FROM PREEMTIVE TO PREVENTIVE ANALGESIA - Muhammad. Ramli Ahmad

CURRICULUM VITAE

Name : dr.M. Ramli Ahmad, Sp.An-KAP,KMN

Address : Jl. A.P.Pettarani Blok GA 7/9

Job : Dosen FK UNHAS

Education : - FK UNHAS

- Anestesiologi FK UNAIR

Organization : - IDI

- Ketua PERDATIN SUL-SEL

FROM PREEMTIVE TO PREVENTIVE ANALGESIA

Muhammad. Ramli Ahmad

Department of Anesthesiology Faculty of Medicine

Hasanuddin University

Makassar

0%

20%

40%

60%

Severe Pain Moderate Pain

31%47%

To breath, cough and move easier

INTRODUCTION

Surgery with Pain Control

Better pathophysiology & pharmacology at the end

1990-s

butMost patients still worried about post operative pain

Apfelbaum JL, Chen C, Mehta SS, Gan TJ. Postoperative pain experience: results from a national survey suggest postoperative pain continues to be undermanaged. Anesth Analg. 2003

Introduction

Optimal Postoperative Pain Management

Progress in medical fields

WHO (2005) Pain : 5th vital sign

Postoperative Pain Management

Introduction

Preemptive Analgesia

Before incision Surgery Post operative

Begin in early of 1920’s by Crile & Lower

Incision(Noxious signal)

Preemptive Analgesia Note :

Pain modulation by CNS takes a place before perception

Central nervous system (CNS) protection until post operative period


Pre - Incision Surgery Post operative

Incision(Noxious Signal)

• Prevent acute pain• Prevent chronic pain as

a result of untreated acute pain


Combination of Local-Regional blockade & General Anesthesia

Pain stimuli : Central Sensitization & “Wind-Up”

• Prevent central sensitization

• hyperalgesia

PREEMPTIVE ANALGESIA

Preemptive therapy (administration of drugs at pre-incision) was consider :

Prevent central sensitization hyperalgesia incidence severity of postoperative pain

but

Since the end of 1980-s, hundreds study (with various quality) failed to proved effectively of pain management at pra-incision compared to post-incision

Clinical study contradictory

New insight

Kissin I, Preemptive Analgesia at the Crossroad, Anesth Analg 2005,100:754-756


Preemptive analgesia problem is no more about timing (pre or post), but what is more important issues are:

1. Duration of Preemptive Analgesia , must include not only tissue injury phase but also phase of inflammatory process

2. Completeness of nociceptive blockade during both phases above

Kissin I, Preemptive Analgesia at the Crossroad, Anesth Analg 2005,100:754-756

Preventive Analgesia

Pre - Incision Surgery Post operative

Incision(Noxious signal )


Duration of action from the agent is longer than preemptive target


or

Duration of action from the agent covering entire perioperative period

Broader definition of preemptive



Pre- Incision Surgery Post operative

Incision(Noxious Signal)

Analgesic effect must covers entire perioperative period, whenever the drug was administered

Multimodal Analgesia

Target of Preventive Analgesia

Perioperative period

Preoperative Intraoperative Postoperative

Peripheral & central sensitization

Definition


Preventive analgesia is prevention

Prevent before central sensitization occur

Analgesic given prior to the surgery

A preventive approach that aims to block transmission of the primary afferent injury barrage before, during, and after surgery

Targets of a preventive Analgesia

Perioperative period

Preoperative (days before surgery and just minutes before skin incision)

Intraoperative (after incision to those initiated just prior to the end of surgery)

Postoperative (after the end of surgery and may extend for days thereafter

Preemptive to Preventive Analgesia

Earlier Definition:

Preemptive Analgesia has been defined as:

1. Antinociceptive treatment starting before surgery

2. Antinociceptive treatment that prevents central sensitization

New Definition:

3. Preventing centra sensitization induced by TISSUE INJURY and INFLAMANTORY INJURY (extending the period beyond the initial postoperative period)

Preemptive means “ preventive” but this not simply just “before incison”

CENTRAL SENSI-

TIZATION

P A I N

Initial NoxiousStimulus

Changes inDorsal Horn

(e.g. surgical incision)


PREVENTIVE ANALGESIA AS IMPROVEMENT OF PREEMPTIVE ANALGESIA

Preventive AnalgesiaTo

CENTRAL SENSI-

TIZATION

P A I N

Another NoxiousStimulus

(intraoperativemanipulation)

Postoperative Inflammation

Pain ManagementAlso applied intra-

& postoperative

Cousins MJ. Physiology and Psychology of acute pain. In Acute Pain Management: Scientific Evidence. Second Edition. Australian and Newzealand Collage of Anesthetists. Australia 2005. 1-17Moiniche SM, Kehlet H, Dahl JB. A Qualitative and Quantitative Systemic Review of Preemptive Analgesia for Postoperative Pain Relief. Anesthesiology 2002; 96:725-41Kissin I. Preemptive Analgesia at the Crossroad. Anesth Analg 2005; 100:754-6

Pain ManagementBefore Initial

Stimulus

TARGET

POSTOPERATIVE HYPERALGESIA

PERIODS : PRE (Pre emptive analgesia, pre emptive anti hyperalgesia)

INTRA

POSTOPERATIVE (general as well regional anesthesia)

DRUG MECHANISMS :

PRIMARY SENSITIZATION (PERIPHERY)

AINS

Local anesthetics

SECONDARY SENSITIZATION (CENTRAL)

NMDA receptors

Kétamine, Dextromorphan …

Voltage gated calcium channels (anti hyperalgesic drugs)

Gabapentine, gabapentinoids, Nefopam…

a2 adrenegic drugs descending inhibiting pathways)

Clonidine

PHARMALOGICAL CONTROL OF POSTOPERATIVE HYPERALGESIA

CONTROL OF HYPERALGESIA

Primary SecondaryBULBO-SPINALDESCENDINGINHIBITORYCONTROLS

MORPHINEa2 ADRENERGICS

(Clonidine)

N.S.A.I.Ds

“Inflammatory soup”

HistaminSerotoninBradykininProstaglandins.......................

Susbtance (SP)NeuropeptidesCGRPExcitatory A.A.....................……

• NMDA Receptors

• Voltage gated calcium channels

Péripheral

NMDA RECEPTOR Kétamine

Dextromorphan

CentralLOCAL

ANAESTHETICS

Proteinkinases

Protooncogen- C Fos- C Jun

Second messengerr

+

+

+

WIND.UP

Axon Reflex

5HTN.E.

Synapse

PREPOST

+

VOLTAGE GATED CALCIUM CHANNELS

. Nefopam

. Gabapentine

Clinical Applications of Preemptive Analgesia

Pro-Contra

Pre - Incision Post - Incision


Post incisionalAnalgesia

• NSAIDs• Epidural Analgesics• Local Anesthetic Infiltration• Opioid• NMDA antagonist

RCTSs Review, Moiniche dkk.,

• Pain intensity• Onset rescue analgesic • Total analgesic requirement

PREEMPTIVE ANALGESIA

Moiniche et alOng et al

Controversial

80 RCT

Evaluated preemptive analgesia of NSAID, epidural,

wound infiltration, opiate, NMDA antagonist

No difference in effectifitybetween preemptive analgesia

and post-incision analgesia

66 RCT

Evaluated preemptive analgesia of NSAID, epidural, wound

infiltration, opiate, NMDA antagonist

Epidural analgesia preemptive:

Pain intensity in 24-48 hours post-operative, onset of first

rescue analgesia, & total supplement analgesic

Local infiltration, NSAID, opiate, & NMDA antagonist preemptive: total supplement analgesic ,onset

of first rescue analgesia & failed to improved pain intensity

CLINICAL APPLICATIONS OF PREEMPTIVE ANALGESIA

NON STEROID ANTI INFLAMMATIONS DRUGS (NSAID)

Pra-Incision Post-incision

duration of analgesiaOpiate consumption in 24 hours

Incidental pain score

Ruben et al

No benefict effect

Moniche et al

Analgesic consumption Onset of First analgesic administration

Not improved pain score

Ong et al


NMDA RECEPTOR ANTAGONISTS


Positive effect of preemptive analgesic, uncertain dose response

McCartney et al

Analgesic effect not consistent Analgesic consumption (67%)

pain score (58%)

Ong et al

Activation of NMDA receptor has important role in central sensitization

On focus in preventive & preemptive analgesia


LOCAL ANESTHETICS


No epidural regiment that improve postoperative pain control,

Wound Infiltration, peripheral nerve block, and intraperitoneal infiltration regiment

had no benefit effect

Moniche et al

Wound Infiltration regiments decreased analgesic drugs consumption & extend duration of analgesia, but no effect

on pain score

Ong et al

Epidural regiment :

Improve pain intensityLong duration of action

Ong et al

Had more advantages than

Katz & McCartneyIts imporatant to give multimodal analgesic therapy at all perioperative periode

CLINICAL APPLICATIONS OF PREVENTIVE ANALGESIA

Central Sensitization & Neuroplasticity of Nocisepsy Input

Pra-Incision Intraoperative Intraoperative

More extent than preemptive analgesia, involved all perioperative pain control regiment

From Preemptive to Preventive analgesia

Clinical Implication

A QUALITATIVE SYSTEMATIC REVIEW OF THE ROLE OF N-METHYL-D-

ASPARTATE ANTAGONISTS IN PREVENTIVE ANALGESIA

Mc CARTNEY C.J.L., SINHA A., KATZ J. Anesth Anal 2004;98:1385-400

META ANALYSIS

USING A MEDLINE (1966 - 2003) AND EMBASE(1985-2003) SEARCH

FORTY ARTICLES MEETING THE INCLUSION CRITERIA OUTCOMES :

Primary reduction of pain, analgesic cunsumption Secondary : time for first analgesic request,

adverse effects

PREVENTIVE EFFECTS OF :

Dextromorphan (12 articles) = 67 % Ketamine (24 articles) = 58 % Magnesium ( 4 articles) = none

Clinical Implication

Clinical Implication (cont.)

Korean J Anesthesia 2005:48:S 21-5

British Journal of Anaesthesia 100 (2): 256–62 (2008)

Reg Anesth Pain Med2008;33:44-51.

Coll. Antropol. 31 (2007) 4: 1071–1075Original scientific paper

Summary of studies of preemptive and preventive analgesia according to target agent administered

AgentsNo. of studies

Preemptive effects(%) Preventive effects(%) Opposite effects(%)

Total No. effects(%)Positive Negative Positive Negative

Local anesthetics

65 8(10.7) 16(21.3) 27(36.0) 18(24.0) 6(8.0) 75(100)

Opioids 25 7(25.0) 5(17.9) 10(35.7) 3(10.7) 3(10.7) 28(100)

NSAIDs 25 3(11.5) 12(46.2) 1(3.8) 8(30.8) 2(7.7) 26(100)

NMDA anatgonists

31 5(13.2) 6(15.8) 19(50.0) 7(18.4) 1(2.6) 38(100)

Clonidine 2 0(0.0) 0(0.0) 2(100.0) 0(0.0) 0(0.0) 2(100.0)

Local anesthetics and opioids

21 4(17.4) 5(21.7) 7(30.4) 6(26.1) 1(4.3) 23(100)

Multimodal 6 2(25.0) 0(0.0) 2(25.0) 3(37.5) 1(12.5) 8(100)

Total 175 29(14.5) 44(22.0) 68(34.0) 45(22.5) 14(7.0) 200(100)

• Katz J, Clarke H. Preventive analgesia and beyond: current status, evidence, and future directions. In: Macintyre PE,

Walker SM, Rowbotham DJ, eds. Clinical pain management: acute pain. 2nd ed. London: Hodder & Staughton, 2008: 154-

99.



99.

Katz J, Kavanagh BP, Sandler AN et al. Preemptive analgesia. Clinical evidence of neuroplasticity contributingto postoperative pain. Anesthesiology. 1992; 77: 439–46.



99.

PREVENTIVE ANALGESIA

Summary

Thank you!

FROM PREEMTIVE TO PREVENTIVE ANALGESIA - Muhammad. Ramli Ahmad

Health & Medicine

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