Rhabdomyolysis

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Rhabdomyolysis
ICD-10	M62.8, T79.6
ICD-9	728.88
DiseasesDB	11472
MedlinePlus	000473
MeSH	D012206

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

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Overview

Rhabdomyolysis is the rapid breakdown of skeletal muscle tissue due to traumatic injury, either mechanical, physical, or chemical. The principal result is a large release of the creatine kinase (CK) enzymes and other cell byproducts into the blood system and acute renal failure due to accumulation of muscle breakdown products, several of which are injurious to the kidney. Treatment is with intravenous fluids, and dialysis if necessary.

History

First reports of rhabdomyolysis are thought to be from the Bible. The Book of Numbers reports many Israelites dying with “stained urine” during the exodus from Egypt. Historical reports indicate that consumption of quail that had eaten hemlock seeds on the island of Lesbos caused rhabdomyolysis. Quail related rhabdomyolysis still occurs in Greece and Algiers.

Causes

Injury leading to rhabdomyolysis can be due to mechanical, physical, and chemical causes:

• mechanical: crush trauma, burns, excessive exertion, intractable convulsions, choreoathetosis, surgery, compression by a tourniquet left for too long, local muscle compression due to comatose states, compartment syndrome, rigidity due to neuroleptic malignant syndrome
• physical: high fever or hyperthermia, electric current, extreme physical exertion (although most heavy exercise does not cause kidney damage)
• chemical: metabolic disorders, anoxia of the muscle (e.g., Bywaters' syndrome, toxin- and drug-related); various animal toxins, certain mushrooms like Tricholoma equestre, some antibiotics, statins, first-generation H1-receptor antagonists (e.g., diphenhydramine), alcohol, heritable muscle enzyme deficiencies, electrolyte abnormalities, infections, or endocrinopathies. Skeletal muscle relaxants that are consumed in overdose are rarely associated with this condition.

Any drug that directly or indirectly impairs the production or use of adenosine triphosphate (ATP) by skeletal muscle, or increases energy requirements so as to exceed ATP production, can cause rhabdomyolysis.

Complete Differential Diagnosis of Rhabdomyolysis

• Drugs

  • Alcohol
  • Amlodipine
  • Amphetamine
  • Cocaine
  • Heroin
  • Lipid Lowering Agents (gemfibrozil and statins)
  • PCP (phencyclidine)

• Exertion

  • Status Epilepticus/Asthmaticus
  • “Weekend Warrior”
  • Psychotic, Heat Stroke

• Metabolic

  • Hypokalemia
  • Hypophosphatemia
  • Hyperosmolar
  • Hyponatremia
  • Hypothyroid

• Direct Injury

  • Crush

    • Prolonged Immobilization
    • Burns
    • Frostbite
    • Electric Shock

• Infections(5% overall)

  • Viral

    • Various
    • 50% Influenza A.(higher risk of renal failure).

  • Bacterial

    • Legionella
    • Tularemia
    • Streptococcus
    • Clostridia

• Hereditary Defects

  • Enzyme

    • Classical is Mcardle’s Disease (myophosphorylase deficiency), many others.

  • Sickle Cell Trait

    • Presumable through muscle ischemia

Pathophysiology

Severe cases of rhabdomyolysis often result in myoglobinuria, a condition wherein the myoglobin from muscle breakdown spills into the urine, making it dark, or "tea colored" (myoglobin contains heme, like hemoglobin, giving muscle tissue its characteristic red color). This condition can cause serious kidney damage in severe cases. The injured muscle also leaks potassium, leading to hyperkalemia, which may cause fatal disruptions in heart rhythm. In addition, myoglobin is metabolically degraded into potentially-toxic substances for the kidneys. Massive skeletal muscle necrosis may further aggravate the situation, by reducing plasma volumes and leading to shock and reduced bloodflow to the kidneys.

Diagnosis

In general, the diagnosis is made when an abnormal renal function and elevated CPK are observed in a patient. To distinguish the causes, a careful medication history is considered useful. Testing for myoglobin levels in blood and urine is rarely performed due to its cost, but may be useful.

Often the diagnosis is suspected when a urine dipstick test is positive for blood, but no cells are seen on microscopic analysis. This suggests myoglobinuria, and usually prompts a measurement of the serum CPK, which confirms the diagnosis.

Approach to the Evaluation of Rhabdomyolysis

• Minimum Evaluation

  • Etiology certain:

    • CBC (complete blood count)
    • CK
    • Chemistries
    • Liver function tests
    • Urine pH

  • Consider looking for hypothyroidism and sickle cell trait.

• Extensive Evaluation:

  • If etiology is uncertain, can check:

    • Thyroid stimulating hormone
    • Erythrocyte glycolytic enzymes
    • CPT I/II in leukocytes
    • Serum carnitine
    • Organic acids in urine.

Symptoms

• Constitutional symptoms
• Muscle swelling stiffness, weakness of especially postural muscles (Only 50% will have primary muscular complaints)
• Decreased urine output and red urine
• Familial cases tend to be recurrent and can be precipitated by multiple factors (see below). Ask if symptoms are related to fasting or exercise. Symptoms can be prominent during first 10 minutes of exercise then get better with rest. (Second wind phenomenon).
• Anesthesia induced muscle problems: (myopathy, tetany)

Physical Examination

• Physical usually reveals no abnormalities: May see tenderness, weakness or atrophy

Laboratory Studies

• Urinalysis

  • Blood (+)
  • No red blood cells on microscopy. This situation is either hemoglobin in the urine or myoglobin. The serum will be pink with hemoglobinuria.

• Serum Markers

  • Elevated serum creatinine kinase

    • CK elevation: Generally accepted >5 times normal. Corresponds to about 200g of muscle.
    • Begins to rise 2-12 hrs after onset. Peaks 1-3 days in. Declines 3-5 days after the process stops.

  • Myoglobin

    • Myoglobin: Starts earlier than CK but clears faster, so serum and urine myoglobin useful early in course of the disease. Myoglobin is eventually urinated and/or converted to bilirubin.
    • All myoglobinuria is caused by rhabdomyolysis, but not all rhabdomyolysis causes myoglobinuria. Urine changes color when >1mg/ml.

  • LDH (lactic dehydrogenase)
  • Aldolase, AST (aspartate aminotransferase), ALT (alanine aminotransferase), carbonic anhydrase III (most specific)

Electrocardiogram

The EKG can show non specific ST T wave changes and T wave inversions. Despite the very high level of CK, the criteria for MI requires a 5% MB index (may vary by assay and gender).

Other Diagnostic Studies

• Muscle biopsy

  • Look for viral inclusions and examine histochemically for metabolic/biochemical deficiency.

Therapy

The main therapeutic measure is hyperhydration (by administering intravenous fluids), and, if necessary, the use of osmotic diuretics (to prevent fluid overload). Alkalinisation of the urine with bicarbonate reduces the amount of myoglobin accumulating in the kidney.

Hydration should be aggressive and patients may require as much as 10 liters of fluid. The fluid may be third spaced into muscle. Once the patient has been hyperhydrated, then forced diuresis is utilized. The urine can be alkalinized with D5W + 2/3 amp Bicarbonate. However, be aware that thisi may worsen hypocalcemia. Avoid replacement of calcium since it will chelate with phosphate. When rhabdomyolysis resolves, patients will often become hypercalcemic. Patients may require dialysis for hyperkalemia, uremia or volume overload.

As the electrolytes are frequently deranged, these may require correction, especially hyperkalemia (elevated potassium levels in the blood). Calcium levels are initially low (hypocalcemia), as circulating calcium precipitates in the damaged muscle tissue, presumably with phosphate released from intracellular stores. When the acute renal failure resolves, vitamin D levels rise rapidly, causing hypercalcemia (elevated calcium). Although this resolves eventually, high calcium levels may require treatment with bisphosphonates (e.g., pamidronate).

If the exacerbating cause includes overdose of skeletal muscle relaxants and/or tricyclic antidepressants, the treatment protocols include gastric decontamination. This procedure is fairly effective because the anticholinergic effects of tricyclics and cyclobenzaprine delay gastric emptying; and, therefore, it becomes possible to obtain tablet residues even after significant time elapse. Ventricular arrhythmias, QRS widening, or intraventricular conduction abnormalities should be treated with sodium bicarbonate 1 meq/kg IV bolus and repeated if arrhythmias persist. This should be followed by IV infusion of sodium bicarbonate to produce an arterial pH of 7.5; the mechanism of sodium bicarbonate's action in this role is unknown. However, sodium bicarbonate's beneficial effect on kidney function is known to be via the effects of alkalinisation both increasing the urinary solubility of myoglobin leading to its increased excretion and stabilizing ferryl myoglobin complex so preventing myoglobin-induced lipid peroxidation.

Complications

• Acute renal failure/Uremia: Estimated (1/3). Etiology multifactorial. Not only from pigmenturia. Has been seen with CKs as low as <20,000.
• Metabolic:

  • Hyperphosphatemia
  • Hyperkalemia: Can be to life threatening levels
  • Hypocalcemia: Thought to be caused by chelation of calcium phosphate into muscle. Eventually resolves and may overshoot.
  • Hyperuricemia

• Compartment syndromes: Compressive ischemia from swelling

Acknowledgements

The content on this page was first contributed by: Resident Report by Duane Pinto and Editor-In-Chief: C. Michael Gibson, M.S., M.D. [3].

References

• Dennis Ausiello; Goldman, Lee. Cecil Textbook of Medicine Single Volume e-dition -- Text with Continually Updated Online Reference. Philadelphia, PA: W.B. Saunders Company. ISBN 0721639011.CS1 maint: Multiple names: authors list (link)
• Edward Benz; David Weatherall; David Warrell; Cox, Timothy J.; Firth, John B. Oxford Textbook of Medicine. Oxford [Oxfordshire]: Oxford University Press. ISBN 0198569785.CS1 maint: Multiple names: authors list (link)
• Holt SG, Moore KP (2001). "Pathogenesis and treatment of renal dysfunction in rhabdomyolysis". Intensive care medicine. 27 (5): 803–11. PMID 11430535.
  Subsequent reply:
  * Korantzopoulos P, Galaris D, Papaioannides D (2002). "Pathogenesis and treatment of renal dysfunction in rhabdomyolysis". Intensive care medicine. 28 (8): 1185, author reply 1186. PMID 12400515.CS1 maint: Multiple names: authors list (link) * Llach F, Felsenfeld AJ, Haussler MR (1981). "The pathophysiology of altered calcium metabolism in rhabdomyolysis-induced acute renal failure. Interactions of parathyroid hormone, 25-hydroxycholecalciferol, and 1,25-dihydroxycholecalciferol". N. Engl. J. Med. 305 (3): 117–23. PMID 6894630.CS1 maint: Multiple names: authors list (link)
• de Meijer AR, Fikkers BG, de Keijzer MH, van Engelen BG, Drenth JP (2003). "Serum creatine kinase as predictor of clinical course in rhabdomyolysis: a 5-year intensive care survey". Intensive care medicine. 29 (7): 1121–5. doi:10.1007/s00134-003-1800-5. PMID 12768237.CS1 maint: Multiple names: authors list (link)
• Subramaniam PN Garcia CA Hill MK. ECG abnormalities in myoglobinuria: review of the literature. Am J Med Sci (1987 Jan) 293(1):45-9.
• Curry SC Chang D Connor D. Drug- and toxin-induced rhabdomyolysis. Ann Emerg Med (1989 Oct) 18(10):1068-84.
• Singh U Scheld WM. Infectious etiologies of rhabdomyolysis: three case reports and review. Clin Infect Dis (1996 Apr) 22(4):642-9.
• Poels PJ Gabreels FJ. Rhabdomyolysis: a review of the literature. Clin Neurol Neurosurg (1993 Sep) 95(3):175-92.
• Bessa O Jr. Alcoholic rhabdomyolysis: a review. Conn Med (1995 Sep) 59(9):519-21.

External links

• Baggaley, P. (1997). "Rhabdomyolysis". Retrieved 2007-10-14.

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