MALIGNANT

HYPERTHERMIA
Greg Gordon MD
February 2005
 Malignant Hyperthermia
Objectives
Things to know and do:
Participants will:

1. be able to explain the:

pathophysiology,
clinical presentations,
testing for and
management of malignant hyperthermia
and the MHS patient
2. be able to explain the significance of MMR
and its management.

3. keep MH somewhere in mind as they monitor patients,

and not hesitate to give dantrolene.

4. easily correctly answer the questions in the MH Quiz.

 Malignant Hyperthermia

“If any institution does not feel it can manage

the MHS child then they should not be
anaesthetising any children at all, since it is
not the identified child with a nontriggering
technique who will cause grief, but the
undiagnosed child given a trigger.”

Helen Holtby M.B.,B.S.

Director of Cardiovascular Anaesthesia
Hospital for Sick Children
Toronto, Canada
PAC List, 10 Dec 04
 pharmacogenetic
hypermetabolic state of
skeletal muscle
induced by inhalational anesthetics
or succinylcholine
(and maybe stress/exercise)
Drugs + Genes =

Pharmacogenetic
 Historical MH
1960 Denborough and Lovell

1960’s families and pigs

Gordon (?) calls it Malignant Hyperthermia

1975 dantrolene saves pigs

1979 FDA approves dantrolene

1980’s muscle biopsy for HCCT

1990’s genetic markers/RYR1

halothane
enflurane
isoflurane
desflurane
sevoflurane
200,000
1

(without sux)
60,000
1

(with sux)
 Incidence - Current Concepts

Clinically based information:

One in 20,000 to 50,000 anesthetics
depending on drugs, population

Molecular Genetics based information:

MH trait in 1 in 2,000-3,000 patients.
Low penetrance
 Normal excitation-contraction coupling

ACh at NMJ depolarizes sarcolemma

SR (RYR) releases Ca
Ca + troponin
actin-myosin slide
ATP hydrolyzed
SR (RYR?) re-uptake of Ca
 RYR1

ryanodine receptor
Ca release channel
protein (5,032 amino acids)
connects SR to T-tubules
Ca gate from SR
chromosome 19, region 13.1
 Excitation-contraction coupling in MH

Defective RYR Ca release channel

Too much free intracellular

calcium
 Too much free Ca
ATP depletion
lactic acidosis
VO2 way up
Too much CO2
myonecrosis/rhabdomyolysis/↑↑K
myoglobinemia/uria/renal failure
 Diagnosis of MH

tachycardia +
tachypnea +
ETCO2 increasing +
metabolic acidosis =
MH =
dantrolene IV
 HCCT for MH
vastus muscle
2-3 months after MH episode
nontriggers
no dantrolene
gentle handling of muscle
test within 5 hours
About $6,000
 Guidelines for Molecular Genetic Testing

 Determine MHS by HCCT

 If MH positive , screen for known mutation

 If mutation positive,

test other family members for the mutation

 If mutation negative,

cannot screen family for mutations or determine MH status

Treatment of an acute episode of MH
Stop triggers
100% oxygen 10L/min

Dantrolene 3 mg/kg
To 10 mg/kg

Rx metabolic acidosis, HCO3

Cool, iced NS IV

Rx dysrhythmias, hyperkalemia

Monitor ETCO2, ABGs, K,

UOP, clotting tests
verapamil + dantrolene =

severe hyperkalemia
+
myocardial depression
dantrolene
 5 year-old boy

for T&A

halothane induction

succinylcholine

jaw “stiff” for 3 minutes

then relaxed
 Masseter muscle rigidity (MMR)

amyotonic mytonia

temporomandibular joint (TMJ) dysfunction

not enough succinylcholine

not enough time

 The stiff jaw
subclinical: normal

interferes with intubation:

1-3% of children

“jaws of steel”:
true MMR
50% MHS
Kaplan
 MMR
Rosenberg

cancel elective
dantrolene 1-2 mg/kg
observe overnight
(myoglobinuria, fever,
hyperkalemia, CPK)
muscle biopsy
strongly considered
 MMR
Gordon

AVOID SUX
Malignant hyperthermia susceptible (MHS) patient
A safe plan

prepare to treat MH
use safe drugs
be happy
 7 year-old girl

preop for T&A

needles terrify her
history of hernia repair:
fever and
stiff jaw
went for muscle biopsy:
normal
Malignant hyperthermia susceptible (MHS) patient
A safe plan

prepare to treat MH
use safe drugs
be happy
 Malignant Hyperthermia
For more information

MHAUS

MetroHealthAnesthesia.com

Lesson

Quiz