#### Intravenous Anesthesia - General Considerations

### Pharmacokinetic Fundamentals and IV Anesthesia

I. There are two important fundamental parameters (Cl and V_{d}) and one frequently misleading derived parameter (T

_{1/2}).

**Cl = clearance = Dose/AUC**

- AUC =
**a**rea**u**nder the**c**urve; i.e., the drug level vs. time curve - Clearance may be thought of as the volume of plasma that appears to be entirely cleared of drug per unit time.
- Most useful in determining dosage regimens (e.g.: rate of continous infusion to maintain a given plasma level.)

**V**

_{d}= Dose/Cp_{i}- Cp
_{i}= initial plasma drug concentration - Quantitatively characterizes extent of tissue distribution

- Important in determining loading dose

- An "apparent" volume

- In a multicompartmental model, V
_{dss}= sum of all individual compartment volumes

**T**

_{1/2}= (0.693V_{d})/Cl- Time required for drug concentration to decrease by 50%

- Not a fundamental pharmacokinetic parameter

- Not as useful as Cl or V
_{d}

- In a multicompartmental model there are as m any T
_{1/2}'s as there are compartments

II. Pharmacokinetic parameter estimation

How is it done? Compartmental modeling.

Compartment modeling seeks to estimate a set of parameters that adequately describe the disposition of a drug in a population.

Modeling theory:

Modeling methodology:

raw data -> analyzed data (computer aided nonlinear regression analysis) -> results: A, B, alpha, beta -> V

_{d}, Cl

III. Context-Sensitive Half-Time

Time necessary to achieve a 50% decrease in plasma concentration after termination of a continuous infusion.

IV. TIVA

TIVA =

**t**otal

**i**ntravenous

**a**nesthesia

TIVA means the use of IV agent(s) exclusively to provide a complete anesthetic. This involves achieving the desired elements of the 4 components of general anesthesia ala Woodbridge (1957): block of mental, reflex, sensory and motor function; or, the

**3 A's of Anesthesia**(with or without muscle relaxation):

- Amnesia (anxiolysis, ataraxia)
- Autonomic areflexia (CV, resp, GI)
- Analgesia
- +/- muscle relaxation

**ketamine**: the most complete of our IV agents provides 3 A's.

TIVA may be administered by repeated bolus injections, or, preferably by

**continuous infusion**.

Advantages of TIVA:

- Combination of drugs, separately infused, allows titration of each to the specific dose required to meet the specific needs of the case.
- The anesthetic is completely independent of the patient's airway and breathing. (Especially advantageous when patient's airway or breathing are compromised or when surgery involves the airway or lungs.)
- Very portable. Simplifies "remote" anesthesia. No anesthesia machine (vaporizers) needed.

Need Cp desired and Cl to compute Cp x Cl = infusion rate to maintain Cp;

and need estimate of loading dose to get to Cp in the first place.

Four ways to get to Cp:

- Memorize, look up, ask approximate safe induction dose of drug
- Loading dose = Cp x V
_{d}

But need to use the right volume of distribution. V_{dss}is too big.

Use V_{dpe}, volume of distribution at peak effect.

V_{dpe}= V_{i}(%Cpi remaining at peak effect) - Easier: Just infuse faster than Cp x Cl until desired effect (clinical signs), then slow rate to Cp x Cl. Makes up for interindividual variation.
- Perhaps Easiest: Use a computer; CACI = computer assisted continuous infusion.

Enter population parameters and turn on. Monitor.