Novel Analgesia

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Novel Analgesia

• When the simple stuff just isnt enough

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Acute pain is simple

• Acute Pain is Nociceptive Pain
• Somatic nervous system
• Pain from nociceptors (pain receptors)
• Limited duration
• Varied Aetiology

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Acute pain model Periphery
Tissue injury
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Acute pain model CNS
Central Control
PAIN
opiate receptors
Action System
Gate control System

-
Fast fibres touch / pressure

T
SG

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Slow pain fibres
-


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Acute pain model Drugs
NSAID Paracetamol
And
As required opiate
Local, Regional and Neuraxial Techniques
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Or is it that simple?

• Contraindicated analgesics / Side effects
• Neuropathic component
• Neuropathies (diabetic)
• Opiate resistance
• Hyperalgesia

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Analgesic alternatives

• Non-Pharmacological
• Hypnotherapy
• Relaxation techniques
• Music
• Acupuncture / Acupressure
• TENS
• Cryotherapy

• Pharmacological
• Cannabinoids
• Systemic local anaesthetics
• Clonidine
• Gabapentin / Pregabalin
• Ketamine

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Non-pharmacological techniques Hypnotherapy

• Poor evidence
• Difficult to do large trials
• For the enthusiast only

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Non-pharmacological techniquesRelaxation

• Some evidence, Included in one Cochrane review
• RCTs very difficult
• If it helps it helps

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Non-pharmacological techniquesMusic

• Cochrane review
• It helps (a little)
• C.f. relaxation
• Clinical application unclear

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Non-pharmacological techniquesAcupuncture

• Cochrane review (acute pain) not complete
• Numerous trials variable results
• Very few placebo (sham acupuncture) controls
• Benefit generally seen when patients know they
  are getting acupuncture.
• More data in chronic pain

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Non-pharmacological techniquesTENS

• Loads of evidence for use in chronic pain
• It works (how much?)
• One good EBM review for acute pain
• It works
• Location of electrodes ? Important ?
• Lack of true placebo controls
• Trials with strong or sub noxious tend to do
  well

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Non-pharmacological techniques Cryotherapy

• Good RCTs and EBM reviews
• Works 25 -40 reductions in pain scores
  reported)
• Doesnt always seem to translate to better
  outcomes e.g. joint mobility with physio
• Does seem good at getting patients up and out
  fast!

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Pharmacological

• Cannabinoids
• Clonidine
• Systemic local anaesthetics
• Gabapentin / Pregabalin
• Ketamine

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Cannabinoids
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Cannabinoids

• Lots of interest
• Mainly chronic pain
• MS
• Ongoing research -
• Acute Pain Studies
• Little evidence for efficacy in acute pain
• Variable reporting of side effects
• Dependant on formulation

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Clonidine

• ?2 agonist
• Widely studied and used as per-operative
  analgesic
• Effective intrathecally
• Effective systemically
• Side effects
• Hypotension
• Sedation

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Systemic local anaesthetics

• Majority of evidence related to neuropathic pain
• It works
• Acute and chronic
• Big doses
• 1-5mg/kg/hr
• Side effects similar in frequency and severity to
  opiates

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Hyperalgesia

• Same stimulus - increased percieved pain
• Decreased dependance on initial stimulus
• Allodynia

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Hyperalgesia
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Nociceptive hyperalgesia
Tissue
Nerve
Trauma
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Opiate induced hyperalgesia

• Chronic opiate user
• Opiate abuser
• High intensity short term opiate administration
• Morphine
• Remifentanil
• Fentanyl

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Opiate induced hyperalgesia
Opioid
?-opioid receptor
Gs coupled opioid receptor
M3 glucuronide

NMDA receptor
On-cells In RVM
Spinal dynorphins
Antiglycinergic activity
Excitatory
Central sensitisation
Descending facilitation
Hyperalgesia
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Gabapentinoids

• Majority of studies looking at gabapentin
• Pregabalin likely to be similarly effective?
• Better tolerability
• Better absorption

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Gabapentin

• Analgesic effect distinct from anticonvulsant
  effect
• Analgesia via VGCa ionophores
• Reduces release of excitatory neurotransmitters
• Reduces hyperalgesia
• ? Dorsal horn neurons excitability

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Gabapentin

• Well studied in chronic pain and neuropathic pain
• Effective
• Acute pain less well studied
• 27 RCTs in postoperative pain
• Variation in techniques studied
• Single dose vs continued admin
• Doses 300 1200mg
• Preoperative vs postoperative

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Gabapentin

• ? pain relief in 19 / 27 trials
• ? opioid requirements in 21/27
• ? Better for movement related pain
• One dose finding study
• Demonstrated ceiling effect at 600mg single dose

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Gabapentin- Tolerability

• High incidence of side effects?
• NNtH Sedation 35
• NNtH Dizziness 12
• Reflect doses used
• Up to 1800mg in 24 hours
• Not titrated up
• Problem with day case surgery?

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Ketamine

• General anaesthetic agent
• Atypical
• Preserves CVS / resp function
• Airway reflexes / patency generally preserved
• Bronchodilator
• Analgesic
• Famous side effects
• Hallucinations

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Ketamine

• NMDA receptor antagonist
• NMDA receptors shown to have role in development
  of hyperalgesia
• Blockade of NMDA receptors may prevent
  development of opioid tolerance
• Established opioid sparing effect

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Ketamine

• Analgesic at low doses
• 10 of anaesthetic doses
• LOADS of studies
• Cochrane review
• It works
• 30-50 reduction in opiate doses
• Reduced PONV

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Ketamine

• Systematic reviews
• Subramaniam et al Anesth Analg 2004
• Analysed trials for quality and patient groups
• 21/38 trials showed benefit
• Opiate reduction in line with Cochrane (30-50)
• More benefit in major surgery
• More benefit shown in trials with high mean VAS
• No bias with quality of trial

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Subramaniam et al

• IV bolus
• Pre-incision
• Post-incision
• IV infusion
• PCA addition of Ketamine no benefit
• 1/5 trials positive (poor quality score)
• But no worsening of adverse affects!

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Ketamine

• How to give it?
• Single dose ?
• Continuous infusion ?
• Added to PCA X
• Epidurally ? ?

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Ketamine Side effects?

• Doses low
• Tolerability good in all trials
• Reduced PONV pruritis
• Some increased sedation
• Low incidents of hallucination / vivid dreaming
• Non sig in all trials

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Summary 1

• Acute pain is not as simple as once thought
• Hyperalgesia opioid / nociceptive
• Variety of techniques helpful
• Most evidence for Gabapentin Ketamine
• Greatest utility in difficult patients
• Chronic pain / opioid users
• Suspected opioid hyperalgesia

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Summary 2

• Gabapentin
• Effective in single dose
• Reduced opiate requirements 30mg / 24hrs
• Dizziness 112
• Ketamine
• Low doses effective
• Single perioperative dose reduces pain scores and
  opioid consumption for 24-48hrs
• Infusions for continued therapy
• Well tolerated