from preemtive to preventive analgesia - muhammad. ramli ahmad
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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
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FROM PREEMTIVE TO PREVENTIVE ANALGESIA
Muhammad. Ramli Ahmad
Department of Anesthesiology Faculty of Medicine
Hasanuddin University
Makassar
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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
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Introduction
Optimal Postoperative Pain Management
Progress in medical fields
WHO (2005) Pain : 5th vital sign
Postoperative Pain Management
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Introduction
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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
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Preemptive Analgesia
Pre - Incision Surgery Post operative
Incision(Noxious Signal)
• Prevent acute pain• Prevent chronic pain as
a result of untreated acute pain
Preemptive Analgesia
Combination of Local-Regional blockade & General Anesthesia
Pain stimuli : Central Sensitization & “Wind-Up”
• Prevent central sensitization
• hyperalgesia
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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
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Clinical study contradictory
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New insight
Kissin I, Preemptive Analgesia at the Crossroad, Anesth Analg 2005,100:754-756
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Preemptive Analgesia
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
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Preventive Analgesia
Pre - Incision Surgery Post operative
Incision(Noxious signal )
Preventive Analgesia
Duration of action from the agent is longer than preemptive target
Preventive Analgesia
or
Duration of action from the agent covering entire perioperative period
Broader definition of preemptive
Preventive Analgesia
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Preventive Analgesia
Pre- Incision Surgery Post operative
Incision(Noxious Signal)
Analgesic effect must covers entire perioperative period, whenever the drug was administered
Multimodal Analgesia
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Target of Preventive Analgesia
Perioperative period
Preoperative Intraoperative Postoperative
Peripheral & central sensitization
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Definition
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Preventive Analgesia
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
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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
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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”
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CENTRAL SENSI-
TIZATION
P A I N
Initial NoxiousStimulus
Changes inDorsal Horn
(e.g. surgical incision)
Preemptive Analgesia
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
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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
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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
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Clinical Applications of Preemptive Analgesia
Pro-Contra
Pre - Incision Post - Incision
Preemptive Analgesia
Post incisionalAnalgesia
• NSAIDs• Epidural Analgesics• Local Anesthetic Infiltration• Opioid• NMDA antagonist
RCTSs Review, Moiniche dkk.,
• Pain intensity• Onset rescue analgesic • Total analgesic requirement
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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
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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
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CLINICAL APPLICATIONS OF PREEMPTIVE ANALGESIA
NMDA RECEPTOR ANTAGONISTS
Pra-Incision Post-incision
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
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CLINICAL APPLICATIONS OF PREEMPTIVE ANALGESIA
LOCAL ANESTHETICS
Pra-Incision Post-incision
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
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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
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From Preemptive to Preventive analgesia
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Clinical Implication
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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
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Clinical Implication
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Clinical Implication (cont.)
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Clinical Implication (cont.)
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Korean J Anesthesia 2005:48:S 21-5
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British Journal of Anaesthesia 100 (2): 256–62 (2008)
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Reg Anesth Pain Med2008;33:44-51.
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Coll. Antropol. 31 (2007) 4: 1071–1075Original scientific paper
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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)
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• 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.
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• 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.
Katz J, Kavanagh BP, Sandler AN et al. Preemptive analgesia. Clinical evidence of neuroplasticity contributingto postoperative pain. Anesthesiology. 1992; 77: 439–46.
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• 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.
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• 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.
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PREVENTIVE ANALGESIA
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PREVENTIVE ANALGESIA
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Summary
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Thank you!