TIVA In Children

1. TIVA In Children PIP Meeting Thursday 4th June 2009 Dr Oliver Bagshaw

2. Definitions • TIVA – anaesthetic technique involving no inhalational agents, including volatiles and nitrous oxide • TCI - Infusion by a microprocessor-controlled syringe pump, which automatically and variably controls the rate of infusion of a drug to attain a user-defined target level in an effect site in the patient (usually blood)

3. TIVA – Indications in Children • Known MH patient • MH susceptibility – central core disease, multiminicore disease, KD syndrome • MH risk – muscular dystrophies, arthrogryposis, osteogenesis imperfecta • Patients requiring muscle biopsy

4. TIVA – Indications in Children • Previous N&V post anaesthesia • High risk of N&V post anaesthesia, e.g. strabismus, Ts&As, orchidopexy • Scoliosis surgery • Myasthenia gravis • Reduce blood loss – e.g. FESS procedure

5. Advantages Less pollution Less N&V Improved quality of recovery - delerium No laryngospasm No risk of MH Disadvantages Need IV access Can’t monitor blood levels Delivery problems may go unrecognised Requires ‘metabolism’ Risks of large doses of propofol – PRIS More ‘fiddly’ & wasteful TIVA in children

6. TIVA in children – Practical issues • Can’t always establish IV access prior to induction • Propofol induction often prolonged with TCI – kids may squirm a bit! • Try and avoid relaxants • Can’t always have IV cannula exposed

7. TIVA in children - Options • Manual infusion regime • TCI regime

8. Manually Controlled Infusion • Traditionally 10, 8, 6 regime – decreasing every 10 minutes • Adapted in children – 15, 13, 11, 10, 9 regime – decreasing at variable intervals (15 mins to 1 hr)* • Estimated Cp of 3mcg/ml *McFarlan et al. Paediatr Anaesth 1999; 9: 209-16

9. Manually Controlled Infusion – Effect of age *mg/kg/hr Steur et al. Paediatr Anaesth 2004: 14: 462-7

10. Manual Infusion – 3m

11. Manual Infusion – 2y

12. Manual Infusion – 6y

13. Advantages: Uses valid pharmacokinetic data Bolus incorporated Can quickly adjust target level More accurate estimate of plasma/effect site concentrations Disadvantages: Need specific TCI pumps Data sometimes not available for younger children May be less accurate in younger patients Need some knowledge of appropriate targets TCI

14. Paediatric TCI models • Paedfusor – developed in 1990s Showed need for larger bolus and greater infusion rates in children Can be used down to 5kg • Kataria – also developed in 1990s Based on samples from >50 children Age range 3-16 years Minimum weight 15kg

15. Marsh vs Kataria vs Paedfusor

16. Why Paediatric models? Paedfusor Marsh

17. Plasma vs Effect Site Targeting • Cp = most commonly used • Ce depends on accuracy of PK models • Ce targeting leads to much higher plasma concentrations initially • Concentration gradient needed to drive drug into effect site • Overshoot determined by model (ke0) • Fast ke0 = less overshoot • Ce targeting more accurately predicts loss of consciousness

18. Plasma TCI

19. Effect site TCI

20. Adult propofol target concentrations (effect site)

21. Cp/Ce Equilibration Times – Manual Infusions • Propofol: Manual infusion alone – 20-30 mins Bolus & manual infusion ≈5 mins • Remifentanil: Manual infusion alone – 5-10 mins Bolus & manual infusion <2 mins

22. Cp/Ce Equilibration Times – Targeted Infusions • Propofol: Plasma TCI – 15-20 mins Effect site TCI <5 mins • Remifentanil: Plasma TCI – 5-7 mins Effect site TCI ≈1 min

23. How accurate are TCI systems?

24. Assessment of accuracyMeasurement or predictive performance of a TCI system Bias This value represents the direction (over or under-prediction) of the performance error (median performance error) No Bias Significant bias Calculated concentration Measured concentration

25. Assessment of accuracyMeasurement or predictive performance of a TCI system Precision This is an indication of the size of the typical error from the predicted concentration (median absolute performance error) Small Scatter (No Bias) Large Scatter (No Bias) Calculated concentration Measured concentration

27. Accuracy of Paedfusor • Bias (MPE) – 4.1% (10%) • Precision (MAPE) – 9.7% (20%) • ‘Wobble’ – 8.3% • Performs better than adult models • Also better than ET volatile concentration monitoring (20% bias)

28. Arterial isoflurane tension = 45 – 80% of end-tidal!!!

29. Context Sensitive Half-time

30. Context Sensitive Half-time - propofol

31. Opioid – hypnotic interactions

32. Isobolograms Drug B Drug A

34. 7 min • 6 min • 12 min Propofol-Remifentanil Interaction Vuyk et al. Anesthesiology 1997; 87: 1549-62

35. Remifentanil • May reduce clearance of propofol • Can lead to under prediction of target concentrations • Synergistic effect with propofol • Does it produce tolerance?

36. Influence of remifentanil on propofol Cp50 Struys. Anesthesiology 2003; 99: 802-12

37. Effect of remifentanil and RA on propofol Ce

38. Propofol-remi interactions • 32 children; 3-10yrs UGIE • Three remi groups – 0.025, 0.05 and 0.1 mcg/kg/min • Propofol ED50 decreased from 3.7 to 2.8 mcg/ml with addition of remi • No benefit from increasing dose above 0.025mcg/kg/min – more complications Drover D et al. Anesthesiology 2004; 100: 1382-86

39. Propofol-remi interactions Drover D et al. Anesthesiology 2004; 100: 1382-86

40. Propofol-remi interactions – effect on awakening (Cp50 – 2.2)

41. Propofol-remi interactions – effect on awakening (Cp50 – 2.7)

42. Propofol-remi interactions – effect on recovery • propofol 6mg/kg/hr and remi 0.15mcg/kg/min vs propofol 3mg/kg/hr and remi 0.45mcg/kg/min • No significant difference in recovery times if propofol or remi pronounced • Less variation in recovery times if remi pronounced Hackner C et al. BJA 2003; 91: 580-2

43. Remifentanil – Spontaneously breathing • 32 children (2-7 yrs); dental Rx • Big variation in dose tolerated – 0.05 -0.3mcg/kg/min • Median 0.127mcg/kg/min • RR <10 = best predictor of apnoea Ansermino JM et al. Pediatric Anesthesia 2005; 15: 115-121

44. Remifentanil – Spont breathing & effect of age • 45 children for stabismus surgery – 6m to 9yrs • Propofol – State entropy value 40-45 • Final propofol rate about 12mg/kg/hr • Remifentanil – RD50 to RR ≤10 (mcg/kg/min) • No obvious relationship to age, weight or height Barker N et al. Pediatr Anesth 2007; 17: 948-55

45. Remifentanil SV – RD50 Barker N et al. Pediatr Anesth 2007; 17: 948-55

46. Remifentanil SV – Maximum tolerated dose Barker N et al. Pediatr Anesth 2007; 17: 948-55

47. Remifentanil infusion rates – Adults vs Children • Adults (20-60yrs) vs children (3-11yrs) • IR50 block somatic response to skin incision • Propofol 6mcg/ml 3mcg/ml • IR50 adults = 0.08mcg/kg/min • IR50 children = 0.15mcg/kg/min Munoz H et al. Anesth Analg 2007; 104: 77-80

48. Propofol/remifentanil – spontaneously breathing • 100 children for MRI – mean age about 3 yr • Propofol (10mg/ml) and remifentanil (10mcg/ml) Tsui BC et al. Pediatric Anaesthesia 2007; 15:397-401

49. Remifentanil – Timing of Morphine Bolus • 120 adult patients – lap chole • Morphine bolus at various time intervals from end of surgery (<20 mins to >40 mins) • Pain scores similar in all groups • Least postoperative morphine consumption in >40 mins group Munoz H et al. Br J Anaesth 2002; 88: 814-8

50. TIVA – What I do Manual infusion regime: • Propofol 1% 50mls/Remifentanil 1mg/Ketamine 25mg • 15-12-10-8mg/kg/hr - <6yo • 12-10-8-6mg/kg/hr - >6yo • Aiming for target of about 3mcg/ml