary – take home points

ACEM fellowship syllabus

7-10% of ARF is 2˚ to Rhabdo

Case 1 – ‘Young crush’

26yo male Crush injury to R arm, 4x4 rolled back onto R arm

whilst under car Posterior compartment R Arm bruised and swollen Numbness and paraesthesia Suspected brachial plexus, CT Neck unremarkable

Labs results in resus (16/9/12 19:36)

Ph 6.92, Lactate 21, Cr 96 CK 419

Urine dipstick – Haematuria ++ Urine myoglobinuria not ordered

What do you think?

Is Rhabdomyolysis present? How do we make the diagnosis? What are the key features?

If it is Rhabdomyolysis? What is the management? What are his risks of ARF & death?

Progress

2nd CK 4 hours later CK 2,353 U/L

Admitted under trauma surgery Aggressive fluids, good UO

Serial CKs 17/9/12

03:11 – 3,999 U/L 06:00 – 4,604 U/L 14:30 – 6,275 U/L, Na 142, K 4.2, Ur 5.4, Cr 96

Pain and paraesthesia improving day 2 Patient discharged against medical advice!!

Rhabdomyolysis Rhabdmyolysis = ‘destruction of striated muscle’

Muscle breakdown and necrosis, Leaking of intracellular constituents into Circulation & ECF

Severity Ranges from Asymptomatic illness (with mild CK) to life threatening

condition extreme CK, Electrolyte imbalances, ARF & DIC

Causes Most commonly – muscular trauma Less commonly – muscle enzyme deficiencies, electrolyte abnormalities

Presentation Limb weakness, myalgia, swelling and tea coloured urine Commonly assoc with myoglobinuria, if severe can cause ARF

Investigations - CK >5,000 indicates serious muscle injury Management

ALS (airway breathing & circulation) Followed by measures to preserve renal function=vigorous hydration Use of alkalysing agents and osmotic diuretic – common by unproven

benefitHuerta-Alardin A, Varon J, Marik P. Bench-to-bedside review: Rhabdomyolysis -- an overview for clinicians. Critical Care. 2005;9(15774072):158-169.

Rhabdomyolysis - epidemiology Seen in 85% of patients with traumatic

injury Common in Earthquakes Acute Kidney injury in 10-50%

7-80% mortality Outcome generally good, but…

Co-existing valculopathy – mortality 32% In ICU patients – 22% mortality if RF

absent, 59% if RF present

Categories of cause

Physical Trauma (Crush syndrome) Exertion (strenuous exercise, siezure, AWS) Muscle hypoxia (limb compression, prolonged

immobilisation or LOC, major artery occlusion) Non Physical

Genetic defects (glycolysis or glyconeogenesis) Infections (legionella, malaria, herpes) Body temp changes Metabolic and electrolyte disorders (Na,K) Drugs and toxins (cocaine, statins) Endocrine/Autoimmune causes (polymyositis) Idiopathic

Clinical Illustrations

Dengue viral myositis 17 yo boy, fever and myalgia Day 4 developed oliguria, CK 60,000 (rpt 90,000) Reduced Calcium, elevated Phospate Oliguria and refractory hypotension – leading to

death Viral infections Rhabdomyolyis

Young male, heroin OD Elevated CK, Hyperkalaemia, Hypocalcaemia,

Sunderalingam et al “Dengue viral myositis complicated with rhabdomyolyis and super infection of methicillin resistant Staphylococcus aureus” awaiting publication

Pathophysiology

Method (and mechanism) of cellular destruction Direct injury to cell membrane

(crushing, tearing, dissolving) Muscle cell hypoxia leading to depletion ATP

(Anaerobic conditions, shock states, vascular occlusion and tissue compression)

Electrolyte disturbance disrupting the Na/K

pump (K :vomiting diarrhoea, extensive diuresis, Na: water intoxication)

Pathophysiology

Huerta-Alardin A, Varon J, Marik P. Bench-to-bedside review: Rhabdomyolysis -- an overview for clinicians. Critical Care. 2005;9(15774072):158-169.

How does Myoglobin cause ARF?

Perutz (Hb), Kendrick (Myoglobin)

Myoglobin

Haemoglobin

Myoglobinuric ARF

2 Cruicial Factors-Hypovolaemia/dehydration-Aciduria

ARF

Haem protein toxicity-Renal vasoconstriction-Diminished renal circulation-Intraluminal cast formation & direct haem protein-induced cytotoxicity

“in absence of hypovolaemia & aciduria heme proteins have minimal nephrotoxic effects”

Cast formation enhanced by urine Ph

It is suggested that ARF is caused by tubular obstruction

Pigmented Cast formation

The New England journal of medicine. 2009;361(19571284):62-72.

Investigations

CK levels >5000 U/L related to ARF (norm 45-260) Rises within 12 hrs, peak 1-3 days, declines 3-5days post muscle

injury After peak drops by 40% per day (T ½ 1.5d)

Myoglobinuria Urine dipstick positive for “blood” no red bood cells in urine sediment

Electrolytes K+, PO4, Uric acid, LDH, ALT, AST, carbonic anhydrase III Ca++, (initially low as moves into cells, may increase later)

Coagulation studies DIC may develop

Tox screen Etoh commonly associated with diagnosis Heroin and other illicit drugs

Urinalysis

Management

Advance Life Support Aggressive fluid therapy Urinary Alkalinisation +/-Mannitol Follow up CK and Electrolytes If suspect ARF

Cardiac monitoring Dialysis if necessary

Commonly used but controversial-Little clinical evidence

-Rationale “preserving urine flow in ARF may reduce damage”

-Useful if become fluid overloaded whilst being treated for Rhabdomyolysis

Case 3 – Could it be renal colic

65 year-old male presenting with right-sided flank pain radiating to the groin.  The following CT scan was taken to confirm a presumed diagnosis of renal colic:

http://lifeinthefastlane.com/2009/12/renal-riddle-001/

CT scan

-Right sided retro peritoneal blood- AAA

Patient went for emergency AAA repair

Routine post op biochemistry

• increased urea and creatinine (with urea-to-creatinine ratio)• hyperphosphataemia, hypocalcaemia, hyperkalaemia • increased CK (usually to greater than 40,000)

http://lifeinthefastlane.com/2009/12/renal-riddle-001/

Rhabdomyolysis - treatment

aggressively correct hypovolaemia Target UO 2-3ml/kg/hr

Monitor K closely and treat hypokalaemia Alternate N/Saline with 1L litre of D5W

Avoid K & lactate containing solutions 100mmol of HCO3 if urine pH <6.5

“Consider” mannitol, up to 200g/day, not > 800g total dose.

Consider haemodyalysis if resistant hyperkalemia of more than 6.5mmol/L

Bosch X, Poch E, Grau JM. Rhabdomyolysis and acute kidney injury. The New England journal of medicine. 2009;361(19571284):62-72.

Hyperkalaemia (>5.5) in Rhabdo Check K every 4 hours when CK>60,000

Treat hyperkalaemia aggressively ECG

CaCl or CaGluconate Consider cardiac monitoring if K>6 Check plasma Calcium (aggravates hyperK)

K>6 1) Insulin and glucose, Salbutamol, 2) NaHCO3 if acidaemia (may worsen HypoCa, not efficacious as

no1 above) Optional - Remove potassium

Resins (sodium polystyrene sulfonate) Haemodialysis Loop diuretics (only once fluid level has been expanded

The New England journal of medicine. 2009;361(19571284):62-72.

Summary

Rhabdomyolysis – muslce necrosis Limb weakness, myalgia, swelling and tea coloured

urine Can be life threatening, common cause of ARF (7-10%)

Multiple causes – Physical and Non Physical Most commonly crush injury & immobility Can be drugs, tox

CK rise >5,000 Rx – Vigorous hydration – protect kidneys

Monitor electrolytes & correct hyperkalaemia Alkalinisation if Urine ph<6.5, Mannitol if fluid overload

References/Acknowledgements Critical Care

Huerta-Alardin A, Varon J, Marik P. Bench-to-bedside review: Rhabdomyolysis -- an overview for clinicians. Critical Care. 2005;9(15774072):158-169.

NEJM Bosch X, Poch E, Grau JM. Rhabdomyolysis and acute kidney injury. The New England

journal of medicine. 2009;361(19571284):62-72.

LTFL Paul Young (Intensivist Wellington, NZ) http://lifeinthefastlane.com/2009/12/renal-riddle-

001/

Free EM talks (Joe Lex) Garry Gaddis (Orthopaedic Surgeon) – talk “Rabdomyolysis & compartment syndrome” Cancun

Trauma conference 2008 (http://freeemergencytalks.net/2010/04/gary-gaddis-rhabdomyolysis-and-compartment-syndrome/)

Personal discussion/case reports unpublished data Darren Roberts (Clinical Pharm and Tox, UK) Vinothan Sunderalingam (Physician Trainee, Sri Lanka) Jorge Sesperz (Trauma researcher)

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(http://freeemergencytalks.net/2010/04/gary-gaddis-rhabdomyolysis-and-compartment-syndrome/)

Discussion: …..Time for your thoughts!

Extra slides

BUN : Cr Ratio

http://en.wikipedia.org/wiki/BUN-to-creatinine_ratio

BUN: Cr ratio is low in Rhabdomyolysis

Mannitol & Loop diuretics??

Limited evidence for Diuretics preventing acute kidney injury Diuretics decreasing Mortality

Diuretics are useful if become fluid overloaded whilst being treated for Rhabdomyolysis

Gary Gaddis MD, Orthopaedist “Rhabdomyolysis & Compartment Syndrome

Talk at Orthopaedic Emergencies and Trauma (Cancun 2008) Pod cast from Joe Lex @ http://freeemergencytalks.net/

Huerta-Alardin A, Varon J, Marik P. Bench-to-bedside review: Rhabdomyolysis -- an overview for clinicians. Critical Care. 2005;9(15774072):158-169.