Management Acute Pain

ADVANCED NEUROLOGY LIFE SUPPORT
Management of
Acute Pain
ANLS 2017
JAKARTA, 2 – 3 DESEMBER 2017
Definition Pain
“An unpleasant sensory and emotional
experience associated with actual or
potential tissue damage or described
in term of such damage”
International Association for

the Study of Pain,(IASP), 1986
Haddox, 1990; Mariano, 2001
pain
Psychological
b a
Nociceptive
Diagram Nyeri
(Farrar.J.T)
Physical state environment
nociceptor Reflex action
Perception
Response
Memory & Affect/mood

expectation Actions
Symptoms &
Evaluation
signs
Painful : Non-Painful :
Klasifikasi Sindroma Nyeri
Pathophysiology Duration
Acute Chronic
Nociceptive mixed Neuropathic idiopatik
Somatic Visceral Peripheral Central

-superficial -Acute : < 3-6 months, mostly nociceptive
-deep -Chronic : > 3-6 months, mostly neuropathic
Klasifikasi Nyeri
• Nyeri nosiseptik (nyeri inflamasi/nyeri akut) :
nyeri terjadi oleh berbagai stimuli yg menimbulkan
kerusakan jaringan.
• Nyeri neuropatik (nyeri kronik) : nyeri krn lesi
primer atau disfungsi sistem saraf perifer atau sentral
• Nyeri idiopatik/psikogenik : nyeri yang kausanya
tidak jelas.
• Nyeri campuran : nyeri terjadi karena kerusakan
jaringan dan sistem saraf
Kausa Sindroma Nyeri

• Post-operative Pain
• Traumatic injury-related Pain
• Burn Pain
• Acute Herpes Pain
• Acute Pain in Obstetrics
• Sickle Cell Pain
• Cancer-related Pain
Kausa Sindroma Nyeri .. 2

• Headache
– Musculoskeletal : muscle tension
– Vascular : migraine, aneurysm
– Complex : compound headache
• Musculoskeletal Pain (back pain)
• Ischemic Pain
• Chest Pain
– Angina/ischemia
– Esophagitis/reflux
– Pleuritic pain : effusion, pneumonia, inflammation
Kausa Sindroma Nyeri .. 3

• Abdominal Pain
– Acute exacerbation of Pancreatitis
– Acute abdomen : perforation, obstruction,
aneurysm dissection/rupture
– Renal colic
• Neurogenic Pain
– Herniated disk
– Nerve compression
Kausa Nyeri (Patofisiologi)
Neuropathic Pain Nociceptive Pain

Mixed Pain
Pain initiated or caused by a Pain caused by injury to
Pain with
primary lesion or dysfunction body tissues
neuropathic and
in the nervous system (musculoskeletal,
nociceptive
(either peripheral or cutaneous or visceral)2
components
central nervous system)1
Examples
Peripheral Examples Examples
• Postherpetic neuralgia
• Trigeminal neuralgia • Low back pain with • Pain due to inflammation
• Diabetic peripheral neuropathy radiculopathy • Limb pain after a fracture
• Postsurgical neuropathy • Cervical radiculopathy • Joint pain in osteoarthritis
• Posttraumatic neuropathy • Cancer pain • Postoperative visceral pain
Central • Carpal tunnel syndrom
• Poststroke pain Common descriptors2
Common descriptors2 • Aching
• Burning • Sharp
• Tingling • Throbbing
• Hypersensitivity to touch or cold
1. International Association for the Study of Pain. IASP Pain Terminology.
2. Raja et al. in Wall PD, Melzack R (Eds). Textbook of pain. 4th Ed. 1999.;11-57
LBP & Lumbal Radiculopati
karena HNP (mixed Pain)
Activation of peripheral nociceptors –

cause of nociceptive pain component
Disc herniation
Lumbar
vertebra
Compression and inflammation of nerve root –

cause of neuropathic pain component
Derajat Rasa Nyeri
Jenis-jenis Serabut Saraf

Fiber type Function Ø fiber Conduction Hypoxia Pressure LA
(mm) velocity (m/s)
Aα Propriception 12-20 70-120 ++ +++ +
somatic motor
Aβ Touch, pressure 2-12 30-70
Aγ Motor to muscle 3-6 15-30
spindle
Aδ Pain,cold, touch 2-5 12-30
B Preganglionic <3 3-15 +++ ++ +
otonomic
C dorsal root Pain, temperature 0.4-1.2 0.5-2 ++ ++ +++
mechanoreception,
reflex response
C Postganglionic 0.3-1.3 0.7-2.3
simpatetik sympathetic
A and B fibers are myelinated, C : fibers unmyelinated, LA : local anesthetic

+: least susceptible, ++ : intermediated susceptibility, +++ : most susceptible
Mekanisme Rasa Nyeri

Iskemik, Spasme Kortek
Cedera, dll A myelin/fast Talamus
C unmyelin/slow
1
Cornu
Nosiseptor NAP 3 4
2 dorsalis
free nerve
ending
Substanse P GABA, Glycine
Adenosine
Platelet - serotonin
Bombesin
Histamine Mass cell - histamin
Cholecystokinin
K*, bradikinin
1. Transduksi Dynorphin
Prostaglandin
2. Transmisi Enkephalin
5-HT
3. Persepsi Neuropeptide-Y
4. Modulasi
Mekanisme Rasa Nyeri .. 2

Dapat dibagi menjadi 4 tahap yaitu :
1. Tranduksi : proses timbulnya aktivitas listrik krn
stimulasi noksius pd reseptor “nerve ending”
2. Transmisi : menjalarnya impul nyeri dr nosiseptor
aferen primer(NAP) ke kornu dorsalis med spinalis
3. Persepsi : Impul rasa nyeri diterima talamus kmd
diproyeksikan ke kortek somatosensorik & kortek
asosiasi timbul kesadaran rasa nyeri
Mekanisme Rasa Nyeri .. 3

4. Modulasi : aktivitas selektif sel saraf untuk meng-
hambat transmisi rasa nyeri via serabut saraf Aδ,
medula spinalis, medula oblongata & midbrain.
Ada 2 teori modulasi,
a. Gate control hypothese - modulasi nyeri saraf asenden
yaitu jika serat saraf C di aktivasi terjadi inhibisi inter-
neuron pintu nyeri akan terbuka, jika serat saraf Aδ di
aktivasi terjadi eksitasi interneuron pintu nyeri akan
tertutup
b. Sistem opioid endogen - modulasi nyeri saraf desenden
berasal dari :
modulasi
(a)
a. Midbrain : periaquaduct gray-
matter (PAG) mengandung μ midbrain
reseptor yg dpt mengaktivasi
opioid endogen.
b. Medula oblongata, di :
- nucleus raphe magnus (NRM) (b)
melepas serotonin.
med.obl
- NPRG (nucl reticularis para (b)
giganto cellularis) melepas
noradrenalin
c. Cornu dorsalis Med spinalis,
dapat menghambat trasmisi
med.spin (c)
nosiseptor.
Rasa nyeri ↓ atau menghilang.
Stress Response Post-Injury

spinothalamic
S neospinothalamic Lateral kortek
P C thalamus somasensorik Sensation
I O
N R
A D reticular medial associative Affect
L formation thalamus cortex
spinoreticular paramedian
Corticotropin-releasing factor
Vasoactive-intestinal peptide
hypothalamus sympatic
Nerv syst Nor-eph
Mediator Humoral Pituitary. gl

Perifer
β endorphin
Interleukin 1 & 2 *propiomelano- Epineph
TNF/tumor necr F adrenal
cortin ACTH gland Enkephalins
Bradykinin *growth horm Aldosterone
α interferon *prolactin cortisol
PGE1,PGE2, etc *vasopressin pancreas glucagon
Stress Response Post-Injury

• Endocrine : ↑stress hormone, ↑metabolic rate,
↑heart rate & water retention
• Immune : impaired immune functions
• Pulmonary : ↓flow and ↓volume  retained
secretions and atelectasis.
• Cardiovascular : ↑cardiac rate, ↑systemic vascular
resistance, ↑peripheral vascular resistance,
↑coronary vascular resistance  ↑blood pressure
and myocardial oxygen consumption
Post-Injury Stress Response .. 2

• Gastrointestinal : delayed return of gastric and
bowel function
• Musculoskeletal : decreased muscle function,
fatigue and immobility.
Stress Response Post-Injury .. 2

1: cedera jaringan merang-
Painful stimulus
sang pembentukan prosta-
glandin sensitivitas no-
Pain-sensitive tissue
siseptor ↑ (pain)
Prostaglandin 2: Nosiseptor melepas

1 Substance P Blood vessel substance P  pemb drh
Mast cell
melebar & dilepas media-
Histamine tor inflamasi yi Bradykinin
(redness and heat)
Bradykinin
Substance P
2 3: Substance P juga me-
3 rangsang degranulasi mass
cells, dilepas zat histamin
Nociceptor (swelling)
Gejala klinik
Nyeri Nosiseptif Akut
• Onset mendadak
• kualitasnya tajam, tertikam, tertusuk
• Lokalisasi
• Self-limiting
• mungkin ada manifestasi fisiologis dgn berbagai
sistem organ yg lain.
• Response Autonom: palpitasi, ↑tekanan darah,
berkeringat , etc
• Biasanya kausa jelas
• Dipengaruhi keadaan fisiologis
Karakteristik
Nyeri Somatik Dalam
• kualitas nyeri : tumpul dan sakit
• kurang terlokalisir dibanding nyeri superfisial
• berhubungan dgn hiperalgesia kutaneus,
allodinia, lemas, reflek otot spasme , hiper-
aktivitas simpatis.
Prinsip tatalaksana Nyeri Akut

• Beri terapi adekuat utk kontrol rasa nyeri
• Cegah resiko rasa nyeri bertambah herat
• Pertahankan kemampuan fungsional untuk
menjaga faktor psikologis tetap baik
• Tingkatkan kualitas hidup
• Usahakan rawat inap tidak lama/singkat
utk mengurangi biaya.
Prinsip Terapi Nyeri Akut & Berat
Beri analgesik dosis maksimal

Alur Terapi Nyeri Kronik
(WHO ANALGESIC LADDER 1996)
Freedom from pain
Opioid for moderate to severe pain Step 3

+/- Adjuvant
Persisting Pain
Opioid for mild to moderate pain Step 2

+/- Non opioid , +/- Adjuvant
Persisting Pain
Step 1
Non opioid +/- Adjuvant
Tatalaksana Nyeri Akut

• Terapi farmakologik :
– Analgetik opioid
– Analgetik non opioid
– Antikonvulsan
– antidepresan
• Terapi intervensi/operasi
– Perawatan luka, fiksasi fraktur atau operasi
– Terapi intervensi : epidural, spinal analgesia, nerve block
• Terapi non-farmakologik  nyeri kronis
– neurostimulasi (TENS),
– psikologis (kognitif behavior, relaksi, hipnosis).
Analgesik Opioid
• Analgesik potent
• Obat pilihan utk nyeri sedang dan hebat
• Pemakaian harus diawasi karena side efeknya al :
– Adiksi : phisik dan psikis (euphoria).
– SSP : aktivitas mental & motorik ↓, euphoria &halusinasi
– Bronchokonstriksi : depressi pernafasan, nafas dangkal & RR ↓
– Sistem sirkulasi darah : vasodilatasi perifer (keringat basah,
hipotensi dan bradikardia
– GI Tract : obstipasi
– Saluran urogenital : retensi urine, kontraksi uterus ↓
– Pelepasan histamine : pruritus dan urticaria.
Analgesik Opioid .. 2
• Variabilitas diantara pasien 10 kali lipat.
• Semua opioid mempunyai SE yg sama, tapi
ratio (efikasi : SE) berbeda utk tiap orang
• Jika mungkin beri terapi per oral.
Jenis Obat Pot Equal-aalgesic Keterangan
Oral parenteral
Morphine 30mg 10mg Long acting oral 8-12 jam yg dpt diberikan
rektal, hati-hati pd pts CRF dpt myoclonus
hydromorphone 7.5mg 1.5mg Opioid poten, bisa utk pts disfungsi renal
Oxycodone 20mg - Long acting diberikan o/rectal/8-12jam
Methadone 5mg ** Waktu paruh >24jam, penyesuaian dosis
harus hati2, diberikan 6-8 jam utk th/
nyeri, dipakai utk nyeri neuropatik, ratio
equal analgesik berubah dg dosis morphin
oral >100mg, konsul spesialis
Levorphanol 4mg Sering dikombinasi dgn analgesik non-
opioid,
Derby, 1998 American Pain Society, Principles of Analgesic Use in the

Treatment of Acute Pain and Cancer Pai, 5th edition, 2003
Jenis Obat Pot Equal-analgesic Keterangan
Oral parenteral
Levorphanol 4mg 2mg Poten opioid dgn bbrp aktivitas NMDA
antagonis
Meperidine 300mg 75mg Metabolisme normoperidine, stimulan CNS,
dpt menimbulkan kejang pd pts dgn gagal
ginjal.
Fentanyl *** - 100mcg Short-acting, bisa patch transdermal dan
buccal
Codein 200mg 130mg 5-10% ras kaukusia tdk bisa merubah codein
ke morphin, SE nausea dan konstipasi > dp
opioid lain, efek narkose pd pts gagal ginjal
Derby, 1998 American Pain Society, Principles of Analgesic Use in the

Treatment of Acute Pain and Cancer Pai, 5th edition, 2003
Non-Opioid Analgesics
• Acetaminophen
• NSAIDs (Aspirin, Ibuprofen, Ketorolac,
COX-2 Inhibitors)
• Lidocaine Patch (Lidoderm)
NSAIDs
• Relieve of Mild to Moderate Pain
• Complication:
– GI Discomfort
– GI Bleeding (Inhibition of COX-1)
– Nephrotoxicity
– Inhibition of Platelet Aggregation
– Osteogenesis
Ketorolac
• Potent Analgesic
• Parenteral (IV or IM)
• 15-30 mg Q 6hr
• Patients Older than 16 yrs
• Should not Exceed 5 days
Lidoderm
• 5% Lidocaine Patch
• Indicates for Pain Relief in Post-herpetic
Neuralgia
• Each Patch Contains 700 mg of Lidocaine
• Should be Applied to Intact Skin
• About 3% is Absorbed
• 1-3 Patches Once a Day for 12 hrs
Lidoderm
Farmako Terapi Nyeri Inflamasi

NYERI RINGAN
FARMAKOTERAPI TINGKAT I
Nama Obat Dosis Jadwal
Aspirin 325-650 mg, mak 4 g/hr 4 jam sekali
Asetaminofen 325-650mg 4-6 jam sekali
FARMAKOTERAPI TINGKAT II
Ibuprofen 200mg 4-6 jam sekali
Sodium Naproxen Awal 440mg, selanjutnya 220mg 8-12 jam sekali
Ketoprofen 12,5mg 4-6jam sekali
Farmako Terapi Nyeri Inflamasi .. 2
NYERI SEDANG
FARMAKOTERAPI TINGKAT III
Asetaminofen 4 jam sekali
Ibuprofen Penyesuaian dosisi misal 4-6 jam sekali
Aspirin 1000mg
Sodium naproxen 8-12 jam sekali
Ketoprofen 4-6 jam sekali
FARMAKOTERAPI TINGKAT IV
Jika terapi tk. III, OAINS yg dipilih dapat diganti, pilihan OAINS ke-2 sebaiknya dr
kelompok kimia yg berbeda (lihat tabel analgesik non-opioid yg sering digunakan
FARMAKOTERAPI TINGKAT V
Opioid (misal : codein)
FARMAKOTERAPI TINGKAT VI
Tramadol 50-100mg 4-6 jam
Farmako Terapi Nyeri Inflamasi .. 3

NYERI BERAT
FARMAKOTERAPI TINGKAT VII
Nama Obat Indikasi Mekanisme
Morfin Bila th/ non-narkotik tdk efektif dan 4 jam sekali
terdapat riwayat th/ narkotik untuk
nyeri
Campuran agonis - Blok aktivasi
antagonis pentazosin komponen mμ
komplek reseptor
Agonis parsial idem
Analgetik Non Opioid yang

Paling Sering Digunakan
Aspirin 325-1000mg 4-6 jam sekali
Kalium diklofenak 50-200 mg 8 jam sekali
Natrium diklofenak 50 mg 8 jam sekali
Ibuprofen 200-800 mg 4-8 jam sekali
indometasin 25-50 mg 8-12 jam sekali
Ketoprofen 25-75 mg 6-12 jam sekali
Asam Mefenamat 250 mg 6 jam sekali
naproxen 250-500 mg 12 jam sekali
Analgetik Non Opioid yang

Paling Sering Digunakan .. 2
Piroxicam 10-20 mg 12-24 jam sekali
Tenoxsicam 20-40 mg 24 jam sekali
Meloxicam 75 mg 24 jam sekali
Celecoxib 100 mg 12 jam sekali
Nimesulfid 100 mg 12 jam sekali
Ketoralax 10-30 mg 4-6 jam sekali
Asetaminofen 500 mg 6-8 jam sekali
Tramadol 50-100 mg 8 jam sekali
Anticonvulsants used as
adjuvant analgesics
Drug Effective daily dose Doses/day Evidence
Gabapentin 300 - 3600 mg 1-4 CT
Carbamazepine 100 - 1600 mg 2-4 CT
Valproate 500 - 3000 mg 2 OLT
Phenytoin 100 - 300 mg 1-3 CT
Clonazepam 1 - 10 mg 1-3 OLT
Lamotrigine 150 - 500 mg 2 CT
Topiramate 25 - 400 mg 2 CT
Pregabalin 300 - 600 mg 1-2 CT
Oxcarbazepine 300 - 2400 mg 2 OLT
CT : control trials, OLT : open label trials,
Interventional Management
• 1. Epidural Analgesia
– Continuous Lumbar or Thoracic Epidural
Catheter Placement,
– PCEA : Patient Control Epidural Analgesia
• 2. Spinal Analgesia
• 3. Peripheral Nerve Block
– Single Shot
– Continuous
1. Epidural Anesthesia
• Lumbar Epidural: Lower Extrimity, Pelvic, and
Lower Abdominal Procedures
• Thoracic Epidural: Upper Abdomen and
Thoracic Procedures
• Caudal Injection: More Commonly Used for
Pediatric Patients (Genitourinary and Lower
Abdominal Procedures)
Advantages
• Superior Pain Relief
• Less Systemic Side Effects
• Lower Incidence of DVT and Pulmonary Emboli
• Decrease Blood Loss Intraoperatively during
Orthopedic, Urologic, Gynecologic and Obstetric
Procedures
• More Rapid Recovery of Bowel Function
• Earlier Ambulation
• Better PFT
• Suppression of Neuroendocrine Stress Response
Grass JA. The Role of Epidural Anesthesia and Analgesia in Postoperative Outcome. Anesthesiol Clin
North America 01-JUN-2000; 18(2): 407-28
Contraindications
• Absolute • Relative
 Patient Refusal  Uncooperative
 Coagulopathy Patient
 Increased ICP  Pre-existing Neurologic
 Skin Infection Disorder
 Anatomical
Abnormalities
Spinal Anesthesia
• Spinal Anesthesia is Induced by Injecting
Small Amount of Local Anesthetic
(Bupivicaine) in the CSF
• Results in Rapid Onset of Block
• More Rapid Onset and Requiring less
Medicine Compared to Epidural Analgesia
Spinal Anesthesia
• CSE, Used in Labor

• Preservative Free Morphine (Duramorph)
Provides Pain Relief for Abdominal, Pelvic,
or Lower Extrimity Surgeries
• Complications Similar to Epidural Technique
Except for Higher Risk of PDPH
Peripheral Nerve Block

• Anesthetizing the Nerve that is Innervating
Surgical or Painful Area
• Single Shot or Continuous Infusion through
Catheter
• Upper Extrimity: Brachial Plexus, Median,
Ulnar or Radial Nerve
Peripheral Nerve Block

• Lower Extrimity: Sciatic, Femoral, Posterior
Tibial, Sural, Saphenous, Deep and
Superficial Peroneal Nerve
• Intercostal Nerve Block
• Surgical Wound Infiltration of Local
Anesthetic
Non Farmakologi
1.Physical treatment
- Heat: diathermy, ultrasonic.
- Cold: compress, ice massage, vapo-coolant spray.
- Massage
- Exercise
- Ortosis.
- TENS, accupuncture.
2. Psychological therapy
Relaxation, biofeedback, education, hypnosis.
SCS - equipment
Spinal Cord Stimulator

Kesimpulan
1. Nyeri akut adalah respon fisiologis atas
stimulasi noksius (mengancam/merusak
jaringan atau tubuh).
2. Persepsi nyeri bersifat individual, dasar
mekanisme fisiologisnya sangat komplek
3. Tatalaksana nyeri kronik/neuropatik ber-
sifat multidisiplin meliputi terapi farmasi
non farmasi, dan terapi bedah.
Trigeminal Neuralgia
Surgical Treatment of TN
• Microvascular decompression (MVD)
• Percutaneous ablative procedures
– Radiofrequency gangliolysis
– Glycerol rhizolysis
– Balloon compression
• Stereotactic radiosurgery
– Gamma knife
– Linac-based
• Peripheral ablative procedures (V1 and V2 pain)
– Peripheral branch neurectomy
– Alcohol neurolysis
• Open destructive procedures
– Partial sensory rhizotomy
– Subtemporal ganglionectomy (Frazier-Spiller procedure)
MVD vs. Percutaneous Procedures

INITIAL PAIN RELIEF
• MVD 98%
• RF rhizotomy 98%
• Balloon 93%
• Glycerol 91%
RECURRENCE RATES
• Glycerol 54% (4 years)
• RF rhizotomy 23% (9 years)
• Radiosurgery 25% (3 years)
• Balloon 21% (2 years)
• MVD 15% (5 years)
Taha J, Tew J: Neurosurgery 38:865—871, 1996

Equianalgesia
Opioid PO Parenteral
(IV/SC)
Morphine 10 mg 5 mg
Codeine ~ 60-100mg N/A
(4-fold variability)
Hydromorphone 2 mg 1 mg
Oxycodone 5 mg N/A
Cox-2 Inhibitors
Drug Dose
Celecoxib (Celebrex) 100-200mg PO Bid
Rofecoxib (Vioxx)
Valdecoxib (Bextra) 10-20mg PO Qd
Parecoxib 20-40mg IM
20-100mg IV
Patient Controlled Analgesia (PCA)

• Small Doses of Analgesic Drug (Usually Opioids),
are Administered (IV) by Patient
• Allows Basal Infusion and Demand Boluses
• Over Dosage is Avoided
by Limiting the Amount
and Number of Boluses
in a Set Period of Time
Dose Regimens for PCA

Drug Bolus Dose Lock-Out
(mg) (Minutes)
Morphine 0.5-2 5-15
Hydromorphone 0.1-0.2 5-10
Fentanyl 0.01-0.02 5-10

Routes of Administration
• PO
• PR
• IV
• IM
• Transdermal
• Transmucosal
• Epidural
• Intrathecal
Pharmacologic Management
• Alter Nerve Conduction (Local Anesthetics)
• Modify Transmission in the Dorsal Horn
(Opioids, Antidepressants)
Opioid Analgesics
• Bind to Opioid Receptors:
Mu, Delta and Kappa
• Morphine, Hydromorphone, Meperidine,
Fentanyl, Codeine, Methadone, Oxycodone,
Hydrocodone, Tramodol
• Opioids may be Combined with NSAIDs to
Enhance the Opioid Analgesic Effect
Opioid Analgesics
• Equianalgesic Conversion Charts are used
when Converting form one Opioid to
Another, or Converting from Parenteral to
Oral Form
• Respiratory Monitors may be Used
Depending on the Patients Age, Co-existing
Medical Problems, or Route of Opioid
Administered
Opioid Analgesics
Conversions: Morphine
Oral Parenteral Epidural Intrathecal

300 100 10 1
Opioids
Drug PO IV Starting Oral Comments
mg mg Dose mg
Morphine MS Contin, Release 8-12 hrs

30 10 15-30
MSIR for BTP
Hydro- Duration Slightly Shorter than
7.5 1.5 4-8 Morphine
morphone
Meperidine Duration Slightly Shorter than
300 75 Morphine
Normeperidine Causes CNS
Toxicity
Methadone Long Half-Life, 24-36 hrs
20 10 5-10 Qd
Accumulates on Days 2-3
Fentanyl 0.02- Fentanyl Patch, 12 hrs Delay
0.05 Onset and Offset
Opioids
Drug PO mg Comments Precautions
Combined With Nonnarcotic Maximal Dose for
Codeine 30-60 Analgesics Acetaminophen
4gm/d
Percocet Acetaminophen or
Oxycodone 5-10 Aspirin toxicity
Percodan
Oxycodone 10-30mg Q 4h
Oxycontin 10mg Q 12h
Vicodin or Lortab Acetaminophen
Hydro- 5-10 Toxicity
codone
Central Acting, Affinity for Maximal Dose 400
Tramodol 50-100 Mu Receptors mg/d
Q4-6hr
Opioids
• 10 fold variability between patients
• All opioids have same side effects but
efficacy:side effect ratio is different for
everyone
• Stick with what works and keep it simple
• Always by mouth if possible
• Avoid pro-drugs ie. codeine
• Avoid combo preparations
Efek samping analgetik opioid (umum)
1. Depresi SSP, mis : sedatif, depresi pernafasan & batuk, miosis,

hipothermia, mual & muntah (karena rangsangan pd CTZ / chemo triggrer
zone), penurunan aktivitas mental & motorik, euforia, perasaan
termangu, halusinasi .
2. Bronchokonstriksi saluran nafas, shg pernafasan menjadi dangkal &
frekuensinya menurun.
3. Sistem sirkulasi darah : vasodilatasi perifer (jika pd kulit, keluar keringat
berlebihan), hipotensi & bradikardi (dosis tinggi).
4. Saluran GI : obstipasi karena peristaltik berkurang, kolik batu empedu
karena kontraksi sfingter kandung empedu.
5. Saluran urogenital : retensi urin (karena tonus sfingter kandung kemih
naik), kontraksi uterus berkurang (memperpanjang waktu persalinan).
6. Pelepasan histamin : pruritus, urticaria.
7. Kebiasaan & ketagihan
Systemic Analgesia
• Opioids
– Potent analgesics
– Drug of choice for moderate to severe pain
– Unfortunately, they are often the only drug
ordered
– Side effects:
Importance of
Pain Management
• Adequate Pain Control
• Reduce the Risk of Adverse Outcomes
• Maintain the Patient’s Functional Ability, as
well as Psychological Well-being
• Enhance the Quality of Life
• Shortened Hospital Stay and Reduced Cost
2. ANALGETIK NARKOTIKA / OPIOID

• Adalah obat yg daya kerjanya meniru opioid endogen / endorfin dg
memperpanjang aktivasi reseptor opioid (reseptor µ) di SSP shg
persepsi nyeri & respon emosional terhadap nyeri berubah / dikurangi.
• Mekanisme kerja analgetik narkotik :

analgetik opioid berikatan dg (sisa) reseptor opioid pd SSP (yg belum
ditempati endorfin) shg mengubah persepsi & respon thd stimulus
nyeri sambil menghasilkan depresi SSP secara umum.
• Minimal ada 4 macam reseptor opioid, yaitu reseptor µ, k, δ, ε, dan σ,

sbg tempat pengikatan analgetik narkotik untuk menghasilkan efek
analgesia yg menyerupai endorfin.
• UU narkotika no.22 tahun 1997

• Propoksifen, pentazosin, tramadol → tidak termasuk UU narkotika,
karena bahaya ketagihan/adiksi & kebiasaan ringan, penggunaan lama
tidak dianjurkan.
opioid
• obat yg daya kerjanya meniru opioid endogen /endorfin
dgn memperpanjang aktivasi reseptor opioid (reseptor µ)
di SSP sehingga persepsi nyeri dan respon emosional thd
nyeri berubah /dikurangi.
• Analgetik opioid dpt digunakan sendiri/kombinasi dgn
analgetik non-opioid utk nyeri sedang atau hebat.
• Efek samping opioid :
– Depressi SSP : penurunan aktivitas mental & motorik
– Bronchokonstriksi saluran nafas : nafas dangkal dan RR↓
– Sistem sirkulasi : vasodilatasi perifer  berkeringat,
hipotensi, bradikardia
– Saluran cerna : obstipasi, saluran urogenital – retensi urine
– Pelepasan histamin : pruritus, urticaria
Klasifikasi analgetik opioid berdasarkan cara kerja pd reseptor opioid :
1. Agonis Opiat
• Menyerupai morfin, bekerja sebagai agonis terutama pd reseptor μ dan mungkin
pd reseptor k.
• alkaloid candu : morfin, codein, heroin, nicomorfin.
• Zat sintetis : metadon & derivatnya (dextromoramida, propoksifen, bezitramid),
petidin & derivatnya (fentanil, sufentanil), tramadol.
2. Antagonis Opiat
• Tidak memiliki aktivitas agonis pd semua reseptor.
• Ex : nalokson, naltrekson, nalorfin, pentazosin, buprenorfin, nalbufin.
3. Kombinasi
• Zat ini mengikat pd reseptor opiat tapi tidak mengaktivasi kerjanya dg sempurna.
a). Agonis-antagonis opiat
Bekerja sebagai agonis pd beberapa reseptor & sebagai antagonis (agonis lemah)
pd reseptor lain. Ex : nalorfin, pentazosin, nalbufin, dezosin, butorfanol,
buprenorfin.
b). Agonis parsial (buprenorfin, pentazosin).
• Indikasi analgetik opioid (umum)
• Analgetik opioid bisa digunakan sendiri / kombinasi dg analgetik

non-opioid dalam penatalaksanaan nyeri sedang – hebat.
• Analgetik opioid juga telah digunakan sbg :

- analgetik selama persalinan.
- pra bedah (sedasi praoperatif).
- intrabedah
- pascabedah
- adjuvan anestesia
- dalam perawatan intensif untuk analgesia, sedasi &
antinsietas.
- antitusif (penekan rangsang batuk kering, mis : codein)
Farmakokinetik analgetik opioid (umum)
1. Absorpsi
50% obat diabsorpsi dari sal. GI & diabsorpsi sempurna
dari tempat injeksi i.m.
2. Distribusi
umumnya didistribusikan secara luas, menembus
plasenta & masuk ASI.
3. Metabolisme
umumnya di hati, reaksi metabolisme berbeda
tergantung @ obat.
4. Ekskresi
melalui ginjal.
5. Waktu paruh eliminasi
berbeda tergantung @ obat.
Kebiasaan (habituasi) & ketagihan (adiksi)

• Mekanisme kerja Kebiasaan & ketagihan :
bila analgetik opioid dipakai terus-menerus, pembentukan reseptor
opioid yg baru terus distimulasi & produksi endorfin di ujung saraf otak
dirintangi.
• Penyebab :
– Penggunaan jangka lama
– Toleransi, yaitu efektifitas opioid berkurang karena dipercepatnya
absorpsi / eliminasinya / menurunnya sensitifitas jaringan sehingga
diperlukan dosis yg lebih besar untuk mencapai efek yg sama
seperti semula.
– penggunaan dosis besar lebih baik bagi si pengguna & tidak
menimbulkan gejala intoksikasi.
• Ada 2 jenis ketergantungan / ketagihan, yaitu fisik & psikis (efek

psikotrop / euforia).
Lanj…Kebiasaan (habituasi) & ketagihan (adiksi)
• Abstinensi (withdrawal syndrome) : penghentian penggunaan obat opioid

secara mendadak.
• Gejala abstinensi : ketakutan, berkeringat, mata berair, mual-muantah,
diare, insomnia, tachycardia, mydriasis (pembesaran pupil), tremor, kejang
otot, TD naik, diikuti reaksi psikis (gelisah, mudah tersinggung, marah,
takut mati).
• Pengobatan adiksi (perhatikan tingkat ketergantungan fisik pecandu) :
– Terapi substitusi ( pemberian metadon sbg obat pengganti heroin /
morfin atau klonidin untuk menurunkan TD, pusing, mengurangi
gejala insomnia, mudah marah, & jantung berdebar-debar).
– Antagonis opioid (obat yg melawan ES opioid tanpa mengurangi efek
analgetiknya, berdasarkan penggeseran opioid dari reseptor opioid di
SSP).
Con : nalokson, naltrekson, nalorfin.
Penggunaan analgetik opioid

pd kehamilan & laktasi
• Opioid dapat melintasi plasenta.
• Boleh digunakan beberapa waktu sebelum persalinan.
• Bila diminum terus, merusak janin akibat depresi
pernafasan & memperlambat persalinan.
• Bayi dari ibu yg ketagihan juga menderita gejala
abstinensi.
• Selama laktasi, ibu dapat menggunakan opioid karena
hanya sedikit terdapat dalam ASI.
Perhatian & kontraindikasi
• Gunakan opioid hati-hati pd :

1. Penyakit ginjal, hati, pulmoner parah (asma).
2. Hipotiroidisme
3. Pasien lansia / pasien lemah (penyakit saraf / otot)
4. Nyeri abdomen / hipertrofi prostat yg tidak terdiagnosa.
5. Insufisiensi adrenal
6. Alkoholisme
7. Anak-anak (meningkatkan resiko kejang akibat akumulasi
normeperidin)
8. Pasien dg riwayat hipotensi sebelumnya (mis : pasca perdarahan).
9. Kurangi dosis opioid pd pasien lansia, malnutrisi, gangguan fungsi
ginjal / hati (mis : pre-eklamsia).
Perhatian & kontraindikasi
• Kontraindikasi :
1. Hipersensitifitas
2. Kehamilan / laktasi (penggunaan kronis)
3. Penggunaan dg MAOI (Monoamin oksidase inhibitor) yg baru
berjalan (14 – 21 hari).
4. Peningkatan tekanan intrakranial / konsentrasi CO2 (penyakit
pernafasan yg berat).
Interaksi
1. Analgetik opioid vs obat gol. Depresan SSP lain (alkohol;
antihistamin; sedatif-hipnotik = barbiturat & benzodiazepin; obat
anestesi = nitrogen oksida; metoklopramida; fenotiazin /
proklorperazin; antidepresan trisiklik) → depresi SSP >>>.
2. Analgetik opioid (meperidin, pentazosin,tramadol) vs MAO

Inhibitor atau SSRI (selective serotonin re-uptake inhibitor) atau
probakarbazin → menimbulkan hiperpireksia disertai hipotensi /
hipertensi yg fatal, dihindari selama 14 – 21 hari sesudah terapi
MAOI dihentikan.
3. Analgetik opioid vs metoklopramid, cisapride & domperidon →

stasis lambung.
Interaksi
4. Analgetik opioid (meperidin, metadon, fentanil, morfin) vs

simetidin / ranitidin (antagonis H2) → menghambat enzim
mikrosomal shg metabolisme opioid dicegah, akibatnya konsentrasi
opioid meningkat (apnea & gejala kebingungan).
5. Opioid (meperidin, pentazosin) vs antikonvulsan (fenitoin,

karbamazepin, fenobarbiton); rifampisin; estrogen & tembakau →
menginduksi enzim hati shg eliminasi opioid dipercepat, akibatnya
efek opioid menurun → pemberian opioid harus lebih sering /
dosisnya dinaikkan.
6. Opioid vs siklizin → edema paru (jarang terjadi).

Cegah Nyeri Akut Jadi Kronik
Acute Chronic
(nociceptive) (neuropathic)
Terapi adekuat :
Biological Biological
-Cegah nyeri kronik
function (+) function (-)
-Cegah Yellow Flag
disadvantage
Avoid
tissue damage
Physical Psychological
*impairment *triad :
Advantage *disablity
*health Pain
*well being
Sleep Mood
> Dysfunction  ↓QoL

> Socioeconomic loss
Metabolic and Endocrine

responses to injury
Endocrine ↑catabolic hormons ↑ِACTH, cortisol , ADH, growth H,
Catecholamine, angiotensin II,
aldosterone, glocagons, IL-1, TNF, IL-6
↓anabolic hormons ↓insulin, testosterone
Metabolic
carbohydrate Hyperglycemia, glucose ↑glycogenolisis, gluconeogenesis
intolenrance, insulin (cortisol, glucagon, growth H,
resistence adrenalin, free fatty acid). ↓insulin
secretion/activation.
Protein Muscle prot catabolism ↑cortisol, adrenalin, glucagon, IL-1,
↑synthesis of acute IL-6 dan TNF.
phase proteins
Lipid ↑lypolysis & oxidation ↑catecholamine, cortisol, glucagon,
growth H.
Metabolic and Endocrine

responses to injury .. 2
water and retention of water and ↑catecholamine, aldosterone, ADH,
electrolyte sodium. ↑ excretion of cortisol, angiotensin II, prostaglandin
potassium, ↓functional and othersfactors.
flux ECF with shifts to ICF
Note: ICF - intracellular fluid, EC F- extracellular fluid, TNF - tumor necrosis factor
Source: acute pain management; the scientific evidence (NHMRC, 1999)
Medula spinalis
• Sistem sensorik meliputi :
• Spinothalamic
– 1. protopathic : basic essential activities – pain, touch and
temperature.
– 2. epicritic (discriminatory) : tactile, propioceptive (posisi,
vibrasi, sensasi otot dan sendi).
• Spinocelebellar : reflex propioception.
• Spinoreticular :
– Somatic motor activity
– Visceral activity : respirasi, heart rate, vomiting
– Consciousness, wakefulness and alertness
Tatalaksana Nyeri Akut

• Tujuan : mencegah nyeri akut menjadi kronik
– Terapi nyeri akut harus adekuat
– Cegah “yellow flags”
• Terapi
– Kausal : merawat luka, reposisi dan fiksasi fraktur,
operasi.
– Farmakologik : analgetik opioid, non-opioid,
analgetik ajuvan (AED, antidepresan, dll)
– Non Farmakologik : terapi fisik, psikologis, dll
Tatalaksana Sindroma Nyeri

Kausal :
• Medis
– Antibiotika
– Kemoterapi
– radioterapi
• Surgical
– Perawatan luka
– Operasi/mengangkat tumor
– Fiksasi/operasi fraktur
Sensory Afferent Neurons

1. Large myelinated Aβ fibers, very fast conduction velocity,
respond to innocuous stimuli.
2. Small myelinated Aδ & C unmyelinated fibers, have slow
conduction velocity, respond to noxious stimuli
Large
A
fibers
Dorsal root
ganglion Dorsal Horn
A
Small
fibers
C Peripheral sensory
Nerve fibers
Klasifikasi Nyeri
• Nyeri sederhana/fisiologik
nyeri timbul oleh berbagai stimuli yang tidak
menimbulkan kerusakan jaringan
• Nyeri patologis/klinis
1. nyeri inflamasi (nyeri akut/nyeri nosiseptik)
nyeri timbul oleh berbagai stimuli yang me-
nimbulkan kerusakan jaringan.
2. nyeri neuropatik : nyeri krn lesi primer atau
disfungsi sistem saraf perifer atau sentral
3. nyeri idiopatik/psikogenik : nyeri yg kausanya
tidak jelas
Derajat Rasa Nyeri .. 2

VISUAL ANALOG SCALE (VAS)
NUMERIC PAIN RATING SCALE (NPRS)
Faces Pain Rating Scale (untuk anak)

Consequences of Pain
Endocrine:
stress hormone, metabolic rate, heart
rate & water retention
Immune:
Impaired immune functions
Pulmonary:
flow and volume retained secretions and
atelectasis
Cardiovascular:
cardiac rate
systemic vascular resistance
peripheral vascular resistance
coronary vascular resistance 
blood pressure and myocardial
oxygen consumption
Gastrointestinal:
Delayed return of gastric and bowel function
Musculoskeletal:
Decreased muscle function, fatigue and immobility
Nyeri Nosiseptive (Akut)
• Nyeri akut: mekanisme

tubuh utk melindungi &
mencegah, supaya jaring-
an yang cedera tdk ber-
tambah parah, jaringan
tsb dibatasi kemampuan
gerak/mobilitasnya.
• Waktu berkisar 1-3 bulan
• Th/ jika tidak adekuat 
CHRONIC PAIN
www.physiologyonline.org
BERDASARKAN INTENSITAS NYERI

(Numeric Pain Rating Scale)
INTENSITAS NPRS
NYERI RINGAN 1-3
NYERI SEDANG 4-7
NYERI BERAT 7 - 10
Trigeminal Nerve Complications

MVD PRFTG PGR PBC
Numbness 2 98 60 72
Dysesthesia 0.5 24 16 19
AD 0 1.5 1.8 0.1
Corneal reflex 0.05 7 3.7 1.5
Keratitis 0 1 1.8 0
Motor 0 24 1.7 66
Taha J, Tew J: Neurosurgery 38:865—871, 1996

Epidural Anesthesia
• Anesthestizes the Emerging Nerve Roots of the
Spinal Cord
• Epidural Injection of Anesthetic Produces a
Regional Dermatomal “band” of Anesthesia
Spreading Cephalad and Caudad from the Site of
Injection
• Level of Anesthesia Depends on :
– Volume of the Drug
– Level of Injection
The different kinds of pain

• Acute
• Chronic
• Neuropatic
• Malignant
• Non-malignant
• Somatic
• Visceral
Acute pain
• Begins suddenly
• Sharp in quality
• Clear defined cause – injury, tissue damage
• Specific disease
Chronic pain
• Pain may subside as healing proceeds
• Continues over time
• Dull or more severe
• Lasts for more than 3 months
Neuropathic
• Damage to nerve
Malignant
From cancer
• radiation therapy
• chemotherapy
Non-malignant
• Not life-theatening
Somatic
…Coming from
• skin
• Bone
• Joint
• muscle
Visceral
• Coming from internal organs

Management Acute Pain

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ADVANCED NEUROLOGY LIFE SUPPORT

International Association for

Haddox, 1990; Mariano, 2001

Physical state environment

nociceptor Reflex action

Memory & Affect/mood

Klasifikasi Sindroma Nyeri

Nociceptive mixed Neuropathic idiopatik

Somatic Visceral Peripheral Central

Kausa Sindroma Nyeri

Kausa Sindroma Nyeri .. 2

Kausa Sindroma Nyeri .. 3

Neuropathic Pain Nociceptive Pain

karena HNP (mixed Pain)

Activation of peripheral nociceptors –

Compression and inflammation of nerve root –

Jenis-jenis Serabut Saraf

A and B fibers are myelinated, C : fibers unmyelinated, LA : local anesthetic

Mekanisme Rasa Nyeri

Mekanisme Rasa Nyeri .. 2

Mekanisme Rasa Nyeri .. 3

Stress Response Post-Injury

Mediator Humoral Pituitary. gl

Stress Response Post-Injury

Post-Injury Stress Response .. 2

Stress Response Post-Injury .. 2

Prostaglandin 2: Nosiseptor melepas

Prinsip tatalaksana Nyeri Akut

Beri analgesik dosis maksimal

(WHO ANALGESIC LADDER 1996)

Freedom from pain

Opioid for moderate to severe pain Step 3

Opioid for mild to moderate pain Step 2

Tatalaksana Nyeri Akut

Derby, 1998 American Pain Society, Principles of Analgesic Use in the

Derby, 1998 American Pain Society, Principles of Analgesic Use in the

Farmako Terapi Nyeri Inflamasi

Farmako Terapi Nyeri Inflamasi .. 3

Analgetik Non Opioid yang

Analgetik Non Opioid yang

• CSE, Used in Labor

Peripheral Nerve Block

Peripheral Nerve Block

Spinal Cord Stimulator

MVD vs. Percutaneous Procedures

Taha J, Tew J: Neurosurgery 38:865—871, 1996

Celecoxib (Celebrex) 100-200mg PO Bid

Valdecoxib (Bextra) 10-20mg PO Qd

Patient Controlled Analgesia (PCA)

Dose Regimens for PCA

Hydromorphone 0.1-0.2 5-10

Fentanyl 0.01-0.02 5-10

Oral Parenteral Epidural Intrathecal

Morphine MS Contin, Release 8-12 hrs

Efek samping analgetik opioid (umum)

1. Depresi SSP, mis : sedatif, depresi pernafasan & batuk, miosis,

2. ANALGETIK NARKOTIKA / OPIOID

• Mekanisme kerja analgetik narkotik :