1
Q
What is malignant hyperthermia?
A
Inherited disorder of skeletal muscle
2
Q
What triggers Malignant Hyperthermia?
A
Triggered in susceptible humans or animals by volatile inhalation agents or succinylcholine
3
Q
What anesthetics can cause Malignant Hyperthermia?
A
- Sevoflurane
- desflurane
- isoflurane
- halothane
- enflurane
- ether
4
Q
What are other triggers for Malignant Hyperthermia?
A
Vigorous exercise and heat**
5
Q
What is malignant hyperthermia characterized by?
A
- Hyper metabolism
- Skeletal muscle damage
- Hyperthermia
- Death
6
Q
True incidence of Malignant Hyperthermia is ________
A
Unknown
7
Q
What is the genetic component of Malignant Hyperthermia?
A
Autosomal dominant
8
Q
What is the clinical incidence in adults with Malignant Hyperthermia?
A
1 in 3,000 – 1 in 50,000 anesthetics
9
Q
What is the pediatric incidence of Malignant Hyperthermia?
A
Children under 15 years comprise approx. 52% of all reactions
10
Q
Which gender is more like to cause Malignant Hyperthermia?
A
More common in males (2.5-4.5 times)
11
Q
What is the autosomal dominant traits for Malignant Hyperthermia?
A
One abnormal gene needed to manifest symptoms
12
Q
How many mutations are associated with Malignant Hyperthermia?
A
Associated with 34 genetic mutations
13
Q
What are the most common genetic mutations for Malignant Hyperthermia?
A
- RYRI (70%) (ryanodine receptor for Ca++ release at SR)
- CACNA1S (1%) (subunit of dihydropyrdine Ca++ channel on T-tubes)
14
Q
What is variable penetrance mean in association with Malignant Hyperthermia?
A
Susceptible patient does not necessarily trigger to every exposure
15
Q
Review genetic components of Malignant Hyperthermia.
A
16
Q
The gene for the RYR 1 receptor is located on _________
A
chromosome 19
17
Q
Where are all of the genetic mutations associated with Malignant Hyperthermia located?
A
chromosome 19
18
Q
Where is calicum stored?
A
Invaginations of plasma membrane known as t-tubules which are surrounded by sarcoplasmic reticulum which stores intracellular calcium.
19
Q
What is the unique feater of the sarcolemma?
A
- It has holes in it.
- These “holes” lead into tubes called transverse tubules (or t-tubules for short).
- These tubules pass down into the muscle cell and go around the myofibrils.
- However, these tubules do not open into the interior of the muscle cell; they pass completely through and open somewhere else on the sarcolemma (i.e., these tubules are not used to get things into and out of the muscle cell).
20
Q
What is the function of the T-tubules?
A
The function of t-tubules is to conduct impulses from the surface of the cell (sarcolemma) down into the cell and, specifically, to another structure in the cell called the sarcoplasmic reticulum.
21
Q
How is the muscle fiber excited?
A
- A muscle fiber is excited via a motor nerve that generates an action potential that spreads along the surface membrane (sarcolemma) and the transverse tubular system into the deeper parts of the muscle fiber.
- A receptor protein (DHP) senses the membrane depolarization, alters its conformation, and activates the ryanodine receptor (RyR) that releases Ca2+ from the SR. Ca2+ then bind to troponin and activates the contraction process
22
Q
Review the normal skeletal muscle.
A
23
Q
Describe the normal skeletal muscle diagram.
A
Interior of skeletal muscle cell:
- Plasma membrane
- Invagination of plasma membrane into the cell (t-tubule)
- Protein embedded in the wall of the t-tubule – Dihydropyridine protein
- Large protein in sarcoplasmic reticulum - ryanodine
- Sarcoplasmic reticulum that stores calcium in the cell
- Contractile proteins in the cell
- Reuptake of intracellular calcium after contraction
Bottom left = mitochondria (energy producers)
24
Q
What does the dihydropyridine receptor sense?
A
- The dihydropyridine receptor senses the membrane depolarization, alters its conformation, and activates the ryanodine receptor (which releases Ca2 from the sarcoplasmic reticulum, a Ca2 storage area).
- Ca2 binds to troponin and activates the contractile machinery.
- In classic malignant hyperthermia, uncontrolled Ca2 release from the SR leads to an increased pump activity and heat production, mainly by the adenosine triphosphate-dependent Ca2 reuptake into the SR.
- To cope with the increased energy consumption, glycogen stores will be depleted for maximal adenosine triphosphate production
25
What can the myoplasmic Ca2 overload may stimulate?
also stimulate Ca2 sensitive proteases, liposomal enzymes, and nuclear DNases, potentially resulting in rhabdomyolysis.
26
What is the MOA of Malignant Hyperthermia?
Dysregulation in intracellular calcium homeostasis
27
MH: Calcium released from the sarcoplasmic reticulum in quantities that _______ normal
far exceed
28
What does excess calcium release lead to?
Leads to actin and myosin continually contracting = contracture
29
What do accelerations in cellular processes lead to? (8)
* Heat production
* Excess lactate
* Oxygen consumption → Anaerobic metabolism, lactic acid
* Carbon dioxide production
* Depleted ATP stores
* Cell breakdown with contents entering circulation and causing downstream effects
* Acidosis, hyperthermia and ATP depletion lead to destruction of the sarcolemma
30
What moves into the extracellular fluid with malignant hyperthermia?
K+, myoglobin and creatine kinase move into extracellular fluid
31
What are the clinical signs of Malignant Hyperthermia?
* Tachycardia\*\*
* Unanticipated increase in ETCO2 levels (\>55mmHg) that are out of proportion to MV\*\*
* Tachypnea
* Skin mottling
* Rigidity
* Hyperthermia
* Myoglobinuria
* Mottled, cyanotic skin
* Decreased SaO2
* Arrhythmias and labile BP
* Mixed metabolic and respiratory acidosis
32
What are the hallmark signs of malignant hyperthermia?
* Tachycardia\*\*
* Unanticipated increase in ETCO2 levels (\>55mmHg) that are out of proportion to MV\*\*
33
What are the characteristics of Rigidity with malignant hyperthermia?
Rigidity (present in 75% of cases): masseter muscle or generalized
34
What are the characteristics of hyperthermia with malignant hyperthermia?
* Hyperthermia (1-2 degrees Celsius increased every 5 min)
* May be early or late sign
35
What are the characteristics of Myoglobinuria with malignant hyperthermia?
* Myoglobinuria (cola colored urine)
* Myoglobin released from inside muscle cell
36
What causes of arrhythmias and labile BP with malignant hyperthermia?
Caused by acidosis, hyperkalemia and hyperthermia
37
What are the laborarotry findings for Malignant Hyperthermia?
* ABG: Respiratory and metabolic acidosis
* Serum potassium \>6 mEq/L
* CK \>20,000 units/L
* Serum myoglobin \>170 mcg/L
* Urine myoglobin \>60 mcg/L
38
What is the onset of Malignant Hyperthermia?
Intraoperatively or shortly afterwards
39
What is the different types of rate of onset?
* Fulminant
* Indolent
40
Define Fulminant.
Onset of full-blown syndrome within minutes of induction of general anesthesia
41
What effects does succinylcholine have on the timing of malignant hyperthermia?
Succinylcholine may accelerate onset and increase MH severity
42
What is the compenents of differential diagnosis for malignant hyperthermia?
Tachycardia, hyperpyrexia, tachypnea, hypercapnia and masseter muscle rigidity can be found in other disease states
43
Other than MH, what could lead to an elevated end tidal carbon dioxide? (3)
* Malfunction in the one-way valves of the circle system
* Problem with carbon dioxide absorbent
* Retained CO2 with pneumoperitoneum and subcutaneous air
44
What other (disease) states may mimic malignant hyperthermia?
* Insufficient anesthetic depth
* Hypoxia
* Pheochromocytoma
* Sepsis
* Hyperthyroidism/Thyrotoxicosis
* Neuroleptic malignant syndrome
45
What would an end tidal waveform look like in a patient with malignant hyperthermia?
46
What is the overall treatment of Malignant Hyperthermia Crisis?
* Call for help / Alert operating room staff
* Turn off triggering agents (inhalational anesthetics)
* Hyperventilation with FIO2 1.0
* Cool
* Consider cognitive aid
47
What is the medication treatment for malignant hyperthermia?
Dantrolene or Ryanodex
48
What is the malignant hyperthermia phone number?
1-800-MH-HYPER (MHAUS)
49
What is the hyperventilation components of malignant hyperthermia?
* High gas flows
* Adding charcoal filter to circuit to scrub residual agent
50
What diseases have a strong clinical and/or genetic links to MH susceptibility found with?
* Central Core disease
* King Denborough syndrome
* Multi-minicore disease
51
Define Multi-minicore disease.
A rare, inherited condition which causes degeneration of the muscle fibers
52
Define central core disease.
Genetic disease of the ryanodine receptor
53
Define king denborough syndrome.
Rare genetic non-dystrophic myopathy characterized by the triad of congenital myopathy, dysmorphic features and susceptibility to malignant hyperthermia
54
What diseases have no risk or link to MH?
There is NO risk for MH beyond the normal general population in patients with Duchenne or Becker muscular dystrophy, neuroleptic malignant syndrome, myotonia congenita or myotonic dystrophy
55
What should be done first if MH is suspected?
Notify surgeon to halt surgery ASAP
56
What needs to be done for your anesthetic in a MH crisis?
* D/C inhalational agents (succinylcholine)
* If surgery must continue - switch to TIVA
57
Who needs to be called in a MH Crisis?
Call for help! (call 911 if at an ASC); call MHAUS
58
What needs to be brought into the room in a MH Crisis?
MH cart
59
Why is hyperventilation of MH Crisis needed?
* Hyperventilate (to rid agent and drive down PaCO2) at high flows (at least 10L/min)
•Remove vaporizers
* flush machine
* add charcoal filter (saturate at about 1 hour)
60
What is the dose of the medication for MH Crisis?
Dantrolene 2.5 mg/kg rapidly via large bore IV until patient responds (lower HR, lower CO2, decreased rigidity (may require up to 10 mg/kg)
61
What labs need to be monitored for MH Crisis?
* Obtain ABG and treat metabolic acidosis (BE \> 8)
* Monitor serum electrolytes, blood glucose, coagulation profile, CK, blood and urine myoglobin and liver enzymes
62
What is the dose of bicarbonate for the treatment of metabolic acidosis with MH Crisis ?
1-2 mEq/kg of bicarbonate
63
What is the process of cooling a patient for MH Crisis?
Cool patient if temp \> 39 C, stop when \< 38.5 C – cooling lavage (orogastric, bladder, open cavities), chilled IV saline, cooling blanket, ice (groin axilla and neck)
64
What electrolytes need to be treated with MH crisis?
* Hyperventilation, bicarbonate, glucose/insulin
65
What can be used to treat refractory hyperkalemia?
B-agonist such as albuterol, kayexalate, dialysis, ECMO
66
What should be avoided for the treatment of dysrhythmias?
avoid Ca++ channel blockers – When given with dantrolene may cause life threatening myocardial depression and hyperkalemia
67
What kidney interventions need to happen when treating MH?
Diurese to \>1ml/kg/hr urine output with hydration, furosemide (0.5-1mg/kg and mannitol prn
68
What needs to be followed as a result of MH crisis?
HR, core temperature, ETCO2, minute ventilation, blood gases, K+, CK, urine myoglobin and coagulation studies as warranted by the clinical severity of the patient
69
What is the MOA of Dantrolene?
* Muscle relaxant that doesn’t work at neuromuscular junction
* Binds to ryanodine calcium channel and reduces calcium efflux from sarcoplasmic reticulum
70
What are the two preparations of Dantrolene?
* Dantrium/Revonto
* Ryanodex
71
What is the dose for Dantrium/Revonto?
* 20mg vial to be reconstituted with 60mL of sterile water
* 3 grams of mannitol in each 20mg vial
* Dose is 2.5mg/kg for initial dose
72
What is the solubility of Dantrium/Revonto?
Very poor water solubility
73
What is the dose of Ryanodex?
* 250mg vial to be reconstituted with 5mL of sterile water
* 0.125 gram of mannitol in each 250mg vial
74
Review the effect of dantrolene.
* Effect of dose of dantrolene on MH symptoms
* Time on x-axis
* Minute ventilation and end tidal carbon dioxide on y-axes
* After 6 hours of anesthesia time minute ventilation (blue line) and end tidal carbon dioxide increase
* At 12 hours recognized as MH
* Dantrolene administered at white arrow and symptoms resolve quickly
75
What happens After Immediate Crisis?
Transfer to hospital
76
If admitted to the ICU how long is the admission for MH last.
ICU admission for 36 hours minimum
77
What are the monitoring that should be completed after the immediate crisis?
* Continuous central temperature monitoring
* Serial labs
78
What needs to be monitored for peak levels?
CK peaks many after hours the event. Monitor for peak and declination
79
How long should dantrolene be administered?
1. Continue dantrolene for minimum 24 hours
2. Dose: 1mg/kg every 4-6 hours as a bolus OR 0.25mg/kg/hr via continuous infusion
80
What is the rate of reoccurrence of MH?
Recrudescent rate 25% in first 24 hours, mean 13 hours
81
What can be administered for kidney protection?
* Saline and NaHCO3
* Myoglobin is toxic to kidneys
82
What needs to be done after the MH crisis?
* Patient and family counseling
* ID bracelet/necklace
83
What registry does patient needed to be added to after MH crisis?
North American Malignant Hyperthermia Registry
84
What form needs to be completed following a MH crisis?
AMRA (Adverse Metabolic Reaction to Anesthesia) form
* To be completed by anesthesia providers involved in case
* Can be anonymous or with patient information with patient consent
85
What do patients need to be referred to after a MH crisis?
* Testing
* Refer to MH testing center
86
What is not the gold standard for MH testing?
Genetic testing is not the gold standard because we don’t yet understand all of the mutations that may make an individual susceptible to MH
87
What is the gold standard for MH testing?
**Caffeine Halothane Contracture Test**
* Skeletal muscle sample contractile response to caffeine, halothane or both
88
What is the MOA of the Caffeine Halothane Contracture Test?
Invasive - Uses fresh vastus lateralis muscle biopsy and test must be completed within hours of muscle harvest
89
What are properties of the Caffeine Halothane Contracture Test?
* Requires travel to 1 of 4 designated centers in North America
* Expensive
90
Review components of the Caffeine Halothane Contracture Test.
91
Identify the normal versus abnormal test.
* X-axis = time
* Y-axis = tension
* Top graph – tension increases after exposure to caffeine or halothane
* Bottom graph – muscle tension significantly increases with exposure.
* Diagnosed with MH susceptibility
92
Define sensitivity.
* (measures how often a test correctly generates a positive result for people who have the condition that’s being tested for)
* Very few false negatives
93
Define specificity.
* (measures a test’s ability to correctly generate a negative result for people who don’t have the condition that’s being tested for)
* Significant number of false positives
94
What is the sensitivity and specificity?
95
What should be done for MH Susceptible Patients?
* Standard monitors and consider a cooling blanket under the patient
* Consider regional or local anesthetic if possible
* Use of a non-triggering general anesthetic
96
What should be done to the AGM for MH Susceptible Patients?
Remove trace anesthetic gases from AGM (review specific AGM instructions)
* Change CO2 absorbant
* Ensure vaporizers are disabled by removing or taping them off
* Flush AGM and ventilator with oxygen at ≥10 L/min for 20-104 minutes
* Use new breathing circuit and reservoir bag
* Add charcoal filters to inspiratory and expiratory limbs
* Have MH cart in OR
* Monitor postoperatively for a minimum of 2 hours
97
Where can you find information regarding the AGM for MH susceptible patients?
review specific AGM instructions
98
How long should MH susceptible patients be monitored after uneventful anesthesia?
* The patient susceptible to MH undergoing outpatient surgery may be discharged on the day of surgery if the anesthesia has been uneventful.
* A minimum period of 1 hour in PACU monitoring vital signs at least every 15 minutes and an additional hour is phase II PACU/step down unit is recommended.
99
Can calcium gluconate or calcium chloride be used when treating hyperkalemia cardiac toxicity during an MH crisis?
Yes
100
Is MH linked to other serious medical problems? If so, which ones?
* Central core disease
* King Denborough syndrome
* Multi-minicore disease
101
If you were responsible for making the MH kit for your operating room, what supplies would you include?
* **Required Medications**
* Dantrolene 36 vials
* Ryanodex?
* Sterile water
* Sodium bicarbonate
* Dextrose
* Mannitol
* Furosemide
* Antidysrhythmic drugs
* Necessary Equipment
* Temperature probes
* Nasogastric tubes
* Assorted catheters
* Blood collection tubes
* Syringes
* Needles
* Normal saline
102
What is the hotline number to call during a MH crisis?
1-800-MH-HYPER
2-General Principles Exam 3
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