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Dr James F Peerless November 2012

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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?

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