Induction Recovery

Concentration = Partial pressure x Solubility tissue

 Pulmonary ventilation  Respiratory rate  V tidal – V dead space  Anesthetic concentration  Blood-gas partition coefficient  Concentration effect  Second gas effect

Table 1 Characteristics of Inhalational Anesthetics AnestheticsMAC (% of 1 atm) Oil:Gas Partition Coefficient Blood:Gas Partition Coefficient Desflurane Ether Enflurane Halothane Isoflurane Methoxyflurane Nitrous oxide Sevoflurane

 Pulmonary ventilation  Concentration effect  Second gas effect  Respiratory rate  V tidal – V dead space  Anesthetic concentration  Blood-gas partition coefficient  Pulmonary blood flow  Gradient of P arterial / P venous  Cardiac output

 Anesthetic concentration  Pulmonary ventilation  Concentration effect  Second gas effect  Blood-gas partition coefficient  Tissue blood flow  Gradient of P arterial / P Tissue Redistribution Diffusion hypoxia  Pulmonary blood flow  Gradient of P arterial / P venous  Cardiac output  Tissue-Blood partition coefficient

Stages of Ether Anesthesia Stage IAnalgesiaClouding  Spinal cord sensory neurons (Substantia gelatinosa) Stage IIDelirium (Excitement) Loss of consciousness Hypersensitive  small Golgi type interneurons  excitatory neurons Stage IIISurgical anesthesia Loss of somatic pain  Ascending pathway of recticular activating system  Spinal reflex Stage IVMedullary depression Loss of visceral pain  Medulla (respiratory, cardiovascular center)

AnestheticsMAC (% of 1 atm) Oil:Gas Partition Coefficient Blood:Gas Partition Coefficient Desflurane Ether Enflurane Halothane Isoflurane Methoxyflurane Nitrous oxide Sevoflurane Table 1 Characteristics of Inhalational Anesthetics

Stages of Ether Anesthesia Stage IAnalgesiaClouding  Spinal cord sensory neurons (Substantia gelatinosa) Stage IIDelirium (Excitement) Loss of consciousness Hypersensitive  small Golgi type interneurons  excitatory neurons Stage IIISurgical anesthesia Loss of somatic pain  Ascending pathway of recticular activating system  Spinal reflex Stage IVMedullary 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  GABA A

TASK-1  Activated by inhalational anesthetics ( mM)  Two pore background K + channels  pH-sensitive, pH o <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, pH i <7, channels open  Outward rectification

 Gaseous anesthetics  Nitrous oxide (N 2 O)  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  N 2 O pockets formed in closed spaces  Occluded middle ear  Pneumothorax  Embolism  Pneumoencephaly  Obstructed intestine

Nitrous Oxide Normal N2N2 N2N2 N2N2 N2ON2O Blood vessel

Nitrous Oxide  Benefits  No CV side effect  Rapid induction  Second gas effect  Harms  Weak potency  Diffusion hypoxia  Megaloblastic anemia  N 2 O pockets formed in closed spaces  Occluded middle ear  Pneumothorax  Embolism  Pneumoencephaly  Obstructed intestine

HalothaneEnfluraneIsofluraneDesfluraneSevoflurane 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 Ca 2+ uptake by sarcoplastic recticulum in skeletal muscle, genetic mutation of ryanodine receptors  Treatment with dantrolene  Incidence if coadministration with succinylcholine

HalothaneEnfluraneIsofluraneDesfluraneSevoflurane Analgesia+/-++++ Muscle relaxation-+++ Fast Induction Potency /-++++/-++ Metabolism /--++(+) Airway irritation++-+/-- Nausea, vomiting+---- Malignant Hyperthermia++--- Arrhythmia++++++/- - Hypotension+++++ Cardiac output decrease Hepatic toxicity+++--+/- Renal toxicity++ --+/- Seizure F-F- Cough

Intravenous Anesthetics  Barbiturates  Thiopental (Pentothal)  Methohexital (Brietal)  Thiamylal (Surital)  Benzodiazepines  Diazepam (Valium)  Lorazepam (Ativan)  Midazolam (Dormicum)  Dissociate anesthetic  Ketamine (Ketaral)  Etomidate (Hypnomidate)  Propofol (Diprivan)  Butyrophenones  Droperidol  Opioids  Fentanyl

Ultrashort Barbiturates  GABA A -Cl - current  Contraindication  Porphyria  Shock  Respirator not available  Pain threshold  Laryngeal spasm  Unpurpose movement  Thiopental  Redistribution  Slow recovery  Short t 1/2  Methohexital  Rapid recovery  Hiccup

Benzodiazepines  GABA A -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: H 1 antagonists, H 2 antagonists  Antiemetics: Benzquinamide, Odansetron, diphenhydramine, metocloprmide

Mechanism of Action: GABA A receptor TM2 segment of  2  1 subunit of GABA A receptor  Binding site different to that of GABA  Potentiating GABA effect at low concentrations  Directly inducing GABA current at high concentrations  Preventing GABA A receptor desensitization

Discovery of Inhalational Anesthetics  1842 Crawford W. Long Surgeon  1844 Horace Wells Dentist  1846 Willium T. G. Morton Charles J. Jackson Mr. ifs N2ON2OEther Time: 1846, October 16 Place: Massachusetts General Hospital Surgeon: John Collins Warren

Concentration Effect N 2 O (blood/gas =0.5) 40 % 20 % 0.2 * 40 % = 8 % 80 % 40 % 0.4 * 80 % = 32 % P alveola P blood