‘Diprifusor’ TCI system
Tagged ‘Diprivan’ PFS loaded in syringe pump
Full ‘Diprivan’ PFS
is loaded correctly
Finger grip Tag = PMR
(Programmaable Magnetic Resonance*)
Aerial
‘Diprifusor’ TCI Subsystem
Recognition software/electronics
‘Diprifusor’ TCI Software/
2 microprocessors
Pump hardware
Pump
software
Recognition tag in finger grip of ‘Diprivan’ PFS
Important safety features
Correct drug identification and usage
l Operates in ‘Diprifusor’ TCI mode only with tagged
‘Diprivan’ PFS – no other drugs
l Confirms ‘Diprivan’ concentration (1% or 2%) for
correct infusion at requested target concentration
l Erases tag when PFS is nearly empty and prevents
refilling/reuse
‘Diprifusor’ TCI Subsystem
Installed in syringe pumps that incorporate ‘Diprifusor’
Functions
l Control unit for syringe pump
l Recognition of tagged ‘Diprivan’ PFS
8 cm
‘Diprifusor’ TCI Software*
Installed in ‘Diprifusor’ TCI Subsystem
l Three-compartment pharmacokinetic model
Specific set of pharmacokinetic parameters for
‘Diprivan’ (propofol)
l Two independent algorithms for infusion control
Fail-safe mechanism to enhance patient safety
*© University of Glasgow
‘Diprifusor’ TCI System
Main components
Anaesthetist
inputs
patient data
(age, body weight)
Anaesthetist
selects and inputs
target blood
concentration
Patient
‘Diprifusor’ TCI
Subsystem
Microprocessor
+ pharmacokinetic
program
Infusion pump
incorporating
‘Diprifusor’
Syringe pumps incorporating ‘Diprifusor’
Commercially-available infusion systems*
l Graseby 3500
l Vial Médical Master TCI
l ALARIS IVAC TIVA TCI
* Contact manufacturer for details and availability
Display panel of Graseby 3500
During ‘Diprifusor’ TCI
Liquid Crystal Display (LCD)
CALCULATED concentration
TARGET
concentration
TCI status indicator
TCI status indicator
Access TOTAL amount
of ‘Diprivan’ infused
Small
increment
Small
decrement
Access INFO on effect
site (brain) concentration,
time to target...
TCI status indicators
, the word CALCULATED
and symbol blink during infusion
Consult Instruction Manual for details of display and operation
Display panel of Vial Médical Master TCI
During ‘Diprifusor’ TCI
Graphical Liquid Crystal Display (LCD)
Decrement time
(to predict time of awakening)
Target
concentration
Concentration µg/ml
Effect-site concentration
Calculated
concentration
Time (minutes/hours)
Current infusion rate
Consult Operator’s Guide for details of display and operation
Main display of ALARIS IVAC TIVA TCI
During ‘Diprifusor’ TCI
Calculated
concentration
Target
concentration
Pump
status
Volume of
‘Diprivan’ infused
Effect-site (brain) concentration
and estimate time
Chevron keys for Trend graph of calculated
concentration
increment/decrement
Consult Directions for Use for details of display and operation
Syringe pumps incorporating ‘Diprifusor’
Common features of commercially-available pumps

Input/entry of patient details
– age 16–100 years
– body weight 30–150 kg

Recognition of ‘Diprivan’ 1% or 2%

Set and adjust target blood concentrations 0.1–15 µg/ml

Display of target concentration

Display of continuously changing calculated concentration

Access/display calculated effect-site (brain) concentration

Predict time to target and patient waking time

Access/display infusion rate and volume of ‘Diprivan’
Consult pump manufacturer for detailed specification
Target concentrations with ‘Diprifusor’ TCI
Principles of setting and adjusting targets
1200
8
Calculated concentration
(automatic calculation and display by system)
Target concentration
(selected by anaesthetist, displayed)
5
Infusion rate (ml/h)
2
3
4
100
4
50
2
1
0
0
0
5
10
15
Time (minutes)
20
25
30
35
Blood concentration (µg/ml)
6
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,MDPE)
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,MDAPE)
Small Scatter
(No Bias)
Calculated concentration
Measured concentration
Large Scatter
(No Bias)
Predictive performance of ‘Diprifusor’ TCI
Median absolute performance error (MDAPE)
General surgical patients *
(median values)
Overall
10%
MDAPE
20%
40%
24.1%
n = 46
Young (18 – 40 years)
n = 10
Middle (41 – 55 years)
n = 15
Older (56 years)
30%
22.6%
25.0%
24.2%
n = 21
Cardiac patients
(pre-bypass) †
(mean value) n = 21
23%
20%
40%
Proposed maximum acceptable range ‡, ¶
* Swinhoe CF et al. 1998 † Barvais L et al. 1996 ‡ Schüttler J et al. 1988 ¶ Glass PJA et al. 1990
-------UK
Population Kinetics !!
Individual Kinetics ?
CAUSE OF PHARMACOKINETIC VARIATIONS
drug concentration errors
measurement errors in drug assay
inadequate mixing at high infusion rates
dose dependent pharmacokinetics
technical errors in administration
errors in delivery systems
patient variability
Target concentration and induction time
Guidance based on results of ‘Diprifusor’ TCI clinical trial programme
Titrate against the response of the patient in order to achieve
the depth of anaesthesia required
l In adults (under 55 years of age) – usually 4 to 8 µg/ml
l In premedicated patients – initial target 4 µg/ml
l In unpremedicated patients – initial target 6 µg/ml
l Induction time with these targets is generally within the range of
60 to 120 seconds
l A lower initial target should be used in patients:
– over the age of about 55 years
– ASA grades III or IV
Consult full, local prescribing information
Initial target concentration for induction
UK study with prototype ‘Diprifusor’ TCI system----mean indiction time
103s in group 5 µg/ml.
Target concentration
Percentage of patients
successfully induced
100%
5 µg/ml
4 µg/ml
75%
50%
90%
75%
3 µg/ml
40%
25%
n = 20
n = 20
Failure of induction (patients not induced within 3 minutes
of achieving the target concentration): target increased to 6 µg/ml
n = 20
Chaudhri S et al. 1992
Induction time with ‘Diprifusor’ TCI
UK study of mainly ASA grade I or II 106 patients
Mean induction time (seconds)
20
‘Diprifusor’
TCI
40
60
80
55
n = 79
(SD 10.6)
p < 0.01
Manual control
75
n = 80
(SD 18.8)
The initial infusion rate was higher with `Diprifusor´ TCI (1,200 ml/h) than with manual control
(600ml/h). The mean dose of `Diprivan´ administered at the time of insertion of the laryngeal mask
air way was significantly higher (p < 0.05) with `Diprifusor´ TCI (201 mg) than with manual control (160 mg)
Russell D et al. 1995
Quality of induction with ‘Diprifusor’ TCI
UK study of mainly ASA grade I or II patients
Percentage of patients
‘Diprifusor’ TCI
Manual control
Poor 2.5%
Adequate
22.8%
Good 74.7%
Poor 5.0%
Adequate
22.5%
Good 72.5%
n = 79
The initial infusion rate was higher with `Diprifusor´ TCI (1,200 ml/h) than with manual control
(600 ml/h). The mean dose of `Diprivan´ administered at the time of insertion of the laryngeal mask
air way was significantly higher (p < 0.05) with `Diprifusor´ TCI (201 mg) than with manual control (160 mg)
n = 80
Hutton P et al. 1995
Quality of maintenance with ‘Diprifusor’ TCI
UK study of mainly ASA grade I or II patients
Percentage of patients (assessed by observer)
‘Diprifusor’ TCI
Manual control
Poor 0%
Poor 3.8%
Adequate
22.4%
Good 77.6%
Adequate
27.5%
Good 68.7%
n = 76
The initial infusion rate was higher with `Diprifusor´ TCI (1,200 ml/h) than with manual control
(600 ml/h). The mean dose of `Diprivan´ administered at the time of insertion of the laryngeal mask
air way was significantly higher (p < 0.05) with `Diprifusor´ TCI (201 mg) than with manual control (160 mg)
n = 80
Hutton P et al. 1995
Movement in response to initial surgical incision
UK study of mainly ASA grade I or II patients
NS p = 0.19
Percentage of patients
30%
28.8%
20%
19.7%
10%
Manual
control
‘Diprifusor’
TCI
n = 80
n = 76
The mean overall infusion rate during maintenance was significantly greater (p = 0.001) in the
‘Diprifusor’ TCI group (13.2 mg/kg/h) than in the manual control group (8.2 mg/kg/h)
Russell D et al. 1995
Movement during the remainder of maintenance period
Excluding initial surgical incision in UK study
p = 0.02
Percentage of patients
30%
26.2%
20%
10%
11.8%
Manual
control
‘Diprifusor’
TCI
n = 80
n = 76
The mean overall infusion rate during maintenance was significantly greater (p = 0.001) in the
‘Diprifusor’ TCI group (13.2 mg/kg/h) than in the manual control group (8.2 mg/kg/h)
Russell D et al. 1995
Need for supplementary manual bolus doses
Maintenance: UK study of mainly ASA grade I or II patients
Percentage of patients requiring
supplementary manual bolus doses to
deepen anaesthesia
50%
10%
3 – 5 doses
25%
40%
1 – 2 doses
0%
Manual
control
‘Diprifusor’
TCI
n = 80
n = 75
The mean overall infusion rate during maintenance was significantly greater (p = 0.001) in the
‘Diprifusor’ TCI group (13.2 mg/kg/h) than in the manual control group (8.2 mg/kg/h). Setting
a higher target concentration with ‘Diprifusor’ TCI results in automatic administration of a bolus
Hutton P et al. 1995
Maintenance target concentrations
Overall results from ‘Diprifusor’ TCI clinical trial programme
Patient type
Mean maintenance
target concentration
Healthy adult patients (ASA I or II)
3.5 to 5.3 µg/ml
Cardiac patients (ASA II, III or IV)
2.8 to 3.4 µg/ml
Age over 55 years
3.5 µg/ml
Haemodynamic effects during ‘Diprifusor’ TCI
Overall results from clinical trial programme
Induction
Maintenance
Healthy adults
Patients >55
years
Cardiac
patients
systolic BP
(mean
12 – 26%)
diastolic BP
(mean
16 – 28%)
(comparable to
manual
administration)
systolic and
diastolic BP
(similar pattern to
younger age
groups)
Hypotensive
effect
exacerbated
when opioid
infusion was
started before
Diprifusor’ TCI
‘’
Usually little
further change
in BP from
induction
Changes in
systolic BP
>younger age
groups
Usually little
further change in
BP from
induction
Recovery after ‘Diprifusor’ TCI
Overall results from clinical trial programme
Consistent with rapid early-phase recovery profile
of ‘Diprivan’
l Prompt, clear-headed recovery
l After short procedures (up to 40 minutes),
mean recovery time 5.0 – 10.3 minutes
l After long procedures (up to 6 hours),
mean recovery time 9.6 – 21.3 minutes
l Waking (eyes open) usually occurs at calculated
blood concentration 1 – 2 µg/ml
Patient characteristics
‘Diprifusor’ TCI clinical trial programme
Wide range of adult patients
(induction and maintenance)
l Age range 16 to 83 years (mean 45.4 years)
l Male (n = 186) or female (n = 131)
l ASA Class I, II, III and IV
l Inpatients and outpatients/day cases
l Spontaneous breathing and controlled ventilation
n = 317
Types of surgery
‘Diprifusor’ TCI clinical trial programme
Variety of procedures
(duration of treatment 10 minutes to >8 hours)
l
l
l
l
l
l
General
Cardiac
Gynaecological
Orthopaedic
Arthroscopic
Neurosurgery
n = 317
Other drug therapy
‘Diprifusor’ TCI clinical trial programme
Wide range of premedicants and supplementary
analgesics
l Premedication
– benzodiazepines (temazepam, diazepam, midazolam)
– ranitidine
l Pre-induction analgesia
– opioids (alfentanil, fentanyl, sufentanil)
– ketorolac
l Supplementary analgesia
– nitrous oxide
– alfentanil
– sufentanil
– alfentanil + nitrous oxide/oxygen
– fentanyl + nitrous oxide
l Neuromuscular blocking drugs
n = 317
Value of TCI in patients with anaesthetic problems
Case reports with ‘Diprifusor’ TCI or prototypes
l Bronchopleural fistula
Donnelly JA & Webster RE, 1991
l Undrained pneumothorax
Crofts SL & Hutchison GL, 1991
l Drained pneumothorax
Millar FA et al. 1992
l Difficult airway due to fixed-flexion deformity of cervical spine
MacKenzie RE & McFadzean WA, 1992
l Myotonic dystrophy
Tzabar Y & Marshall R, 1995
Benefits
l Maintain precise control of depth of anaesthesia with small
incremental changes in target concentrations
l Allow most patients to be anaesthetised without episodes
of apnoea or exposure to nitrous oxide
Tolerability profile of ‘Diprifusor’ TCI
Clinical trial programme
l Tolerability profile of ‘Diprivan’ (propofol) is unchanged
when administered by TCI
l Similar pattern of adverse events with ‘Diprifusor’ TCI and
manually-controlled infusions of ‘Diprivan’
l Hypotension (1.58%) and sinus bradycardia (1.26%) were
the only events with frequency > 1%
l No unexpected adverse events revealed
l No reports of awareness
n = 317
TCI FOR HIGH RISK PATIENTS
select a low target concentration of propofol such
as 1µg/ml and WAIT to observe the effect
time MUST be allowed for adequate equilibration of
the effector site
increase in steps of 0.5-1.0 µg/ml until the desired
effect is achieved
10
8
6
4
2
0
0
10
20
30
10
8
6
4
2
0
0
10
20
30
User preferences on ease of use (convenience)
Assessed by questionnaire in ‘Diprifusor’ TCI UK study
Feature or variable
Number of anaesthetists (n=8) expressing
preference
‘Diprifusor’ TCIManual control No preference
Ease of set-up
Ease of setting target or infusion rate
Ease of adjusting depth of anaesthesia



Easier to use
Preferred choice of infusion technique
Statistical analysis was not performed












Portability
Reliability



Russell D et al. 1995
User preferences for ‘Diprifusor’ TCI
Assessed by questionnaire in European multicentre study
Overall
preference
93
7
p < 0.05
7
p < 0.05
25
p < 0.05
18
p < 0.05
0
Setting of
initial target/
infusion rate
93
Overall ease
of set-up
57
Adjustment
of depth of
anaesthesia
18
79 4
0%
25%
50%
75%
100%
Percentage of anaesthetists (n = 28) expressing
preference
‘Diprifusor’ TCI
Manual control
No difference
Continued ...
Servin F, 1997
User preferences for ‘Diprifusor’ TCI
Assessed by questionnaire in European multicentre study
continuation
Overall
preference
93
Management of
depth of anaesthesia
during syringe change
57
Management of
depth of anaesthesia
during unexpected
syringe changes
50
11
25
Overall
ease of use
89
0%
25%
50%
7
75%
7
p < 0.05
32
p < 0.05
25
NS
4
p < 0.05
100%
Percentage of anaesthetists (n = 28) expressing
preference
‘Diprifusor’ TCI
Manual control
No difference
Servin F, 1997
Movement in response to surgical stimuli
European multicentre study
Percentage of non-paralysed patients
p < 0.05
15%
14.6%
10%
5%
4.6%
Manual
control
‘Diprifusor’
TCI
n = 144
n = 153
Mean overall infusion rate: 11.0 mg/kg/h in manual control group and 12.1mg/kg/h (p < 0.05) in TCI group.
Servin FS, 1998
‘Diprifusor’ TCI: conclusions
European multicentre study
l ‘Diprifusor’ TCI was easily learnt and well accepted by
anaesthetists
l For anaesthesia with ‘Diprivan’, the clinical profiles of
‘Diprifusor’ TCI and manual control are very similar
l Overall user preference: of the two techniques, ‘Diprifusor’
TCI was preferred by most anaesthetists (93%) and they
found it easier to use (89%).
Servin FS, 1998
Main points about ‘Diprifusor’ TCI
Induction and maintenance of anaesthesia in adult patients
Clinical trial programme
l
Provides guidance on target concentrations in relation to age,
ASA status, premedication and supplementary analgesia
l Confirms that ‘Diprifusor’ TCI provides the major benefits of
‘Diprivan’:
– smooth induction
– good quality of maintenance
– rapid, clear-headed recovery with low frequency of PONV
l Shows that ‘Diprifusor’ TCI compared with manuallycontrolled infusion of ‘Diprivan’ offers additional advantages:
– more convenient administration (easier to use)
– improved control (more predictable and precise control
of the depth of anaesthesia)
Benefits to anaesthetist of ‘Diprifusor’ TCI
Induction and maintenance of anaesthesia in adult patients
Convenience and control
l
l
l
l
More convenient than
manually-controlled infusion
Avoids the need for time-consuming
calculation of infusion rates
Continuous process for
induction and maintenance
– more convenient than
intravenous induction/vaporizer
for maintenance
Allows wider appreciation and
experience of the clinical benefits
of ‘Diprivan’
静脉麻醉的相对不足
RELATIVE DISADVATAGES OF INTRAVENOUS ANESTHESIA
1. 全凭静脉麻醉或靶控输注麻醉的价格昂贵, 特 别是长时
间手术的麻醉
TIVA OR TCI: MUCH MORE EXPENSIVE THAN
INHALATION ANESTHESIA, ESPECIALLY IN LONG-TERM
SURGERY
2. TCI 技术尚不普及
TCI: NOT POPULAR IN CLINICAL
3. 诱导期血压易波动
BLOOD PRESSURE: EASY BEING FLUCTUITED
DURING INDUCTION
4. 给药后麻醉药必须在体内经过完整的药物代谢过程
INTRAVENOUS ANESTHETICS MUST BE
METABOLIZED AFTER INJECTION
THANK YOU！