Malignant hyperthermia definition (fill in the blanks)

________ hyper _________ state in _______

Tissue following exposure to a

__________________

Untreated fatality > 70%

Treated (in timely manner) 4%

• Defect in either the dihydropyridine or the ryanodine receptor
• Non-physiologic stimuli (ie: drugs) opens receptor and it stays open a long time
• Causes prolonged Ca++ release (huge amounts) from S.R.
• Large amts. of intracellular Ca++ Cause prolonged interaction between actin and myosin filaments
• Leads to increased/ prolonged interaction between actin and myosin filaments.

• muscle rigidity
• increased lactic acid
• increased CO2 production
• Muscle breakdown

Halothane

Sevoflurane

Isoflurane

desflurane

Succinylcholine

Possible heat/ exercise

Opioids

Non-depolarizing muscle relaxants

Ketamine

Propofol

Anxiolytics

Nitrous Oxide

Pediatric incidence of MH?

Adult incidence?

Overall Incidence?

peds: 1: 15,000

Adults: 1: 40,000

Overall: 1:10,000

Where are the high incidence areas in the U.S.?

True or False;

MH is an autosomal dominant disorder.

You are in pre-op and your patient says, "I have had surgery under general anesthesia before, and I didn't have any problems."

Should you worry about M.H.?

You should at least be "suspicious"

Because nearly 50% of patients with MH have had a previous uneventful surgical anesthetic.

What is the most specific and sensitive sign of M.H. in the O.R.?

What can mask this sign?

Is this a late sign or an early sign?

Sudden rise in ETCO2 is the most specific and sensitive sign of M.H.

Can be masked by hyperventilation

Considered the earliest sign of MH

What are the initial signs of M.H.?

What can cause you to miss these signs?

Initial: tachycardia and tachypnia

can be missed because these are usually blunted by general anesthetic drugs

Increase in BP

Vent. Dysrhythmias

Muscle rigidity (80%) of cases

Increase in body temp: 1-2 degrees every 5 minutes

CO2 absorbent activation (will get very hot!)

What will I see on ABG with "classic" MH?

Hyperkalemia

Hypercalcemia

lactic acidosis

myoglobinuria

Elevation of creatine kinase exceeding 20,000 (CK) within first 12-24 hours

Okay so I got this guy-

Almost died, but we saved him because we gave him a crap ton of Dantrolene. 

Now he is stable-

I report to the ICU nurse not to worry because we fixed him.  Is this statement entirely true?  Why or why not?

Not entirely true.  The ICU nurse should be vigilant as this syndrome can reappear in 24 to 36 hours.

We also have a problem now with myoglobinuria which can lead to renal failure and possible DIC

Rigidity of the jaw muscles after the administration of succinylcholine is called what?

More common in adults or children?

At what ages does this problem peak?

Masseter Muscle Rigidity (MMR)

More common in children

Peaks between ages of 8-12

True or False?

Additional doses of Succs or NDMRs may be needed in order to relieve Masseter Muscle Rigidity.

Why do I care about Masseter Muscle Rigidity?

What if it coincides with limb rigidity?

1. Myotonic syndrome

2. Temporomandibular joint dysfunction

3. Underdosing Succs

4. Intubating before succs works

5. increased succs tension in presence of fever or elevated plasma epinepherine.

1. Mild (Normal response to depolarization)

2. Moderate  (Can still intubate and ventilate)

3. JAWS OF STEEL (AHHH!)

Don't spaz out but Um.. your pt's masseter muscle IS spasming...

What now?

DON'T PANIC

1. If possible d/c anesthetic and postpone surgery

2. If continuing surgery move to anesthetic with non triggering agents (TIVA)

3. Pt should be observed for 12-24 hours for myoglobinuria and signs of M.H.  Dantrolene may be considered 1-2 mg/kg

4. Keep family informed of episode of MMR and potential risk for M.H.

5. Ck levels should be checked q 6 for 24 hours.

6. If CK levels >20,000 perioperatively and myopathy is not present- diagnosis of MH is very likely.  If negative- family members not usually tested.

According to the M.H. organization:

What happens to kids with Duchennes and Becker's muscular dystrophy?

What type of M.H. is this?

Kids with muscular dystrophy have succs. induced hyperkalemia that is NOT associated with M.H.

(so there is no type of M.H.-trick question)

This hyperkalemia is dangerous however (60% death) and needs to be treated like other hyperkalemic events.

Core Central Disease (CCD) is a congenital myopathy characterized by ________________ and is a result of a mutation in the ______________

receptor. 

What complication is CCD associated with?

Muscle weakness

ryanodine receptor

Several cases of MH have been associated with CCD.

True or False:

All pts with Central Core Disease (CCD) should have alternative anesthetics (ie: No volatiles)

True- High incidence of M.H.

Probably would avoid succs. as well.

Besides Core Central Disease,

What other defects or disorders would cause me to be suspicious of M.H.?

The myotonias (Steinherts dx, hypo/hyperkalemic periodic paralysis and others)

King Denborough syndrome: marked slanted eyes, low set ears, pectus deformity, scoliosis, small in stature

Osteogenesis imperfecta

Strabismus or the presence of ptsosis

[image]

[image]-----> you see this waveform

You notice your pt's temp is increasing

You touch the Absorbant and damn near burn your finger to the nub.....

Pucker factor has increased to Defcon 4 What now?

Holy Crap it might be Malignant hyperthermia!

Some hot dude better give iced fluids fast ladies!

1.  Stop volatile

-purge circuit

-change the absorbant

2.  Hyperventilate with 100% O2 at 10L/min

3. Dantrolene: 2.5 ml/kg q 15 unit symptoms resolve up to 10 mg/ kg

4. Bicarbonate for severe metabolic acidosis

-2-4 meq/kg

5. Glucose/insulin/hyperventilation/bicarb/ Ca Chloride 10 mg/kg or 1 gm IV for arrhythmias (following hyperkalemia treatment guidlines)

6. IV fluids (without K ie: NO LR), ice  packs, cooling blankets, cold gastric lavage

7. Furosemide- flush kidneys

(accounting for rhabdomyolysis producting myoglobinuria)

8. Tachycardias:

Lidocaine is the drug of choice. 

9.  Lab data

1) What drugs (for tachycardias) should be avoided in MH and why?

2) When do arrythmias usually resolve in MH?

1) Calcium Channel Blockers should not be used.

Verapamil will react with Dantrolene causing hyperkalemia

2) When the pt is dead or hypercarbia and hyperkalemia resolve

1) How does dantrolene work?

2) How is it dosed? 

3) Oh Yeah smart ass?  How do you reconstitute it?

1) directly in the muscle cell and binds on the ryanodine receptor and reduces the release of Ca++ from the SR

2)  2.5 mg/kg IV can repeat until symptoms resolve up to 10 mg/kg.  Repeat dose after 4-6 hours

3) 20 mg vials are reconstituted w/ 50-60 mls of STERILE WATER

True or False: (and explain why please)

1) While treating an episode of M.H. you notice arrhythmias. One of the culprits is more than likely the Dantrolene.

2) When using Dantrolene you probably want a foley catheter

1) False.  Dantrolene has little effect on the myocardium in prescribed doses

2) Dantrolene contains 300 mg of mannitol per vial.  Furthermore- you are already going to be worried about Rhabdo.

36 vials of Dantrolene cost how much?

$909/year or $2.51 per day.

(certainly less than Tim's dream date on this slide)

Timmmmmaaaaaayyyyyyyy!!!!!

Current concepts in M.H. (AKA: freakishly long True or false card)

1) Muscle rigidity may not be present in MH

2) Increased ETCO2 is an early sign

3) With proper treatment M.H. will not reoccur

4) Temperature increase is an early sign

5) MH may occur at any given point during an anesthetic

1) True

2) True

3) False

4) False

5) True

On poor little piggies with a ryanodine mutation.

I hear dantrolene injected bacon is delicious.

How do we test for MH in humans to confirm diagnosis? 

What are the pros and cons of this testing?

• Halothane/caffeine contracture test using muscle biopsy (vastus lateralis)- Gold Standard
• $> 5,000 usually covered by insurance
• Must go to center (there are 5 in U.S.)
• Many false positives
• Genetics looking for mutation of RYR-1 receptor hits only 30% positive so far.

Encouraged to be genetically tested.

If mutation known to be causative for MH is identified it is possible to determine MH susceptibility in other family members by examining the RYR-1 gene for that mutation.

Those with the defect are considered high risk for MH, however those who test negative can not be considered negative for MH.

1) The RYR-1 gene is big or small?

2) How long to sequence it?

3) How many mutations are known?

4) Do all mutations cause M.H.?

1) Huge (per gayle)

2) 3 months

3) 80 mutations

4) no

• thyroid storm

• Pheochromocytoma
• Sepsis
• Drug induced hyperthermia
  • Neuroleptic malignant syndrome
  • Serotonin syndrome
• Iatrogenic hyperthermia
• hypothalmic or brainstem injury

What is the Emergency 24/7 Phone number for MH?

You have a patient that is high risk for MH.

What do you do?

• Avoid MH triggers (hey ya think?)
• Anti anxiet medications
• Change soda lime and breathing circuit
  • Remove vaporizers
  • flush machine with 10L O2 for at least 20 minutes OR 10 minutes if the fresh gas hose is also changed
• Meticulous monitoring
• Cooling blanket
• MH stuff/ cart near by
• Cold fluids (at least 3 liters)

Pain perception is dependent on specialized ____________ that function as ______________

detecting the stimulus and then transducing and conducting it into the _____________.

1) neurons

2) receptors

3) Central Nervous system

Either protopathic or epicritic. 

Protopathic can be futher subdivided into fast and slow pain

What are the main points regarding Epicritic Pain/sensation?

I mean, If I were trying to annoy my wife with my newfound knowledge what would I likely tell her about epicritic pain?

• Considered Non-noxious
• Includes:
  
  • Light touch (A-β)
  • pressures (A-β)
  • proprioception (A-γ)
  • temperature discrimination (A-δ)
• Receptors that conduct epicritic sensations have low thresholds and these stimuli are usually conducted by large myelinated nerve fibers (See above: alpha beta/alpha gamma)

True or false:

Protopathic pain is considered noxious and receptors have a low threshold

False: high threshold

protopathic pain is considered noxious however

We know that protopathic pain can be further divided into fast and slow pain. 

Describe Fast Pain:

Describe Slow pain:

Fast Pain: Short, localized stabbing sensations that match the stimulis (ex: pin prick or surgical skin incision)  The pain begins with stimulis and stops when stimulis is removed

Slow pain:  Throbbing, burning, or aching sensation that is poorly localized and less specific.

Pain continues long after simulis is removed.

How is fast pain conducted?

How is slow pain conducted?

Fast: Alpha Delta fibers (lightly myelinated) at a conduction velocity of 12-30 m/s.

Slow: Via the unmyelinated C nerve fibers with conduction velocities of .5-2m/s.

In 1968 Margo McCaffery went down in nursing infamy because she declared in a bellowing voice

this:

All nociception produces pain but not all pain results from nociception.

What the hell does that mean?

Acute pain is primarily due to what?

What are the 3 types of acute pain?

nociception.

Superficial, Deep somatic, Visceral

Is usually d/t disease or abnormal function of an internal organ or covering (ie: parietal pleura, pericardium or peritoneum, dura) 

Visceral pain can be true or deferred

Chronic pain my be d/t nociception but also has other factors that often play a major role.

What are they?

There are 3 types of pain receptors.

What are they?

1) Mechanical Receptors

2) mechanothermal

3) Polynodal pain receptors

What do polynodal receptors respond to?

How do they conduct their impulses?

Mechanical, thermal, and chemical stimuli.

Conduct their impulses by the way of unmyelinated C Fibers.

True or False:

Pain receptors are highly adaptable which is important as a protective mechanism

False

Pain receptors do not adapt- which is an important protective mechanism

Tissues rate of metabolism

ie: muscle ishemia can be felt in 15-20 seconds

Skin- 20-30 minutes

Fill in the blanks (FROM HELL!! Hahha haha ah)

1) Pain signals from the periphery are carried via ____________________ (rapid conducting) and the ________________________ (slow conducting)

2) These Afferent fibers have their bodies in the ____________ ganglia and end in the __________.

3) In the dorsal horn they synapse with the ___________ neuron and __________ which may synapse with sympathetic neurons and ____________ neurons.

 1) Myelinated alpha delta fibers, Unmyelinated C Fibers

2) Dorsal root,  Dorsal Horn

3) second order, interneurons,  ventral horn motor

Myelinated tend to migrate medially

Unmyelinated small fibers become more lateral.

Your first order neurons like your Alpha delta or C fibers will synapse sometimes with ________ neurons then on to ____________ neurons in the dorsal horn of the spinal tract.

Then via the aforementioned neurons the signal crosses over to the ____________ tract then travels to the thalmus. 

So why is this interesting?

Interneurons

2nd order neurons

spinothalmic

Interesting because pain in the Right side of the body is then interpreted by the left side of the brain.  (and vice versa)

Pain fibers can ascend or descend 1-3 spinal chord segments via this tract before synapsing with the second order neurons in the gray matter of the ipsilateral (same side) dorsal horn. 

Why is this important to us in anesthesia?

Lissauer tract

OR

Posterior Funiculus

Important: because this is why we overshoot with epidurals- in case pain travels via this tract.

A-Delta fibers synapse with cells in which lamina primarily?

And to a lesser extent?

C- Fibers

Lamina I and V

Lesser Extent: II, III, IV, V

C-Fibers synapse with cells in which lamina primarily?

To a lesser extent?

Lamina I, II

Lesser extent: V

Rexed Lamina II, AKA- Substantia gelatinosa

Has Mu receptors that are important for opioid action!