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TIVA in childrenPeter SquireRCH, Melbourne
BENEFITSTYPES OF SURGERYDELIVERY SYSTEMS (and TCI)NEW TECHNOLOGY
TIVA in childrenPeter SquireRCH, Melbourne
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Society of Intravenous Anaesthesia
Berlin 2009 Singapore 2011
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~75 articles related to propofol/TIVA in last 5 years
Same number as the ten years preceeding
Growing enthusiasm
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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”?
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Simple anaesthetic delivery systems
EASY TO USEVARIABLE RATESSYRINGE SIZES and MAKEALARMSDOWNLOAD DATAROBUSTBATTERY LIFE
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Simple anaesthetic delivery systems...
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Benefits:Post-operative nausea and vomiting
European Journal of Anaesthesiology 1998, 15, 433-570 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”
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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)
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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”
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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
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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?
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Benefits:Post Anaesthesia Emergence Delirium (PAED)
Incidence Scoring systems Risk factors Prevention
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16 retinoblastoma kids1-5 yoAll had Sevo inductionRandomised to Sevo or Propofol Had alternate agent for next exam
....good study but small numbers!
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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”
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AANA JournalDec 2010Vol 78, p471
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Benefits:Laryngospasm/ Bronchospasm
Lancet 2010; 376; p773Prospective multivariate analysis9297 questionnaires
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Scoliosis surgery
SSSSSSEP’s
SSEP’s and MEP’s suppressed by volatile agentsSSEP’s and MEP’s suppressed by volatile agentsNo muscle relaxantsNo muscle relaxantsClonidine +/- KetamineClonidine +/- Ketamine
Types of surgery:
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NeurosurgeryMaintain CO2 /CBF coupling
Avoid BP fluctuations
Clear-headed emergence
Avoid coughing/ICP surges
(TIVA interferes with mapping for epilepsy surgery)
Types of surgery:
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Inhaled foreign body
ENT/Bronchoscopy
Tonsillectomy?
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CARDIAC SURGERY
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Types of surgery
Radiology/ catheter lab
Cardiac
Burns baths
Hospital transfers
ICU sedation
...most surgery suited to TIVA really
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Age Vd (ml/kg) Elimination t1/2 (min)
Clearance (ml/min/kg)
1-3 yo 9500 188 53
3-11yo 9700 398 34Adult 4700 312 28
Propofol differences between children & adults
DELIVERY SYSTEMS and PROPOFOL TCI
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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’
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Propofol pharmacokinetics
20 children, adult algorithmHigh targets required as model over-predictedRevised model 10 children, better accuracy
Diprifusor 1996
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Anesthesiology 1994, 80(1):104
53 children age 3-11 yrsAnaesthesia maintained with Halothane/N2O658 Venous specimens20: 3mg/kg then nil else18: 3.5mg/kg then 9mg/kg/hr15: 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
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Anesthesiology 1994, 80(1):10453 children age 3-11 yrsAnaesthesia maintained with Halothane/N2O20: 3mg/kg then nil else18: 3.5mg/kg then 9mg/kg/hr15: 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))
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Anesthesiology 2000; 92:727-38Pooled data from multiple small studies270 patients, 4,000 specimens (some arterial, some venous)(96 children, 1113 specimens including Kataria’s data of 657)Some bolus only, some with infusions
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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%
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Absalom et al; BJA 2003 91(4):507-13
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Linking Pk and PD: the elusive ke0
BIS/ Entropy/ AAEP’s “more precise” targeting of where your drug works Bigger initial bolus
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Anesthesiology 2004; 101:126925 adults, 25 childrenA-Line monitorSub-maximal propofol bolus“peak effect” recordedValues entered into Kataria & Paedfusor algorithms
results:
keo 0.41 min‾1 Katariakeo 0.91 min-1 Paedfusor
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....what about inter-individual variability?
Our traditional skills in monitoring and titrating agents are still essential in TIVA
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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
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Patient 2
0
10
20
30
40
50
60
70
80
90
100
0 30 60 90 120 150 180
Time after Start of TCI Propofol (minutes)
Ave
rage
BIS
Rea
ding
0.0
2.0
4.0
6.0
8.0
10.0
12.0
14.0
16.0
18.0
20.0
Prop
ofol
pla
sma
leve
l (m
cg/m
L)
AVGBIS
Cpred
Cmeas
2 per. Mov. Avg. (Cpred)
4 yo posterior fossa craniotomy & excision of ependymoma
(Hx of severe emergence agitation)
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Patient 1
0
10
20
30
40
50
60
70
80
90
100
0 30 60 90 120 150 180 210 240
Time after Start of TCI Propofol (minutes)
Ave
rage
BIS
rea
ding
0.0
1.0
2.0
3.0
4.0
5.0
6.0
7.0
8.0
9.0
10.0
Prop
ofol
pla
sma
leve
l (m
cg/m
L)
AVGBIS
Cpred
Cmeas
2 per. Mov.Avg. (Cpred)
5 yo craniotomy for debulking glioma
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Patient 1
0
10
20
30
40
50
60
70
80
90
100
0 30 60 90 120 150 180 210 240
Time after Start of TCI Propofol (minutes)
Ave
rage
BIS
rea
ding
0.0
1.0
2.0
3.0
4.0
5.0
6.0
7.0
8.0
9.0
10.0
Prop
ofol
pla
sma
leve
l (m
cg/m
L)
AVGBIS
Cpred
Cmeas
Remi x10
2 per. Mov.Avg. (Cpred)
2 per. Mov.Avg. (Remix10)
5 yo craniotomy for debulking glioma (showing remifentanil)
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Patient 5
0
10
20
30
40
50
60
70
80
90
100
0 30 60 90 120 150 180 210 240 270 300 330 360 390 420 450 480 510 540 570 600 630 660
Time after Start of TCI Propofol (minutes)
Ave
rage
BIS
re
adin
g
0.0
1.0
2.0
3.0
4.0
5.0
6.0
7.0
8.0
9.0
10.0
Pro
po
fol p
lasm
a le
vel (
mcg
/mL)
AVGBIS Cpred Cmeas 2 per. Mov. Avg. (Cpred)
6 yo posterior fossa tumour resection (obstructive hydrocephalus)
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Propofol synergists
Remifentanil
Ketamine/ “Ketofol”
Clonidine/ Dexmedetomidine
“low-dose”volatile agents
BZD’s
...remember to give a balanced anaesthetic! (Lundy)
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Anesthesiology 2003; 99: 802Struys et al.
45 women
BIS, AAI
LORverbal LORlash LORnoxious
Minto’s Remi effect-site algorithm
..LOR at higher BIS levels and lower Ce propofol when adding Remi
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Integrated anaesthetic tools
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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
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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
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Propofol synergists.....Ketamine
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Dexmedetomidine
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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
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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
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New propofol formulations
Involved study Similar pharmacokinetics/dynamics Reduced microbial contamination More pain on injection No difference in haematological or renal side effects
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Pharmaceutics
Lipuro (MCT’s) Fospropofol Where’s the 2%? ....or 6%?
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Closing the loop
BIS paediatric ,Entropy-need to correlate different levels with different Propofol levels Anesthesia & Analgesia 106; 4; April 2008 p1109 (cerebral pharmacodynamic feedback may help adapt Cpt and blunt interindividual variability)
Awareness could be 8X^ adults- does this matter? EEG study at RCH currently Children have different autonomic responses to
anaesthesia Effect of drugs
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Expired propofol metabolites
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Anesthesiology 2007 ; 106:659-6411 patientsElective surgery (with epidural) Constant rate manual infusions (3mg/kg/hr for one hr-then 6mg/kg/hr for one hr- then 9mg/kg/hr)Proton Transfer Mass Spectrometry plus blood levels
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Rapid propofol analyser
Frequent sampling possible
Finally allows studies more efficiently?
Accuracy?
Cost?
Potential advances in TCI are huge
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Conclusion
Choose your patient, list and procedure TCI Propofol as a mainstay Pick the model you’re comfortable with Add a synergist- must be titratable! Close the loop (BIS, Entropy, AEP’s) Enjoy the benefits START A TRIAL
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THANK YOU!
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