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
IM WORRIED THAT I WONT
WAKE UP AFTER THE OPERATION

After 1990, Due to the safe of

anesthesia, those words are not
oftenly be hear
IM WORRIED TO HAVE PAIN

Pain Conitinues to be Undertreated

Patients (%)
100
90
80
70
60
50
40
30
20
10
0

77

83

1995
2003

Patients worst pain

49 47

19

Any pain

23 21

13

Slight
pain

Warfield & Kahn. Anesthesiology 1995;83:1090

Apfelbaum et al. Anesth Analg 2003;97:534

18
8

Moderate
pain

Severe
pain

Extreme
pain

Traditional Postoperative Pain Management

Using Monomodality drug
10 mg morphine, IM and PRN
done by SURGEON.
Multimodal Analgesia has
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

Prof. Henrik Kehlet, MD, PhD.

Department of Surgical Gastroenterology, Hvidovre University Hospital, Hvidovre Denmark

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 bioequivalent dose of propacetamol .

Number of CMEs on day 1 after

laparoscopic cholecsytectomy

Opioid Dose and Clinically

Meaningful
Once threshold
reached,
every further 34
mg
Opioid
Related
Adverse
Events
increase will be
associated with 1 (CME)
clinically meaningful opioidrelated symptom
> 3 events

Reduction in
clinically meaningful
opioid related ADE

2 events

1 event

No event
33%
0

ADE = adverse drug

event

5
10
15
20
Morphine equivalent dose in 24 hours (mg)

25

Zhao et al, J Pain Symp Manag

2004;28:35

Benefits of Multimodal
Analgesia
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

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 the pain
multifaceted and
sources.

is a
multiple-

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.

Pain is always associated with surgery,

but how far these doctors concern about it

Pathophysiology of
Surgical Trauma

Inflammato
ry
Soup

Surgical
Injury
Peripheral
Nerve
Injury

Peripheral
Sensitisation
of
Nociceptors

Central
Sensitisation
of Dorsal
Horn

Primary
hyperalgesi
a
Secondary
Hyperalgesi
a
Long-Term
Potentiatio
n

Chroni
cPain

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

Basic Principle of Postop

Pain Management is

prevent the occurrence of

Peripheral
and
Central
sanitization

reduced the process ofNeuroplasticity

Preventive
Multimoda
l
Analgesia

By Giving
Antihyperalgesic
& Antiallodynic
drugs

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 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
Opioid-induced
Hyperalgesia

Coutersy by Prof. S. A. Schug

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

ANALGESIC DRUGS

NONOPIOIDSOPIOIDS 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

What is the most

regiments
Opioid

doses of each analgesic

Improved

Potentiation

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

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

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

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

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.

Sedation can be interpreted as a negative outcome of

gabapentin ,however its can be benefical in the
perioperative setting as an anxiolysis

Choice of Analgesic Technique

(Analgesic Ladder of WFSA)
Pain
Intensity

Opiate
And
NSAID
and
Paracetamol

Oral route available give

orally

NSAID
and
Paracetamol

Pain
decreases
as time
passes

Paracetamol

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
Analgesi
a

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

Paracetamol
NEW but OLD DRUG
Acetominophen/P
Acetominophen/P
AAP
AAP

Analgesic
Effects

Antipyretic
Effect

No Anti-Inflammation
Effect
Route of Administration
Orally
Rectally
Intravenously available in Indonesia
since 2009
Bertolini A, et al CNS Drugs reviews,