Rhabdomyolysis is a syndrome characterized by the breakdown of skeletal muscle fibers leading to the release of myoglobin into circulation, which can cause acute kidney injury and other complications. It has various causes, including trauma, exertion, infections, and medication use, and can present with symptoms like dark urine, muscle pain, and fatigue. Aggressive fluid resuscitation is crucial for treatment, along with monitoring for complications and implementing prevention strategies such as hydration, avoiding over-exertion, and being cautious with certain medications.

1. DR. FATHI NEANA
CHIEF OF ORTHOPEDICS
DR. FAKHRY & ALRAJHY HOSPITAL
SAUDI ARABIA
NOVEBER, 30 - 2016
Rhabdomyolysis
Causes, Pathophysiology & Management
Rhabdo
•Striated
Myo
•Muscle
Lysis
•Breakdown

2. RhabdomyolysisRhabdo
• Striated
Myo
• Muscle
Lysis
• Breakdown
Breakdown of skeletal muscle fibers
Potentially life-threatening syndrome
Leakage of muscle contents into the circulation

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

4. History
• 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
syndrome.
– 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.

5. The incidence of
rhabdomyolysis varies with
the underlying cause
Levels increase with disasters
- eg, earthquakes & in war
zones
Rhabdomyolysis account for
~7- 8% of all new cases of
acute kidney injury
Epidemiology

7. Definitions
• 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,
Devascularization
Also known as Traumatic
rhabdomyolysis

8. Rhabdomyolysis
Why all the
worry?

9. 1- Acute Renal Failure
ARF
2- Sudden Cardiac Death among young
athletes
SCD
3- Acute compartment syndrome
ACS
Sequelae of ACS -> contractures, deformities, long
life disability & even amputation
ex. Volkmann contracture
Why all the worry?
Devastating consequences is the answer (ASA)

10. Mechanisms of ARF in rhabdomyolysis
• Hypovlemia -> renal
vasoconstriction ->
diminished renal perfusion
• Cast formation leads to
tubular obstruction
• Direct Myoglobin
nephrotoxicity
• Haeme produced free
radicles -Oxidants
• When muscle is damaged, a protein
pigment called myoglobin is released
into the bloodstream and filtered out of
the body by the kidneys.
• The broken down myoglobin may block
the structures of the kidney, causing
damage such as acute tubular necrosis
or kidney failure.
• Dead muscle tissue may cause a large
amount of fluid to move from the blood
into the muscle, leading to
Hypovolemic shock. Causing reduced
blood flow to the kidneys.

11. 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
Sudden Cardiac Death among young athletes

12. Sarcolemma damage release the content of
sarcoplasm of muscle cells including potassium ions
(K+) -> Electrolyte imbalance
->> Cardiac electrical activity changes
may precipitate
Sudden Cardiac Arrest
Sudden efflux of potassium ions in the
blood stream
+
High catecholamine level (exercises)
Mechanisms of SCD in
rhabdomyolysis

13. 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
region.

14. 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

15. Acute compartment syndrome
• DBP - ICP = >30mmhg –> Non-
operative techniques to delay the
onset of ischemia & preserve soft
tissues.
• 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

16. 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
Complications of A. compartment syndrome
late sequelae of A. compartment syndrome

17. Skeletal Muscle

19. 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

20. Skeletal Muscle Cell
function

21. 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

22. Electrolyte disturbances
Hyperkalaemia
Hypocalcaemia
Hyperphosphatemia
Hyperuricaemia
Metabolic acidosis
Pathogenesis of Rhabdomyolysis 2
Revascularization
• Fluids trapped in damaged tissue
• Oedema of affected limb
• Haemoconcentration and shock
(hypovolaemia)
• Myoglobin, potassium, phosphate
enter venous circulation
Lysed cell release
Potassium
Phospate
Creatine kinase
Myoglobin
Lysed cell retain
Ca
water

23. Causes of Rhabdomyolysis (Muscle Breakdown)
Traumatic Nontraumatic
-Multiple Trauma
-Crush Injury
-Surgery
-Coma
-Immobilization
Exertional Non exertional
-Exertion
-Heat illness
-Seizures
-Metabolic myopathies
-Malignant
hyperthermia
-Neuroleptic Malignant
Syndrome
-ETOH (ethyl alcohol
Abuse)
-Drugs ( statins, OTC,
illicit)
-Infection
-Electrolytes

24. Causes
• Trauma
• Exertion
• Infection – viral myositis
• Body temperature change:
heat stroke, hypothermia
• Connective tissue diseases
• Genetic defects: metabolic
disorders
• Drugs and toxins:
statins, OTC, illicit drugs

25. TABLE 1
Medications and Toxic Substances That Increase the Risk of Rhabdomyolysis
HMG-CoA = 3-hydroxy-3-methylglutaryl coenzyme A; LSD = lysergic acid diethylamide;
MDMA = 3,4-methylene dioxymethamphetamine.
Direct myotoxicity
HMG-CoA reductase inhibitors,
especially in combination with
fibrate-derived lipid-lowering
agents such as niacin (nicotinic
acid; Nicolar)
Cyclosporine (Sandimmune)
Itraconazole (Sporanox)
Erythromycin
Colchicine
Zidovudine (Retrovir)
Corticosteroids
Indirect muscle damage
Alcohol
Central nervous system depressants
Cocaine
Amphetamine
Ecstasy (MDMA)
LSD
Neuromuscular blocking agents

26. Statins act by inhibiting HMG-CoA reductase
(3-hydroxy-3-methyl-glutaryl-CoA Reductase)
All metabolic functions further down the pathway are affected (isoprenoids)
HMG-CoA reductase inhibitors

27. Clinical Mmanifestations of Rhabdomyolysis ?
Range from asymptomatic to acute renal failure and DIC
Triad : muscle pain , weakness , dark urine
Systemic features
• Coca-cola coloured urine
– Results from Myoglobinuria
• General weakness
• Confusion, unconsciousness
• Fever, nausea/vomiting,
Tachycardia
• Less frequent urination
• In severe cases: AKI (acute kidney
injury) renal failure
• Disseminated intravascular
coagulation
Additional symptoms
Overall Malaise - Fatigue - Joint pain – Seizures - Weight gain
Local features
• Muscle pain, swelling, stiffness &
tenderness
• Bruising & compartment syndrome
• Muscle & Limb weakness

28. Complications of Rhabdomyolysis
Early complications (< 12-
72 hrs)
• Hypovolaemia
• Hyperkalaemia
• Hypocalcaemia
• Cardiac arrhythmias
• Cardiac arrest
Late complications (< 12-
72 hrs)
• Kidney damage
• Acute tubular necrosis
• Acute renal failure 15%
• DIC
• ARDS
• sepsis
Early or late complications
Acute compartment syndrome

29. 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

30. Laboratory Findings
High CPK levels may be seen in people
who have:
Brain injury or stroke
Convulsions
Delirium tremens
Dermatomyositis or polymyositis
Electric shock
Heart attack
Inflammation of the heart muscle
(myocarditis)
Lung tissue death (pulmonary
infarction)
Creatine phosphokinase
Creatine phosphokinase (CPK) an enzyme found mainly in
heart, brain, skeletal muscle
Muscular dystrophies
Myopathy
Rhabdomyolysis
Other conditions
that may give positive test results
include:
Hypothyroidism
Hyperthyroidism
Pericarditis following a heart attack

31. Prevention
• 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

32. 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

33. Treatment
• A B C
• Fluids Early aggressive fluid
resuscitation.
• Electrolyte replacement.
• Alkalinization of urine?
• Treat hyperkalaemia
• Treat underlying cause.
• Fasciotomy.
• Free radical scavengers and
antioxidants

34. 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.

35. Fluid Resuscitation
• Give as much fluid as you would give a severely burned
patient.
• Optimal fluid and rate of repletion are unclear.
• No studies comparing efficacy/safety of different types and rate of fluid
administration.
• 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
RESUCITATION!

36. Algorithm
Isotonic 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

37. 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
administered.
Dialysis
• Use of dialysis to remove myoglobin, hemoglobin, or uric acid in order to
prevent the development of renal injury has not been demonstrated.

38. 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

39. Prognosis of Rhabdomyolysis
• The outcome varies depending on the
extent of kidney damage.
Source: Silberber, 2007
Automatic Positive
Airway Pressure

40. 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

41. 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
Females
• May occur in infants, toddlers, and adolescents

42. Summary and Conclusions
• High index of suspicion (coca-
cola coloured urine, muscle
pain, nausea, confusion)
• On scene treatment
Aggressive fluid treatment
Adequate monitoring
• Recognition & early
treatment of complications
Laboratory tests:
Plasma creatine kinase levels
Plasma potassium levels
urine myoglobin assay

43. 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.

44. Keep always hydrated
Well supplemented with electrolytes &
carbohydrates
Avoid drugs, alcohol, excessive heat &
over-exercising
Summary and Conclusions
Prevention strategies