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INHALATIONAL ANAESTHETICS
PRESENTER: Dr. Karthick. DMODERATOR: Dr Anand H.Kulkarni
Topics Covered
Comparison of commonly used inhalational anaesthetics,
- physical/chemical properties
- various organ system effects
- metabolism and toxicityNitrous oxide
ISOFLURANE
SEVOFLURANE
HALOTHANE
PHYSICAL AND CHEMICAL PROPERTIES OF INHALED
ANAESTHETICS
BOILING POINT/ VAPOUR PRESSURE
Boiling Point (° C )
Vapour pressure(mmHg) at 20°C
HALOTHANE 50.2 243.3
ISOFLURANE 48.5 250
DESFLURANE 22.8 664
SEVOFLURANE 58.5 160
Implication
Desflurane cannot be administered using standard vapourizer
Physical properties (cont..)HALOTHANE Clear, non-explosive, non-
inflammable liquid at room temperature, non-pungent odor
ISOFLURANE Clear, non-inflammable liquid at room temperature, pungent ethereal odor.
SEVOFLURANE Non pungent minimal odor
DESFLURANE Pungent odor , irritating and unpleasant to inhale.
Implication
In regard to negligible airway irritant activity sevoflurane followed by halothane are very suitable for inhalational induction
STRUCTURE
Halothane: Halogenated alkane derivative
2 chloro, 2 bromo 1,1,1 trifluoroethane Other halogenated agents: Halogenated
ether derivatives
STRUCTURE
Isoflurane
Sevoflurane
ii H
Implication
Effect on ozone layerSensitization of heart to epinephrineToxicity
BLOOD GAS PARTITION COEFFICIENT
HALOTHANE 2.5
ISOFLURANE 1.4
SEVOFLURANE 0.69
DESFLURANE 0.42
Implication
Lower the blood gas partition coefficient ……….. Rapid is the induction and recovery from anaesthesia
STABILITY
HALOTHANE ISOFLURANE
SEVOFLURANE
ALKALI Some decomposition
Stable Stable
UV LIGHT Decomposes Stable Stable
METAL May react Stable Stable
STABILITY
Halothane - - - susceptible to decomposition to hydrochloric acid, chlorine, bromide and phosgene.
Stored in amber coloured bottlesPreservative - - - Thymol (0.01%)
METABOLISM
Oxidative and Reductive metabolism
HALOTHANE 20%
ISOFLURANE 0.2%
DESFLURANE 0.02%
SEVOFLURANE 4%
MINIMUM ALVEOLAR CONCENTRATION
MAC in oxygen(%)
Halothane 0.75
Enflurane 1.68
Isofurane 1.15
Sevoflurane 2
Desflurane 6
Nitrous oxide 105
Xenon 71
EFFECTS ON VARIOUS ORGAN SYSTEM
CARDIOVASCULAR SYSTEM
MEAN ARTERIAL PRESSURE
Halothane, Isoflurane, Desflurane, Sevoflurane ……… dose dependant decrease in MAP.
Halothane/ Enflurane ….. Decreases cardiac contractility
Isoflurane/Desflurane/Sevoflurane
……….. principally decreases systemic vascular resistance
HEART RATE
INHALATIONAL ANAESTHETIC
HEART RATE
HALOTHANE DECREASES
ISOFLURANE/ENFLURANE/DESFLURANE/SEVOFLURANE
INCREASES
CARDIAC OUTPUT AND STROKE VOLUME
Halothane ……. Dose dependent decrease in cardiac output
Isofurane/Sevoflurane ….. Very minimal decrease
Nitrous oxide ……. Moderate increase
SYSTEMIC VASCULAR RESISTANCE
ISOFLURANE/DESFLURANE/SEVOFLURANE
Decrease
HALOTHANE No net effect
NITROUS OXIDE No effect
PULMONARY VASCULAR RESISTANCE
Halogenated volatile anaesthetics ……. No predictable effect
Nitrous oxide …. Increases
CORONARY BLOOD FLOW
Isoflurane ….. Most potent coronary vasodilator
….. Small coronary vessels
….. Coronary steal phenomenon halothane/ Sevoflurane
….. Cause coronary vasodilatation
EPINEPHRINE INDUCED ARRYTHMIAS
Halothane precipitates arrhythmias in combination with epinephrine.
Epinephrine tolerated: micrograms/kg
Halothane: 1.5
Isoflurane, sevoflurane,desflurane: 4.5
When used at MAC levels.
RESPIRATORY SYSTEM
PATTERN OF BREATHINGHalothane/ Desflurane/ Sevoflurane … dose
dependant increase in the frequency of breathing
Isoflurane
…. Upto 1 MAC – dose dependant increase
> 1 MAC – no further increase
TIDAL VOLUME ..
all inhalational anaesthetics --- decrease
PATTERN OF BREATHING
Net effect :
Rapid/ shallow pattern of breathing
Minute ventilation … ?
Decreases
MINUTE VENTILATION
VENTILATORY RESPONSE TO CO2
All inhalational anaesthetics… decrease in ventilatory response to CO2
Mediated principally at the level of medulla.
N2O ----- doesn't increase PaCO2
VENTILATORY RESPONSE TO O2
Volatile anaesthetics and N2O ….. Attenuate ventilatory response to hypoxemia in dose- dependant manner.
Peripheral chemoreceptors appear to be the major site of this inhibitory response.
AIRWAY RESISTANCE
All volatile anaesthetics ---- potent bronchodilators
Halothane ….. Most potent
followed by isoflurane and sevoflurane.
AIRWAY RESISTANCE
AIRWAY IRRITABILITY
Desflurane ----- most irritantEnflurane/ Isoflurane ------ irritantHalothane/ Sevoflurane ------ non – irritant
thus preferred for inhalational induction.
What if irritant agents are used for inhalational induction?
MUCOCILIARY FUNCTION
Postoperative hypoxemia and atelectasis – common causes of postoperative morbidity
Halothane ---- dose dependant decrease in mucociliary function.
CENTRAL NERVOUS SYSTEM
CEREBRAL BLOOD FLOWVolatile anaesthetics administered during
normocapnia in conc > 0.6 MAC
…. Cerebral vasodilatation
…. Decreased cerebral vascular resistance
…. Dose dependant increase in CBFGreatest increase in CBF---- Halothane (200%)Least increase ----- Isoflurane( minimal/no
increase)
CEREBRAL BLOOD FLOW
AUTOREGULATION:
HALOTHANE ABOLISHED
ISOFLURANE IMPAIRED
SEVOFLURANE INTACT
CEREBRAL BLOOD FLOW
CEREBRAL METABOLIC OXYGEN REQUIREMENT
All volatile anaesthetics …. Dose dependent decrease in CMRO2
Isoflurane = Desflurane = Sevoflurane > Halothane
CBF / CMR
CEREBROSPINAL FLUID
CSF PRODUCTION ABSORPTION
HALOTHANE ↓(30%) ↓
ISOFLURANE -- ↑
ENFLURANE ↑ ↓
Increase in ICP parallels increase in CBF.Enflurane …… increased incidence of
epilepsy Iso/Des/ Sevoflurane …. No evidence of
convulsive activity on EEG.N2O administration …. Increases motor
activity with clonus and opisthotonus even in clinically used concentrations.
HEPATIC SYSTEM
HEPATIC BLOOD FLOW
BLOOD FLOW HALOTHANE ISOFLURANE
PORTAL VEIN ↓ ↓
HEPATIC ARTERY
↓ ↑
NET FLOW ↓ Maintained
Desflurane/ Sevoflurane ……. Similar to isoflurane
HEPATIC BLOOD FLOW
DRUG EFFECTS
Interference of drug clearance by volatile anaesthetics is due to,
1, decrease in hepatic blood flow
2, inhibition of drug metabolizing enzymes
Halothane … inhibits oxidative metabolism of drugs
HEPATOTOXICITY
TFA (Trifluoro acetic acid)
HALOTHANE Large amounts
ISOFLURANE/ ENFLURANE/ DESFLURANE
Minute quantities
SEVOFLURANE Nil
-- depends on the quantity of drug getting metabolised
RENAL SYSTEM
All volatile anaesthetics : dose related decrease in renal blood flow, glomerular filtration rate and urine output.
Reflects the effect of volatile anaesthetic on systolic B.P and cardiac output.
NEPHROTOXICITY
Flouride induced nephrotoxicity
Methoxyflurane, Enflurane, Sevoflurane
Vinyl halide induced nephrotoxicity
Sevoflurane
FLOURIDE INDUCED NEPHROTOXICITY
High output renal failure
Manifestations : polyuria, hypernatremia, hyperosmolarity, inability to conc. urine.
First observed after methoxyflurane administration
FLOURIDE INDUCED NEPHROTOXICITY
Renal threshold limit of plasma flouride(toxicity)
…… 50μm/litSource of fluoride :
intrarenal production …. Methoxyflurane/ enflurane
hepatic metabolism …. sevoflurane
FLOURIDE INDUCED NEPHROTOXICITY
VINYL HALIDE NEPHROTOXICITY
Reaction of CO2 absorbents with sevoflurane.Degradation products : Compound A – ECompound A …. Fluromethyl 2,2 difluoro 1 trifluro methyl
vinyl ether. …. Proximal renal tubular injury.Precipitating factorsDegradation of compound A to reactive thiol.
SKELETAL MUSCLE EFFECTS
SKELETAL MUSCLE RELAXATION
Sevoflurane/ Desflurane/ Isoflurane …. Two fold greater skeletal muscle relaxation than halothane.
N20 …. No relaxation
> 1 MAC …. Skeletal muscle rigidity
INTERACTION WITH NEUROMUSCULAR BLOCKING AGENTS
Dose dependant enhancement …. All volatile anaesthetics
Isoflurane / Desflurane/ Sevoflurane >= Halothane
N2O …. No significant potentiation
CARBONMONOXIDE TOXICITY
Reflects degradation of volatile anaesthetics that contain a CHF2 moiety ( desflurane, enflurane, isoflurane) by the strong bases present in carbondioxide absorbents.
Desflurane > Enflurane / IsofluraneHalothane/ Sevoflurane…. No CO
formation
NITROUS OXIDE
INTRODUCTION OF NITROUS OXIDE
Humpry Davy …. 1800 first observed its analgesic effect …. Laughing gas
HORACE WELLS …. 1844
Used N2O to facilitate
the extraction of a toothUnfortunately, his first
public demonstration
was a failure.
N2O USAGE IN THE INITIAL DAYS
PHYSICAL PROPERTIES
Molecular weight : 44Boiling point : - 88°CColourless, sweet smelling, non-
inflammable and non – irritant gas.MAC …. 105 %
PHYSICAL PROPERTIES
Blood gas partition coefficient … 0.42Metabolism … nilExcretion … lungsSupply :
…. Pure nitrous oxide( 5000 kPa at 20°C)
…. Entonox (15000 kPa at 20°C)
NITROUS OXIDE CYLINDERS
Full cylinder at room temperature contains liquid
The pressure in these cylinders will not reflect how much N2O it contains as long as there is liquid N2O in the cylinder.
Critical temperature …. 36.5 °C
ENTONOX
Mixture of equal parts of N2O and O2.
Supplied in cylinders pressurized to 15000 kPa at 20°C.
Pseudocritical temperatureManufactured utilizing Poynting effect Labour analgesia
PHARMACOKINETICS
Low blood gas solubility … rapid equilibration of Fa/Fi ratio.
Second gas effectConcentration effectDiffusion hypoxia or Fink effectN2O …. Enclosed gas – filled cavity within
the body.
CONCENTRATION CONCENTRATION EFFECTEFFECT
Inspired anaesthetic concentration influences Inspired anaesthetic concentration influences alveolar concentration that may be achieved alveolar concentration that may be achieved and the rate at which that concentration may and the rate at which that concentration may be attainedbe attained
Concentration effect states that with higher Concentration effect states that with higher inspired concentrations of an anesthetic, the inspired concentrations of an anesthetic, the rate of rise in arterial tension is greaterrate of rise in arterial tension is greater
CONCENTRATION CONCENTRATION EFFECTEFFECT
The The FFA A / / FFII ratio indicates the percent of ratio indicates the percent of
anesthetic removed by uptake.anesthetic removed by uptake. At 100% inspired concentration, uptake no At 100% inspired concentration, uptake no
longer limits the rise in longer limits the rise in FFA A / / FFII
19% oxygen
80% nitrous oxide
19% oxygen
40% nitrous oxide
32% nitrous oxide
1% second gas
7.6% oxygen
0.4% second gas
1% second gas
Uptake of half of nitrous oxide
Absorbed gases replaced by added ventilation
SECOND GAS EFFECT
SECOND GAS EFFECTSECOND GAS EFFECT
Factors that govern concentration effect also Factors that govern concentration effect also influence the concentration of any gas given influence the concentration of any gas given concomitantly with concomitantly with NN22OO
Loss of volume associated with the uptake of Loss of volume associated with the uptake of NN22O O concentrates the second gasconcentrates the second gas
Replacement of the gas taken up by an increase in Replacement of the gas taken up by an increase in inspired ventilation augments the amount of inspired ventilation augments the amount of second gas in the lungsecond gas in the lung
DIFFUSION HYPOXIA
The uptake of large volumes of N2O into the alveoli during recovery.
Occurance of hypoxia … 2 means
- directly affects oxygenation by displacing oxygen
- by diluting alveolar CO2 , they may decrease respiratory drive and ventilation.
PHARMACODYNAMICS
VARIOUS ORGAN SYSTEM EFFECTS
CENTRAL NERVOUS SYSTEM
Significantly increases CBF and ICP.Minimally increases cerebral metabolismWhen used in neurosurgery … diffuses into
air pockets left within the skull following closure of wound
Thus not recommended for neurosurgical cases.
RESPIRATORY SYSTEM
Pleasant to inhale and not irritating to the airway
Increases the uptake of the accompanying agent in addition to reducing the MAC
Minimal effect on ventilation
RESPIRATORY SYSTEM
Ventilatory response to CO2 … no alteration
Ventilatory response to hypoxia … significantly reduces
Risk of diffusion hypoxia
CARDIOVASCULAR EFFECTS
Direct effect …. Myocardial depressantThis is offset by its stimulation of the
sympathetic nervous system.
TOXICITY
N2O interacts with Vit B12
…. Monovalent cobalt to bivalent cobalt which is no longer methyl group carrier.
Methionine synthesis / THFA synthesis affected.
TOXICITY
Exposure time :
< 30 min – no measurable change in methionine synthase activity.
> 2 hrs – probably interferes with methionine synthase activity.
CLINICAL USES
Good analgesicLabour analgesiaFor anaesthesia used in combination with a
second agent.
-- reduces MAC of second agent.
-- increases rate of induction and recovery
REFERENCES
Miller‘s Anesthesia – sixth editionStoelting‘s Pharmacology and physiology
in anasthetic practicePrys – Roberts – International practice of
anaesthesia 1st editionWylie – text book of anaesthesia 7th editionGoogle images.
