TIVA & TCI Sedation

Dr James F PeerlessNovember 2012

Objectives

• TIVA & TCI– What, why, when, where and how

• Models, Monitoring & Limitations• Context-Sensitive Half-Time– Suitability of drugs for TCI

TCI

• “Target-Controlled Infusion”• An infusion system whereby the target

concentration of a particular agent is selected.

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

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

Pharmacokinetics

Pharmacokinetics

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

Models

• Propofol– Marsh 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)

Induction of Anaesthesia

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

Induction of Anaesthesia

• Select a target concentration• Press ‘go’• Ensure adequate O2• Change settings/increase the target

concentration in slow, small stages

Numbers!

• Propofol TCI– 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

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]

Context-Sensitive Half-Time

• The CSHT is:“The time taken for the drug concentration

to reduce by half once an infusiondesigned to maintain a constant plasma

concentration is stopped.”• CSHT for a specific drug will vary depending on

the length of the infusion

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

Upon Stopping the Infusion

Ideal drugs

• Small VD

• Rapid metabolism (no active metabolites)• High Cl• Short CSHT

• Propofol, alfentanil, remifentanil

Remifentanil – wow!

• Rapidly metabolised– 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

Context-Sensitive Half-TimeCS

HT

(min

)

Duration of Infusion (hr)

Fentanyl

Thiopental

Alfentanil

Propofol

Remifentanil

Summary

• Target concentrations are calculated, not measured

• TCI pumps maintain three superimposed infusions, one at a constant rate to replace drug elimination and two exponentially decreasing infusions to match drug removed from central compartment to other peripheral compartments of distribution

Questions?