10/21/13

Rhabdomyolysis

Claudia Goettler Vidant Heath/East Carolina University Greenville North Carolina

goals

• Discuss pathogenesis of rhabdo • Discuss treatment of rhabdo • Rhabdo and infusion therapy

Rhabdo and infusion therapy

• Ovid search • 1965 to current • Human and animal • All languages

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Rhabdo and infusion therapy

• Ovid search • 1965 to current • Human and animal • All languages

History of rhabdo

• Book of Exodus – Flight from Egypt – Mass poisoning – quail • Socrates – Extract of hemlock • First medical description – 1900’s – Meyer-Betz syndrome – Germany

London Blitz

• Starting 7 September 1940, London was bombed for 57 consecutive nights. • Over a one million London houses were destroyed or damaged • About 40,000 civilians were killed, almost half in London • 46,000 to 139,000 wounded in Britain

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History of rhabdo • Pathophysiology described – 1941--Bywaters and Beal – 5 cases entrapped – 1944—experimental evidence of myoglobin induced ARF – Prevented renal failure in 95/186 pts in second bombing with hydration and alkalinization

History of rhabdo

• Many wars – Major cause of mortality – Poor evacuation – No renal replacement until 1946 • Vietnam war – Decreased mortality – Rapid field evacuation – Intravenous therapy – dialysis

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But we have not come very far!

• Malarial “black water disease” • “white collar rhabdo” • Raver’s HematuriA • “pseudo-crush” syndrome in torture

definition

• Breakdown of striated muscle • Release of breakdown products into the blood stream and extracellular space

population • Mostly pressure induced – Compression injury 39% – 27% surgery, ave time 7.5 hrs – Can occur within 30 minutes – Mostly compartment syndrome (93%) • Seizures 24% • Infection 5% • Mostly males (5:1) • Mostly intoxication (62-67%)

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Direct injury Trauma Surgery Found down Explosion causes Immobility Assault Straight jacket crush Spinal cord injury Pneumatic antishock garments Compression Excessive activity Seizure Delirium tremens Tetanus Posturing Congo drumming Keyboard operation Boot camp marathons

causes temperature Natural substances Malignant hyperthermia Hemlock Heat stroke Quail Neuroleptic malignant syndrome Tricholoma mushrooms Hypothermia Viper venom Seritonin syndrome Carbon monoxide poisoning Licorice ingestion Bee venom Spider bite Scorpion sting Giant desert centipede Poison dart frog poisoning Kidney beans ELECTRICITY Peanut oil ELECTROCUTION

LIGHTNING STRIKE

ELECTRICAL CARDOVERSION

causes

Recreational drugs

Heroin toxins Alcohol Cocaine Methanol PCP Ehtylene glycol Ecstasy Toluene Caffeine Hydrocarbon inhalation Amphetamines Lsd Toluene Methadone mushrooms

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Legionella Shigella causes Influenza a/b Salmonealla Coxackieirus Strep pneumonia infection Epstein-barr Staph aureua Adenovirus Herpes symplex virus Echovirus Varicella zoster virus Hiv West inle virus Cytomegalovirus Group a strep Enterovirus Clostridum Bacillus Enterobacter Borellia burgdorferi Francissella tularensis Brucella H flu Campylobacter Listeria coxiella Aspergillus E coli candida

Paracetamol causes Penacillamine Pentamidine Salcyalates drugs Succinylcholine Theophylllne Terbutaline Statins Thiazides Fibrates Vasopressin Benzodiazepines Quinine Barbiturates Paralytics Antihistamines Cyclic Amitryptaline antidepressants Haldol Interferon Lithium Valproate Ssri Nicotinic acid Neuroleptics Levodopa Propofol Trimiethoprin-sulfa Colchicine

causes Rhem d/o Hereditary enzyme d/o Mcardle’s disease Polymyositis Tarui disease Dermatomyositis Phosphoglycerate mutase deficiency Sjogren’s syndrome Carnitine palmitoyltransferse deficiency Systemic Lupus Erythematosis Phosphorylase kinase Vascultitis Lactate dehydrogenase Muscular dystrophy Carnitine deficiency Paraneoplastic necrotizing Myoadenylate deaminase deficiency myopathy Duchenne’s muscular dystrophy Brody myopathy Debrancher enzyme Miyoshi myopathy ETF dehydrogenase deficiency Myofilamentous cylindrical spiral Trifunctional enzyme deficiency myopathy Aconitase Deficiency GSPDHdeficiency Conenzyme q deficiency

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MISCELANEOUS causes Electrolyte d/o SEPSIS COMA Dka Nonketotic hyperosmolar coma SEVERE DYSTONIA Hypokalemia ACUTE MANIA Hyphosphatemia THROMBOEMBOLISM Hyponatremia Hypernatremia SICKLE CELL DISEASE Refeeding syndrome CARDIAC ARREST Respiratory alkalosis starvation IDIOPATHIC PAROXYSMAL MYOGLOBINURIA endocrinopathies DIARRHEA HYPEREMESIS GRAVIDARIUM Primary hypoaldosteronism Severe hypothyroidism WATER INTOXICATION Severe hyperthyroidism ATRIAL MYXOMA pheochromocytoma PANCREATITIS

clinical symptoms

Clinical triad Typical symptoms • Muscle pain • Fever • Weakness • Malaise • Dark colored urine • Tachycardia • Found in only 10% • Nausea/vomiting – More than 50% do not have pain and/or weakness

diagnosis

• High index of suspicion • Many patients have concomitant drug and alcohol use • Muscle swelling may not be apparent until after hydration

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Dark urine: diagnosis

Myoglobinuria hematuria • Clear • Cloudy • Dip positive for blood • Dip positive for blood • Ua negative for red cells • UA positive for red cells • Ua may have myoglobin casts and dead epithelial cells

diagnosis • Laboratory elevation of CPK – Half life of 1.5 days – Gold standard of diagnosis – Cpk greater than 1000 • Urine or serum myoglobin – Half life of 2-4hrs – Variably predictive of renal failure – Variable turn around time – Present in urine only 19% – More expensive ($97 vs $15 for CK/2004)

• Muscle injury causes pathophysiology • Influx of calcium ions causes • Intensive Interaction between actin and myosin causes • Cell protease release causes • muscle fiber necrosis causes • Release of myoglogin, CK and phosphates

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Clinical complications

Electrolyte Disorders dysrhythmias

• Hyperkalemia • Troponins may be elevated • Early hypocalcemia • Serial monitoring of electrolytes • Late hypercalcemia and EKG • Acidosis – Lactate and sulfate

Clinical complications

Hepatic dysfunction

Disseminated intravascular coagulation – Cause unknown – Rare – Thromboplastin – Usually transient – Tissue plasminogen – Hypoalbuminemia is bad prognostic sign – Rare – Follow serial coag labs

Compartment syndrome

• Cause and Effect • Reperfusion increases swelling and increases cell death • Persistent source of myoglobin until released • Serial compartment checks

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Compartment syndrome

• surgical compartment release • Serial debridements of necrotic muscle

Renal Failure? • Myoglobin precipitates in the renal tubules • LEVEL OF CK PROPORTIONAL TO AMOUNT • Myoglobin casts OF MUSCLE BREAKDOWN – May cause low flow • RISK OF RENAL FAILURE – May be result of low flow EXISTS FOR CK GREATER • Myoglobin precipitation 5000 depends on pH of urine • HIGHER RISK WITH HYPOVOLEMIA AND OR – Much more in acidic urine HYPOTENSION – Much less in alkaline urine

Renal Failure!

• Cytokine acitvation by myoglobin casues renal vasoconstriction and ischemia • Reperfusion injury worsens cytokine release

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Renal Failure!

• Myoglobin causes direct cytotoxicity to renal cells • Urate preciptates and causes casts with obstruction • Free radical oxidative damage

treatment • Volume • Forced diuresis--Urine output 3 cc/kg/hr • Volume • May need 10 to 18 liters in • Volume 24 hrs • More volume • Avoid potassium containing fluids • Avoid hyperchloremic acidosis

treatment

Alkalinization? Diuresis?

• Bicarbinated fluids • No loop diuretics--aciduria – Urine ph greater than 6.5 • Acetezolamide – Buffer blood ph – Alkalinizes urine – Prevent precipitation of myoglobin – case studies – No proof of reducing renal failure • Use mannitol to induce diuresis – Does not produce aciduria – Free radical scavenger – May help compartment syndrome – Can cause osmotic nephrosis

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Renal Failure!!

• Acute renal failure 33% • Delayed initiation of volume • Related to peak Ck levels loading (after 6-12 hrs) does – Greater than 15,000 has 72% not protect renal function rate of ARF • Pre-extrication hydration is • Requires dialysis in 50-70% Indicated • Cause of 5-7% of all ARF in • Dialysis US – does not remove myoglobin – For standard renal failure indications

• Overall mortality 8% mortality • Due to Multisystem organ failure • Acute renal failure increases mortality from 17-22% to 51-59% • Disaster Relief Task Force (1995) – Dialysis attack team— – decreased mortality to 19% for arf after mass casualty

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Treatment summary

• Treat the cause! • Hydrate like crazy • +/- bicarb • +/- Mannitol

Bibliography • Al-Ismaili, Z., Piccioni, M., & Zappitelli, M. (2011). • Malinoski, D. J., Slater, M. S., & Mullins, R. J. (2004). Rhabdomyolysis: pathogenesis of renal injury and Crush injury and rhabdomyolysis. Critical Care Clinics , management. Pediatric Nephrology , 26 (10), 1781-8. 20 (1), 171-92. • Better, O. S., & Abassi, Z. A. (2011). Early fluid • Parekh, R., Care, D. A., & Tainter, C. R. (2012). resuscitation in patients with rhabdomyolysis. Nature Rhabdomyolysis: advances in diagnosis and treatment. Reviews Nephrology , 7 (7), 416-22. Emergency Medicine Practice , 14 (3), 1-15. • Camp, N. E. (2009). Drug- and toxin-induced • Singh, U., & Scheld, W. M. (1996). Infectious etiologies Rhabdomyolysis. Journal of Emergency Nursing , 35 of rhabdomyolysis: three case reports and review. (5), 481-2. Clinical Infectious Diseases , 22 (4), 642-9. • Cervellin, G., Comelli, I., & Lippi, G. (2010). • Thomas, R. (2010). Towards evidence based emergency Rhabdomyolysis: historical background, clinical, medicine: best BETs from the Manchester Royal diagnostic, and therapeutic features. Clinical Chemistry Infirmary. Bet 1. Rhabdomyolysis and the use of sodium & Laboratory Medicine , 48 (6), 749-56. bicarbonate and/or mannitol. Emergency Medicine • Criddle, L. M. (2003). Rhabdomyolysis. Journal , 27 (4), 305-8. Pathophysiology, recognition, and management. Critical • Visweswaran, P., & Guntupalli, J. (1999). Care Nurse , 23 (6), 14-22, 24-6, 28 passim; quiz 31-2. Rhabdomyolysis. Critical Care Clinics , 15 (2), 415-28. • Khan, F. Y. (2009). Rhabdomyolysis: a review of • Warren, J. D., Blumbergs, P. C., & Thompson, P. D. the literature. Netherlands Journal of Medicine , 67 (2002). Rhabdomyolysis: a review. Muscle & Nerve , 25 (9), 272-83. (3), 332-47. • Wilson, S. (2006). Rhabdomyolysis made easy. Australian Nursing Journal , 14 (2), 21-3.

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