TIVA in children Peter Squire RCH, Melbourne TIVA in childrenPeter SquireRCH, Melbourne BENEFITS TYPES OF SURGERY DELIVERY SYSTEMS (and TCI) NEW TECHNOLOGY
Society of Intravenous Anaesthesia Berlin 2009 Singapore 2011
~75 articles related to propofol/TIVA in last 5 years Same number as the ten years preceeding Growing enthusiasm
TIVA advantages • Simple delivery systems • No pollution • Portable • PONV • PAED • MH proof • Spinal surgery (controlled hypotension; motor-evoked potentials) • Neurosurgery (ICP,Cerebral metabolic protection) • Shared airway procedures (eg. bronchoscopy) • Cheaper? • Less airway “spasms”?
Simple anaesthetic delivery systems EASY TO USE VARIABLE RATES SYRINGE SIZES and MAKE ALARMS DOWNLOAD DATA ROBUST BATTERYLIFE
Benefits:Post-operative nausea and vomiting European Journal of Anaesthesiology 1998, 15, 433-5 70 trials (57 adult, 13 children) 4074 vomiting as end-point; 3516 nausea; 742 n and v “3.5 and 5.7-fold reductions in vomiting in adults and children respectively when propofol used at induction and maintenance”
PONV (ctd) BJA 2002; 88(5):659-68 Volatile anaesthetics may be the main cause of early but not delayed postoperative vomiting: a randomized controlled trial of factorial design C.C Apfel et al 5 way factorial design (gender, type of surgery, anaesthetic maintenance, opiod use, antiemetic use) 1180 patients (593 children) elective ENT or strabismus surgery Strongest risk factor for vomiting was use of volatile anaesthetics compared with propofol (Odds ratio for Iso and Sevo were 3.4 and 2.8)
BJA 2002; Apfel et al (ctd) Early post-op period (0-2 hrs) showed volatiles as also being the clear risk factor (40% PONV cw 10% PONV with propofol) (Adjusted Odds ratios: Iso 19.8, Sevo 14.5) Depends somewhat on degree of exposure “Irrespective of volatile type this factor alone was several orders of magnitude stronger than all other factors (including antiemetics) in early post-op period”
PONV (ctd)Pediatric Anesthesia 2004 14:251-5 135 boys with Hx motion sickness/PONV Sevo vs Prop/Ketamine; all had Ilioinguinal block. No premed or nitrous No opiates
Anesth Analg 2003; 97:62 “PONV is debilitating, costly and prevalent” 2X incr vomiting in children Adenotonsillectomy, squint repair, herniae, orchiopexy and penile surgery Use of Propofol and avoiding volatiles was most efficacious measure (1A evidence) Should we be extending the benefit to paediatric day-case?
Benefits:Post Anaesthesia Emergence Delirium (PAED) • Incidence • Scoring systems • Risk factors • Prevention
16 retinoblastoma kids 1-5 yo All had Sevo induction Randomised to Sevo or Propofol Had alternate agent for next exam ....good study but small numbers!
Paeds Anesthesia 2009; 19; 748-55 Prospective study of 179 dental patients No difference in PAED scores Sevo group significantly higher PONV and nursing interventions Propofol group discharged 10 mins later “...PAED is hard to quantify”
AANA Journal Dec 2010 Vol 78, p471
Benefits: Laryngospasm/ Bronchospasm Lancet 2010; 376; p773 Prospective multivariate analysis 9297 questionnaires
Types of surgery: Scoliosis surgery SSSS SSEP’s and MEP’s suppressed by volatile agents No muscle relaxants Clonidine +/- Ketamine SSEP’s
Types of surgery: Neurosurgery Maintain CO2 /CBF coupling Avoid BP fluctuations Clear-headed emergence Avoid coughing/ICP surges (TIVA interferes with mapping for epilepsy surgery)
Inhaled foreign body ENT/ Bronchoscopy Tonsillectomy?
Types of surgery Radiology/ catheter lab Cardiac Burns baths Hospital transfers ICU sedation ...most surgery suited to TIVA really
DELIVERY SYSTEMS and PROPOFOL TCI Propofol differences between children & adults
Why TCI? Bolus: Ct x V1 Elimination: Ct x Cl = Ct x V1 x k10 Transfer: Ct x V1(k12e-k21t + k13e-k31t) So the dose: Ct x V1(k10+k12e-k21t+k13e-k31t) Do we need all this maths!! TCI provides a simple way of adjusting the proportion of drug in a plasma or ‘effect-site’
Propofol pharmacokinetics 20 children, adult algorithm High targets required as model over-predicted Revised model 10 children, better accuracy Diprifusor 1996
Anesthesiology 1994, 80(1):104 53 children age 3-11 yrs Anaesthesia maintained with Halothane/N2O 658 Venous specimens 20: 3mg/kg then nil else 18: 3.5mg/kg then 9mg/kg/hr 15: 3.5mg/kg then 12mg/kg/hr (30min) then 7.5mg/kg/hr until conclusion ....Complicated pharmacokinetic analyses to achieve “best”estimate of volumes and clearances to describe the observed concentrations in all the children
Anesthesiology 1994, 80(1):104 53 children age 3-11 yrs Anaesthesia maintained with Halothane/N2O 20: 3mg/kg then nil else 18: 3.5mg/kg then 9mg/kg/hr 15: 3.5mg/kg then 12mg/kg/hr (30min) then 7.5mg/kg/hr until conclusion ....Complicated pharmacokinetic analyses to achieve “best”estimate of volumes and clearances to describe the observed concentrations in all the children NO FORMAL PROSPECTIVE ANALYSIS OF PREDICTIVE PERFORMANCE Kataria’s model one of the most widely used (Anesthesia & Analgesia 2008; 106,no.4;p1109 Rigouzzo et al.The relationship between BIS and propofol during TCI))
Anesthesiology 2000; 92:727-38 Pooled data from multiple small studies 270 patients, 4,000 specimens (some arterial, some venous) (96 children, 1113 specimens including Kataria’s data of 657) Some bolus only, some with infusions
BJA 2003; 91(4): 507-13 • Prospective evaluation of 29 patients • Age 1-15 • Cardiac surgery with CPB (22) or cardiac cath procedures (7) • Maitre Alfentanil TCI for surgery group • Arterial levels (up to 9 per patient) • 212 specimens • Performance errors 4-10%
Linking Pk and PD: the elusive ke0 • BIS/ Entropy/ AAEP’s • “more precise” targeting of where your drug works • Bigger initial bolus
Anesthesiology 2004; 101:1269 25 adults, 25 children A-Line monitor Sub-maximal propofol bolus “peak effect” recorded Values entered into Kataria & Paedfusor algorithms results: keo0.41 min‾1 Kataria keo 0.91 min-1Paedfusor
....what about inter-individual variability? Our traditional skills in monitoring and titrating agents are still essential in TIVA
RCH study 40 patients aged 3-16 Kataria or Paedfusor Arterial access Specimens in a similar fashion to Absalom et al (2003) Use a BIS where possible (many neurosurgical patients) Look for accuracy and benefits
4 yo posterior fossa craniotomy & excision of ependymoma (Hx of severe emergence agitation)
6 yo posterior fossa tumour resection (obstructive hydrocephalus)
Propofol synergists Remifentanil Ketamine/ “Ketofol” Clonidine/ Dexmedetomidine “low-dose”volatile agents BZD’s ...remember to give a balanced anaesthetic! (Lundy)
Anesthesiology 2003; 99: 802 Struys et al. 45 women BIS, AAI LORverbalLORlashLORnoxious Minto’s Remi effect-site algorithm ..LOR at higher BIS levels and lower Cepropofol when adding Remi
Propofol synergists...Remifentanil • “a drug that needs another drug” • Remifentanil the obvious choice (effects on BIS-Perth study Anesthesia & Analgesia 2007 104; 2; p325; Anaesthesia 2009, 64, p 301; BJA 2003 90(5) p623-9 ; hyperalgesia?; rates for spont venting…(Pediatric Anesthesia 2007 17: 948-95) • Ketamine-great complement • Dexmedetomidine/Clonidine
Double aortic arch (using PIVA) 6 kg, 4 mth old Stridor and difficulty feeding. Bronchoscopy and CT spiral angio Left thoracotomy Remi/Sevo then surgical intercostal LA plus 0.1mg/kg Morphine- extubate and feed 30 mcg/kg/50ml »» 10ml/hr = 0.1 mcg/kg/min
TIVA disadvantages • Needs to be considered in the context of available alternative techniques • Awareness • Vagal responses • Involuntary movements • Pain on injection • Anaphylactoid/Anaphylactic reactions are rare (what do we do with egg, peanut and food allergies?) • PRIS • Infection of infusion solutions • Line dead space, Anti-reflux, flow rates, excess fluid loads in small patients
Propofol Infusion Syndrome Rare Potentially fatal May be preventable Is it the drug or the carrier vehicle? Mitochondria: respiratory chain inhibition or impaired fatty acid metabolism Anaesthesia 2007; 62 p690-701; PCA Kam, D Cardone
New propofol formulations Involved study Similar pharmacokinetics/dynamics Reduced microbial contamination More pain on injection No difference in haematological or renal side effects
Pharmaceutics • Lipuro (MCT’s) • Fospropofol • Where’s the 2%? ....or 6%?