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Ian Power
Anaesthesia, Critical Care and Pain Medicine

www.anaes.med.ed.ac.uk/
 µProspect¶
° Procedure specific postoperative pain
management
° Integrated surgical and anaesthetic approach
° www.postoppain.org
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K. Physiology and 5. Regionally and locally
Psychology of Acute administered analgesic
Pain drugs
2. Assessment and 6. Routes of systemic
Measurement drug administration
3. Provision of safe and 7. Techniques of drug
effective management administration
4. Systemically 8. Non-pharmacological
administered techniques
analgesic drugs
 Ö 

I Evidence obtained from a systematic review of all
relevant randomised controlled trials.
II Evidence obtained from at least one properly designed
randomised controlled trial
III-K Evidence obtained from well-designed pseudo-
randomised controlled trials (alternate allocation or
some other method)
NHMRC K
 ã 



 

K. Paracetamol is an effective analgesic for acute pain (Level I*).

2. Paracetamol is an effective adjunct to opioids (Level I).
3. NSAIDs given in addition to paracetamol improve analgesia
(Level I).
4. IV paracetamol is an effective analgesic after surgery (Level II),
is as effective as ketorolac (Level II) and equivalent to
morphine after dental surgery with better tolerance (Level II).
 ã  |R

K. NSAIDs are effective analgesics for the acute pain of surgery,

low back pain and renal colic (Level I*).
2. NSAIDs are effective adjunct to opioids (Level I).
3. NSAIDs given in addition to paracetamol improve analgesia
(Level I).
 ã   
 

K. COX-2 inhibitors and NSAIDS are effective analgesics of

similar efficacy for acute pain (Level I*).
2. COX-2 inhibitors are effective adjunct to opioids (Level II).
ã 


 |R

 !

 

K. Paracetamol is an effective analgesic for acute pain (Level

I*).
2. NSAIDs and COX-2 inhibitors are effective analgesics of
similar efficacy for acute pain (Level I*).
3. NSAIDs given in addition to paracetamol improve analgesia
(Level I).
4. With careful patient selection and monitoring, the incidence
of NSAID-induced perioperative renal impairment is low
(Level I*).
5. Paracetamol, NSAIDs and COX-2 inhibitors are valuable
components of multimodal analgesia (Level II).
 |
 
 
 
NNT ( 5%CI)
Codeine 60 mg K6.7 (KK-48)
Paracetamol K000 mg 3.8 (3.4-4.4)
Morphine K0 mg (IM) 2. (2.6-3.6)
Ketorolac K0 mg 2.6 (2.3-3.K)
Ibuprofen 400 mg 2.4 (2.3-2.6)
Diclofenac 50 mg 2.3 (2.0-2.7)
Paracetamol K
/ Codeine 60 mg 2.2 (K.7-2. )
Parecoxib 40 mg (iv) 2.2 (K.8-2.7)
Lumiracoxib 400mg 2.K (K.7-2.5)
Diclofenac K00mg K. (K.6-2.2)
Oxford acute pain league table
www.jr2.ox.ac.uk/bandolier/booth/painpag/Acutrev/Analgesics/Leagtab.html
  |R

 !
 

K. NSAIDs (including COX-2 inhibitors) given parenterally or

rectally are not more effective and do not result in fewer
side-effects than the same drug given orally (Level K*).
¢

 
   

¢
K. New information on non-
selective NSAIDs
2.
eneral advice on
prescribing NSAIDs and
coxibs
3. Background
4. Conclusions to date
Prof
Duff
Commission on Human Medicines
Oct 2006
www.mhra.gov.uk

|"
 




 
|R
° Small increased risk of thrombotic attacks.
° Diclofenac (K50 mg ) = etoricoxib.
° Ibuprofen K200mg or below - no increase of
myocardial infarction.
° Naproxen - lower incidence of thrombotic risk
than coxibs.
° All NSAIDs - risk greater with high doses, long
term Rx.
  #


 
 

|R

 
° Lowest effective dose, shortest time.
° Rx based on drug safety profiles and patient risk
profiles.
° Don¶t switch without considering safety profiles.
° Concomitant aspirin (possibly other antiplatelet drugs)
- greatly increase
I risks of NSAIDs and severely
reduce any advantages of coxibs.
  $
%  

° 2000 - increased risk with coxibs?
° 2004 - voluntary withdrawal of rofecoxib.
° 2005 - European-wide review, coxibs contraindicated in
IHD, cardiovascular disease, peripheral arterial
disease.
° Non-selective NSAIDs?
www.mhra.gov.uk
 ã 

 

° Coxibs - three additional events per K000 patients per
year, compared with placebo.
° Some NSAIDs may be associated with a small increase
in thrombotic events when used at high doses and for
long term treatment.
° NSAIDs Product Information to be updated.
° CHA setting up a cross-specialty expert group to
consider the safe use of these products.
www.mhra.gov.uk
 

 
R 
&
ùThe European
Medicines Agency has
concluded that the
benefit-risk balance for
non-selective NSAIDs
remains favourable.´
Press Release
Oct 2006
 µProspect¶

° Procedure specific postoperative pain

management
° Integrated surgical and anaesthetic approach
° Cholecystectomy, total hip arthroplasty,
hysterectomy.
www.postoppain.org
 µProspect¶
ùAs with any surgical procedure, the techniques
employed during the operation, as well as
analgesic medication delivered pre-, intra- and
post-operatively can have an impact on patient
outcomes´
www.postoppain.org
 Prospect  

   
  &  &
Pre-operative
Institute analgesia in good time; clonidine (if further data
confirms benefit); dexamethasone
Operative techniques
Low pressure CO2 pneumoperitoneum (? Lavage, suction)
Intra-operative analgesia
Short-acting strong opioids; intraperitoneal local anaesthetic at
the end of surgery; plus incisional local anaesthetic (nb dose);
clonidine (if further data confirms benefit).
 Prospect  

   
  &  &
Post-operative analgesia
° NSAID
° COX-2 inhibitors
° Paracetamol
° Weak opioids
° Epidural local anaesthetics/ opioids (high-risk, open)
° Consider ketamine
 Prospect  

   
  &  &
mp to six hours post-operatively (including the PACm)
ùA step-up approach should be employed. However, for patients
with more severe pain, starting at step 2 or 3 may be
appropriate´
Step K NSAID/Cox-2 + paracetamol
Step 2 Add weak opioids if pain persists
Step 3 Add strong short -acting opioids if pain persists

(After six hours: use low doses of strong opioids in Step 3)

     




.K Postoperative pain
.2 Acute spinal cord injury pain
.3 Acute burns injury pain
.4 Acute back pain
.5 Acute musculoskeletal pain
.6 Acute medical pain
.7 Acute cancer pain
.8 Acute pain management in intensive care
. Acute pain management in emergency departments
 

& &

° 5.3% incidence of severe pain in the first 24

hours.
° BMI, duration of anaesthesia, type of surgery.
° The best predicator of severe pain at home is
inadequate analgesia in the first few hours after
surgery.
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° Acute pain in patients with cancer often signals disease
progression: sudden severe pain should be recognized as a
medical emergency.

   

  
K0.K The paediatric patient
K0.2 The pregnant patient
K0.3 The elderly patient
K0.4 Aboriginal and Torres Strait Islander patients
K0.5 Other ethnic groups and non-English speakers
K0.6 The patient with obstructive sleep apnoea
K0.7 The patient with concurrent hepatic or renal disease
K0.8 The opioid-tolerant patient
K0. The patient with a substance abuse disorder
 | troxy


 

° Nitroparacetamol exhibits anti-inflammatory and anti-

nociceptive activity. al- Swayeh OA et al. Br J
Pharmacol 2000;K30:K453-K456

° A comparison of the effect of nitroparacetamol and

paracetamol on liver injury. Futter LE et al. Br J
Pharmacol 200K;K32:K0-K2
 | troxy


 

Acetaminophen hepatotoxicity: NO to the rescue.

Wallace JL. Br J Pharmacol 2004;K43:K-2
ùThere is also substantial evidence that a NO-releasing
derivative of acetaminophen offers several advantages
over acetaminophen itself, including enhanced
analgesic potency and reduced liver toxicity.´
 | troxy


 

° Low doses of nitroparacetamol or dexketoprofen

trometamol enhance fentanyl antinociceptive activity.

aitan
et al. Eur J Pharmacol 2003;48K:K8K-K88.

° Enhancement of fentanyl antinociception by

subeffective doses of nitroparacetamol (NCX-70K) in
acute nociception and in carrageenan-induced
monoarthritis.
aitan
et al. Life Sciences 2005;77:85-
5.
 ã  R'

  |R





K. Ketamine has an opioid-sparing effect in postoperative pain
although there is no concurrent reduction in opioid-related
side effects (Level I).
2. NMDA receptor antagonist drugs may show preventive
analgesic effects (Level I).
3. Ketamine improves analgesia in patients with severe pain that
is poorly responsive to opioids (Level II).
4. Ketamine may reduce opioid requirements in opioid-tolerant
patients (Level IV).
 ã  ãR'

  R




 
K. Anticonvulsants are effective in the treatment of chronic
neuropathic pain states (Level I).
2. Perioperative gabapentin reduces postoperative pain on
movement and opioid requirements (Level I).
 ã  R'

  




K. Membrane stabilisers are effective in the treatment of chronic
neuropathic pain states, particularly after peripheral nerve
trauma (Level I).
2. Perioperative intravenous lidocaine reduces pain on
movement and morphine requirements following major
abdominal surgery (Level II).
 #







° The analgesic effects of perioperative gabapentin on

postoperative pain: A meta-analysis. Hurley RW et al.
Regional Anesthesia and Pain Medicine 2006: 3;237-
247.

° The analgesic efficacy of celecoxib, pregabalin, and

their combination for spinal fusion surgery. Reuben SS
et al. Anesth Analg 2006:K03;K27K-K277.
 Rcute neuropath c pa n
° pain initiated or caused by a primary lesion or
dysfunction in the nervous system¶ (Merskey & Bogduk
K 4)
° burning, shooting, stabbing
° paroxysmal, spontaneous
° dysaesthesia, hyperalgesia, allodynia, hypoaesthesia
° regional autonomic features
° phantom phenomena
   

 
 


° K-4%?
° Nerve injury?
° Persistent, severe
° Diagnose early and treat««
 | 
 


3K. Anticonvulsants and antidepressants have been shown
by meta-analysis to be effective in the treatment of
neuropathic pain (I - McQuay K 6)
 ±

 
 
 


Drug class Example Level
Tricyclics Amitryptiline, doxepin I
Anticonvulsants Carbamazepine, valproate I
Newer anticonvulsants
abapentin, lamotrigine I
Membrane stabilisers Lidocaine II
Corticosteroids Dexamethasone II
Alpha2 agonists Clonidine II
NMDA antagonists Ketamine, dextromethorphan II
 R



 
 
 


||±


(


Efficacy Adverse Severe

events effects

Trigeminal neuralgia 2.6 3.4 24

Diabetic neuropathy 3.0 2.5 20
McQuay and Moore K 8
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° Acute spinal cord injury
° Acute postamputation pain syndromes
° Acute medical pain
Abdominal
Acute herpes zoster
Neurological disorders (Multiple sclerosis, Stroke,
uillain-
Barre)
 R 

 
'&
Pain
° Nociceptive (somatic, visceral)
° Neuropathic (ùcentral´ pain)
° Phantom
° CRPS
 ±

&

Type Location Description
Neuropathic Above level Area of sensory
preservation
At level Segmental pain
Below level Pain below the injury
Other CRPS

Nociceptive Somatic Musculoskeletal; procedure

related; dysreflexic
headache
Visceral mrinary tract (e.g. calculi)
 ±

 

 
 





 
'&
° Opioids
° Ketamine
° Lidocaine
° Antidepressants
° Anticonvulsants
K. IV opioids, ketamine and lignocaine (lidocaine)
decrease acute spinal cord injury pain (Level
II)
2.
abapentin is effective in the treatment of
acute spinal cord injury pain (Level II)
(No specific evidence for the treatment of acute
nociceptive and visceral pain in spinal cord injury
patients. Treatment is based on evidence from other
studies of nociceptive and visceral pain)

Rcute Pa n: Sc ent
c E ence E t on 2

R|R 2005
 Rcute 

 
'&


° 22 year old male
° RTA - spinal injury TK2, neurological deficit
° Surgical fixation
° PCA fentanyl, paracetamol for analgesia
° K2 to 24 hours - severe neuropathic pain, rapidly
increasing PCA fentanyl use
 Rcute 

 
'&


° Lidocaine 0.5 to K mg/kg/hour
(nb PCA fentanyl)
Then,
°
abapentin
° Paracetamol, oral opioid (oxycodone),
ibuprofen
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&
 
° Stump pain, localised to the site of the
amputation.
Acute - usually nociceptive
Chronic - usually neuropathic
° Phantom sensation
° Phantom pain (preamputation pain, stump pain,
chemotherapy)
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&
 
K. There is a lack of evidence to guide specific
treatment of postamputation pain syndromes (Level
I).
2. Continuous regional blockade via nerve sheath
catheters provides effective postoperative analgesia
after amputation, but has no preventive effect on
phantom limb pain (Level II).
3. Calcitonin, morphine, ketamine, gabapentin and
sensory discrimination training reduce phantom limb
pain (Level II).
 R  





&
 
4. Ketamine and lignocaine (lidocaine) reduce stump
pain (Level II).
5. Perioperative epidural analgesia reduces the
incidence of severe phantom limb pain (Level III-2).

Rcute Pa n: Sc ent
c E ence E t on 2

R|R 2005
 Rcute  





&
 
° 46 year old female
° Presented acutely with a gangrenous arm
° Severe pain
° Septic, confused, tachycardic, hypotensive,
acidotic, hypoxic
° History of alcohol abuse
° Abnormal liver function tests
 Rcute  





&
 
° Surgery - general anaesthesia, interscalene
nerve block, ketamine, opioid
Day K-3
° Postoperative pain relief: ketamine K0 mg/ hour
sc, opioid (oxycodone), paracetamol,
gabapentin
° Stump pain - controlled
° Phantom sensation - immediate
° Phantom pain - immediate, controlled
 Rcute  





&
 
° Stump pain - worsened day 3-5 (Rx oxycodone
increased +TENS added)
° Phantom sensation - continuous
° Phantom pain increased from day 3, tricyclic
added to gabapentin (opioid, TENS)