Anesthetic Gases & Vaporizers – Comprehensive Bullet Notes

Roadmap & Unit Scope

• Welcome to Unit 2: Anesthetic Gases and Vaporizers (ANES 503)

• Key content pillars covered in the unit:

  • History of inhaled anesthetics (IA) & vaporizers

  • Core physicochemical data (vapor pressure, partition coefficients)

  • Pharmacodynamics: anesthetic mechanisms & MAC

  • Pharmacokinetics: $F<em>I$, $F</em>A$, $F_a$, uptake, distribution, elimination

  • Clinical pharmacology & utility of common IA ((\text{N}_2\text{O},\;\text{Hal},\;\text{Iso},\;\text{Des},\;\text{Sev},\;\text{Xe}))

  • Vaporizer evolution: Copper Kettle → Tec series → Tec 6 (Des) → Aladin cassette → electronic injectors

  • Safety, hazards, altitude effects, CO(_2) absorber degradation

Historical Development of Inhaled Anesthetics

• 1772–1800 Nitrous Oxide

  • Joseph Priestley discovers gas; Humphry Davy publishes 580-page monograph (1800) predicting surgical use.

  • Early entertainment use (“laughing gas”).

  • First dental anesthesia: Gardner Colton & Horace Wells (1844).

• Diethyl Ether

  • Synthesised 1540 (Valerius Cordus); clinical fame after public demo by Morton (Oct 16 1846, Boston) → “Gentlemen, this is no humbug!”.

• Chloroform (1831/1847)

  • Introduced by Sir James Simpson for labor pain; later abandoned (arrhythmia, hepatotoxicity).

• Inter-war agents

  • Ethyl chloride (1894), Ethylene (1923), Cyclopropane (1929 discovery, 1934 clinical), Divinyl ether (1930), Trichloroethylene (1940s, WWII non-flammable choice).

• Fluorinated Hydrocarbons

  • Freon (1930) → search for non-combustible anesthetics.

  • Halothane (Suckling, 1951 → released 1956): revolutionized IA; criteria—volatility, stability, potency.

  • Methoxyflurane (1958), Enflurane (1963) & Isoflurane (1965; released 1981 after purity hurdles).

  • Desflurane (1992), Sevoflurane (1994), Xenon rediscovered with modern scavenging.

Classification & Physical Chemistry

• Non-volatile true gases: $\text{N}_2\text{O},\;\text{Xe}$ (gas @ RT)

• Volatile agents (vapors of liquids): Halothane, Isoflurane, Desflurane, Sevoflurane

  • Volatile = low vapor pressure relative to ATM → must be delivered via vaporizer.

• Key definitions:

  • Vapor pressure (SVP): gas P above liquid at equilibrium; rises with T, independent of ambient P.

  • Boiling point: T where SVP = atmospheric P (Des boils at $22.8^{\circ}\text{C}$).

  • Partition coefficient ((\lambda)) e.g. $\lambda<em>{b/g}=\frac{C</em>{blood}}{C_{gas}}$ at equilibrium; governs solubility & speed.

  • Specific heat, latent heat of vaporization, thermal conductivity guide vaporizer material choice (copper, bronze).

Pharmacodynamics

Unitary Lipid Theory (Meyer–Overton Rule)

• Potency (\propto) olive-oil/gas solubility (spans 10,000-fold potency range).

• Limitations: stereoselectivity of enantiomers, protein binding evidence.

Protein-Target Evidence

• IA bind hydrophobic pockets on GABA(A), NMDA, 5-HT, K({ATP}) channels.

• Mutagenesis ↓ anesthetic modulation ⇒ protein binding is causal.

Minimum Alveolar Concentration (MAC)

• Definition: alveolar partial pressure preventing movement in $50\%$ of subjects to surgical incision.

• Utilisations:

  • Standardised potency comparison.

  • Mirrors brain P(_\text{a}) at equilibrium.

• Dosing landmarks:

  • $1.3\,\text{MAC} \Rightarrow EC_{95}$ (no movement in $95\%$).

  • $0.4\text{–}0.5\,\text{MAC}$ → loss of awareness; $0.15\text{–}0.3\,\text{MAC}$ → eye opening.

  • MAC values are roughly additive: $0.5\,\text{MAC}\;\text{N}_2\text{O}+0.5\,\text{MAC Iso}=1\,\text{MAC}.$

• Age effect: $\text{MAC}<em>{\text{age}}=\text{MAC}</em>{40\,\text{yr}}\times(1-0.06\times\text{decades})$ (≈$6\%$ ↓ per decade).

• Factors ↑ MAC: hyperthermia, chronic EtOH, hypernatremia, hyperthyroid.
  ↓ MAC: hypothermia, hyponatremia, pregnancy, anemia, opioids, sedatives.

Neurotoxicity & Protection

• IA in neonates: apoptosis in animals; SmartTots/FDA caution for <$3$ yr prolonged exposure.

• Pre-conditioning: IA open K(_{ATP}), ↓ ROS; protection in CABG.

• NMDA antagonists (N(_2)O, Xe) provide neuro- & cardio-protection.

Pharmacokinetics

Key Variables

• $F<em>I$ (inspired fraction), $F</em>A$ (alveolar), $F_a$ (arterial).

• Uptake equation (Fick): $V<em>B=\lambda</em>{b/g}\;Q\;(P<em>A-P</em>v)/P_B$.

• Time constant for circuit rise: $\tau=V_C/FGF$ → $95\%$ equilibrium ≈ $3\tau$.

• Alveolar rise (no uptake): $F<em>A=F</em>I\bigl(1-e^{-t/\tau}\bigr)$ with $\tau=FRC/\dot V_A$.

Determinants of Uptake

1. Blood solubility ((\lambda_{b/g})) ↑ ⇒ slower rise.

2. Cardiac output ((Q)) ↑ ⇒ more uptake, slower induction (opposite for low CO).

3. $P<em>A-P</em>v$ gradient (tissue uptake).

Special Phenomena

• Overpressurisation: deliver FI>target FA to speed equilibrium (like IV bolus).

• Concentration Effect: high FI accelerates FA/FI rise (marked with $\text{N}_2\text{O}$ at $70\%$).

• Second-Gas Effect: high-volume gas (N(_2)O) accelerates uptake of potent 2nd gas.

• Ventilation-Perfusion mismatch: R→L shunt slows poorly soluble agent induction; oppositely, affects soluble less.

Ventilation & Perfusion

• ↑ (\dot V_A) speeds rise, especially for soluble agents.

• Spont breathing creates safety feedback (IA depress drive when deep).

Elimination & Recovery

• Dominated by solubility & duration.

• Rule-of-thumb liquid usage: $\text{mL/hr}=3\times\text{FGF (L/min)}\times\text{vol\%}$.

• Diffusion hypoxia with N(2)O ⇒ give $100\%$ O(2$) for$5\text{–}10$min.</p></li></ul><h3 id="13192d22-c5e2-4970-bca3-f4d254f0272d" data-toc-id="13192d22-c5e2-4970-bca3-f4d254f0272d" collapsed="false" seolevelmigrated="true">Clinical Pharmacology: Individual Agents</h3><h4 id="a82667f4-0b5d-42d1-a0de-fbfac69ade7c" data-toc-id="a82667f4-0b5d-42d1-a0de-fbfac69ade7c" collapsed="false" seolevelmigrated="true">Nitrous Oxide (N(_2)O)</h4><ul><li><p>NMDA antagonist, MAC$104\%$, (\lambda_{b/g}=0.46).</p></li><li><p>Analgesia, sympathetic stimulation; expands compliant air spaces ((\approx3\times) in$30$min at$75\%$).</p></li><li><p>Contra: pneumothorax, VAE, eye/ear procedures, bowel obstruction, intra-cranial air.</p></li><li><p>Eliminated unchanged via lungs.</p></li></ul><h4 id="6c8357ea-b2e2-4c9c-9658-8f923d6fafb2" data-toc-id="6c8357ea-b2e2-4c9c-9658-8f923d6fafb2" collapsed="false" seolevelmigrated="true">Halothane</h4><ul><li><p>Alkane, MAC$0.75\%$, (\lambda_{b/g}=2.5).</p></li><li><p>Direct myocardial depression, sensitises to epi arrhythmias.</p></li><li><p>"Halothane hepatitis" (immune TFA adducts) rare; avoid repeat use.</p></li></ul><h4 id="79dd56b5-d3f3-4aa6-9cbc-82048cb73203" data-toc-id="79dd56b5-d3f3-4aa6-9cbc-82048cb73203" collapsed="false" seolevelmigrated="true">Isoflurane</h4><ul><li><p>Ether, MAC$1.17\%$, (\lambda_{b/g}=1.46).</p></li><li><p>Maintains CO via reflex tachycardia; coronary vasodilator (steal debated).</p></li><li><p>Pungent—no mask induction.</p></li></ul><h4 id="37c22b68-dd8c-40ec-b2fb-d66587023dc9" data-toc-id="37c22b68-dd8c-40ec-b2fb-d66587023dc9" collapsed="false" seolevelmigrated="true">Desflurane</h4><ul><li><p>Ether (Cl→F swap vs Iso), MAC$6.6\%$, (\lambda_{b/g}=0.42).</p></li><li><p>Boils near RT; delivered via heated vaporizers (Tec 6, D-Vapor).</p></li><li><p>Rapid changes ⇒ sympathetic surge (↑HR/BP); airway irritant.</p></li></ul><h4 id="16a2c558-d81f-4f84-b093-956e8c27cd26" data-toc-id="16a2c558-d81f-4f84-b093-956e8c27cd26" collapsed="false" seolevelmigrated="true">Sevoflurane</h4><ul><li><p>Sweet, MAC$1.8\%, (\lambda_{b/g}=0.65); ideal for inhalational induction.

• Forms Compound A with dry soda lime; no human nephrotoxicity shown (maintain FGF > 2$L/min for long cases).</p></li></ul><h4 id="f69e3072-1af1-443a-93bf-75687bed0c20" data-toc-id="f69e3072-1af1-443a-93bf-75687bed0c20" collapsed="false" seolevelmigrated="true">Xenon</h4><ul><li><p>Noble gas, MAC$71\%, (\lambda_{b/g}=0.115).

• NMDA inhibition, cardio-stable, neuro-protective, no MH; high cost limits use.

Vaporizer Evolution & Physics

Milestones

• Copper Kettle (1952): flow-through bubbler, copper bath for thermal stability.

• TECOTA, Verni-Trol: first agent-specific, temp-comp devices enabling halothane era.

• Variable-Bypass Concept: split FGF into bypass vs vaporising chambers; concentration dial sets splitting ratio.

• Modern Mechanical Series: GE Tec 5/7/850; Dräger Vapor 2000/3000 (flow-over wick, bimetal temp compensation).

Variable-Bypass Mechanics

• Splitting ratio determined by dial-controlled variable orifice.

• Output stabilised over 20\text{–}35^{\circ}\text{C}$via bimetal strip/expansion element.</p></li><li><p>Formula example (Sevo at$20^{\circ}\text{C}$):</p><ul><li><p>SVP$=160\;\text{mmHg} \Rightarrow 21\%$vapor.</p></li><li><p>For 1 vol\% output ⇒ bypass : chamber ≈$20:1.

Factors Influencing Output

1. FGF extremes: <250\,\text{mL/min} or >15\,\text{L/min} alter turbulence & output.

2. Temperature: auto-compensation keeps (\pm\,\approx5\%) accuracy.

3. Intermittent back-pressure (pumping effect): PPV/O(_2 flush) → minor modern impact.

4. Carrier gas: Viscosity differences (N(2)O < O(2$) ↓ Tec 6 output ≈$20\% at low flows.

Safety & Hazards

• Keyed fillers, interlock (one-vapour-at-a-time), anti-spill design.

• Mis-filling, tilting, over-filling → overdose (liquid into bypass).

• Leaks (loose cap, O-rings) → awareness & OR pollution.

Desflurane-Specific Vaporizers

Tec 6 / D-Vapor Principles

• Electrically heat sump to 39^{\circ}\text{C}$→ vapour P ≈$1500\,\text{mmHg}.

• Dual-circuit gas blender; pressure-balanced restrictors R1 (carrier) & R2 (vapour).

• Output vol\% constant; partial pressure varies with altitude ⇒
  \text{Dial}{\text{new}} = \frac{\text{Dial}{\text{sea}} \times 760}{P_{\text{ambient}}}.

• Safety shut-off (no output) if: tilt, low agent (<20\,\text{mL}), power fail, pressure fault.

Electronic & Cassette Vaporizers

GE Aladin

• Permanent electronic core + interchangeable agent cassette (magnet-coded).

• CPU receives: dial, temp, sump pressure, bypass & chamber flow sensors, carrier composition.

• Flow-control valve meters vapour; one-way check valve stops backflow (critical for Des > boiling point).

• Heated fan assists when high vapour demand (Des or Sevo mask induction).

Injector Systems (Maquet FLOW-i, Dräger DIVA)

• "Fuel-injection" metered droplets into heated chamber in FGF stream.

• Real-time agent analysis feeds closed-loop control.

CO(_2) Absorber Interactions

• Compound A: Sevo + strong bases (esp Ba(OH)(_2) lime, desiccated) at low flows ⇒ vinyl ether; rat nephrotoxin, no human harm.

• Carbon Monoxide & Heat: Dry absorbent + Des/Sev/Iso → CO + exotherm (Des highest CO, Sevo highest heat). Removal of Ba-lime & switch to Ca(OH)(_2$) products mitigates risk.

Clinical Utility Across Peri-operative Phases

• Induction: Sevo (non-pungent, insoluble) ideal, esp kids/uncooperative adults; IA preserve spontaneous ventilation & offer feedback safety.

• Maintenance: Volatiles dominate for titratability, muscle relaxation, cerebral & myocardial protection; drawbacks—no analgesia, PONV, greenhouse effect.

• Emergence: Depends on solubility, duration, minute ventilation; Des fastest, Iso slowest; ensure 100\% O(2 after N(2)O to avoid diffusion hypoxia.

Essential Formulae & Numeric References

• Uptake (Fick): $V<em>B=\lambda</em>{b/g}\,Q\,(P<em>A-P</em>v)/P_B$

• Liquid usage: $\text{mL/hr}=3\times \text{FGF(L/min)}\times\text{vol\%}$

• Tec 6 altitude dial: $\text{Dial}<em>{req}=\frac{\text{Dial}</em>{sea}\times 760}{P_{amb}}$

• Agent half-times (context-sensitive): Des < Sev < Iso.

Ethical & Environmental Notes

• Des & N(_2)O are potent greenhouse gases; Sevo less so; Xe neutral but energy-intensive to harvest.

• Occupational exposure reduced via scavenging; modern vaporizers have closed filling to minimise leakage.

Practical Implications & Safety Checklist

• Verify vaporizers are:

  • Correct agent, sufficient level, upright, locked in interlock.

  • No leaks (negative-pressure check with dial ON).

• During low-flow anesthesia: monitor Fi agent with gas analyser; ensure CO(_2 absorbent moisture; maintain flows >2$$ L/min with Sevo for long cases.

• At altitude or hyperbaric settings: adjust Tec 6 dial per pressure; conventional variable-bypass deliver correct partial pressure automatically.