"Uptake and distribution of anesthetic gases
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Dr.J.Edward Johnson M.D.(Anaes),D.C.H.Asst. Professor,Dept. of Anaesthesiology,Kanyakumari Govt. Medical College Hospital.
"Uptake and distribution of anesthetic gases is virtually incomprehensible"
wroteLawson: Gas Man Review, Anesthesia and Analgesia, August 1991
Goal To develop and maintain a
satisfactory partial pressure or tension of anesthetic at the site of anesthetic action in brain.
Alveolar concentration of anaesthetic gas is indirectly reflects brain concentration.PA PB
VaporizerBreathing CircuitAlveoli (lungs)Arterial BloodTissues (VRG [brain], MUS,FAT)Venous blood (coming back to lungs)Alveoli (lungs, again)Breathing Circuit (to be rebreathed)
Tension equalizes when
Concentration equilibrates
Concentration does not drive molecular motion
Tension drives molecular motion
Tension = Partial PressureImporta
nt
Inspired Tension drives Alveolar Tension
Alveolar Tension drives Arterial Tension
Arterial Tension drives Tissue Tensions
Brain is the important Tissue for Anesthesia
Brain Tension drives depth of anesthesia
Time constant
FI
FA
FDMAC
Brain Partial pressure drives depth of anesthesia
Equilibrates
Ventilation
λB/G CO
PA - PV
λT/BTissue blood flow
[Parterial - PTissue]
12
FA/FI
Concentration and second gas effects
Time constant
VRG
a) The inspired concentration (FI) Inspired concentration - FA/FI
b) The alveolar ventilation (Valveolar) - Minute alveolar ventilation - FA/FI - Larger the FRC - slows raise of alveolar concentration
c) The time constantd) Anesthetic uptake by the bloode) The concentration and second gas effects
Increase in Minute alveolar ventilation Increases FA/FI
The change is greatest for more soluble anesthetics
Halothane depress Valveolar
and limit the raise of alveolar concentration
Hyperventilation reduces cerebral blood flow so induction time is function of solubilityNitrous oxide and Halothane –
slows inductionEther – faster induction
If 10 liter box is initially filled with oxygen and 5 l/min of nitrogen flow into box then,
TC is volume (capacity)/flow. TC = 10 / 5 = 2 minutes ( 1 Time
Constant) So, the nitrogen concentration at end of
2 minutes is 63%.
O2 10 Lt 5 Lt/min
2 Mts 4 Mts 6 Mts 8 Mts
63% 86% 95% 98%
N2
Time Constant at Lungs
Increase FA/FI Decrease FA/FI Comment
Low blood solubility High blood solubility
As the blood solubility decreases, the rate of rise in FA/FI increases.
Low cardiac output High cardiac output The lower the cardiac output, the faster the rate of rise in FA/FI
High minute ventilation Low minute ventilation The higher the minute ventilation, the faster the rate of rise in FA/FI
Factors that Increase or Decrease the Rate of Rise of FA/FI
Uptake from the lung = Blood solubility x Cardiac Output x [PA-PV] / Barometric pressure
50%O2
50%N2O2Lt
2Lt
4Lt
33%N2O
66%O2
3Lt
2Lt
1Lt
Uptake of half of the N2O
38%N2O
62%O2
1Lt of N2O
1 Lt 50%O2 + 50%N2O
Ventilation Effect Inspired Gas
1.5Lt
4Lt
2.5Lt
1% Isoflurane
49%O2
50%N2O
1.3% Isoflurane
1.25% Isoflurane
4Lt 4Lt3Lt
1.960Lt
2Lt 1Lt
40ml
Uptake of half of the N2O
1Lt of N2O
65.3%O2
33.3%N2O
1.960Lt
40ml
Inspired Gas1Lt
1 Lt 50%O2 + 49%N2O + 1% Isoflurane490ml 500ml 10ml
1.5Lt
2.450Lt
50ml
61.25%O2
37.5%N2O
65% nitrous oxide produces a more rapid rise in the FA/FI ratio of nitrous oxide than the administration of 5%
FA/FI ratio for 4% desflurane rises more rapidly when given with 65% nitrous oxide than when given with 5%
Concentration effect
Second gas effect
We have LearnedFactors raising the alveolar concentration
(FA/FI ) I. The inspired concentration (FI) II. The alveolar ventilation (Valveolar)
III. The time constantIV. Anesthetic uptake by the bloodV. The concentration and second gas
effects
Factors determining uptake by Factors determining uptake by bloodblood
A.A.Solubility in bloodSolubility in blood
B.B.Cardiac OutputCardiac Output
C.C.The mixed venous anesthetic The mixed venous anesthetic concentrationconcentration
Tissue uptake of anestheticTissue uptake of anesthetic Uptake from the lung = Blood solubility x Cardiac Output x [PA-PV] Barometric pressure
Solubility is defined in terms of the partition coefficient
Partition coefficient is the ratio of the amount of substance present in one phase compared with another, the two phases being of equal volume and in equilibrium [λB/G = CB ] CG
GasBlood
Partition Coefficient = Ratio of Concentration
Concentrations Equilibirates
Partial pressure Equalize
CG =CB
PG = PB
Halothane
λB/G = CB = 2.5 = 2.5 CG 1
Equal volume
GasBlood Tissue
Concentrations Equilibirates
Partial pressure Equalize
CG =CB = CT
PG = PB = PT
Equal volume
The more soluble the anesthetic
The more drug will be taken up by the blood
The slower the rise in alveolar concentration
15
1.4
0.65
0.47Poor solubility Rapid induction
High solubility Slow induction
Greater the cardiac output
The more drug will be taken up by the blood
The slower the rise in alveolar
concentration
Cardiac output is lowered
cerebral circulation
less maintained (shock) Induction Induction slower rapid
The difference between partial pressure in the alveoli and that in venous blood
Partial pressure in venous blood depends on tissue uptake of anesthetic
At equilibrium, (no tissue uptake) The venous partial pressure = arterial partial pressure = alveolar partial
pressure PA – PV = 0
Rate of rise of the mixed venous concentration depends on the tissue uptake of the anesthetic
AT EQUILIBRIUM
No
tissu
e up
take
PA
PV
PA – PV = 0PA = PV
FA/FI
FAT
VRG
MG
4-8mts
2-6Hrs
3-4 days
The tissue uptake equals the uptake from the lungs
1. The tissue/blood partition coefficient (tissue solubility)
2. The tissue blood flow.
3. The tissue anesthetic concentration Tissue Uptake = Tissue solubility x Tissue blood flow x [Parterial - PTissue]
Atmospheric pressure
Tissue Group
Characteristic Vessel Rich (brain, heart, lungs, kidney,
splanchnic bed,
glands)
Muscle Fat
Vessel Poor
(bones, cartilage, ligaments)
Percent Body Mass 10 50 20 20
Percent Cardiac Output 75 19 6 0
Equilibration of the VRG complete in 4 to 8 minutes
After 8 minutes, the Muscle group (MG) determines most of uptake.
Once MG equilibration is complete Fat group (FG) determines the uptake
Time Constant = Tissue solubility x Volume Flow
The time constants for the fat
(in Hours)
1 TC 2 TC 3 TC
1.3 2.6 3.8
25 50 75
20 40 60
28 57 85
15 30 45
27 53 80
3 6 8
21 42 63
The time constants for the muscle
(in Minutes)
1 TC 2 TC 3 TC
40 80 120
97 193 290
57 113 170
113 227 340
67 133 200
103 207 310
43 87 130
53 107 160
The time constants for the brain(in Minutes)
1 TC 2 TC 3 TC
1.1 2.2 3.3
1.6 3.2 4.8
1.4 2.8 4.2
1.9 3.8 5.7
1.3 2.6 3.9
1.7 3.4 5.1
2 4 6
1.4 2.8 4.2
Gas
Nitrous Oxide
Isoflurane
Enflurane
Halothane
Desflurane
Sevoflurane
Diethyl Ether
Methoxyflurane
λ Brain/Bld: N2O 1.1 Sevo 1.7 Metho 1.4
λ Fat/Bld: N2O 2.3 Sevo 48 Metho 38
3 TC 95%
Initial Rise - Alveolar Wash-In
First knee – Solubility with blood
Second knee – Equilibration with VRG 8 mts
Third knee - Equilibration of the MGA
B
C
8AB
BC
C8
MOUTH LUNG
VRG
MG
FATBlood Supply
75%
18%
5.5%
Ventilation
Anesthetic Gas
Cylinders : represent the inspired reservoir (mouth), the alveolar gas, vessel rich group, the muscle group, and the fat group
Cross sectional : surface of each cylinder corresponds to its capacity (λB/T * volume)
Diameter of the pipes : correlates to the λB/G * CO to each group
Height of the column of fluid : in each cylinder corresponds to the partial pressure of the anesthetic in that cylinder
MOUTH LUNG
VRG
MG
FATBlood Supply
75%
18%
5.5%
Ventilation
All compartments are small
Pipes are represented as small because low solubility of anaesthetic is less carried by the given blood flow
To achieve equilibrium for low soluble anaesthetic small quantity of anaesthetic has to go in to the system
Anesthetic Gas
MOUTH LUNG
VRG
MG
FATBlood Supply
75%
18%
5.5%
Ventilation
All compartments are large
Pipes are represented as larger because high solubility of anaesthetic is more carried by the given blood flow
To achieve equilibrium for high soluble anaesthetic large quantity of anaesthetic has to go in to the system
Anesthetic Gas
Time constant
FI
FA
FDMAC
Brain Partial pressure drives depth of anesthesia
Equilibrates
Ventilation
λB/G CO
PA - PV
λT/BTissue blood flow
[Parterial - PTissue]
12
FA/FI
Concentration and second gas effects
Time constant
VRG
INDUCTION RECOVERY
Induction can be accelerated Induction can be accelerated by Over Pressure( which by Over Pressure( which offset solubility and uptake)offset solubility and uptake)
The inspired concentration The inspired concentration cannot be reduced below zerocannot be reduced below zero
All the tissues initially have All the tissues initially have the same anesthetic partial the same anesthetic partial pressure—zeropressure—zero
On recovery, the tissue partial On recovery, the tissue partial pressures are variablepressures are variable
100% 60% 10%
0% Recovery
1. Increased solubility slows recovery
2. Increasing ventilation may help the recovery from potent agents
3. Prolonged anaesthesia delays recovery
4. There is no concentration effect on emergence
The large outpouring of nitrous oxide diluting the inspired oxygen at the conclusion of a case in the first 3-5 minutes after terminating the nitrous oxide
Managed with supplemental oxygen for a few minutes following termination of the nitrous.
Eger's The Pharmacology of Inhaled Anesthetics
Miller's Anesthesia, Seventh Edition
Barash : Handbook of Clinical Anesthesia (6th Ed. 2009)
http://www.anesthesia2000.com/
www.gasmanweb.com
Download www.anaesthesianews.com
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