Inhalational Anesthetic Agents
Pharmacokinetics
The depth of general anesthesia depends on the partial pressure (or gas fraction) exerted by the inhalational
agent in the patient's brain (b). This brain partial pressure depends on arterial (a) blood partial pressure
which depends on alveolar (A) partial pressure which depends on partial pressure of agent in the inspired gas (I):
pI -> pA -> pa -> pb, or
FI -> FA -> Fa -> Fb
Recall that:
partial pressure of a component gas = (fraction of total gas that is component gas) x (total pressure), or
pc = Fc x P
To change Fb in our patient's brain, we monitor and control FI and, indirectly,
FA and Fa.
Controlling Inspired Fraction of Agent, FI
FI depends on total fresh gas flow (FGF in L/min), total volume of the breathing system or circuit,
and any absorption of agent by the anesthesia machine and breathing system.
Factors Affecting Alveolar Fraction of Agent, FA
FA depends on three variables: uptake of agent from the lung, pulmonary ventilation and
inspired concentration of agent.
- Uptake of agent from the lung alveoli into the alveolar capillary blood depends on
- solubility of agent in blood,
- alveolar blood flow, and
- alveolar-venous partial pressure difference.
For relatively the insoluble agents
- N2O and desflurane,
- slow uptake leads to
- fast rise in FA.
Degree of solubility is expressed in the blood:gas solubility ratio, lambdab/g:
| Agent |
|
Blood/Gas |
|
Brain/Blood |
|
Muscle/Blood
| |
Fat/Blood
|
| Nitrous oxide |
|
0.47 |
|
1.1 |
|
1.2 |
|
2.3 |
| Halothane |
|
2.4 |
|
2.9 |
|
3.5 |
|
60 |
| Enflurane |
|
1.9 |
|
1.5 |
|
1.7 |
|
36 |
| Isoflurane |
|
1.4 |
|
2.6 |
|
4.0 |
|
45 |
| Desflurane |
|
0.42 |
|
1.3 |
|
2.0 |
|
2.7 |
| Sevoflurane |
|
0.65 |
|
1.7 |
|
3.1 |
|
48 |
|
Alveolar blood flow depends on pulmonary blood flow which depends on (is normally essentially equal to)
cardiac output.
FA rises more rapidly when cardiac output is low.
Low cardiac output predisposes to overdose of soluble agents.
Alveolar-venous partial pressure difference (gradient) depends on tissue uptake which depends on
tissue blood flow and arterial-tissue gradient.
In terms of inhalational agent uptake, body tissues may be classified into four groups:
- Vessel-Rich Group
- brain
- heart
- liver
- kidneys
- endocrine glands
- Muscle Group
- Fat
- Vessel-Poor Group
- Increasing pulmonary ventilation increases FA:FI ratio.
More significant for soluble agents.
Agents that decrease vetilation create a negative feedback loop,
enhancing safety during spontaneous ventilation.
- Increasing FI increases both FA and dFA/dt (rate of rise of FA).
The increase dFA/dt caused by increasing FI is called the
concentration effect, and is due to:
- the concentrating effect and
- the augmented inflow effect.
Concentration effect of one gas on another is called the second gas effect.
Factors Affecting Arterial Fraction of Agent, Fa
Fa < FA because of
- venous admixture
- alveolar dead space
- nonuniform alveolar gas distribution
- ventilation/perfusion (V/Q) mismatch
increases FA especially for more soluble agents
decreases Fa especially for poorly soluble agents
Elimination of Inhalational Anesthetic Agents
- Biotransformation (minimal)
- Transcutaneous loss (insignificant)
- Exhalation depends on
- extent of rebreathing
- FGF
- volume of breathing system
- absoption by breathing system components
- solubility of agent
- cerebral blood flow
- ventilation
Beware diffusion hypoxia with N2O
Prevent by 2-10 minutes of 100% O2 breathing after N2O turned off.