Novel Techniques for Post Caesarean Analgesia

1. Novel Techniques for Post Caesarean Analgesia Dr Nolan McDonnell FANZCA MClinRes School of Women’s and Infants Health and School of Medicine and Pharmacology University of Western Australia

2. 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

3. 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

4. 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

5. 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)

6. Plan • TAP Blocks • Primary oral opioid • Neuraxial magnesium • “Worth a mention” • Extended Release Epidural morphine • Gabapentin • Worth a mention but won’t have time..... • Neuraxial neostigmine • IV Ketamine

7. British Medical Journal Christmas 2001

8. 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

9. 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

10. McDonnell et al Anesth Analg Jan 2008

11. McDonnell et al Anesth Analg Jan 2008

12. Multiple operators • Ultrasound guided • Ropivacaine 0.5% 20 ml per side • Placebo (saline) control group • IV Morphine PCA plus paracetamol/ibuprofen Belavy et al BJA 103 (5) 2009

13. 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

14. 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?

15. ` • 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) Costello et al Reg Anest Pain Med Nov/Dec 2009

16. 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

17. 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

18. Median time 4 vs 8 hours (p=0.01) Kanazi et al Anesth Anal August 2010

19. Kanazi et al Anesth Anal August 2010

20. 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

21. 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 Oral Analgesia

22. 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

23. McDonnell et al IJOA Jan 2010

24. 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

25. Neuraxial Magnesium

26. 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

27. 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

28. 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

29. 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

30. Ghrab et Al Ann Fr Anesth Reanim May 2009

31. 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

32. Techniques worth a mention…..

33. 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

34. 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

35. 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) VAS with Movement Moore et al Anesth Anal Jan 2011

36. Gabapentin Moore et al Anesth Anal Jan 2011

37. 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

40. 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

41. 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

42. 70 patients • Epidural solution 15 mins post CSE • Neostigmine 500 mcg + Clonidine 75 mcg • 9 vs 2 delivered before first request for additional analgesia Van de Velde IJOA 2009

43. 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