2017B Question 05

Outline the factors which influence the time taken for loss of consciousness (not wash-in) during an inhalational induction of anaesthesia.

Examiner Report

50.2% of candidates achieved a pass in this question.

A general statement about the effect of partial pressure of volatile anaesthetic in the brain being responsible for loss of consciousness was required. To achieve a desired partial pressure, bulk transfer of volatile anaesthetic must occur with volatile moving down concentration gradients from the circuit to the alveoli, from the alveoli to the blood and finally from the blood to the brain. Within the anaesthetic circuit, increasing the dial concentration, the fresh gas flows or reducing the circuit volume will speed the increase of volatile concentration.

Increasing the concentration of volatile delivered, increasing alveolar ventilation or increasing the alveolar ventilation to functional residual capacity ratio can reduce alveolar wash in time. Adding nitrous oxide in high concentration, which will lead to concentration and second gas effects, can also augment increased alveolar concentration. Transfer of anaesthetic agent from the alveolus to blood is determined by the alveolar partial pressure, the solubility of the agent as reflected by blood gas partition coefficient and cardiac output.

Any change in mixed venous concentration of agent such as by shunt or V/Q mismatch, tissue solubility or increased delivery to muscle will affect the rate of rise of partial pressure in the blood. Transfer from the blood to the brain will be dependent upon the concentration in the blood and proportion of cardiac output delivered to the brain.

Finally pharmacodynamic changes will alter the time to loss of consciousness and include the effect of co-administered anaesthetic agents, sensitivity of the brain to the volatile, age related changes, tolerance and the effect of pregnancy or other drugs.

Model Answer


  • Introduction
  • Circuit-alveolus
  • Alveolus-V1
  • MAC-awake ↑/↓
  • MAC awake variation between drugs


Factor Detail
Determinants of time to LOC

1. Rate of equilibration between circuit and lungs

2. Rate of equilibration between lungs and vessel rich group (V1)

3. V1 partial pressure associated with unconsciousness (MAC-awake)

Rate of rise of alveolar partial pressure reflects rate of rise in effect site.

Wash-in curve
Putative effect site

- Ascending reticular activating system, thalamus, frontal cortex

- Partial pressure correlates with that in V1

- Often not be included in kinetic model

- Rate of equilibration between effect site and VRG ∝:

 - Blood flow to brain per unit mass (not % cardiac output to brain)

 - 1/(brain-blood partition coefficient)

Circuit → Alveolus

Factor ↓ Time To loss of consciousness
↑ Inspired %

- User-controlled

- Partly MAC-dependent: N2O 105%, des 6.6%, sevo 2%, iso 1.2%

↑ FGF : Circuit volume

- ↑ FGF rate (user-controlled, max ~18L/min

- ↓ CV: e.g. Mapleson F circuit cf. circle circuit


- ↑ VA (↑ Neonate/crying/pregnant/shock)

- ↓ FRC (↓ Supine/pregnant/obese)

- Affects soluble (e.g. Halothane) > insoluble agents (e.g. Desflurane)

Concentration effect

- Seen only with high volume carrier gases

- Switch from N2/O2 to N2O/O2

- Rapid uptake N2O from alveolus (BGPC 0.47), but very slow output of N2 (BGPC 0.014)

- Reduction in alveolar volume and pressure → Rapid inflow of N2O-rich fresh gas

- Accelerated ↑ FA/FI N2O

Second gas effect

- Rapid uptake N2O from alveolus, but very slow output of N2

- Reduction in alveolar volume → ↑ Concentration of remaining volatile

Alveolus → V1

Factor ↓ Time to loss of consciousness
↓ Blood-gas partition coefficient

- ↓ Rate of uptake but ↑ rate of equilibration

- Drug: Iso 1.4, sevo 0.69, N2O 0.47, des 0.42

- Patient: ↑ If obese/lipaemic/adult, ↓ if neonate/malnourished/anaemic

↓ Cardiac output

- Affects soluble > insoluble agents

- ↓ Rate of uptake but ↑ rate of equilibration

- Drug: Halothane → Myocardial depression

- Patient: ↓ shock/elderly, ↑ neonate/pregnant/obese

↑ V/Q matching

- ↓ Dilution of volatile-containing blood with shunt blood

- Affects insoluble > soluble agents

- Note volatile anaesthetics → Impaired HPV → Impaired V/Q matching

↓ Tissue uptake

(→ ↑ Mixed venous partial pressure → ↓ Rate of uptake but ↑ rate of equilibration)

- ↓ Tissue volume (↑ obese/pregnant) – muscle most important

- ↓ Tissue-blood partition coefficient

 - Muscle-blood: N2O 1.2, des 1.9, iso 2.9m sevo 3.1

 - Fat-blood: N2O 2.3, des 27, iso 45, sevo 48

- ↓ Tissue blood flow (↑ obese/pregnant/neonate, ↓ shock/elderly)


Factor MAC-awake (Faster induction) MAC-awake (Slower induction)

- Age: Neonate, elderly

- Pregnancy: ↓ 30% (progesterone)

- Obesity: Inflammatory cytokines

- Age: Max at 6 months then ↓ 6% per decade

- Red hair


- ↓ MAP (≤40mmHg)

- ↓ PO2 (≤40mmHg)

- ↑ PCO2 (>60mmHg sedation, >80mmHg anaesthesia)

- ↓ Temp

- ↓ PH

- ↓ [Na+]

- ↑ Temp

- ↑ [Na+]

Drug interactions

- Acute depressants: Propofol, barbiturates, benzodiazepines, opioids, local anaesthetics, Mg2+

- Chronic stimulant: (e.g. Amphetamines)

- Acute stimulant

- Chronic depressant

MAC-Awake Variation Between Drugs

Factor Detail
Drug values

- Isoflurane 0.45 MAC

- Sevoflurane 0.36 MAC

- Desflurane 0.4 MAC

- Halothane 0.53 MAC

- N2O 0.64 MAC

Cause of differences

- ?Differential effects

 - Unconsciousness: Reticular activating system, thalamus, (frontal) cortex

 - Immobility: Spinal cord

Last updated 2021-08-23

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