INHALATIONAL INHALATIONAL ANAESTHETIC AGENTSANAESTHETIC AGENTS

History & Minimum History & Minimum alveolar concentration alveolar concentration

Presenter: Dr.Anoop Kumar

Moderator:Dr.Anand Kulkarni

HistoryHistory

Jean Baptiste Van Helmont(1577-1644)Jean Baptiste Van Helmont(1577-1644)

invented the word Gas invented the word Gas Boyle, Dalton & Charles out lined the Boyle, Dalton & Charles out lined the

basic properties of gases basic properties of gases Joseph priestley & Carl scheele (1742-Joseph priestley & Carl scheele (1742-

1786) performed first investigation on 1786) performed first investigation on gas inhalation gas inhalation

History ContdHistory Contd....

On Dec 10On Dec 10thth ,1844 Prof Colton ,1844 Prof Colton presented his exhibit featuring presented his exhibit featuring inhalation of nitrous oxide at union inhalation of nitrous oxide at union hall in Hartford, Connecticut.hall in Hartford, Connecticut.

On Oct 16On Oct 16thth 1846 Morton 1846 Morton demonstrated Ether anaesthesia at demonstrated Ether anaesthesia at Massachusetts general hospital. Massachusetts general hospital.

History contd…History contd…

Wells, Morton and Jackson all claimed Wells, Morton and Jackson all claimed to have discovered anaesthesia.to have discovered anaesthesia.

In 1847 David Waldie at Edinburgh In 1847 David Waldie at Edinburgh Medical school England suggested Medical school England suggested Chloroform as an alternativeChloroform as an alternative agent. agent.

History contd…History contd…

In 1951 Halothane was synthesised In 1951 Halothane was synthesised by Suckling and introduced into by Suckling and introduced into clinical practice in 1956 clinical practice in 1956

Between 1959 & 1966 Terrell and Between 1959 & 1966 Terrell and colleagues at Ohio medical products colleagues at Ohio medical products synthesised more than 700 productssynthesised more than 700 products

History contd…History contd…

347347thth and 469 and 469thth compounds were compounds were Enflurane & IsofluraneEnflurane & Isoflurane

Wallin and colleagues at Travenol Wallin and colleagues at Travenol

laboratories described other new laboratories described other new compounds in 1970-Sevoflurane compounds in 1970-Sevoflurane

Desflurane was introduced in 1993 Desflurane was introduced in 1993

Minimum Alveolar concentrationMinimum Alveolar concentration(MAC)(MAC)

Eger and colleagues defined this Eger and colleagues defined this concept.concept.

““The alveolar concentration of an The alveolar concentration of an inhaled anaesthetic at 1 atm inhaled anaesthetic at 1 atm pressure in 100%Oxygen at pressure in 100%Oxygen at equilibrium, that produces immoblity equilibrium, that produces immoblity in 50% of those subjects exposed to in 50% of those subjects exposed to a standardized noxious stimuli.a standardized noxious stimuli.””

Determination of MACDetermination of MAC

For humans the noxious stimulus is a For humans the noxious stimulus is a surgical incision of the abdomen.surgical incision of the abdomen.

In animals it is usually produced by In animals it is usually produced by clamping of tail or passing electric clamping of tail or passing electric current through subcutaneous current through subcutaneous electrodes. electrodes.

MAC Contd…MAC Contd…

It mirrors brain partial pressure after It mirrors brain partial pressure after a period of equilibration.a period of equilibration.

Best estimate of anaesthetic potency Best estimate of anaesthetic potency

of an inhalational anaesthetic.of an inhalational anaesthetic.

Allows comparison between agents Allows comparison between agents and provides a standard for and provides a standard for experimental evaluation.experimental evaluation.

MAC Contd…MAC Contd…

MAC values are roughly additive.MAC values are roughly additive.

MAC for other response parameter MAC for other response parameter

are not additive.are not additive.

Relatively constant within species Relatively constant within species

and between species. and between species.

MAC contd..MAC contd..

Analogous to EDAnalogous to ED50 50 expressed for expressed for intravenous drugs. intravenous drugs.

1.3 MAC would prevent 95 % 1.3 MAC would prevent 95 % subjects from moving and is subjects from moving and is equivalent to EDequivalent to ED95.95.

MAC AwakeMAC Awake

MAC of anaesthetic that would allow MAC of anaesthetic that would allow opening of eyes on verbal commands opening of eyes on verbal commands during emergence from anaesthesia during emergence from anaesthesia

=0.3-0.4 MAC=0.3-0.4 MAC

MAC IntubationMAC Intubation MAC that would inhibit movement MAC that would inhibit movement

and coughing during endotracheal and coughing during endotracheal intubation.=1.3 MACintubation.=1.3 MAC

MAC BarMAC Bar

MAC of anaesthetic necessary to MAC of anaesthetic necessary to prevent adrenergic response to skin prevent adrenergic response to skin incision, as measured by conc. of incision, as measured by conc. of catecholamine in venous blood catecholamine in venous blood =1.5 MAC =1.5 MAC

When different agents are compared When different agents are compared the ratio of MAC skin incision to MAC the ratio of MAC skin incision to MAC intubation or MAC awake is relatively intubation or MAC awake is relatively constant constant

MAC RationaleMAC Rationale Why this measures anaesthetic Why this measures anaesthetic

potency?potency?

Alveolar conc. can be easily Alveolar conc. can be easily measuredmeasured

Near equilibrium alveolar and brain Near equilibrium alveolar and brain tension are virtually equaltension are virtually equal

High cerebral blood flow produces High cerebral blood flow produces rapid equilibrationrapid equilibration

Factors supporting use of MACFactors supporting use of MAC

MAC is invariant with variety of MAC is invariant with variety of noxious stimuli.noxious stimuli.

Individual variability is small.Individual variability is small.

Doses of anaesthetic in MAC are Doses of anaesthetic in MAC are additive.additive.

HypothermiaHypothermia Hyperthermia(If >42Hyperthermia(If >4200 C) C) Hyponatremia & HypocalcemiaHyponatremia & Hypocalcemia Hypoxia(PaOHypoxia(PaO22<38mm of Hg)<38mm of Hg) Induced hypotension Induced hypotension

(MAP<50mmHg)(MAP<50mmHg)

Factors affecting MACFactors affecting MAC

MACMAC

Factors sing MAC contd…Factors sing MAC contd…

Hypercarbia(PaCOHypercarbia(PaCO22>95mm of Hg)>95mm of Hg) Anemia(Hematocrit<10%)Anemia(Hematocrit<10%)

PregnancyPregnancy Acute ethanol administrationAcute ethanol administration Hypo osmolalityHypo osmolality Increasing age(max. at 6months)Increasing age(max. at 6months)

Local anaesthetics(except cocaine)Local anaesthetics(except cocaine) Opioids.Opioids. Ketamine,Barbiturates,Benzodiazapines.Ketamine,Barbiturates,Benzodiazapines. Sympatholytics.Sympatholytics. Verapamil, Lithium.Verapamil, Lithium. c/c administration of amphetamine.c/c administration of amphetamine.

Drugs MACDrugs MAC

Factors MACFactors MAC

Chronic ethanol use.Chronic ethanol use. Hypernatremia.Hypernatremia. a/c admin. of amphetamine.a/c admin. of amphetamine. Cocaine.Cocaine. Ephedrine.Ephedrine. MAO inhibitors.MAO inhibitors. Levodopa.Levodopa.

No changes in MACNo changes in MAC Gender.Gender. Hypo/Hyper thyroidism.Hypo/Hyper thyroidism. Duration of inhaled anaesthetic Duration of inhaled anaesthetic

Administration.Administration. Hypercalcemia.Hypercalcemia. Metabolic alkalosis.Metabolic alkalosis.

Clinical implications of MACClinical implications of MAC

Understanding of MAC helps in prevention Understanding of MAC helps in prevention of awareness.(will not occur at end tidal of awareness.(will not occur at end tidal conc. of 1MAC).conc. of 1MAC).

Tool to measure anaesthetic potency.Tool to measure anaesthetic potency. Helps to study side effects of inhalational Helps to study side effects of inhalational

anaesthetics at equipotent doses.anaesthetics at equipotent doses. Combinations are additive.Combinations are additive.

MAC of common MAC of common inhalational anaestheticsinhalational anaesthetics

N2ON2O 105105

HalothaneHalothane 0.750.75

IsofluraneIsoflurane 1.21.2

SevofluraneSevoflurane 22

Enflurane Enflurane 1.61.6