Pain Management in Anaesthesia

8/2/2019 Pain Management in Anaesthesia

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Background 50% of all consultations in primary

healthcare are pain-related

40% have suffered more than 3 months85% suffer from musculoskeletal pain

Chronic pain = poor quality of life, suffering,

reduced ability to work and poorer socialfunction



Why treat pain? Untreated pain increases anxiety and pain perception.

Stress response is invoked by pain (andanxiety!).Neuroendocrine response (ACTH, Epi, NE,glucagon, etc increased)

Results: Increased VO2, CO2 production, catabolic state

The more pronounced the stress response, the higher the

mortality. Animal models show that repeated pain during “infancy”

causes alterations in the adult brain: Altered painsensitivity, anxiety, hyperactivity, impaired social skills,self-destructive behavior.



As anaesthetists We need to understand pain

We need to prevent pain and chronification – perioperative analgesia!

When needed, we have to know how to treat chronic

pain conditions



Agenda Physiology of pain

Acute and chronic pain

Nociceptiv versus neuropathic pain

Strategies for the treatment of established painconditions

Some pharmacological principles for analgetic drugs

Conclusion



Definition IASP (International Assosiation for the Study of Pain):

Pain is an unpleasant sensory and emotionalexperience associated with actual or potenial tissuedamage, or described in terms of such damage.

Pain is what the patient describes as painful.



Pain

Depression/anxiety Sleep disturbance

The pain triangle



Pain has a purpopse

Localise pain stimulus aninitialise responses in order

to reduse tissue damage

Initialise actions andaffective reactions that can

influence future behavior



Pain has a purpose ? But:

Intense and prolonged pain signals will lead to changes

in the pain signal pathways that may lead to thedevelopment of chronic pain!



Chronic pain after surgeryPerkins and Kehlet, Anesthesiology 93:1123, 2000

11 %Inguinal hernia

3 –

56 %Gallbladder surgery

11 – 57 %Mamma surgery

47 %Thoracotomy

30 – 81 %Extremety amp.

IncidenseSurgery



And this is one reason to Optimise the perioperative analgesia

Preemptive/preventive analgesia-premedication

Intraoperative analgesia Postoperative analgesia

Basics – paracetamol + NSAIDs

PCA/NCA

Epidurals or continuous regional blocks Loco-regional analgesia

Field blocks

Thoracic epidurals



Pain

Acute - chronic

Physiologic

Somatic nociceptiv

Neuropathic



Physiological Pain

(Cervero and Laird, 1991)

“A brief noxious sensation that initiatesalerting/withdrawal responses limitingtissue injury”



Nociceptors: “Peripheral Pain Detectors”

Nociceptors are primary afferent neurons found inskin, bone, muscle, joints and some visceral tissues.

Nociceptors

Nociceptor activation initiates an inward Ca++Current (generator potential) which depolarizes sensorynerve fibers (A-delta and c fibers)

Ca++

NoxiousMediators,PGE-2, BK,

sP

Na+



Nociceptive (Somatic) Pain

Activation of nerve endings in somaticstuctures (skin, muscle, bone) in

response to irritation or injury Pain is persistent, well localized, sharp

or crushing

Includes: trauma, surgical pain, tumorinvasion, arthritis and muscle spasm



Nociceptive (Visceral) Pain

Activation of nerve endings in gastro-intestinal organs and peritoneum in

response to irritation or distentionPain is persistent, poorly localized

cramping, periodic (colicky)

Includes: bowel or urethral obstruction,peritonitis and appendicitis



The primary noxiousmediator released fromdamaged tissue isprostaglandin (PG)

PG is responsible fornociceptor activationand sensitization

PG plays a major rolein peripheralinflammation

Nociceptor Activation (Transduction)



Is modulated by the number of chemical substances.

Mediators influence ;

Degree of nerve activity

Intensity of pain sensation

Repeated stimulation causes sensitization of the nerve

fibers causing; Lower pain threshold

Spontaneous pain

Chemical signaling protect the injury area by producing behaviours that keep away from thestimulus.



Sensitization:

Tissue Injury

Repetitive Stimulation of C-fibers

Progressive Increase in Action Potentials

Prolonged Increase in Spinal Cord Excitability



Neural Responses to Tissue Injury

Primary hyperalgesia:

- Increased pain sensitivity at the injury site

- Related to peripheral release of cellular orhumoral noxious mediators

Secondary hyperalgesia:

- Increased pain sensitivity at adjacent,uninjured sites

- Related to changes in excitability of spinalneurons

Urban and Gebhart, Med Clin North Am 1999; 83: 585



Pain Transmission After Traumatic

Injury (Hyperalgesia)

Textbook of Pain 4th Edition 1999, Wall and Melzack;Churchill Livingstone, New York: 451

PNS

CNS

Pain

Low intensity stimulus

Hyperexcitabledorsal horn neuron

Sensitized nociceptor

A and C

Low threshold

mechanoreceptor A



Action potential is produced

Transmitted by nociceptive nerve fibers to the dorsalroute of the spinal cord.

The fibers synapse with ascending spinothalamicfibers to the CNS

These spinothalamic fibers are clustered into two

specific pathways; A delta fibers innervates cells of the lamina I (MARGINAL

ZONE)

C fiber innervates cells of the lamina ii (SUBSTANSIA GELATINOS)

Through synapsing of nociceptive fibers with motorfibers in the SC muscle rigidity can occur. It can lead tohypoventilation and hypoxemia.



signals can be altered by electrochemical means tomodulate the sensation, either to amplify it ordiminish it.

significant areas for modulation are at the junction of

the peripheral and central nervous systems, at thedorsal horn, and in the ascending and descendingtracts to and from the brain



Glu

Glu

Glu

SP

GluSP

SP

Glu

SP

Mg++

-

-

NK-1Receptor

AMPAReceptor

NMDAReceptor

Primary AfferentNerve Fiber

Spinal Sensory Neuron

InhibitoryInterneuron

Pain Processing in Spinal Cord

Second MessengerFormation

Ca++

Glu

Na+

Copyright

R. Sinatra MD2002Spinal Cord Neuron

GlycineReceptor

GLY

Neurochemical Anatomical Alterations



A-fiberConnections

AxonSprout

Synaptic

Removal

MicroglialCells

NOS

Nitric Oxide

2nd Messengers, (IP, PK, cGMP)

Genome Activation, RNA& Protein Synthesis,Hyperexcitability, Toxicity

NONO

NO

NO, PG

Aracadonic Acid

COX-2

PGE2, PGI2

InterneuronCell Death

Inflammation

HyperexcitabilityToxicity?

NMDA

PG

PG

PG

NO,

PG

Neurochemical-Anatomical AlterationsLeading to Persistent Pain

++

Ca++

sPGlu

Glu

CopyrightR. SinatraMD, 2002

Spinal Sensory Neuron

Primary AfferentNerve Fiber

Interneuron



The neurochemistry of these processes involves anextraordinary array of compounds, including

endorphins

neurokininsprostaglandins,

biogenic amines,

GABA,neurotensin

cannabinoids

purines and many others



PERCEPTION Pain message reaches the center of the brain where is

percieved.

Pain sensation transmitted by the marginal zonereaches the thalamus, while those by the substansiagelatinos reaches the brainstem, hypothalamus andthalamus.

Projections is made to the limbic system then tothesensory cortex in the parietal lobe and allow clientto describe the sensory characteristics of the pain



MODULATION Production of endogenous opoids by the CNS such as

beta-endophins.

It inhibits the production of substance p and blocktransmission of pain sensation in the spinal cord andproduces analgesia.



Neuropathic Pain

Pain caused by irritation(inflammation!) or direct injury

or dysfunction of the peripheralor central nervous system.

Neuropathic pain is usually continuous and described asburning, electrical and shooting



It may mimic the quality of somatic pain, but also isfrequently described in terms that warrant thedescriptor “dysesthetic:” an uncomfortable, unfamiliar

sensation such as burning, shock-like or tingling. Neuropathic pain syndromes may be associated with

referred pain, allodynia (pain induced by non-noxiousstimuli, e.g. light touch), hyperalgesia (increased

response to a noxious stimuli), or hyperpathia(exaggerated pain responses following a stimulus, oftenwith aftersensation and intense emotional reaction).



Treatment of pain patients; a practical

approach

Investigation and examination

Diagnosis

Treatment-strategy

Pre-op

Intra-op

Post-op



Importance of Perioperative Pain Management

Prevention and effective relief of acute perioperativepain may:

Improve clinical outcomes

Decrease complications

Improve quality of life

Improve patient satisfaction



NMDA-Antagonists

Ketamine 0.2-0.5mg/kg

Acetaminophen- 650mg maxi◦ Mechanism of action uncertain

◦ Peripheral Decreased prostaglandin synthesis

Interference with NO pathways

◦ Central Modulation of descending pain pathways Modulation of dynorphin release

◦ Excellent safety profile at doses of 1g Q 6 hours

◦ Toxicity (>4g/d)

Hepatotoxicity



NSAIDs

◦ Advantages: Anti-inflammatory, analgesic, limited sedation,non-addicting, +cheap, available OTC

◦ Concerns: available OTC in multiple preps, GI effects, renal and hepatic toxicity, platelet effects, f luid retention

Ketorolac◦

Potent analgesic◦ Mild anti-inflammatory ◦ Absence of ventilatory or cardiac depression◦ May cause excessive GI bleeding (limit course to 5d)◦ Meta-analysis

36% reduction in opiate requirements Ketorolac 10-30mg equivalent to Morphine 10-12 mg Onset less than 10 min Duration 6-8hrs



Anticonvulsants

Pro: Neuropathic pain: lancinating, burning

Con: Ataxia, sedation, confusion (esp elderly)

DrugsCarbamazepine (Tegretol) Gabapentin (Neurontin), Pregabolin (Lyrica)

Lamotrigine (Lamictal)

Topiramate (Topomax), Zonisamide (Zonegran)

Oxcarbazepine (Trileptal), Clonazepam (Klonapin)**



Intra op and post op Regional anesthesia

◦ Spinal◦ Epidural

◦ Peripheral nerve blocks

Local anesthesia◦ Well documented

◦ Injection of triggerpoints and myoses◦ Should be used routinely on all operations◦ Long duration preferrable◦ Combination with steroids

D d i i t ti



Drug administration

NSAIDs-Coxibs Paracetamol

Steroids

Co-analgetics Opioids



Paracetamol and NSAIDs Both groups are ”weak analgesics” – former peripheral

analgesics

Both over-the-counter

Both are combined by many

NSAIDs vs. coxibs



Paracetamol: do we use enough?

Dosage:

Children: 15 mg/kg, recommended daily dose 45 mg/kg,max 60-75 mg/kg

Does not divide between per-oral and rectal

Adults: 500-1000 mg X 3

70 kg = 14,3 mg/kg, max daily dose 43 mg/kg



Facts ?

Anti-pyretic effect: 12-15 mg/l – central effect!

Analgesia ??

Relative bio-availibility of rectal administration = 0.54(Anesthesiology 1999; 90: 411-421)

Relative prolonged upptake (35 vs. 4,5 min) rectal,upptake starts later (40min)



Facts?

Analgesic effect is correlated to peak plasmaconcentration – transfer to CSF?

Intravenous>peroral>>rectal

Longer halflife in CSF than plasma (3.2 hours versus

2.4, Br J Clin Pharmacol 1992; 34: 79-81)



Paracetamol dosing

Acute pain, adults >50 kg: 1,5-2g, then 1gx4

Acute pain, adults < 50 kg: 1-1,5g, then 1gx4

Children, suppositories: first dose: 30-40mg/kg, then15mg/kg x 4

Children, per-oral: first dose 20-30mg/kg,then 15 mg/kg x 4

* Iv paracetamol!



Experience on patients



Combination in acute pain Author n Typeoperation

efficacy

Breivik EK 1999 120 Oral surgery Diclofenac 100 + Parac 1g= D 100 mg + P 1g > D >P+K > P

Siddik SM 2001 80 CS Diclofenac 100 +Propacetamol 2g >= D 100> Propa 2 > Placebo

Montgomery 1996 60 AbdHysterectomy

Diclofenac100 + Paracet1,5g > D 100 > P 1,5 g

Fletcher D 1997 60 Back surgery Ketoprofen 50 mg +propacetamol 2g > K 50>/= P 2g > Placebo

Dahl V 2000 60 ACL-plastic Ibuprofen 800 mg +paracet 1g = IB 800 >

Paracet



Steroids Well documented in surgery and other acute pain

conditions

Analgesia and less PONV

Metabolic effect: Good against kacheksia?

Cheap

Little side-effects in short-time use

Dexamethasone 8mg iv



Opioids: The Alternative Buffet



Opioids most opioids = μ-receptor agonists

Genetically codet several subunits μ-receptors

Patients are different – different efficacy and side-effects of the different opioids

Dose/response varies from patient to patient

Combination with paracetamol/NSAIDs



Sites of Opioid Action Peripheral nerve endings◦ Stim of peripheral opioid receptors may block central transmission

and release of inflammatory mediators (beta endorphin,proenkephalin A)

Dorsal horn, spinal cord◦ Dynorphin, enkephalin rich

Midbrain, brainstem, thalamus◦ Dynorphin, enkephalin rich,◦

Receive beta endorphin innervation from hypothalamus

Limbic system, cortex◦ Emotional dimension of pain, rich in dynorphin, enkephalin,

have beta endorphin input as well



Opioids Effects Nausea, vomiting Ileus, constipation

Pruritis Sedation, confusion Respiratory depression Bradycardia Cough respiration Tolerance Dependence Addiction



”Weak” opioids Codeine (Kodein®, Pinex Forte®)

Tramadol (Nobligan®)

Buprenorfin (Temgesic®, Subutex®, Norspan®)



”strong” Opioids Morphine (inj, epidural, oral, Dolcontin®) Ketobemidone Pethidine Oxycodone (Oxynorm®,Oxycontin®) Pentazocin (Fortralin®)

Hydromorfon (Palladon®)

Fentanyl (Leptanal®, ActiQ®, Durogesic® )

Sufentanil (Sufenta®)

Alfentanil (Rapifen®)

Remifentanil (Ultiva®)



Opiates

Effective Analgesics

Variety of Administration Routes

Adverse events with opiate usage Drowsiness and sedation (30%)

Nausea and Vomitting (31%)

Pruiritis (18%)

Urinary Retention(17%) Ventilatory Depression(3%)

Tolerance



Morphine Prototypical opioid

Slower onset (5-10min)

Causes histamine release

Careful in renal patients IV, PO, epidural, spinal

Dosage; 1-4mg IV bolus

1-10mg IV infusion

Duration;

3-4hrs



Hydromorphone

Congener of morphine

Less accumulation in renal/hepatic insufficiency

Faster onset than Morphine (3-5min) More potent than Morphine

Dosage;

0.2-1mg bolus

0.2-2mg infusion



Fentanyl Synthetic, highly lipid soluble

Fast onset(1-5min), short duration(0.5-4hrs)

IV, respiratory depression can be profound, but brief due to redistribution of drug

Transcutaneous—stable drug level at 12- 24 hr; IV, PO,Epidural, spinal

Dosage; 25-100mcg bolus

25-200mcg infusion



Meperedine

Less potent than morphine

Onset; 5-10min

Duration; 2-4hrs

May actually cause tachycardia

Active metabolite-normeperidine—CNS excitation,

seizures Dosage;

75-100mg IM



Opioids As little as possible

Opioid rotation

Avoid combination preparations

Per-oral, slow release

For non-malign pain: make agreements withthe patient ( WHO guidelines)



WHO-guidelines

• All other treatment options must havebeen tried

• The pain must be opioid sensitive

• Psychosocial status must be known

• Written agreement

• Preferrably long-acting opioids

• Treatment must be monitored

Eija Kalso, SASP, WHO

B e

E l ti



eh a n d l i n g

Evaluation• Pain intensity:

numeric (NRS):

or visual analog scale (VAS):

• Psychometric methods (HAD, GHQ)

• Quality og life (SF-36, EORTC)

Ingen

smerter

Verst

tenkelige

smerte

(10 cm)

Ingen

smerter

Verst

tenkelige

smerte

0 1 2 3 4 5 6 7 8 9 10

5. PerceptionM l i d l A l i



5 e cept o

3. Transmission

1. Transduction

Multimodal Analgesia

--

Copyright R. Sinatra MD.2002

6. CNS Responses

Muscle Relaxants,Beta Blockers

NSAIDS, COX-2 Inhibitors, Anti-Histamines, TopicalLocal Anesthetics

Peripheral Nerve Block

Local Anesthetics

Epidural BlockLocal Anesthetics

Opioids,Clonidine,

COX-2 Inhibitors

Opioids, Paracetamol,Clonidine, Ketamine,Gabapentin, Tricyclics

PAIN

4. Modulation

2. Conduction



Conclusion 1

Pain is what the patient say it is

Acute pain may become chronic pain, especially when

under-treated

Neuropathy: Pain caused by pathology in the painsignalling system

Patient investigation: Nociceptive, neuropathic ormixed pain?



Conclusion 2 Time limited plan for treatment

Multimodal pharmacological treatment

Multidisciplinary treatment

Simultaneousness

Pain Management in Anaesthesia

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