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Anesthesia Agents II

Anesthesia Agents II. Wayne E. Ellis, Ph.D., CRNA. Minimum Alveolar Concentration (MAC). MAC: MAC that prevents skeletal muscle movement in 50% of patients MAC-Awake: MAC at which 50% of pts will respond to the command “Open your eyes”

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Anesthesia Agents II

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  1. Anesthesia Agents II Wayne E. Ellis, Ph.D., CRNA

  2. Minimum Alveolar Concentration (MAC) MAC: MAC that prevents skeletal muscle movement in 50% of patients MAC-Awake: MAC at which 50% of pts will respond to the command “Open your eyes” Usually associated with a loss of recall (~1/3 – ¼ MAC) MAC-BAR: MAC necessary to block adrenergic response to skin incision (HR,B/P) Expressed as MAC-BAR50 or MAC-BAR95 Exceeds the requirement of MAC

  3. Inhaled Agents: Agent: MAC% with 60% N2O Nitrous Oxide 104 --- Desflurane 6.0 (2.8) Sevoflurane 2.6 (1.4) Isoflurane 1.28 (0.56) Ethrane 1.58 (0.57) Halothane 0.75 (0.29)

  4. Metabolism of volatile anesthetics Methoxyflurane > Halothane > Sevoflurane > Enflurane > Isoflurane > Desflurane Desflurane almost totally inert to metabolism Metabolism Cytochrome P450 enzymes in liver Oxidize anesthetics

  5. Metabolism & Toxicity Liver most susceptible to toxicity Halothane Chloroform Halothane is only anesthetic that undergoes metabolic reduction Penthrane (Methoxyflurane) Kidneys

  6. Inhaled Agents: % Metabolized Halothane 15.00 – 20.00 % Sevoflurane 5.00 % Ethrane 2.00 – 3.00 % Isoflurane 0.20 % Desflurane 0.02 % Nitrous Oxide 0.004 %

  7. Ideal Volatile Anesthetic Agent Rapid Induction and Emergence Pleasant (non-irritating) Easily change the depth of anesthesia Skeletal and smooth muscle relaxation Low toxicity Good safety profile (minimal side effects) Inexpensive (equipotent dosing)

  8. Ideal Volatile Anesthetic Agent Nonarrhythmogenic Resistant to biodegradation Nonflammable Physically Stable Short post-operative recovery time

  9. Carbon Dioxide End product of metabolism Can become anesthetic to CNS at concentrations > 5% inhaled Normal levels Arterial 40 mm Hg Venous 45 mm Hg Human production 4 ml/kg Basis of absorption = ability to form carbonic acid in water

  10. Carbon Dioxide CO2 + H2O <--> H+ + HCO3- H+ + HCO3- --> 2 H+ + CO3-- Nonvolatile carbonate salts formed with various cations Reuse of volatile anesthetics dependent on removal of CO2 from circuit

  11. Nitrous Oxide Odorless to sweet smelling Low Potency, Low blood solubility Very "fast-on, fast-off" Inhalation administration well tolerated <25% remains conscious Discovered 1772 Joseph Priestly Clinical Use 1884 Horace Wells Combined with Ether 1870 Andrews Greatest advantage: WEllis 7/31/2014 11

  12. Properties Low molecular weight 44 Vapor pressure 800 torr @ 25 C Odor Sweet Stable in Soda Lime Solubility Blood/Gas 0.46 – 0.47 Brain/Gas 1.1 Oil/Gas 1.4 MAC 104/105

  13. Properties Low molecular weight Nonflammable Supports Combustion Vapor pressure 800 torr @ 25 C Stable in Soda Lime Low potency (MAC = 104/105) WEllis 7/31/2014 13

  14. Nitrous Oxide (N2O) N = N+ - O- <--> N- = N+= O Resonance structure Incomplete anesthetic MAC = 105% Synthesized in 1776 Demonstrated at Mass General Hospital 1845 Considered failure Reintroduced in 1863

  15. Nitrous Oxide Most commonly used inhalant adjunct to general anesthetic agents Reduce amount of other agent Supports combustion Oxidant Supplied in Blue cylinders 745 psi Boiling point -88o C Low solubility, High volatility

  16. Properties Solubility Blood/gas coefficient 0.47 Oil/gas coefficient 1.4 Poor blood solubility No preservative Stored as a liquid under pressure 745 psi WEllis 7/31/2014 16

  17. Properties Low blood solubility Raid induction and emergence No preservative Nonflammable Supports Combustion Stored as a liquid under pressure (750 psi) Blue Tank How do you calculate remaining quantity of N2O in tank

  18. Advantages Little to no depression of cardiovascular and respiratory systems With volatile agent Reduction in amount of volatile anesthetic requirement Reduce unwanted effects of the agent Hypotension Cardiac depression Speed of induction improved WEllis 7/31/2014 18

  19. Advantages Analgesic effects prominent Analgesia may involve Release of endogenous opioids Enhancement of nervous pathways Irregular depression of cortical brain No depression of vital centers in absence of hypoxia Minimal biodegradation WEllis 7/31/2014 19

  20. Advantages Promotes amnesia (usually 60 to 70%) Used in combination with narcotic and muscle relaxant Nitrous-narcotic technique Include benzodiazepine for amnesia No effect on skeletal muscle No effect on kidneys Does not cross placenta Eliminated via lungs WEllis 7/31/2014 20

  21. Advantages Little to no depression of cardiovascular and respiratory systems With volatile agent Reduction in amount of volatile anesthetic requirement (2nd Gas Effect) Reduce unwanted effects of the agent Hypotension Cardiac depression Speed of induction improved

  22. Advantages Analgesia may involve Release of endogenous opioids Enhancement of nervous pathways No depression of vital centers in absence of hypoxia Minimal biodegradation No effect on kidneys Eliminated via lungs

  23. Disadvantages Irregular depression of cortical brain Increased heart rate and blood pressure Increased cerebral blood flow and intracranial pressure Predisposition to atelectasis 0.1-0.4 MAC depress central responsiveness to Hypoxia Increased muscle tone in larynx and abdomen “Tight Chest” possible Skeletal muscle relaxation is absent Inactivates B12

  24. Disadvantages Increased heart rate and blood pressure Increased cerebral blood flow and intracranial pressure Predisposition to atelectasis 0.1-0.4 MAC depress responsiveness to Hypoxia Increased muscle tone in larynx and abdomen “Tight Chest” possible Skeletal muscle relaxation is absent WEllis 7/31/2014 24

  25. Disadvantages 75% causes reduction in fetal oxygenation Decreased APGAR Scores Lower neurobehavioral scores Enlargement of closed air spaces Endotracheal tube cuffs Middle ear procedures Nitrous Oxide off > 30 minutes before graft placed Pneumothorax WEllis 7/31/2014 25

  26. Disadvantages Air emboli Nitrogen (B/g of 0.015) does not leave as fast as nitrous oxide enters Volume expands rapidly Avoid in patients with potential for air emboli or with methyl methacrylate Increased incidence of nausea (> 15%) Supports combustion WEllis 7/31/2014 26

  27. Disadvantages Possibility of problems with DNA synthesis Potential for increased spontaneous abortion Potential for Diffusion Hypoxia Decreased DNA Synthesis (50% for 2 hrs < DNA synthesis 1-6 days) Can be abused by practitioners WEllis 7/31/2014 27

  28. Disadvantages Decreased DNA Synthesis (50% for 2 hrs < DNA synthesis 1-6 days) Possibility of problems with DNA synthesis following the 7th day Potential for increased spontaneous abortion Potential for Diffusion Hypoxia Abused Drug by practitioners

  29. Diethyl ether (US) CH3CH2OCH2CH3 First complete anesthetic Demonstrated in 1846 (Crawford Long) More potent than nitrous oxide Flammable/explosive Stimulates emesis

  30. Diethyl Ether

  31. Diethyl ether (US) CH3CH2 - O - CH2CH3 First complete anesthetic Demonstrated in 1846 (Crawford Long) More potent than nitrous oxide Flammable/explosive Stimulates emesis

  32. Chloroform Trichloromethane CHCl3 Introduced Animals 1847 (Flourens) Man 1848 (Simpson) First halogenated anesthetic Pleasant odor What movies were made of Nonflammable Liver Toxicity

  33. Cyclopropane C3H6 Hydrocarbons without halogen burn quickly Discovered in 1929 Tested at University of Wisconsin Used clinically for > 30 years Flammable and explosive

  34. Halogenated structure provides Nonflammable Intermediate blood solubility Anesthetic potency Molecular stability 04/15/96 WEE / UIOWA / CON 9

  35. Modern Fluorinated Anesthetics Goals when making anesthetics Reduce or eliminate toxicity (metabolism) Reduce or eliminate flammability Increase speed of induction and recovery Basic structures Ethane (Halothane) Methyl ethyl ethers Propyl methyl ether

  36. Halothane (Fluothane) Only ethane anesthetic Non-ether Simply halogenated hydrocarbon Added halogens to eliminate flammability, increase potency, increase tolerance of patient to inhalation

  37. Halogenated alkane 2-bromo-2chloro-1,1,1-trifluoroethane (CF3CHClBr) Synthesized 1951 Clinical use 1956 Clear, nonflammable liquid Volatile at room temperature Intermediate solubility, High potency Results in rapid onset and recovery from anesthesia Halothane 04/15/96 WEE / UIOWA / CON 8

  38. Properties Molecular weight 197 Boiling Point 50.2 oC Vapor pressure 244 torr @ 20 C Odor Sweet, non pungent Partition Coefficients Blood/gas 2.3 - 2.54 Brain/gas 1.9 Oil/Gas 224 MAC Nitrous Oxide 0.29 Oxygen 0.75 - 0.77 Not stable in soda lime Contains 0.01% thymol as inhibitor (preservative, antioxidant)

  39. Halothane Halogenated alkane Synthesized 1951 Clinical use 1956 Sweet, nonpugent odor Intermediate solubility High potency Results in rapid onset and recovery from anesthesia WEllis 7/31/2014 39

  40. Halothane Introduced in 1956 Sweetish odor, non pungent 2-bromo-2chloro-1,1,1-trifluoroethane (CF3CHClBr) Contains 0.01% thymol as inhibitor (preservative, antioxidant)

  41. Halothane Boiling Point 50.2o C MAC 0.74% Halothane Hepatitis 1:30,000 Related to metabolism Coupled with hypotension, hypovolemia, and aminoglycocides

  42. Halothane Halogenated structure would provide nonflammablility, intermediate blood solubility, anesthetic potency, and molecular stability Carbon-fluorine decreases flammability Triflurocarbon contributes to the molecular stability Carbon-chlorine and carbon-bromine bond plus the retention of a hydrogen atom ensures anesthetic potency

  43. Advantages Sweet, nonpungent odor - well suited for inhalation induction Less incidence of tachycardia Depression of Carotid Sinus baroreceptors Decreased firing of Sinus node "Inhalation Inderal" Decreased BP accompanied by a stable or decreased HR Less depression of ventilation, best suited for the spontaneous breathing patient

  44. Advantages Sweet, nonpungent odor - well suited for inhalation induction Less incidence of tachycardia Depression of Carotid Sinus baroreceptors Decreased firing of Sinus node "Inhalation Inderal" Decreased BP accompanied by a stable or decreased HR Less depression of ventilation, best suited for the spontaneous breathing patient

  45. Used as inhibitor or preservative in Halothane Sticky, yellow deposit as halothane vaporized Thymol

  46. Thymol Anti- oxidant Used as inhibitor or preservative in Halothane Sticky, yellow deposit as halothane vaporized Requires that vaporizers be cleaned, restrung, and recalibrated annually OH OH CH CH3 CH3

  47. Properties Clear, nonflammable liquid Volatile at room temperature Molecular weight 197 Vapor pressure 244 torr @ 20 C Solubility Blood/gas 2.3 Oil/gas 224 MAC 70% Nitrous Oxide = 0.29 100 % Oxygen = 0.77 Not stable in soda lime WEllis 7/31/2014 47

  48. Halothane Halogenated structure provides Nonflammablility Intermediate blood solubility Anesthetic potency Molecular stability WEllis 7/31/2014 48

  49. Halothane Carbon-fluorine decreases flammability Triflurocarbon contributes to the molecular stability Carbon-chlorine and carbon-bromine bond plus the retention of a hydrogen atom ensures anesthetic potency WEllis 7/31/2014 49

  50. Susceptible to spontaneous oxidation Hydrochloric acid Hydrobromic acid Chloride Bromide Phosgene Stored in amber colored bottles (sensitive to UV Light) Oxidation and Decomposition WEllis 7/31/2014 50

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