What area of the brain regulates temperature?
Hypothalamus
most improtant area for temp regulation
Gain center: posterior hypothalamus
Loss center: anterior hypothalamus
For each 1 degree fahrenheit change, basal metabolic rate will change how much?
7%
Routes of heat loss - in %
Radiation 40%
Convection 30%
Evaporation (burn pt)
Conduction
MH incidence?
1:8,000 to 1:50,000 adults (depending on the source cited)
Higher in children
How does someone get MH?
Genetic susceptibility;
autosomal dominant RYR mutations are common in MH patients
MH pathophysiology (generalized)?
It is a syndrome
a chain of clinical responses to muscle hypermetabolism ("decoupling"; ATP needed for Ca release)
issue with innapropriate Ca++ release
4 earliest signs of MH and other s/s?
4 earliest:
- hypercarbia
- tachycardia
- tachypnea
- masseter spasm
Other:
- hyperthermia (inc 1-2°C every 5 min)
- hypertension
- dysrhythmias (r/t acid/base imbalance, hyperkalemia)
- metabolic acidosis
- hyperkalemia
- myoblobinuria
- hypoxemia
- elevated CPK with rhabdo
- coke-colored urine
**Most common to be noted 1st in clinical practice - hyperthermia**
What are triggers of MH?
Inhalational agents (probably excluding nitrous oxide)
Succinylcholine
Mild MH triggers: exercise in hot conditions, neuroleptic drugs (haldol, dopamine), alcohol, infections
How does someone get tested for MH?
1 gram of muscle is tested with the halothane -caffeine contracture test
How does dantrolene work?
Reduces muscle tone and metabolism
Prevents ongoing release of Ca++ from muscle (SR)
Blocks external entry of Ca++ into sarcoplasm
**Stabilizes calcium induced calcium release and stabilizes the negative feedback**
dantrolene
Side effects
Significant muscle weakness
- can last long → ICU for 36h
Phlebitis - especially through peripheral IV
- watch it
Dantrolene interaction?
CCB will cause life thretening hyperkalemia and myocardial depression
You want the place you work to have how much dantrolene?
36 vials
Also lots of sterile water to mix with
Sequence of events the second you realize your patient has MH
Call for help
get MH cart
D/C volatile agent, sux
Change circuit and soda, use highest flow possible of O2 through the machine or ideally change to new dedicated MH safe machine
hyperventilate 100% oxygen and switch to TIVA
Dantrolene
Tx acidosis with sodium bicarb
-
Monitor with capnography & q 15 minute ABG
Monitor core temperature & Cooling to 38°C
Maintain urine output with diuretics and fluids (NOT LR)
- U/O >2 ml/kg/hr
Tx dysrhythmias
- give lidocaine or procainamide 15mg/kg IV (NOT CCB)
Tx hyperkalemia
- 1mL/kg D50 glucose and 0.15 units/kg regular insulin
- calcium chloride 5-10 mg/kg IV
Continue dantrolene sodium for at least 72 hours after control of episode (≈1 mg/kg q 6 hours)
Dantrolene dose?
Bolus 2.5 mg/kg
Then maintenance dose 2 mg/kg IV q5min up to 10 mg/kg
Then 1 mg/kg q6h for 72h
Each vial of dantrole contains 20 mg dantrolene and 3g mannitol; needs to be diluted with 60 mL sterile water
What lab tests do you want to get for someone having an MH episode?
ABG CK myoglobin Electrolytes thyroid
LDH PT/PTT fibrinogen FSP CBC
lactic acid Urine for myoglobin/hemoglobin
What muscle diseases are definitely associated with MH (predispose MH reactions)
- Central core disease
- King-Denborough syndrome
- Evan's myopathy
Direct association with muscle dystrophy is not likely
- however, can still develop rhabdomylosis & hyperkalemia without hypermetabolic issues so avoid triggering agents anyway
Neuroleptic malignant syndrome presentation?
Mimics MH
Presents with muscle rigidity, fever (cardinal sign), autonomic instability, delirium & cognitive changes, elevated CPK
relieved by NMB (as opposed to MH)
pt population at risk: those on antipsychotics (haldol, prolixin, thorazine)
What is the presentation of occult myopathy in young males having surgery?
Mimics MH
Sudden cardiac arrest, especially soon after use of sux,
muscle rigidity
hyperkalemia
How does basal metabolic rate (oxidative metabolic consumption) chnage in regards to change in °C?
1°C = 11.2% change in BMR
Radiation
Electromagnetic waves that directly transport ENERGY through space
50% of heat loss
Convection
Transfer of heat from one place to another by the actual movement of fluids (warmed matter, either liquids or gases)
Heat transfer in a gas or liquid by the circulation of currents from one region to another
30% heat loss
Evaporation
In a liquid the particles have a range of energies. At the surface of the liquid some particles will have enough energy to escape from the liquid and overcome the attraction of the other liquid particles. This leaves the less energetic particles still in the liquid and so the liquid is cooler.
H2O is transferred from the surface to the atmosphere, the process by which water changes from a liquid to a gas
How do burn patients lose most H2O?
Through evaporation
Conduction
Is the movement of thermal energy through a material without the particles in the material moving.
Transfer of energy through matter from particle to particle
MH
mutations
Ryanodine receptor 1 (RYR-1) - on chromosome 19
CACNA1S gene - provides instructions for making calcium channels - on chromosome 1
STAC3 gene - protein encoded by this gene is a component of the excitation-contraction coupling machinery of muscles- on chromosome 12
MH pathophysiology - cascade of events
- membrane depolarization
- Ca++ release
- failure of negative feedback (that would otherwise decrease subsequant Ca++ release)
- increased myoplasmic Ca++ release
- hypoxemia and cell death and other events
Lots of ATP needed and used up for Ca++ release, reuptake into SR, and troponin “decoupling” (hypermetabolism)
Aerobic metabolism replaces ATP with heat and CO2 → lactic acidosis
Excess Ca++ also signals cell death
Myoglobin released causes rhabdo, hyperkalemia
When ATP is depleted = CV collapse
what is the key event in MH pathophysiology
uncontrolled myoplasmic Ca++ release
how does Succinylcholine trigger MH?
succinylcholine acts indirectly by activating the nicotinergic acetylcholine receptor (nAChR), a nonspecific cation channel, resulting in continuous local depolarization
The depolarization can trigger propagated action potentials and will further activate the dihydropyridine receptors (DHPR, CaV1.1)
this leads to the gating of both Ca++ release from the SR via RyR1 and L-type Ca++ current from the extracellular space
how do inhalational agents trigger MH?
inhalational agents dirrectly on RYR1
they stimulate Ca++ release via RYR1
