Multimodal Analgesia for Postoperative Pain Management

Department of Anesthesiology, IC and Pain ManagementFaculty of Medicine, Hasanuddin University

Makassar

A. Husni Tanra

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”

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

Any pain Slightpain

Moderatepain

Severepain

Extremepain

0102030405060708090

100

Patients (%)1995

77

19

49

23

8

83

13

47

21 18

2003Patient’s worst pain

Pain Conitinues to be Undertreated

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

Prof. Henrik Kehlet, MD, PhD.Department of Surgical Gastroenterology, Hvidovre University Hospital, Hvidovre Denmark

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 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)

Postoperative pain is a strong pain Strong pain needs strong analgesic

strong analgesic is opioid

Opioids are needed to treat severe pain

BUT they are impairing recovery and rehabilitation!

THEREFORE opioid;sparing techniques are needed!

Opioid in Postoperative pain

Paracetamol in Opioid Sparing Effects

I.V. paracetamol in these studies was administered as a bio-

equivalent dose of propacetamol.

Opioid Dose and Clinically MeaningfulOpioid Related Adverse Events (CME)

0 5 10 15 20Morphine equivalent dose in 24 hours (mg)

25

Num

ber o

f CM

Es o

n da

y 1

afte

r la

paro

scop

ic c

hole

csyt

ecto

my

2 events

1 event

No event

–33%

Zhao et al, J Pain Symp Manag 2004;28:35

> 3 events

Reduction in clinically meaningful opioid related ADE

ADE = adverse drug event

‘Once threshold reached, every further 3–4 mg increase will beassociated with 1 clinically meaningful opioid-related symptom’

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

Potentiating/Synergic

• REDUCED DOSES of each analgesic

• IMPROVED EFFECACY due to synergistic or additive effects

• REDUCE SIDE EFFECTS of each drugParacetamol

NSAIDs, & Coxibsnerve blocks

Benefits of Multimodal Analgesia

Opioids

COMBINE DRUGS MAY HAVE 3 EFFECTS

1. Synergetic ............. 2+2>4

2. Additive ................ 2+2=4

3. Subadditive ........... 2+2=3

Why we need multimodal analgesia for posoperative pain?

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

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

Most of the pain is a multifaceted and multiple-sources.

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

Long-TermPotentiatio

n

SecondaryHyperalgesi

a

Primaryhyperalgesi

a

CentralSensitisation

of Dorsal Horn

PeripheralSensitisation

of Nociceptors

PeripheralNerve Injury

Inflammatory

“Soup”Surgical Injury

ChronicPain

Pathophysiology of Surgical Trauma

After surgery Pain Sensitization:Hyperalgesia and Allodynia

Normalpain response

Sensitisedpain response

Injury

X

HYPERALGESIA

Stimulus intensity

Pain intensityfor stimulus X

normalpain response

Pain intensityfor stimulus X

sensitisedpain response

ALLODYNIA

Pain

inte

nsity

10

8

6

4

2

0

• HYPERALGESIA

• ALLODYNIA

CLINICAL PAIN (PATHOPHYSIOLOGICAL

PAIN )

Vanished after healing

Chronic PainX

Clinical Features of Postoperative Pain

Primary Hyperalgesia

Secondary Hyperalgesia

Basic Principle of Postop Pain Management is

PreventiveMultimodal Analgesia

Peripheral and

Central sanitizationprevent the occurrence of

reduced the process of NeuroplasticityBy Giving

Anti-hyperalgesic & Anti-allodynic drugs

Anti-hyperalgesic Therapy: Opioid-Sparing

~30%reduction

Opi

oid

Opi

oidPa

in in

tens

ity

XStimulus intensity

Anti-hyper

algesic

Normalpain

response

Sensitisedpain response

Partially desensitisedpain response

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 AnalgesiaNot 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.

• Some drugs may act at several point at nociceptive

pathway.

Local anesthetics

CorticosteroidsNSAIDsCOXIBs

Local Anesthetic

CNS

DRG

OpioidsGabapentinoids

Clonidine

Modify by AHT

KetaminParacetamol

COXIBs

Transduction

TransductionModulation

Perception

TransmissionModulation

Target Point of Analgesic Drugs

ANALGESIC DRUGS

NONOPIOIDS OPIOIDS ADJUVANTS• Mild Opioid( codeine & tramadol )• Strong Opioid( Morphine & Fetanyl )

• Paracetamol• NSAID (nonselective)• Coxib (selective NSAID)

•Steroid (dexamethason)•Alpha2 agonist (Clonidine)•Ketamine (NMDA

antagonist)•(gabapentin & pregabaline)

OPIOIDSNEURAXIAL BLOCKSPERIPHERAL NERVE

BLOCKS

NON-OPIOIDANALGESICS

ADJUVANTS

MULTIMODAL

ANALGESIA

Multimodal Analgesia

Potentiation

Opioid

Paracetamol NSAIDs or Coxibs

Nerve blocks

What is the most regiments

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

Ketamine Dexamethazone

Alpha;2 AgonistsGabapentinoids

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

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

1. Can be given to all age – from Infant to Elderly

2. From pregnant to Lactating Woman

3. Can be used for patients with renal and

hepatic impairment.

Paracetamol

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 88(2): 199–214.

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

Qualitative Review of Paracetamol, NSAIDs-or their Combination in postoperative pain.

Quantitative Systemic Review 2010Paracetamol and NSAIDs (cox1 and cox2)

Combination of paracetamol and an NSAIDs may offer superior analgesia

compared with either drug alone

(Anesth Analg 2010)

SYSTEMIC REVIEWNSAIDs vs COXIBs For Postoperative Pain

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.

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

Combination of paracetamol and parecoxib may useful in patients

who are susceptible to haemorrhagic complications of NSAIDs

Parecoxib and Acetominophen

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

Paracetamol + Tramadol

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

ParacetamolOral route available – give

orally

NSAID and

Paracetamol

ParacetamolPain decreases 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 SettingAn 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; 116:248-73

Multimodal Analgesia

Improved Analgesia

Lowered Dose Reduced Side Effects

• Early Mobilization• Early Enteral Feeding• Rapid Recovery • low cost

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

prevent the occurrence of chronic pain after surgical

Crile 1913

“Patients Given Inhalation anesthesia still need to be protected by regional anesthesia, otherwise they might suffer persistent central nervous systems changes and enhanced postoperative pain ”

Stated That: This is not new

Thank youvery much

Paracetamol NEW but OLD DRUG

Route of Administration Orally Rectally Intravenously available in Indonesia since 2009

Bertolini A, et al CNS Drugs reviews, 2006;12:250-275

Acetominophen/PAAP

Analgesic Effects Antipyretic Effect

No Anti-Inflammation Effect