Acute Postoperative

Pain

SURGERY AND PAIN

Surgery

Tissue damage
Inflamed tissue

Nociceptive
input

PAIN

Surgery has a biphasic insults to the body

1. Trauma to tissue
2. Inflammatory response

1.Peripheral
sensitization

ASIC/BNC

.Central Sensitization
Tissue damage

Hyperalgesia

Spontaneous
pain

Allodynia

Primary Hyperalgesia

CENTRAL
SENSITIZATION

PERIPHERAL
ACTIVITY

Nerve damage

Decreased
threshold to
peripheral
stimuli

Expansion of
receptive
field

Secondary Hyperalgesia

Increased
spontaneous
activity

So, after the surgery

there is a change in NS

what we called:

Neuro-Plasticity of the
Nervous System

Neuro-Plasticity of the NS
Central
sensitization

CNS

Spinal windup

Inflammatory
mediators
Histamine,
Histamine,
Leukotrienes,
Leukotrienes,
Norepinephrine,
Norepinephrine,
Cytokines,
Cytokines, Bradykinin,
Bradykinin,
Prostaglandins,
Prostaglandins,
Neuropeptides,
Neuropeptides, 5-HT,
5-HT,
Purines,
Purines, H+/K+ions
H+/K+ions

Secondary
hyperalgesia

Peripheral
sensitization

Primary
hyperalgesia

Inflammatory Pain
PAI
C
NN
S

Central
sensitizati
on
(wind-up)

Inflammatory Mediators
Histamine,
Bradykinin
Leukotrienes,
Cytokines,

Prostaglandi
ns,
5-HT, H+/K+ions

NSAID

(Cox1 or Cox2)

Peripheral
sensitizati
on

Sensitizatio
n of
Nociceptor
s

After surgery Pain Sensitization:

Hyperalgesia and Allodynia
HYPERALGESIA
10

Pain intensity

8
6
4
2

Sensitised
pain response

Pain intensity
for stimulus X
sensitised
pain response

Normal
pain response

Injury

Pain intensity
for stimulus
X
normal
pain
response

ALLODYNIA

X
Stimulus intensity

Clinical Features of
Postoperative Pain

HYPERALGESI

Primary
Hyperalgesia

ALLODYNIA

CLINICAL PAIN
(PATHOPHYSIOLO
GICAL PAIN )

Secondary
Hyperalgesia

Vanished
after healing

Chronic
Pain

Postoperative pain
Under treatment of postoperative
pain
Increased
sympathetic
activity

GI effects

Myocardial
O2
consumption

GI motility

Myocardi
al

ischaem
ia

GI = gastrointestinal

Delayed
recover
y

Shallow
breathing

Increased
catabolic
demands

Anxiety
and fear

Atelectasis
hypoxaemia
hypercarbia

Poor wound
healing/muscle
breakdown

Sleeplessne
ss,
helplessnes
s

Pneumo
nia

Weakness
and
impaired
rehab.

Psychological
distress

Peripheral/
central
sensitisation

Neuroplasticity

Chron
ic
pain

Ketamine for Cancer pain

Basic Principle of Postop

Pain Management is

prevent the occurrence

Peripheral
of
and
Central
sanitization

reduced the process ofNeuroplasticity

Preemptiv
e/
preventive
analgesia

By Giving
Antihyperalgesic
or Antiallodynia

Preemptive vs Preventive
SURGE
RY

Incision
al Pain

Inflammat
ory Pain

Perioperative Analgesia
Preemptive Analgesia

Preventive Analgesia
Courtesy by Dr. KY

Preventive analgesia
Is broader definition of preemtive
analgesia
Includes perioperative analgesic
regimen ability to control pain
induced sensitization of the CNS.
Decrease development and
persistence of pathological pain
Kissin I. Anesthesiology 2000;93:1138-43

ANALGESIC DRUGS

NONOPIOIDSOPIOIDS ADJUVANTS
Paracetamol
NSAID
(nonselective)
Coxib (selective
NSAID)

Mild Opioid
( codeine &
tramadol )

Strong Opioid
( Morphine &

Steroid
(dexamethason)
Antidepressant
(tricyclic)
Gabapentinoid

Multimodal Analgesia
Opioids

REDUCED DOSES
of each
analgesic

Potentiation IMPROVED

EFFECACY
due
to synergistic or
additive effects

NSAIDs,
Paracetamol
nerve blocks

REDUCE SIDE
EFFECTS
of
each drug
1

Kehlet H et al. Anesth Analog. 1993;77:1048-

Multimodal

OPIOIDS

Analgesia

NEURAXIAL BLOCKS
PERIPHERAL NERVE
BLOCKS

MULTIMOD
AL
ANALGESI
A
NON-OPIOID
ADJUVANTS
ANALGESICS

Choice of Analgesic Technique

(Analgesic Ladder of WFSA)
Pain
Intensity

Opiate
And
NSAID
and
Paracetamol

Oral route available give orally

Oral route unavailable

Rectal paracetamol & NSAID

Opiate: High Tech: PCA
Low tech: IM algorithm Epidural
infusion analgesia

NSAID
and
Paracetamol

Pain
decreases
as time
passes

Paracetamol

Paracetamol
NEW but OLD DRUG
Acetominophen/PAA
P
Analgesic Effects

Antipyretic Effect

No Anti-Inflammation
Effect

Route of Administration
Orally
Rectally
Intravenously available in Indonesia s

Bertolini A, et al CNS Drugs reviews, 2006;12

Paracetamol
Paracetamol is very safe drug as
long as it is given within
recommended doses

4 gr/day,
children
20-40
1.(Adult
Can <
be
given Infant
to alland
age
from
mg/kgBW)

Infant to Elderly
2. From pregnant to Lactating
Woman

The Current COX

concept

Arachidonic
Acid

COX-1
constitutive
Inhibition
undesirable
Homeostatic
functions
Gastrointestinal tract
Renal tract
Platelet Function
Macrophage
differentiation

Cytokines IL-1, TNF

Growth factors

+
COX-2

induced
Inhibition
desirable

inflammation

Glucocorticoids
Cytokines IL-4

Adverse Effects of common

NSAIDs
Upper GI

Renal

Dyspepsia
Erosions
Anemia GI Bleeding
Ulcer
bleeds/perforations

Renal dysfunction
Renal failure acute/chronic
Blood pressure
Heart failure

Anti-platelet effects

Contributes to blood loss

COX-2: A New Anti-inflammatory Drug

Target

Arachidonic acid
COX-1
(Constitutive)
()

Stomach
Intestine
Kidney
Platelet

COX-2
(Inducibl
e)

Glucocorticoids
()
TARGET FOR A
SPECIFIC COX2
INHIBITOR

NSAI
Inflammatory site:
Ds
Macrophages
Synoviocytes
Endothelial cells

COX-1 vs Cox-2 Selective

Inhibitor (COXIB)

Selective COX-2 more safety than

Non-selective COX inhibitor
But, it still had disadvantages
such as : Cardiovascular Problem

OPIOID

COXI
B

NSAI
D

(Morphine, Pethidine or
Fentanyl)

PARACETAMOL

Classification
Preferentially COX-2 inhibitor :
Diclofenac (VOLTAREN)

Antman M. et al, 2005

Pairet et al, 1996

Cox-1 Selective Inhibitor vs Cox-2

Less GI side effects
More GI side effects
Diclofenac Celecoxib
Acetosal Indomethacin Ibuprofen
Meloxicam Rofecoxib
Ketorolac Piroxicam Ketoprofen
Nimesulide Valdecoxib

COXIB

non- preferentially
COX-1
COX-2
COX-1 selective COX-2
selective selective
selective selective
COX
inhibitor inhibitor
inhibitor
inhibitor
inhibitor
preferentially

anti-inflammatory

analgesic

NSAIDs For Post Operative Pain

Less GI side effects
More GI side effects

COX-1
selective
inhibitor

preferentially

COX-1
selective
inhibitor

Diclofenac

Ketoprofen

VOLTAREN

nonselective
COX
inhibitor

preferentially

COX-2
selective
inhibitor

anti-inflammatory

analgesic

Ketorolac

PIROXICAM

Coxib

COX-2
selective
inhibitor

In conclution

Only Selective Cox-2 and

referentially Selective Cox-2
Among nonopioid analgesic

Has benefit in
preventive analgesia

SEKIAN
DAN
TERIMA

KASIH

Nature of Postoperative Pain

Somatic
Pain

Nocicept
ors
sensitiza
tion

muscle,
muscle, fascia,
fascia,
ligament

Visceral
Pain

Referred
pain

Postop
pain

Reflex
response
Muscle
spasm

Cortical
Responses

Cutaneous
Somatic
pain

Different surgical
procedures have
characteristic pain profiles
Different pain
intensity

Different types
of pain

Different
procedures
Different risks
and benefits of
analgesic
techniques

Different
location of
pain

Not All Drugs Have Same

Effect to All Surgery
Paracetamol

Good for:
Oral surgery
Dental extraction

Not so good for:

Episiotomy
Orthopaedic surgery

Multimod
al
Analgesi
a

Conclusion
Improved
Analgesia
Lowered Dose

Reduced
Side
Effects

Early
Mobilization
Early Enteral
Feeding
Rapid Recovery
multimodal
analgesia
low cost

Aggressive preventive
including epidural or nerve block not
produce optimal analgesia but also may

only
prevent

Philosophy of Multimodal
Analgesia
Not only just giving 2 or more drugs which
different mechanism, but;
One drug should be effective at

peripheral sensitization and other at

central sensitization.
Combine drugs must be synergetic or
addictive.
Must be proven by laboratory or clinical
data.

Target Point of Analgesic Drugs

Ketamin
Paracetamol
Percepti
on

Opioids
Gabapentinoid
s
Clonidine

CNS
Modulatio
n

Transducti
on

DR
G

Modulatio
n
COXIBs

Corticosteroi
ds
NSAIDs
COXIBs
Local
Anesthetic

Transducti
on

Transmiss
ion
Local
anesthetics
Modify by

Postoperative Pain Sensitization

Analgesic Agents
Normal Sensory Threshold

Abnormal Sensory
Threshold

Antihyperalgesic /
antiallodynic Agents

Hyperalgesia /
Allodynia

Courtesy by Dr. KY

Anti-hyperalgesic Therapy:
Opioid-Sparing
Sensitised
pain response

Opioid

Opioid

Pain intensity

~30%
reduction

Partially desensitised
pain response

Normal
pain
response
Antihyper
algesic

X
Stimulus intensity

KETAMIN
Low-dose ketamine is not really an
analgesic, but better described
as:
anti-hyperalgesic
anti-allodynic
tolerance-protective of
opioid
Opioid-induced

Coutersy by Prof. S. A. Schug

WHAT IS THE MOST

REGIMENTS
There are many regiments for multimodal
analgesia, but the most popular are:
Paracetamo
l
NSAIDs and
Coxibs
NMDA
Antagonist
(Ketamin)

Opioid

-2 agonist
(Clonidine)

Local
Anesthetic
2 (subunit
of Ca
Channel)
agonist
(Gabapentinoi
d)

Mechanism Of Action
Central Antinociceptive Effect

Central COX
(Cyclooxygenase) Inhibition

Activation of the
endocannabinoid system and
serotonergic pathways)
prevent
prostaglandin
production at
the cellular
level.

Bertolini et al, 2006; Botting, 2006; Pickering et al, 2006; Mallet et al, 2008; Pickering et al,

Qualitative Review of Paracetamol,

NSAIDs-or their Combination in
postoperative pain.

Paracetamol can be the best

alternative to NSAIDs for high risk
patients.
It is appropriate to administer
Acetaminophen with NSAID, additive
or synergistic effects

Intravenous form of paracetamol

has more predictable onset and
duration of actions
Hyllested M, Jones S, Pedersen JL et al (2002) Comparative effect of paracetamol, NSAIDs or
their combination in postoperative pain management: a qualitative review. Br J Anaesth

Fast onset of action *

Rapid onset: 5min

Peak at ideal time: 30min

Good residual effect at >6hrs

IV paracetamol for
dental
1.

Sindet-Pedersen S.1997. Data on file.

* I.V. paracetamol was administered as a bio-equivalent dose of

propacetamol.
Sindet-Pedersen S, 1997

Review 2010

Paracetamol and NSAIDs (cox1 and cox2)

Combination of paracetamol and an

NSAIDs may offer superior analgesia
compared with either drug alone
(Anesth Analg 2010)

SYSTEMIC REVIEW
NSAIDs vs COXIBs For Postoperative
Pain

Demonstrate Equipotent Analgesic

Efficacy After Minor and Major
Surgical Procedure

NSAIDs

COXIBs

COXIBs Better Alternative

TO NSAIDs in the
perioperative setting

COXIBs associated with:

Reduce gastrointestinal
side effects

Absence of anti-platelet
activity

Romsing J & Moiniche S (2004) A systematic review of COX-2 inhibitors compared with traditional NSAIDs, or different COX-2
inhibitors for post-operative pain. Acta Anaesthesiol Scand 48(5): 52546.

Parecoxib and
Acetominophen

Combination of paracetamol and parecoxib may

useful in patients
who are susceptible to haemorrhagic
complications of NSAIDs

Paracetamol + Tramadol

Tramadol/paracetamol
combination tablets provided
analgesic efficacy with a better
safety profile to tramadol
capsules in patients
postoperative pain following
ambulatory hand surgery.

Paracetamol as a part of
multimodal analgesia
Paracetamol is an effective analgesic for acute
pain; the incidence of adverse effects comparable
to placebo (Level I [Cochrane Review])
Paracetamol given in addition to PCA opioids
reduces opioid consumption but does not result in
a decrease in opioid-related side effects (Level I)
NSAIDs given in addition to paracetamol improve
analgesia compared with paracetamol alone
(Level I)
Acute Pain Management: Scientific Evidence, Australian and New Zealand College of Anaesthetists
and Faculty of Pain Medicine, 2010

Practice Guidelines for Acute Pain Management in the

Perioperative Setting
An Updated Report by the American Society of
Anesthesiologists Task Force on Acute Pain Management 2012

Recommendations for Multimodal

Techniques.
Whenever possible, anesthesiologists should use
multimodal pain management therapy.
Central or nerve blockade with LA should be
considered.
Unless contraindicated, patients should receive an
ATC regimen of COXIBs, NSAIDs, or acetaminophen .

Dosing regimens shoud be optimize efficacy while

minimizing the risk of adverse events.
The choice of medication, dose, route, and
duration of therapy should be individualized.

Anesthesiology 2012; 116:248-7

Central/
Peripheral nerve block

OPIOID

Mg

Alpha-2 Agonists

Ketamine

B
Tramado
l
Gabapentinoi

NSAI
D
COXI

(Morphine,
Fentanyl)

PARACETAMOL

Can be a basic component of multimodal

Multimod
al
Analgesi
a

Conclusion
Improved
Analgesia
Lowered Dose

Reduced
Side
Effects

Early
Mobilization
Early Enteral
Feeding
Rapid Recovery
multimodal
analgesia
low cost

Aggressive preventive
including epidural or nerve block not
produce optimal analgesia but also may

only
prevent

This is not new

Crile
Stated
1913That:

Patients Given
Inhalation
anesthesia still
need to be
protected by
regional
anesthesia,
otherwise they
might suffer

Thank you
very much

What is multimodal
analgesia?
Is a combination of two or
more analgesics that act
at different mechanisms,
produce additive or
synergistic analgesia
Main goals of Multimodal Analgsia is to reduce the amount of Opioid

Benefits of Multimodal
Analgesia
Opioids

REDUCED DOSES
of each
analgesic
Potentiation

NSAIDs,
Paracetamol
nerve blocks

IMPROVED
EFFECACY
due
to synergistic or
additive effects
REDUCE SIDE
EFFECTS
of
each drug

Kehlet H et al. Anesth Analog. 1993;77:1048-1056.

Prof. Henrik Kehlet, MD, PhD.

Department of Surgical Gastroenterology, Hvidovre University Hospital, Hvidovre Denmark

Why we need multimodal analgesia for

posoperative pain?

Most of the pain is a

multifaceted and multiplesources.
No
single
analgesic
is
perfect
and
no
No single analgesic is perfect and no
single
analgesic
can
treat
all
types
of
pain.
single analgesic can treat all types of pain.

Multimodal Analgesia is
potentiating in efficacy,
reduced doses, minimal adverse
effect. Improve the outcome.

90%
90%of
ofCancer
CancerPain
Paincan
canbe
bemanaged
managedby
by
using
usingWHO
WHOStep
StepLadder.
Ladder.
WHO Step Ladder

Mild Pain
Nonopioid
adjuvant
Acetaminophen
Ibuprofen
Celecoxibe

Moderate Pain
Mild Opioid
nonopioid
adjuvant

Codein or Tramadol
Paracetamol
or
NSAID or Coxib

Severe Pain
Strong Opioid
nonopioid
adjuvant

Morphine
- Rapid relies; tab
or liquid
- Slow relies MST

Fentanyl Patch
Modify AHT

WHO three step ladder

Paracetamol
adjuvants
Increasing pain

Weak Opioid for

mild to moderate
pain
Paracetamol
adjuvants

Strong Opioid for

severe pain
(Morphine)
Celecoxib
adjuvants

GABAPENTINOIDS
Gabapentin and Pregabalin
Gabapentin

Gabapenti
n and
pregabali
n

Pregabalin

Enhanced Analgesic
effects of:

can synergically with

NSAID

and Celecoxib

Morphin
e

NSAIDs

COXIBs

Provide antihyperalgesia

Superior to either
single drugs for
postoperative pain
following spinal
fusion surgery

Eckhardt K, Ammon S, Hofmann U, Riebe A, Gugeler N, Mikus G. Anesth Analg. 2000;91:185191.

Hurley RW, Chatterjea D, Rose Feng M, Taylor CP, Hammond DL.. Anesthesiology. 2002; 97:12631273.
Gilron I, Orr E, Tu D, ONeill JP, Zamora JE, Bell AC. Pain. 2005;113:191200.
Reuben SS,Buvanendran A,Kroin JS, Raghunathan. Anesth Analg. 2006;103:12711277.

PARACETAMOL , NSAIDS & COXIBS

Guidelines line for postoperative pain
management state that:

Unless contraindication, all

patients should receive an
around-the clock(ATC)
regiment on NSAIDs, COXIBs,
or Paracetamol.
American Society of Anesthesiologists Task Force on Acute Pain
Management 2004;100:1573-1581

Postoperative Pain Sensitization

Analgesic Agents
Normal Sensory Threshold

Abnormal Sensory
Threshold

Antihyperalgesic /
antiallodynic Agents

Hyperalgesia /
Allodynia

Courtesy by Dr. KY

UNIVERSITAS
HASANUDDIN

UNIVERSITAS
HASANUDDIN

Ketamin
More Frequently Use in Postorthopedic Surgical Pain
Management

Arthroscopic
Anterior Cruciate
Ligament Surgery

Outpatient
Knee
Arthroplasty
Total Knee
Arthroplasty

A Single intraoperative injection

of ketamin (0,15 mg/kg)
improved analgesia and passive
knee mobilization 24 hour after
surgery

Improved Postoperative
Outcome

When combine with epidural or

femoral nerve block, increase
postoperative pain relief for
total knee arthroplasty.

Menigaux C, Guignard B, Fletcher D, Dupont X, Guirimand F, Chauvin M. Anesth Analg. 2000;90:129135.

Menigaux C, Guignard B, Fletcher D, Sessler DI, Dupont X, Chauvin M. Anesth Analg. 2001;93:606612.
Himmelseher S, Ziegler-Pithamitsis D, Agiriadou H, Martin Jjelen-Esselborn S, Koch E. Anesth Analg.
2001;92: 12901295.

Limitation of Traditional NSAIDS:

(Aspirin/NSAID) sensitive asthma

The COX-2 selective

inhibitors
celecoxib1,2 and rofecoxib3,4
given orally do not cause
bronchospasm in patients
with aspirin/conventional
NSAID-sensitive asthma

1. Gyllfors et al. Allergy Clin Immunol 2003;111:1116;

2. Martin-Garcia et al. J Investig Allergol Clin Immunol 2003;13:20;
3. Stevenson et al. J Allergy Clin Immunol 2001;108:47;
4. Martin-Garcia et al. Chest 2002;121:1812

Clinical Features of
Postoperative Pain.
ALLODYNIA
HYPERALGESIA
PROLONGED PAIN
REFERRED PAIN

PATHOPHYSIOLOGICAL PAIN
(CLINICAL PAIN)

Practice Guidelines for Acute Pain Management in the

Perioperative Setting
An Updated Report by the American Society of
Anesthesiologists Task Force on Acute Pain Management

Recommendations for Multimodal Techniques.

Whenever possible, anesthesiologists should use
multimodal pain management therapy.
Central regional blockade with LA should be considered.
Unless contraindicated, patients should receive an aroundthe-clock regimen of COXIBs, NSAIDs, or acetaminophen.

Dosing regimens should be administered to optimize

efficacy while minimizing the risk of adverse events.
The choice of medication, dose, route, and duration of
therapy should be individualized.

2. KETAMIN
Anesthesia Dose more than 2 mg/kg (iv) anesthesia + produce side effects such
us Psychomimetic effect

Excessive sedation
Cognitive Dysfunction
Hallucination
Nightmares
Subanesthesia Dose (Low Dose) < 1 mg/kg
demonstrated significant analgesic efficacy without these
side effects
Very Low dose (0,15 mg/kg) single intraoperative
injection of ketamine 0,15 mg/kg improve analgesia and
passive knee mobilization 24 hour after arthroscopy

PARACETAMOL
Opioid

(Gabapentin, Pregabalin)

Gabapentanoid

(Clonidine,
Dexmedetomidine)

Alpha-2
Agonist

NSAI
D
COXI
B
Tramado
l
Ketamin
e

Local Anesthetic
(Epidural Block, Nerve
Block, Infiltration)

Nature of Postoperative pain

Central Sensitization

Peripheral Sensitization

Damaged Zone
Sensitization and activation

ALLODYNIA
HYPERALGESIA
Bombardment
Input

BK2 - BK1
PGs, H+

CNS

ATP
NGF

blood
vessel

SP, CGRP

C-fibre
A fibre

A fibre

BK

5HT

Vasodilation+plasma extravasation

Transmitter
release - neuronal
excitability

Secondary hyperalgesia
(allodynia)
Primary hyperalgesia

Non-Specific NSAIDs and COXIB

as a part of multimodal analgesia
Non-selective NSAIDs and coxibs are effective
analgesics of similar efficacy for acute pain (Level I)
Non-selective NSAIDs are effective in the treatment of
acute postoperative and low back pain, renal colic and
primary dysmenorrhoea (Level I [Cochrane
Review])
Non-selective NSAIDs given in addition to PCA opioids
reduce opioid consumption and the incidence of nausea,
vomiting and sedation (Level I)
Coxibs given in addition to PCA opioids reduce opioid
consumption but do not result in a decrease in opioidrelated side effects (Level I)
Acute Pain Management: Scientific Evidence, Australian and
New Zealand College of Anaesthetists and Faculty of Pain

PARACETAMOL
(Gabapentin, Pregabalin)

Gabapentanoid

NSAI
D
COXI
B
Tramado
l
Ketamin
e

OPIOID

(Morphine, Fentanyl)

Antihyperalgesic Drugs

NSAIDs (Nonsteroidal anti-inflammatory drugs)

COXIBs (Selective COX-2 inhibitors)
lidocaine (iv and topical)
Ketamine (low-dose) and other NMDA
antagonist
Clonidine (iv and Intrathecal)
Gabapentinoid (Gabapentin and Pregabalin)
Amitriptyline
TENS
Midazolam (Intratheca

Antiallodynic Drugs
Lidocaine iv
Ketamine (low-dose) & other NMDA
antagonist
Gabapentin (Oral and intrathecal)
Clonidine (iv and intrathecal)
Propofol (low dose)
Midazolam (intrathecal)

Practice Guidelines for Acute Pain Management in the

Perioperative Setting
An Updated Report by the American Society of
Anesthesiologists Task Force on Acute Pain Management

Practice Guidelines for Acute Pain Management in the

Perioperative Setting
An Updated Report by the American Society of
Anesthesiologists Task Force on Acute Pain Management

Multimodal techniques with systemic analgesics:

Meta-analyses of RCTs report improved pain scores
and reduced analgesic use when intravenous
morphine combined with ketorolac (Category A1
evidence) is compared with intravenous morphine
equivocal findings are reported for nausea and
vomiting (Category C1 evidence).
Multimodal techniques with central regional
analgesics:
Meta-analyses of RCTs report improved pain scores
(Category A1 evidence) and equivocal findings for
nausea and vomiting and pruritus (Category C1
2012; 116:248
73
evidence) when epiduralAnesthesiology
morphine combined
with

Acute Pain Management: Scientific Evidence

Australian and New Zealand College of
Anaesthetists
and Faculty of Pain Medicine
Approved by the NHMRC on 4 February 2010

Perioperative Multimodal
Analgesia
Parecoxib
Ibuprofe
n
iv

iv

Cox-2 agents

Ketamine

NMDA
antagonists

iv

NSAIDs

Better analgesia
synergy

Multimodal

additivity
Reduced side effects

Paracetamol
iv

iv

Opioids

NorAdr & iv
5HT antagonists

Local Anaesthesia
Jin et al. J Clin Anesth;13:524, 2001

Tramado
l

Kehlet et al. Anesth Analg;77:1048. 1998

Woolf CJ, Science, 288:1765-1768, 2000

Normal condition
R

S
Physiological pain
Pathological condition
R

S
Pathological pain

Paracetamol has Opioid Sparing Effects

I.V. paracetamol in these studies

was administered as a bioequivalent dose of propacetamol.

2. KETAMIN
Anesthesia Dose more than 2 mg/kg (iv) anesthesia + produce side effects such
us Psychomimetic effect

Excessive sedation
Cognitive Dysfunction
Hallucination
Nightmares
Subanesthesia Dose (Low Dose) < 1 mg/kg
demonstrated significant analgesic efficacy without these
side effects
Very Low dose (0,15 mg/kg) single intraoperative
injection of ketamine 0,15 mg/kg improve analgesia and
passive knee mobilization 24 hour after arthroscopy

Ketamin
More Frequently Use in Postorthopedic Surgical Pain
Management

Arthroscopic
Anterior Cruciate
Ligament Surgery

Outpatient
Knee
Arthroplasty
Total Knee
Arthroplasty

A Single intraoperative injection

of ketamin (0,15 mg/kg)
improved analgesia and passive
knee mobilization 24 hour after
surgery

Improved Postoperative
Outcome

When combine with epidural or

femoral nerve block, increase
postoperative pain relief for
total knee arthroplasty.

Menigaux C, Guignard B, Fletcher D, Dupont X, Guirimand F, Chauvin M. Anesth Analg. 2000;90:129135.

Menigaux C, Guignard B, Fletcher D, Sessler DI, Dupont X, Chauvin M. Anesth Analg. 2001;93:606612.
Himmelseher S, Ziegler-Pithamitsis D, Agiriadou H, Martin Jjelen-Esselborn S, Koch E. Anesth Analg.
2001;92: 12901295.

KETAMIN
Low-dose ketamine is not really an
analgesic, but better described
as:
anti-hyperalgesic
anti-allodynic
tolerance-protective of
opioid
Opioid-induced

GABAPENTINOIDS
Gabapentin and Pregabalin
Gabapentin

Gabapenti
n and
pregabali
n

Pregabalin

Enhanced Analgesic
effects of:

can synergically with

NSAID

and Celecoxib

Morphin
e

NSAIDs

COXIBs

Provide antihyperalgesia

Superior to either
single drugs for
postoperative pain
following spinal
fusion surgery

Eckhardt K, Ammon S, Hofmann U, Riebe A, Gugeler N, Mikus G. Anesth Analg. 2000;91:185191.

Hurley RW, Chatterjea D, Rose Feng M, Taylor CP, Hammond DL.. Anesthesiology. 2002; 97:12631273.
Gilron I, Orr E, Tu D, ONeill JP, Zamora JE, Bell AC. Pain. 2005;113:191200.
Reuben SS,Buvanendran A,Kroin JS, Raghunathan. Anesth Analg. 2006;103:12711277.

Sekian dan Terima Kasih

Semoga Ada Manfaatnya

Gabapentinoids as a part
of Multimodal Analgesia
Perioperative gabapentinoids
(gabapentin/ pregabalin) reduce
postoperative pain and opioid
requirements and reduce the
incidence of vomiting, pruritus and
urinary retention, but increase the
risk of sedation (Level I)
Acute Pain Management: Scientific Evidence, Australian and
New Zealand College of Anaesthetists and Faculty of Pain

The role of multimodal

analgesia in pain management
after ambulatory surgery
Implementation of evidence-based multimodal
analgesic regimens in the perioperative period can
maximize the short-term and long-term benefits of
the therapy.
The use of multimodal analgesia is rapidly
becoming the standard of care for preventing pain
after ambulatory procedures at most surgery
centers throughout the world
The use of multimodal analgesia technique offers
multiple benefits for the patient and the healthcare
system in line with the goals of modern ambulatory
(day-case) surgery

Lazoa OL., White PF. Current Opinion in Anesthesiology 2010,

23:697703

PAIN
Perception

Modulation

Peripheral sensitisation

Projection
Transmission

Injur
y

Ser
NK
Pg
Hist

C, A-delta
Conduction

Transduction

hl & Moiniche. Br Med Bull (2004) 71 (1). 13-27.

WD
R

Modulation A-beta
Central sensitization
(Pain memory)

Prof. Henrik Kehlet, MD, PhD.

Department of Surgical Gastroenterology, Hvidovre University Hospital, Hvidovre Denmark

Why I gave her ketamin low dose to this patient?

Peripheral and Central

Sensitization
Central Sensitization of Spinal
Cord Dorsal Horns Neuron
Dorsal root
ganglion

Amplification of the
Pain Message to the
brain

Peripheral
Sensitization

CENTRAL SENSITIZATION
Receptive field
enlargement

Willis WD et al,
2002

AA: Arachidonic acid

PG: Prostaglandin

Recruitment
Ongoing activation after
injury, the receptive fields
of these neurons expand,
leading to spread of pain.

Action potential discharge in

Second order spinal neurons

Wind-Up
60
50
40

-u p
d
win

30
20

NMDA unblocked
NMDA blocked (AP5)

10
0

progressive
increase in
response of second
order neurons to
repetitive C-fiber
Mendel and Wall, 1965
input

8
6
1
4
1 1
2
2 4to
Stimulus frequency0applied
C-fiber nerve endings

Now is appreciated
that
wind-up is a crucial
factor for chronic pain
after surgery

Pathophysiology

Inflammato
ry
Soup

Surgical
Injury
Peripheral
Nerve
Injury

of Surgical

Peripheral
Sensitisation
of
Nociceptors

Central
Sensitisation
of Dorsal
Horn

Trauma

Primary
hyperalgesi
a
Secondary
Hyperalgesi
a
Long-Term
Potentiatio
n

Secondary Hyperalgesia
Commonly ignored or discounted in the
evaluation and treatment of
postoperative pain
Neuroplastic changes in the CNS that
may amplify pain perception
Not relieved or may be worsened by
conventional medications
Persistence of CNS sensitization may
lead to chronic post-surgical pain

er-Smith OHG, Arendt-Nielsen L. Anesthesiology 2006;104:601-607

Pain Classification
PHYSIOLOGICAL PAIN
CONVENTIONAL PERIOPERATIVE ANALGESIA

PATHOLOGICAL PAIN
PREVENTION OF CENTRAL AND
PERIPHERALSENSITISATION

Auret K and Schug SA. Drugs Aging 2005;22:641-54

Goals of Postoperative Pain Treatment

Improve quality of life for patient
Facilitate rapid recovery and return to full
function
Reduce morbidity and mortality
Allow early discharge from hospital
Prevent development of chronic pain

Incidence of Chronic Postsurgical Pain

Kehlet H, et al. Lancet 2006;367:1618-1625

Aim of Multimodal

Analgesia

Monotherapy: inadequate analgesia and/or

intolerable adverse effects (at doses required
for effective analgesia)
Rationale for combination therapy:
Pain has multiple aetiologies and mechanisms
Most analgesics act via a specific mechanism
Combinations may increase analgesia and reduce
adverse effects

Preemptive Analgesia
To protect the peripheral and central nervous system from
afferent nociceptive inputs and to prevent pathological
modulations that are associated with pain transmission
Analgesia is started before tissue injury and maintained
throughout and after surgery
Goals
Prevention of acute intra- and postoperative pain
Prevention of pain-related pathological modulation of the CNS
Prevention of persistent postoperative pain and development of
chronic pain

Grape S, Tramer MR. Best Prac Res Clin Anaesth 2007;21:51-63

Preventive Analgesia
Broader definition of preemptive
analgesia
Includes perioperative analgesic regimen
ability to control pain-induced
sensitization of the CNS
Decrease development and persistence of
pathological pain
Kissin I. Anesthesiology 2000;93:1138-43

Multimodal Analgesia

Definition: Adjuvants
Compounds that by themselves have
undesirable side-effects or low potency but in
combination with opioids allow a reduction of
opioid dosing for postoperative pain control
Role for adjuvants
Supplement postoperative pain management
Reduce opioid-related side effects
Prevent opioid-induced hyperalgesia
Prevent or reduce post-surgical chronic pain
Buvanendran A, Kroin JS. Best Prac Res Clin Anaesth 2007;21:31-49

Buvanendran A, Kroin JS. Best Prac Res Clin Anaesth 2007;21:31-49

Aim of Postoperative Pain

Management
Provision of subjective comfort
(Pain free)
2. Inhibition of trauma induce
nociceptive impulses (Stress free)
1.

To blunt autonomic and somatic

reflex responses .
To enhance restoration of body
function.
These effects reduces pulmonary,
cardiovascular, thromboembolic and
so on.
PAIN
May FREE
lead to
postoperative
ISimprove
NOT SYNONYM
WITH
outcome STRESS FREE