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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.
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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