Pharmacokinetics of Pharmacokinetics of Inhalation AnestheticsInhalation Anesthetics

Dr.Doaa KamalDr.Doaa KamalDepartment of Anesthesia, Ain Department of Anesthesia, Ain Shams UniversityShams UniversityEmail adress: Email adress: mkjamaluddeen@hotmail.commkjamaluddeen@hotmail.com

PharmacokineticsPharmacokinetics::The study of The study of AAbsorption.bsorption. DDistribution.istribution. MMetabolism.etabolism. EExcretion.xcretion.AimAim::

For a better understanding of the factors For a better understanding of the factors that governthat govern inductioninduction andand recoveryrecovery from from anesthesia.anesthesia.

KEY POINTsKEY POINTs::

►► Alveolar partial pressureAlveolar partial pressure (FA)(FA) governs the governs the partial pressure of volatile anesthetic in all body partial pressure of volatile anesthetic in all body tissues: all must approach and ultimately equal tissues: all must approach and ultimately equal alveolar partial pressure.alveolar partial pressure.

► ► EquilibrationEquilibration occurs occurs rapidlyrapidly between between alveolaralveolar & & brainbrain anesthetic partial pressure. anesthetic partial pressure.

► ► Therefore Therefore Alveolar concentrationAlveolar concentration is ultimately is ultimately the the principal factorprincipal factor in determining the in determining the onset of onset of actionaction..

►►DiffusionDiffusion occurs from a region of occurs from a region of higher higher concentrationconcentration to a region of to a region of lower lower concentrationconcentration (down a (down a concentration gradientconcentration gradient).).

(A) Factors Affecting (A) Factors Affecting InspiredInspired gas gas concentration concentration (Fi)(Fi)1)1) Fresh Gas Flow rateFresh Gas Flow rate:: ↑↑ FGF → ↑ speed of induction & recovery. FGF → ↑ speed of induction & recovery.

(If pt awakens in the middle of surgery on (If pt awakens in the middle of surgery on low flow → low flow → ↑↑ FGF). FGF).

2)2) VolumeVolume of breathing circuit of breathing circuit ((apparatus dead space): ): ↑ volume → ↑ volume → slower induction dt.dilution of anesthetic slower induction dt.dilution of anesthetic gases. (Eg. MRI breathing circuits = 3m, gases. (Eg. MRI breathing circuits = 3m, circuit priming for pediatrics, circuit priming circuit priming for pediatrics, circuit priming for single breath technique for sevoflurane).for single breath technique for sevoflurane).

3)3) AbsorptionAbsorption by the breathing circuit: by the breathing circuit: rubber tubing absorbs rubber tubing absorbs ˃˃ plastic & silicon plastic & silicon → → delays induction & recovery. Not used for pt delays induction & recovery. Not used for pt with suspected malignant hyperthermia with suspected malignant hyperthermia (release of trace anesthetic gases).(release of trace anesthetic gases).

(B) Factors Affecting (B) Factors Affecting AlveolarAlveolar concentration concentration (F(FAA))

(a) DELIVERY:(a) DELIVERY:

1)1) ConcentrationConcentration..

2)2) VentilationVentilation:: ↑ minute ventilation → ↑ minute ventilation → ↑ delivery (Eg. child crying).↑ delivery (Eg. child crying).

(B) Factors Affecting (B) Factors Affecting AlveolarAlveolar concentration concentration (F(FAA))

(b) UPTAKE:(b) UPTAKE:RULERULE:: ↑ uptake uptake → slower slower

rate of induction!! dt. rate of induction!! dt. Slower build up ofSlower build up of Alveolar Alveolar Partial PressurePartial Pressure..

1)1) Blood/gas solubilityBlood/gas solubility coefficientcoefficient..

↑ solubility solubility → ↓ rate of induction. (Blood & tissues act like a sponge).

(B) Factors Affecting (B) Factors Affecting AlveolarAlveolar concentration concentration (F(FAA))

(b) UPTAKE:(b) UPTAKE:2)2) Pulmonary blood flowPulmonary blood flow:: ((Cardiac outputCardiac output))

↑ ↑ Alveolar blood flow (COP) → ↑ uptake → Alveolar blood flow (COP) → ↑ uptake → slower build up of alveolar partial pressure slower build up of alveolar partial pressure slower inductionslower induction..N.B. This effect is greater with soluble agents N.B. This effect is greater with soluble agents (Eg.halothane) (Eg.halothane) ˃˃ insoluble agents (N insoluble agents (N22O).O).

►►Children with Children with F4 → → rapid induction due to ↓ pulmonary blood flow.

(B) Factors Affecting (B) Factors Affecting AlveolarAlveolar concentration concentration (F(FAA))

(b) UPTAKE:(b) UPTAKE:3)3) Tissue UptakeTissue Uptake:: partial pr difference partial pr difference

between alveolar gas & venous blood. between alveolar gas & venous blood. ↑ Tissue uptake → lower partial ↑ Tissue uptake → lower partial pressure of venous blood → ↑ uptake pressure of venous blood → ↑ uptake → slower rate of induction.→ slower rate of induction.

(a) Tissue (a) Tissue solubilitysolubility of anesthetic agent. of anesthetic agent.

(b) Tissue (b) Tissue blood flowblood flow..

(c) (c) Partial pressure differencePartial pressure difference between between Arterial bloodArterial blood and and tissuestissues..

(B) Factors Affecting (B) Factors Affecting ArterialArterial concentration concentration (Fa)(Fa)

Depends on Depends on Ventilation/Perfusion matchingVentilation/Perfusion matching::

(a) (a) VentilatedVentilated non perfused areas: [ non perfused areas: [dead space]]

↓ ↓ arterial concentration.arterial concentration.

(b) (b) PerfusedPerfused non ventilated areas: non ventilated areas: [[intrapulmonary shunting] ] == shunt fraction. shunt fraction.

↓ ↓ arterial concentration.arterial concentration.

SUMMARYSUMMARY(1) Inspired gas (Fi):1- FGF rate.

2- Absorption by breathing circuit.

3- Volume of breathing circuit.

(3) Arterial concentration (Fa):

V/Q mismatching.

(2) Alveolar gas (FA):

DELIVERY:

1- Concentration.

2- Minute Ventilation.

UPTAKE:

1- Blood gas solubility.

2- Alveolar blood flow.

3- Tissue uptake.

NN22OO is is 30 times more soluble30 times more soluble than than NN22 in in the blood.the blood.

ApplicationsApplications::

1- Concentration effect/ 21- Concentration effect/ 2ndnd gas effect gas effect (induction).(induction).

2- Diffusion hypoxia 2- Diffusion hypoxia (recovery).(recovery).

3- Contraindication of N3- Contraindication of N22O in presence of O in presence of closed air spaces.closed air spaces.

(1) (1) Concentration Effect/ 2Concentration Effect/ 2ndnd Gas Effect Gas Effect

NN22OO diffuses rapidly from alveoli to diffuses rapidly from alveoli to blood much faster than blood much faster than NN22 diffuses out. diffuses out. This decreases the total volume of gas This decreases the total volume of gas in the alveolus → ↑ fractional in the alveolus → ↑ fractional concentration of other anesthetic concentration of other anesthetic agent.agent.

(2) (2) Diffusion HypoxiaDiffusion Hypoxia ((opposite the concentration effect)opposite the concentration effect)

►►At the end of anesthesia after discontinuation At the end of anesthesia after discontinuation of of NN22OO, , NN22OO diffuses from blood into the diffuses from blood into the alveoli much faster than alveoli much faster than NN22 diffuses from diffuses from alveoli into the blood.alveoli into the blood.

►►↑↑ Total volume of gas in the alveolus Total volume of gas in the alveolus →→ fractional concentration of gases in the alveoli fractional concentration of gases in the alveoli is diluted by is diluted by NN22OO →→ ↓ PaO↓ PaO22 & & PaCOPaCO22 → → hypoxia. This occurs in the first 5-10 mins of hypoxia. This occurs in the first 5-10 mins of recovery. Therefore it is advised to use 100% recovery. Therefore it is advised to use 100% OO22 after discontinuation of after discontinuation of NN22OO..

(3) (3) N2O is Contraindicated in Presence of Closed N2O is Contraindicated in Presence of Closed Air SpacesAir Spaces

The higher solubility of The higher solubility of NN22OO than than NN22 in the in the blood makes it contraindicated in the presence blood makes it contraindicated in the presence of closed air spaces:of closed air spaces: Intestinal obstructionIntestinal obstruction.. PneumothoraxPneumothorax.. PneumocephalusPneumocephalus.. Air embolismAir embolism.. TympanoplastyTympanoplasty..

xx 2-3 fold2-3 fold increase in size within 15 minutes!! increase in size within 15 minutes!!