2017B05 Outline the factors which influence the time taken for loss of consciousness
(not wash-in) during an inhalational induction of anaesthesia.



·      Intro

·      Circuit-alveolus

·      Alveolus-V1

·      MAC-awake↑/↓

·      MAC awake variation between drugs



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**

Compartment model

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

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

o 1/(brain-blood partition coefficient)


↑Circuit <->alveolus:

↑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:

↓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 -> 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

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

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

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


↓MAC-awake (faster induction):


·   Age: neonate, elderly

·   Pregnancy: ↓30% (progesterone)

·   Obesity: inflammatory cytokines


·   ↓mAP (<40mmHg)

·   ↓pO2 (<40mmHg)

·   ↑pCO2 (>60mmHg sedation, >80mmHg anaesthesia)

·   ↓Temp

·   ↓pH

·   ↓[Na+]

Drug interactions

·   Acute depressants: propofol, barbiturates, benzodiazepines, opioids, local anaesthetics, Mg2+

·   Chronic stimulant: (e.g. amphetamines)


↑MAC-awake (slower induction)


·   Age: max at 6 months then ↓6% per decade

·   Red hair


·   ↑Temp

·   ↑[Na+]

Drug interactions

·   Acute stimulant

·   Chronic depressant


MAC-awake variation between drugs:

Drug values

·  Isoflurane 0.45

·  Sevoflurane 0.36

·  Desflurane 0.4

·  Halothane 0.53

·  N2O 0.64

Cause of differences

·  ? Differential effects

o Unconsciousness: reticular activating system, thalamus, (frontal) cortex

o Immobility: spinal cord



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