· 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 |
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Wash-in curve |
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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) |
↑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: FRC |
· ↑VA (↑neonate/crying/pregnant/shock) · ↓FRC (↓supine/pregnant/obese) · Affects soluble (e.g. halothane) > soluble 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 |
↓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 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) |
Physiology |
· Age: neonate, elderly · Pregnancy: ↓30% (progesterone) · Obesity: inflammatory cytokines |
Pathology |
· ↓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) |
Physiology |
· Age: max at 6 months then ↓6% per decade · Red hair |
Pathology |
· ↑Temp · ↑[Na+] |
Drug interactions |
· Acute stimulant · Chronic depressant |
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 o Unconsciousness: reticular activating system, thalamus, (frontal) cortex o Immobility: spinal cord |
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