Malignant Hyperthermia

Question 1

Malignant Hyperthermia

Answer 1

Potentially lethal disorder triggered by Succinylcholine and/or volatile anesthetics in susceptible individuals with resulting hypermetabolism, skeletal muscle damage, hyperthermia, acidosis, dysrhythmias

Question 2

inhaled anesthetics

Answer 2

all potential triggers except NO

Question 3

paralytic trigger

Answer 3

succinycholine

Question 4

Gene mutation

Answer 4

most common RYR1 (ryanodine receptor gene)
50 DNA variants

Question 5

Ryanodine receptor

Answer 5

Major calcium release channel in sarcoplasmic reticulum

Question 6

Ryanodine receptor dysfunction results

Answer 6

Leads to UNCONTROLLED release of calcium from the sarcoplasmic reticulum in muscle (sustained contractions)
Reuptake mechanism attempt to remove excess calcium
Depletion of ATP stores
Increased metabolism (increase oxygen consumption)
Accelerate heat and carbon dioxide production
Increasing lactic acid production

Question 7

Acidosis, Hyperthermia & ATP depletion results

Answer 7

Sarcolemma destruction
Marked increased in potassium levels
Myoglobin
Increased creatine kinase levels
Marked increased intracellular calcium

Question 8

Clinical signs

Answer 8

-First signs: Sinus Tachycardia, Hypercarbia, Masseter spasm (sometimes)

-Elevated end-tidal CO2 (increased PaCO2)

-Most common pattern: Respiratory acidosis with muscular abnormalities
Tachypnea in spontaneously breathing patient
Overbreathing (if not paralyzed) with mechanical ventilation
Rapid exhaustion of CO2 absorbent (Hot canister)

-Trunk or total body muscle rigidity
-Elevated temperature (may be early MH sign)
-Hypercalcemia
-Myoglobinuria

Question 9

Core body temperature

Answer 9

Core body temperature can be as high as 45 ° C. Can increase 1 ° C every 5 minutes.

Question 10

Lab results

Answer 10

-hyperkalemia
-hypercalcemia
-mixed respiratory & metabolic acidosis
-lactic acidosis
-marked increase CK levels
-myoglobinuria (due to rhabdo)

Question 11

Complications of MH

Answer 11

Hyperthermia (excessive cooling)
DIC
renal failure (d/t myoglobinuria)
Drug interactions
Death

Question 12

Preparation for MH crisis

Answer 12

Knowledge (assessment and interventions)
Dantrolene: on MH cart, backpack, and supply box
Crisis management though teamwork
-MH hotline
-cognitive aids
-adequate personnel to help during crisis
-simulation for preparedness

Question 13

Supplies needed for MH Crisis

Answer 13

-Dantrolene (IV access), Anesthesia drugs, emergency medications, Oxygen/airway, CODE CART
-MH App, MH Hotline, Cognitive Aids
-Team Communication System
-IVFs, IV supplies, IV pumps
-Supplies for multiple lab draws (istat, transporter)
-Bags of ice, Cooling blanket
-NG Tube with cool fluids for lavage
-Foley catheter
-Arterial line equipment, central line

Question 14

Emergency treatment of acute MH even

Answer 14

call for help

1: notify surgeon to halt procedure ASAP
2: discontinue volatile agents and succinylcholine triggers
3. get dantrolene/MH cart
4. hyperventilate with 100% O2 at flows of 10L/min to flush volatile anesthetics and lower ETCO2
5. insert activated charcoal filters

Question 15

Vapor-Clean (activated charcoal filters)

Answer 15

The Vapor-Clean™filter may become saturated after one hour; therefore, a replacement set of filters should be substituted after each hour of use.

Filters contain granules of activated charcoal to capture volatile anesthetic vapor molecules

concentration of vapor <5ppm in less than 2 minutes

Question 16

Dantrolene

Answer 16

Skeletal muscle relaxant
Acts within the muscle cell, reduces calcium release by the SR
Half-life of intravenous Dantrolene ~12 hours
Use with caution with neuromuscular disease
Give every 6 hours after MH clinical crisis episode
Muscle weakness can last for 24 hours
Side effects: muscle weakness, double vision, dizziness, nausea, diarrhea

Question 17

Ryanodex

Answer 17

250mg vial reconstituted w/ 5mls of sterile water

Loading dose 2.5mg/kg IV (actual weight) for either formulation

3 vialsshould be available in each institution where MH can occur, each to be diluted at the time of use with 5 ml of sterile water for injection, USP (without a bacteriostatic agent).

Question 18

Other adjunct medications

Answer 18

Obtain blood gas (venous or arterial) to determine degree of metabolic acidosis. Consider administration of sodium bicarbonate, 1-2 mEq/kg dose, for base excess greater than -8 (maximum dose 50 mEq).

Question 19

cooling the patient

Answer 19

Cool the patient if core temperature is >39°C or less if rapidly rising. Stop cooling when the temperature has decreased to <38°C.

Question 20

Dantrolene MHAUS requirement

Answer 20

Dantrolene must be available for all anesthetizing locations within 10 minutes of the decision to treat for MH.

Should have at least 36 vials readily available at your institution

Dantrolene must be available for all anesthetizing locations where MH trigger agents are used

Question 21

Dantrolene formulations

Answer 21

2.5mg/kg (actual weight) rapidly though large-bore IV - repeat until patient responds with decrease in ETCO2, decreased muscle rigidity, and/or lowered HR

. Large doses (>10mg/kg) may be required for patients with persistent contractures or rigidity (MHAUS). No ceiling dose of Dantrolene

Dantrium/Revono: each 20mg vial needs 60mls of sterile water for injection (36 vials - 15min prep)

Question 22

Ryanodex MH Protocol

Answer 22

Less than 1 minute for reconstitution and administration of a loading dose (2.5 mg/kg) in an MH crisis
Fewer vials required to treat MH (1 vial contains 250 mg of dantrolene sodium)
1 vial of RYANODEX® contains the same amount of dantrolene sodium as 12.5 vials of other approved dantrolene sodium formulations

Over 99% less sterile water for injection than otherdantrolene sodium IV treatments
1 vial provides a loading dose (2.5 mg/kg) for patients up to 100 kg

Question 23

Hyperkalemia treatment for MH

Answer 23

If hyperkalemia (K > 5.9 or less with ECG changes) is present, treat with:

Calcium chloride 10 mg/kg (maximum dose 2,000 mg) or calcium gluconate 30 mg/kg (maximum dose 3,000 mg) for life-threatening hyperkalemia

Sodium bicarbonate: 1-2 mEq/kg IV (maximum dose 50 mEq)

Glucose/insulin

– For pediatric patients: 0.1 units regular insulin/kg IV and 0.5 grams/kg dextrose (% in formulation not important)
– For adult patients: 10 units regular insulin IV and 50 ml 50% dextrose
–Check glucose levels hourly
For refractory hyperkalemia, consider albuterol (or other beta-agonist), kayexelate, dialysis, or ECMO if patient is in cardiac arrest.

Treat dysrhythmias - standard medication but avoid calcium channel blockers.

Diurese to >1ml/kg/hr urine output. If CK or K+rise, assume myoglobinuria and give bicarbonate infusion of 1 mEq/kg/hr, to alkalinize urine (more mannitol in Dantrium dosing vs. Ryanodex)

Question 24

indicators of stability

Answer 24

When stable, transfer to post anesthesia care unit or intensive care unit for at least 24 hours.

Key indicators of stability include:
ETCO2is declining or normal
Heart rate is stable or decreasing with no signs of ominous dysrhythmias
Hyperthermia is resolving
If present, generalized muscular rigidity has resolved

Question 25

Masseter muscle rigidity

Answer 25

Marked difficulty in manual mouth opening that interferes with and impedes direct laryngoscopy and tracheal intubation without the presence of temporomandibular joint dysfunction. When MMR occurs in response to administration of succinylcholine in the absence of an underlying temporomandibular joint disorder or myotonia, it may be an initial sign of MH. More common in children & young adults” (MHAUS) Not relieved by additional Sux or NMBDs Differential diagnosis Myotonic syndrome, TMJ, underdosing of Sux, insufficient time allowed for Sux onset, increasing resting tone after Sux associated with fever or elevated plasma epinephrine, MH

Question 26

MH cart contents

Answer 26

Dantrolene sterile water NaHCO3 D50 Calcium chloride Regular Insulin Charcoal filters syringes IV catheters NGT Toomy irrigation syringes

Question 27

MH testing

Answer 27

muscle biopsy (halothane-caffeine contracture test) genetic testing

Question 28

Conditions resembling MH

Answer 28

Neuroleptic malignant syndrome - Symptoms include high fever, sweating, unstable blood pressure, stupor, muscular rigidity, and autonomic dysfunction. Pheochromocytoma Thyrotoxicosis Sepsis Hypoxic encephalopathy Mitochondrial myopathies

Question 29

predisposing conditions

Answer 29

Central core disease Central core disease is a disorder that affects muscles used for movement (skeletal muscles). Most people with central core disease experience persistent, mild muscle weakness (hypotonia, floppy) that does not worsen with time. This weakness affects the muscles near the center of the body (proximal muscles).  Multiminicore disease Multiminicore disease is a disorder that primarily affects muscles used for movement (skeletal muscles). This condition causes muscle weakness and related health problems that range from mild to life-threatening. King Denborough Syndrome The King-Denborough syndrome (KDS) is a congenital myopathy associated with susceptibility to malignant hyperthermia, skeletal abnormalities and dysmorphic features with characteristic facial appearance. Although the cause of King-Denborough syndrome is not fully understood, at least some cases have been attributed to the ryanodine receptor gene (RYR1), which has been tied to malignant hyperthermia and central core disease.

Question 30

Safe anesthetic drugs for MH patient

Answer 30

Intravenous anesthetics, nitrous oxide, local anesthetics, opioids, benzodiazepines, and/or non-depolarizing muscle relaxants TIVA with Propofol (general), regional, MAC, or local anesthesia technique Recommend first case of the day Change CO2 absorbent & breathing circuit Use charcoal filters Notify team of plan and increase MH risk **Remove Succinylcholine from area. Remove or tape off Vaporizers to avoid accidental use. Have Dantrolene and all necessary equipment readily available. Alert pharmacist and staff of MH or MH susceptible patient.

Question 31

Preparation for the MHS patient

Answer 31

Disable vaporizers (remove or tape in “OFF” position) Attach new breathing circuit and reservoir bag. Place bag on circuit & set ventilator to inflate bag periodically [flush anesthetic gases from the system] New machines: 10L/min FGF for up to 104 minutes Older machines: 10L/min FGF for up to 20 minutes Option: add activated charcoal filters to circuit to remove anesthetic gases (eliminates need to purge the system). NOTE: Anesthesia machine will still need to be flushed with high fresh gas flows (≥ 10 L/min) for 90 seconds prior to placing the activated charcoal filters on both the inspiratory and expiratory ports.

Question 31

Preparation for the MHS patient

Answer 31

Disable vaporizers (remove or tape in “OFF” position) Attach new breathing circuit and reservoir bag. Place bag on circuit & set ventilator to inflate bag periodically [flush anesthetic gases from the system] New machines: 10L/min FGF for up to 104 minutes Older machines: 10L/min FGF for up to 20 minutes Option: add activated charcoal filters to circuit to remove anesthetic gases (eliminates need to purge the system). NOTE: Anesthesia machine will still need to be flushed with high fresh gas flows (≥ 10 L/min) for 90 seconds prior to placing the activated charcoal filters on both the inspiratory and expiratory ports.