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Non-opioid medication in acute pain

management

Ian Power

Anaesthesia, Critical Care and Pain Medicine

www.anaes.med.ed.ac.uk/

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Prospect

Procedure specific postoperative pain

management

Integrated surgical and anaesthetic approach www.postoppain.org

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Acute Pain Management:

Scientific Evidence (2nd Edition)

1. Physiology andPsychology of AcutePain

2. Assessment andMeasurement

3. Provision of safe andeffective management

4. Systemicallyadministeredanalgesic drugs

5. Regionally and locallyadministered analgesicdrugs

6. Routes of systemicdrug administration

7. Techniques of drugadministration

8. Non-pharmacologicaltechniques

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Levels of evidence

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-1 Evidence obtained from well-designed pseudo-

randomised controlled trials (alternate allocation or

some other method)NHMRC1999

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4.2.1 Paracetamol

1. 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).

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4.2.2 NSAIDs

1. 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).

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4.2.3 Cox-2 inhibitors

1. 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).

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4.2 Paracetamol, NSAIDs and COX-2

inhibitors

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

I*).

2. NSAIDs and COX-2 inhibitors are effective analgesics ofsimilar 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 incidenceof NSAID-induced perioperative renal impairment is low

(Level I*).

5. Paracetamol, NSAIDs and COX-2 inhibitors are valuable

components of multimodal analgesia (Level II).

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Number-needed-to-treat (v

placebo)NNT (95%CI)

Codeine 60 mg 16.7 (11-48)

Paracetamol1000 mg 3.8 (3.4-4.4)

Morphine 10 mg (IM) 2.9 (2.6-3.6)

Ketorolac10 mg 2.6 (2.3-3.1)

Ibuprofen 400 mg 2.4 (2.3-2.6)

Diclofenac 50 mg 2.3 (2.0-2.7)

Paracetamol1G / Codeine 60 mg 2.2 (1.7-2.9)

Parecoxib 40 mg (iv) 2.2 ( 1.8-2.7)

Lumiracoxib 400mg 2.1 (1.7-2.5)

Diclofenac100mg 1.9 (1.6-2.2)

Oxford acute pain league tablewww.jr2.ox.ac.uk/bandolier/booth/painpag/Acutrev/Analgesics/Leagtab.html

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6. NSAIDs and COX-2 inhibitors

1. 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 (Level1

*).

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Safety of selective and non-selective

NSAIDs

1. New information on non-selective NSAIDs

2. General advice onprescribing NSAIDs and

coxibs

3. Background

4. Conclusions to dateProfGDuff

Commission on Human MedicinesOct 2006

www.mhra.gov.uk

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1. New information on non-selective

NSAIDs

Small increased risk of thrombotic attacks.

Diclofenac (150 mg ) = etoricoxib.

Ibuprofen

1200mg or below - no increase ofmyocardial infarction.

Naproxen - lower incidence of thrombotic riskthan coxibs.

All NSAIDs - risk greater with high doses, longterm Rx.

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2. General advice on prescribing

NSAIDs and coxibs

Lowest effective dose, shortest time.

Rxbased on drug safety profiles and patient riskprofiles.

Dont switch without considering safety profiles. Concomitant aspirin (possibly other antiplatelet drugs)

- greatly increase GI risks of NSAIDs and severelyreduce any advantages of coxibs.

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3. Background

2000 - increased risk with coxibs?

2004 - voluntary withdrawal of rofecoxib.

2005 - European-wide review, coxibs contraindicated in

IHD, cardiovascular disease, peripheral arterialdisease.

Non-selective NSAIDs?

www.mhra.gov.uk

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4.Conclusions to date

Coxibs - three additional events per1000 patients peryear, compared with placebo.

Some NSAIDs may be associated with a small increase

in thrombotic events when used at high doses and forlong 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

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European Medicines Agency

The EuropeanMedicines Agency hasconcluded that the

benefit-risk balance fornon-selective NSAIDsremains favourable.

Press Release

Oct 2006

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Prospect

Procedure specific postoperative pain

management

Integrated surgical and anaesthetic approach

Cholecystectomy, total hip arthroplasty,

hysterectomy.

www.postoppain.org

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Prospect

As 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

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Prospect- laparoscopic

cholecystectomy

Pre-operative

Institute analgesia in good time; clonidine (if further dataconfirms benefit); dexamethasone

Operative techniques

Low pressure CO2pneumoperitoneum (? Lavage, suction)

Intra-operative analgesia

Short-acting strong opioids; intraperitoneal local anaesthetic atthe end of surgery; plus incisional local anaesthetic (nb dose);

clonidine (if further data confirms benefit).

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cholecystectomy

Post-operative analgesia

NSAID

COX-2 inhibitors

Paracetamol

Weak opioids

Epidural local anaesthetics/ opioids (high-risk, open)

Consider ketamine

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cholecystectomy

Up to six hours post-operatively (including the PACU)

A step-up approach should be employed. However, for patientswith more severe pain, starting at step 2 or 3 may beappropriate

Step 1 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)

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9. Specific clinical situations

9.1 Postoperative pain

9.2 Acute spinal cord injury pain

9.3 Acute burns injury pain

9.4 Acute back pain

9.5 Acute musculoskeletal pain

9.6 Acute medical pain

9.7 Acute cancer pain

9.8 Acute pain management in intensive care

9.9 Acute pain management in emergency departments

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9.1.3Day surgery

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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9.7Acute cancer pain

Acute pain in patients with cancer often signals disease

progression: sudden severe pain should be recognized as a

medical emergency.

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10. Specific patient groups

10.1 The paediatric patient

10.2 The pregnant patient

10.3 The elderly patient

10.4 Aboriginal and Torres Strait Islander patients

10.5 Other ethnic groups and non-English speakers

10.6 The patient with obstructive sleep apnoea

10.7 The patient with concurrent hepatic or renal disease

10.8 The opioid-tolerant patient

10.9 The patient with a substance abuse disorder

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Nitroxyparacetamol

Nitroparacetamol exhibits anti-inflammatory and anti-nociceptive activity. al- Swayeh OA et al. Br JPharmacol 2000;130:1453-1456

A comparison of the effect of nitroparacetamol andparacetamol on liver injury. Futter LE et al. Br JPharmacol 2001;132:10-12

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Nitroxyparacetamol

Acetaminophen hepatotoxicity: NO to the rescue.Wallace JL. Br J Pharmacol 2004;143:1-2

There is also substantial evidence that a NO-releasingderivative of acetaminophen offers several advantagesover acetaminophen itself, including enhancedanalgesic potency and reduced liver toxicity.

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Nitroxyparacetamol

Low doses of nitroparacetamol or dexketoprofentrometamol enhance fentanyl antinociceptive activity.Gaitan Get al. Eur J Pharmacol 2003;481:181-188.

Enhancement of fentanyl antinociception bysubeffective doses of nitroparacetamol (NCX-701) inacute nociception and in carrageenan-induced

monoarthritis. Gaitan Get al. Life Sciences 2005;77:85-95.

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4.3.2 Adjuvant drugs - NMDA

antagonists

1. 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 preventiveanalgesic 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).

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4.3.4Adjuvant drugs - Anticonvulsant

drugs

1. 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).

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4.3.5Adjuvant drugs - Membrane

stabilisers

1. 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 onmovement and morphine requirements following major

abdominal surgery (Level II).

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Gabapentin, pregabalin

The analgesic effects of perioperative gabapentin onpostoperative 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 2006:103;1271-1277.

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Acute neuropathic pain

pain initiated or caused by a primary lesion or

dysfunction in the nervous system (Merskey & Bogduk

1994)

burning, shooting, stabbing

paroxysmal, spontaneous

dysaesthesia, hyperalgesia, allodynia, hypoaesthesia

regional autonomic features phantom phenomena

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Postoperative neuropathic pain

1-4%?

Nerve injury?

Persistent, severe

Diagnose earlyandtreat

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Neuropathic pain

31. Anticonvulsants and antidepressants have been shown

by meta-analysis to be effective in the treatment of

neuropathic pain (I - McQuay1996)

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T

reatment of neuropathic painDrug class Example Level

Tricyclics Amitryptiline, doxepin I

Anticonvulsants Carbamazepine, valproate I

Newer anticonvulsants Gabapentin, lamotrigine I

Membrane stabilisers Lidocaine II

Corticosteroids Dexamethasone II

Alpha2agonists Clonidine II

NMDA antagonists Ketamine, dextromethorphan II

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Anticonvulsants for neuropathic pain:

NNT - carbamazepine

Efficacy Adverse Severe

events effects

Trigeminal neuralgia 2.6 3.4 24

Diabetic neuropathy 3.0 2.5 20

McQuay and Moore 1998

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Non standard acute pain problems

Acute spinal cord injury

Acute postamputation pain syndromes

Acute medical painAbdominalAcute herpes zoster

Neurological disorders (Multiple sclerosis, Stroke, Guillain-

Barre)

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Acute spinal cord injury

Pain

Nociceptive (somatic, visceral)

Neuropathic (central pain) Phantom

CRPS

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Taxonomy (Siddall 2002)

Type Location Description

Neuropathic Above level Area of sensorypreservation

At level Segmental painBelow level Pain below the injury

Other CRPS

Nociceptive Somatic Musculoskeletal; procedurerelated; dysreflexic

headache

Visceral Urinary tract (e.g. calculi)

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Treatment of acute neuropathic pain

after spinal cord injury

Opioids

Ketamine

Lidocaine Antidepressants

Anticonvulsants

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1. IV opioids, ketamine and lignocaine (lidocaine)

decrease acute spinal cord injury pain (Level

II)

2. Gabapentin 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)

Acute Pain: Scientific Evidence Edition 2

ANZCA 2005

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Acute spinal cord injury pain

22 year old male

RTA - spinal injury T12, neurological deficit

Surgical fixation PCA fentanyl, paracetamol for analgesia

12 to 24 hours - severe neuropathic pain, rapidly

increasing PCA fentanyl use

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Acute spinal cord injury pain

Lidocaine 0.5 to 1 mg/kg/hour

(nb PCA fentanyl)

Then,

Gabapentin

Paracetamol, oral opioid (oxycodone),

ibuprofen

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Acute postamputation pain

syndromes

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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syndromes1. There is a lack of evidence to guide specific

treatment of postamputation pain syndromes (Level

I).

2. Continuous regional blockade via nerve sheathcatheters 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).

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syndromes4. Ketamine and lignocaine (lidocaine) reduce stump

pain (Level II).

5. Perioperative epidural analgesia reduces the

incidence of severe phantom limb pain (Level III-2).

Acute Pain: Scientific Evidence Edition 2

ANZCA 2005

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syndrome Surgery - general anaesthesia, interscalene

nerve block, ketamine, opioid

Day1-3

Postoperative pain relief: ketamine 10 mg/ hour

sc, opioid (oxycodone), paracetamol,

gabapentin

Stump pain - controlled

Phantom sensation - immediate

Phantom pain - immediate, controlled

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syndrome Stump pain - worsened day 3-5 (Rx oxycodone

increased +TENS added)

Phantom sensation - continuous

Phantom pain increased from day 3, tricyclicadded to gabapentin (opioid, TENS)

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