Transcript Pharmacokinetics of Inhalation Anesthetic Agents

Pharmacokinetics of
Inhalation Anesthetics
Dr.Doaa Kamal
Department of Anesthesia, Ain Shams University
Email adress:
[email protected]
Pharmacokinetics:
The study of
 Absorption.
 Distribution.
 Metabolism.
 Excretion.
Aim:
For a better understanding of the factors
that govern induction and recovery from
anesthesia.
KEY POINTs:
► Alveolar partial pressure (FA) governs the
partial pressure of volatile anesthetic in all body
tissues: all must approach and ultimately equal
alveolar partial pressure.
► Equilibration occurs rapidly between alveolar
& brain anesthetic partial pressure.
► Therefore Alveolar concentration is ultimately
the principal factor in determining the onset of
action.
►Diffusion occurs from a region of higher
concentration to a region of lower
concentration (down a concentration gradient).
(A) Factors Affecting Inspired gas
concentration (Fi)
1) Fresh Gas Flow rate:
↑ FGF → ↑ speed of induction & recovery.
(If pt awakens in the middle of surgery on
low flow → ↑ FGF).
2) Volume of breathing circuit
(apparatus dead space): ↑ volume →
slower induction dt.dilution of anesthetic
gases. (Eg. MRI breathing circuits = 3m,
circuit priming for pediatrics, circuit priming
for single breath technique for sevoflurane).
3) Absorption by the breathing circuit:
rubber tubing absorbs ˃ plastic & silicon →
delays induction & recovery. Not used for pt
with suspected malignant hyperthermia
(release of trace anesthetic gases).
(B) Factors Affecting Alveolar
concentration (FA)
(a) DELIVERY:
1) Concentration.
2) Ventilation: ↑ minute ventilation →
↑ delivery (Eg. child crying).
(B) Factors Affecting Alveolar
concentration (FA)
(b) UPTAKE:
RULE: ↑ uptake → slower
rate of induction!! dt.
Slower build up of Alveolar
Partial Pressure.
1) Blood/gas solubility
coefficient.
↑ solubility → ↓ rate of
induction. (Blood & tissues
act like a sponge).
(B) Factors Affecting Alveolar
concentration (FA)
(b) UPTAKE:
2) Pulmonary blood flow: (Cardiac output)
↑ Alveolar blood flow (COP) → ↑ uptake →
slower build up of alveolar partial pressure
slower induction.
N.B. This effect is greater with soluble agents
(Eg.halothane) ˃ insoluble agents (N2O).
►Children with F4 → rapid induction due to
↓ pulmonary blood flow.
(B) Factors Affecting Alveolar
concentration (FA)
(b) UPTAKE:
3) Tissue Uptake: partial pr difference
between alveolar gas & venous blood.
↑ Tissue uptake → lower partial
pressure of venous blood → ↑ uptake
→ slower rate of induction.
(a) Tissue solubility of anesthetic agent.
(b) Tissue blood flow.
(c) Partial pressure difference
between Arterial blood and tissues.
(B) Factors Affecting Arterial
concentration (Fa)
Depends on Ventilation/Perfusion matching:
(a) Ventilated non perfused areas: [dead space]
↓ arterial concentration.
(b) Perfused non ventilated areas:
[intrapulmonary shunting] = shunt fraction.
↓ arterial concentration.
SUMMARY
(1) Inspired gas (Fi):
(2) Alveolar gas (FA):
1- FGF rate.
2- Absorption by breathing
circuit.
3- Volume of breathing
circuit.
DELIVERY:
1- Concentration.
2- Minute Ventilation.
(3) Arterial concentration
(Fa):
V/Q mismatching.
UPTAKE:
1- Blood gas solubility.
2- Alveolar blood flow.
3- Tissue uptake.
N2O is 30 times more soluble than N2 in
the blood.
Applications:
1- Concentration effect/ 2nd gas effect
(induction).
2- Diffusion hypoxia (recovery).
3- Contraindication of N2O in presence of
closed air spaces.
(1) Concentration Effect/ 2nd Gas Effect
N2O diffuses rapidly from alveoli to
blood much faster than N2 diffuses out.
This decreases the total volume of gas
in the alveolus → ↑ fractional
concentration of other anesthetic agent.
(2) Diffusion Hypoxia
(opposite the concentration effect)
►At the end of anesthesia after discontinuation
of N2O, N2O diffuses from blood into the
alveoli much faster than N2 diffuses from
alveoli into the blood.
►↑ Total volume of gas in the alveolus →
fractional concentration of gases in the alveoli
is diluted by N2O → ↓ PaO2 & PaCO2 →
hypoxia. This occurs in the first 5-10 mins of
recovery. Therefore it is advised to use 100%
O2 after discontinuation of N2O.
(3) N2O is Contraindicated in Presence of Closed
Air Spaces
The higher solubility of N2O than N2 in the
blood makes it contraindicated in the presence
of closed air spaces:

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Intestinal obstruction.
Pneumothorax.
Pneumocephalus.
Air embolism.
Tympanoplasty.
x 2-3 fold increase in size within 15 minutes!!