Determinants of alveolar partial pressure

[Ref: SH4:p24]

Alveolar partial pressure (PA) is determined by input minus loss.

 

Input depends on

• Inhaled partial pressure (PI)
• Alveolar ventilation
• Characteristics of delivery system

 

Loss (uptake) depends on

• Solubility in tissues
• Cardiac output
• Alveolar to venous partial pressure difference

 

Inhaled partial pressure (PI)

High PI increases input of anaesthetics to offset uptake.

Concentration effect

The higher the PI, the more rapidly PA approaches PI.

Due to the concentrating effect and the ventilation effect

Concentrating effect

Uptake of all gases leads to:

• Smaller lung volume
  --> Concentration of inhaled anaesthetics increases
• Augmentation of tracheal inflow
  --> Increased alveolar ventilation

Second gas effect

High-volume uptake of one gas (first gas) accelerates the rise in the PA of a concurrently administered gas (second gas)

Due to:

1. Increased tracheal inflow of all gases
2. Concentrating effect on the second gas as a result of high-volume uptake of the first gas

 

NB:

Uptake of gas can be compensated by

• Increased tracheal inflow
• Decreased expiration
• Reduction in lung volume

 

Alveolar ventilation (VA)

Increased alveolar ventilation increases input of anaesthetics to offset uptake.

 

However,

Hyperventilation
--> Decreased PaCO2
--> Cerebral blood flow decreases
--> Decrease delivery of anaesthetics to brain

Thus,

Hyperventilation may increase PA and Pa, but may slow down equilibration of Pbr with Pa.

Alveolar ventilation to FRC ratio

In spontaneously breathing adult, ratio of alveolar ventilation to FRC = 1.5:1

In spontaneously breathing neonate, ratio of alveolar ventilation to FRC = 5:1
* Due to higher metabolic rate

Thus,

Induction of anaesthesia is faster in neonates (spontaneously breathing)

Negative-feedback mechanism in spontaneous ventilation

Inhalational agents exert dose-dependent depressant effects on alveolar ventilation

Thus,

• When anaesthesia is deep, alveolar ventilation (and thus uptake of anaesthetics) decreases
• When anaesthesia is light, alveolar ventilation increases

 

Effect of solubility

The greater the solubility
--> The greater the impact of alveolar ventilation on rise of PA

i.e.,

More soluble agents (e.g. hal, iso) is more influenced by changes in ventilation than less soluble agents (e.g. nitrous oxide)

Nitrous oxide uptake is rapid regardless of alveolar ventilation because uptake is limited (thus drop in PA due to uptake is limited).

Anaesthetic breathing system

Characteristics that influence PA:

• Volume of the breathing system
  * The higher the volume, the greater the buffer
• Fresh gas flow into the breathing system
  * The high gas flow negates the buffer effect
• Solubility of the inhaled agent in the rubber or plastic component of the breathing system

 

Solubility

Partition coefficient

Solubility of inhaled anaesthetics is denoted by partition coefficient

A partition coefficient is a distribution ratio describing how the inhaled anaesthetic distributes itself between two phases at equilibrium (i.e. where partial pressures in both phases are equal)

For example,

Blood:gas partition coefficient of 2
--> Concentration in blood is twice that in alveolar gas at equilibrium

Partition coefficient and temperature

Partition coefficient are temperature dependent

--> Solubility of a gas in a liquid is decreased when temperature rises

Blood:gas partition coefficient

Rate of rise in PA towards PI is inversely related to the solubility of the agent in blood

When solubility is low
--> Minimal amounts need to be dissolved to achieve equilibrium
--> Rapid induction
e.g. PA is >80% of PI in 10min for N2O, des, and sevo

NB:

• When haematocrit is low
  --> Blood:gas partition coeffient is decreased
  --> More rapid onset of anaesthetics
• Blood solubility for more soluble agents (hal, en, methoxyflurane, iso) is about 18% less for neonates and elderly, when compared with young adults
• During bypass operations
  * Crystalloid prime and hypothermia
  --> Affects blood:gas partition coefficient by 2%

Tissue:gas partition coefficient

Fat takes a long time to equilibrate with PA because:
* High capacity to hold anaesthetics
* Low blood flow

Oil:gas partition coefficient

Oil:gas partition parallel anaesthetic requirements
--> MAC can be estimated by 150 divided by the oil:gas partition coefficient

Nitrous oxide and closed air space

• Blood:gas partition coefficient of N2O = 0.46
• Blood:gas partition coefficient of N2 = 0.014

Thus,

N2O is 34 times more soluble
--> N2O can leave blood to enter an air-filled cavity 34 times more rapidly than nitrogen can enter blood to leave the cavity
--> Pressure / volume of an air-filled cavity increases

 

The magnitude of the increase depends on

• Partial pressure of N2O
• Blood flow to the cavity
• Duration of N2O administration

Implication

• Middle ear pressure may increase if eustachian tube patency is compromised by inflammation or oedema
  --> May be partly responsible for N&V caused by N2O
• Rapid increase the volume of pneumothorax
• Also increase volume of bowel gas, but slowly
  --> Probably not clinically significant in the absence of bowel obstruction
• Intraocular gas bubbles are used for internal retinal tamponade
  --> May persist for 10 weeks post-op
  * During this time, N2O will result in rapid increase in the volume of intraocular gas

Cardiac output

Increased cardiac output
--> Increased uptake
--> Decreases PA
--> Onset of anaesthesia is delayed

NB:

Increased cardiac output hastens equilibration between Pa and Pbr (and partial pressure at tissues)

BUT, PA is reduced. Thus Pa is lower than otherwise.

Cardiac output and effect of solubility

Changes in cardiac output have more impact on more soluble anaesthetics

Thus,

Rise in PA of N2O would be rapid regardless of cardiac output (or alveolar ventilation)

Positive-feedback mechanism in spontaneous ventilation

Inhaled anaesthetics which exert dose-dependent cardiac depressant effect can have a positive-feedback effect

When anaesthesia is too deep
--> Cardiac output decreases
--> PA increases
--> Further deepens anaesthesia

NB:

Unlike negative-feedback in alveolar ventilation

Effect of right-to-left shunt

When there is a right-to-left shunt
--> Pa would be lower than PA
* Especially when solubility is poor

When solubility is low
--> Uptake is minimal
--> Dilution effect is greater

Alveolar-to-venous partial pressure difference

A-v difference reflects tissue uptake of the inhaled anaesthetics.

Affected by:

• Tissue solubility
• Tissue blood flow
• Arterial-to-tissue partial pressure difference

 

=======

Anxiety delays onset because of

Increased sympathetic stimulation

Decreased % of CO going to brain

Hypocapnia decreases cerebral blood flow

 

Hypovolaemia hasten onset because of

Increased % of CO going to brain

 

In lung disease (V/Q mismatch and/or shunt)

Onset is delayed --> More so if AA is less soluble