Anda di halaman 1dari 45


Causes, Pathophysiology & Management

• Striated

• Muscle

• Breakdown


NOVEBER, 30 - 2016
• Striated
• Muscle

• Breakdown

Breakdown of skeletal muscle fibers

Potentially life-threatening syndrome

Leakage of muscle contents into the circulation

First clue
1- Tea or coca cola like urine
2- +ve urine myoglobin
3- Oliguria

• Tea or coca cola like urine : breakdown of muscle fibers, specifically the sarcolemma resulting in
release of myoglobin -> may cause acute kidney injury or renal failure
• Oliguria : Shift of extracellular fluid into injured muscles -> hypovolaemia & under perfusion of the
• First reported in 1881, in the German literature .
• In 1910 Myer-Betz Syndrome, (German physician) - Triad: Muscle Pain,
Weakness, Brown Urine.

• World War II
– First described in the victims of crush injury . Dr Bywaters described patients
during London Bombings (Battle of Britain 1941).
– Oliguria, pigmented casts, limb oedema, shock & death.

• In 1943, in animal models, Bywaters & Stead identified myoglobin as the

offending agent, & formulated the first treatment plan.

• In 1950 Korean War, dialysis reduces mortality rate from 84% to 53%.

• Natural Disasters – Earthquakes

– 1976 Tangshan (near Beijing): 20% of 242,000 deaths due to crush
– In 1995, British nephrologists introduced the Disaster Relief Task Force
to prevent acute renal failure.
– 1999 Marmara (Turkey): 7.2 Richter scale earthquake. 12% hospitalised
patients had renal failure, 76% received dialysis, 19% fatality rate.

The incidence of
rhabdomyolysis varies with
the underlying cause

Levels increase with disasters

- eg, earthquakes & in war

Rhabdomyolysis account for

~7- 8% of all new cases of
acute kidney injury
• Rhabdomyolysis - destruction of
striated muscle (multiple causes)

• A crush injury is direct injury resulting

from a crush

• A crush syndrome is the systemic

manifestation of muscle cell damage

Resulting from 3 criteria

Crushing, Prolonged pressure,

Also known as Traumatic

Why all the
Why all the worry?
Devastating consequences is the answer (ASA)

1- Acute Renal Failure


2- Sudden Cardiac Death among young


3- Acute compartment syndrome


Sequelae of ACS -> contractures, deformities, long

life disability & even amputation
ex. Volkmann contracture
Mechanisms of ARF in rhabdomyolysis
• Hypovlemia -> renal
vasoconstriction ->
diminished renal perfusion

• Cast formation leads to

tubular obstruction
• When muscle is damaged, a protein
pigment called myoglobin is released
into the bloodstream and filtered out of
the body by the kidneys.
• Direct Myoglobin
• The broken down myoglobin may block
nephrotoxicity the structures of the kidney, causing
damage such as acute tubular necrosis
or kidney failure.

• Dead muscle tissue may cause a large

• Haeme produced free amount of fluid to move from the blood
into the muscle, leading to
radicles -Oxidants Hypovolemic shock. Causing reduced
blood flow to the kidneys.
Sudden Cardiac Death among young athletes

Rhabdomyolysis after an injury can be a cause of

Sudden Cardiac Death among young athletes
Usually in athletes, skeletal muscles are prone to injury either due to
over exercises or any sports related injury
Mechanisms of SCD in
Sarcolemma damage release the content of
sarcoplasm of muscle cells including potassium ions
(K+) -> Electrolyte imbalance

Sudden efflux of potassium ions in the

blood stream
High catecholamine level (exercises)

->> Cardiac electrical activity changes

may precipitate
Sudden Cardiac Arrest
Acute compartment syndrome

ACS = Critical increase of interstitial pressure

within a confined closed fascial compartment

->> decline in the perfusion pressure to the

compartment tissue

Without timely diagnosis & treatment ->>

microvascular compromise , ischaemia &
cellular necrosis

Ultimately permanent disability of the affected

Acute compartment syndrome
• Immediate fasciotomy & decompression of all
tissues within the affected compartment

• Normal resting ICP is around 0 - 8 mmHg in adults

& slightly higher (13 to 16 mmHg) in children

• DBP – ICP = >30mmhg –> surgical assessment ->

conservative -> normal muscle function at follow
up - (McQueen and Court-Brown)

• DBP – ICP = < 30 -> (fasciotomy)

NB: Differential pressure = ( DBP) diastolic BP – (ICP) Intra

compartment Pressure
Acute compartment syndrome

• DBP - ICP = >30mmhg –> Non-

operative techniques to delay the
onset of ischemia & preserve soft

• All restrictive dressings , tight pop

cast should be loosened and removed.
• Extremity elevation to maximize
venous return and minimize edema.
• Fracture reduction to limit ongoing
soft tissue damage.
• AVI System
Complications of A. compartment syndrome
late sequelae of A. compartment syndrome

Severe deformity, chronic pain, paralysis

& even amputation.

The best treatment is immediate

Decompression Fasciotomies &
prevention of late contractures

Deformities depend on the most fibrotic

& ischemic muscles
Skeletal Muscle
Skeletal Muscle Cell

The sarcolemma is the

cell membrane of a
muscle cell. The
membrane is designed
to receive and conduct
stimuli and surround
The sarcoplasm
Skeletal Muscle Cell
Pathogenesis of Rhabdomyolysis 1
• Compressive forces  cellular
hypoperfusion  hypoxia

• Decrease in ATPase  failure of ATPase

pump & sacrolemma leakage

• Lysed cell release inflammatory mediators

• platelet aggregation

• Vasoconstriction

• increase vascular permeability

Pathogenesis of Rhabdomyolysis 2
Lysed cell release
Potassium Electrolyte disturbances
Phospate Hyperkalaemia
Creatine kinase
Myoglobin Hypocalcaemia
Lysed cell retain Hyperuricaemia
Ca Metabolic acidosis

• Fluids trapped in damaged tissue
• Oedema of affected limb
• Haemoconcentration and shock
• Myoglobin, potassium, phosphate
enter venous circulation
Causes of Rhabdomyolysis (Muscle Breakdown)

Traumatic Nontraumatic

-Multiple Trauma Exertional Non exertional

-Crush Injury
-Surgery -Exertion
-Coma -Heat illness -ETOH (ethyl alcohol
-Seizures Abuse)
-Metabolic myopathies -Drugs ( statins, OTC,
-Malignant illicit)
hyperthermia -Infection
-Neuroleptic Malignant -Electrolytes
• Trauma
• Exertion
• Infection – viral myositis
• Body temperature change:
heat stroke, hypothermia
• Connective tissue diseases
• Genetic defects: metabolic
• Drugs and toxins:
statins, OTC, illicit drugs
Medications and Toxic Substances That Increase the Risk of Rhabdomyolysis

Direct myotoxicity Indirect muscle damage

HMG-CoA reductase inhibitors, Alcohol

especially in combination with
Central nervous system depressants
fibrate-derived lipid-lowering
agents such as niacin (nicotinic Cocaine
acid; Nicolar) Amphetamine
Cyclosporine (Sandimmune) Ecstasy (MDMA)
Itraconazole (Sporanox) LSD
Neuromuscular blocking agents
Zidovudine (Retrovir)

HMG-CoA = 3-hydroxy-3-methylglutaryl coenzyme A; LSD = lysergic acid diethylamide;

MDMA = 3,4-methylene dioxymethamphetamine.
HMG-CoA reductase inhibitors

Statins act by inhibiting HMG-CoA reductase

(3-hydroxy-3-methyl-glutaryl-CoA Reductase)
All metabolic functions further down the pathway are affected (isoprenoids)
Clinical Mmanifestations of Rhabdomyolysis ?
Range from asymptomatic to acute renal failure and DIC
Triad : muscle pain , weakness , dark urine

Local features Systemic features

• Muscle pain, swelling, stiffness & • Coca-cola coloured urine
– Results from Myoglobinuria
• Bruising & compartment syndrome
• General weakness
• Muscle & Limb weakness
• Confusion, unconsciousness
• Fever, nausea/vomiting,
• Less frequent urination
• In severe cases: AKI (acute kidney
injury) renal failure
• Disseminated intravascular
Additional symptoms
Overall Malaise - Fatigue - Joint pain – Seizures - Weight gain
Complications of Rhabdomyolysis
Early complications (< 12- Late complications (< 12-
72 hrs) 72 hrs)
• Hypovolaemia • Kidney damage
• Hyperkalaemia • Acute tubular necrosis
• Hypocalcaemia • Acute renal failure 15%
• Cardiac arrhythmias • DIC
• Cardiac arrest • ARDS
• sepsis

Early or late complications

Acute compartment syndrome
Laboratory Findings
• Creatine kinase: >5x ULN (1500-100,000) (heart, brain,
skeletal muscle)
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 three
to five days of cessation of muscle injury1,2.

• Myoglobinuria
• Hyperkalemia
• Hyperphosphatemia
• Hypocalcemia
• Hyperuricemia
Laboratory Findings
Creatine phosphokinase
Creatine phosphokinase (CPK) an enzyme found mainly in
heart, brain, skeletal muscle

High CPK levels may be seen in people Muscular dystrophies

who have: Myopathy
Brain injury or stroke Rhabdomyolysis
Delirium tremens
Dermatomyositis or polymyositis
Electric shock Other conditions
that may give positive test results
Heart attack include:
Inflammation of the heart muscle Hypothyroidism
(myocarditis) Hyperthyroidism
Lung tissue death (pulmonary Pericarditis following a heart attack

• Balanced diet & exercise

• Risk: Antipsychotics, statin & fibrate medications for
high cholesterol , Selective serotonin reuptake
inhibitors, Zidovudine, Colchicine, lithium,
Antihistamines, and several others
• Don’t: Over exercising in extreme heat conditions, take
drugs & alcohol
• Keep: hydrated – electrolytes
How can I prevent Rhabdomyolysis

• Drink plenty of fluids after

strenuous exercise to dilute the
urine and flush the myoglobin
out of the kidney

• Proper hydration is also

necessary after any condition or
event that may involve damage
to skeletal muscle

• Fluids Early aggressive fluid
• Electrolyte replacement.
• Alkalinization of urine?
• Treat hyperkalaemia
• Treat underlying cause.
• Fasciotomy.
• Free radical scavengers and
EMS Treatment

1. Immediately obtain intravenous

access with a large-bore catheter.

2. Administer isotonic crystalloid

500 mL/h and then titrate to
maintain a urine output of 200-
300 mL/h.
Fluid Resuscitation
• Give as much fluid as you would give a severely burned

• Optimal fluid and rate of repletion are unclear.

• No studies comparing efficacy/safety of different types and rate of fluid

• Early and aggressive fluids (hydration) may prevent complications

by rapidly remove myoglobin out of the kidneys. Administer
isotonic crystalloid fluids (Normal Saline or Lactated Ringer’s).
• Studies of patients with severe crush injuries resulting in Rhabdomyolysis
suggest that the prognosis is better when prehospital personnel provide FLUID

-Initial Resuscitation: 1-2 L/hr

CK>5000 Isotonic Saline -100-200 ml/hr (if hemolysis
induced injury)
-Correct electrolyte abnormalities

Titrate IVF UOP goal: 200-300ml/hr

Serial CK measurements

CK<5000 Stop Treatment

Bicarbonate, Mannitol, Dialysis
Bicarbonate: Forced alkaline diuresis
• May reduce renal heme toxicity
• May also decrease the release of free iron from myoglobin, the formation of
vasoconstricting F2-isoprostanes, and the risk for tubular precipitation of
uric acid3,4
• No clear clinical evidence that an alkaline diuresis is more effective than a
saline diuresis in preventing AKI.
Mannitol: Forced diuresis
• May minimize intratubular heme pigment deposition and cast
formation, and/or by acting as a free radical scavenger, thereby minimizing
cell injury6,7.
• Net clinical benefit remains uncertain, therefore, not routinely

• Use of dialysis to remove myoglobin, hemoglobin, or uric acid in order to
prevent the development of renal injury has not been demonstrated.
Free radical scavengers and antioxidants
• The magnitude of muscle necrosis caused by ischemia-reperfusion injury has
been reduced in experimental models by the administration of free-radical
scavengers .
• Many of these agents have been used in the early treatment of crush
syndrome to minimize the amount of nephrotoxic
material released from the muscle

• Pentoxyphylline is a xanthine derivative used to improve

microvascular blood flow. In addition, pentoxyphylline acts to
decrease neutrophil adhesion and cytokine release
• Vitamin E , vitamin C , lazaroids (21-aminosteroids) and
minerals such as zinc, manganese and selenium all have
antioxidant activity and may have a role in the treatment of the
patient with rhabdomyolysis
Prognosis of Rhabdomyolysis
• The outcome varies depending on the
extent of kidney damage.

Automatic Positive
Airway Pressure
Source: Silberber, 2007
Summary and Conclusions

Rhabdomyolysis is the breakdown of

skeletal muscles

ATP depletion ->> increase in

intracellular Ca2+ ->> triggering a
series of proteolytic enzymes =>>
myocyte destruction ->> leakage of
cell components in blood stream
(myoglobin, creatine kinase, K, P,
electrolytes, etc.)
Summary and Conclusions
• Excess myoglobin —>> precipitate in glomerular
filtrate —>> acute renal failure
• Rhabdomyolysis accounts for an estimated 8-15% of
cases of acute renal failure

• The overall mortality rate for patients with

Rhabdomyolysis is approximately 5%

• Rhabdomyolysis is more common in Males than in

• May occur in infants, toddlers, and adolescents
Summary and Conclusions

• High index of suspicion (coca-

cola coloured urine, muscle
pain, nausea, confusion)

• On scene treatment
Laboratory tests:
Aggressive fluid treatment
Adequate monitoring Plasma creatine kinase levels

Plasma potassium levels

• Recognition & early
urine myoglobin assay
treatment of complications
Summary and Conclusions

• When rhabdomyolysis is suspected aggressive

fluid resuscitation should started to prevent
pigment nephropathy.

• Titrate to UOP 200-300cc/hr.

• The use of bicarbonate, mannitol, and dialysis:

net clinical benefit has not been shown.
Summary and Conclusions
Prevention strategies

Keep always hydrated

Well supplemented with electrolytes &


Avoid drugs, alcohol, excessive heat &