MH and Dantrolene Flashcards Preview

Summer Pharm (2016) ** > MH and Dantrolene > Flashcards

Flashcards in MH and Dantrolene Deck (53):

MH incidence?

1:8,000 to 1:50,000 adults (depending on the source cited)

Higher in children


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


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)


Drugs needed in the MH cart/kit

  1. Dantrolene 36 vials
  2. Sterile water to reconstitute dantrolene: 1,000 ml x 2
  3. Sodium bicarbonate (8.4%): 50 ml x 5
  4. Furosemide: 40 mg/amp x 4 ampules
  5. D50: 50 ml vials x 2
  6. CaCl (10%): 20 ml vial x 2
  7. Regular insulin: 100 units/ml x 1  (refrigerated)
  8. Lidocaine HCl (2%): 1 box = 2 grams or 10 ml/100 mg preloaded vial


What are triggers of MH?

Inhalational agents (probably excluding nitrous oxide)


Mild MH triggers: exercise in hot conditions, neuroleptic drugs (haldol, dopamine), alcohol, infections


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


How does basal metabolic rate (oxidative metabolic consumption) chnage in regards to change in °C?

1°C = 11.2% change in BMR


MH - laryngospasm treatment


positive pressure



what sould Dantrolene be mixed with?

Sterile water (without bacteriostatic agent) 


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


What area of the brain regulates temperature?


most improtant area for temp regulation

Gain center: posterior hypothalamus

Loss center: anterior hypothalamus


patient susceptible to MH - uneventful surgery

may be discharged on the day of surgery

Minimum of 4 hours observation is strongly suggested


MH Compensatory mechanisms

Heat loss

  • Sweating
  • Cutaneous vasodilatation

Sympathetic hyperactivity:

  • ↑ circulating catecholamines
  • ↑ HR, ↑ SVR, ↑ CO
  • Cutaneous vasoconstriction

↑ ventilation

  • as the CO2 increases,  minute ventilation goes up
  • may be masked by fentanyl 



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


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



Electromagnetic waves that directly transport ENERGY through space

50% of heat loss


How does someone get MH?

Genetic susceptibility;

autosomal dominant RYR mutations are common in MH patients


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**


CPK levels in MH

↑ >20,000

During episode - Very high, up to 100,000


May be elevated up to 2 weeks after the event

Elevation correlates

  • Best with rhabdomyolysis
  • Less well with fever & acidosis


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


How does someone get tested for MH?

1 gram of muscle is tested with the halothane -caffeine contracture test


Myoglobinuria in MH

Myoglobin "leaked" from damaged cells → urine

may occur within a few hours

should be anticipated & treated to prevent acute tubular necrosis

  • Mannitol, diuresis, & ↑ fluids


You want the place you work to have how much dantrolene?

36 vials

Also lots of sterile water to mix with



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





E½t 10-15h

Redosing Q 6hrs 


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



how do inhalational agents trigger MH?

inhalational agents dirrectly on RYR1

they stimulate Ca++ release via RYR1


Occult Myopathy therapy

Therapy should be directed at treatment of hyperkalemia:

  • Calcium chloride
  • Bicarbonate
  • Insulin
  • Glucose
  • Hyperventilation
  • Dialysis & cardiopulmonary bypass may be required


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)


MH kit - other supplies needed 

  1. Large sterile Steri-Drape (for rapid drape of wound) – you may need to start CPR
  2. Three-way irrigating foley catheters → size appropriate for patient population
  3. Urine meter x 1
  4. Irrigation tray with piston syringe
  5. Rectal tubes [Sizes (Malecot Drain) 14F, 16F, 32F, 34F]
  6. Large clear plastic bags for ice x 4
  7. Small plastic bags for ice x 4
  8. Bucket for ice


Rapid rhabdomyolysis vs. slow rhabdomyolysis

Rapidly developing rhabdomyolysis includes rapid ↑ in  K+ → leading to dysrhythmias

Slowly developing rhabdomyolysis is safer → K+ is redistributed before blood levels can ↑


How is the Anesthesia Machine Prepared for MHS Patients?

  1. Ensure anesthetic vaporizers disabled by removing them from the machine
  2. Change CO2 absorbent (soda lime/baralyme)
  3. Flow 10 L/m O2 though circuit via ventilator for the amount of time specified by machine manufacturer (20-100 minutes)
  4. During this time a disposable unused breathing bag should be attached to the Y-piece of the circle system & the ventilator set to inflate the bag periodically
  5. Use new or disposable breathing circuit


what is the key event in MH pathophysiology

uncontrolled myoplasmic Ca++ release


Dantrolene interaction?

CCB will cause life thretening hyperkalemia and myocardial depression



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


Acidosis in MH

High lactate & acidosis with very low pH

  • may be < 7

Cardiac contractility falls at low pH

  • the response to NE and epi are GREATLY reduced



Side effects


Significant muscle weakness

  • can last long → ICU for 36h

Phlebitis - especially through peripheral IV 

  • watch it



4 earliest signs of MH and other s/s?

4 earliest:

  1. hypercarbia
  2. tachycardia
  3. tachypnea
  4. masseter spasm


  1. hyperthermia (inc 1-2°C every 5 min)
  2. hypertension
  3. dysrhythmias (r/t acid/base imbalance, hyperkalemia)
  4. metabolic acidosis
  5. hyperkalemia
  6. myoblobinuria
  7. hypoxemia
  8. elevated CPK with rhabdo
  9. coke-colored urine

**Most common to be noted 1st  in clinical practice - hyperthermia**


Masseter muscle rigidity (MMR)

sustained contracture of the jaw muscles following succinylcholine disallowing mouth opening → may be a forewarning of MH

  • A mild ↑ in masseter muscle tone following succinylcholine with limb flaccidity may be a normal response
  • Immediately check K+ & ABG
  • Clinical signs of MH occur in about 20% of cases of MMR

Not possible to determine, clinically, whether that ↑ in tone represents an MH reaction or not

If generalized rigidity also occurs → then MH is highly likely


MH monitor equipment

  1. Esophageal or other core temperature probes
  2. CVP kits: size appropriate to patient population
  3. Transducer kits for arterial & central venous cannulation


Dantrolene and NMB

Dantrolene does not significantly potentiate effects of nondepolarizing relaxants or interfere with reversal of muscle relaxants

May cause significant muscle weakness in patients with pre-existing muscle disease (MS, MD ect.)

  • still give with extreme caution



Routes of heat loss - in %

Radiation 40%

Convection 30%

Evaporation (burn pt)



how much Dantrolene should you have in the cart

36 vials (720 mg) sufficient for a 70-kg person

each vial = 20 mg

Needed if succinylcholine is available for resuscitation even if it's a facility in which volatile anesthetics are not used


Isolated Trismus 

May be early sign usually can still open the mouth for airway instrumentation

Stiff jaw but still can open –need to get airway secured incase something happens

Don't cancel the case, but be extra vigilent 


general equipment needed in the MH cart/kit

  1. Syringes (60 ml x 5) to dilute dantrolene
  2. Mini-spike® IV additive pins x 2 & Multi-Ad fluid transfer sets x 2 (to reconstitute dantrolene)
  3. Angiocaths: (4 ea.) (for IV access and arterial line – need to start an artline and more IVs)
  4. 20G, 2-inch; 22G, 1-inch; 24G, ¾-inch
  5. D5W 250 ml x 1 
  6. Micro Drip IV set x 1
  7. NG tubes (Size appropriate for patient population)
  8. Irrigation tray with piston syringe (x1) for NG irrigation
  9. Toomey irrigation syringes (60 ml x 2) for NG irrigation


Dantrolene class & MOA 

postsynaptic muscle relaxant

antagonizes ryanodine receptors

inhibits Ca2+ ions release from sarcoplasmic reticulum → depresses excitation-contraction coupling in skeletal muscle


MH treatment besides Dantrolene

Fluids and Mannitol - kidney protection


PPV & hyperventialtion - to remove CO2

Bicarb (HCO3) - for acidosis

Insulin & Glucose, Calcium - hyperkalemia 

Ice packs

AVOID Ca++ channel blockers in dysrhythmias


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


For each 1 degree fahrenheit change, basal metabolic rate will change how much?



Pre-treatement with Dantrolene 

Prophylaxis treatment is not recommended




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

  1. membrane depolarization
  2. Ca++ release
  3.  failure of negative feedback (that would otherwise decrease subsequant Ca++ release) 
  4. increased myoplasmic Ca++ release 
  5. 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 other conditions might look like MH?

Neuroleptic Malignant Syndrome

Light Anesthesia


Thyroid storm (Hyperthyroid)

Pheochromocytoma (esp if doing a bowel resection)

occult myopathy