COMPLICATION IN PAIN

MANAGEMENT

DR.dr. Suwarman, SpAn-KIC, KMN,

Mkes
Bagian Anestesi dan Terapi Intensif
FK UNPAD/ RS Hasan Sadikin Bandung
 OPIOID COMPLICATION
TOLERANCE
– Loss of analgetic potency increasing dose
requirements and decreasing effectiveness over
time.
– NMDA receptor antagonists block the
development of tolerance to morphine
PHYSICAL DEPENDENCE
– development of an altered physiological state that
is revealed by an opioid withdrawal syndrome
involving autonomic and somatic hyperactivity
 OPIOID COMPLICATION-Ctd
OPIOID-INDUCED IMMUNOLOGIC EFFECTS
• cellular immune suppression and decreased
resistance to bacterial infection
• increased incidence of infections in heroin
addicts and as a cofactor in the pathogenesis
of human immunodeficiency virus
• endorphins)  induce immunoactivation
 OPIOID COMPLICATION-Ctd
– acute and chronic opioid administration can cause
inhibitory effects on antibody and cellular immune
responses, natural killer cell activity, cytokine
expression, and phagocytic activity
OPIOID-INDUCED HORMONAL CHANGES
 OPIOID COMPLICATION-Ctd
OPIOID-INDUCED HYPERALGESIA
• increasing pain despite increasing doses of
opioids
• Long-term use and high doses of opioids may be
associated with the development of hyperalgesia
• NMDA receptor agonism has a major role in the
development of hyperalgesia
• ketamine (a NMDA antagonist) prevented
fentanyl-induced hyperalgesia
 OPIOID COMPLICATION-Ctd
OPIOID-INDUCED SEDATION
• Opioid-induced sedation and drowsiness are
thought to be caused by the anticholinergic
activity of opioids
• dose initiation and rapid dose escalation may
result in sedation and consequently lead to
noncompliance and/or reduced quality of life
• Opioid dose reduction, opioid rotation, and
use of psychosomatic stimulants
(Methylphenidate)
 OPIOID COMPLICATION-Ctd
OPIOID-INDUCED SLEEP DISTURBANCES
• common in cancer patients
• no correlation has been found between pain
severity and sleep disturbance
• Opioids increase the number of shifts in
sleepwaking states , and decrease total sleep
time, sleep efficiency , delta sleep, and REM
sleep
 OPIOID COMPLICATION-Ctd
PSYCHOMOTOR PERFORMANCE IN OPIOID
THERAPY
• management of pain with opioids , patients’
abilities to operate heavy equipment may be
diminished and so they should not be allowed
to drive automobiles
 OPIOID COMPLICATION-Ctd
OPIOID-INDUCED CONSTIPATION
• Occur in 40% to 95% of patients treated with
opioids  even with a single dose of morphine
• the long-term consequences of constipation can
result in significant morbidity and mortality
• Chronic constipation can result in hemorrhoid
formation, rectal pain and burning, bowel
obstruction, and potential bowel rupture and
death
 OPIOID COMPLICATION-Ctd
• Unlike the other side effects of opioids
(respiratory depression, nausea, sedation),
constipation is unlikely to improve over time
 must be anticipated, monitored, and
addressed throughout the opioid treatment
course
• NO TOLERANCE
 OPIOID COMPLICATION-Ctd
OPIOID-INDUCED BLADDER DYSFUNCTION
• significant problem in postoperative patients
• Urinary retention is much more likely to occur
after epidural injection of morphine rather
than intravenous or intramuscular injection
 OPIOID COMPLICATION-Ctd
CARDIAC EFFECTS OF OPIOIDS
• Morphine has been associated with histamine
release and consequent vasodilation and
hypotension
• partially blocked by H1 antagonism but
completely reversed by naloxone
• a syndrome of QT prolongation and torsade des
pointes (Tdp) has drawn some attention partially
due to an increase in use of methadone for
treatment of chronic pain
• Tdp mortality rate  17%
• TdP adalah gangguan irama jantung berupa
takikardi ventrikuler tipe polimorfik dengan
frekwensi antara 200-250 kali/menit secara
tidak beraturan dengan sumbu QRS bervariasi
 Adverse Effects of Specific Opioids
CODEINE
• active metabolite nya adalah Morphine
• Hati2 pada pemakaian post partum
• Pernah ada kasus : bayi menyusui meninggal
karena overdose morphine
• Ibunya  ultrarapid metabolizer of
cytochrome p450 2D6  produce more
morphine
• HYDROCODONE/ACETAMINOPHEN
• Effective for acute and chronic pain
• Adverse Reaction: dizziness, nausea, vomiting,
drowsiness, and euphoria
• Sometimes : AR : Hearing loss
OROS HYDROMORPHONE
• controlled-release formulation that uses an
active osmotic system to deliver consistent
levels of hydromorphone over 24 hours
• most common side effects included
constipation (20.9%), nausea (19.8%),
vomiting (9.7%), headache (14.0%), and
somnolence (14.0%)
OXYCODONE CR
• long-acting opioid used for the treatment of
noncancer pain
• most common adverse events included
constipation (15%) and nausea (12%). Other
adverse events included somnolence (8%),
vomiting (7%), and depression (2%)
• most serious adverse events : chest pain and
accidental injury
MORPHINE
• used for the treatment of noncancer pain 
Osteoarthritis
• NSAID  many side effect
• Primary Adverse Event: Constipation
FENTANYL
• for the treatment of chronic low back pain
• Transdermal Fentanyl (TDF) and sustained
release morphine (SRM) showed similar pain
relief with both medications but TDF caused
significantly less constipation
Really high or overdose?
Really high Overdose
• Pupil miosis • Pupil miosis

• Mengantuk tapi respons • Tidak respons terhadap nyeri

terhadap rangsang nyeri • Bradipneu hingga apneu
• Bicara terganggu/lambat • Sianosis
• Frekuensi nafas >8 x/menit • Airways tidak aman

>> Stimulate and observe >> Rescue breathe + give naloxone

NSAIDs
29
30
COMPLICATION OF PERIPHERAL
NERVE BLOCK
• Nerve injury
• Hematoma
• Local Anesthetic Systemic Toxicity
• Infection
• Secondary Injury
 NERVE INJURY
• Incidence 0,5-1%
• Permanent nerve damage : 1,5/10.000
• Transient neurological deficits: 8-10% in the
immediate days following the block
 LOCAL ANAESTHETIC SYSTEMIC TOXICITY
(LAST)
LAST range from:
• Mild systemic symptom (auditory changes,
circumoral numbness, mettallic taste, and
agitation)
• Central nervous system (CNS) finding: (seizure,
coma, respiratory arrest)
• Cardiovascular events (hypertension,
hypotension, tachycardia, bradicardia,
ventricular arrhythmias, cardiac arrest)
• Fatal complication,
• Occuring in up to 1/500 peripheral nerva
blocks
• Treatment: Intravenous lipid emulsion (ILE) 
antidote to LAST
• Epinephrine can impair resuscitation from
LAST and reduce the efficacy of lipid rescue.

• Avoid high doses of epinephrine and use

smaller doses, e.g., <1mcg/kg, for treating
hypotension.
 INTERVENTIONAL PAIN MANAGEMENT
COMPLICATION
• Allergic reactions
• • Medication side effects
• • Pneumothorax
• • Infection
• • Bleeding
• • Nerve damage
• • Spinal cord injury
• • Brain and/or brainstem injury
• • Death
 ADVERSE EFFECTS OF EPIDURAL
ANALGESIA
• Neurological injury
• Epidural haematoma
• Epidural abscess
• Respiratory depression
• Hypotension
• Postural puncture headache
• Treatment failure
ADVERSE EFFECTS OF EPIDURAL
ANALGESIA
• Neurological injury
• Epidural haematoma
• Epidural abscess
• Respiratory depression
• Hypotension
• Postural puncture headache
• Treatment failure
Efek Samping Analgesik Neuroaxial

• hipotensi, depresi respirasi.

• opioid tunggal tanpa anestesi local jarang
menimbulkan hipotensi.
• Mual ,muntah -----single dose sebesar 20-50 %,
tergantung dari dosis
– migrasi kearah cephalad di dalam CSF menuju ke area
postrema di dalam medulla.
• pruritus berkisar antara 60%, central aktivasi
dari “itch center”, pada medulla

• reseptor opioid pada nucleus trigeminalis,

melalui aktifasi afferent primer
“nonhistamine itch”.
• depresi respirasi------ naloxone 0,1-0,4 mg,
dilanjutkan infuse kontinyu 0,5-5 ug/kg/jam.

• Retensi urine--- interaksi opioid + reseptor

opioid pada spinal cord
– mendepresi kekuatan kontraksi otot-otot detrusor
Efek samping intrathecal opioid
Depresi ventilasi

• berhubungan dengan dosis.

• sedikit laporan terjadinya depresi ventilasi
dosis kurang 0,4 mg IT morphine.
• Depresi ventilasi terjadi beberapa menit
sampai beberapa jam setelah pemakaian
opioid liphopilik sufentanyl dan fentanyl
• sedang pada pemakain morphine terjadi 6-12
jam bahkan ada laporan sampai 19 jam
setelah pemakaian
• opioid-naïve state
• Opioid secara sistemik
• meningkatnya usia
• penyakit paru obstruktif
• sleep apnea.
Pruritus

• Migrasi kearah cephalad,interaksi dengan

reseptor opioid di nucleus trigeminus daerah
suferficial medulla

• Angka kejadian antara 20-100 %

• tergantung dosis

• Morphine lebih tinggi di banding fentanyl

MUAL/MUNTAH

• 20-40% , umumnya 4 jam setelah pemakaian,

(morphine).
• penyebaran kearah cephalad, interaksi obat
dengan reseptor opioid di area postrema.
• Mekanismenya tidak berhubungan dengan
absorpsi sistemik
• sebanding dengan pemberian intra vena,
epidural.
Retensi urine

• Tidak bersifat dose dependent

• lebih sering intra thecal morphine

– ikatan dengan reseptor opioid-menghambat

system saraf parasimpatis sacral

– relaksasi muskulus detrusor dan

meningkatnya kapasitas kandung kencing
Sedasi

• dose –dependent pada pemakaian IT opioid.

• lebih sering pada pemakaian sufentanyl
dibanding opioid lainnya
EFEK SAMPING OPIOID EPIDURAL
DEPRESI RESPIRASI

• Tegantung dosis
• insiden lebih rendah jika dibandingkan dengan
opioid sistemik
• opioid-naïve state, opioid sitemik , sedative ,
meningkatnya usia
Mual dan muntah

• insiden 20-50 %
• epidural infuse kontinyu 45-80 %
• juga tergantung besarnya dosis
• reseptor opioid di area postrema
• chemotactic trigger zone di daerah medulla
Pruritus opioid epidural

• Aktivasi itch center pada medulla

• interaksi dg reseptor opioid trigeminal cervical
atas spinal cord
• tidak ada hubungannya dengan histamine
release perifer
• lebih tinggi jika dibandingkan dengan
pemberian sistemik 60% vs 15-18%
• Tidak jelas hubungannya dengan dosis yang
diberikan
Retensi urine

• menurunnya kekuatan kontraksi otot detrusor.

• Kejadiannya lebih inggi jika dibandingkan
dengan pemberian sistemik 70-80 %
berbanding 18%
• Tidak ada hubungannya dengan dosis.
KOMPLIKASI SNRI
 Efek samping
• SSRI berinteraksi dengan receptor serotonin pada
gastro intestinal sehingga dapat menyebabkan mual,
muntah, abdominal kram dan diare
• SSRI mengaktifasi SSP sehingga dapat menyebabkan
insomnia, tremor dan gangguan akitifitas fisik.
• SSRI menyebabkan gangguan sexual, penurunan
libido, ereksi dan gangguan orgasme.
• Central efek SSRI menyebabkan hipertensi, demam,
myoclonus dan kejang.
 SEROTONIN-NOREPINEPHRINE REUPTAKE INHIBITORS
(SNRI)

• SNRI secara selective memblok reuptake

serotonin dan norepinephrine
• Efek samping yang lebih kecil dibandingkan
dengan SSRI, sangat baik untuk pasien yang
tidak menoleransi efek samping dari
antidepresan
 Komplikasi dalam penanganan nyeri
• MACAM2 KOMPLIKASI
• TERAPI FARMAKOLOGIK
• ES OPIOID – MUAL MUNTAH, OVER SEDASI, SD DEPRESI
NAFAS. BGMN CARA mengatasinya, cara pemberian nalokxon.
Bagaimana mengenali efek samping obat
• OPIOID RESISTENT; definisi, tanda2, cara penanganannya
• OVER TREATMENT BIASANYA KARENA PAIN ASSESSMENT
TIDAK TEPAT  KARENA CARA ASESSMENT ATAU WAKTU
ASESSMENT TIDAK TEPAT.
• KEMBALI KE RUMUS 1-2-8
• TERAPI INTERVENSI
• KARENA NEEDLING, ES karena tusukan jarum, cara
pengenalannya, gejalanya, dan cara penanganannya
• KARENA TINDAKAN INTERVENSINYA; ES karena injeksi obat ke
saraf, ES pembakaran saraf, ES injeksi alkohol
KOMPLIKASI DALAM PAIN MANAGEMENT

• KARENA OBAT YANG DIPAKAI

– Opioid
– Gabapentin
– Nsaid
– Anestesi lokal
– Alergi/ reaksi hipersensitif
• KARENA TINDAKAN YANG DILAKUKAN
– Needling
– Kerusakan saraf
– terlalu