Pain Process after Surgery & Use of NSAID in Pain Control

Professor Dr. Win KoDepartment of Orthopaedics &

TraumatologyUMM

Prof; Win Ko

Prof; Win Ko

NocioceptorsNocioceptors are free nerve

endingsHigh thresholdUbiquitous distributionChemically activated in

response to tissue damageNocioceptors can be sensitized

Prof; Win Ko

Slow pain◦C fibers, unmyelinated, slow burning

aching pain, Substance P

Fast pain◦A delta fibers, myelinated, sharp

prickly pain, glutaminergic

Prof; Win Ko

How postoperative pain generate?

Prof; Win Ko

A delta fibers project to projection neurons in laminas I and V

C fibers project to projection neurons in lamina II

Both also project to inhibitory and excitatory interneurons

Prof; Win Ko

Dorsal Horn SynapsesNeurotransmitters

◦ Glutamate◦ Substance P◦ CGRP◦ CCK◦ Opiates

Receptors◦ NMDA◦ Neurokinin-1◦ ?◦ ?◦ Endorphin (mu,

kappa, sigma)

Prof; Win Ko

Prof; Win Ko

Prof; Win Ko

Modulation of Pain Information

Gate Control Theory◦ Nocioception arises from activation of

nocioceptors◦ Pain sensation is a product of several

interacting neural systems◦ Afferent transmission relies on a balance in

the activity of both the pain fibers and large proprioceptive/mechanosensory fibers

◦ Inhibitory interneurons are spontaneously active and inhibit projection neurons

Prof; Win Ko

Causes of postop pain1. Incisional- skin and subcutaneous tissue2. Deep- cutting, coagulation, trauma 3. Positional- bed sore, nerve compression &

traction4. IV site- needle trauma, extravasation, venous

irritation5. Tubes- drains, nasogastric tube, ETT6. Respiratory- from ETT, coughing, deep

breathing7. Rehab- physiotherapy, movement, ambulation8. Surgical- complication of surgery9. Others- cast, dressing too tight, urinary

retention

Prof; Win Ko

Factors affecting postop painA. Surgical factors: 1. site of incision and nature of the

surgeryupper abdomen > thoracotomy >

lower abdomen > limbs2. complications, eg wound infection,

intraabdominal sepsis, distension

B. Patient factors:Psychology, genetic, hx of substance

abuse, hx of chronic pain

Prof; Win Ko

Consequences of poorly managed acute post-operative painThe Patient suffers

◦ CVS: MI, dysrhythmias◦ Resp: atelectasis, pneumonia◦ GI: ileus, anastamosis failure◦ Endocrine: “stress hormones”◦ Hypercoagulable state: DVT, PE◦ Impaired immunological state

Infection, cancer, wound healing

◦ Psychological: Anxiety, Depression, Fatigue, Sleep Deprivation

◦ Chronic Pain

Prof; Win Ko

Postsurgical Stress ResponseResults in increased oxygen

consumption, increased carbon dioxide production, hyperglycemia, and generalized catabolic state with negative nitrogen balance

The magnitude of the response correlates with mortality

Prof; Win Ko

Why Treat Pain?Basic human right!↓ pain and suffering↓ complications ↓ likelihood of chronic pain

development↑ patient satisfaction↑ speed of recovery → ↓ length of

stay → ↓ cost↑ productivity and quality of life

Prof; Win Ko

Questions Regarding Pain ControlWhat about the 20% who do not get relief

from the WHO ladder or the 46% of those whose families stated we failed?* ◦ Have the opioids been titrated aggressively?◦ Is the pain neuropathic?◦ Has a true pain assessment been accomplished? ◦ Have invasive techniques been employed?◦ Have you examined the patient?◦ Is the patient receiving their medication?◦ Is the medication schedule and route

appropriate?

*Tolle 2001

Prof; Win Ko

Management of postoperative pain1. Optimal postoperative pain management begins in the

preoperative period

2. Measure pain regularly using a validated assessment tool

3. Ensure all postoperative patients receive safe and effective analgesia

4. Monitor and manage adverse effects

5. Communicate ongoing pain management plan to both patients and primary healthcare professionals at discharge.

Australian and New Zealand College of Anaesthetists Acute Pain Management: Scientific Evidence, 2nd ed, 2005, updated Dec 2007Therapeutic Guidelines: Analgesic, Version 5, 2007

Prof; Win Ko

Pain Assessment

Pain History◦O – Onset ◦P – Provoking / Palliating factors◦Q – Quality / Quantity◦R – Radiation◦S – Severity ◦T – Timing

Prof; Win Ko

Pain Assessment Visual Analogue Scale

Prof; Win Ko

Pain

Step 1±Nonopioid± Adjuvant

Pain persisting or increasing

Step 2Opioid for mild to moderate pain

±Nonopioid ± Adjuvant

Pain persisting or increasing

Pain persisting or increasing

Step 3Opioid for moderate to severe pain

±Nonopioid ±Adjuvant

Invasive treatments

Opioid Delivery

Quality of Life

Modified WHO Analgesic Ladder

Proposed 4th Step

The WHOLadder

Deer, et al., 1999

Prof; Win Ko

Multimodal Analgesia

Using more than one drug for pain control◦Different drugs with different mechanisms/sites of

action along pain pathway◦Each with a lower dose than if used alone◦Can provide additive or synergistic effects◦Provides better analgesia with less side effects

(mainly opiate related S/E)

Always consider multimodal analgesia when treating pain

Prof; Win Ko

Prof; Win Ko

Acute Pain Transmission

Prof; Win Ko

Prof; Win Ko

Prof; Win Ko

NSAIDs Mechanism

◦ Block cyclooxygenase (COX) enzyme → ↓ prostaglandin synthesis Preferential COX-1 inhibitor – aspirin,

indomethacin, piroxicam; Nonselective COX inhibitor – diclofenac,

ibuprofen, naproxen; Preferential COX-2 inhibitor – meloxicam,

nimesulide; Selective COX-2 inhibitor – celecoxib, rofecoxib, valdecoxib, parecoxib, etoricoxib.

Prof; Win Ko

Prof; Win Ko

Cell Membrane Phospholipids

Arachidonic Acid

Phospholipase

Prostaglandins Prostaglandins

Gastric ProtectionPlatelet Hemostasis

Acute PainInflammationFever

COX-2 COX-1

Prof; Win Ko

NSAIDs

-         Mild and moderate pain-         Opoid sparing-         SE: peptic ulcer and bleeding,

platelet aggregation inhibition, bronchospasm, renal impairment, allergy

- Do not use celecoxib is history of anaphylaxis or severe cutaneous reaction (Steven-Johnson sydrome, etc.) with a sulfonamide

Prof; Win Ko

NSAIDs

Warnings: ↓dose / avoid if◦ GI ulceration ◦ Bleeding disorders / Coagulopathy◦ Renal dysfunction◦ High cardiac risk – COXII inhibitors◦ Asthma◦ Allergy◦ hypovolaemia, ◦ pregnancy, breast feeding

?Avoid celecoxib if allergic to Sulpha

Concern for anastomotic leaks?

Prof; Win Ko

Prof; Win Ko

Prof; Win Ko

COX-2 inhibitor

No effects on platelets!

Better GI tolerability◦ Less dyspepsia, less N/V

Equivalent analgesic efficacy with non-selective COX-inhibitors

Prof; Win Ko

Prof; Win Ko

Contra-indications to NSAIDs

Patients with the “ASA triad”◦ Risk of severe asthma, angioedema

precipitated with COX-inhibitor

Renal insufficiency or risk there of ◦ especially if risk of hypovolemia periop◦ Patient on ACE inhibitors or ARBs◦ Vascular patients having aortic cross-clamp

and/or probable angiogram peri-operatively

Prof; Win Ko

Contra-indications to Celecoxib/NSAIDsPoorly controlled hypertension

◦ Especially if pt. is on ACE inhibitor, potent loop diuretics

Congestive heart failure◦Fluid/sodium retention

Active peptic ulcer disease

Prof; Win Ko

Acetaminophen

Typical dose: 650 to 1000 mg PO Q6H

Inhibit prostaglandin synthesis in CNS → analgesia

Max dose: 4 g / 24 hrs from all sources

Warning: ↓ dose / avoid in those with liver damage

Prof; Win Ko

Paracetamol is a centrally acting agent

Action depend on the bulbo-spinal serotoninergic pathway

It selectively inhibits nervous system PG synthesis probably via COX-3

Paracetamol hepatotoxicity was found to be very rare (<1 / 2,500

Prof; Win Ko

KetorolacPotent AnalgesicParenteral (IV or IM)15-30 mg Q 6hrPatients Older than 16 yrsShould not Exceed 5 days

Prof; Win Ko

Cox-2 Inhibitors

Drug Dose

Celecoxib (Celebrex) 100-200mg PO Bid

Rofecoxib (Vioxx)

Valdecoxib (Bextra) 10-20mg PO Qd

Parecoxib 20-40mg IM20-100mg IV

Prof; Win Ko

Prof; Win Ko

Celecoxib OR Diclofenac

□ Celecoxib 200 mg po daily X 3 days

□ Diclofenac 50 mg po q8h X 3 days (may give first dose PR)

□ Diclofenac 50 mg pr q12h X 3 days

Prof; Win Ko

NSAID, Coxibs and Acetaminophen

CONCEPT # 1The foundation of all acute pain Rx

protocols. ”First on last off”

sole agent in mild /moderate pain Analgesic efficacy is limited inherently In contrast, with opioids efficacy is limited by

S/EOpioids added as requiredopioid sparing effect 30-60 %

Prof; Win Ko

COX-INHIBITORS vs. OPIOIDS

EfficacyLimited Inherently Limited by S/E

Inter-patient dose variabilitySmall Large, making dose

titration difficult

Life threatening complicationsUpper GI bleeding Resp. depression

With chronic use Risk is early

Prof; Win Ko

COX-INHIBITORS vs. OPIOIDS

Toxicity, S/ETissue/organ toxic neurologic

dysfunc Drug tolerance

Not evident tolerance is part of

normal response

Abuse potentialNil Yes

Prof; Win Ko

Cyclo-oxygenase inhibitors

Acetaminophen

NaproxenCelecoxib

Ketorolac

Numerous others

Prof; Win Ko

Why a COX-2 inhibitor?

No effects on platelets!

Better GI tolerability◦ Less dyspepsia, less N/V

Equivalent analgesic efficacy with non-selective COX-inhibitors

Prof; Win Ko

Prof; Win Ko

THANK YOU