Keynote Address: Advances in Children’s Pain Control

1. Keynote Address: Advances in Children’s Pain Control Graham Bell, Consultant Anesthetist, Yorkhill

2. Advances in Pain Control for Children Dr Graham Bell Consultant anaesthetist & lead clinician for acute pain service RHSC, Yorkhill, Glasgow

3. Pain Relief Research • Increasing interest in the safety of current techniques • Large scale audits conducted to estimate incidence of rare complications • There is a change in the way anaesthetic / pain research is conducted in last 10 years, fewer small studies, better statistical review, multicentre trials & meta analyses, better editorial control. • Most of these changes are good for the quality of practice

4. Other factors driving changes in practice • Day surgery / 23 hour surgery • National patient safety agency • Concerns about litigation • H@N = Hospital at night / Junior Doctors hours

5. Large audits

6. NAP3 complications of neuraxial block • Included adults and children = 3% of denominator. No serious complications in <16 yr olds • Approx 50% single shot blocks, 50% catheter techniques • Indwelling catheters had twice the incidence of side effects compared to single shot techniques, CSE had highest complication rate • Only 1 out of the 6 deaths described as ‘healthy’ preop • Permanent injury 8-17 per 100 000 blocks • 61% of major neurological complications recover (no info collected on moderate / minor complications)

7. National Paediatric epidural audit • 10 633 children, all epidurals with catheters • All but 1 inserted with the patient anaesthetised • No deaths • 5 serious incidents, • Epidural abcess, Cauda equina syndrome = only incident with consequences at 1 yr, • 2 moderate • Local anaesthetic toxicity, periph nerve injury • 43 minor • PDPH, inadvertent spinal, local infection. Caudal catheters not assoc higher rate of infection

8. Comparisons / conclusions from regional anaesthesia audits • Self report audits can only ever estimate minimum incidence • Children do not appear to have a high rate of complications from regional techniques • Placement of catheters asleep appears to have low incidence of problems - but NAP3 did not capture nerve injury data; so no direct comparison • Immunosupression & steroids frequently associated with infection – data from small series too • Single shot caudal has an extremely good safety profile

9. New equipment for regional techniquesincreases operator confidence and popularity SonoSite MicroMaxx SLA26 6-13MHz HFL38 6-13MHz Modern laptop technology; better software Broad band width; better hardware

11. Conformation of correct catheter placement by injection Dura mater Reverberation artefact Catheter tip Suspensory (Dentate) ligament Lung

12. Catheter passing through epidural space showing striated appearance In smaller patients almost the entire length of the catheter can be seen Arrow Flextip Plus catheter with stylet Catheters with a wire spiral are more echogenic Catheters with stylets tend to go in a strait line

13. Simple analgesics

14. Paracetamol Analgesia • increased levels of endogenous cannabinoids Paracetamol inhibitor of cellular anandamide uptake Deacetylated to p-aminophenol conjugated with arachidonic acid : N-arachidonoylphenolamine (AM404) • an endogenous cannabinoid & • agonist at TRPV1 (vanilloid) receptors CB(1) receptor antagonist completely prevents the analgesic activity of paracetamol

15. What do we know about paracetamol toxicity? • Most common indication for paediatric hepatic transplant • After maternal overdose, fetal / neonatal outcome is better than maternal • slower oxidation & better glutathione synthesis • >75mg/kg/day for over 24hrs in a febrile child is a risk • Doses of 90mg/kg/day common in hospital for 48hrs, reduce thereafter. • Research on dosing regimes continues

16. Paracetamol Toxicity • We don’t know what dose may cause sub-acute toxicity, but sub-acute toxicity is the most common form in children • If used regularly for more than a few days ? reduce dose further • There is no consensus on interpreting blood paracetamol levels after sub-acute overdose in children • raised transaminases & positive history  treat

17. Use of paracetamol in babies increases the risk of developing asthma five years later, a study of more than 200,000 children suggests. Those given the painkiller for fever in the first year of life had a 46% increased risk of asthma by the age of six or seven ? Glutathione important in the mechanism?

18. A review of 70 studies suggested more than 50% of parents gave their children the wrong doses of paracetamol or ibuprofen to bring down temperatures. Underlines the need for clear information & research

19. NSAIDs & Asthma • 70 known asthmatics attending teaching hospital respiratory clinic given effervescent diclofenac 1-1.5mg/kg • none had >15% reduction in peak flow • Aspirin exacerbated disease is rare in children ~ 1 in 50 • Usually in adults with asthma / nasal polyps • COX II NSAIDs should not trigger bronchospasm even in susceptible patients

20. NSAIDs & Bone GrowthBackground • NSAIDs inhibit new bone growth • Unequivocal evidence from animal studies; # don’t heal as well with NSAID use • But • Not paediatric • No pain scores • High dose regimes in animals

21. NSAIDs & Bone Growthclinical practice? In Practice 40% of anaesthetists avoid after scoliosis surgery Evidence No large prospective human studies Femoral # in adults has marked association between non union and NSAIDs use: Odds ratio 10.74(CI 3.35-33, p 0.000001)

22. NSAIDs & Bone Growth(my) practical approach Usually does not matter. Butif bone is grafted or healing is expected to be prolonged they are best avoided Cox II inhibitors only slightly better than non-selective NSAIDs

23. Although NSAIDs aid pain control in healing bones, # of the bony callous is extremely painful

24. NSAIDs & BabiesCNS effects • Prostaglandins involved in sleep regulation • NSAIDs alter • sleep pattern • stop normal temperature fall at night • melatonin secretion • the clinical implications of these effects are unclear • Ibuprofen • no increase in intraventricular haemorrhage • Data from patients given NSAIDs for Persistent Ductus Arteriosis closure

25. NSAIDs & BabiesRenal effects • COX inhibition has huge effects on developing kidney • 20% reduction in GFR in Neonates • babies who receive indomethacin for PDA closure have double the risk of renal failure • This is a COX2 effect • In children > 3 months old, NSAID induced renal damage is rare • Large trial (84 000) of paracetamol vs ibuprofen for Rx of fever showed no differences in renal function • Cautions • pre-existing renal disease • nephrotoxic drugs e.g.aminoglycosides • Ibuprofen leads to a fourfold increase in bilirubin concentrations in Ex-prem neonates

26. OSA is becoming a more common indication for tonsillectomy, especially in younger (i.e. preschool) children. Sore throat / tonsillitis becoming a less common indication Different anaesthetic concerns More caution with opiates Likely to become a day stay operation Already is in Epsom ..... Tonsillectomy

27. Post tonsillectomy pain • Significant pain, sleep & behavioural disturb for 5-8 days • LA infiltration improves early pain (Grade B recommendation) • But there are reports (incl deaths) with carotid injection • Ketamine is good analgesic but more side effects than opiates • Combination of simple analg and opiates is best (Grade A) • Paracetamol; orally preop is better than PR and reduces PONV as well as pain • Dexamethasone good for PONV but high doses seem to be associated with a higher postop bleeding rate • NSAIDS …..

28. NSAIDs & post tonsillectomy haemorrhage2 meta analysis & a Cochrane review 2003 Otolaryngology:1136 patients NSAIDS & postop haemorrhage odds ratio = 1.29 (not signif) Aspirin odds ratio 1.94 (signif) Conclusion, non aspirin NSAIDs don’t increase risk of bleeding 2003 Anesthesia & Analgesia: 970 patients Re-operation more common in NSAID group Peto odds ratio 2.23(1.12-4.83) ignores trials with zero events Shadish & Haddock OR 1.92(1.00-3.71)includes all trials Conclusion, the evidence for NSAIDs to increase the incidence of bleeding after tonsillectomy remains ambiguous Cochrane Review 2005; NSAIDS did not cause any increase in bleeding requiring surgical intervention (13 trials, 955 patients)

29. NMDA Antagonists

30. Ketamine • Is it useful systemic analgesic? • Mixed picture in the literature

31. Is it useful systemic analgesic in the postop period? Only 4RCTs in children No advantage when added to PCA no decrease in morphine consumption no enhanced VAS pain score v. small increase in side effects (dreams) Ketamine

32. Is it useful systemic analgesic in the postop period? ? Some advantage as iv infusion 50% of trials demonstrate some benefit side effects profile not too worrying Ketamine

33. Is it useful systemic analgesic? Mixed picture in the literature 37 RCTs overall 4 RCTs in children 50% overall benefit small increase in CNS side effects 50% no benefit Cant draw any real conclusions specific to children Ketamine

34. Ketamine Conclusions on Ketamine • Much better epidural adjunct than systemic when considering acute post-op pain • Adult studies show encouraging reduction in chronic pain with intra/post-op ketamine

35. Saline MK-801= NMDA antagonist

36. Ketamine in neonates? Saline MK-801= NMDA antagonist NMDA antagonists trigger an increase in neuronal apoptosis in the developing brain • in common with several other centrally active drugs ?? NMDA may be the central pathway for this trigger

37. Is it time to stop injecting NMDA antagonists into any central neurological space?

38. Is it time to stop injecting NMDA antagonists into any patient with a developing nervous system? • NMDA receptor mediation is involved in many types of anaesthesia • Is Sub Arachniod Block (spinal) safer • GAS study • GA vs Spinal

39. Modes of administration

40. Pain Management: Systemic AnalgesicsModes of administration, advances? • PCA • routine down to 6 yo • ? Video game test • Excellent safety record even in high risk • e.g. spinal surgery : myopathic patients with high dose requirement Problems reported with oversedation / respiratory depression & PCAs tend to be associated with concomitant use of other sedative drugs

41. Modes of administration, advances? • Nurse CA • excellent for infants but needs a reliable nursing infrastructure & continuing education • In units with established NCA • reduced total opiate requirement vs infusion • lockout at least 15 minutes • high dependency environment

42. Pain Management: Systemic AnalgesicsModes of administration, advances? • Parent CA • has established a place in terminal care but not in acute pain • Verbal & written instructions • 24 hour family presence • continuous monitoring • up to 3 “pain managers” from the family • careful selection required

43. Parent CA experience from Baltimore; 212 children on Parent or Nurse CA, 9 received naloxone, 4 (1.7%) of these for desaturation or apnea no identifiable high risk groups Adult PCA 0.2- 0.7% for desaturation or apnea Pain Management: Systemic AnalgesicsModes of administration, advances?

44. Pain Management: Systemic AnalgesicsModes of administration, advances? • Transdermal? • Fentanyl patches • smallest delivers equivalent of 25mcg/hr • cant cut them up • 12.5mcg patch available soon • drug absorbed from normal skin for up to 24hrs after removal of patch • no role in acute pain • death reported

45. Pain Management: Systemic AnalgesicsModes of administration, advances? • Morphine gel • The presumed mechanism of action is by interaction with opioid receptors which are sited on sensory nerve terminals and which may be up-regulated in inflammation. • Good results in epidermolysisbullosa • ? Role in burns or surgical wound pain • (1774 topical opium for haemarrhoids )

47. National Patient Safety Agency

48. Patient safety alert 21 Safer practice with epidurals • 3 patient deaths 2000-2004 following bupivacaine given IV rather than epidural route • NPSA reviewed reports 1/01/2005-31/05/2006 concerning incidents involving epidural injections and infusions • 346 incidents – mostly no or low harm • Included epidural drugs given IV and vice versa, wrong drug given, wrong dose.

49. 6 recommendations 1. Clearly label infusion bags and syringes 2. Minimise the likelihood of confusion between different types and strengths of epidural injections/infusions 3. Store epidural infusions separately from IV 4. Clearly label epidural administration sets and catheters 5. Use easily distinguishable pumps, lines etc 6. Adequate training for all staff