1. ICU18/10/2006

2. The Patient ● 66 yr male ● 4 days of malaise Paracetamol ● Collapse ● A&E via GP

3. The Patient ● 66 yr male ● 4 days of malaise Paracetamol ● Collapse ● A&E via GP ● Confused ● 'On the floor all night' ● Dysarthric ● Fast AF (HR188) ● Pyrexial 38.9 ° C ● R-sided weakness

4. The Patient ● 66 yr male ● 4 days of malaise Paracetamol ● Collapse ● A&E via GP ● Confused ● 'On the floor all night' ● Dysarthric ● Fast AF (HR188) ● Pyrexial 38.9 ° C ● R-sided weakness PMH HypercholesterolaemiaAF IDDM

5. EADU

6. Portsmouth Sign NORMAL PHYSIOLOGY SICK V. V..... !

7. EADU

8. ICU ● Sick ! ● Profoundly dehydrated ● Sub-arachnoid blood ● Pyrexial ● Anuric ● Gram +ve cocci

9. Rhabdomyolysis “A clinical and biochemical syndrome resulting from an injury which damages the integrity of the sarcolemma of skeletal muscle, leading to the release of potentially toxic muscle cell components into the circulation.”

10. History ● First described in 1881 ● Well recognised during London Blitz – Victims buried for 3-4 hrs – Renal failure / hyperkalaemia lead to death ● Significance of non-traumatic causes

11. Causes ● Congenital ● Acquired ● Deficiencies of glycogen(olytic) enzymes ● Abnormal lipid metabolism ● Other

12. Causes ● Congenital ● Acquired ● Trauma ● Ischaemic ● Toxic / Therapeutic ● Seizures/Exertion ● Sepsis ● Viral ● Environmental ● Metabolic

13. Drugs ! Paracetamol Statins

14. Pathophysiology ATP depletion Mitochondrial dysfunction Ca 2+ influx Ca 2+ and Na + /K + pump dysfunction Disturbance of lipid metabolism Disturbance of carbohydrate metabolism Tissue hypoxia Hypokalaemia Hypernatraemia Hyperosmolar state Enzyme deficiency Toxins CELL DEATH Osmotic swelling Activation of lipases and proteases Mechanical / thermal injury Lysis / Leakage of cell contents

15. Features Classical ● Skeletal muscle injury ● Dark urine ● Renal impairment Delayed ● 'Distracting' pathology ● Minimal muscle signs ● Metabolic derangement

16. Skeletal muscle ● 40-50% of body weight ● 70% of body potassium ● Largest concentration of Na + /K + ATP-ase Na + Ca + Water K + Purines Myoglobin

17. Metabolic changes ● Hyperkalaemia ● Hypocalcaemia – Hypercalcaemia ● Hypophosphataemia ● Myoglobinaemia ● Metabolic acidosis

18. Myoglobin ● 153 aa ● MW 17000 ● P 95 5.3kPa ● 3-80µg/dl ● 230mg/dl threshold ● Dissociates at pH<5.6

19. Nephrotoxicity ● Ferrihemate ● Myoglobin casts ● Vasoconstriction

20. Diagnosis

21. Treatment ● Volume resuscitation ● Diuresis – Furosemide – Mannitol ● Alkalinization ● Electrolyte correction ● Dialysis ● Compartment syndromes

22. Outcomes ● Mortality 5% ● CK predictive of ARF ● Good outlook ● Underlying causes ● Yellow card ?