Case 25 - Malignant Hyperthermia Flashcards
1
Q
What is MH?
A
- MH is a life-threatening familial hypermetabolic disorder of the skeletal muscle
- precipitated by SuX and volatile inhaled anes
- symptoms: tachycardia, tachypnea, hyperthermia, generalized muscle rigidity, acidosis, increased EtCO2 levels.
2
Q
What is the physiology of normal muscle contraction?
A
- in normal state, depolarization of skeletal muscle fiber membrane leads to Ca2+ release from sarcoplasmic reticulum (SR).
- calcium binds to sites on troponin, leading to normal excitation-contraction coupling.
- Ryanodine receptor = group of high-conducance SR calcium channels in muscle cells.
3
Q
What is the pathophysiology of MH?
A
- Ryanodine receptor (high-conductance SR calcium channels in muscles) undergo mutation and are dysfunctional.
- In MH, mutation of ryanodine receptor leads to uncontrolled release of Ca2+ from SR into cytoplasm, and decrease reuptake of Ca2+ back into SR. Overall, muscle cytoplasmic Ca2+ is increased
- Result = sustained muscle contraction, sustained hypermetabolic state, subsequent loss of cellular integrity.
4
Q
Why is hypermetabolic syndrome, like that of MH, detrimental?
A
hypermetabolic state produces:
- increased lactate levels due to constant energy being utilized
- high adenosine triphosphate (ATP) consumption,
- increase CO2 concentration due to energy consumption
- increase heat production secondary to sustained muscle contractions
Result:
- ATP production ceases –> loss of energy source, cell membranes unable to maintain its integrity and begin to break down.
- failure of intracellular pumps
- ischemic cells causes leakage of electrolytes into plasma (Hyperkalemia, hypercalcemia, increase creatine phosphokinase (CK), myoglobin.
- End result = arrythmias, end-organ damage, death
5
Q
What are the clinical features of MH (early vs late signs)?
A
MH characterized:
Early Signs
- sustained jaw rigidity/masseter rigidity
- tachycardia, PVCs, unstable BP
- tachypnea, increased ETCO2
- rising temperature, hypoxia (increased O2 consumption), acidosis (resp and metabolic), hyperkalemia.
Late Signs
- generalized muscle rigidity
- severe cardiac arrhythmias
- cardiovascular collapse
- rapid increasing temp
- life-threatening hyperkalemia,
- increased CPK
- DIC
- Myoglobinemia
6
Q
DDx of MH
A
Anesthesia Machine
- inadequate anesthesia/analgesia (increase O2 consumption due to anxiety/pain)
- insufficient ventilation/FGF
- overwarming
- exothermic reaction in absorber
Disorders / Diseases
- anaphylaxis
- sepsis
- pheochromocytoma
- neuromuscular disorders
- thyroid crisis
- carcinoid
Meds
- cocaine toxicity
- antimuscarinics
7
Q
What is masseter muscle rigidity?
A
- Masseter muscle rigidity (MMR) is the inability to open the jaw (trismus).
- can occur after SUX administration
- may be an early indicatior, but not pathognomonic, for MH.
8
Q
masseter muscle rigidity DDX
A
- inadequate dose of succinylcholine
- outdated/expired succinylcholine
- rapid succinylcholine hydrolysis
- underling myotonic dystrhopy
- trismus secondary to facial trauma
- Early sign of MH
9
Q
How do you manage masseter muscle rigidity?
A
Assume worst case scenario and proceed accordingly. Worst case scenario is early sign of MH.
- discontinue all triggering agents (sux, inhaled volatile anes)
- administer 100% oxgen
- continue monitoring for evidnece of other signs of MH (PVC, arrhythmia, tachycardia, increased ETCO2, increase core temp, tachypnea in spontaneous breathing patient)
- obtain ABG to look for resp or metabolic acidosis. If this is present, then treat for MH.
- if ABG does not show combined resp or metabolic acidosis, and if other clinical features of MH are not present, then you have three options:
- option 1 = postpone surgery, awake patient, continuous postop monitoring
- option 2 = convert to nontriggering anesthesia, proceed with surgery, carefully monitor for MH
- option 3 = if emergent and cannot be delayed, proceed with option 2, maintain high vigilance for MH.
10
Q
What are triggering agents of MH?
A
- potent inhaled volatile anesethetics (Sev, Des, Iso)
- Succinylcholine
11
Q
What are non-triggering agents of MH?
A
Anything that is NOT potent inhaled volatile anesthetics and SUX.
- Nitrous oxide
- propofol
- ketamine
- barbiturates
- BZD
- NMBDs
- all opioids
- all anesthetics
12
Q
What is the Dantrolene and MOA?
A
- Dantrolene is a muscle relaxant
- binds to the ryanoidine receptor, inhibiting calcium release from the sarcoplasmic reticiulum (SR).
- depresses the excitation-coupling system and thereby reverses the hypermetabolic state of MH.
13
Q
What does excitation-contraction coupling mean?
A
- physiological process of converting an electrical stimulus to a mechanical response
Skeletal Muscle:
- membrane potential of skeletal muscle cell is depolarised by an action potential (e.g. from synaptic activation from an alpha motor neuron)
- This depolarisation activates non-gated voltage sensors, dihydropyridine receptors (DHPRs)
- This activates ryanoidine receptor –> calcium is released from the SR into the local junctional space, leads to a calcium spark.
- causes a cell wide increase in calcium
- The calcium released into the cytosol binds to Troponin C by the actin filaments, resulting in muscle contraction
- The sarco/endoplasmic reticulum calcium-ATPase (SERCA) actively pumps calcium back into the SR
- As calcium declines back to resting levels, the force declines and relaxation occurs
14
Q
Dantrolene dose for MH tx?
A
MH Tx with Dantrolene
- Loading dose of 2.5mg/kg IV
- additional doses up to 10 mg/kg
- maintain with 1 mg/kg q 4-6 hours at least for 24 hours after MH episode.
15
Q
Dantrolene Side Effects?
A
- Dantrolene contains mannitol –> diuresis and possibly hypovolemia as a result
- muscle weakness
- respiratory failure (muscle relaxant because it decreases intracellular calcium in muscle cells)
- extravasation from vessel leads to tissue necrosis
- dizziness, n/v confusion
- should not administer along with CCB
- prophylactic preop admin of dantrolene to MH susceptible patients is NOT recommended
17
Q
Overall management of MH?
A
management includes prompt recognition and treatment.
Overall:
- immediately discontinue offending agents (sux, inhaled anes), increase minute ventilation, 100% oxygen, increase fresh gas flows (help eliminate inhaled anesthetics quicker).
- Call for Help
- Communicate with surgeon to terminate surgery ASAP . Patient safety = primary goal.
Acute Tx:
- call for help, alert sx
- get MH cart and crash cart
- remove vaporizer, swith to TIVA
- hyperventilate with 100% oxygen
- obtain larger bore IV access, place a-line
- perform ABG analysis to assess resp/metb acidosis
- administer dantrolene (2.5 mg/kg, repeat as needed up to 10mg/kg)
- treat hyperthermia
- treat arrhythmias
- Treat electrolyte abnormalities like hyperkalemia.
18
Q
How to treat metabolic disturbances in MH?
A
Hyperthermia (Stop when < 38 C)
- iced saline, cooling blankets
- cool irrigation of body cavities, ice packs
Hyperkalemia
- hyperventilation
- dextrose + insulin (adult dose = 10 U + 50 mL of Dextrose 50%)
- sodium bicarb (50 mEq/L over 5 min)
- CaC2 for life threatening hyperkalemia (10 mg/kg)
Arrhythmias
- usually resolves with tx of acidosis and hyper K
- avoid CCB
Acidosis
- respiratory - hyperventilate
- metabolic - sodium bicarb is pH < 7.2
Myoglobinuria
- hydration to maintain UOP > 2 mL/kg/hr
- furosemide, mannitol
- urine alkalinization
