Total intravenous anesthesia (TIVA) and target controlled infusion (TCI) were discussed. TCI uses infusion models like Marsh and Schnider to calculate the target effect-site concentration of drugs like propofol and opioids to achieve anesthesia. Monitoring anesthetic depth with tools like BIS or AEP is recommended to optimize drug delivery and avoid overdose. While TIVA is commonly used in adults, data in pediatrics is still limited especially for infants, and propofol requires caution for prolonged sedation in ICU. No consensus was reached on whether volatile or intravenous agents lead to better outcomes in cardiac surgery. Office-based anesthesia requires adequate monitoring, emergency equipment, and staff training for patient safety.

1. Total intravenous anesthesia (TIVA) &
Target Controlled Infusion(TCI)
台北榮總麻醉部
王審之

2. TIVA
• Total intravenous anesthesia
– Amnesia and analgesia
• Sedation in intensive care unit
• Day surgery
• Office based anesthesia
– Muscle relaxant

3. What is TCI ?

4. TCI
• Target controlled infusion
– Amnesia: propofol
• Infusion model: Marsh, Schnider
– Analgesia: opioid
• Fentanyl
• Alfentanil
• Remifentanil
• Sufentanil

5. Time (min)
Alfentanil effect site concentration
in endoscopic submucosa dissection petients

6. TCI for adult: propofol

7. Infusion mode for Propofol
• Marsh
– Derived from Gept’s model (1987)
• Regional anesthesia combined propofol infusion
• Total 18 patients
• No BMI data
– Scarecely adequate in the elderly
• Anaesthesia 1998;53:Suppl. 1:61-67
• Ann Fr Anesthn Reanim 2000;19:R027
• For patients less than 70y/o

8. Infusion mode for Propofol
• Modified Marsh
– Anesthesiology 2000;92:399-406
– 20 women (health volunteers), age: 18-60y/o
• Obesity is excluded
• Target concentration 5.4μg/ml
– A biophase model combining the Marsh kinetics and a time to peak
effect of 1.6 min accurately predicted the time course of propofol
drug effect.

9. Infusion mode for Propofol
• Schnider
– Anesthesiology 1998; 88: 1170-1182
– Patient population: 25-81y/o health volunteers
• Patient number: 24
• Body weight: 44.4~123 kg
– Covariates
• Age, gender, height and body weight, lean body mass
• BMI: <43 (M) and <35(F)

10. lower keo demand a higher concentration gradient between plasma and
effect-site to achieve a certain effect-site target concentration,

12. Which is better
• In a recent clinical trial, changes in the BIS correlated better with effect
site concentration predictions by the original Marsh model than with the
Schnider model.
– Anesthesia 2007; 62: 661-6
• Potential benefits with the Marsh II and Schnider models are reduced
hemodynamic and respiratory effects.
– Age is included as a pharmacokinetic co-factor in the Schnider model

13. TCI for adult: opioid

14. Fentanyl
Context sensitive half time:
The time required for the drug
concentration to decrease to
half of it’s value.

15. Fentanyl recipe
• Bolus 3 μg/kg over 30sec
• Followed by 2 μg/kg/hr for 30min
• 1.5 μg/kg/hr from 31-150min
• 1 μg/kg/hr until 30min before skin closure

16. Alfentanil
• The model of Scott
– J Pharm Experiment Ther 1987; 240: 159-166
– More accurate than the model of Maitre
• Anesthesiology 1990;73:66-72
• Anesth Analg 1993;77:801-810
– Clearance mainly dependent on liver metabolism
• Enzyme inhibitor: cimetidine, fluconazole, diltiazem, macrolide (erythromycine),
imidazole

17. Hypnotic combined opioid

18. Alfentanil

19. TCI diy

20. TIVA trainer for simulation
• Download from EuroSIVA website
– 100 Euro for registration

21. Should we routinely monitor
anesthetic depth in TIVA?

22. Propofol infusion syndrome
• Defined as acute bradycardia progressing to asystole
combined with lipemic plasma, fatty liver enlargement,
metabolic acidosis with negative base excess > 10mmol/l,
rhabdomyolysis or myoglobinuria associated with propofol
infusion.
– Large dose, prolonged duration.
• A hereditary mitochondrial fatty acid metabolism impairment
resembling medium chain acyl-CoA dehydrogenase deficiency
is responsible for the susceptibility to the development of
propofol infusion syndrome.
• Minerva anestesiol 2009;75:339

23. TCI without monitoring
• Driving with one eye closed.
– Expert opinion

24. AEP guided propofol infusion
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Concentration/ml痢
8
7
6
5
4
3
2
1
0
Inf.Rate(ml/hr)+Decr.Time
10009008007006005004003002001000

25. BIS
• Processed EEG
– 40-60: general anesthesia
– >90 awake, memory intact
• Limitations
– Not useful during Ketamine anesthesia
– Insufficient information on effects of N2O, high-dose opioid &
neurologic disease.
– False-elevated BIS
• EMG activity
• High electrode impedances
– Does not predict the moment consciousness returns

26. NEJM 2008
• No difference in awareness.
• Not associated with reduced administration of volatile
anesthetic gases.
• Awareness occurred even when BIS values were within the
target ranges.

27. AEP
• Not significantly affected by opioids.
• Auditory modality is the most receptive sensory channel for
perception during anesthesia.
• Limitations
– False elevated AEP
• EMG activity
– BIS and AAI markedly decreased after administration of myorelaxant . A&A
2008; 107(4): 1290-4
• Noise ??

28. BIS vs AEP
• The range of values obtained at
the time of loss of eyelash reflex
AEP: 15-99
BIS: 39-83

29. BIS vs AEP
• The awake values for AAI were less and showed more variation between
subjects than BIS.

30. Closed loop system
• The input
– Drug delivery (etc. propofol, opioids)
• The output
– evoked potential, bispected index (BIS), blood pressure, pulse rate.

31. Discussion …
• Can anesthetic depth monitoring decrease unnecessary
propofol use?
– Putative early propofol infusion syndrome: typical symptoms without
cardiac involvement.
• Monitor pH, lactate, base excess and creatinine kinase is recommended.

32. Can we applied propofol continuous
infusion for children or even infant ?

33. Infusion mode for Propofol
• Kataria
– Anesthesiology 1994; 80: 104-122
– Patient population: 3-11y/o children receiving body surface surgery.
• Patient number: 53
– Three-compartment pharmacokinetic model
• Weight-adjusting the volumes and clearances significantly improved the accuracy.

34. Infusion mode for Propofol
• Marsh (Pediatric)
– BJA 1991; 67: 41-48
• Marsh (Pediatric)
– Patient population: 1-12y/o children receiving minor surgery
• Patient number: 20

35. Infusion mode for Propofol
• Paedfusor
– BJA 2003; 91: 507~513
– 32 children of ASA status II±III, undergoing elective cardiac surgery or
cardiac catheterization were enrolled.
– The effect of bypass
• system was negative during bypass: -5.5%
• Large volume of distribution (ml): 270: 4600: 1340: 8200
– No outcome data

37. For pediatric anesthesia
• Propofol is not indicated for use in children < 3y/o.
– Pediatric Anesthesia 2004; 14: 374-379
– Still lack of FDA approval
• Propofol is not approved for sedation in pediatric ICU
patients.
• Minerva anestesiol 2009;75:339

38. For MEP monitoring
• J Neurosurg Pediatrics 7:000–000, 2011
– From Texas
– For 10 children age under 3 year old (mean age: 16.8 months)
receiving complex spine surgery
– Sevo induction
– Maintenance: propofol 6-15mg/kg/hr
– No mention of OP time
• Discussion: The loss or absence of MEP amplitude may be minimized
when propofol is administered in small, titrated doses (6-15mg/kg/hr) in a
child younger than 3 years of age.

39. In PICU in Australia and NZ
• The majority of practitioners (82%) use propofol infusion in
children in PICU
– the main indication being for short-term sedation in children requiring
procedures.
• 67% of paediatric intensivists use maximum infusion doses
that may be considered dangerously high (> or = 10 mg/kg/h)
• 19% use propofol infusion for prolonged periods (> 72 hours).
• A smaller proportion (15%) of respondents indicate that they
may use both higher doses and prolonged periods of infusion
• Anaesth Intensive Care. 2002 Dec;30(6):786-93.

40. For prolonged sedation
• Propofol should be used with extreme caution for prolonged
sedation in intensive care unit patients, at dose rates of below
5 mg/kg per h
• Curr Opin Anaesthesiol. 2003 Jun;16(3):285-90
• TIVA with propofol in infants younger than 1 year old requires
extensive experience with TIVA in older children and with the
handling of this special age group and should be undertaken
with maximum precautionary measures.
– Infusion rate up to 9mg/kg/hr over 2-4hours are recommended for
TIVA in children.
• Anaesthesist. 2003 Sep;52(9):763-77.

41. BIS for children
• The Bispectral Index correlates well with the Ramsay score in
the normal sedated child.
• Pediatric Critical Care Medicine: January 2003 ; 4(1) 60-64

42. Can patient outcome be determined
by anesthetic agent we used?

43. TIVA in cardiac surgery
• Still no conclusion
– 30-day mortality in acute procedure was significantly lower in the
propofol group.
– 30-day mortality caused by infection, pulmonary causes or renal
causes was significantly lower in the propofol group.
– J Cardiothorac Vasc Anesth 2007;21:664-71
– Volatile anesthetic in AVR: better preservation of myocardial function
and a reduced postoperative release of troponin I.
– Less ICU stay in the volatile anesthetic group.
– Anesth Analg 2006;103:289-96

44. Safety issues for office-based
anesthesia

45. 2008 ASA statement
• A reliable source of oxygen and backup oxygen sources.
• An adequate and reliable source of suction.
• Reliable system for scavenging waste anesthetic gases.
– while inhalation anesthetics are administered…
• Adequate illumination of the patient, anesthesia machine and
monitoring equipment.
– Hard to define adequate illumination.
• Sufficient space to accommodate necessary equipment and
personnel.
– Most critical part in most circumstances in our hospital.
• Sufficient electrical outlets

46. 2008 ASA statement
• Anesthetic equipment
– a self-inflating hand resuscitator bag capable of administering at least
90 percent oxygen as a means to deliver positive pressure ventilation
– adequate anesthesia drugs, supplies and equipment for the intended
anesthesia care
– adequate monitoring equipment
• An emergency cart
– a defibrillator
– emergency drugs
– equipment adequate to provide cardiopulmonary resuscitation
• adequate staff trained to support the anesthesiologist and a
reliable means of two-way communication to request
assistance.

47. 2008 ASA statement
• Appropriate postanesthesia management should be provided.
– Our weak point.

48. Statement on safe use of propofol
• ASA 2009 statement
– The practitioner should be present throughout the procedure and be
completely dedicated to that task.
– manage the potential medical complications of sedation/anesthesia.
– proficient in airway management
– have advanced life support
– understand the pharmacology of the drugs used.
– Monitoring
• Ventilation: Monitoring for the presence of exhaled carbon dioxide should
be utilized because movement of the chest will not dependably identify
airway obstruction or apnea.
• oxygen saturation
• heart rate
• blood pressure.

49. Summary
• Safer environment
– Oxygen supply and suction should be close to the patient.
• Safer equipment
– Emergency cart: defibrillator
– Keep ABC in mind
– End-tidal CO2 monitoring

50. Thanks for your attention