Induction

Recovery

Concentration = Partial pressure x Solubilitytissue

Pulmonary ventilation

Respiratory rate Vtidal – Vdead space

Anesthetic concentration

Blood-gas partition coefficient

Concentration effect Second gas effect

Table 1 Characteristics of Inhalational Anesthetics

Anesthetics MAC

(% of 1 atm)

Oil:Gas Partition

Coefficient

Blood:Gas Partition

Coefficient

Desflurane 7.0 19 0.42

Ether 1.9 65 12

Enflurane 1.7 98 1.9

Halothane 0.75 225 2.3

Isoflurane 1.2 98 1.4

Methoxyflurane 0.16 825 13

Nitrous oxide 105 1.4 0.47

Sevoflurane 2.0 53 0.63

Pulmonary ventilation

Concentration effect Second gas effect Respiratory rate

Vtidal – Vdead space

Anesthetic concentration

Blood-gas partition coefficient

Pulmonary blood flow Gradient of Parterial / Pvenous

Cardiac output

Anesthetic concentration Pulmonary ventilation Concentration effect Second gas effect

Blood-gas partition coefficient

Tissue blood flow Gradient of Parterial / PTissue

•Redistribution

•Diffusion hypoxia

Pulmonary blood flow Gradient of Parterial / Pvenous

Cardiac output

Tissue-Blood partition coefficient

Stages of Ether Anesthesia

Stage I Analgesia Clouding Spinal cord sensory neurons

(Substantia gelatinosa)

Stage II Delirium

(Excitement)

Loss of consciousness

Hypersensitive

small Golgi type interneurons

excitatory neurons

Stage III Surgical anesthesia

Loss of somatic pain Ascending pathway of recticular activating systemSpinal reflex

Stage IV Medullary depression

Loss of visceral pain Medulla

(respiratory, cardiovascular center)

Anesthetics MAC

(% of 1 atm)

Oil:Gas Partition

Coefficient

Blood:Gas Partition

Coefficient

Desflurane 7.0 19 0.42

Ether 1.9 65 12

Enflurane 1.7 98 1.9

Halothane 0.75 225 2.3

Isoflurane 1.2 98 1.4

Methoxyflurane 0.16 825 13

Nitrous oxide 105 1.4 0.47

Sevoflurane 2.0 53 0.63

Table 1 Characteristics of Inhalational Anesthetics

Stages of Ether Anesthesia

Stage I Analgesia Clouding Spinal cord sensory neurons

(Substantia gelatinosa)

Stage II Delirium

(Excitement)

Loss of consciousness

Hypersensitive

small Golgi type interneurons

excitatory neurons

Stage III Surgical anesthesia

Loss of somatic pain Ascending pathway of recticular activating systemSpinal reflex

Stage IV Medullary depression

Loss of visceral pain Medulla

(respiratory, cardiovascular center)

Mechanisms of Action

Lipid bilayer-Meyer and Overton Theory Membrane fluidity Membrane expansion

Voltage-gated ion channels Na+

K+

GIRK TASK, TREK: 2P, pH-sensitive, open rectifier

Ca+2

Ligand-gated ion channels NMDA nACh Glycine 5HT3 GABAA

TASK-1

Activated by inhalational anesthetics (0.1-0.4 mM)

Two pore background K+ channels

pH-sensitive, pHo <7, channels close

Open rectifier, instaneous activation No time dependence

Slight outward rectification

TASK-2 might also be the target Time-dependent outward rectifier

TREK-1

Activated by inhalational anesthetics (higher) pH-sensitive, pHi <7, channels open

Outward rectification

Gaseous anesthetics Nitrous oxide (N2O)

Volatile anesthetics Ether Chloroform Halothane Enflurane Isoflurane Desflurane Sevoflurane

Inhalational Anesthetics

Nitrous Oxide

Benefits No CV side effect Rapid induction Second gas effect

Harms Weak potency Diffusion hypoxia Megaloblastic anemia N2O pockets formed in

closed spaces Occluded middle ear Pneumothorax Embolism Pneumoencephaly Obstructed intestine

Nitrous OxideNormal

N2

N2

N2

N2O

Blood vessel Blood vessel

Nitrous Oxide

Benefits No CV side effect Rapid induction Second gas effect

Harms Weak potency Diffusion hypoxia Megaloblastic anemia N2O pockets formed in

closed spaces Occluded middle ear Pneumothorax Embolism Pneumoencephaly Obstructed intestine

  Halothane Enflurane Isoflurane Desflurane Sevoflurane

Analgesia +/- + + + +

Muscle relaxation - + ++ ++ ++

Fast Induction - + ++ ++++ ++

Potency ++++ +++/- +++ +/- ++

Metabolism ++++ ++ +/- - ++(+)

Airway irritation + + - +/- -

Nausea, vomiting + - - - -

Malignant Hyperthermia + + - - -

Arrhythmia +++ ++ +/- +/- -

Hypotension + + + + +

Cardiac output decrease ++ ++ - - -

Hepatic toxicity ++ + - - +/-

Renal toxicity ++ ++ - - +/-

dantrolene

Malignant hyperthermia

Genetic susceptibility:

1 in 15,000 to 50,000

Failure of Ca2+ uptake by sarcoplastic recticulum in

skeletal muscle, genetic mutation of ryanodine

receptors

Treatment with dantrolene

Incidence if coadministration with succinylcholine

  Halothane Enflurane Isoflurane Desflurane Sevoflurane

Analgesia +/- + + + +

Muscle relaxation - + ++ ++ ++

Fast Induction - + ++ ++++ ++

Potency ++++ +++/- +++ +/- ++

Metabolism ++++ ++ +/- - ++(+)

Airway irritation + + - +/- -

Nausea, vomiting + - - - -

Malignant Hyperthermia + + - - -

Arrhythmia +++ ++ +/- +/- -

Hypotension + + + + +

Cardiac output decrease ++ ++ - - -

Hepatic toxicity ++ + - - +/-

Renal toxicity ++ ++ - - +/-

Seizure

F-

Cough

Intravenous Anesthetics

Barbiturates Thiopental (Pentothal)

Methohexital (Brietal)

Thiamylal (Surital)

Benzodiazepines Diazepam (Valium)

Lorazepam (Ativan)

Midazolam (Dormicum)

Dissociate anestheticKetamine (Ketaral)

Etomidate (Hypnomidate)

Propofol (Diprivan)Butyrophenones

Droperidol

OpioidsFentanyl

Ultrashort Barbiturates GABAA-Cl- current

Contraindication Porphyria Shock Respirator not available

Pain threshold Laryngeal spasm Unpurpose movement

Thiopental Redistribution Slow recovery Short t1/2

Methohexital Rapid recovery Hiccup

Benzodiazepines GABAA-Cl- current

Diazepam Amnesia Reflex No analgesic action Endoscopy,Cardiocatheter respiration CV function

Midazolam More rapid onset Shorter duration More potent Water soluble Antidote: flumazenil Emergency room

Ketamine NMDA receptor blocker

Dissociation anesthesia Sedation Analgesic CV stimulation Muscle tone Nightmare Trauma, Emergency, Radiotherapy

Etomidate GABA uptake inhibitor

Onset rapid (< 5min), redistribution No CV and respiratory depression No analgesia Nausea vomiting, myoclonic twitch Adrenocortical supprssion Sedative-hypnotic in ICU Used in hypovolumic shock, Burn trama

Propofol GABA uptake inhibitor

Rapid psychomotor recovery Unpurpose movement Allergic reaction Antiemetic Not suggested in obstetrical procedures Respiratory and cardiovascular depression

Neuroleptic Analgesia

Droperidol D2 receptor blocker

Antiemetic Antianxiety, Indifference motor activity

Antifibrilation Anticonvusion

Diagnosis only when used alone

Extrapyramidal dyskinesia

Fentanyl Opioid receptor agonist Nausea vomitting

Skeletal muscle rigidity

Analgesia

Premedication of Anesthesia

Benzodiazepine: Diazepam

Barbiturates: Secobarbital, Phenobarbital

Narcotics: Meperidine, Morphine

Anticholinergics: Atropine, scopolamine

Antihistamines: H1 antagonists, H2 antagonists

Antiemetics: Benzquinamide, Odansetron, diphenhydramine, metocloprmide

Mechanism of Action: GABAA receptor

TM2 segment of 21 subunit of GABAA receptor

Binding site different to that of GABA

Potentiating GABA effect at low concentrations

Directly inducing GABA current at high concentrations

Preventing GABAA receptor desensitization

Discovery of Inhalational Anesthetics

1842 Crawford W. Long Surgeon

1844 Horace Wells Dentist1846 Willium T. G.

MortonCharles J. Jackson

Mr. ifs

N2O

Ether

Time: 1846, October 16Place: Massachusetts General HospitalSurgeon: John Collins Warren

Concentration Effect

N2O (blood/gas =0.5)

40 % 20 %

0.2 * 40 % = 8 %

80 % 40 %

0.4 * 80 % = 32 %

Palveola Pblood