8/19/2019 ske b blok 9

1/3

KEMENTERIAN

PENDIDIKAN

DAN

KEBUDAYAAN

UNIVERSITAS

SRIWIJAYA

FAKULTAS

KEDOKTERAN

UNIT

PENDIDIKAN

KEDOKTERAN

(UPK)

Zono F. Gedung

I Kompus Unsri

tndroloyo

Ol

Sumofero

Seloton,

lndonesio

Telp.

071

I

-

580061

qtou

I

or

Jl.

dr.

Muh.

Ali

Komplek

RSUP

Potembong

30126.

lndonesio,

Telp.

07i

1

-352342,

Fox. 071

1

-

373438,

Skenario

B

Blok

9

Tahun

2013

Tn. lndra, umur

35

tahun

akan

menjalani

tindakan

pembedahan

umum.

Spesialis

Anastesi

(SpAn)

berencana

memberikan

anestesi umum

berupa

inhalasi

halothane. Sebelumnya,

telah dilakukan

konsultasi

dengan bagian Penyakit

Dalam

yang

menyatakan

tidak

ditemukan adanya

kelainan

jantung

dan

paru.

Keesokan

harinya, setelah

pemberian

succinylcholine

intravena dilakukan

intubasi

dilanjutkan

dengan

pemberian

inhalasi halothane.

Pada

saat

pembedahan

berlangsung

Tn lndra

mengalami

kekakuan

pada

otot, suhu

tubuh

meningkat

sampai

40oC

dan tekanan darah

menjadi

L7A/90 mmHg

dan denyut

jantung

120

kali/menit.

Dokter SpB

dan

Dokter

SpAn

menduga terjadinya

suatu

Malignant

hyperthermia.

Analisa

molekuler

menunjukkan adanya

mutasigen

pada

kromosom 19.

Learning

objective

1. Mahasiswa

dapat

menjelaskan mekanisme

kerja,

penggunaan

klinis

serta efek samping

succinylcholine

dan

halothane, serta

interaksi

keduanya.

2. Mahasiswa

dapat

menjelaskan

patofisiologi

terjadinya

Malignant

hyperthermia

(MH)

3.

Mahasiswa

dapat

menjelaskan

pada

tingkat

genetik

gen

yang

berhubungan

dengan

terjadi

MH

4. Menjelaskan

analisis

molekuler

untuk

mendeteksi

mutasigen

Keterangan

: Fokus

pembahasan

tidak termasuk

treatment

&

prognosis

MH

Klarifikasi

istilah

1.

Anestesi inhalasi

2.

Halothane

3. Succinylcholine

4. lntubasi

5. Kekakuan

pada

otot

6.

MalignanthyPerthermia

7.

Mutasi

ldentifikasi

masalah

L.

Tn-

lndra,

umur 35

tahun

akan menjalani

pembedahan

umum

2. Setelah

pemberian

succinylchaline

intravena

dilakukan

intubasi dilanjutkan

dengan

pemberian

Inhalasi

holothane

3.

pada

saat pembedahan

berlangsung,

Tn

lndra

mengalami

kekakuan

pada

otot,

suhu tubuh

meningkat

sampai

40oC

dan tekanan

darah menjadi

L7A|$O

mmHg

dan denyut

jantung

120

kali/menit,

4.

Dokter

SpB

dan

Dokter

SpAn

menduga

terjadinya

suatu

Malignant

hypertherrnia

5.

Analisa

molekuler

menunjukkan

adanya

mutasigen

pada

kromosom

19

{main

problem)

Analisis masalah

1. Apa

yang

dimaksud

dengan

pembedahan

umum?

2. a.

Bagaimanakah

mekanisme

kerja

succinylcholine?

'

Succinylcholin

(SC)

merupakan

obat

yang

secara

struktural analog

dengan asetilkolin

dan

bekerja

sebagai

agonis

reseptor

nikotinik

dari

motor

end-plate

pada

neuromuscular

junction.

Sebagaimana

asetilkolin,

SC

dapat

menyebabkan

stimulasi dan

depolarisasi

persisten

sel

otot.

8/19/2019 ske b blok 9

2/3

b.

Apa

adverse

effect

pemberian

succinylcholine?

'

X15:':X:Hli

n'tott"ne'

pemberian

sc

akan

menvebabkan

(MH)

pada

o"ng

a"ngan

polimorfisme

gen

tertentu

'

ffiffi:

dihubungkan

dengan,1111y.'^*I'".:,'1"'1:1ff'["*

genetik

,.ru

'a'lvt;;;

bentui<

enzim

vang

atipik

yang

malignant

hYPerthermia

plasma

YanB

bersifat

menYebabkan

Paratlsls

diafragma

2.

a.

Bagaimanakah

mekanisme

kerja

halothane?

'

;:

;;;

k;nraindikasi

pemberian

halothane?

-'

;

Anak-anak

usia

<

18

tahun

.Riwayatjaunuiceataudemamsetelahmendapatkan-halothanesebelumnya

.Pasiendenganpredisposisi,"*'l..,",ukmengalamiMalignanthyperthermia.

c.

Apakah

adverse-effect

pemberian

halothane?

,

HePatotoksisitas

'

Peningkatan

tekanan

'

Menurunkankontraktilitasuterus

g

eas.i

m

a

;*k;;il

ilf

n|,1,tf;;,*U;X{]:^ffi

ffff

ili[ffi,

ya

ns

m

e

nsa

ra

mi

m

utasi

pa d a

gen

ryanodine

.

,^-^r r^.,^^rrharrni2?

4

B,B.,I,1{:i;T*|[T:Jfl'J,Ii,T,1|il*'JJiiff',il-l,ebabkan

r,"p,T::karsium

dengan

jumtah

tidak

teikendali..

Hal

;;i;k;-

mengakibatft"n

tttjtOinya

kontraksi

otot

dalam

waktu

yang

lama.

sila

kontraksju.rrrngrrng

tr*'

*uta

sel-sel

otot

akan

mati

dan

melepaskan

isi

selnya

termarit]U.rUug.iroLkul,

protein'

enzim

ya.ng

dapat

dideteksi

dalam

darah

(potassium,

*rr*'ioi:r,

cl.rtinin"

phosphokinase)'

Peningkatan

kadar

zat-

zat

ini

dalam

darah

orn

,.nin"g;.i"vi

.rrt'

tubuh

akan

menyebabkan

kerusakan

organ

s.

saeaimai:l'J:'-ffil'*11l"li': :lf;dap

teriadinva

Marignant

hvperthermia?

.

MH

terjadi

pada

individu

y*f

*.ngatami

,':'.ti

ptou

s"n

reseptor

ryanodine

yang

mengatur

pelepasan

kalsium

;:i;;t;t

yane

t1r-e-t1k

pada

kromosom

19'

6.

Bagaimana

cara

*"nt"gutt

terjadinya

Malignant

hyperthermia?

,.

,*r,rux;::ffi;:iJ[i,u,

,nrrn

mendeteksivariasi

gen

pada

penderita

ini?

O

PCR,

RFLP

r

DNA

squensing

HYPothesis

.

Tn

lndra,

35

tahun

mengarami

Malignant

hyperthermia

yang

diinduksi

oleh

interaksi

succinylcholin

dengan

halothane

akibat

mutasi

gen

pada

kromosom

19'

Malignant

HYPerthermia

What

Marignant

hyperthermia

is

a

disorder

of

skeletal

muscte

and

is

characterized

by.

proronged

muscle

contraction

and

increased

body

temperature

after

being

.*por"J

io

certain

kinds

of

anesthesia

or

muscre

reraxants.

lt

is

inherited

in

an

autosomar

dominant

*.nn"i-

Arthough

this

condition

can

be

life-

threatening,

it

can

u"

tr"ut"a

if the

sympt;;;

;*.ognized

..;il;";

theiapv

is

promptly

initiated'

Who

The

incidence

of

marignant

hyperthermia

has

been

reported

from

1

in

5,000

to

1

in

10'000

children

and

1

in

50,000

to

1

in

ro-o,ooo

adults

*h"

,;;;;;

tn"'it't'i''

il;;;it

';ale

predominance

with

a

male

to

female

ratio

of

't"

i'

n

it

considered

to

be

a

rare

condition'

8/19/2019 ske b blok 9

3/3

Signs

and

Symptoms

people

with

malignant

hyperthermia

have no

symptoms

untit

they

are

exposed

to

halogenated

aneithetics

or depolarizini

muscte

relaxants,

the

most

frequent

triggers

of a

crisis.

Examples

of

triggering

anesthetics

include

halothane,

isoflurane,

enflurane,

sevoflurane,

and

desflurane"

Succinylcholine

is

an example

of a

depolarizing

muscle

relaxant.

Other

triggers

include

exercise

in

hot

conditions,

seizure

rnedication,

alcohol

use

and

infections.

Most

people

present

with

symptoms

during

an

operation

while

under

anesthesia.

Symptoms

include

a

sudden

increase

in

heart rate,

sudden

increase

in body

temperature

and

prolonged muscle

contraction.

Symptoms

may

even

present

2

%

hours

after

initial

exposure

to

the anesthesia

or

in

the

recovery

room.

While

in

recovery

the

patient

begins

to

have

a

gradual increase

in

temperature

that

is unexplained

accompanied

by muscle

pain

and

cramping.

Other

patients may also experience

hemolysis

which

is

the

rupture

of

red

blood

cells.

Some

p*opi.

who

have

had

previous

exposure

to

the

anesthestic

without

incidence

can

later

develop

malignant

hyperthermia

with

subsequent

exposure.

Some early

symptoms

that

may

arise

while

under

anesthesia

include:

rigidity

of the masseter

muscle

found

in the

face,

blood

that

is

acidic

due

to troubled

breathing,

low

oxygenation,

increased

output

of

carbon

dioxide

from

the

lungs,

elevated

muscle

protein

levels

in the

btood

(myoglobin

or

creatine

phosphokinase) or

urine

(myoglobin)

due

to

muscle

breakdown

and

heart

rhythm

abnormalities.

Possible

Causes

Most

patients

with

malignant

hyperthermia

have

point

mutations

in

the

ryanodine

receptor

gene

on

chromosome

19.

This

gene

is

involved

in

the

regulation

of

calcium

release

in

the

muscle.

The

mutated

receptor

allows

calcium

to

be released

from the

muscle

cetls

at

an uncontrolled

rate.

This causes

the

muscles

to

contract

for

a

prolonged

period

of time.

When

the

muscle

contracts

for

such a

long time,

the

muscle cells

begin

to

die

and

they

release

their

contents

which

include

various molecules,

proteins

and

enzymes

that

can

be

detected

in

the

blood

(i.e.

potassium,

myoglobin,

creatinine

phosphokinase)'

lncreased

levels

of these

substances

in

the blood

and

the

elevated

body

temperature

are very

dangerous,

potentially

leading to damage

of

organs

like

the

kidney and

the

heart.

Although

the

mutation in

the

ryanodine

receptor

gene

on

chromosome 19 is

most common,

others

with

malignant

hyperthermia

have

mutations

in

genes

on

other

chromosomes

{chromosomes

L,7,3,5,

L7l.

The role

and function

of these

genes

that lead

to malignant

hyperthermia

have

yet

to

be determined.

Diagnosis

There

are

no specific

findings to

diagnose malignant

hyperthermia.

The

diagnosis

is through

the

clinical

symptoms

and

certain

laboratory

findings

such

as an

increased

blood concentration

of

potassium,

creatinine

phosphokinase,

and aldolase.

Muscle biopsy

will

show

a

variety

of

muscle

cell

abnormalities

to

help

a

pathologist

confirm

the

diagnosis.

Treatment

During a

crisis

the

offending

anesthestic

is

discontinued

and the

drug dantrolene

is used

to

reverse the

effects

of

muscle

rigidity.

Oxygenation

and

cooling

measures

are

initiated,

as well

as corrections

of

the

other

blood

abnormalities.

People

with a

family

history

of

malignant

hyperthermia

or

other

complications

due

to

anesthesia

should

consider

being

screened

for

their

risk

of

malignant

hyperthermia.

The test

involves

taking

a

muscle sample

and

exposing

it

to

caffeine

and

halothane.

The

amount

of

contraction

is

measured

and

compared

to

normal

samples

in

order

to

assess

whether

an

abnormal

reaction

occurred.

Since

this

test

is invasive,

alternative

tests

are under

investigation

but most

are

not used

as

screening

tools.

Prognosis

The release

of

muscle

cetl

contents

and the

increased

body

temperature

during

malignant

hyperthermia

crisis

can

cause

multiple

organs

to

fail,

including the

heart which can

lead to

death.

However,

if

the

symptoms

are

recognized

early,

they

can

be

treated

with

minimal

residual

effects.

Other

family