Management of Acute Pain

(1)

ADVANCED NEUROLOGY LIFE SUPPORT

Management of

Acute Pain

(2)

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

(3)

Nociceptive

Psychological

pain

a b

Haddox, 1990; Mariano, 2001

(4)

Physical state

Perception

nociceptor Reflex action environment

Affect/mood

Evaluation Memory &

expectation Actions

Response

Symptoms &

signs Painful : Non-Painful :

Diagram Nyeri

(Farrar.J.T)

(5)

Klasifikasi Sindroma Nyeri

Nociceptive

Duration Pathophysiology

mixed Neuropathic

Somatic Visceral Peripheral Central -superficial

-deep

-Acute : < 3 months, mostly nociceptive -Chronic : > 3 months, mostly neuropathic

Acute Chronic

idiopatik

(6)

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

(7)

• Trauma

• Infeksi

• Inflamasi

• Tumor / malignancy

• Vascular

Kausa Sindroma Nyeri

(8)

• 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 .. 2

(9)

• Abdominal Pain

– Acute exacerbation of Pancreatitis

– Acute abdomen : perforation, obstruction, aneurysm dissection/rupture

– Renal colic

• Neurogenic Pain

– Herniated disk

– Nerve compression

Kausa Sindroma Nyeri .. 3

(10)

Nyeri sebagai Tanda Vital ke 5

1. Tekanan darah 2. Nadi

3. Frekuensi Pernafasan 4. Suhu

5. NYERI

(11)

Alat Untuk Mengukur/Menilai Nyeri

Uni-dimensional measurement tools

(selection):

• Visual analogue scales

• Verbal rating scales

• Graphic rating scales

• Numerical rating scales

• Verbal descriptor scales

• Body diagrams

• Computer graphic scales

• Picture scales

• Coin scales

Multi-dimensional pain measurement tools (selection)

• McGill pain questionnaire (short and long)

• Brief pain inventory (short and long)

• Behavioural pain scales

• Pain/comfort journal

• Multidimensional pain inventory

• Pain information and beliefs questionnaire

• Pain and impairment relationship scale

• Pain cognition questionnaire

• Pain beliefs and perceptions inventory

• Coping strategies questionnaire

• Pain disability index

• Hospital anxiety and depression questionnaire (HAD scale)

• Neuropathic signs and symptoms ( Leeds assessment of neuropathic symptoms and signs (LANSS) (Bennett, 2001).

• Cognitively impaired/dementia pain scales

(12)

Derajat Rasa Nyeri

(13)

(14)

“Red Flags”

History

• Nyeri pada malam hari, demam, penurunan BB, riwayat keganasan?cancer

• Penyalahgunaan obat2 IV

• Gangguan BAB dan atau BAK (retensi urin/alvi, inkontinensia urin/alvi), kelemahan anggota gerak bawah

• Trauma

Possible Diagnosis

• Tumor

• Infeksi (discitis, epidural abscess)

• Cauda-equina syndrome

• Fractur kompressi

(15)

Examples Peripheral

• Postherpetic neuralgia

• Trigeminal neuralgia

• Diabetic peripheral neuropathy

• Postsurgical neuropathy

• Posttraumatic neuropathy Central

• Poststroke pain Common descriptors²

• Burning

• Tingling

• Hypersensitivity to touch or cold

Examples

• Pain due to inflammation

• Limb pain after a fracture

• Joint pain in osteoarthritis

• Postoperative visceral pain

Common descriptors²

• Aching

• Sharp

• Throbbing Examples

• Low back pain with

radiculopathy

• Cervical radiculopathy

• Cancer pain

• Carpal tunnel syndrom

Mixed Pain

Pain with neuropathic and

nociceptive components

Neuropathic Pain

Pain initiated or caused by a primary lesion or dysfunction

in the nervous system (either peripheral or central nervous system)¹

Nociceptive Pain

Pain caused by injury to body tissues

(musculoskeletal, cutaneous or visceral)²

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

Presentation Across Pain States Varies

(16)

Lumbar vertebra

Disc herniation

Activation of peripheral nociceptors – cause of nociceptive pain component

Compression and inflammation of nerve root – cause of neuropathic pain component

LBP & Lumbal Radiculopati

karena HNP (mixed Pain)

(17)

Jenis-jenis Serabut Saraf

Fiber type Function Ø fiber (mm)

Conduction velocity (m/s)

Hypoxia Pressure LA Aα Propriception

somatic motor

12-20 70-120 ++ +++ +

Aβ Touch, pressure 2-12 30-70

Aγ Motor to muscle spindle

3-6 15-30

Aδ Pain,cold, touch 2-5 12-30 B Preganglionic

otonomic

<3 3-15 +++ ++ +

C dorsal root Pain, temperature mechanoreception, reflex response

0.4-1.2 0.5-2 ++ ++ +++

C

simpatetik

Postganglionic sympathetic

0.3-1.3 0.7-2.3

A and B fibers are myelinated, C : fibers unmyelinated, LA : local anesthetic +: least susceptible, ++ : intermediated susceptibility, +++ : most susceptible

(18)

Dorsal Horn Dorsal root

ganglion

Peripheral sensory Nerve fibers A

A

C Large

fibers

Small fibers

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

(19)

Iskemik, Spasme Cedera, dll

Nosiseptor free nerve

ending

Histamine K*, bradikinin Prostaglandin

5-HT

Mekanisme Rasa Nyeri

NAP Cornu

dorsalis

A myelin/fast C unmyelin/slow

Substanse P

Platelet - serotonin Mass cell - histamin

1. Transduksi 2. Transmisi 3. Persepsi 4. Modulasi

GABA, Glycine Adenosine

Bombesin

Cholecystokinin Dynorphin

Enkephalin

Neuropeptide-Y Kortek Talamus

2 3 4

1

(20)

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 .. 2

(21)

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 :

Mekanisme Rasa Nyeri .. 3

(22)

midbrain

med.obl (a)

(b) (b)

med.spin (c)

a. Midbrain : periaquaduct gray- matter (PAG) mengandung μ reseptor yg dpt mengaktivasi opioid endogen.

b. Medula oblongata, di :

- nucleus raphe magnus (NRM) melepas serotonin.

- NPRG (nucl reticularis para giganto cellularis) melepas noradrenalin

c. Cornu dorsalis Med spinalis, dapat menghambat transmisi nosiseptor.

Rasa nyeri ↓ atau menghilang.

modulasi

(23)

S P C I O N R A D L

Lateral thalamus

kortek somasensorik

ACTH

associative cortex medial

thalamus reticular

formation

hypothalamus

Mediator Humoral Perifer

Interleukin 1 & 2 TNF/tumor necr F

Bradykinin α interferon PGE1,PGE2, etc

Pituitary. gl

sympatic Nerv syst

adrenal gland

pancreas spinothalamic

neospinothalamic

spinoreticular paramedian

*propiomelano- cortin

*growth horm

*prolactin

*vasopressin

Nor-eph

Epineph Enkephalins Aldosterone cortisol

glucagon β endorphin

Affect Sensation

Corticotropin-releasing factor Vasoactive-intestinal peptide

Stress Response Post-Injury

(24)

• 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

Stress Response Post-Injury

(25)

• Gastrointestinal : delayed return of gastric and bowel function

• Musculoskeletal : decreased muscle function, fatigue and immobility.

Post-Injury Stress Response .. 2

(26)

2: Nosiseptor melepas substance P  pemb drh melebar & dilepas media-

tor inflamasi yi Bradykinin

(redness and heat)

3: Substance P juga me- rangsang degranulasi mass cells, dilepas zat histamin

(swelling)

Pain-sensitive tissue

Painful stimulus

Prostaglandin

Substance P

Histamine

Mast cell

Blood vessel

Bradykinin

Nociceptor

Substance P

2 3

1

1: cedera jaringan merang- sang pembentukan prosta- glandin sensitivitas no- siseptor ↑ (pain)

Stress Response Post-Injury .. 2

(27)

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

(28)

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.

(29)

Prinsip Tatalaksana Nyeri Akut

• Beri terapi adekuat utk kontrol rasa nyeri

• Cegah resiko rasa nyeri bertambah berat atau menjadi kronis persisten

• Pertahankan kemampuan fungsional untuk menjaga faktor psikologis tetap baik

• Mengurangi intensitas dan durasi keluhan nyeri

• Tingkatkan kualitas hidup dengan mengoptimalkan

kemampuan pasien untuk melakukan aktivitas sehari-hari.

• Meminimalkan reaksi tak diinginkan atau intoleransi terhadap terapi nyeri

• Usahakan rawat inap tidak lama/singkat utk mengurangi

biaya.

(30)

Cegah Nyeri Akut Jadi Kronik

Acute (nociceptive)

Chronic (neuropathic)

Biological function (+)

Biological function (-)

Avoid tissue damage

disadvantage

Psychological

*triad : Physical

*impairment

*disablity

Pain

Mood Sleep

> Dysfunction  ↓QoL

> Socioeconomic loss Advantage

*health

*well being

Terapi adekuat : -Cegah nyeri kronik -Cegah Yellow Flag

(31)

Prinsip Terapi Nyeri Akut & Berat

Beri analgesik dosis maksimal

(32)

Alur Terapi Nyeri Kronik

(WHO ANALGESIC LADDER 1996)

Non opioid +/- Adjuvant

Opioid for mild to moderate pain +/- Non opioid , +/- Adjuvant

Opioid for moderate to severe pain +/- Adjuvant

Step 1

Step 2 Step 3

Persisting Pain Persisting Pain

Freedom from pain

(33)

33

WHO Analgesic Ladder

Non Opioidl or ± Adjuvant analgesic

0 1 2 3 4 5 6 7 8 9 10

mild moderate severe

Non Opioid±

Adjuvant analgesic

± weak opioid

Strong Opioid ± Non Opioid ±

Adjuvant analgesic

Pain Threshold Pain Tolerance

(34)

• Terapi non-farmakologik  nyeri kronis

– Bed rest

– neurostimulasi (TENS),

– psikoterapi (kognitif behavior, relaksi, hipnosis).

• Terapi farmakologik :

– Analgetik non opioid – Analgetik opioid

– Antikonvulsan – Antidepresan

• Terapi intervensi/operasi

– Perawatan luka, fiksasi fraktur atau operasi

– Terapi intervensi : epidural, spinal analgesia, nerve block

Tatalaksana Nyeri Akut

(35)

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.

(36)

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.

(37)

Opioids

Drug PO mg Comments Precautions

Codeine 30-60

Combined With Nonnarcotic Analgesics

Maximal Dose for Acetaminophen 4gm/d

Oxycodone 5-10

^Percocet

Percodan

Oxycodone 10-30mg Q 4h Oxycontin 10mg Q 12h

Acetaminophen or Aspirin toxicity

Hydro- codone

5-10

Vicodin or Lortab Acetaminophen Toxicity

Tramodol 50-100 Q4-6hr

Central Acting, Affinity for Mu Receptors

Maximal Dose 400 mg/d

(38)

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, 5^th edition, 2003

Analgesik Opioid .. 3

(39)

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, 5^th edition, 2003

Analgesik Opioid .. 4

(40)

Non-Opioid Analgesics

• Acetaminophen

• NSAIDs (Aspirin, Ibuprofen, Ketorolac, COX-2 Inhibitors)

• Lidocaine Patch (Lidoderm)

(41)

NSAIDs

• Relieve of Mild to Moderate Pain

• Complication:

– GI Discomfort

– GI Bleeding (Inhibition of COX-1) – Nephrotoxicity

– Inhibition of Platelet Aggregation

– Osteogenesis

(42)

Ketorolac

• Potent Analgesic

• Parenteral (IV or IM)

• 15-30 mg q 6hr

• Patients Older than 16 yrs

• Should not Exceed 5 days

(43)

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

(44)

Lidoderm

(45)

Analgetik Non Opioid yang Paling Sering Digunakan

Nama Obat Dosis Jadwal

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

(46)

Nama Obat Dosis Jadwal

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 Ketoralac 10-30 mg 4-6 jam sekali Asetaminofen 500 mg 6-8 jam sekali Tramadol 50-100 mg 8 jam sekali

Analgetik Non Opioid yang

Paling Sering Digunakan .. 2

(47)

COX-2 INHIBITOR SPESIFIK

Drug Dose

Celecoxib (Celebrex) 100-200mg PO Bid Rofecoxib (Vioxx)

Etoricoxib (arcoxia) 60 – 120 mgPO bid Valdecoxib (Bextra) 10-20mg PO Qd

Parecoxib 20-40mg IM

20-100mg IV

(48)

Farmakologi untuk Nyeri Neuropatik

Opioids Tramadol, Fentanil, Morfin, Oxycodone

Antidepresan

TCA

SNRI

Amitriptilin, Nortriptilin, esipramin, Imipramin, Doxepin

Duloxetin, Venlafaxin

Anticonvulsan Carbamazepin, Valproat, Lamotrigin, Topiramat, Oxcarbazepin, Gabapentin, Pregabalin, Phenitoin

NMDA Antagonis Memantin, Amantadine, Dextromethorphan

Topical Lidocaine, Capsaicin

(49)

Recommendation for first- and second-line treatment (EFNS Guideline)

Pain Condition First Line Level of Evidence

Second Line Level of Evidence Painful

Peripheral Neuropathy

Pregabalin Gabapentin TCA

Opioid

A A A A

Lamotrigin SNRI

Tramadol

B A A

PHN Pregabalin

Gabapentin TCA

Lidocai topical

A A A B

Capsaicin topical Tramadol

Opioid Valproate

B B A B Trigeminal

Neuralgia

Oxcarbazepin Carbamazepin

B A

IPM Surgery Central Pain Pregabalin (in SCI)

Gabapentin (in SCI) Amitriptilin (in Stroke)

B B B

Lamotrigin (stroke) Cannabinoid (MS) Opioid (Muscle etiologi)

B B C

(50)

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

Anticonvulsants used as adjuvant analgesics

CT : control trials, OLT : open label trials,

(51)

Non- opioids

Weak opioids +/- non- opioids

Strong opioids

Recovery Operation

Treatment of Pain

World of Misery

Non-pharmacological

methods

(52)

Non- opioids

Weak

opioids +/- non-opioids

Strong opioids

Recovery Operation

Treatment of Pain

Non-pharmacological methods

(53)

Interventional Pain 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

(54)

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)

(55)

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

(56)

Contraindications

• Absolute

 Patient Refusal

 Coagulopathy

 Increased ICP

 Skin Infection

• Relative

 Uncooperative Patient

 Pre-existing Neurologic Disorder

 Anatomical

Abnormalities

(57)

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.

(58)

(59)

Effects of acute pain:

• Neuroendocrine response to stress

– Increased metabolic rate – Increased cardiac output – Impaired insulin response – Increased retention of fluids

– Increased risk for physiologic disorders

– Decreased deep breathing and mobility

(60)

Persistent Pain

Secondary Physical Problems

Sleep Disturbance

Depression Anxiety

Functional Disability Increased Stresses

Substance Abuse

(61)

Addiction

Secondary Physical Problems

Sleep Disturbance

Depression Anxiety

Functional Disability Increased Stresses

Substance Abuse

Seddon Savage, M.D.

(62)

Addiction

Secondary Discomforts

Sleep Disturbance

Depression Anxiety

Functional Disability

Increased Stresses

Pain

Drug

Dependence

Seddon Savage, M.D.

(63)

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.

(64)

(65)

Trigeminal Neuralgia

(66)

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)

(67)

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

(68)

(69)

(70)

(71)

Equianalgesia

Opioid PO Parenteral

(IV/SC)

Morphine 10 mg 5 mg

Codeine ~ 60-100mg (4-fold variability)

N/A

Hydromorphone 2 mg 1 mg

Oxycodone 5 mg N/A

(72)

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

(73)

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

(74)

Dose Regimens for PCA

Drug Bolus Dose

(mg)

Lock-Out (Minutes)

Morphine 0.5-2 5-15

Hydromorphone 0.1-0.2 5-10

Fentanyl 0.01-0.02 5-10

(75)

Routes of Administration

• PO

• PR

• IV

• IM

• Transdermal

• Transmucosal

• Epidural

• Intrathecal

(76)

Pharmacologic Management

• Alter Nerve Conduction (Local Anesthetics)

• Modify Transmission in the Dorsal Horn

(Opioids, Antidepressants)

(77)

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

(78)

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

(79)

Opioid Analgesics

Conversions: Morphine

Oral Parenteral Epidural Intrathecal

300 100 10 1

(80)

Opioids

Drug PO mg

IV mg

Starting Oral

Dose mg

Comments

Morphine

30 10 15-30

MS Contin, Release 8-12 hrs MSIR for BTP

Hydro-

morphone

7.5 1.5 4-8

Duration Slightly Shorter than Morphine

Meperidine

300 75

Duration Slightly Shorter than Morphine

Normeperidine Causes CNS Toxicity

Methadone

20 10 5-10 Qd

Long Half-Life, 24-36 hrs Accumulates on Days 2-3

Fentanyl 0.02-

0.05

Fentanyl Patch, 12 hrs Delay Onset and Offset

(81)

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

(82)

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

(83)

Systemic Analgesia

• Opioids

– Potent analgesics

– Drug of choice for moderate to severe pain – Unfortunately, they are often the only drug

ordered

– Side effects:

(84)

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

(85)

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.

(86)

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

(87)

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).

(88)

• 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)

(89)

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.

(90)

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).

(91)

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.

(92)

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.

(93)

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).

(94)

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).

(95)

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.

(96)

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).

(97)

(98)

Metabolic and Endocrine responses to injury

ِ

↑ ACTH, cortisol , ADH, growth H, Catecholamine, angiotensin II,

aldosterone, glocagons, IL-1, TNF, IL-6

↑catabolic hormons

Endocrine

↓insulin, testosterone

↓anabolic hormons

Metabolic

↑glycogenolisis, gluconeogenesis (cortisol, glucagon, growth H,

adrenalin, free fatty acid). ↓insulin secretion/activation.

Hyperglycemia, glucose intolenrance, insulin resistence

carbohydrate

↑cortisol, adrenalin, glucagon, IL-1, IL-6 dan TNF.

Muscle prot catabolism

↑synthesis of acute phase proteins

Protein

↑catecholamine, cortisol, glucagon, growth H.

↑lypolysis & oxidation Lipid

(99)

Metabolic and Endocrine responses to injury .. 2

↑catecholamine, aldosterone, ADH, cortisol, angiotensin II, prostaglandin and othersfactors.

retention of water and sodium. ↑ excretion of potassium, ↓functional ECF with shifts to ICF

water and electrolyte flux

Note: ICF - intracellular fluid, EC F- extracellular fluid, TNF - tumor necrosis factor Source: acute pain management; the scientific evidence (NHMRC, 1999)

(100)

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

(101)

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

(102)

Kausal :

• Medis

– Antibiotika – Kemoterapi – radioterapi

• Surgical

– Perawatan luka

– Operasi/mengangkat tumor – Fiksasi/operasi fraktur

Tatalaksana Sindroma Nyeri

(103)

Dorsal Horn Dorsal root

ganglion

Peripheral sensory Nerve fibers A

A

C Large

fibers

Small fibers

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

(104)