Transcript MH Slide Presentation

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