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 = area under the curve; 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 = total intravenous anesthesia
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

If all 4 components are desired, we need a combination of drugs since no single available agent provides all 4. Most IV anesthetics provide only the first 1 or 2 A's. NOTE: remarkable exceptional 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.

TIVA: How To Do It:
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.

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