"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.

"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)

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