"Uptake and distribution of anesthetic gases

1
"Uptake and distribution of

anesthetic gases

• Dr.J.Edward Johnson M.D.(Anaes),D.C.H.
• Asst. Professor,
• Dept. of Anaesthesiology,
• Kanyakumari Govt. Medical College Hospital.

2

"Uptake and distribution of
anesthetic gases
is
virtually incomprehensible"
wroteLawson Gas Man Review, Anesthesia and
Analgesia, August 1991
3
"Uptake and distribution of

anesthetic gases

• 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
4
Path of anesthetic tension

• Vaporizer
• Breathing Circuit
• Alveoli (lungs)
• Arterial Blood
• Tissues (VRG brain, MUS,FAT)
• Venous blood (coming back to lungs)
• Alveoli (lungs, again)
• Breathing Circuit (to be rebreathed)

5
Alveolar Tension is important
Tension Partial Pressure
Important

• Tension equalizes when Concentration equilibrates
• Concentration does not drive molecular motion
• Tension drives molecular motion

6
If we know Alveolar Tension, we know the hard part

• 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

7
Basics of Uptake and Distribution Birds eye
view
1
2
FD
MAC
Fi
Ventilation
?B/G
?T/B
Fa
Equilibrates
CO
Tissue blood flow
PA - PV
Parterial - PTissue
Fa/Fi
VRG
Time constant
Brain Partial pressure drives depth of anesthesia
Concentration and second gas effects
Time constant
8
I. Alveolar concentration
Factors raising the alveolar concentration
(Fa/Fi )

• The inspired concentration (Fi)
  Inspired concentration -
  Fa/Fi
• The alveolar ventilation (Valveolar)
  - Minute alveolar ventilation -
  Fa/Fi -
  larger the FRC - slows raise of alveolar
  concentration
• The time constant
• Anesthetic uptake by the blood
• The concentration and second gas effects

9
b)The alveolar ventilation (Valveolar)
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 solubility Nitrous
oxide and Halothane slows induction Ether
faster induction
10
c) The time constant
11
c) The time constant - example

• 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. 

Time Constant at Lungs
8 Mts
2 Mts
4 Mts
6 Mts
O2
N2
5 Lt/min
10 Lt
86
95
98
63
12
d) Anesthetic uptake by the blood

Uptake from the lung Blood solubility x
Cardiac Output x PA-PV / Barometric pressure

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
13
e) The concentration effect
4Lt
3Lt
4Lt
50O2
2Lt
66O2
Uptake of half of the N2O
2Lt
62O2
2.5Lt
33N2O
1Lt
1Lt of N2O
2Lt
50N2O
38N2O
1.5Lt
Ventilation Effect
Inspired Gas
1 Lt 50O2 50N2O
14
e) The second gas effect
4Lt
4Lt
3Lt
1 Isoflurane
40ml
1.3 Isoflurane
1.25 Isoflurane
40ml
50ml
61.25O2
49O2
Uptake of half of the N2O
65.3O2
1.960Lt
1.960Lt
2.450Lt
33.3N2O
1Lt
1Lt of N2O
2Lt
50N2O
37.5N2O
1.5Lt
Inspired Gas
1Lt
1 Lt 50O2 49N2O 1
Isoflurane 490ml 500ml 10ml
15
Concentration and second gas effect
Concentration effect
65 nitrous oxide produces a more rapid rise in
the Fa/Fi ratio of nitrous oxide than the
administration of 5
Second gas effect
Fa/Fi ratio for 4 desflurane rises more rapidly
when given with 65 nitrous oxide than when given
with 5
16
I. Alveolar concentration

• We have Learned
• Factors raising the alveolar concentration (Fa/Fi
  )
• The inspired concentration (Fi)
• The alveolar ventilation (Valveolar)
  
• The time constant
• Anesthetic uptake by the blood
• The concentration and second gas effects

17
II. Uptake from lung

• Factors determining uptake by
  blood
• Solubility in blood
• Cardiac Output
• The mixed venous anesthetic concentration
• Tissue uptake of anesthetic

Uptake from the lung Blood solubility
x Cardiac Output x PA-PV


Barometric pressure
18
Solubility / Partition
Coefficient

• 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 ?B/G CB
  CG

19
Blood gas partition coefficient ?B/G
Partition Coefficient Ratio of Concentration
Concentrations Equilibirates
CG CB
Gas
Halothane ?B/G CB 2.5 2.5 CG
1
Equal volume
Blood
PG PB
Partial pressure Equalize
20
Blood tissue partition coefficient ?B/T
Concentrations Equilibirates
CG CB CT
Tissue
Gas
Equal volume
Blood
PG PB PT
Partial pressure Equalize
21
A.Solubility in blood
Poor solubility Rapid induction
0.47
The more soluble the anesthetic The
more drug will be taken up by the
blood The slower the rise in alveolar
concentration
0.65
1.4
15
High solubility Slow induction
22
B.Cardiac Output
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
23
C. The Alveolar-to-Venous
Anesthetic Gradient

• 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
24
The Alveolar-to-Venous
Anesthetic Gradient
PA
Fa/Fi
VRG
4-8mts
No tissue uptake
AT EQUILIBRIUM
MG
PA PV
2-6Hrs
PA PV 0
FAT
3-4 days
PV
25
D.Tissue uptake of anesthetic

• 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

26
III. Distribution to tissues
Tissue Group Tissue Group Tissue Group 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
27
III. Distribution to tissues (Contd...)
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
28
Tissue Time Constant
Time Constant Tissue solubility x
Volume Flow

The time constants for the fat (in Hours) The time constants for the fat (in Hours) 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) The time constants for the muscle (in Minutes) 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) The time constants for the brain (in Minutes) 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
? Fat/Bld N2O 2.3 Sevo
48 Metho 38

? Brain/Bld N2O 1.1
Sevo 1.7 Metho 1.4

3 TC 95
29
The Alveolar Tension
CurveSynthesis of Factors Governing the Rise in
Fa/Fi Ratio
AB
Initial Rise - Alveolar Wash-In
BC
8
First knee Solubility with blood
C
8
C
B
Second knee Equilibration with VRG 8 mts
A
Third knee - Equilibration of the MG
30
Mapleson Hydraulic Model
Cylinders represent the inspired reservoir
(mouth), the alveolar gas, vessel rich group,
the muscle group, and the fat group
VRG
Anesthetic Gas
75
MG
18
Ventilation
Blood Supply
FAT
MOUTH
LUNG
5.5
Cross sectional surface of each cylinder
corresponds to its capacity (?B/T volume)
Diameter of the pipes correlates to the ?B/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
31
Mapleson Hydraulic Model Low
solubility anaesthetic

• All compartments are small

VRG

• Pipes are represented as small because low
  solubility of anaesthetic is less carried by
  the given blood flow

75
Anesthetic Gas
MG
18
Ventilation
Blood Supply
FAT
MOUTH
LUNG
5.5

• To achieve equilibrium for low soluble
  anaesthetic small quantity of anaesthetic has to
  go in to the system

32
Mapleson Hydraulic Model High
solubility anaesthetic

• All compartments are large

VRG

• Pipes are represented as larger because high
  solubility of anaesthetic is more carried by
  the given blood flow

Anesthetic Gas
75
MG
18
Ventilation
FAT
Blood Supply
MOUTH
LUNG
5.5

• To achieve equilibrium for high soluble
  anaesthetic large quantity of anaesthetic has to
  go in to the system

33
Basics of Uptake and Distribution
1
2
FD
MAC
Fi
Ventilation
?B/G
?T/B
Fa
Equilibrates
CO
Tissue blood flow
PA - PV
Parterial - PTissue
Fa/Fi
VRG
Time constant
Brain Partial pressure drives depth of anesthesia
Concentration and second gas effects
Time constant
34
RECOVERY
INDUCTION RECOVERY
Induction can be accelerated by Over Pressure( which offset solubility and uptake) The inspired concentration cannot be reduced below zero
All the tissues initially have the same anesthetic partial pressurezero On recovery, the tissue partial pressures are variable
100
60
10
Recovery
0
35
Recovery from an inhalational anesthetic

• 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

36
Diffusion Hypoxia

• 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.

37
Further References

• 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

38
Thank you
Download
www.anaesthesianews.com