Novel Techniques for Post Caesarean Analgesia

Dr Nolan McDonnell FANZCA MClinResSchool of Women’s and Infants Health and

School of Medicine and PharmacologyUniversity of Western Australia

Introduction• A number of options for post

caesar pain relief available– Method chosen depends on a

number of factors:• Mode of anaesthesia

– 92% performed under regional anaesthesia in Australia

• Local resources• Maternal contra-indications

and requests

Introduction• Post caesarean pain is:– Multifactorial in origin– Difficult to predict degree

• Tendency to over treat– A significant cause of persistent

post surgical pain– A subject of considerable

ongoing research

What is “novel”?

• Novel definition:– “new or unusual in an

interesting way”– “fresh: original, of a kind

not seen before”

• What is “novel” depends on perspective

Options for Analgesia at KEMH• Oral/IV Paracetamol• Oral/IV Anti-inflammatories• Oral/IV Tramadol• Oral Oxycodone• Intrathecal:

– Intrathecal morphine and/or clonidine– Continuous spinal analgesia

• Epidural– Pethidine PCEA– Epidural morphine (single shot and PRN)– Continuous infusions plus PCEA

• TAP Blocks/Rectus sheath blocks• Intravenous PCA (Morphine or fentanyl)

Plan1. TAP Blocks2. Primary oral opioid3. Neuraxial magnesium4. “Worth a mention”– Extended Release Epidural morphine– Gabapentin

5. Worth a mention but won’t have time.....– Neuraxial neostigmine– IV Ketamine

British Medical Journal Christmas 2001

Transversus Abdominis Plane Blocks

• Landmark technique first published in 2007 by McDonnell– Led to significant interest and

research

• Concerns have been expressed secondary to:– Potential for bowel and liver injury– High plasma levels of local

anaesthetic

• Ultrasound guidance now widely recommended

TAP Blocks

• First obstetric study published in 2008 by McDonnell• Single experienced operator– 50 patients, 25 per group– Landmark technique– 1.5 mg/kg ropivacaine per side (max 150 mg per side) vs

saline control– Rectal diclofenac and paracetamol– IV Morphine PCA

McDonnell et al Anesth Analg Jan 2008

McDonnell et al Anesth Analg Jan 2008

McDonnell et al Anesth Analg Jan 2008

Belavy et al BJA 103 (5) 2009

• Multiple operators– Ultrasound guided– Ropivacaine 0.5% 20 ml per side– Placebo (saline) control group– IV Morphine PCA plus paracetamol/ibuprofen

• Associated with in the TAP block group:– Improved satisfaction• Median VAS 96 vs 77 (p=0.008)

– Decreased nausea and antiemetic use (p=0.03)

Belavy et al BJA 103 (5) 2009

Comments:

• The TAP block, in addition to multimodal analgesia including IV PCA opioid, appeared to have significant benefits for post CS analgesia

• But the place of the TAP block when compared to IT morphine still needed investigation– Is the TAP block as effective as IT morphine?– Does the TAP block, in addition to IT morphine,

have any benefit?

`

Costello et al Reg Anest Pain Med Nov/Dec 2009

• 2 investigators, US guided, blinded– 100 women– Spinal anaesthesia with 100 mcg IT morphine (all patients)– 20 ml Ropivacaine 0.375% or saline placebo per side– Regular paracetamol/diclofenac– Morphine on request (IV and oral)

• No additional benefit of TAP block in conjunction with IT morphine– Less patients needed supplemental opioid in first

6 hours post surgery in TAP group – No difference in VAS scores with rest and

movement at 6, 12, 24 and 48 hours– No difference in satisfaction

Costello et al Reg Anest Pain Med Nov/Dec 2009

Kanazi et al Anesth Anal August 2010

• 3 investigators, all experienced, US guided– 2 groups:• IT Morphine 200 mcg and placebo TAP• IT saline and 20 ml 0.375% bupivacaine/adrenaline per

side

– Rectal diclofenac and IV paracetamol– Breakthrough pain managed with IV tramadol

Kanazi et al Anesth Anal August 2010

Median time 4 vs 8 hours (p=0.01)

Kanazi et al Anesth Anal August 2010

Where does this leave the TAP block?

• Little evidence to support it’s use in addition to IT morphine

• As an adjunct to IV opioids– When IT morphine not appropriate– GA caesarean deliveries

• Beware of potential for toxicity and bowel/liver injury

Oral Analgesia

• Primary oral opioid administration is in use in a number of units across Australia, New Zealand and the UK

• Audit data suggests that efficacy and maternal satisfaction is high

• Limited number of RCTs available

• Double blind, placebo controlled, 120 subjects– ITM group: 100 mcg IT Morphine– Oral oxycodone: 20 mg SR oxycodone in recovery

followed by 10 mg IR oxycodone every 6 hours– All subjects had regular paracetamol and

diclofenac– Breakthrough pain managed with tramadol

McDonnell et al IJOA Jan 2010

McDonnell et al IJOA Jan 2010

Oral analgesia

• Regimens still need significant refining– Regular opioid administration in conjunction with

PRN dosing for breakthrough recommended

• Offers a number of advantages for staff and patients– Particularly in resource limited environments– Midwifery staff in particular are attracted to the

ease of administration

Neuraxial Magnesium

Neuraxial Magnesium

• Naturally occurring NMDA receptor antagonist– Modulation important in both

acute and chronic pain states• IV administration has been

shown to have efficacy, but results have been limited– Central (CNS) levels change

little with IV administration– CSF levels appear tightly

regulated

Neuraxial Magnesium

• To date there have been 6 obstetric and 7 non obstetric studies published using epidural or intrathecal magnesium– All from relatively lesser known centres• A number of issues surrounding design and conduct

– 12 (of 13) have had positive results– FDA/TGA approval required for studies to be

conducted and published in the USA and Australia

• Conventional spinal anaesthesia• Randomised to three groups:– IT Morphine 100 mcg– IT Magnesium 100 mg– IT Morphine and Magnesium

Ghrab et Al Ann Fr Anesth Reanim May 2009

Results

• Time to first analgesic request (p<0.01):– 28 +/- 8 hours Group MMg– 19 +/- 6 hours Group M– 7 +/- 6 hours Group Mg

• Improved satisfaction in Group MMg

Ghrab et Al Ann Fr Anesth Reanim May 2009

Ghrab et Al Ann Fr Anesth Reanim May 2009

Neuraxial Magnesium

• Words of caution– Safety record appears good• Numerous animal neurotoxicity studies conducted–Only one study showed potential evidence of toxicity

• Magnesium is naturally occurring in the CSF– DBL MgSO4 contains no preservatives, only same pH

adjusters as heavy bupivacaine and IT morphine

– Further data is needed before widespread recommendations can be made

Techniques worth a mention…..

Extended Release Epidural Morphine• Morphine encapsulated in lipofoam

– Lipofoam slows release of morphine– Prolongs drug delivery into second post op day– Beneficial in patients in whom post op epidural may be risky-eg

febrile patients, severe pre-eclampsia

Extended Release Epidural Morphine (Depodur)

• 2 Obstetric studies to date:– Confirms prolonged analgesia

• Downsides:– Cost: Approx $200 per dose (10 mg)– Lipofoam may become unstable in the presence of local

anaesthetic agents– Not readily available in Australia presently

Gabapentin

• One obstetric study to date– N=46

• 600 mg pre op Gabapentin– 1 hour prior to surgery– IT Morphine in both groups

• Significant improvement in post op pain– Improved satisfaction– But: 19% had “severe”

sedation (vs 0% in control)

Moore et al Anesth Anal Jan 2011

VAS with Movement

Gabapentin

Moore et al Anesth Anal Jan 2011

Conclusions

• A large body of research continues to be conducted into post caesarean pain relief– Increased awareness of persistent post caesarean pain– Future studies should examine the impact on persistent pain

• “Scott’s Parabola” should be born in mind when reviewing potentially new techniques– The role of the TAP block is now relatively well defined– Oral opioid techniques require further refining at a local level– Neuraxial magnesium and oral gabapentin both appear to

have significant potential

Neuraxial Neostigmine

• Muscarinic receptors are present in the dorsal horn of the spinal cord– Stimulation produces analgesia in humans which is

reversed by atropine• Intrathecal neostigmine produces dose dependant

nausea and vomiting– Essentially precludes its use by this route

• Numerous studies of epidural neostigmine outside of caesarean analgesia– Generally promising results, especially when combined

with neuraxial morphine

Neuraxial Neostigmine

• Only one post caesarean study:– Kaya et al 2004– Conventional CSE with

bupivacaine/fentanyl• Epidural neostigmine 75,

150, 300 mcg or placebo

Kaya et al Anesthesiology Feb 2004

Van de Velde IJOA 2009

• 70 patients• Epidural solution 15 mins post CSE

• Neostigmine 500 mcg + Clonidine 75 mcg• 9 vs 2 delivered before first request for

additional analgesia

• 10 mg IV ketamine post delivery• No difference in initial post op analgesia– 35% were symptomatic with ketamine bolus

• BUT:– Women in the ketamine group reported less pain

at 2 weeks post-operatively– Needs further investigation

Bauchat et al IJOA Jan 2011