Total Intravenous Anesthesia:

Theoretical Foundation and

Practical Considerations

Talmage D. Egan, M.D.

University of Utah School of Medicine

October 21

, 2022

Disclosures

In the last 2 years, Dr. Egan has the following industry

relationships to disclose:

• Founder and equity partner: Medvis

• Research support: Medtronic

• Scientific Advisory Board Member: Acacia Pharma

(Brief introduction to TIVA theory and practice…)

Overall Goal

Establish the scientific and

practical foundation upon which

to base a TIVA practice.

TIVA vs Inhaled Drug Delivery

Gaining access to the circulation via

the lung affords fundamental

advantages that have set a standard

for innovation in TIVA practice since

the mid 1990s.

Key Point

Egan (J Clin Anesth 1996)

(Circa 1990s)

Egan (J Clin Anesth 1996)

(Circa 1990s)





Anesthesia Posology

Anesthesia posology (the study

of drug dosing) is fundamentally

different than other specialties

of medicine.

Key Point

Kuck & Egan (Br J Anaesth 2017)

A last try at popularizing

the term “posology….”

“Combining the Greek words

‘posos’ (how much) and ‘logos’

(science), posology can be thought

of more simply as ‘dosology’.”

Egan (Anesth Analg 2018)

General Approach to Anesthesia Posology

Kuck & Egan (Br J Anaesth 2017)

Anesthesia Posology

A surfing analogy is helpful in

understanding the modern

approach to anesthesia posology.

Key Point

Egan & Shafer (Anesthesiology 2003)

TIVA Practice Domains

There are three TIVA practice

domains (i.e., dose, concentration,

& effect). The effect domain is

optimal.

Key Point

Egan (Anesth Analg 2018)

Three TIVA Practice Domains

Egan (Anesth Analg 2018)

The Dose Domain

 Simple to use

 Familiar to all

 Ignores temporal

changes

 Slow to steady-state

 Ignores intersubject

variability

Egan (Anesth Analg 2018)

The Concentration

Domain

 Automates dosage

calculations

 Accounts for temporal

changes

 Quick to steady-state

 Accounts for co-

variate effects (PK)

 Ignores intersubject

variability

 Less familiar (USA)

Egan (Anesth Analg 2018)

The Effect Domain

 Automates dosage

calculations

 Accounts for temporal

changes

 Quick to steady-state

 Accounts for co-

variate effects (PKPD)

 Accounts for intersub-

ject variability

 Complicated control

system (automated)

 Suboptimal sensors

 Less familiar

 Unintended conse-

quences?

(or Open Loop)

Usually Best!

Most important!

Egan (Anesth Analg 2018)

Crucial Drug Behaviors and TIVA

Certain pharmacokinetic attributes

inform TIVA posology for bolus and

infusions conditions. These attributes

are best understood through PK-PD

simulation.

Key Point

Obara & Egan

(in Hemmings & Egan, Elsevier 2019)

Simulations

Normalized to

peak Ce!

Any anesthetic drug…

Fast, medium, &

slow drugs…

Surprisingly long for

most anesthetic drugs…

Steady State

What amount of

decrease is required?

How long will it take?

A given decrement almost

always takes longer

with longer infusions…

Longer and longer…

Crucial Drug Behaviors and TIVA

Certain pharmacodynamic concepts

inform TIVA posology. Chief among

these are propofol-opioid

pharmacodynamic interactions.

Key Point

Ogura & Egan (in Hemmings & Egan, Elsevier 2019)

most important feature?

Propofol Clinical Pharmacology & TIVA

Simulation of propofol’s

pharmacokinetic behavior helps

inform posological decisions in TIVA.

Key Point

Rapid onset, moderately

rapid offset (depends on dose)…

50-year-old, 75 kg, 175 cm male

Concentrations rise throughout the

course of a typical length case…

Induction bolus produces “supra-

therapeutic” concentrations for a

time, then gradual rise begins…

Target Controlled Infusion!

Back-end behavior changes

as the infusion goes on…

Standard Infusion!

Back-end behavior slightly

different for standard infusions

(i.e., not at steady-state)…

Obara & Egan (in Hemmings & Egan, Elsevier 2019)

Context sensitive half-time

assumes TCI administration…

Opioid Clinical Pharmacology & TIVA

Simulation of remifentanil and

fentanyl pharmacokinetic behavior

helps inform posological decisions in

TIVA.

Key Point

Fentanyl slower peak,

much slower offset…

Normalized to

peak Ce!

Remifentanil reaches steady-

state rapidly; fentanyl does

not reach steady-state…

Remifentanil levels

rapidly decline...

Egan et al (Anesthesiology 1993)

Remifentanil is the only TIVA

drug with a time independent

context sensitive half-time…

The clinical state changes

quite a bit with these fentanyl

fluctuations…

Tips and Tricks of the TIVA Trade

Certain practical tips are helpful for

successful TIVA practice.

Key Point

Obara & Egan (in Hemmings & Egan, Elsevier 2019)

Supplementary Material

Egan (Anesthesiology 2003)

Egan et al (Br J Anaesth 2020)

Target Controlled Infusion Practice

Low High

GAIN

TCI is the most

sophisticated titration…