Ashifa Maulidya Shibly

04011381419194
PDU GAMMA 2014
Tutorial 1 skeario A

SUCCINYLCHOLINE
Obat-obatan yang mempengaruhi kerja otot skeletal terbagi menjadi 2 kelompok utama yaitu
-

Penghambat neuromuscular, yaitu obat yang digunakan selama tindakan bedah dan unit
perawatan intensif guna mendapatkan paralisis. Obat ini mengganggu transmisi impuls pada
endplate dan biasa digunakan sebagai penunjang anastesi umum. Penghambat neuromuskular
dapat terjadi melalui dua mekanisme. Yaitu obat kompetitif/antagonis(non-depolarisasi)
seperti obat tubokurarin, dan obat agen depolarisasi seperti succinylcholine
Spasmolitik , obat yang digunakan untuk mengurai spasmotika pada kasus-kasus neurologik.
Contohnya yaitu Diazepam, baklofen dan dantrolen

Succynylcholine sebenarnya merupakan 2 molekul asetilkolin yang dihubungkan ujung-ujungnya.

Farmakokinetik
Semua obat penghambat neuromuskular bersifat polar dan tidak aktif jika diberikan per oral. Obatobatan tersebut harus selalu diberikan intravena.
Setelah diberikan dosis tunggal suksinilkolin intravena 0,5-1 mg/kg, suksinilkolin akan mulai bekerja
merelaksasi otot dalam waktu 1 menit, maksimal dalam 2 menit, lalu efeknya hilang sekitar 5 menit.
Kerja suksinilkolin yang sangat pendek disebabkan oleh adanya hidrolisis yang cepat dari
kolinesterase plasma (butirilkolinesterase, pseudokolinesterase), suatu enzim hati dan plasma. Zat ini
dimetabolisir menjadi asma suksinat dan kolin. Kolinesterase plasma mempunyai kemampuan yang
sangat besar menghidrolisis suksinilkolin dalam waktu singkat sehingga hanya sebagian kecil dosis
intravena asli yang mencapai NMJ. Kerja Suksinilkolin lebih lama dibanding Ach karena tidak adanya
kolinesterase plasma pada NMJ, karena it juga kerja suksinilkolin berakhir melalui difusi keluar dari
endplate masuk ke cairan ekstraselular. Karena itu plasma kolinesterase mempengaruhi lama kerja
SCH dengan cara mengatur jumlah obat yang sampai di endplate.
Farmakodinamik
kerja suksinilkolin terbagi menjadi 2 fase
Fase 1 (Fase depolarisasi)
Suksinilkolin bereaksi dengan reseptor nikotinik untuk membuka saluran dan menyebabkan
depolarisasi endplate. Karena suksinilkolin tidak dimetabolisir secara efektif pada sinaps, membran
yang mengalami depolarisasi tetap dalam keadaan depolarisasi dan tidak responsif terhadap impuls
tambahan. Selanjutnya, karena penggabungan eksitasi-konsentrasi memutuhkan repolarisasi endplate
dan pancaran berulang untuk mempertahankan tegangan otot, terjadilah paralisis flasid.

Fase 2 (Fase desensitiasi)

Dengan pemaparan berkelanjutan suksinilkolin, depolarisasi awal endplate berkurang dan membran
menjadi repolarisasi. Meskipun dalam keadaan repolarisasi, membran tidak dapat didepolarisasi lagi
oleh Ach selama suksinilkolin ada. Keadaan ini disebut dengan desensitisasi membran terhadan efek
Ach. Karena itu fase ini disebut dengang penghambatan desensitisasi. Saluran tersebut berlaku
seakan-akan gerbang dalam keadaan tertutup.

Efek kelemahan otot terjadi sebentar, dapat dilihat terutama pada otot dada dan abdomen, selama efek
paralasis berjalan, otot-otot lengan, leher, dan kaki juga mlemah, otot-otot muka dan faring hanya
mendapat sedikit efek.
Efek kerja
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Kardiovaskular : suksinilkolin menyebabkan berbaga jenis aritmia jantung. Obat merangsang

semua kolineseptor otonom : reseptor nikotinik baik pada ganglion simpatis/parasimpatetis
dan reseptor muskarinik dalam nodus sinus jantung.
Hiperkalemia

Interaksi dengan obat lain

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Anestetik : obat-obat anastetik inhalasi meningkatkan penghambatan neuromuskular terhadap

pelemas otot nondepolarisasi dalam batas dosis yang ada.

Sediaan, administrasi, dan dosis

Succinylcholine chloride ( Anectine, quelicin, sucostrin, sux-cert)
dijual dalam bentuk sterile powder (0.5 dan 1 g), dan bentuk sterile solutin mengandung 20,50, and
100 mg/ml.
dalam prosedur operasi pada orang dewasa dosis intravena biasanya antara 10-30mg.
Therapeutic Uses
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Digunakan untuk penunjang anastesi umu, untuk merelaksasi otot skeletal terutama dinding
abdomen. Muscle relaxant juga digunakan dalam berbagai prosedur ortopedi.
Memfasilitasi intubasi dengan endotracheal tube
Untuk menjalankan laryngoscopy, bronchoscopy, dan esophagoscopy dikombinasikan dengan
general anestesi.
Mencegah trauma pada electroshock therapy
Diagnostic use

Pharmacodynamics
Structurally, SCH consists of two acetylcholine (ACh) molecules linked end to end by their acetyl
groups . ACh is the endogenous agonist of the nicotinic acetylcholine receptor (nAChR), a ligandgated, nonspecific cation channel that is formed by five subunits organized around a central pore.
There are two 1 subunits, and one 1, , and subunits. Each subunit of the nACHR is encoded by
one of four genes ( is encoded by CHRNA1, 1 is encoded by CHRNB1 , 1 is encoded
by CHRND, and is encoded byCHRNE) .The nAChR is located on the motor end plate of
neuromuscular junction (NMJ) of the skeletal muscle membrane, also known as the sar- colemma.
Binding of an agonist, such as ACh or SCH, promotes the open state of the channel. When the nAChR
opens, sodium ions rush into the cell and potassium ions rush out, resulting in membrane
depolarization and generation of an action potential. In myocytes, depolarization stimulates muscle
contraction.
L-type voltage-gated calcium channels, also known as dihydropyridine receptors (DHPR), are located
on invaginations of the sarcolemma called the transverse tubules (T- tubules). The DHPR is a complex
of four subunits ( 1, 2 , , ) and a distinct gene encodes each subunit. CACNA1Sencodes the
1 subunit (also called Cav1.1), the primary subunit of the channel that contains the voltage sensor,
gating apparatus, and channel pore of .The DHPR is mechanically coupled to the ryanodine receptor
(RYR1), a homotetrameric voltage-gated calcium channel that is located on the sarcoplasmic
reticulum (SR) and encoded by the RYR1 gene . When skeletal muscles are at rest, the troponin
complex allosterically inhibits the formation of a cross-bridge between myosin and actin. When
calcium is released into the myoplasm, it binds the troponin complex and allows myosin to bind to
actin to initiate muscle contraction and continues for as long as ATP is freely available .Upon
depolarization of the sarcolemma, the DHPR undergoes a conformational change and transmits a
signal to RYR1, which opens to release SR cal- cium stores into the myoplasm to initiate muscle
contraction. Muscle relaxation occurs when calcium ATPases on the sarcoplasmic reticulum (SERCA)
remove calcium from the myoplasm and pump it back into the SR .
Because it is a depolarizing neuromuscular blocking agent, SCH first induces muscle fasciculations,
followed by flaccid muscle paralysis. SCH takes effect within 60 s of intrave- nous administration and
paralysis lasts between 4 and 6 min, during which time patients are monitored with an electric nerve
stimulator . Because of its short half-life, SCH is indicated for medical procedures requiring shortterm muscle paralysis, such as endotracheal intubation, neuromuscular surgery, and electroconvulsive
therapy. Because SCH paralyzes the respiratory muscles, patients require mechanical ventilation and
close monitoring for the duration of paralysis. It exerts no direct effect on smooth or cardiac muscle
contraction. SCH is often administered in combination with other anesthetics, analgesics, and narcotics because although it blocks muscle contraction it has no effect on pain perception .
Pharmacokinetics
SCH is rapidly hydrolyzed by butyrylcholinesterase (BCHE, also known as plasma cholinesterase and
pseudocholinesterase), which is synthesized in the liver and present in plasma. BCHE hydrolyzes
SCH to succinylmonocholine, succinic acid, and choline (see pathway diagram). The duration of the
neuromuscular block caused by SCH is determined both by its rate of dissociation from the nAChR as
well as the rate of metabolism by BCHE in the plasma. ACh is rapidly metabolized by
acetylcholinesterase, but unlike acetylcholinesterase, BCHE is not present in the synaptic cleft of the
NMJ. Consequently, SCH is hydrolyzed more slowly and remains bound to the nAChR for longer
than ACh. For as long as SCH is bound to the nACHR, it maintains the membrane potential above the

threshold for repolarization and ACh cannot trigger depolarization of the sarcolemma until it has been
repolarized .

Pharmacogenomics
BCHE
The BCHE gene is located on chromosome 3q26.126.2 and is ~ 64 kb long. Since the initial
discovery of the A-variant ofBCHE, over 60 polymorphisms in the BCHE gene have been reported .
Genetic variants that impair BCHE enzyme activity can be broadly classified as being either
qualitative or quantitative variants. The qualitative variants affect BCHE enzyme substrate affinity,
whereas the quantitative variants affect the quantity of enzyme that is produced without affecting
BCHE substrate affinity. Both types of variants increase a patients risk of prolonged apnea in the
presence of SCH, but the duration of the apnea depends on the type and the number of variants. A list
of the most common genetic variants of BCHE.

MALIGNANT HYPERTHERMIA

SCH can also trigger malignant hyperthermia (MH) in some patients. MH was first described in
Australia in 1960. A patient expressed concern about being under general anesthesia for his surgery
because ten of his family mem- bers had died while under anesthesia or shortly afterward. The doctor,
assuming that ether had been the cause of death, administered halothane instead, but shortly after
being administered halothane, the patient experienced a severe decrease in blood pressure and a rapid
increase in body temperature. By packing the patient with ice, the doctor stabilized the patients body
temperature and saved his life. The patient was referred to the geneticist Dr Michael Denborough. Dr
Denborough concluded that the patient was a carrier of an autosomal dominant muta- tion of
incomplete penetrance that made him and mem- bers of his immediate family susceptible to
hyperthermia in the presence of general anesthesia .Other case studies emerged of patients who
experienced masseter spasm and jaw rigidity in addition to hyperthermia after administration of SCH
Malignant hyperthermia susceptibility (MHS) is inherited in an autosomal dominant manner that
manifests in a subset of patients who are administered depolarizing muscle relaxants, such as SCH, or
potent inhalational anesthetics such as sevoflurane, isoflurane, or desflurane. Epidemiological reports
provide the occurrence of MH as ranging anywhere from one in 5000 to one in 100, 000 patients;
however, as it only reveals itself in the presence of potent inhalational anesthetics and depolarizing
muscle relaxants, the genetic prevalence of MHS has been estimated to be as high as one in 2000.
Given that the overall incidence of MH in the general population is low, it is likely that sporadic
causative mutations are rare . Most MHS-causative mutations are inherited in an autosomal dominant
manner, which explains why MHS heritability is so high.
Multiple epidemiological studies also show that males are overrepresented among surgical patients
diagnosed with MH. For example, in two retrospective studies of patients who had experienced MH
episodes during anesthesia, between 64.8 and 70% were male . This could be because of bias in the
types of surgeries requiring general anesthesia that may be more commonly performed in men.
However, one study found that men were more likely to be diagnosed with MHS than women on the
basis of in-vitro contracture test (IVCT, see below) even when there was no statistically significant
difference in the numbers of men and women in the samples .
Early symptoms of MH include metabolic (elevated CO2 production and O2 consumption),
cardiovascular (tachycardia and arrhythmia), and muscular abnormalities (masseter spasm and muscle
rigidity). Later and more severe symptoms can include a rapid increase in body temperature
(hyperthermia), rhabdomyolysis, hyperkalemia, severe metabolic and respiratory acidosis, and cardiac
arrest . A clinical grading scale is a scoring system used to estimate the likelihood that a patient
adminis- tered anesthesia has experienced an MH episode on the basis of multiple indicators, such as
the aforementioned symptoms .The mortality rate for patients who experience an MH crisis has
decreased significantly to between 5 and 10% with the introduction of dantrolene, an RYR1 inhibitor;
before dantrolene, the mortality rate was as high as 70%.
MH is characterized by a rapid and uncontrolled increase in myoplasmic calcium levels in skeletal
muscle in response to depolarizing muscle relaxants or potent inhalational anesthetics, followed by a
hypermetabolic state caused in part by the ATP-intensive removal of excess calcium by SERCA and
other calcium pumps . Two mechanisms of extracellular calcium entry have been proposed to explain
how an MH crisis can be maintained if SR calcium stores are limited. Store-operated calcium entry
promotes extracellular entry of calcium into cells when SR calcium stores are depleted and excitation
contraction-coupled entry promotes extracellular calcium entry independent of SR calcium stores, but
is triggered by prolonged depolarization of the sarcolemma . There is evidence that store-operated
calcium entry as well as excitation contraction-coupled entry are induced in muscles with RYR1

mutations, but not in wild-type muscles in the presence of low levels of halothane. The identities of all
of the calcium channels responsible for extracellular calcium entry are still being discovered.
The role of SCH as a trigger in MHS individuals is still unclear because although it has been reported
to trigger MH when administered alone, the majority of MH crises have occurred when SCH was
coadministered with a potent inhalational . One retrospective analysis reported that the relative risk of
MH is greater when potent inhalational anesthetics and SCH are coad- ministered rather than when
either is administered alone . A more recent analysis concluded that there was no significant
difference in the severity of MH when comparing between those who were administered potent
inhalational anesthetics alone and those who were co-administered SCH. However, the study did
report that the onset of an MH crisis was significantly more rapid in patients who were
coadministered SCH and potent inhalational anesthetics compared with either alone . A third study
reported that SCH was associated with greater elevations of serum creatine kinase levels in MHS
patients compared with when SCH was not administered .
Genetics of malignant hyperthermia
The most commonly reported mutations in MHS individuals are in RYR1. As of October 2013, there
were at least 397 reported SNPs in RYR1, but only 33 have been functionally characterized and
designated as MHS causative by the European Malignant Hyperthermia Group (EMHG), a research
consortia specializing in MH . There are also polymorphisms in CACNA1S, associated with MHS, but
3050% of patients who are diagnosed with MHS have no known MHS-causative mutations in
either CACNA1S or RYR1 . Studies in vitro, in mouse models, as well as in humans have shown an
association between mutations in RYR1 and CACNA1S, MHS, and elevated basal levels of
myoplasmic calcium in skeletal muscle. Why some mutations in RYR1 or CACNA1S could lead to
elevated basal calcium is not yet known, although elevated calcium has been attributed to increased
sensitivity of RYR1 to agonists because of increased passive leaks from the SR . The American
College of Medical Genetics 2013 report for recommendations on reporting incidental findings in
clinical exome and genome sequencing also includes RYR1 and CACNA1S in their list of genes to
report .
RYR1
RYR1, the primary locus of MHS, is located on chromosome 19q13.113.2. RYR1 is found complexed
with other proteins, but because most pharmacogenetic studies of MHS are on RYR1, they will not be
discussed here. Early efforts to sequence RYR1 were hampered because of the large size of the
gene; RYR1 is ~ 16 kb and contains 106 exons.There are three recognized hot-spots in RYR1 in
which SNPs are often found: the N-terminus, C-terminus, and a central region that includes exons 39,
40, and 4446. The location of individual mutations in RYR1 orCACNA1S is likely to determine the
specific mechanism responsible for producing elevations in resting calcium levels, but with so many
different MH causative mutations (particularly in RYR1), a single mechanism is not likely to be found.
For example, a study in one RYR1 knockin mouse (Tyr522Ser) reported that the mutation was
associated with increased RYR1 sensitivity to pharmacologic agonists as well as to stimulation by
depolarization, but it had no effect on basal calcium levels . A second study in a different RYR1
knockin mouse (Arg163Cys) reported that the mutation was associated with elevated basal calcium
levels as well as increased sensitivity to RYR1 agonists compared with the wild-type mouse .
Several mutations in RYR1 are also associated with var- ious neuromuscular diseases including central
core dis- ease (CCD) and multiminicore disease. The clinical presentation of these diseases is variable
and they may be distinguished histologically .Some individuals may experience hypotonia and

delayed motor development from infancy, whereas others may be unaware that they have a
neuromuscular disease until they are diag- nosed for muscle weakness or tested for MHS well into
adulthood .Although SCH and potent inhalational anesthetics are contraindicated in patients with
CCD, the disease does not always segregate with MHS, nor do MHS causative RYR1 mutations
always segregate with CCD, further complicating the relationship between RYR1 and MHS .
The currently accepted gold standard for diagnosis is the IVCT. An almost identical procedure called
the caffeinehalothane contracture test (CHCT) is used in the USA . The IVCT is an invasive test that
requires freshly dissected muscle fibers. Muscle fibers are exposed to caffeine and halothane
separately, and the force of contracture is measured using a myoelectrical transducer. An MHSpositive IVCT is when the force of the contracture is greater than 2 mN in the presence of 2mmol/l or
less of caffeine and 0.44mmol/l or less of halothane . Patients can be diagnosed as MHS (sensitive to
both halothane and caffeine) or MH nega- tive (sensitive to neither). Patients who are sensitive to
either halothane or caffeine, but not both, are MHSc for caffeine or MHSh for halothane . The EMHG
has recently revised its guidelines regarding the use of genetic testing to diagnose MHS. Now, IVCT
is no longer the primary diagnostic test for MHS and anyone in whom an MHS-causative mutation is
detected is now automatically diagnosed as MHS. The EMHG still recommends that MHS individuals
and relatives in whom an MHS-causative mutation is not detected should still be tested with IVCT
because of the possibility of false negative diagnosis, due in part to the possible presence of novel
MHS-causative mutations in RYR1 .The EMHG has established guidelines for how to recognize and
treat patients during a fulminant or an abortive MH crisis, guidelines for molecular genetic testing,
and a protocol for IVCT testing. In the case of a positive MH diagnosis, positive IVCT, or MHSpositive genetic test, the EMHG strongly recommends that IVCT and genetic counseling be offered to
first-degree relatives of the proband . The Malignant Hyperthermia Association of the United States
explains that RYR1 hot spots are sequenced first in an effort to detect the pre- sence of known
causative mutations (33 as of the writing of this manuscript) and the remaining exons are sequenced if
no causative mutations are found in those hot spots . Discordance between IVCT phenotype
and RYR1genotype may possibly be because of the heterogeneity of the RYR1 gene and complexity of
the MHS phenotype.
CACNA1S
CACNA1S, the second gene implicated in MHS, is 93.5kb long and is located on chromosome 1q.32.
Currently, there are two missense SNPs inCACNA1S that are designated to be MHS causative by the
EMHG carried out a linkage analysis in a large French family after the death of a proband following a
suspected MH crisis shortly after he was administered SCH and isoflurane. Ten out of eighteen
members of his family were subsequently diagnosed with MHS and three were diagnosed with MHEh
by IVCT. After determining the locus that segregated with MHS, the authors carried out sequence
analyses and discovered the causative mutation in CACNA1S. The mutation causes an arginine residue
to be substituted by a histidine at position 1086. This polymorphism was also found in a large North
American casecontrol study in two patients diagnosed with MHS by IVCT .n b The second SNP
was discovered in a study that sequenced CACNA1S cDNA in 50 MHS-positive individuals in the
UK. The mutation was found to segregate with MHS in one family and was not found in any of the
samples from MHN patients .Polymorphisms at additional loci, including the gene encoding the 2
subunit of the DHPR, have been proposed as being MHS causative, but no strong associations
between those polymorphisms and MHS have emerged .

MALIGNANT HYPERTHERMIA
MH merupakan penyakit genetik yang diturunkan secara autosomal dominant with reduced
penetrance, yang dikarakteristikkan dengan penaikan suhu secara drastis , sekitar 39-42 derajat celcius
yang merupakan respons dari anestesi inhaasi seperti halothane, methoxyflurane, cyclpropane, dan
ethyl ether atau jenis pelemas otot terutama succinylcholine.
Penyebab dari MH adalah mutasi yang terjadi pada gen RYR1 atau pada gen CACNA1S
(dihydopyridine subunit encoding gene).
Gen RYR1 terletak di kromosom 19q13.1-13.2. gen ini berukuran besar yaitu 16kb dan mengandung
106 exons. Bagiandari gen yang sering termutasi yaitu pada N-terminus, C-terminus, dan central
region yaitu exon 39,40, dan 44-46. RYR1 berfungsi meregulasi kalsium myoplasmik yaitu bekerja
untuk membuka channel calsium dan melepaskan calsium unutk kontraksi otot jika mendapat sinyal
dari DHPR.
Gen yang kedua yang berhubungan dengan MH yaitu CACNA1S pada kromosom 1q.32. panjangnya
93.5 kb , dan subunit protein yang dihasilkan berfungsi untuk meregulasi kadar kalsium myoplasmik
dengan cara mengirim sinyal ke RYR1 jika terdeteksi perubahan potensial pada membran
sarcollemma (terjadiya depolarisasi)
Manifestasi klinis:
Respiratory acidosis The presence of end-tidal CO2 >55 mmHg or PaCO2
>60 mm Hg with controlled ventilation, PETCO2 >60 mmHg or PaCO2 >65
mmHg with spontaneous ventilation.
Metabolic acidosis Base deficit >8 mEq, pH <7.25
Muscle rigidity Either severe masseter muscle rigidity or generalized rigidity.
Muscle breakdown Serum CK >20,000 IU/L or >10,000 IU/L without the use
of succinylcholine, cola colored urine in the postoperative period.
Temperature Rapidly increasing temperature, or core temperature >38.8 C
(101.8F).
Normal muscle physiology:
Depolarization via transverse tubule system activates DHP receptors in T-tubule
membrane couples to RYR-1 receptors, which are calcium channels in wall of sarcoplasmic
reticulum
Calcium releases into the intracellular space combines with troponin allows actin and myosin to
cross-link MUSCLE CELL CONTRACTION
Reuptake of calcium by the sarcoendoplasmic reticulum calcium ATPase MUSCLE CELL
RELAXATION
Malignant hyperthermia:
Mutations encoding for abnormal RYR-1 or DHP receptors trigger unregulated passage of
Calcium ACUTE MH CRISIS
Accumulation of myoplasmic calcium causes sustained muscle contraction generates heat
Accelerated levels of aerobic metabolism produce carbon dioxide and cellular acidosis depletes
oxygen and ATP muscle death rhabdomyolysis hyperkalemia and myoglobinuria

Mekanisme hiperthermia/ kenaikan suhu pada MH tidka melibatkan mekanisme pengaturan

suhu pada thermolegulator, melainkan disebabkan oleh hipermetabolisme dan akibatnya
panas yang dihasilkan melebihi kemampuan tubuh untuk mengeluarkannya.

Diagnosis:
-

Gold standard (IVCT)

DNA analysis

Differential diagnosis:
-

Pemberian anestesi dan analgesik yang tidak adekuat

Alat alat /mesin anaestetik seperti breathing circuit, fresh gas flow, dan ventilsi yang tidak
adkuat
Penyakit endokrin : pheochromocytoma, thyrotoxicosis
Sepsis
Hypoxic encephalophaty
Penyakit otot lainnya

Hal yang harus dilakukan pada pasien MH:

1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
11.

Hentikan pemberian agenanestesi pemicu dan akhiri proses operasi jika masih memungkinkan
Beri 100% oksigen kepada pasien
Ubah mesin anestesi menjadi vapour-free machine
Pertahankan anastesi menggunakan agen anestesi lain seperti propofol
Beri dantrolene iv 1-2mg/kg diberikan setiap 5 min sampai suhu dan CO2 berhenti
meningkat, sampai total dosis 10 mg/kg
Mengatasi asidosis dengan memberikan sodium bikarbonat 8.4%
Hiperkalemia diberikan insulin dan glukosa
turunkan suhu tubuh dengan cara mendingin kan permukaan tubuh dengan memberi cooling
balnkets, atau dikompres dengan es, dan infus dengan saline
menyeimbangkan pengeluaran urin >1ml/kg/h dengan memberi diuresis. Hal ini untuk
mengeluarkan excess myoglobinemia dan hyperkalemia.
Pindahkan pasien ke ICU untuk terapi yang suportif, menhindari komplikasi
Mengatur pemeriksaan untuk biopsi otot pasien untuk mendiagnosis

Anesthesia in patients with Malignant hyperthermia susceptibility:

1.

Ensure dantrolene is available.

2.

Use a vapour-free anesthetic machine, flushed with 100% oxygen for 5

minutes at a fresh gass flow rate of 10 litres/minute.

3.

All circuits should be disposable and new.

4.

The soda lime should be previously unused.

5.

Regional anesthesia is safe.

6.

Drugs which are considered safe include barbiturates, narcotics, nitrous oxide,
propofol, benzodiazepines, non-depolarizing muscular blocking agents.

7.

A total intravenous technique using propofol along with an infusion of short

acting opioids is safest.

Dantrolene
Dantrolene merupakan turunan hidantoin yang mempunyai daya spasmolitik
tersendiri diluar CNS.
dantrolene mengurangi kekuatan otot skelet karena mengganggu penyatuan
eksitasi-kontraksi serabut otot. Dantrolene mengganggu pelepasan aktivator kalsium
dari reticulum sarkoplasma.
Jadi kerja obat ini bukan melibatkan sinaps pusat atau pada NMJ akan tetapi bekerja
intraselular pada organ efektor.
Hanya kira-kira 1/3 dosis dantrolene yang diabsorpsi, waktu paruh obat 8jam.
Dantrolene merupakan penggunaan khusus dalam pengobatan malgina
hyperthermia.

Sumber:
https://www.pharmgkb.org/pathway/PA166122732
http://medchrome.com/minor/anaesthesia-minor/malignant-hyperthermia-mhclinical-features-diagnosis-management/
Wilson, Braunwald (1991). Harrisons principles of Internal Medicine, 12th edition. New
York:McGraw Hill
Gilman, Alfred Goodman. (1978). Goodman and Gilmans The Pharmacological Basis of
Therapeutics ,sixth edition. New York: Macmillan Pulishing.
Katzung,Bentram G(1995). Farmakologi dasar dan klinik edisi IV. Indonesia: EGC