MALIGNANT

HYPERTHERMIAGreg Gordon MD

February 2005

Malignant HyperthermiaObjectives

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.

“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

Malignant Hyperthermia

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

halothaneenfluraneisofluranedesfluranesevoflurane

200,0001

(without sux)

SUX

60,0001

(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 triggers100% oxygen 10L/min

Dantrolene 3 mg/kgTo 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 minutesthen 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 MMR50% MHS

Kaplan

MMRRosenberg

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

preop for T&A

needles terrify her

history of hernia repair:

fever and

stiff jaw

went for muscle biopsy:

normal

7 year-old girl

Malignant hyperthermia susceptible (MHS) patient A safe plan

prepare to treat MH

use safe drugs

be happy

MHAUS

Malignant HyperthermiaFor more information

MetroHealthAnesthesia.com

Lesson

Quiz