CURRICULUM VITAENama : Dr. dr. Muh. Ramli Ahmad, Sp.An-KAP-KMNNIP : 19590323 198702 1 001Status Dosen : Dosen Biasa NegeriTempat/Tanggal lahir : Bone. 23 Maret 1959Pangkat/Golongan : Pembina Utama Muda / IV cJabatan Struktural : KPS Bagian Ilmu Anestesi, Perawatan Intensif & Manajemen Nyeri Fakultas Kedokteran UNHASAlamat : Jl. A.P.Pettarani Blok GA7 No.9

Komp IDI Panakukang Makassar Telp/HP : 0411-456144 / HP: 0811442733 / Flx: 0411-5068281Alamat Kantor : Bagian Ilmu Anestesiologi, Perawatan Intensif & Manajemen Nyeri Fakultas Kedokteran UNHAS

RS. Dr. Wahidin Sudirohusodo Jl. Perintis Kemerdekaan Km.11 Tamalanrea Makassar 90245Riwayat Pendidikan : Jenjang S1, Bidang Kedokteran, Tamat tahun 1986Profesi, Bidang Kedokteran Umum, Tamat tahun 1986 Fakultas Kedokteran Universitas HasanudddinSpesialis, Bidang Anestesiologi, Tamat tahun 1996, Fakultas Kedokteran Universitas AirlanggaKonsultan Pediatric Tahun 2009Konsultan Manajemen Nyeri Tahun 2010S3 Kedokteran Pasca Sarjana Universitas Hasanuddin Makassar-Indonesia Tahun 2012 

The Role of Opioidin Epidural Analgesia

Muh. Ramli AhmadDepartment of Anesthesiolgy, IC and Pain Management

Faculty of Medicine, Hasanuddin UniversityMakassar, Indonesia

Introduction• Epidural Analgesia Small catheter inserted

into epidural space, where nerve roots come out from the spinal cord.

• Target delivery of opioid to spinal cord opioid receptors, less dose required → less systemic side effects, better analgesia

• Central neuraxial block

Introduction (cont.)

• Epidural opioids have the advantage of producing analgesia without motor or sympathetic blockade

• Opioids may be used alone• More commonly as adjuncts to local

anaesthetics with which they have a synergistic effect.

• Drugs used: local anaesthetic +/-fentanyl +/-morphine +/- Meperidine

Spinal cord opioid receptor

Adverse effects of epidural analgesia

• Neurological injury• Epidural haematoma• Epidural abscess• Respiratory depression• Hypotension• Postural puncture headache• Treatment failure

BASIC CONCEPT EPIDURAL ANALGESIA

BASIC CONSEP EPIDURAL ANALGESIA

Epidural Autonomic Organ Innervation:

BASIC CONCEPT EPIDURAL ANALGESIA

Reuben SS, Acute Pain Management 2009

Neural Patway

Humoral Patway

Humoral stress response

Epidural Analgesia

BASIC CONCEPT EPIDURAL ANALGESIA

Dimodifikasi dari Reuben SS, Acute Pain Management 2009Pebedahan/ luka operasi

NYERI

Proses Humoral (Mediator Inflamasi)

Pelepasan TNF-, IL-1β, IL-6, dan IL-10

SensitisasiPerifer

Proses Neural (Nosisepsi)

AktivasiCOX-2Otak

Aktivasi COX-2 Sirkulasi

Alur Nosisepsi dan Humoral

Transduksi

Modulasi

Transmisi

Persepsi

SensitisasiSentral

COX-2Medulla Spinalis

BASIC CONCEPT EPIDURAL ANALGESIA

Epidural BlockLocal Anesthetic

NeuroendocrineStress Response

ACTHADHGHTSH

Central COX-2

inhibition

CytokinesIL-1βIL-2IL-6TNF

NorepinephrineEpinephrineCortisolAldosteroneRenin

Sympathetic efferent

Modify by AHT

Humoral stress response

COX-2

Lipophilic OpioidsRapid Onset, Short Duration, Low CSF Solubility

Advantages Rapid Analgesia Ideal for

Continuous Infusion or PCEA

a low risk of delayed respiratory depression

Disadvantages Systemic

Absorption Brief Single Dose

Analgesia Limited Thoracic

Analgesia with Lumbar Administration

ANAESTHESIA TUTORIAL OF THE WEEK 230 4th JULY 2011

Hydrophilic OpioidsSlow Onset, Long Duration, High CSF Solubility

Advantages Prolonged Single

Dose Analgesia Thoracic Analgesia

with Lumbar Administration

Minimal Dose Compared with IV Administration

Disadvantages Delayed Onset of

Analgesia Unpredictable

Duration Delayed Respiratory

Depression

ANAESTHESIA TUTORIAL OF THE WEEK 230 4th JULY 2011

Opioid for Epidural Analgesia• Spinal cord opioid

receptor• Opioid Lipid solubility

– Lipophilic opioid : fentanyl– Hydrophilic opioid :

morphine • amount of opioid needed

to provide a given level of analgesia – Intravenous > epidural >

intratechal

ANAESTHESIA TUTORIAL OF THE WEEK 230 4th JULY 2011

The “Fate” of agent for epidural analgesia solution

EPIDURAL INJECTION

Epidural Venous diffusion through Plexus the duramater

Diffusion across the subdural space dural cuffs surrounding Systemic spinal nerve roots Circulation CSF

Centripetal diffusiontoward the neuraxis

Bind receptors In brain

Spinal root block

LongitudinalSpread up & down

1

2

Epidural analgesia

• Level I evidence – Provide superior analgesia than PCA.– Improve oxygenation and reduce

pulmonary infection and other pulmonary complication compared with iv opioid.

– Is not assoicated with increase risk of anastomotic leakage after bowel surgery

Level I evidence-thoracic epidural analgesia

• For open abdominal aortic surgery reduces the duration of tracheal intubation and mechanical ventilation and incidence of MI

• Used for CABG reduces postoperative pain, risk of dyrhythmias, pulmonary complications and time to extubation compared with ivi opioid analgesia

• Improves bowel recovery after abdominal surgery and colorectal surgery.

• Extended > 24 hours reduces the incidence of postoperative MI

• Reduces need for ventilation in patient with muliple rib fracture and reduce incidence of pneumonia

Morphine• The 1st reported & mostly studied opioid for

epidural analgesia• Lipid insoluble opioid (hydrophilic)• Slow onset (30 min.)* & long duration (12-24 hrs.)*

• Increased risk of delayed side effects after intratechal bolus, therefore;– Continuous administration have some clinical

advantages– And also, the recent study shows that quality of

analgesia appears to be more complete when using continuous technique

*: After epidural adminbistration

Meperidine

• Metabolit toxic - Normeperidine seizures - Exkresi melalui renal. local anesthetic properties• Inotropik negatif • Menyebabkan tachycardia (anticholinergic)• Interaksi dengan MAO inhibitors,

menyebabkan MAO syndrome • Berguna untuk mengatasi shivering

FentanylHighly lipophylic• Strong opioid agonist• 80x more potent than morphine• Available in parenteral, transdermal,

transbuccal preparation• Transdermal formulation onset 6 – 12

hour ,duration 3 – 6 days.

Fentanyl

• Highly potent lipid soluble opioid (lipophilic)• Rapid onset (10 min.)* & short duration (2-4 hrs.)*

• Preferentially undergo vascular absorption rather than meningeal penetration– No clinical advantages to administer via epidural

route compared to the IV route

IV fentanyl provides equivalent analgesia to the epidural routes, but slightly increased incidence of nausea & vomitting

- Guinard et al.-

*: After epidural adminbistration

ADJUVANT AGENTS IN NEURAXIAL BLOCKADE ANAESTHESIA TUTORIAL OF THE WEEK 230 4th JULY 2011

Epidural Opioids: intermittent dose, onset, duration

Epidural opioid dosesdrug Single dose Onset

( min )Duration

( h )Infusion solution ( μg/ml )

Continuous Infusion

Fentanyl 50 – 100 μg 5 - 10 2.5 - 4 5-10 25 – 100 μg/h

Sufentanyl 10 – 50 μg 5 2 - 4 1 10 – 20 μg/h

Meperidine 20 – 50 mg 5 -15 6 2500 10 – 30 mg/h

Methadone 2 – 8 mg 10 6 - 10 10 – 15 0.1 – 0.3 mg/h

Morphine 1 – 5 mg 30 -60 18 10 0.05 – 0.1 mg/h

Hydromorphone 0.5 – 1 mg 10 - 15 10 -12 5 -10 0.05 – 0.1 mg/h

Level of catheter insertion

Thoracotomy Th 5 -7

Upper abdominal incision Th 7 – 9

Lower abdominal laparatomy Th 10 – 11

Pelvic sugery/ Lower limb surgery L 2-4

Level of insetion shoud be in the middle of dermatome of planned incision.

Opioid and Local anesthetic combination

• synergistically.• decreased concentration of the local anesthetic and

a lower dose of the opioid may be possible. • Provides better analgesia with fewer side effects

Common opioids concentration Common LA concentrationMorphine 10 mcg/mlHydromorphone 10mcg/mlFentanyl 2-5mcg/mlMeperidine 2mg/ml

Common infusion rate : 5 – 14 cc / hr

Bupivacaine 0.1% (1mg/ml).Bupivacaine 0.05% (0.5mg/ml)Ropivacaine 0.2% (2mg/ml)

Recommended Level, Agents and days for removal of Epidural

Grass JA, Problems in Anesthesia1998,10(1):45-70

Anesth Analg 1997;85:3804)

PERBANDINGAN EFEKTIFITAS KOMBINASI BUPIVAKAIN + PETIDIN DENGAN BUPIVAKAIN+FENTANIL PADA

ANALGESIA EPIDURAL

Muhammad Ramli Ahmad, Abd Azis

Kombinasi bupivacaine + petidin sama Efektifnya dengan kombinasi bupivacaine + fentanyl pada analgesia epidural

HASIL PENELITIAN

Karakterisitik Kelompok Petidin(n=30)

Kelompok Fentanyl(n=30)

Nilai p

Jenis Kelamin Laki-laki : 4 (13,3%)Perempuan : 26 (86,7%)

Laki-laki : 13 (43,3%)Perempuan : 17 (56,7%)

0,110

Umur 40,5±13,1 49,5±16,5 0,062Operasi Obgyn 13 (43,3%) Obsgyn 6

(20%)

0,366

Digestif 8 (26,7%) Digestif 17 (56,7%)

Ortopedi 8 (26,7%) Ortopedi 6 (20%)

Urologi 1 (3,3%) Urologi 1 (3,3%)

Data disajikan dalam bentuk prosentase. Nilai p diuji dengan X2Test. Nilai p<0,05 dinyatakan signifikan

Tabel. Karakteristik sampel

Tabel. Perbandingan derajat nyeriPetidin (n=30) Fentanyl (n=30) p

2 jam pascabedah

Nyeri ringan : 30 (100%) Nyeri ringan : 30(100%)0,161

24 jam pascabedah

Tidak nyeri :16 (53,3%) Nyeri ringan :14 (46,7%)

Tidak nyeri : 19 (63,3%)Nyeri ringan: 11 (36,7%) 0,415

Akhir pelepasan kateter epidural

Tidak nyeri :18 (60%) Nyeri ringan :12 (40%)

Tidak nyeri : 21(70%)Nyeri ringan : 9(30%) 0,421

Data disajikan dalam bentuk prosentase. Nilai p diuji dengan Mann Whitney U Test. Nilai p<0,05 dinyatakan signifikan

CLOPEDIN

CONCLUSIONS• Opioids are commonly added to local anaesthetic

for operations performed under epidural.• Neuraxial opioids improve the quality of

intraoperative analgesia, delay regression of sensory blockade prolong postoperative analgesia.

• Multiple trials have shown that the addition of opioids to local anaesthetic solutions significantly improves pain relief after thoracic, abdominal and orthopaedic surgery.

Thank you! FOR YOUR ATTENTION