INHALational drugs and ANAESTHET PART 1.pptx

Inhalational anaesthesia

1. 2022-12-16 1 Volatile Anaesthetics PART - 1

2. 2 Inhaled Ana. : Vapor Press Hyperbaric Chamber MAC Effect Factors Affecting ana. Depth Sur. Stimulus-Effect on MAC MAC-Factors effecting B / G Coefficient Meyer-Overton Correl. 2022-12-16

3. 3 Mis filled Vap .-Output Calculation Desflurane Vaporizer- Physics Vaporizer Output at Altitude Factors affecting Vaporizer Output Vaporizer Output - Calculation 2022-12-16

4. 4 Anast . Uptake-Solubility coefficient FA / FI Volatile Anasthetic Inh . Ana. Uptake R to L Shunt Inhaled Anaesthetic uptake 2022-12-16 Concentration Effect Time Constant definition Upta . Inh . anae . V/Q mismatch Uptake & Distribution

5. 5 Bronchodilatation – Anesth drugs Desflurane adverse CV effects Isoflurane – CNS effects Isoflurane – CMRO2 effect 2022-12-16 Anesth . effects-cerebral perfusion Isoflurane & Ventilation Physiologic Effects

6. 6 NMB / Volatile anesth interaction Inhalation anesth . Resp. effects Impaired vent response to Hypoxia 2022-12-16 Muscle Relaxation anesth agents Physiologic Effects

7. 7 CO from CO2absorber CO2 Absorbers: Volat . Ana toxicity MH: Periop management 2022-12-16 Desflurane - CO Production Toxicity & Metabolism / MH

8. 8 N2O – Intestinal Obstruction Nitrous Oxide Bowel distension N2O and intraocular gas Nitrous Oxide Closed Spaces 2022-12-16 Hyperbaric N2O Nitrous Oxide :CBF/CMRO2 Nitrous Oxide

9. 9 Uptake & Distribution MAC – Vapor Pressure – B G P C GA Definition / Mechanisms Chemistry 2022-12-16 Characteristics Physiological Effects Inhaled Anaesthetics

10. 10 Xenon Future Toxicity & Metabolism Malignant Hyperthermia 2022-12-16 Nitrous Oxide Inhaled Anaesthetics

11. 2022-12-16 11

12. 2022-12-16 12 Chemistry of inhaled Anaesthetics

13. 2022-12-16 13

14. C linically Used Inhalational Anesthetics: 2022-12-16 14 Chemistry of Inhaled Anesthetics : Non-Halogenated Anesthetics : Halogenated Alkanes: Halothane: Nitrous Oxide:

15. C linically Used Inhalational Anesthetics: 2022-12-16 15 Chemistry of Inhaled Anesthetics : Halogenated Ethers :

16. Historical 199 4 Fluorination increases Potency and decreases flammability L ow BGPC – (fast Onset) L ow BGPC – (fast Onset) Resistant to Metabolism Vp (needs Special Vaporizer) 1992 199 4

17. A irway irritability SNS stimulation Carbon monoxide formation New vaporizer required 2022-12-16 17 Desflurane : Sevoflurane: Blood Gas Solub ility : Fast Onset Precise control Prompt Recovery But……. Expensive Compound - A Desflurane Sevoflurane

18. 2022-12-16 18 General Anesthesia – Reversible State of “Loss of Sensation” :

19. 2022-12-16 19 General Anesthesia – Reversible State of “Loss of Sensation” :

20. 2022-12-16 20 General Anesthesia – Reversible State of “Loss of Sensation” :

21. For experimental purposes defined as: Immobility in response to surgical stimulation: Amnesia for intraoperative events 2022-12-16 21 Anesthetic Stat e: MAC (spinal cord mediated) Supraspinal structures likely target (amygdala-hippocampus- and cortex)

22. The > solubility of inhaled anaesthetic in olive oil, the more potent it is. 2022-12-16 23 Oil Gas Partition Coefficient : O G P C MAC DESFLURANE 19 6.6% SEVOFLURANE 53 1.4 – 3.3 % ISOFLURANE 91 1.17 %

23. 2022-12-16 25 Mechanism of action

24. 2022-12-16 26 Mechanism of general Anaesthetics

25. I nhaled anaesthetics exert their effects by binding directly to ion channels, as ligands binding to a receptor---ultimate action is on specific neuronal membrane proteins. Enhance function of inhibitory ion channels Blocking the function of excitatory ion channels Other: affect the release of neurotransmitters 2022-12-16 27 Majority Theory : G ABA – Glycine N M D A

26. Mechanisms of General Anaesthesia: Increased lipid solubility Increased Potency Receptors

27. e 2022-12-16 30 V:

28. 2022-12-16 31 ASSESSING ADEQUACY OF DEPTH OF ANAESTHESIA

29. e 2022-12-16 32 e:

30. 2022-12-16 33 Minimum alveolar concentration

31. Nere 2022-12-16 34 e:

32. e 2022-12-16 35 e:

33. Nure 2022-12-16 36 Vaporizers at Altitude:

34. ure 2022-12-16 37 tude :

35. Physiological Changes: Blood pressure, Heart Rate, Respirations (if no NMBs) 2. Electroencephalogram (BIS) 3. Population Statistics (MAC) 2022-12-16 38 Assessing Adequacy of Depth of Anaesthesia :

36. 2022-12-16 39 Dosing of inhaled anesthetics

37. “Alveolar concentration (%) at steady state as measured by anaesthetic gas monitors from sampled expired alveolar gases at one atmosphere at which 50 % of patients will not move to surgical incision” 2022-12-16 40 M A C : Minimum Alveolar Concentration :

38. Determined in humans by response to surgical to stimulation (Incision) Measure of Potency 2022-12-16 41 Minimum Alveolar Concentration : Isoflurane ------1.15 % Sevoflurane-----2.05 % Desflurane -----7.25 % Nitrous Oxide----110 % Potency

39. M A C awake ----------- 0.33 MAC 2022-12-16 42 M A C Variations: A D 95 ----------------- 1.3 MAC M A C BAR ------------- 1.5 MAC

40. 2022-12-16 43 Mac as a partial pressure

41. Desflurane 6 % 0.06 X 760 = 45.6 mmHg 2022-12-16 44 M A C Variations: Sevoflurane 2 % 0.02 X 760 = 15.2 mmHg Isoflurane 1.2 % 0.12 X 760 = 09.1 mmHg

42. Vp mmHg @ 20°C 664 157 238 243 -- MAC (%) 6.0 1.4 – 3.3 1.28 0.75 71 MAC awake 0.33 MAC 0.3 MAC 0.38 MAC 0.52MAC -- MAC (pp)mmHg 45.6 10.6-25.1 9.7 5.7 -- BGPC 0.42 0.69 1.4 2.3 0.14 Metabolites (%) <<0.2 2 - 5 0.2 20 Desflurane Sevoflurane Isoflurane Halothane Xenon

43. Gender, duration, ethnicity, physiologic variables(within usual variations). Thyroid disease (if not hyper – or hypothermic), decerebrate (animals) Co-administered anesthetics (lidocaine, midazolam, Fentanyl, dexmedetomidine, etc ), 2022-12-16 46 Clinical Factors and MAC:

44. Inhaled anaesthetanaesthetics 2022-12-16 47 M A C Variations:

45. Inhainhaled anaesthetics 2022-12-16 48 Inhaled Anaesthetics and QT Interval

46. 2022-12-16 49 PARTITION COEFFICIENTS

47. 2022-12-16 50 BLOOD GAS PARTITION COEFFICIENT

48. 2022-12-16 51 Vaporizers at altitude

49. It is partial pressure (not concentration) that is important No change vaporizer dial necessary for Isoflurane, Sevoflurane Note: If Vaporizer used that was calibrated at sea level, it will actually put out higher concentration when at altitude. Need to change (Desflurane) dial (increase when at altitude, decrease when at depth) to maintain constant partial pressure 2022-12-16 52 Vaporizers at Altitude :

50. Isoflurane @ 6000 feet = 610 mm Hg (atm pressure) 2% 2. 8% Similar ; No dial change required 15 mm Hg 17 mm Hg 2 % x 760 = 2.8 % x 610= 244 760 = 32 % 244 610 = 39 %

51. 10% 10 % Have t o increase dial to get same partial pressure 12.7 x 610 = 76 mmHg 76 mm Hg 61 mm Hg 10 % x 760 = 10 % x 610 = 39° C 1500 mm Hg @2 atm Desflurane at Altitude : 6000 ft.

52. Vaporizer output at altitude Definition The definition of MAC is the concentration of the vapor (measured as a percentage at 1 atmosphere, i.e the partial pressure) that prevents the reaction to a standard surgical stimulus in 50% of subjects. Since most of us work at about 1 atmosphere, we can still think in terms of % concentration, but what is physiologically important is the partial pressure (mm Hg), not the concentration. Modern conventional vaporizers (for halothane, isoflurane, sevoflurane) are agent specific, temperature compensated, variable bypass vaporizers. They automatically compensate for changes in altitude because they put out a partial pressure that is determined by the position of the dial. Even though the units on the dial are percentages, it’s actually partial pressure that is determined. The partial pressure of the anesthetic agent is what determines whether a patient is anesthetized, and it does not change at different altitudes. So if you are doing anesthesia with isoflurane at high altitude, setting the dial to 1% will have the same effect as it would at sea level.

53. However, if the question relates to volume concentration then use equation: VO= ( CGxSVP )/(Pb-SVP) Where VO=vapor output (ml), CG= carrier gas flow( mL.min ), SVP=saturated vapor pressure (mm Hg) at room temp, and Pb is barometric pressure (mm Hg) At a higher altitude where the barometric pressure is ½ that at sea level, the amount of isoflurane vapor output increases due to the lower barometric pressure. Therefore, the settings that delivered 2% isoflurane now deliver 4% isoflurane. However, according to Dalton’s law, the partial pressure of isoflurane delivered would be approximately the same at both altitudes since 2% isoflurane at 760mm Hg (15.2 mm Hg) is the same as 4% isoflurane at 380mm Hg (15.2 mm Hg). According to Shafer, who presents an example on Stanford University’s website, “we find that to deliver 8.4 mm Hg (1 MAC) of isoflurane at 8000 feet, we need an anesthetic concentration of 1.5%. However, our vaporizer, set for 1.1%, is actually producing 1.7%, or a partial pressure of 9.9 mm Hg. Thus, the vaporizer slightly overcompensates for the reduced atmospheric pressure… Note that this does NOT apply to the desflurane vaporizer“(Source 1).

54. Alternatively, the desflurane vaporizer is electrically heated to 39 degrees centigrade, which creates a vapor pressure of 2 atmospheres inside the vaporizer, regardless of ambient pressure. The number on the dial reflects the percentage that will be delivered. So at any altitude, when you dial 5%, it will give you 5%. But when that 5% desflurane leaves the vaporizer at high altitude, what is delivered to the patient is 5% of a decreased ambient pressure, so the partial pressure of desflurane in the alveoli will be much less that it would be at sea level. Thus, you will need to dial a higher concentration at high elevation to attain the same clinical effect as at sea level with desflurane (Tec-9) vaporizer.

55. 2022-12-16 58 Vaporizer filling errors

56. Anaesthetic agent Vapor Pressure (mmHg) M A C (%) Desflurane 664 6 Isoflurane 238 1.28 Halothane 244 0.75 Sevoflurane 157 2.05 Enflurane 172 1.68 Note: 1. Desflurane in a Sevo/Iso/Halo vaporizer would be catastrophic –massive delivery of Des with possible hypoxia and 2. a Halothane vaporizer could be used to deliver Isoflurane ( same Vp) and the dial setting (%) would be what is delivered to the patient

57. 2022-12-16 60 Blood gas partition coefficient

58. The blood : gas partition coefficient is  an important determinant of the speed of anesthetic induction and recovery . It describes the partition of an agent between a gaseous phase, such as alveolar air, and the blood. The greater the blood : gas partition coefficient , the greater the solubility in blood. It describes the relative affinity of an anesthetic for two phases and therefore the partitioning of that anesthetic between the two phases at equilibrium (equilibrium=no difference in partial pressure between phases) 2022-12-16 61 Blood Gas Partition Coefficient :

59. I soflurane BGPC =1.4. Iso in blood is 1.4 x that in gas (alveolar) phase. Partition coefficients are temperature dependent Solubility of a gas in a liquid decreases when temperature increases Lower the BGPC the lower blood solubility, and faster the onset and offset of action –Faster induction and faster Recovery 2022-12-16 62 Blood Gas Partition Coefficient :

60. Vp mmHg @ 20°C 664 157 238 243 -- MAC (%) 6.0 1.4 – 3.3 1.28 0.75 71 MAC awake 0.33 MAC 0.3 MAC 0.38 MAC 0.52MAC -- MAC (pp)mmHg 45.6 10.6-25.1 9.7 5.7 -- BGPC 0.42 0.69 1.4 2.3 0.14 Metabolites (%) <<0.2 2 - 5 0.2 20 Desflurane Sevoflurane Isoflurane Halothane Xenon

61. 2022-12-16 64 Partition coefficients

62. Agent Blood / Gas Brain / Blood Muscle / Blood Fat / Blood Nitrous Oxide 0.47 1.1 1.2 2.3 Halothane 2.4 2.9 3.5 60 Isoflurane 1.4 2.6 4.0 45 Desflurane 0.42 1.3 2.0 27 Sevoflurane 065 1.7 3.1 48 Blood Gas Partition Coefficient : These values are averages derived from multiple studies and should be used for comparison purposes, not as exact numbers. Note: sevoflurane awakening time is similar to isoflurane after several hours of anaesthetic delivery (note Fat/Blood)

63. The between phases) 2022-12-16 66 Blood Gas Partition Coefficient :

64.   an important determinant of the speed of between phases) 2022-12-16 67 Blood Gas Partition Coefficient :

65. Anaesthetic Uptake & distribution

66. F G F F I F A F a FGF is determined by the vaporizer and flowmeter settings F I (inspired gas concentration) is determined by 1)FGF Rate 2) breathing circuit volume 3) Circuit absorption F A (alveolar gas concentration) is determined by 1) uptake (uptake = bgpc x C (A-V) X Q: 2) Ventilation 3) the concentration effect and second gas effect –a) concentrating effect b) augmented inflow effect Fa (arterial gas concentration) is affected by ventilation / perfusion mismatching

67. F G F F I F A F a

68. 1 ATM = 760 mmHg 21 % O2 = 0.21 x 760 = 160 mm Hg O 2 partial Pressure 1% Isoflurane = 0.01 x760 = 7.6 mmHg Isoflurane partial pressure 2022-12-16 71 Anaesthetic Uptake : Partial Pressure Concept: Liquid Gas Partial Pressure Dissolved

69. Rate of rise of partial pressure of the anesthetic agent in the alveolus and NOT the amount dissolved in solution (blood) t hat correlates with rate of onset of anesthetic state 2022-12-16 72 Anesthetic uptake :

70. Alveolar ventilation (S>I) Inspired Concentration (F I ) Second Gas effect System 2022-12-16 73 Rise in Alveolar Partial Pressure : Delivery : Loss: Cardiac Output (S>I) Solubility in blood V / Q mismatch (I>S) Large A-V partial pressure difference S = soluble inhaled anaesthetics I= insoluble anaesthetics

71. Low Cardiac Output (Shock) speeds onset anaesthetic state (Iso< Des, Sevo) Endobronchial intubation (V /Q mismatch) will slow onset anaesthetic state (Des, Sevo>Iso) Right to Left shunt (i.e. Tetralogy of Fallot) will slow onset anaesthetic state Left-to-right shunts have little effect Speed onset: Low B/G agent, high vaporizer setting (over pressure), increase FGF, reduce circuit volume(i.e. collapse rebreathing bag) 2022-12-16 74 FA / FI : Clinical Factors Effecting :

72. Concentration effect explains why N2O (higher concentration administered) has faste r FA/FI then Des although Des B:G is lower 2022-12-16 75 Lower B:G Solubility and Faster Rate of Rise of Alveolar Partial Pressure :

73. Concentration & second gas effects

74. 2022-12-16 77 Concentration and Second Gas Effect :

75. Anaesthetic elimination

76. hases ) 2022-12-16 79 Anesthetic Elimination :

77. Anaesthetic Uptake

78. Anaesthetic Uptake : partial pressure concept

79. 2022-12-16 82 Clinical factors & mac

80. hases ) 2022-12-16 83 Blood Gas Partition Coefficient :

81. hases ) 2022-12-16 84 Blood Gas Partition Coefficient :

82. 2022-12-16 85

83. Inhaled anaesthetics prolong QT Interval Relative tendency of each anaesthetic to prolong the QT Interval has not been compared systematically Clinical significance of QT prolongation with Sevo and other inhaled anaesthetics in susceptible individuals is unclear NOTE: patients with long QT syndrome are treated with beta blockers Patients with LQTS and concurrently treated with beta bl ockers have been safely anaesthetized with all modern inhaled anaesthetics 2022-12-16 86 Inhaled Anaesthetics and QT Interval

84. 2022-12-16 87 Desflurane & SNS STIMULATION

85. Inhaled anaesthetics prolong QT Interval Relative tendency of each anaesthetic to prolong the QT Interval has not been compared systematically Clinical significance of QT prolongation with Sevo and other inhaled anaesthetics in susceptible individuals is unclear NOTE: patients with long QT syndrome are treated with beta blockers Patients with LQTS and concurrently treated with beta bl ockers have been safely anaesthetized with all modern inhaled anaesthetics 2022-12-16 88 Inhaled Anaesthetics and QT Interval

86. 2022-12-16 89 vapor pressure – Factors effecting

87. Inhaled anaesthetics 2022-12-16 90 Compound-A :

88. 2022-12-16 91 vapor pressure

89. 2022-12-16 92

90. St 2022-12-16 93 Operating principles of Variable bypass Vaporizers

91. 2022-12-16 94 Measured flow vaporizer