Intravenous Anesthesia - General Considerations
Pharmacokinetic Fundamentals and IV AnesthesiaI. There are two important fundamental parameters (Cl and Vd) and one frequently misleading derived parameter (T1/2).
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.)
Vd = Dose/Cpi
- Cpi = initial plasma drug concentration
- Quantitatively characterizes extent of tissue distribution
- Important in determining loading dose
- An "apparent" volume
- In a multicompartmental model, Vdss = sum of all individual compartment volumes
T1/2 = (0.693Vd)/Cl
- Time required for drug concentration to decrease by 50%
- Not a fundamental pharmacokinetic parameter
- Not as useful as Cl or Vd
- In a multicompartmental model there are as m any T1/2'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.
raw data -> analyzed data (computer aided nonlinear regression analysis) -> results: A, B, alpha, beta -> Vd, Cl
III. Context-Sensitive Half-Time
Time necessary to achieve a 50% decrease in plasma concentration after termination of a continuous infusion.
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)
- +/- muscle relaxation
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 Vd
But need to use the right volume of distribution. Vdss is too big.
Use Vdpe, volume of distribution at peak effect.
Vdpe = Vi(%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.