1. What is Anesthesia? Franklin Scamman, MD

2. Topics to Cover This Lecture 1.What is “anesthesia” 2.History and mechanism of anesthesia 3.Uptake and distribution of inhaled anesthetics 4.CNS effects of anesthesia 5.Minimal alveolar concentration (MAC) 6.Properties of inhaled anesthetics 7.System effects of inhaled anesthetics 8.Delivery systems for inhaled anesthetics

3. “Anesthesia” Insensitivity to pain May be from local or general agents Term introduced by Oliver Wendell Holmes in 1847 in response to work by WTG Morton using ether

4. History of Anesthesia Greeks and Romans: aware of opium and derivatives; oral ethanol Japan: 1820s, mandrake causing cholinergic crisis and unconsciousness TWG Morton, MGH, October 16, 1846 using diethyl ether However, Crawford Long in 1849 described his use of it in 1842

5. MGH “Ether Dome” 1846

6. Mechanisms of Anesthesia No single macroscopic site of action Specific brain areas affected by inhalational Anesthetics causing amnesia –Reticular activating system, –Cerebral cortex –Cuneate nucleus –Olfactory cortex –Hippocampus Anesthetics depress excitatory transmission in the spinal cord supressing movement

7. Mechanisms of Anesthesia General anesthetic action could be due to alterations in any one of several cellular systems including ligand-gated ion channels, second messenger functions, or neurotransmitter receptors. Many anesthetics (the potent agents) enhance (GABA) inhibition of the central nervous system. Other agents (nitrous oxide and xenon) are NMDA agonists with good pain relief, just like ketamine Potency of inhalation agents correlates directly with their lipid solubility (Meyer–Overton rule)

10. Rate of Rise of Alveolar Concentration

11. Factors Determining the Speed of Induction Vaporizer setting (concentration) Fresh gas flow Alveolar minute ventilation Blood-gas partition coefficient (solubility) Cardiac output Alveolar-to-venous partial-pressure difference Brain-blood partition coefficient Cerebral blood flow

12. How fast do you go asleep? The higher the blood/gas coefficient  The greater the anesthetic's solubility  The greater its uptake by the pulmonary circulation.  Alveolar partial pressure rises more slowly  Slow induction

13. Many of the factors that speed induction also speed recovery Elimination of rebreathing High fresh gas flows, low anesthetic-circuit volume, low absorption by the anesthetic circuit, Decreased solubility, High cerebral blood flow, Increased ventilation.

14. Minimal Alveolar Concentration Percent alveolar concentration to prevent purposeful movement in 50% of individuals Corresponds to the ED-50 of oral or IV drugs Lower at extremes of age Lower with other depressant drugs Lower in pregnancy Maximum at 37-39 degrees Maximum age 2-24 (roughly)

15. Properties of the Vapors DesfluraneNitrous Oxide IsofluraneSevoflurane Blood/Gas0.420.471.430.69 Brain/Blood1.291.11.571.70 Fat/Blood27.22.344.947.5 MAC %6.01041.22.0

16. Depth of Anesthesia Anesthesia depth can be assessed by –Lack of movement in non-paralyzed state –Respiration rate and pattern –Respiratory depression (ET CO 2 and V E ) –Eye signs –BP and P less valuable –BIS and Entropy analysis

17. Respiratory Effects Abolish the hypoxic response at less than half MAC concentrations Fantastic bronchodilators by direct action on smooth muscle

18. Cardiovascular Effects (1) All cause cardiac depression Cardiac depression causes an increased rate of concentration rise An increased concentration causes more cardiac depression Positive feedback -> cardiac arrest if not careful

19. Cardiovascular Effects (2) Isoflurane and desflurane cause increased heart rate which may mask depression Systemic vascular resistance –Isoflurane and desflurane decrease (great for starting IVs) –Halothane and nitrous oxide do not change

20. Renal Effects All decrease arterial pressure RBF and GFR will be maintained until threshold of autoregulation, absent other influences (sympathetic tone, renin) Urine output is variable, depending on ADH and aldosterone and other humeral agents Creatinine clearance not effected by UO