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Multimodal Analgesia for Postoperative Pain Management

A. Husni Tanra

Department of Anesthesiology, IC and Pain Management

Faculty of Medicine, Hasanuddin University

Makassar

Meet The Expert, Solo May 6, 2016

What the Patients say for their anesthesiologists?

Before 1990, most patients say

“ I’M WORRIED THAT I WON’T WAKE UP AFTER THE OPERATION

After 1990, Due to the safe of anesthesia, those words are not oftenly be hear

“ I’M WORRIED TO HAVE PAIN

AFTER

THE OPERATION”

Pain Conitinues to be Undertreated

Patients (%) 1995 100 2003 90 83 77 Patient’s worst pain 80 70 60 49 47
Patients
(%)
1995
100
2003
90
83
77
Patient’s worst pain
80
70
60
49
47
50
40
30
23
21
19
18
20
13
8
10
0
Any pain
Slight
Moderate
Severe
Extreme

pain

pain

pain

Warfield & Kahn. Anesthesiology 1995;83:1090 Apfelbaum et al. Anesth Analg 2003;97:534

pain

Pain Conitinues to be Undertreated Patients (%) 1995 100 2003 90 83 77 Patient’s worst pain

Traditional Postoperative Pain Management

Traditional Postoperative Pain Management  Using Monomodality drug  10 mg morphine, IM and done by

Using Monomodality drug

10 mg morphine, IM and done by SURGEON. Multimodal Analgesia has

PRN

undergone a revolution in the last 20 years.

Courtesy S.A. Schug

Kehlet & Dahl The value of Multimodal or Balanced Analgesia in Postop pain (AA) 1993

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 Opio

pain Strong pain needs strong analgesic strong analgesic is opioid

Opioid is really good and effective to treat pain at rest!

BUT:

Not so good to treat pain on movement Significant adverse effects Nausea Vomiting Constipation Sedation, drowsiness, confusion

Potential risk of Opioid Induced Ventilatory Impairment (OIVI)

Opioid in Postoperative pain

Opioids are needed to treat severe pain

BUT they are impairing recovery and rehabilitation!

THEREFORE opioid;sparing techniques are needed!

Paracetamol in Opioid Sparing Effects

I.V. paracetamol in these studies was administered as a bio- equivalent dose of propacetamol.
I.V. paracetamol in these studies
was administered as a bio-
equivalent dose of propacetamol.

Opioid Dose and Clinically Meaningful Opioid Related Adverse Events

‘Once threshold reached, every further 3–4 mg

increase will be

associated with 1 clinically meaningful opioid- (CME) > 3 events related symptom’ 2 events Reduction in
associated with 1 clinically meaningful opioid-
(CME)
> 3 events
related symptom’
2 events
Reduction in
clinically meaningful
opioid related ADE
1 event
No event
–33%
0
5
10
15
20
25
Morphine equivalent dose in 24 hours (mg)
ADE = adverse drug
event
Zhao et al, J Pain Symp Manag
200
4;28:35
Number of CMEs on day 1 after
laparoscopic cholecsytectomy
Opioid Dose and Clinically Meaningful Opioid Related Adverse Events ‘Once threshold reached, every further 3–4 mg
Opioid Dose and Clinically Meaningful Opioid Related Adverse Events ‘Once threshold reached, every further 3–4 mg
Opioid Dose and Clinically Meaningful Opioid Related Adverse Events ‘Once threshold reached, every further 3–4 mg
Opioid Dose and Clinically Meaningful Opioid Related Adverse Events ‘Once threshold reached, every further 3–4 mg
Opioid Dose and Clinically Meaningful Opioid Related Adverse Events ‘Once threshold reached, every further 3–4 mg
Opioid Dose and Clinically Meaningful Opioid Related Adverse Events ‘Once threshold reached, every further 3–4 mg

Analgesia

Analgesia

Opioids Potentiating /Synergic Paracetamol NSAIDs, & Coxibs
Opioids
Potentiating
/Synergic
Paracetamol
NSAIDs, &
Coxibs

nerve blocks

REDUCED DOSES of each analgesic

IMPROVED EFFECACY

due

to synergistic or

additive effects

REDUCE SIDE

EFFECTS

of

each drug

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

COMBINE DRUGS MAY HAVE

3 EFFECTS

1. Synergetic .............

2+2>4

2. Additive ................

2+2=4

Why we need multimodal analgesia for posoperative pain?

Most of

Most of

the pain is a

the pain is a

multifaceted and multiple-

multifaceted and multiple-

sources.

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

Multimodal Multimodal Analgesia Analgesia is is

potentiating potentiating in in efficacy, efficacy,

reduced reduced doses, doses, minimal minimal adverse adverse

effect. Improve the outcome.

Pain is always associated with surgery, but how far these doctors concern about it

Pathophysiology of

Surgical Trauma

Surgical

Surgical

Injury

Injury

Pathophysiology of Surgical Trauma Surgical Surgical Injury Injury Inflammato Inflammato ry ry “Soup” “Soup” Peripheral Peripheral
Inflammato Inflammato ry ry “Soup” “Soup” Peripheral Peripheral Nerve Nerve Injury Injury
Inflammato Inflammato
ry ry
“Soup” “Soup”
Peripheral Peripheral
Nerve Nerve
Injury Injury

Peripheral Peripheral

Sensitisation Sensitisation

of of

Nociceptors Nociceptors

Central Central

Sensitisation Sensitisation

of of Dorsal Dorsal

Horn Horn

Primary

Primary

hyperalgesi

hyperalgesi

a a

Secondary

Secondary

Hyperalgesi

Hyperalgesi

a

a

Long-Term

Long-Term

Potentiatio

Potentiatio

n n

Chroni

Chroni

cPain

cPain

After surgery Pain Sensitization:

Hyperalgesia and Allodynia

HYPERALGESIA Sensitised pain response 10 Normal 8 Pain intensity pain response for stimulus X sensitised 6
HYPERALGESIA
Sensitised
pain response
10
Normal
8
Pain intensity
pain response
for stimulus X
sensitised
6
pain response
Injury Injury
4
Pain intensity
for stimulus
X
2
normal
pain
response
0
X
Pain intensity

ALLODYNIA

Stimulus intensity

Clinical Features of

Clinical Features of

Postoperative Pain

Postoperative Pain

HYPERALGESI HYPERALGESI

A A
A
A

ALLODYNIA

Primary Hyperalgesia Secondary Hyperalgesia
Primary
Hyperalgesia
Secondary
Hyperalgesia
CLINICAL CLINICAL PAIN PAIN (PATHOPHYSIOLO (PATHOPHYSIOLO GICAL GICAL PAIN PAIN ) )
CLINICAL CLINICAL PAIN PAIN
(PATHOPHYSIOLO (PATHOPHYSIOLO
GICAL GICAL PAIN PAIN ) )

Vanished

Vanished

after healing

after healing

XX
XX

Chronic

Chronic

Pain Pain
Pain
Pain

Basic Principle of Postop

Pain Management is

prevent the occurrence of

Peripheral

and

Central

sanitization

Basic Principle of Postop Pain Management is prevent the occurrence of Peripheral and Central sanitization Preventive

Preventive Preventive

Multimoda Multimoda

l l

Analgesia A l i

Basic Principle of Postop Pain Management is prevent the occurrence of Peripheral and Central sanitization Preventive

reduced the process of Neuroplasticity Neuroplasticity

By Giving

By Giving

Anti-

Anti-

hyperalgesic

hyperalgesic

& Anti-

& Anti-

allodynic

allodynic

dru

s

drugs

Basic Principle of Postop Pain Management is prevent the occurrence of Peripheral and Central sanitization Preventive

Anti-hyperalgesic Therapy:

Opioid-Sparing

Partially desensitised

Sensitised pain response pain response ~30% Normal reduction pain response Anti- Anti- hyper hyper algesic algesic
Sensitised
pain response
pain response
~30%
Normal
reduction
pain
response
Anti-
Anti-
hyper
hyper
algesic
algesic
Pain intensity
Opioid
Opioid
Anti-hyperalgesic Therapy: Opioid-Sparing Partially desensitised Sensitised pain response pain response ~30% Normal reduction pain response Anti-

X

Stimulus intensity

KETAMIN as

Antihyperalgesic

Low-dose ketamine (0.1- 0.15

mg/Kg )is not really an ‘analgesic’,

but better described as:

‘anti-hyperalgesic’ ‘anti-allodynic’ ‘tolerance-protective’ of opioid
‘anti-hyperalgesic’
‘anti-allodynic’
‘tolerance-protective’ of
opioid

 Opioid-induced

Hyperalgesia

Coutersy by Prof. S. A. Schug

Philosophy of Multimodal Analgesia

Not Not only only just just giving giving 2 2 or or more more drugs drugs which which

different different mechanism, mechanism, but; 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 Ketamin

 

Paracetamol Paracetamol

Ketamin Ketamin Paracetamol Paracetamol
Ketamin Ketamin Paracetamol Paracetamol
Percepti on
Percepti
on
Opioids Opioids Gabapentinoid Gabapentinoid CNS CNS s s Clonidine Clonidine Modulatio Transducti n on DR G
Opioids
Opioids
Gabapentinoid
Gabapentinoid
CNS
CNS
s
s
Clonidine
Clonidine
Modulatio
Transducti
n
on
DR
G
Transmiss
ion
Local Local
anesthetics anesthetics

Corticosteroi

ds ds

Target Point of Analgesic Drugs Ketamin Ketamin Paracetamol Paracetamol Percepti on Opioids Opioids Gabapentinoid Gabapentinoid CNS

NSAIDs NSAIDs

COXIBs COXIBs

Local Local

Anesthetic

Target Point of Analgesic Drugs Ketamin Ketamin Paracetamol Paracetamol Percepti on Opioids Opioids Gabapentinoid Gabapentinoid CNS

Transducti

on

Target Point of Analgesic Drugs Ketamin Ketamin Paracetamol Paracetamol Percepti on Opioids Opioids Gabapentinoid Gabapentinoid CNS

Modulatio

n

COXIBs COXIBs
COXIBs COXIBs

Modify by

AHT

ANALGESIC DRUGS

ANALGESIC DRUGS NONOPIOIDS ADJUVANTS • Paracetamol • NSAID (nonselective) • Coxib (selective NSAID) • Mild Opioid
ANALGESIC DRUGS NONOPIOIDS ADJUVANTS • Paracetamol • NSAID (nonselective) • Coxib (selective NSAID) • Mild Opioid
ANALGESIC DRUGS NONOPIOIDS ADJUVANTS • Paracetamol • NSAID (nonselective) • Coxib (selective NSAID) • Mild Opioid
ANALGESIC DRUGS NONOPIOIDS ADJUVANTS • Paracetamol • NSAID (nonselective) • Coxib (selective NSAID) • Mild Opioid

NONOPIOIDS OPIOIDS

ADJUVANTS

Paracetamol

NSAID

(nonselective)

Coxib (selective

NSAID)

Mild Opioid

( codeine & tramadol

)

Strong Opioid

( Morphine &

Fetanyl )

Steroid

(dexamethason)

Alpha2 agonist

(Clonidine)

Ketamine (NMDA

Multimodal Analgesia

OPIOIDS

NEURAXIAL BLOCKS PERIPHERAL NERVE BLOCKS

MULTIMODAL

ANALGESIA

NON-OPIOID

ANALGESICS

ADJUVANTS

Multimodal Analgesia OPIOIDS NEURAXIAL BLOCKS PERIPHERAL NERVE BLOCKS MULTIMODAL ANALGESIA NON-OPIOID ANALGESICS ADJUVANTS

What is the most regiments

Opioid Potentiation
Opioid
Potentiation
Paracetamol NSAIDs or Coxibs Nerve blocks Ketamine Dexamethazone Alpha;2 Agonists Gabapentinoids
Paracetamol
NSAIDs or Coxibs
Nerve blocks
Ketamine
Dexamethazone
Alpha;2 Agonists
Gabapentinoids

doses of each analgesic

Improved

anti;nociception

due

to

synergistic/additive

effects

severity of side;effects of each drug

Kehlet & Dahl. Anesth Analg 1993;77:1048

Playford et al. Digestion. 1991;49:198

Paracetamol

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

1. Can be given to all age – from

(Adult < 4 gr/day, Infant and children 20-40

mg/kgBW)

Infant to Elderly

2. From pregnant to Lactating

Woman

3. Can be used for patients with

Qualitative Review of Paracetamol,

Qualitative Review of Paracetamol,

NSAIDs-or their Combination in

NSAIDs-or their Combination in

postoperative postoperative pain. pain.

Paracetamol can be the best

Paracetamol can be the best

alternative to NSAIDs for high risk

alternative to NSAIDs for high risk

patients.

patients.

It is appropriate to administer

It is appropriate to administer

Acetaminophen Acetaminophen with with NSAID, NSAID,   additive additive

or synergistic effects

or synergistic effects

Intravenous form of paracetamol

Intravenous form of paracetamol

has more predictable onset and

has more predictable onset and

duration of actions

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

Review 2010

Review 2010

Paracetamol and NSAIDs (cox1 and cox2)

Combination of paracetamol and an Combination of paracetamol and an NSAIDs may offer superior analgesia NSAIDs
Combination of paracetamol and an
Combination of paracetamol and an
NSAIDs may offer superior analgesia
NSAIDs may offer superior analgesia
compared with either drug alone
compared with either drug alone
(Anesth Analg 2010)
(Anesth Analg 2010)

SYSTEMIC REVIEW

NSAIDs vs COXIBs For Postoperative Pain

Demonstrate Equipotent Analgesic

Demonstrate Equipotent Analgesic

Efficacy After Minor and Major

Efficacy After Minor and Major

Surgical Procedure

Surgical Procedure

NSAIDs

COXIBs

COXIBs associated with:

COXIBs Better Alternative

TO NSAIDs in the

perioperative setting

SYSTEMIC REVIEW NSAIDs vs COXIBs For Postoperative Pain Demonstrate Equipotent Analgesic Demonstrate Equipotent Analgesic Efficacy After

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): 525–46.

Acetominophen

Acetominophen

Acetominophen Acetominophen Combination of paracetamol and parecoxib may Combination of paracetamol and parecoxib may useful in

Combination of paracetamol and parecoxib may

Combination of paracetamol and parecoxib may

useful in patients

useful in patients

who are susceptible to haemorrhagic

who are susceptible to haemorrhagic

complications of NSAIDs

complications of NSAIDs

Paracetamol ++ Tramadol

Paracetamol

Tramadol

Tramadol/paracetamol Tramadol/paracetamol combination tablets provided combination tablets provided analgesic efficacy with a better analgesic efficacy with
Tramadol/paracetamol
Tramadol/paracetamol
combination tablets provided
combination tablets provided
analgesic efficacy with a better
analgesic efficacy with a better
safety profile to tramadol
safety profile to tramadol
capsules in patients
capsules in patients
postoperative pain following
postoperative pain following
ambulatory hand surgery.
ambulatory hand surgery.
Sedation can be interpreted as a negative outcome of Sedation can be interpreted as a negative
Sedation can be interpreted as a negative outcome of
Sedation can be interpreted as a negative outcome of
gabapentin gabapentin ,however ,however its its can can be be benefical benefical in in the the
perioperative perioperative setting setting as as an an anxiolysis anxiolysis

Choice of Analgesic Technique

(Analgesic Ladder of WFSA)

Opiate And Pain NSAID Intensity Oral route available – give and orally Paracetamol NSAID and Paracetamol
Opiate
And
Pain
NSAID
Intensity
Oral route available – give
and
orally
Paracetamol
NSAID
and
Paracetamol
Pain
decreases
Paracetamol
as time
passes

Conclusions:

Multimodal Analgesia

There is Level I evidence for the effectiveness

of the following components of multimodal

analgesia:

Paracetamol

NSAIDs/Coxibs

Alpha;2;Delta Ligands (pregabalin)

Systemic Local Anaesthetics

Ketamine

Alpha;2 Agonists

(clonidine/dexmedetomidine)

Corticosteroids

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

Multimod al al Analgesi Analgesi
Multimod
al
al
Analgesi
Analgesi

a

Improved

Analgesia

Lowered Dose

Reduced

Side

Effects

Early

Mobilization

Early Enteral

Feeding

Rapid Recovery

Aggressive preventive multimodal analgesia

Aggressive preventive multimodal analgesia

low cost

including including epidural epidural or or nerve nerve block block not not only only

produce produce optimal optimal analgesia analgesia but but also also may may prevent prevent

This is not new

Crile

Stated That:

1913

This is not new Crile Stated That: 1913 “Patients Given Inhalation anesthesia still need to be

“Patients Given

Inhalation

anesthesia still

need to be

protected by

regional

anesthesia,

otherwise they

might suffer

Thank you Thank you very much very much
Thank you
Thank you
very much
very much

Paracetamol

NEW but OLD DRUG

Acetominophen/P

Acetominophen/P

AAP

AAP

Paracetamol NEW but OLD DRUG Acetominophen/P Acetominophen/P AAP AAP Analgesic Analgesic Effects Effects Antipyretic Antipyretic Effect
Paracetamol NEW but OLD DRUG Acetominophen/P Acetominophen/P AAP AAP Analgesic Analgesic Effects Effects Antipyretic Antipyretic Effect
Paracetamol NEW but OLD DRUG Acetominophen/P Acetominophen/P AAP AAP Analgesic Analgesic Effects Effects Antipyretic Antipyretic Effect

Analgesic

Analgesic

Effects

Effects

Antipyretic

Antipyretic

Effect

Effect

No Anti-Inflammation

No Anti-Inflammation

Effect

Effect

Route of Administration

Orally

Rectally

Intravenously

since 2009

available in Indonesia

Bertolini A, et al CNS Drugs reviews,