preventive_analgesia

Postoperative Analgesia From Preemptive to Preventive

Ali Eissa, MDProfessor of Anesthesiology and Pain Management

Al-Azhar University in Cairo

“Head Start”Pain like symphonic music, no two people experience it the same way.

Comfort level and recoveryPossibly increasing their self-efficacy in dealing with pain or in mobilization

Different Tissues IncisionSpecific contribution of different tissues to pain-related behaviors and neuronal hyperexcitability after incision.

Postoperative Analgesia: From Preemptive to Preventive

Factors contribute to the development of acute postoperative pain.

INTRODUCTION

Factors contribute to the development of acute postoperative pain.

2- Nongenetic environmental variables • Expectations (anxiety plays a role in the occurrence of chronic pain after surgery)

• Cultural. • Dietary. • Preoperative noxious inputs, and Chronic pain (Already Sensitizes CNS).

1- genetic • Individual experiences that may begin in utero.


Ririe DG, Barclay D, Prout H, et al. Preoperative sciatic nerve block decreases mechanical allodynia more in young rats: is preemptive analgesia developmentally modulated? Anesth Analg 2004; 99:140–145.

A . Pre-operative Factors

Theunissen et al. Preoperative Anxiety and Catastrophizing A Systematic Review and Meta-analysis of the Association With Chronic Postsurgical Pain. ClinJ Pain 2012;28:819–841

INTRODUCTION


B . Intraoperative: discharge from cut primary afferents

and retraction.

1. Nerve growth factor.2. Inflamed tissues.

C . Postoperative: afferent inputs from regenerating wound.

1. Hyperexcitability and ectopic activity in injured and nearby uninjured primary afferents.

2. Inflammatory response.

Factors ontribute to the development of acute postoperative pain.

INTRODUCTION


Successful Surgery = Correction or Excision of The Pathology

But successful Postoperative Pain Releif

=Correct Mainly the Surgical Journey to Reach the Pathology

That Means

1. Different Layers.

2. Different Tissues. Different Mode of Actions3. Different Mediators.

Surgical Treatment Vs. Surgical Pain Treatment

Xu J, Brennan TJ. Guarding pain and spontaneous activity of nociceptors after skin versus skin plus deep tissue incision. Anesthesiology 2010; 112:153–164.

Spontaneous activity of afferent fibers in four groups:

• 1 day after sham procedure,

• 1 day after skin,

• 1 day after skin plus deep tissue incision,

• 7 days after skin plus deep tissue incision

Local chemicals paralleled pain-related behaviors after incision.

(NGF, cannabinoids, IL-6, ischemic mediators, and TRPV1-containing afferents)

The nature of intra-operative tissue damage and nerve injury.


INTRODUCTION


Crile GW. The kinetic theory of shock and its prevention through anoci-association (shockless operation). Lancet 1913;185:7–16

Multimodal Regimen Prevent Development of “anoci-association.”

Reynolds and Hutchins demonstrated that a procaine block during dental procedures prevented the appearance of referred tooth pain.

Hutchins HC, Reynolds OE. Experimental investigation of the referred pain of aerodontalgia. J Dent Res 1947;26:3–8

Wall PD. The prevention of post-operative pain. Pain 1988;33:289–90

In 1988, Patrick Wall coined the term “preemptive preoperative analgesia”

History

Preemptive Preoperative Analgesia

Bach S, Noreng MF, Tjellden NU. Phantom limb pain in amputees during the first 12 months following limb amputation, after preoperative lumbar epidural blockade. Pain 1988;33:297–301

McQuay HJ, Carroll D, Moore RA. Postoperative orthopaedic pain: the effect of opiate premedication and local anaesthetic blocks. Pain 1988;33:291–5

Smith CM, Guralnick MS, Gelfand MM, Jeans ME. The effects of transcutaneous electrical nerve stimulation on post-cesarean pain. Pain 1986;27:181–93

Wall introduced the term “preemptive preoperative analgesia,” with

specific reference to 3 clinical studies (Slide Bottom)


The PRE versus CONTROL the commonly used in the initial clinical studies on preemptive analgesia

None of which used the classic 2-group design*

*Classic 2- group design= Pre-operative Versus Intra-operative OR Post-operative Treatment


Experimental Preemptive Analgesia

Preemptive analgesia reduce postoperative pain.

Preemptive analgesia did not reduce pain behaviors beyond the expected duration of the analgesic effect.

Woolf CJ, Chong M-S. Preemptive analgesia-treating postoperative pain by preventing the establishment of central sensitization. Anesth Analg 1993;77:362–379.

Mehta A, Reynolds ML, Woolf CJ. Partial denervation of the medial gastrocnemius muscle results in growth-associated protein-43 immunoreactivity insprouting axons and Schwann cells. Neurosci 1993; 57:433–442.

Contradictory

Katz J. Phantom limb pain. Lancet 1997;350:1338

1- The preoperative phase• Interventions days before surgery.• Intervension minutes before skin incision.

Timing for drugs administration

2- The intraoperative phase• Interventions immediately after incision.• Interventions just before the end of surgery.

3- The postoperative phase • Interventions immediately after the end of surgery


Controversy and Confusion About Preemptive Analgesia

Katz J, Clairoux M, Kavanagh BP, Roger S, Nierenberg H, Redahan C, Sandler AN. Pre-emptive lumbar epidural anaesthesia reduces postoperative pain and patient-controlled morphine consumption after lower abdominal surgery. Pain 1994;59:395–403

Fagan DJ, Martin W, Smith A. A randomized, double-blind trial of pre-emptive local anesthesia in day-case knee arthroscopy. Arthroscopy 2003;19:50–3

• Intraoperative nociceptive barrage contributes to a greater extent to postoperative pain than does the postoperative nociceptive barrage (Katz et al.)

• While in (Fagan et al.) there was Nosignificant difference.


Classic Two Groups Comparison ?


Katz J, Cohen L. Preventive analgesia is associated with reduced pain disability 3 weeks but not 6 months after major gynecologic surgery by laparotomy. Anesthesiology 2004;101:169–74

Katz J, Cohen L, Schmid R, Chan VW, Wowk A. Postoperative morphine use and hyperalgesia are reduced by preoperative but not intraoperativeepidural analgesia: implications for preemptive analgesia and the prevention of central sensitization. Anesthesiology 2003;98:1449–60


Control Group Importance

• Despite there was significant difference in Pre-operative group Versus Intra-operative Treatment(pain &analgesic consumption).

• There was significant differenceIn both Treated groups Versus Control in pain disablity at home.


Klasen J, Haas M, Graf S, Harbach H, Quinzio L, Jurgensen I, Hempelmann G. Impact on postoperative pain of long-lasting pre-emptive epidural analgesia before total hip replacement: a prospective, randomised, double-blind study. Anaesthesia 2005;60:118–23


Timing Preoperative

Night before or Immediately before surgery

• Despite there was No significant difference in pain score .

• There was significant differenceIn analgesic consumption 48 hours postoperative.


Gordon SM, Brahim JS, Dubner R, McCullagh LM, Sang C, Dionne RA. Attenuation of pain in a randomized trial by suppression of peripheral nociceptive activity in the immediate postoperative period. Anesth Analg 2002;95:1351–7

suggesting that, postoperative factors contribute to a greater extent

to the outcomes than intraoperative factors.


Classic Two Groups with Control

• There was significant Increase in pain scorein Pre-operative group Versus Post-surgery group .

• Analgesic consumption did not differ evenin Control group.


Blumenthal S, Dullenkopf A, Rentsch K, Borgeat A. Continuous infusion of ropivacaine for pain relief after iliac crest bone grafting for shoulder surgery. Anesthesiology 2005; 102:392–7


Post-surgical Vs Control

NOT only Decrease in pain score Immediate postoperative

BUT also long time after surgery

Moiniche S, Kehlet H, Dahl JB. A qualitative and quantitative systematic review of preemptive analgesia for postoperative pain relief: the role of timing of analgesia. Anesthesiology 2002; 96:725–741.Ong CK, Lirk P, Seymour RA, Jenkins BJ. The efficacy of preemptive analgesia for acute postoperative pain management: a meta-analysis. Anesth Analg 2005; 100:757–773.Dahl JB, Mathiesen O, Moiniche S. ‘Protective premedication’: an option with gabapentin and related drugs? A review of gabapentin and pregabalin in the treatment of postoperative pain. Acta Anaesthesiol Scand 2004; 48:1130–1136.

Different Drugs and Techniques

• Peripherally acting or applied drugs give prolonged analgesia with less analgesic consumption (incision-induced sensitization of spinal dorsal horn neurons is maintained at least initially by excitation of primary afferent fibers ).

• The early diminishing effect of a pharmacologic treatment, the wound capable of generating pain behaviors equivalent to a post-treatment group.(Prologed Anti-hyperalgesic effect)

Explanations


Fake or Fact or Needs Explanations

Comparison of the reviews performed by Moiniche et al., Ong et al. and Dahl et al.

• Perioperative opioid may evolve 1. Acute opioid tolerance 2. Opioid-induced hyperalgesia.

• Opioid administration increase the expression of a particular type of N-methyl-D-aspartate (NMDA) receptors

Coadministration of opioids and low dose NMDA antagonists interfere with the development of acute opioid tolerance and opioid-induced hyperalgesia.

Improve pain relief and Reduce opioid consumptionEisenach JC. Preemptive hyperalgesia, not analgesia? Anesthesiology 2000;92:308–9Crain SM, Shen KF. Antagonists of excitatory opioid receptor functions enhance morphine’s analgesic potency and attenuate opioidtolerance/dependence liability. Pain 2000;84:121–31Kissin I, Bright CA, Bradley EL Jr. The effect of ketamine on opioid-induced acute tolerance: can it explain reduction of opioid consumption with ketamine-opioid analgesic combinations? Anesth Analg 2000;91:1483–8Li X, Angst MS, Clark JD. Opioid-induced hyperalgesia and incisional pain. Anesth Analg 2001;93:204–9Nesher N, Ekstein MP, Paz Y, Marouani N, Chazan S, Weinbroum AA. Morphine with adjuvant ketamine vs higher dose of morphine alone for immediate postthoracotomy analgesia. Chest 2009;136:245–52Nesher N, Serovian I, Marouani N, Chazan S, Weinbroum AA. Ketamine spares morphine consumption after transthoracic lung and heart surgery without adverse hemodynamic effects. Pharmacol Res 2008;58:38–44



Preemptive of Opioids

Glial cells are activated

Representing a driving force

(Pain facilitation)Maintain neuronal hyperexcitability in spinal

cord

Central Sensitization

Inflammatory cytokines



Central Sensitization

Diansan Su. et al. Lidocaine Attenuates Proinflammatory Cytokine Production Induced by Extracellular Adenosine Triphosphate in Cultured Rat Microglia. Aneth. Analg. September 2010 • Volume 111 • Number 3

Directly act on microglia.

Inhibiting the increase of intracellular calcium.

Attenuated the production of proinflammatory cytokines (including TNF-, IL-1, and IL-6).

LIDOCAINE




Fake or Fact or Needs ExplanationsAntinociceptive dorsal horn interneurons

Jonathan Short et al. A Single Preoperative Dose of Gabapentin Does Not Improve Postcesarean Delivery Pain Management: A Randomized, Double-Blind, Placebo-Controlled Dose- Finding Trial. Anesth Analg 2012 (December);115:1336–42

Prevent Pain = Stop The Neurochemical Cascade

• NMDA-R antagonists.

• Neuroprotection of antinociceptive dorsal horn interneurons.

• Arresting glial reaction.

In General Anesthesia, with Routine Doses of Opioids;

although unconscious, sensitization largely unaffected


SO,

START PREVENTIVE ANALGESIA


Preventive Analgesia

Pharmacological BlockadeOf The Pain Pathway

Perioperatively To Prevent

• CNS Pain Imprint• Sensitization• Chronic Postsurgical Pain

DrugEfficacy

DrugDurationof action

SufficientTreatment

Time


• Prolonged hypersensitivity is initiated during the injury period.

(Use drugs with prolonged anti-hyperalgesic effect) • Neuronal hypersensitivity and nociception after incision is mainly maintained by the afferent barrage of sensitized nociceptors.

(Use peripherally acting drugs)• Not the timing of administration (Pre, Intra-operatively or postoperative) but efficacy of an analgesic and antihyperalgesic intervention are most important for treating pain and hyperalgesia after surgery.

(Use potent drugs)• Extending a multimodal analgesic treatment into the postoperative period may be superior to preemptive analgesia.

(Use multimodal analgesic for sufficient time postoperative)

Take Home Messages

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