1. Dr James F Peerless November 2012
TIVA & TCI Sedation
Dr James F Peerless
November 2012

2. Objectives TIVA & TCI Models, Monitoring & Limitations
What, why, when, where and how
Models, Monitoring & Limitations
Context-Sensitive Half-Time
Suitability of drugs for TCI

3. TCI “Target-Controlled Infusion”
An infusion system whereby the target concentration of a particular agent is selected.
General term for tiva and sedation

4. TIVA “Total IntraVenous Anaesthesia”
Anaesthesia provided solely by IV route
Generally as an infusion which is titrated at a specific rate to achieve a specific concentration
Cp – plasma concentration
Ce – effect site concentration
But could be crudely as a basic infusion
Cpt – target plasma

5. Indications/Benefits
When:
Inhalational agents unavailable
Administering inhalational agents is difficult
Inhalational agents are contraindicated
Patient has severe PONV
Also:
Reduces staff exposure to inhalational agents
Reduces pollution
NOT:
Unmonitored sedation at home

6. Pharmacokinetics C1 – vrg C2 – muscle C3 – fat
Over time, drug redistributes down conc gradient to other compartments
Rate Constants exist between the compartments representing distribution and redistribution
0  1 drug entering the body
based upon clearance and metabolism – elimination still occurs via c1

7. Pharmacokinetics

8. Why do we use models?
At present in clinical use there is no method of measuring drug concentrations real time analogous to the end tidal volatile agent concentration
Models only – no actual plasma measurements
Most models describe healthy volunteers and there is poor correlation in unwell patients
The trend of increasing obesity does alter pharmacokinetics and accuracy of the pumps

9. Models Propofol Remifentanil Marsh model Schnider model
3-compartment model optimised by weight, gender & age
Schnider model
Diprivan 2% prefilled syringes
Remifentanil
Minto model
Made up to 50 mcg mL-1 (2 mg in
40 mL 0.9% N. Saline)

10. Induction of Anaesthesia
Good IV access – visible at all times!!
Dedicated line where possible
Ensure a dripping drip
Anti-reflux valves
Minimise dead-space

11. Induction of Anaesthesia
Select a target concentration
Press ‘go’
Ensure adequate O2
Change settings/increase the target concentration in slow, small stages

12. Numbers! Propofol TCI Remifentanil
Sedation: 1 – 2 mcg mL-1
Anaesthesia EC50: 6 – 7 mcg mL-1
Remifentanil
0.05 – 0.5 mcg kg-1 min-1
TCI: 4 – 8 ng mL-1
Bear in mind individual variations in pharmacokinetics and drug interactions
4-5 mcg/mL with 67% N20
4-6 mcg/mL with remi
Old people have a low VD
Obese people have a high C3
Children
Models are based upon pharmacokinetic data from HEALTHY individuals
Monitoring: HR, BP, EtCO2, BiS
Use of other drugs – remi, N2O, will alter the requirements

13. Limitations Inability to monitor actual drug concentration
Slow recovery/wake-up after long operations due to distribution across compartments
Increased cost compared with volatile agents
Interruption to TCI delivery may go unnoticed longer than with volatiles
[fighting with other theatres for use of PK pumps]
Accuracy of TCI infusions 
There are changing pharmacokinetics of a drug with age and the effect site concentration is calculated and not measured. Rate of equilibration between blood and effect site depends on cardiac output, central blood volume, and other pharmacokinetic factors such as lipid solubility etc. The elderly have smaller central volume of distribution, decreased clearance and increased time to peak effect.

14. Context-Sensitive Half-Time
The CSHT is:
“The time taken for the drug concentration
to reduce by half once an infusion
designed to maintain a constant plasma
concentration is stopped.”
CSHT for a specific drug will vary depending on the length of the infusion

15. CSHT
During an infusion, drugs will accumulate and equilibrate within all the tissues/compartments.
The longer the duration of the infusion, the higher the degree of accumulation, which will maintain plasma levels once the infusion is stopped.
As a result, some drugs are better suited to infusions than others

16. Upon Stopping the Infusion

17. Ideal drugs Small VD Rapid metabolism (no active metabolites) High Cl
Short CSHT
Propofol, alfentanil, remifentanil

18. Remifentanil – wow! Rapidly metabolised Short t1/2elim High Cl
Non-specific plasma and tissue esterases
Short t1/2elim
1.3 minutes
High Cl
2.5 L kg-1 hr-1
Small VD
0.35 L kg-1
= context-“insensitive” half-time
CSHT of about 3-10 minutes
Remember long-acting opioids

19. Context-Sensitive Half-Time
CSHT (min)
Duration of Infusion (hr)
Fentanyl
Thiopental
Alfentanil
Propofol
Remifentanil
After 8 hrs
Fent 282 min
Alf 64
Prop 41
Remi 9

20. Summary
Target concentrations are calculated, not measured

21. Questions?