Patient Case -

Rhabdomyolysis

Megan Spence
PGY1 Pharmacy Resident
Ascension St. Vincent Evansville
October 27, 2021
Objectives

• Define rhabdomyolysis and identify diagnostic features and relevant labs in

monitoring.

• Recognize patients at risk for rhabdomyolysis

• Identify treatment and management options

• Apply all of the above to a patient scenario

2
Rhabdomyolysis Definition

• Destruction of striated muscle cells

• Muscle necrosis

• Characterized by the release of

intracellular muscle components into
circulation

3
HPI

JH is a 64-year-old male who presented from an outside facility for more

advanced care based on increased altered mental status. According to the
patient, 2 nights ago patient was walking in his home and fell. He claimed to be
on the ground for eight hours as he crawled to a phone to call for help. The next
night, he felt like he was experiencing memory loss; his son noticed and called
EMS to take him to a hospital. He presented as septic with unknown infectious
origin, suspected CAP. Of note, patient is 233kg s/p gastric bypass.

Primary diagnosis was of sepsis, secondary to CAP, with respiratory failure.

4
Past Medical History Home Medications
• Albuterol
• COPD • Amlodipine
• Type 2 DM • Atorvastatin
• Stage III CKD • Carvedilol
• CHF • Chlorthalidone
• Hypertension • Combivent Respimat
• Hyperlipidemia • Fluticasone-Salmeterol
• Anxiety • Furosemide
• Depression • Glipizide
• Lisinopril
• Montelukast
• Potassium Chloride
• Spironolactone
• Venlafaxine
• Warfarin

5
Possible Causes
• Trauma and muscle
compression
• Crush syndromes
• Immobilization
• Exertional, nontraumatic
• Physically untrained
• Hot, humid conditions
• Sickle cell trait
• Hypokalemia d/t sweating
• Thermal extremes
• Malignant hyperthermia
• Hypothermia
• Drugs
• Comas induced by alcohol,
overdoses, or CNS depressants
• Direct myotoxins: statins, colchicine
• Daptomycin
• More on next slide
• Toxins
• Infections
• Electrolyte Disorders
6
Common Medications Associated with Rhabdomyolysis

• Statins (HMG-CoA reductase inhibitors)

• Pathway inactivation of GTPases, which alter cellular function
• In conjunction with cytochrome P450 Inhibitors → increased risk
• Daptomycin
• Spontaneous contraction
• Psychiatric Agents
• Majority high-dose
• Antihistamines
• Overdoses
• Injury through tissue
• Propofol
• Toxic to mitochondria

7
Risk Factors (Based on Patient History)

• Advanced age • Immobilization

• Female • Coma
• CKD • Sickle Cell Trait
• DM • Hypokalemia
• Hypothyroidism • Hypophosphatemia
• Inflammatory or metabolic • Severe dehydration
myopathies • Recreational drug use
• Trauma or crush injuries • Prescribed medications
• Hyperthermia • Acute infections
• Seizures/muscle tremors • Influenza, Coxsackie, EBV, HSV,
• Severe exertion HIV
• Prolonged surgical interventions

9
Signs Symptoms

• Muscle tenderness • Muscle pain

• Muscle swelling • Muscle weakness
• Muscle weakness • Dark urine
• Skin discoloration • Malaise
• Blistering • Fever
• Tachycardia
• Nausea/Vomiting
Patient had a rash on the right lower • Abdominal Pain
extremity and left foot, but no other • Altered Mental Status
physical signs were mentioned.

In JH, muscle weakness (fall) and

altered mental status were the only
two reported symptoms.
10
Laboratory Findings

• Elevated creatine • CPK 2968 at outside facility, 2886

phosphokinase (CPK) here
• At least 5x ULN • Urinalysis:
• Can range from 1500 - 100,000 • Proteinuria, RBC present
• Reddish-brown urine • AST/ALT 88/33
• Caused by myoglobin release • K 5.7
• Proteinuria
• Phos 6.0
• Elevation in aminotransferases
• Ca 8.3
• Electrolyte abnormalities
• Hyperkalemia • pH 7.25
• Hyperphosphatemia • pCO2 49
• Hypocalcemia • HCO3 21
• Hyperuricemia
• Metabolic acidosis

11
Diagnosis

• Testing should be performed in • Evaluation

patients with: • Elevated CPK
• Myalgias and pigmenturia • Urinalysis
• Myalgias OR pigmenturia and with • Neuromuscular illness OR dark
relevant history urine PLUS elevated CPK
• Absence of myalgias and
pigmenturia but with other s/s such
as:
• Muscle tenderness
• Muscle weakness
• Abnormal labs suggestive of cell
breakdown
• Acute kidney injury

12
Kidney Injury and Rhabdomyolysis

• 15-50%
• Risk is lower in patients with CPK <15,000
• For lower values, risk increases with: dehydration, sepsis, acidosis
• Volume depletion results in:
• Renal ischemia
• Tubular obstruction
• Tubular injury

• On admission, JH had a Scr of 3.61, and GFR of 17. Within 10 hours of fluid
administration, Scr was 2.71, with GFR at 24. In two days, Scr was back to
baseline of 1.3, with a GFR of 55.

13
Kidney Injury Pathogenesis and Presentation

• Myoglobin is filtered by the glomerulus and then degraded, releasing heme

pigment.
• Heme pigment injures kidneys:
• Tubular obstruction of heme casts
• Direct proximal convoluted tubule cell injury
• Vasoconstriction → reduced blood flow
• Triad presentation:
• Granular casts in urine
• Red-brown urine
• Elevated CPK

14
Risk Prediction Score
JH’s Score:
• Age > 50 to < 70 yoa (1.5)
• Age > 70 to < 80 yoa (2.5)
•
•
•
Age > 80 yoa (3)
Female sex (1)
Initial Scr 1.4 - 2.2 mg/dL (1.5)
11.5
• Initial Scr > 2.2 mg/dL (3)
• Initial serum calcium < 7.5 mg/dL (2)
• Initial CPK >40,000 (2)
• Underlying cause other than seizures,
syncope, exercise, statins, or myositis (3)
• Initial serum phosphate 4.0 - 5.4 mg/dL (1.5)
• Initial serum phosphate > 5.4 mg/dL (2)
• Initial serum bicarbonate < 19 mEq/L (2)

15
Clinical Course

JH was soon admitted to the CVICU, because there were first concerns about his
congestive heart failure. Nephrology and critical care were consulted when
admitted. Patient was hemodynamically unstable (79/42, 54); normal saline and
norepinephrine drips were started.

Within 10 hours of starting fluids, CPK decreased to 1456. A little over a day
later, CPK was back within normal limits, at a value of 184. However, electrolyte
management then became an issue, with low-normal magnesium and recurring
hypokalemia.

16
Management

• Isotonic Fluids
• NS 125 mL/min
• D/c offending agents
• Atorvastatin and venlafaxine were continued upon admission
• Lisinopril and spironolactone were never continued while inpatient
• Electrolyte management
• Potassium decreased after fluid resuscitation, potassium replacement protocol used
• Magnesium
• Phosphorus elevated on admission, level was not checked again
• Bicarbonate
• Was not administered during clinical course

17
Questions?

18
References
• Miller, M.L. (2021). Clinical manifestations and diagnosis of rhabdomyolysis. In I.N. Targoff, J.S.
Shefner, & J.F. Dashe (Eds.), UpToDate.
• Miller, M.L. (2021). Causes of rhabdomyolysis. In I.N. Targoff, J.S. Shefner, & J.F. Dashe (Eds.),
UpToDate.
• Hohenegger, M. (2021). Drug induced rhabdomyolysis. Current Opinion in Pharmacology, 12(3),
335-339. https://doi.org/10.1016/j.coph.2012.04.002
• Perazella, M.A., Rosner, M.H. (2019). Clinical features and diagnosis of heme pigment-induced
acute kidney injury. In P.M. Palevsky & J.P. Forman (Eds.), UpToDate.
• Neyra J.A., Rocha N.A., Bhargava R., Vaidya O.U., Hendricks A.R., Rodan A.R.
Rhabdomyolysis-induced acute kidney injury in a cancer patient exposed to denosumab and
abiraterone: A case report. BMC Nephrology. 2015;16(1). doi.10.1186/s12882-015-0113-6
• Perazella, M.A., Rosner, N.A. (2019). Prevention and treatment of heme pigment-induced acute
kidney injury. In P.M. Palevsky & J.P. Forman (Eds.), UpToDate.
• Torres, P.A., Helmstetter, J.A., Kaye, A.M., & Kaye, A.D. (2015). Rhabdomyolysis: pathogenesis,
diagnosis, and treatment. The Ochsner journal, 15(1), 58-69.
• Huang S-S, Yang H-Y, Lin Y-C, Chan C-H. Low-dose venlafaxine-induced severe rhabdomyolysis:
A case report. General Hospital Psychiatry. 2012;34(4). doi:10.1016/j.genhosppsych.2012.01.016

19