The document compares the commonly used inhalational anesthetics nitrous oxide, isoflurane, sevoflurane, halothane, and desflurane. It discusses their physical and chemical properties, effects on organ systems like cardiovascular, respiratory, central nervous system, hepatic, renal, and skeletal muscle. Nitrous oxide is also described in detail regarding its history of use, pharmacokinetics, and clinical applications.

1. INHALATIONAL ANAESTHETICS PRESENTER: Dr. Karthick. D MODERATOR: Dr Anand H.Kulkarni

2. Topics Covered Comparison of commonly used inhalational anaesthetics, - physical/chemical properties - various organ system effects - metabolism and toxicity Nitrous oxide

3. ISOFLURANE SEVOFLURANE HALOTHANE

4. PHYSICAL AND CHEMICAL PROPERTIES OF INHALED ANAESTHETICS

5. BOILING POINT/ VAPOUR PRESSURE Boiling Point (° C ) Vapour pressure(mmHg) at 20°C HALOTHANE 50.2 243.3 ISOFLURANE 48.5 250 DESFLURANE 22.8 664 SEVOFLURANE 58.5 160

6. Implication Desflurane cannot be administered using standard vapourizer

7. Physical properties (cont..) HALOTHANE Clear, non-explosive, non- inflammable liquid at room temperature, non-pungent odor ISOFLURANE Clear, non-inflammable liquid at room temperature, pungent ethereal odor. SEVOFLURANE Non pungent minimal odor DESFLURANE Pungent odor , irritating and unpleasant to inhale.

8. Implication In regard to negligible airway irritant activity sevoflurane followed by halothane are very suitable for inhalational induction

9. STRUCTURE Halothane: Halogenated alkane derivative 2 chloro, 2 bromo 1,1,1 trifluoroethane Other halogenated agents: Halogenated ether derivatives

10. STRUCTURE Isoflurane Sevoflurane ii H

11. Implication Effect on ozone layer Sensitization of heart to epinephrine Toxicity

12. BLOOD GAS PARTITION COEFFICIENT HALOTHANE 2.5 ISOFLURANE 1.4 SEVOFLURANE 0.69 DESFLURANE 0.42

14. Implication Lower the blood gas partition coefficient ……….. Rapid is the induction and recovery from anaesthesia

15. STABILITY HALOTHANE ISOFLURANE SEVOFLURANE ALKALI Some decomposition Stable Stable UV LIGHT Decomposes Stable Stable METAL May react Stable Stable

16. STABILITY Halothane - - - susceptible to decomposition to hydrochloric acid, chlorine, bromide and phosgene. Stored in amber coloured bottles Preservative - - - Thymol (0.01%)

17. METABOLISM Oxidative and Reductive metabolism HALOTHANE 20% ISOFLURANE 0.2% DESFLURANE 0.02% SEVOFLURANE 4%

18. MINIMUM ALVEOLAR CONCENTRATION MAC in oxygen(%) Halothane 0.75 Enflurane 1.68 Isofurane 1.15 Sevoflurane 2 Desflurane 6 Nitrous oxide 105 Xenon 71

19. EFFECTS ON VARIOUS ORGAN SYSTEM

20. CARDIOVASCULAR SYSTEM

21. MEAN ARTERIAL PRESSURE Halothane, Isoflurane, Desflurane, Sevoflurane ……… dose dependant decrease in MAP. Halothane/ Enflurane ….. Decreases cardiac contractility Isoflurane/Desflurane/Sevoflurane ……… .. principally decreases systemic vascular resistance

22. HEART RATE INHALATIONAL ANAESTHETIC HEART RATE HALOTHANE DECREASES ISOFLURANE/ENFLURANE/DESFLURANE/SEVOFLURANE INCREASES

23. CARDIAC OUTPUT AND STROKE VOLUME Halothane ……. Dose dependent decrease in cardiac output Isofurane/Sevoflurane ….. Very minimal decrease Nitrous oxide ……. Moderate increase

24. SYSTEMIC VASCULAR RESISTANCE ISOFLURANE/DESFLURANE/SEVOFLURANE Decrease HALOTHANE No net effect NITROUS OXIDE No effect

25. PULMONARY VASCULAR RESISTANCE Halogenated volatile anaesthetics ……. No predictable effect Nitrous oxide …. Increases

26. CORONARY BLOOD FLOW Isoflurane ….. Most potent coronary vasodilator … .. Small coronary vessels … .. Coronary steal phenomenon halothane/ Sevoflurane … .. Cause coronary vasodilatation

27. EPINEPHRINE INDUCED ARRYTHMIAS Halothane precipitates arrhythmias in combination with epinephrine. Epinephrine tolerated: micrograms/kg Halothane: 1.5 Isoflurane, sevoflurane,desflurane: 4.5 When used at MAC levels.

28. RESPIRATORY SYSTEM

29. PATTERN OF BREATHING Halothane/ Desflurane/ Sevoflurane … dose dependant increase in the frequency of breathing Isoflurane … . Upto 1 MAC – dose dependant increase > 1 MAC – no further increase TIDAL VOLUME .. all inhalational anaesthetics --- decrease

31. PATTERN OF BREATHING Net effect : Rapid/ shallow pattern of breathing Minute ventilation … ? Decreases

32. MINUTE VENTILATION

33. VENTILATORY RESPONSE TO CO 2 All inhalational anaesthetics… decrease in ventilatory response to CO 2 Mediated principally at the level of medulla. N 2 O ----- doesn't increase PaCO 2

34. VENTILATORY RESPONSE TO O 2 Volatile anaesthetics and N 2 O ….. Attenuate ventilatory response to hypoxemia in dose- dependant manner. Peripheral chemoreceptors appear to be the major site of this inhibitory response.

35. AIRWAY RESISTANCE All volatile anaesthetics ---- potent bronchodilators Halothane ….. Most potent followed by isoflurane and sevoflurane.

36. AIRWAY RESISTANCE

37. AIRWAY IRRITABILITY Desflurane ----- most irritant Enflurane/ Isoflurane ------ irritant Halothane/ Sevoflurane ------ non – irritant thus preferred for inhalational induction. What if irritant agents are used for inhalational induction?

38. MUCOCILIARY FUNCTION Postoperative hypoxemia and atelectasis – common causes of postoperative morbidity Halothane ---- dose dependant decrease in mucociliary function.

39. CENTRAL NERVOUS SYSTEM

40. CEREBRAL BLOOD FLOW Volatile anaesthetics administered during normocapnia in conc > 0.6 MAC … . Cerebral vasodilatation … . Decreased cerebral vascular resistance … . Dose dependant increase in CBF Greatest increase in CBF---- Halothane (200%) Least increase ----- Isoflurane( minimal/no increase)

41. CEREBRAL BLOOD FLOW AUTOREGULATION: HALOTHANE ABOLISHED ISOFLURANE IMPAIRED SEVOFLURANE INTACT

42. CEREBRAL BLOOD FLOW

43. CEREBRAL METABOLIC OXYGEN REQUIREMENT All volatile anaesthetics …. Dose dependent decrease in CMRO 2 Isoflurane = Desflurane = Sevoflurane > Halothane

44. CBF / CMR

45. CEREBROSPINAL FLUID CSF PRODUCTION ABSORPTION HALOTHANE ↓ (30%) ↓ ISOFLURANE -- ↑ ENFLURANE ↑ ↓

46. Increase in ICP parallels increase in CBF. Enflurane …… increased incidence of epilepsy Iso/Des/ Sevoflurane …. No evidence of convulsive activity on EEG. N 2 O administration …. Increases motor activity with clonus and opisthotonus even in clinically used concentrations.

47. HEPATIC SYSTEM

48. HEPATIC BLOOD FLOW Desflurane/ Sevoflurane ……. Similar to isoflurane BLOOD FLOW HALOTHANE ISOFLURANE PORTAL VEIN ↓ ↓ HEPATIC ARTERY ↓ ↑ NET FLOW ↓ Maintained

49. HEPATIC BLOOD FLOW

50. DRUG EFFECTS Interference of drug clearance by volatile anaesthetics is due to, 1, decrease in hepatic blood flow 2, inhibition of drug metabolizing enzymes Halothane … inhibits oxidative metabolism of drugs

51. HEPATOTOXICITY -- depends on the quantity of drug getting metabolised TFA (Trifluoro acetic acid) HALOTHANE Large amounts ISOFLURANE/ ENFLURANE/ DESFLURANE Minute quantities SEVOFLURANE Nil

52. RENAL SYSTEM

53. All volatile anaesthetics : dose related decrease in renal blood flow, glomerular filtration rate and urine output. Reflects the effect of volatile anaesthetic on systolic B.P and cardiac output.

54. NEPHROTOXICITY Flouride induced nephrotoxicity Methoxyflurane, Enflurane, Sevoflurane Vinyl halide induced nephrotoxicity Sevoflurane

55. FLOURIDE INDUCED NEPHROTOXICITY High output renal failure Manifestations : polyuria, hypernatremia, hyperosmolarity, inability to conc. urine. First observed after methoxyflurane administration

56. FLOURIDE INDUCED NEPHROTOXICITY Renal threshold limit of plasma flouride(toxicity) …… 50 μ m/lit Source of fluoride : intrarenal production …. Methoxyflurane/ enflurane hepatic metabolism …. sevoflurane

57. FLOURIDE INDUCED NEPHROTOXICITY

58. VINYL HALIDE NEPHROTOXICITY Reaction of CO 2 absorbents with sevoflurane. Degradation products : Compound A – E Compound A … . Fluromethyl 2,2 difluoro 1 trifluro methyl vinyl ether. … . Proximal renal tubular injury. Precipitating factors Degradation of compound A to reactive thiol.

59. SKELETAL MUSCLE EFFECTS

60. SKELETAL MUSCLE RELAXATION Sevoflurane/ Desflurane/ Isoflurane …. Two fold greater skeletal muscle relaxation than halothane. N 2 0 …. No relaxation > 1 MAC …. Skeletal muscle rigidity

61. INTERACTION WITH NEUROMUSCULAR BLOCKING AGENTS Dose dependant enhancement …. All volatile anaesthetics Isoflurane / Desflurane/ Sevoflurane >= Halothane N 2 O …. No significant potentiation

62. CARBONMONOXIDE TOXICITY Reflects degradation of volatile anaesthetics that contain a CHF 2 moiety ( desflurane, enflurane, isoflurane) by the strong bases present in carbondioxide absorbents. Desflurane > Enflurane / Isoflurane Halothane/ Sevoflurane…. No CO formation

63. NITROUS OXIDE

64. INTRODUCTION OF NITROUS OXIDE Humpry Davy …. 1800 first observed its analgesic effect …. Laughing gas

65. HORACE WELLS …. 1844 Used N 2 O to facilitate the extraction of a tooth Unfortunately, his first public demonstration was a failure.

66. N 2 O USAGE IN THE INITIAL DAYS

67. PHYSICAL PROPERTIES Molecular weight : 44 Boiling point : - 88°C Colourless, sweet smelling, non- inflammable and non – irritant gas. MAC …. 105 %

68. PHYSICAL PROPERTIES Blood gas partition coefficient … 0.42 Metabolism … nil Excretion … lungs Supply : … . Pure nitrous oxide( 5000 kPa at 20°C) … . Entonox (15000 kPa at 20°C)

69. NITROUS OXIDE CYLINDERS Full cylinder at room temperature contains liquid The pressure in these cylinders will not reflect how much N 2 O it contains as long as there is liquid N 2 O in the cylinder. Critical temperature …. 36.5 °C

70. ENTONOX Mixture of equal parts of N 2 O and O2. Supplied in cylinders pressurized to 15000 kPa at 20°C. Pseudocritical temperature Manufactured utilizing Poynting effect Labour analgesia

72. PHARMACOKINETICS Low blood gas solubility … rapid equilibration of F a /F i ratio. Second gas effect Concentration effect Diffusion hypoxia or Fink effect N2O …. Enclosed gas – filled cavity within the body.

73. CONCENTRATION EFFECT Inspired anaesthetic concentration influences alveolar concentration that may be achieved and the rate at which that concentration may be attained Concentration effect states that with higher inspired concentrations of an anesthetic, the rate of rise in arterial tension is greater

74. CONCENTRATION EFFECT The F A / F I ratio indicates the percent of anesthetic removed by uptake. At 100% inspired concentration, uptake no longer limits the rise in F A / F I

75. SECOND GAS EFFECT 19% oxygen 80% nitrous oxide 19% oxygen 40% nitrous oxide 32% nitrous oxide 1% second gas 7.6% oxygen 0.4% second gas 1% second gas Uptake of half of nitrous oxide Absorbed gases replaced by added ventilation

76. SECOND GAS EFFECT Factors that govern concentration effect also influence the concentration of any gas given concomitantly with N 2 O Loss of volume associated with the uptake of N 2 O concentrates the second gas Replacement of the gas taken up by an increase in inspired ventilation augments the amount of second gas in the lung

77. DIFFUSION HYPOXIA The uptake of large volumes of N 2 O into the alveoli during recovery. Occurance of hypoxia … 2 means - directly affects oxygenation by displacing oxygen - by diluting alveolar CO 2 , they may decrease respiratory drive and ventilation.

78. PHARMACODYNAMICS VARIOUS ORGAN SYSTEM EFFECTS

79. CENTRAL NERVOUS SYSTEM Significantly increases CBF and ICP. Minimally increases cerebral metabolism When used in neurosurgery … diffuses into air pockets left within the skull following closure of wound Thus not recommended for neurosurgical cases.

80. RESPIRATORY SYSTEM Pleasant to inhale and not irritating to the airway Increases the uptake of the accompanying agent in addition to reducing the MAC Minimal effect on ventilation

81. RESPIRATORY SYSTEM Ventilatory response to CO2 … no alteration Ventilatory response to hypoxia … significantly reduces Risk of diffusion hypoxia

82. CARDIOVASCULAR EFFECTS Direct effect …. Myocardial depressant This is offset by its stimulation of the sympathetic nervous system.

83. TOXICITY N2O interacts with Vit B 12 … . Monovalent cobalt to bivalent cobalt which is no longer methyl group carrier. Methionine synthesis / THFA synthesis affected.

84. TOXICITY Exposure time : < 30 min – no measurable change in methionine synthase activity. > 2 hrs – probably interferes with methionine synthase activity.

85. CLINICAL USES Good analgesic Labour analgesia For anaesthesia used in combination with a second agent. -- reduces MAC of second agent. -- increases rate of induction and recovery

86. REFERENCES Miller ‘s Anesthesia – sixth edition Stoelting‘s Pharmacology and physiology in anasthetic practice Prys – Roberts – International practice of anaesthesia 1 st edition Wylie – text book of anaesthesia 7 th edition Google images.

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