Download Non-invasive Ventilation on PICU

TIVA In Children
PIP Meeting
Thursday 4th June 2009
Dr Oliver Bagshaw
Definitions

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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)
TIVA – Indications in
Children

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Known MH patient
MH susceptibility – central core
disease, multiminicore disease, KD
syndrome
MH risk – muscular dystrophies,
arthrogryposis, osteogenesis
imperfecta
Patients requiring muscle biopsy
TIVA – Indications in
Children

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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
TIVA in children
Advantages


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
Less pollution
Less N&V
Improved quality of
recovery - delerium
No laryngospasm
No risk of MH
Disadvantages

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
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

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 – Practical
issues

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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
TIVA in children - Options

Manual infusion regime

TCI regime
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
Manually Controlled
Infusion – Effect of age
Duration
(mins)
Age
0-3 months 3-6 months
6-9 months
9-12 months
1-3 years
0-10
25
20
15
15
12
10-20
20
15
10
10
9
20-30
15
10
10
10
6
30-40
10
10
10
10
6
40-50
5
5
5
5
6
50-60
5
5
5
5
6
>60
2.5
2.5
2.5
2.5
6
*mg/kg/hr
Steur et al. Paediatr Anaesth 2004: 14: 462-7
Manual Infusion – 3m
100
11
10
9
8
7
6
5
4
3
2
1
0
0
0
10
20
30
40
50
60
70
80
90
100
110
120
Manual Infusion – 2y
200
11
10
9
8
7
6
100
5
4
3
2
1
0
0
0
10
20
30
40
50
60
70
80
90
100
110
120
Manual Infusion – 6y
1000
10
900
9
800
8
700
7
600
6
500
5
400
4
300
3
200
2
100
1
0
0
0
10
20
30
40
50
60
70
80
90
100
110
120
TCI
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Advantages:
Uses valid
pharmacokinetic data
Bolus incorporated
Can quickly adjust
target level
More accurate estimate
of plasma/effect site
concentrations
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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
Paediatric TCI models
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
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
Marsh vs Kataria vs
Paedfusor
Marsh
Kataria
Paedfusor
V1
0.228 L/kg
0.52 L/kg
0.458 L/kg
V2
0.463 L/kg
1.0 L/kg
1.34 L/kg
V3
2.893 L/kg
8.2 L/kg
8.20 L/kg
K10 (min –1)
0.119
0.066
70 x Weight -0.3/458.4
K12 (min –1)
0.112
0.113
0.12
K13 (min –1)
0.042
0.051
0.034
K21 (min –1)
0.055
0.059
0.041
K31 (min –1)
0.0033
0.0032
0.0019
Why Paediatric models?
1000
10
9
7
600
6
5
400
Concentration µg/ml
800
Paedfusor
8
4
3
200
2
1
0
0
0
10
20
30
40
50
60
70
80
90
100
110
120
1000
14
800
Marsh
10
600
8
400
Concentration µg/ml
12
6
200
4
2
0
0
0
10
20
30
40
50
60
70
80
90
100
110
120
Plasma vs Effect Site
Targeting
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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
Plasma TCI
600
10
9
500
8
400
7
6
300
5
4
200
3
100
2
1
0
0
0
10
20
30
40
50
60
Effect site TCI
600
12
11
500
10
9
400
8
7
300
6
5
200
4
3
100
2
1
0
0
0
10
20
30
40
50
60
Adult propofol target
concentrations (effect site)
Target (Ce) mcg/ml
Plane of anaesthesia Clinical application
<0.5
Light sedation
Insertion of lines,
awake fibreoptic
intubation
0.5-1.5
Heavy sedation
Radiological
imaging, endoscopy,
surgery with LA
1.5-3.0
Light anaesthesia
Surgery with
analgesia adjuncts
4.0-6.0
General anaesthesia
Major surgery
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

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

How accurate are TCI systems?
Assessment of accuracy
Measurement 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
Calculated concentration
Measured concentration
Significant bias
Assessment of accuracy
Measurement 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)
Calculated concentration
Measured concentration
Large Scatter
(No Bias)
Accuracy of Paedfusor
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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)
Arterial isoflurane tension = 45 – 80% of end-tidal!!!
Context Sensitive Half-time
Context Sensitive Half-time
- propofol
Opioid – hypnotic interactions
Drug B
Isobolograms
Drug A
Plasma remifentanil (ng/ml)
Propofol-Remifentanil
Interaction
10
9
8
7
6
 7 min
Adequate anesthesia
Awakening
 6 min
5
4
3
2
1
0
 12 min
0
2
4
6
8
10
Blood propofol (µg/ml)
Vuyk et al. Anesthesiology 1997; 87: 1549-62
12
14
16
Remifentanil
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May reduce clearance of propofol
Can lead to under prediction of target
concentrations
Synergistic effect with propofol
Does it produce tolerance?
Influence of remifentanil on
propofol Cp50
Remifentanil
0 ng/ml
Remifentanil
2 ng/ml
Remifentanil
4 ng/ml
LOR Verbal
2.9 g/ml
2.4 g/ml
2.2 g/ml
LOREyelash
2.8 g/ml
1.8 g/ml
1.7 g/ml
LORNoxious
4.1 g/ml
1.8 g/ml
1.3 g/ml
Struys. Anesthesiology 2003; 99: 802-12
Effect of remifentanil and
RA on propofol Ce
Propofol Ce
Sedation
Maintenance
of anaesthesia
Nil
Remifentanil
Nitrous oxide
Regional
anaesthesia
1-1.5 mcg/ml
<1 mcg/ml
N/A
<1 mcg/ml
4-6 mcg/ml
3-4 mcg/ml
4-5 mcg/ml
3-4 mcg/ml
Propofol-remi interactions
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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
Propofol-remi interactions
Drover D et al. Anesthesiology 2004; 100: 1382-86
Propofol-remi interactions
–
effect on awakening (Cp50 – 2.2)
1000
14
800
12
600
10
8
400
6
200
4
2
0
0
10
20
30
40
50
60
0
10
20
30
40
50
60
1000
0
10
800
9
8
600
7
6
400
5
4
200
3
2
1
0
0
Propofol-remi interactions
–
effect on awakening (Cp50 – 2.7)
1000
14
800
12
600
10
8
400
6
200
4
2
0
0
10
20
30
40
50
60
0
10
20
30
40
50
60
1000
0
10
800
9
8
600
7
6
400
5
4
200
3
2
1
0
0
Propofol-remi interactions
– effect on recovery
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
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
Remifentanil –
Spontaneously breathing
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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
Remifentanil –
Spont breathing & effect of age
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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
Remifentanil SV – RD50
0.2
0.192
0.15
0.095
0.1
0.075
0.05
0
6m-3yr
3yr-6yr
6yr-9yr
Barker N et al. Pediatr Anesth 2007; 17: 948-55
Remifentanil SV –
Maximum tolerated dose
0.35
0.35
0.3
0.25
0.2
0.167
0.166
3yr-6yr
6yr-9yr
0.15
0.1
0.05
0
6m-3yr
Barker N et al. Pediatr Anesth 2007; 17: 948-55
Remifentanil infusion
rates – Adults vs Children
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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
Propofol/remifentanil –
spontaneously breathing
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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
Remifentanil – Timing of
Morphine Bolus
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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
TIVA – What I do
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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
TIVA – What I do
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TCI:
Propofol 1% 50mls/Ketamine 25mg
Target 10-6-3mcg/ml - <6yo
Target 8-5-3mcg/ml - >6yo
Remifentanil 1-3mg in 50mls
Target 6-4ng/ml - <6yo
Target 6-3ng/ml - >6yo
Spontaneous breathing
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Avoid remifentanil
Add ketamine to propofol
Use local/regional anaesthesia
Greater propofol requirements – may
need to start at 18-20mg/kg/hr; don’t
go below 10-12mg/kg/hr
Propofol Infusion
Syndrome (PRIS)
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First reported in children in 1992
Age 4 weeks to 6 years
All had respiratory illnesses
Propofol 7.4-10.0 mg/kg/hr
Metabolic acidosis, bradycardia, myocardial
failure, lipaemic blood, enlarged liver
PRIS - Pathophysiology
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Like mitochondial cytopathy
Impaired fatty acid oxidation
Accumulation of acylcarnitine esters
Propofol 1% at 4mg/kg/hr = 23g/kg/day lipid
Worse if inadequate glucose
supplemention (6-8mg/kg/min),
steroids and catecholamines
PRIS – Where is the
Evidence? – Case Report 1
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Wolf et al. Lancet 2001; 357:606
2yo head injury
mean propofol dose 5.2mg/kg/hr
Developed signs of PRIS on D4
Propofol stopped and CVVH instigated
High levels of carnitines (malonyl and acyl)
Mean glucose intake ≈ 2.5mg/kg/min
Child survived – markers of fatty acid
oxidation normal at 9 month follow-up
PRIS – Where is the
Evidence? – Case Report 2
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Withington et al. Pediatr Anesth 2004; 14:505-8
5m old post cleft lip repair (3rd attempt)
Mean propofol dose 11.7mg/kg/hr
Developed signs of PRIS on D3
Propofol stopped and charcoal HP instigated
Glucose intake <3mg/kg/hr
Child survived
Samples showed elevated acylcarnitines –
normal at follow-up
PRIS – Does it occur with
Anaesthesia?

3 recent case reports in children:
Age (yrs)
Diagnosis
Prop dose
(mg/kg/hr)
Prop duration Signs of PRIS
(hours)
3
Cerebral
aneurysm
6.5
8
A, HT, ↑CPK
7
Osteogenesis
imperfecta
13.5
2.5
LA
12
Mitral valve
disease
<3
15
LA
16
Mitral valve
disease
<3
8
LA
A - Acidosis; L – Lactic, HT – Hypotension; CPK – creatine phosphokinase
PRIS – What can we do to
prevent it?
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
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
Avoid propofol!
Avoid in high risk cases – PICU patients,
steroids, catecholamines, fatty acid
oxidation disorder
Use 2% propofol
Limit dose – adjuncts, avoid for
postoperative sedation
Maintain adequate glucose intake – 68mg/kg/min
Monitor for lactic acidosis
Questions
?