Rhabdomyolysis

Dr. Muhamed Al Rohani, MD. FISNConsultant Nephrologist

Dibba Hospital, Dibba UAE Associated Prof. UST hospital, Sanaa, Yemen

Hmmm…That’s weird...• “Rhabdomyolysis was first reported in 1881, in the German

literature” (Abbeele, Parker, 1985).• “Rhabdomyolysis was first described in the victims of crush injury

during the 1940-1941 London, England, bombing raids of World War II” (Craig, 2006).

• The overall mortality rate for patients with Rhabdomyolysis is approximately 5%

• Rhabdomyolysis is more common in Males than in Females• May occur in infants, toddlers, and adolescents.

Case report: A 19 year young female experienced 2 episodes of rhabdomyolysis, while playing ‐

competitive ultimate Frisbee. The first episode occurred following a 5 hr Frisbee ‐tournament her playing time was to be 3 hours.at the end of this game she developed severe diffuse muscle soreness, she was unable to straight ten her elbows and knees, it was difficult to stand because of soreness in her back muscles.

Her urine became brown-colored but she did not seek medical attention, the muscles soreness resolved after 3 days.

Her second episode of rhabdomyolysis occurred 2 weeks later. This time she participated in a 2-hr Frisbee scrimmage followed by a 2-hr karate class. Shortly thereafter, she experienced severe muscle cramping, change in urine to black, and sought medical attention. The following day, her CK was 59,000 U/L and increase more in the following days and urine analysis showed heam and myoglobin by dipstick test. rise in s. crea, to 695 umol/l with anuria within 3 days the s. K was 6.3 and metabolic acidosis.

The AKI and failure was established and hemodialysis done, after 2 weeks the urine output became normal and before that the CK fell to 266, after stabilization of her conditions she was discharged and she was advised to avoid that kind support or physical activities.

She tolerated workouts of up to 2 hours without difficulty. She was a sprinter, but could run 2 miles with no problem. It was subsequently determined that she had a genetic predisposition for rhabdomyolysis.

Case presentation: An 84-year-old male patient was admitted to the ED with: Generalized weakness and reduced consciousness for two days. He had a history of

Alzheimer’s disease for one year and he had taken donepezil 5 mg daily for two months. He had no other diseases and he had not taken any other medications. He had no history of

trauma, convulsion, previous fall, or alcohol intake. The physical examination revealed apathy, loss of cooperation, and decreased muscle

strength. Temp. 36.8°C, BP140/90 mm/Hg, and pulse rate 88 bpm. He had bilateral moderate pretibial edema.

Lab. studies: urea: 128 mg/dL; s. crea: 6.06 mg/dL; AST: 93 U/L; CK: 3613; Ca: 8.1 mg/dL; phos: 4.9 mg/dL; Na: 149 mmol/L; K: 4,3 mmol/L; albumin: 3.7 g/dL; LDH: 349 U/L; Hb: 14.2 g/dL; fT3: 3.5 (N: 1.71–3.71 pg/mL); fT4: 1.35 (N: 0.7–1.48 ng/dL); TSH: 2.04 (N: 0.35–4.94 uIU/mL).

Urinary test: 1+ protein and 3+ Haem. RBC, and 2-3 WBC. ABG: PH: 7.44, PCO2: 23 mmHg, PO2: 151 mmHg, SO2: 99.5%, and HCO3: 19 mmol/L.

RFT was normal 2 months ago. The renal USG was normal. Echocardiography was performed and ejection fraction was 60%, left ventricle was concentric hypertrophic, and a minimal pericardial effusion was reported.

The patient was diagnosed as ARF. Donepezil was discontinued. There was no indication for emergent hemodialysis. Intravenous hydration therapy was given. The patient’s renal function tests improved gradually and were normal after 12 days of the treatment. He was discharged with complete recovery.

What is Rhabdomyolysis• Rhabdomyolysis is the breakdown of muscle fibers, specifically of the sarcolemma of

skeletal muscle, resulting in the release of muscle fiber contents (myoglobin) and other intercellular proteins and electrolytes into the circulation.

• Typically; patient has muscle pain and creatine kinase (CK) levels are markedly elevated, the myoglubinuria my occur

• The clinical conditions ranges from asymptomatic to life threatening hyperkalemia and AKI

Skeletal Muscle Cell

The sarcolemma is the cell membrane of a muscle cell. The membrane is designed to receive and conduct stimuli

Source: (Muscle Anatomy & Structure, 2007)

General Mechanism of Rhabdomyolysis:• Source: Adapted from Landau et al. 2012.

Rhabdomyolysis Causes

Traumatic

Crush injury and trauma earthquakes, collapsed buildings road traffic collisions Compartment syndrome alcohol – associated immobility poor perioperative positioning prolonged collapse Electrocution

Non-traumatic

Exertional (Strainful muscle exercise) Body temperature changes Drugs / toxins / alcohol/ cocaine Coma Infection: Bacteria (strep pyogenes, staph aureus) Virus (HIV, CMV, influenza A and B, …..)Metabolic and electrolytes disordersGenetic / idiopathic

Selected drugs that cause rhabdomyolysisAcetaminophenAmoxapine Amphetamines Amphotericin BAnticholinergics Antidepressants Antihistamines Antipsychotics Baclofan Barbiturates BenzodiazepinesBetamethasone Butyrophenones

CaffeineCarbone monoxide Chloral hydrate Chlorpromazine CocaineDexamethasone DiazepamDiuretics Ecstasy EthanolFluoroacetateGlutethimide Heroin

HydrocarbonsHydrocortisoneHydroxyzine Inhalation anesthetics IsoniazidIsopropyl alcohol Ketamine hydrochloride LicoriceLithium LorazepamLysergic acid diethylamideLoxapine Marjuana

MethaphetamineMethanol MineralocoricoidsMorphineNarcotics Neuroleptics Phencyclidine Phenonarbital PhenothiazidesPhenytion Predisone Salicylate Statins

Serotonin antagonistsStrychnineSuccinylcholine Sympathomimetics TheophylineSeptrineVasopressin

Alcohol is associated with rhabdomyolysis, 24% of pts presented with cocaine-related disorders to ED, developed rhabdomyolysis 60% of pts with rhabdomyolysis has positive tests of cocaine or amphetamine Statins can lead to rhabdomyolysis secondary to myopathy meanly Cerivastatin, which was 16

– 80 times higher than other statins, and it was withdraw in 2001

How to diagnose rhabdomyolysis • Clinic Presentation:

• Muscular weakness, myalgia, swelling tenderness, stiffness, • Fever, feeling of nausea, vomiting, tachycardia, dehydration • Oliguria or anuria, in connection with AKI

• Laboratory findings: • CBC includine HB, Hct, and platelets • Serum: , creatine kinase, myoglobin, lactate dehydrogenase, creatinine, BUN, acid-base balance,

coagulation factors , S. electrolytes: K, Phos, Ca. • Urine: myoglobin or positive dipstick test without any RBC, protein

• Radiography: • Computed tomography (CT) of the head (altered sensorium, significant head trauma, seizure, neurologic

deficits of unknown origin) • Magnetic resonance imaging (MRI; assessment of myopathy)

• Electrocardiography (ECG)

• Measurement of compartment pressures

• Muscle biopsy

• Immunoblotting, immunofluorescence, and genetic studies

Creatine kinase: >5x ULN (5000-100,000) Rises within 2 to 12 hours following the onset of muscle injury and reaches its maximum within 24 to 72 hours. A decline is usually seen within 3 - 5 days of cessation of muscle injury.

Elevation in serum creatine kinase (> 5x ULN) acute neuromuscular illness or dark urine without any other symptoms.

Complications of Rhabdomyolysis

Compartment syndrome Muscle ischemia Fluid sequestration Hypovolemia

Fluid sequestration

Hypercalcemia Efflux from damaged muscles

HypocalcemiaInward flux and binding to phosphatidylinositol Avoid giving Calcium

Hyperphosphatemia Muscle breakdown

Hyperkalemia Release from cells Decrease of clearance (AKI)

Disseminated intravascular coagulation (late)Thromboplastin release Thrombotic microangiopathy

Acute Kidney Injury Direct effect of myoglobin Hypovolemia

Manifestations of rhabdomyolysis • Fluid and electrolyte abnormalities:

With or without AKI or Hepatic Injury

• Hyperkalemia: Cardiac dysrhythmias and cardiac arrest

• Hypovolemia: results from “third-spacing” due to the influx of extracellular fluid into injured muscles.

• Compartment Syndrome: when increased pressure in a closed anatomic space. may develop after fluid resuscitation, with worsening edema of the limb and muscle. Increased interstitial pressure in close fascial compartment leading to microvascular

compromise and cellular death. Pressure measuring > 30 mmhg surgical assessment

(dBP – compartment = < 30 fasciotomy

• Disseminated intravascular coagulation: The release of thromboplastin and other prothrombotic substances from the damaged muscle .

Acute Renal InjuryRhabdomyolysis accounts for an estimated 8-15% of cases of acute renal failure.ARF develops in 30-40% of patients with rhabdomyolysis.

Management

General recommendations in ICU:

• Ensure adequate hydration; fluid resuscitation and prevention of AKI ,

• Record urine output. Insert a Foley catheter for careful monitoring of urine output.

• Correction of electrolyte imbalances. Obtain an ECG to monitor effects of hyperkalemia and other electrolyte disturbances.

• Compartment syndrome necessitates immediate orthopedic consultation for fasciotomy.

• DIC should be treated with fresh frozen plasma, platelet transfusions and cryoprecipitate.

• Monitor creatine kinase (CK) levels to show resolution of rhabdomyolysis.

• Once the patient’s condition has been stabilized and life- and limb-threatening conditions have been addressed, he or she may be transferred to another facility if necessary.

• Once they are well hydrated, patients with normal renal function, normal electrolyte levels, alkaline urine, and an isolated cause of muscle injury may be discharged and monitored as outpatients.

AlgorithmIsotonic Saline

-Initial Resuscitation: 1-2 L/hr -100-200 ml/hr (if hemolysis induced injury)-Correct electrolyte abnormalities

Titrate IVF UOP goal: 200-300ml/hr

Serial CK measurements

CK>5000

CK<5000 Stop Treatment

Fluid ResuscitationDehydration: (hematocrit >50, serum sodium level >150 mEq/L, orthostasis, pulmonary wedge pressure

< 5 mm Hg, urinary fractional excretion of sodium < 1%) CK elevation in excess of 2-3 times the reference range.

Administer isotonic fluids at a rate of approximately 400 mL/h (may be up to 1000 mL/h based on type of condition and severity) and then titrate to maintain a urine output of at least 200 mL/h.

In patients with CK levels of 15,000 IU/L or greater, higher volumes of fluid, on the order of at least 6 L in adults, are required.

Remember: • Sepsis

• Hyperkalemia, hypocalcemia or hyperphosphatemia

• Hypoalbuminemia

• urinary alkalization, mannitol, and loop diuretics.

Treatment (Cont.)Depending on the cause of rhabdomyolysis, surgical care may be necessary, as follows: When intracompartmental pressure exceeds 30 mm Hg, a fasciotomy is advocated Limb fractures may call for surgical and orthopedic treatment Lifestyle-related treatment measures may be considered, as follows: Dietary modification to help address metabolic disorders or inborn errors of

metabolism Avoidance of strenuous activities if such activities cause recurrent myalgias,

myopathy, or rhabdomyolysis Maintenance of proper hydration during athletic exertion Prompt attention to indicators of heat exhaustion during hot and humid conditions

Recommended activity• Strenuous activities (eg, competitive sports) should be avoided if they cause

recurrent myalgias, myopathy, or rhabdomyolysis.

• Children and adolescents with recurrent rhabdomyolysis related to exertion require further medical evaluation.

• High-school coaches and trainers must ensure proper hydration and maintain fluid balance during practice sessions and games. Signs and symptoms of heat exhaustion must be evaluated in a timely fashion during hot and humid conditions.[53]