5 Obat Anestetik Lokal Cpd 2012
Transcript of 5 Obat Anestetik Lokal Cpd 2012
OBAT ANESTETIK LOKAL
Workshop Anestesia RegionalCPD
PP. PERDATIN
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tujuan
• Memahami struktur kimia dasar anestetik lokal
• Memahami mekanisme kerja anestetik lokal
• Memahami pengaruh sifat kimia anestetik lokal dan aplikasi klinisnya
• Memahami toksisitas anestetik lokal dan cara mengatasinya
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Perkembangan anestetik lokal
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dimana obat
anestetik lokal
bekerja ??
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Klasifikasi saraf tepi
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OBAT ANESTETIK LOKAL
• Obat-obat yg scr reversibel menghambat konduksi impuls saraf, baik di saraf pusat maupun saraf perifer
• Efek yg dihasilkan berkaitan dgn konsentrasi obat pada tempat kerja/lokasi saraf yg diblokade
Autonom sensorik motorik
rendah (konsentrasi obat) tinggi
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STRUKTUR KIMIA
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STRUKTUR KIMIA
(amida)
(ester)
(Gugus lipofilik) (Gugus hidrofilik)
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STRUKTUR KIMIA
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amida
ester
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MEKANISME KERJA
• Berikatan dgn kanal Na• Shg kanal Na tdk bs diaktifkan lagi• Permeabilitas Na menurun• Tdk terjadi influks Na jika ada stimulus• Potensial ambang (threshold potential)
tdk akan tercapai• Tdk terjadi depolarisasi
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PHYSIO
LOG
YRESTIN
G PO
TENTIAL
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FISIOLOGI PENJALARAN IMPULS SARAF
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MEKANISME KERJA ANESTETIK LOKAL
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MEKANISME KERJA ANESTETIK LOKAL
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MEKANISME KERJA ANESTETIK LOKAL
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SIFAT KIMIA & APLIKASI KLINIS
• Lipid solubility = banyaknya atom karbon ≈ potensi
• Protein binding ≈ lama kerja/durasi
• pKa mendekati pH fisiologik ≈ onset• pH = fraksi tdk terionisasi ≈ onset
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METABOLISME
Gol.Ester:• Pseudocholinesterase (plasma
cholinesterase)• Metabolit: PABA reaksi alergi
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Gol.Amida:• hepar: enzim mikrosom dealkilasi hidrolisis
• metabolit dari Prilocaine & Benzocaine methemoglobin
METABOLISME
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KECEPATAN ABSORPSI
• trgantung lokasi blok regional & ajuvan• Lokasi blok :
IntravenaTrakheal
InterkostalKaudal
Paraservikal/paravertebralEpidural
Pleksus BrakhialSciatic/femoral
Subkutan
cepat
lambat
a b s o
r p s i
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PENYEBARAN OBAT & BLOKADE
• Saraf bermielin lebih cepat mengalami blokade dibandingkan yg tdk bermielin dgn ukuran yg sama
BC , Aδ
AγAβAα
onset
recovery20
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PENYEBARAN OBAT & BLOKADE
Blok simpatis (vasodilatasi perifer & suhu kulit meningkat)
Blok nyeri & Sensasi suhu
Blok proprioseptif
Blok sensasi raba dan penekanan
Blok motorik
onset
recovery21
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• Obat AL menyebar dari sekeliling jaras saraf, difusi ke dalam jaras saraf sesuai gradien konsentrasi, dari jaras saraf terluar sp ke paling dalam
PENYEBARAN OBAT & BLOKADE
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TOKSISITAS
• Lokal– TNS– Cauda equina syndrome
• Sistemik– Kardiovaskular– Respirasi– Susunan saraf pusat,dll
• Efek lain-lain:– Alergi s.d anafilaktik– Hematologi (methemoglobin), dll
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• Toksisitas sistemik terjadi jika kadar puncak obat AL dalam darah mencapai konsentrasi yang cukup untuk menghambat konduksi impuls pada organ-organ tertentu shg terjadi gangguan fungsi organ
TOKSISITAS
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Faktor yg mempengaruhi:1. Injeksi AL intravena 2. Dosis obat3. Kecepatan absorpsi (lokasi, ajuvan
vasokonstriktor)4. Biotransformasi & eliminasi 5. Usia, berat badan, status sehat6. Kehamilan
TOKSISITAS
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TOKSISITAS
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• Susunan Saraf Pusat– Ringan s.d sedang: light-headedness,
dizziness, tinnitus, circumoral numbness, abnormal taste, confusion and drowsiness
– Berat : kejang tonik-klonik s.d hilang kesadaran scr cepat, koma, depresi nafas s.d henti nafas
TANDA & GEJALA TOKSISITAS
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• Kardiovaskular– Ringan s.d sedang:
• takikardia & hipertensi (AL plus adrenalin), • bradikardia & hipotension (AL minus adrenalin)
– Berat : henti jantung • biasanya diperlukan 4-7x dosis yg
mengakibatkan kejang • Henti jantung krn efek depresi langsung pd
miokardium
TANDA & GEJALA TOKSISITAS
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• Aritmia:– prolonged PR, QRS, and QT intervals
potentiating reentrant tachycardias with aberrant conduction
– cardiac resuscitation of such patients may be difficult and prolonged (30-45 min)
TANDA & GEJALA TOKSISITAS
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BERAPA DOSIS MAKSIMUM?
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• Penatalaksanaan– ABC resusitasi– atasi kejang (midazolam, pentotal,
propofol)– Resusitasi cairan– Vasopressor & inotropik– Anti aritmia – Lipid emulsion
TOKSISITAS
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BUPIVACAINE-ASSOCIATED CARDIAC ARREST
Bolus 1 ml/kg/min lipid emulsion 20% Starting infusion of 0,25 ml/kg/min Repeated bolus every 5 minutes, 2-3 times if neededWeinberg G, et al -Reg. Anesth. Pain med.2003;28:198-202 -Reg. Anesth. Pain med.2004;29:74-5
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• Sign of severe toxicity– Sudden loss of consciousness, with of without tonic-‐clonic convulsions
– Cardiovascular collapse : sinus bradycardia, conduc<on blocks, asystole and ventricular tachyarrytmias may all occur
– Local anaesthe<c (LA) toxicity may occur some <me aCer the ini<al injec<on
GUIDELINES FOR THE MANAGEMENT OF SEVERE LOCAL ANAESTHETIC TOXICITY
The Associa<on of Anaesthe<sts of Great Britain & Ireland 2007
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GUIDELINES FOR THE MANAGEMENT OF SEVERE LOCAL ANAESTHETIC TOXICITY
The Associa<on of Anaesthe<sts of Great Britain & Ireland 2007
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• Immediate management :– Stop injec<ng the LA
–Call for help– Maintain the airway and, if necessary, secure it with a tracheal tube
– Give 100% oxygen and ensure adequate lung ven<la<on (hyperven<la<on may help by increasing pH in the presence of metabolic acidosis)
– Confirm or establish intravenous access– Controle seizures : give a benzodiazepine, thiopental or propofol in small incremental doses
– Assess cardiovascular status throughout
GUIDELINES FOR THE MANAGEMENT OF SEVERE LOCAL ANAESTHETIC TOXICITY
The Associa<on of Anaesthe<sts of Great Britain & Ireland 2007
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• Management of cardiac arrest associated with LA injec<on:– Start cardiopulmonary resuscita<on (CPR) using standard protocols
– Manage arrhythmias using the same protocols, recognising that they may be very refractory to treatment
– Prolonged resuscita<on may be necessary; it may be appropriate to consider other op<ons :
• Consider the use of cardiopulmonary by pass if available• Consider treatment with lipid emulsion
GUIDELINES FOR THE MANAGEMENT OF SEVERE LOCAL ANAESTHETIC TOXICITY
The Associa<on of Anaesthe<sts of Great Britain & Ireland 2007
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• Treatment of cardiac arrest with lipid emulsion : (approximate doses are given in red for a 70-‐kg pa<ent)
– Give an IV bolus injec<on of IntralipidR 20% 1.5 ml/kg over 1 min
• Give a bolus of 100 ml
– Con<nue CPR
– Start an intravenous infusion of IntralipidR 20% at 0.25 ml/kg/min
• Give at a rate of 400 ml over 20 min
Con$nue........
GUIDELINES FOR THE MANAGEMENT OF SEVERE LOCAL ANAESTHETIC TOXICITY
The Associa<on of Anaesthe<sts of Great Britain & Ireland 2007
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GUIDELINES FOR THE MANAGEMENT OF SEVERE LOCAL ANAESTHETIC TOXICITY
The Associa<on of Anaesthe<sts of Great Britain & Ireland 2007
Con$nue......
• Treatment of cardiac arrest with lipid emulsion : (approximate doses are given in red for a 70-‐kg pa<ent)– Repeat the bolus injec<on twice at 5 min intervals if an adequate circula<on has not been restored
• Give two further boluses of 100 ml at 5 min intervals
– ACer another 5 min, increase the rate to 0.5 ml/kg/min if an adequate circula<on has not been restored
• Give at a rate of 400 ml over 10 min
– Con<nue infusion un<l a stable and adequate circula<on has been restored
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• Remember :– Con<nue CPR throughout treatment with lipid emulsion
– Recovery from LA-‐induced cardiac arrest may take > 1 h
– Propofol is not a suitable subs$tute for IntralipidR
– Replace your supply of Intralipid 20% aCer use
GUIDELINES FOR THE MANAGEMENT OF SEVERE LOCAL ANAESTHETIC TOXICITY
The Associa<on of Anaesthe<sts of Great Britain & Ireland 2007
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TERIMA KASIH
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