1、Diprifusor TCI system Tagged Diprivan PFS loaded in syringe pump,Diprifusor TCI Subsystem Recognition software/electronics Diprifusor TCI Software/ 2 microprocessors,Pump software,Pump hardware,Finger grip Tag = PMR (Programmaable Magnetic Resonance*),Full Diprivan PFS is loaded correctly,Aerial,Cor
2、rect drug identification and usagel Operates in Diprifusor TCI mode only with taggedDiprivan PFS no other drugsl Confirms Diprivan concentration (1% or 2%) forcorrect infusion at requested target concentrationl Erases tag when PFS is nearly empty and preventsrefilling/reuse,Recognition tag in finger
3、 grip of Diprivan PFS Important safety features,Functionsl Control unit for syringe pumpl Recognition of tagged Diprivan PFS,Diprifusor TCI Subsystem Installed in syringe pumps that incorporate Diprifusor,8 cm,l Three-compartment pharmacokinetic modelSpecific set of pharmacokinetic parameters forDip
4、rivan (propofol)l Two independent algorithms for infusion controlFail-safe mechanism to enhance patient safety,Diprifusor TCI Software* Installed in Diprifusor TCI Subsystem,* University of Glasgow,Diprifusor TCI System Main components,Diprifusor TCI Subsystem Microprocessor + pharmacokinetic progra
5、m,Anaesthetist selects and inputs target blood concentration,Infusion pump incorporating Diprifusor,Patient,Anaesthetist inputs patient data (age, body weight),l Graseby 3500l Vial Mdical Master TCIl ALARIS IVAC TIVA TCI,Syringe pumps incorporating Diprifusor Commercially-available infusion systems*
6、,* Contact manufacturer for details and availability,Display panel of Graseby 3500 During Diprifusor TCI,Access INFO on effect site (brain) concentration, time to target.,Small decrement,Small increment,Access TOTAL amount of Diprivan infused,TCI status indicators , the word CALCULATED and symbol bl
7、ink during infusion,TCI status indicator,TCI status indicator,TARGET concentration,CALCULATED concentration,Liquid Crystal Display (LCD),Consult Instruction Manual for details of display and operation,Display panel of Vial Mdical Master TCI During Diprifusor TCI,Graphical Liquid Crystal Display (LCD
8、),Current infusion rate,Time (minutes/hours),Concentration g/ml,Decrement time (to predict time of awakening),Target concentration,Calculated concentration,Consult Operators Guide for details of display and operation,Effect-site concentration,Main display of ALARIS IVAC TIVA TCI During Diprifusor TC
9、I,Chevron keys for increment/decrement,Trend graph of calculated concentration,Effect-site (brain) concentration and estimate time,Volume of Diprivan infused,Pump status,Calculated concentration,Target concentration,Consult Directions for Use for details of display and operation, Input/entry of pati
10、ent details age 16100 years body weight 30150 kg Recognition of Diprivan 1% or 2% Set and adjust target blood concentrations 0.115 g/ml Display of target concentration Display of continuously changing calculated concentration Access/display calculated effect-site (brain) concentration Predict time t
11、o target and patient waking time Access/display infusion rate and volume of Diprivan,Syringe pumps incorporating Diprifusor Common features of commercially-available pumps,Consult pump manufacturer for detailed specification,Target concentrations with Diprifusor TCI Principles of setting and adjusti
12、ng targets,0,50,100,1200,0,5,10,15,20,25,30,35,4,6,8,0,2,Time (minutes),Infusion rate (ml/h),Blood concentration (g/ml),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 pe
13、rformance error,MDPE),Calculated concentration Measured concentration,No Bias,Significant Bias,Assessment of accuracy Measurement or predictive performance of a TCI system,Calculated concentration Measured concentration,Precision This is an indication of the size of the typical error from the predic
14、ted concentration (median absolute performance error,MDAPE),Small Scatter (No Bias),Large Scatter (No Bias),Predictive performance of Diprifusor TCI Median absolute performance error (MDAPE),10%,20%,30%,40%,MDAPE,20%,40%,Proposed maximum acceptable range , ,24.1%,22.6%,25.0%,24.2%,23%,* Swinhoe CF e
15、t al. 1998 Barvais L et al. 1996 Schttler 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 techni
16、cal errors in administration errors in delivery systems patient variability,Titrate against the response of the patient in order to achieve the depth of anaesthesia requiredl In adults (under 55 years of age) usually 4 to 8 g/mll In premedicated patients initial target 4 g/mll In unpremedicated pati
17、ents initial target 6 g/mll Induction time with these targets is generally within the range of 60 to 120 secondsl A lower initial target should be used in patients: over the age of about 55 years ASA grades III or IV,Target concentration and induction time Guidance based on results of Diprifusor TCI
18、 clinical trial programme,Consult full, local prescribing information,Initial target concentration for induction UK study with prototype Diprifusor TCI system-mean indiction time 103s in group 5 g/ml.,25%,50%,75%,100%,Target concentration,n = 20,n = 20,n = 20,40%,75%,90%,3 g/ml,4 g/ml,5 g/ml,Percent
19、age of patients successfully induced,Chaudhri S et al. 1992,Failure of induction (patients not induced within 3 minutes of achieving the target concentration): target increased to 6 g/ml,Induction time with Diprifusor TCI UK study of mainly ASA grade I or II 106 patients,Mean induction time (seconds
20、),Russell D et al. 1995,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 man
21、ual control (160 mg),Quality of induction with Diprifusor TCI UK study of mainly ASA grade I or II patients,Good 74.7%,Adequate 22.8%,Good 72.5%,Adequate 22.5%,Poor 2.5%,n = 79,n = 80,Poor 5.0%,Diprifusor TCI,Manual control,Percentage of patients,Hutton P et al. 1995,The initial infusion rate was hi
22、gher 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),Quality of maintenance with Diprif
23、usor TCI UK study of mainly ASA grade I or II patients,Diprifusor TCI,Manual control,Percentage of patients (assessed by observer),Good 77.6%,Adequate 22.4%,Good 68.7%,Adequate 27.5%,Poor 0%,n = 76,n = 80,Poor 3.8%,Hutton P et al. 1995,The initial infusion rate was higher with Diprifusor TCI (1,200
24、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),Movement in response to initial surgical incision UK study of main
25、ly ASA grade I or II patients,10%,20%,30%,Manual control n = 80,Percentage of patients,Diprifusor TCI n = 76,28.8%,19.7%,NS p = 0.19,Russell D et al. 1995,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 ma
26、nual control group (8.2 mg/kg/h),Movement during the remainder of maintenance period Excluding initial surgical incision in UK study,10%,20%,30%,Percentage of patients,Manual control n = 80,Diprifusor TCI n = 76,26.2%,11.8%,p = 0.02,Russell D et al. 1995,The mean overall infusion rate during mainten
27、ance 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),Need for supplementary manual bolus doses Maintenance: UK study of mainly ASA grade I or II patients,25%,50%,Percentage of patients requiring supplementary manual bolu
28、s doses to deepen anaesthesia,Manual control n = 80,Diprifusor TCI n = 75,40% 1 2 doses,10% 3 5 doses,0%,Hutton P et al. 1995,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
29、/h). Setting a higher target concentration with Diprifusor TCI results in automatic administration of a bolus,Maintenance target concentrations Overall results from Diprifusor TCI clinical trial programme,Patient type,Mean maintenance target concentration,Healthy adult patients (ASA I or II),Cardiac
30、 patients (ASA II, III or IV),Age over 55 years,3.5 g/ml,2.8 to 3.4 g/ml,3.5 to 5.3 g/ml,Haemodynamic effects during Diprifusor TCI Overall results from clinical trial programme,Healthy adults,Patients 55,years,Cardiac,patients,Induction,systolic BP,(mean,12 26%),diastolic BP,(mean,16 28%),(comparab
31、le to,manual,administration),systolic and,diastolic BP,(similar pattern to,younger age,groups),Hypotensive,effect,exacerbated,when,opioid,infusion was,started before,Diprifusor TCI,Maintenance,Usually little,further change,in BP from,induction,Changes in,systolic BP,younger age,groups,Usually little
32、,further change in,BP from,induction,Consistent with rapid early-phase recovery profile of Diprivanl Prompt, clear-headed recoveryl After short procedures (up to 40 minutes),mean recovery time 5.0 10.3 minutesl After long procedures (up to 6 hours),mean recovery time 9.6 21.3 minutesl Waking (eyes o
33、pen) usually occurs at calculatedblood concentration 1 2 g/ml,Recovery after Diprifusor TCI Overall results from 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
34、IVl Inpatients and outpatients/day casesl Spontaneous breathing and controlled ventilation,Patient characteristics Diprifusor TCI clinical trial programme,n = 317,Variety of procedures(duration of treatment 10 minutes to 8 hours)l Generall Cardiacl Gynaecologicall Orthopaedicl Arthroscopicl Neurosur
35、gery,Types of surgery Diprifusor TCI clinical trial programme,n = 317,Wide range of premedicants and supplementary analgesicsl Premedication benzodiazepines (temazepam, diazepam, midazolam) ranitidinel Pre-induction analgesia opioids (alfentanil, fentanyl, sufentanil) ketorolacl Supplementary analge
36、sia nitrous oxide alfentanil sufentanil alfentanil + nitrous oxide/oxygen fentanyl + nitrous oxidel Neuromuscular blocking drugs,Other drug therapy Diprifusor TCI clinical trial programme,n = 317,l Bronchopleural fistulaDonnelly JA & Webster RE, 1991l Undrained pneumothoraxCrofts SL & Hutchison GL,
37、1991l Drained pneumothoraxMillar FA et al. 1992l Difficult airway due to fixed-flexion deformity of cervical spineMacKenzie RE & McFadzean WA, 1992l Myotonic dystrophyTzabar Y & Marshall R, 1995Benefitsl Maintain precise control of depth of anaesthesia with small incremental changes in target concen
38、trationsl Allow most patients to be anaesthetised without episodes of apnoea or exposure to nitrous oxide,Value of TCI in patients with anaesthetic problems Case reports with Diprifusor TCI or prototypes,l Tolerability profile of Diprivan (propofol) is unchangedwhen administered by TCIl Similar patt
39、ern of adverse events with Diprifusor TCI andmanually-controlled infusions of Diprivanl Hypotension (1.58%) and sinus bradycardia (1.26%) werethe only events with frequency 1%l No unexpected adverse events revealedl No reports of awareness,Tolerability profile of Diprifusor TCI Clinical trial progra
40、mme,n = 317,TCI FOR HIGH RISK PATIENTS,select a low target concentration of propofol such as 1g/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 g/ml until the desired effect is achieved,User preferences on ease of us
41、e (convenience) Assessed by questionnaire in Diprifusor TCI UK study,Feature or variable,Number of anaesthetists (n=8) expressing,preference,Diprifusor TCI,Manual control,No preference,Ease of set-up,Ease of setting target or infusion rate,Ease of adjusting depth of anaesthesia,Portability,Reliabili
42、ty,Easier to use,Preferred choice of infusion technique,Russell D et al. 1995,Statistical analysis was not performed,User preferences for Diprifusor TCI Assessed by questionnaire in European multicentre study,Servin F, 1997,0%,25%,50%,75%,100%,Percentage of anaesthetists (n = 28) expressing preferen
43、ce,Diprifusor TCI,Manual control,No difference,Overall preference,Setting of initial target/ infusion rate,Overall ease of set-up,Adjustment of depth of anaesthesia,7,p 0.05,p 0.05,p 0.05,p 0.05,93,7,93,0,18,57,25,4,79,18,Continued .,User preferences for Diprifusor TCI Assessed by questionnaire in E
44、uropean multicentre study,Servin F, 1997,0%,25%,50%,75%,100%,Percentage of anaesthetists (n = 28) expressing preference,Diprifusor TCI,Manual control,No difference,Overall preference,Management of depth of anaesthesia during syringe change,Management of depth of anaesthesia during unexpected syringe
45、 changes,Overall ease of use,7,p 0.05,p 0.05,NS,p 0.05,93,32,57,25,50,25,4,89,7,11,continuation,Movement in response to surgical stimuli European multicentre study,5%,10%,15%,Percentage of non-paralysed patients,Manual control n = 144,Diprifusor TCI n = 153,14.6%,4.6%,p 0.05,Servin FS, 1998,Mean ove
46、rall infusion rate: 11.0 mg/kg/h in manual control group and 12.1mg/kg/h (p 0.05) in TCI group.,l Diprifusor TCI was easily learnt and well accepted by anaesthetistsl For anaesthesia with Diprivan, the clinical profiles of Diprifusor TCI and manual control are very similarl Overall user preference:
47、of the two techniques, Diprifusor TCI was preferred by most anaesthetists (93%) and they found it easier to use (89%).,Diprifusor TCI: conclusions European multicentre study,Servin FS, 1998,Clinical trial programmel Provides guidance on target concentrations in relation to age,ASA status, premedicat
48、ion and supplementary analgesial Confirms that Diprifusor TCI provides the major benefits ofDiprivan: smooth induction good quality of maintenance rapid, clear-headed recovery with low frequency of PONVl Shows that Diprifusor TCI compared with manually-controlled infusion of Diprivan offers additional advantages: more convenient administration (easier to use) improved control (more predictable and precise controlof the depth of anaesthesia),
