TIVA in children
Peter
Squire
TIVA
in children
RCH,
Melbourne
Peter
Squire
RCH, 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
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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
BATTERY LIFE
Simple anaesthetic delivery systems...
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)
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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
S
No muscle
relaxants
Clonidine
S +/- Ketamine
E
P
’
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)
ENT/
Bronchoscopy
Tonsillectomy?
Inhaled foreign body
CARDIAC SURGERY
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
Age
Vd (ml/kg)
Elimination t1/2
(min)
Clearance
(ml/min/kg)
1-3 yo
9500
188
53
3-11yo
Adult
9700
4700
398
312
34
28
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
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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%
Absalom et al; BJA 2003 91(4):507-13
Linking Pk and PD: the elusive ke0
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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:
keo 0.41 min‾1 Kataria
keo 0.91 min-1 Paedfusor
....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)
100
20.0
90
18.0
80
16.0
70
14.0
60
12.0
50
10.0
40
8.0
30
6.0
20
4.0
10
2.0
0
0.0
0
30
60
90
120
Time after Start of TCI Propofol (minutes)
150
180
Propofol plasma level (mcg/mL)
Average BIS Reading
Patient 2
AVGBIS
Cpred
Cmeas
2 per. Mov. Avg. (Cpred)
5 yo craniotomy for debulking glioma
Patient 1
10.0
90
9.0
80
8.0
Average BIS reading
70
60
50
40
30
Propofol plasma level (mcg/mL)
100
7.0
6.0
5.0
4.0
3.0
AVGBIS
20
2.0
Cpred
10
1.0
Cmeas
0.0
2 per. Mov.
Avg. (Cpred)
0
0
30
60
90
120
150
Time after Start of TCI Propofol (minutes)
180
210
240
5 yo craniotomy for debulking glioma
(showing remifentanil)
100
10.0
90
9.0
80
8.0
70
7.0
60
6.0
50
5.0
40
4.0
30
3.0
20
2.0
10
1.0
0
0.0
Propofol plasma level (mcg/mL)
Average BIS reading
Patient 1
AVGBIS
Cpred
Cmeas
0
30
60
90
120
150
180
210
Remi x10
240
2 per. Mov.
Avg. (Cpred)
Time after Start of TCI Propofol (minutes)
2 per. Mov.
Avg. (Remi
x10)
6 yo posterior fossa tumour resection
(obstructive hydrocephalus)
Patient 5
10.0
90
9.0
80
8.0
70
7.0
60
6.0
50
5.0
40
4.0
30
3.0
20
2.0
10
1.0
0
Propofol plasma level (mcg/mL)
Average BIS reading
100
0.0
0
30
60
90
120
150
180
210
240
270
300
330
360
390
420
450
Time after Start of TCI Propofol (minutes)
AVGBIS
480
510
Cpred
540
570
Cmeas
600
630
660
2 per. Mov. Avg. (Cpred)
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
LORverbal LORlash LORnoxious
Minto’s Remi effect-site algorithm
..LOR at higher BIS levels and lower Ce propofol
when adding Remi
Integrated anaesthetic tools
Propofol synergists...Remifentanil
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“a drug that needs another drug”
Remifentanil the obvious choice (effects on BISPerth 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)
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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
Propofol synergists.....Ketamine
Dexmedetomidine
TIVA disadvantages
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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
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Involved study
Similar pharmacokinetics/dynamics
Reduced microbial contamination
More pain on injection
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No difference in haematological or renal side effects
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Pharmaceutics
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Lipuro (MCT’s)
Fospropofol
Where’s the 2%? ....or 6%?
Closing the loop
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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)
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Awareness could be 8X^ adults- does this matter?
EEG study at RCH currently
Children have different autonomic responses to
anaesthesia
Effect of drugs
Expired propofol metabolites
Anesthesiology 2007 ; 106:659-64
11 patients
Elective surgery (with epidural)
Constant rate manual infusions (3mg/kg/hr for one hrthen 6mg/kg/hr for one hr- then 9mg/kg/hr)
Proton Transfer Mass Spectrometry plus blood levels
Rapid propofol
analyser
Frequent sampling possible
Finally allows studies more
efficiently?
Accuracy?
Cost?
Potential advances in TCI
are huge
Conclusion
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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
THANK YOU!