Rhabdomyolysis lecture for postgraduates in nephrology

1. A 36-year-old male patient with HIV and alcoholism is
brought to the emergency department in a comatose
condition by his neighbour. He was found lying in bed
for >24 hours. Initial labs:
Serum
Na+ = 134 mEq/L
K+ = 3.0 mEq/L
Cl = 100 mEq/L
HCO3 = 16 mEq/L
BUN = 62 mg/dL
Creatinine = 3.6 mg/dL
Glucose = 80 mg/dL
Ca= 6.9 mg/dL
Phosphate = 2.1 mg/dL
Uric acid = 12.6 mg/dL
Urine
Color = reddish-brown
pH = 5.2
RBCs = 5-10
Protein = ++
Sediment = muddy-brown casts
FENa = <1%
Toxicology screen = cocaine, heroin

2. 1. Which one of the following serum tests is MOST
appropriate in this patient?
A. Aldolase
B. Lactate dehydrogenase (LDH)
C. Plasma myoglobin
D. Creatine kinase (CK)

3. 2. The urine myoglobin was 400 mg/mL (normal <50
mg/mL) and CK levels 120,000 U/L (normal <300 U/L). In
the above patient, which one of the following is the
MOST likely to contribute to rhabdomyolysis in this
patient?
A. Hypokalemia
B. Hypophosphatemia
C. Cocaine and heroin
D. HIV
E. All of the above

4. 3. Repeat chemistry is as follows: Na+ 138 mEq/L, K+ 4 mEq/L,
phosphate 4.2 mg/dL, HCO3 14 mEq/L, BUN 54 mg/dL, and
creatinine 3.2 mg/dL. Her urine output is 30 mL/h. Which one of the
following management strategies is MOST appropriate for this
patient?
A. NaHCO3 100 mEq/L of D5W to run at 200 mL/h
B. Initially normal saline followed by NaHCO3 100 mEq/L in D5W to run at 150–200
mL/h
C. D5W at 200 mL/h
D. Normal saline at 200 mL/h followed by furosemide 80 mg
E. Mannitol 12.5 g every 6 h

5. 4. The above patient improved as for serum electrolytes,
creatinine, and CK. Which one the following electrolyte
abnormalities is seen MOST frequently during the recovery
phase of AKI or cessation of rhabdomyolysis?
A. Hypernatremia
B. Hyperkalemia
C. Hypercalcemia
D. Hyperuricemia
E. Hyperphosphatemia

6. RHABDOMYOLYSIS
BY AHMED MEDHAT

7. Rhabdomyolysis: (rhabdo-myo-lysis)
is the breakdown of muscle fibers which in turn
release potentially nephrotoxic intracellular contents
(particularly myoglobin) into the systemic circulation.

8. Causes of rhabdomyolysis:
• Direct muscle damage/ischemia: crush injury, blunt trauma, pressure
necrosis, electric shock, burns, compartment syndrome, acute
ischemia or vascular disease
• Muscle cell exhaustion (ATP depletion): seizures, heat extremes or
severe exercise (specially in untrained individuals)
• Electrolytes disorders:
• Hypokalemia (decreases muscle cells blood flow)
• Hypophosphatemia (defective ATP production since phosphate is involved
in the pathway of ATP production)

9. • Drugs / Toxins:
• Alcohol (direct toxicity on myocytes, may present with seizures,
pressure necrosis from prolonged coma or electrolytes
disturbances)
• Statins (direct toxicity on myocytes especially when increased doses
or if combined with drugs like fibrates, CSA or erythromycin)
• Toxins as cocaine, heroin or cannabis (sympathomimetics agents
that lead to increased muscular activity and can be complicated by
seizures, also can cause vasoconstriction leading to muscle
ischemia or direct toxicity on myocytes by some agents)
• Infections:
• Viral as HIV, Influenza
• Bacterial as Salmonella, Streptococci

10. •Rhabdomyolysis-induced AKI Pathophysiology
• Volume depletion and renal vasoconstriction
• As a result of the sequestration of large amounts of fluid volume (up to 15 to 20 liters)
in the injured muscle site. The resulting hypovolemia activates the sympathetic
nervous system and renin-angiotensin system, resulting in renal vasoconstriction
and ischemia.
• Direct toxicity to tubular cells
• Myoglobin is a 17 kDa molecule freely filtered through the glomeruli and reabsorbed
in the proximal tubules by endocytosis. The globin chain dissociates from the iron-
containing portion of the molecule which normally happens in lysosomes and more in
acidic pH. Iron generates oxygen free radicals which leads to oxidative stress and
toxic injury of the tubular cells.
• Casts formation leading to intratubular obstruction
• Precipitation of myoglobin with Tamm-Horsfall protein and proximal tubular cells may
result in cast formation obstructing the tubular lumen, especially when tubular

11. ASSOCIATED CONDITIONS
• Electrolytes disturbances
• Hyperkalemia and hyperphosphatemia: Hyperkalemia and hyperphosphatemia
result from the release of potassium and phosphorus from damaged muscle cells.
• Hyperuricemia: due to the release of purines from damaged muscle cells and from
reduced urinary excretion if AKI occurs.
• Hypocalcemia: occurs in first few days because of entry into damaged myocytes and
deposition of calcium phosphate salts in damaged muscle. Hyperphosphatemia inhibits
1α-hydroxylase in the kidney with less formation of calcitriol.
• . During the recovery phase, serum calcium levels return to normal and rebound severe
hypercalcemia may occur due to the release of calcium from injured muscle cells, mild
secondary hyperparathyroidism from the acute renal failure, and an increase in
calcitriol production.
• High anion gap metabolic acidosis is common also.

12. • Acute Kidney Injury:
AKI is a common complication of rhabdomyolysis. The reported
frequency of AKI ranges from 15 to over 50 percent of the cases. The
risk of AKI is lower in patients with CK levels at admission less than
20,000 units/L. However, rhabdomyolysis may lead to AKI with
creatinine kinase levels as low as 5000 U/l when coexisting conditions
such as sepsis or dehydration are present.
• Compartment syndrome: (a cause & a complication)
• As the intracompartmental pressure rises, due to bleeding or muscle
tissue-swelling, initially the venous and then the arterial blood flow
are blocked, leading in tissue ischemia & muscle cell lysis.
• This muscle cell injury will lead to accumulation of large fluids
volume and muscle edema leading to compartment syndrome.

13. CLINICAL DIAGNOSIS
•A classic triad of:
• Muscle pain
• Weakness
• Tea-colored urine
•Additional symptoms / signs:
• Nausea, vomiting, abdominal pain, delirium,
fatigue, fever or tachycardia

14. INVESTIGATIONS
• Urine dipstick test and urine analysis to confirm myoglobinuria
• The presence of pigmented granular casts and the lack of RBCs on urine
microscopy coupled with a blood-positive urinary dipstick are important diagnostic
clues for rhabdomyolysis
• Serum CK level:
• Levels at presentation of rhabdomyolysis are usually at least five times the upper
limit of normal (45-300U/L) and are usually greater than 5000 units/L.
• CK begins to rise within 2 to 12 hours following the onset of muscle injury and
reaches its maximum within 48 to 72 hours. A decline is usually seen within three
to five days of cessation of muscle injury.
• Other serum enzymes, indicative of muscle injury, are typically elevated with
rhabdomyolysis as aldolase, aminotransferases, lactate dehydrogenase. But they are
non-specific or sensitive to rhabdomyolysis.

15. •Further Workup:
• Complete blood count: for evidence of infection or hemolysis.
• Blood urea nitrogen, and serum creatinine: for renal function evaluation
and evidence of acute kidney injury (AKI).
• Electrolytes: mainly; potassium, calcium and phosphate to search for
hyperkalemia, hypocalcemia, and hyperphosphatemia.
• Arterial blood gases: to search for metabolic acidosis.
• Alcohol level and toxicology screen: if suspected alcoholism or drug
abusers.

16. TREATMENT
• Early and aggressive IV fluids therapy: Intravenous isotonic saline
should be administered and aiming to target urine output of 200 to 300
ml/h.
• Sodium bicarbonate is recommended in most cases to maintain alkaline
urine and decrease precipitation of myoglobin and cast formation.
However, sodium bicarbonate also can precipitate calcium phosphate
deposition and worsen hypocalcemia and should be avoided in severe
hypocalcemia or metabolic alkalosis.
• The ideal fluid regimen is quite controversial. According to some authors,
the initial administration of 1L isotonic saline then 1L dextrose 5% to which
100 mmol sodium bicarbonate has been added is the ideal combination.

17. • Mannitol has been suggested to be beneficial because of its diuretic,
antioxidant, and vasodilatory properties. It could expand extracellular
volume, and reduce intracompartmental pressure, muscle edema, and
pain. However, mannitol may exacerbate heart failure and nephrotoxicity,
requires close monitoring, and is contraindicated in oliguria,
hypervolemia, hypertension, and heart failure. Mannitol can be considered
if urine flow is higher than 20 ml/h at a rate of 5 g/h added to each liter of
iv fluids and not to exceed 1 to 2 g/kg/day.
• Hypocalcemia is usually asymptomatic but can lead to cardiac
dysrhythmias. Hence, care must be taken to avoid sodium bicarbonate–
induced hypocalcemia, which can trigger tetany, seizures, and
cardiotoxicity. During AKI recovery, rebound hypercalcemia is frequent.
Thus hypocalcemia should be treated only if symptomatic.

18. • It is important to consider when to stop fluid resuscitation.
A general recommendation is to stop when creatine kinase levels
decrease to less than 5000 U/l and myoglobinuria disappears, as
shown by a negative urine dipstick for blood.
• RRT should be considered in hyperkalemia resistant to medical
treatment or metabolic acidosis, anuria or volume overload.

19. A 26-year-old woman with HIV and alcoholism is
brought to the emergency department in a comatose
condition by her parents. She was found lying in bed
for >24 hours.
Initial labs:
Serum
Na+ = 134 mEq/L
K+ = 3.0 mEq/L
Cl = 100 mEq/L
HCO3 = 16 mEq/L
BUN = 62 mg/dL
Creatinine = 3.6 mg/dL
Glucose = 80 mg/dL
Ca= 6.9 mg/dL
Phosphate = 2.1 mg/dL
Uric acid = 12.6 mg/dL
Urine
Color = reddish-brown
pH = 5.2
RBCs = 5-10
Protein = ++
Sediment = muddy-brown casts
FENa = <1%
Toxicology screen = cocaine, heroin

20. 1. Which one of the following serum tests is MOST
appropriate in this patient?
A. Aldolase
B. Lactate dehydrogenase (LDH)
C. Plasma myoglobin
D. Creatine kinase (CK)

21. 1. Which one of the following serum tests is MOST
appropriate in this patient?
A. Aldolase (non-sensitive or specific)
B. Lactate dehydrogenase (LDH) (non-sensitive or specific)
C. Plasma myoglobin (short half-life 2-3h & raapidly excreted by kidneys)
D. Creatine kinase (CK)

22. 2. The urine myoglobin was 400 mg/mL (normal <50
mg/mL) and CK levels 120,000 U/L (normal <300 U/L). In
the above patient, which one of the following is the
MOST likely to contribute to rhabdomyolysis in this
patient?
A. Hypokalemia
B. Hypophosphatemia
C. Cocaine and heroin
D. HIV
E. All of the above

23. 2. The urine myoglobin was 400 mg/mL (normal <50
mg/mL) and CK levels 120,000 U/L (normal <300 U/L). In
the above patient, which one of the following is the
MOST likely to contribute to rhabdomyolysis in this
patient?
A. Hypokalemia
B. Hypophosphatemia
C. Cocaine and heroin
D. HIV
E. All of the above

24. 3. Repeat chemistry is as follows: Na+ 138 mEq/L, K+ 4 mEq/L,
phosphate 4.2 mg/dL, HCO3 14 mEq/L, BUN 54 mg/dL, and
creatinine 3.2 mg/dL. Her urine output is 30 mL/h. Which one of the
following management strategies is MOST appropriate for this
patient?
A. NaHCO3 100 mEq/L of D5W to run at 200 mL/h
B. Initially normal saline followed by NaHCO3 100 mEq/L in D5W to run at 150–200
mL/h
C. D5W at 200 mL/h
D. Normal saline at 200 mL/h followed by furosemide 80 mg
E. Mannitol 12.5 g every 6 h

25. 3. Repeat chemistry is as follows: Na+ 138 mEq/L, K+ 4 mEq/L,
phosphate 4.2 mg/dL, HCO3 14 mEq/L, BUN 54 mg/dL, and
creatinine 3.2 mg/dL. Her urine output is 30 mL/h. Which one of the
following management strategies is MOST appropriate for this
patient?
A. NaHCO3 100 mEq/L of D5W to run at 200 mL/h
B. Initially normal saline followed by NaHCO3 100 mEq/L in D5W to run at 150–200
mL/h
C. D5W at 200 mL/h
D. Normal saline at 200 mL/h followed by furosemide 80 mg
E. Mannitol 12.5 g every 6 h

26. 4. The above patient improved as for serum electrolytes,
creatinine, and CK. Which one the following electrolyte
abnormalities is seen MOST frequently during the recovery
phase of AKI or cessation of rhabdomyolysis?
A. Hypernatremia
B. Hyperkalemia
C. Hypercalcemia
D. Hyperuricemia
E. Hyperphosphatemia

27. 4. The above patient improved as for serum electrolytes,
creatinine, and CK. Which one the following electrolyte
abnormalities is seen MOST frequently during the recovery
phase of AKI or cessation of rhabdomyolysis?
A. Hypernatremia
B. Hyperkalemia
C. Hypercalcemia
D. Hyperuricemia
E. Hyperphosphatemia

28. THANK YOU