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INHALATIONAL ANAESTHETICS PRESENTER: Dr. Karthick. D MODERATOR:  Dr Anand H.Kulkarni
Topics Covered <ul><li>Comparison of commonly used inhalational anaesthetics, </li></ul><ul><li>-  physical/chemical prope...
ISOFLURANE SEVOFLURANE HALOTHANE
PHYSICAL AND CHEMICAL PROPERTIES OF INHALED ANAESTHETICS
BOILING POINT/ VAPOUR PRESSURE Boiling Point (° C ) Vapour pressure(mmHg) at 20°C HALOTHANE 50.2 243.3 ISOFLURANE 48.5 250...
Implication <ul><li>Desflurane cannot be administered using standard vapourizer </li></ul>
Physical properties  (cont..) HALOTHANE Clear, non-explosive, non- inflammable liquid at room temperature, non-pungent odo...
Implication <ul><li>In regard to negligible airway irritant activity sevoflurane followed by halothane are very suitable f...
STRUCTURE <ul><li>Halothane: Halogenated alkane derivative </li></ul><ul><li>2 chloro, 2 bromo 1,1,1 trifluoroethane </li>...
STRUCTURE <ul><li>Isoflurane </li></ul><ul><li>Sevoflurane  </li></ul>ii   H
Implication <ul><li>Effect on ozone layer </li></ul><ul><li>Sensitization of heart to epinephrine </li></ul><ul><li>Toxici...
BLOOD GAS PARTITION COEFFICIENT HALOTHANE 2.5 ISOFLURANE 1.4 SEVOFLURANE 0.69 DESFLURANE 0.42
 
Implication <ul><li>Lower the blood gas partition coefficient ………..  Rapid is the induction and recovery from anaesthesia ...
STABILITY HALOTHANE ISOFLURANE SEVOFLURANE ALKALI Some decomposition Stable  Stable UV LIGHT Decomposes  Stable Stable  ME...
STABILITY <ul><li>Halothane - - - susceptible to decomposition to hydrochloric acid, chlorine, bromide and phosgene. </li>...
METABOLISM <ul><li>Oxidative and Reductive metabolism </li></ul>HALOTHANE 20% ISOFLURANE 0.2% DESFLURANE 0.02% SEVOFLURANE...
MINIMUM ALVEOLAR CONCENTRATION MAC in oxygen(%) Halothane 0.75 Enflurane 1.68 Isofurane 1.15 Sevoflurane 2 Desflurane 6 Ni...
EFFECTS ON VARIOUS ORGAN SYSTEM
CARDIOVASCULAR SYSTEM
MEAN ARTERIAL PRESSURE <ul><li>Halothane, Isoflurane, Desflurane, Sevoflurane ……… dose dependant decrease in MAP. </li></u...
HEART RATE INHALATIONAL ANAESTHETIC HEART RATE HALOTHANE DECREASES ISOFLURANE/ENFLURANE/DESFLURANE/SEVOFLURANE INCREASES
CARDIAC OUTPUT AND STROKE VOLUME <ul><li>Halothane ……. Dose dependent decrease in cardiac output </li></ul><ul><li>Isofura...
SYSTEMIC VASCULAR RESISTANCE ISOFLURANE/DESFLURANE/SEVOFLURANE Decrease HALOTHANE No net effect NITROUS OXIDE No effect
PULMONARY VASCULAR RESISTANCE <ul><li>Halogenated volatile anaesthetics ……. No predictable effect </li></ul><ul><li>Nitrou...
CORONARY BLOOD FLOW <ul><li>Isoflurane ….. Most potent coronary vasodilator </li></ul><ul><li>… .. Small coronary vessels ...
EPINEPHRINE INDUCED ARRYTHMIAS <ul><li>Halothane  precipitates arrhythmias in combination with epinephrine. </li></ul><ul>...
RESPIRATORY SYSTEM
PATTERN OF BREATHING <ul><li>Halothane/ Desflurane/ Sevoflurane … dose dependant increase in the frequency of breathing </...
 
PATTERN OF BREATHING <ul><li>Net effect : </li></ul><ul><li>Rapid/ shallow pattern of breathing </li></ul><ul><li>Minute v...
MINUTE VENTILATION
VENTILATORY RESPONSE TO CO 2 <ul><li>All inhalational anaesthetics… decrease in ventilatory response to CO 2  </li></ul><u...
VENTILATORY RESPONSE TO O 2 <ul><li>Volatile anaesthetics and N 2 O ….. Attenuate ventilatory response to hypoxemia in dos...
AIRWAY RESISTANCE <ul><li>All volatile anaesthetics ---- potent bronchodilators </li></ul><ul><li>Halothane ….. Most poten...
AIRWAY RESISTANCE
AIRWAY IRRITABILITY <ul><li>Desflurane ----- most irritant </li></ul><ul><li>Enflurane/ Isoflurane ------ irritant </li></...
MUCOCILIARY FUNCTION <ul><li>Postoperative hypoxemia and atelectasis – common causes of postoperative morbidity </li></ul>...
CENTRAL NERVOUS SYSTEM
CEREBRAL BLOOD FLOW <ul><li>Volatile anaesthetics administered during normocapnia in conc > 0.6 MAC  </li></ul><ul><li>… ....
CEREBRAL BLOOD FLOW <ul><li>AUTOREGULATION: </li></ul>HALOTHANE ABOLISHED ISOFLURANE IMPAIRED SEVOFLURANE INTACT
CEREBRAL BLOOD FLOW
CEREBRAL METABOLIC OXYGEN REQUIREMENT <ul><li>All volatile anaesthetics …. Dose dependent decrease in CMRO 2   </li></ul><...
CBF / CMR
CEREBROSPINAL FLUID CSF PRODUCTION ABSORPTION HALOTHANE ↓ (30%) ↓ ISOFLURANE -- ↑ ENFLURANE ↑ ↓
<ul><li>Increase in ICP parallels increase in CBF. </li></ul><ul><li>Enflurane …… increased incidence of epilepsy </li></u...
HEPATIC SYSTEM
HEPATIC BLOOD FLOW Desflurane/ Sevoflurane ……. Similar to isoflurane BLOOD FLOW HALOTHANE ISOFLURANE PORTAL VEIN ↓ ↓ HEPAT...
HEPATIC BLOOD FLOW
DRUG EFFECTS <ul><li>Interference of drug clearance by volatile anaesthetics is due to, </li></ul><ul><li>1, decrease in h...
HEPATOTOXICITY -- depends on the quantity of drug getting metabolised TFA (Trifluoro acetic acid) HALOTHANE Large amounts ...
RENAL SYSTEM
<ul><li>All volatile anaesthetics : dose related decrease in renal blood flow, glomerular filtration rate and urine output...
NEPHROTOXICITY <ul><li>Flouride induced nephrotoxicity </li></ul><ul><li>Methoxyflurane, Enflurane, Sevoflurane </li></ul>...
FLOURIDE INDUCED NEPHROTOXICITY <ul><li>High output renal failure </li></ul><ul><li>Manifestations : polyuria, hypernatrem...
FLOURIDE INDUCED NEPHROTOXICITY <ul><li>Renal threshold limit of plasma flouride(toxicity) </li></ul><ul><li>……  50 μ m/li...
FLOURIDE INDUCED NEPHROTOXICITY
VINYL HALIDE NEPHROTOXICITY <ul><li>Reaction of CO 2  absorbents with sevoflurane. </li></ul><ul><li>Degradation products ...
SKELETAL MUSCLE EFFECTS
SKELETAL MUSCLE RELAXATION <ul><li>Sevoflurane/ Desflurane/ Isoflurane …. Two fold greater skeletal muscle relaxation than...
INTERACTION WITH NEUROMUSCULAR BLOCKING AGENTS <ul><li>Dose dependant enhancement …. All volatile anaesthetics </li></ul><...
CARBONMONOXIDE TOXICITY <ul><li>Reflects degradation of volatile anaesthetics that contain a CHF 2  moiety ( desflurane, e...
NITROUS OXIDE
INTRODUCTION OF NITROUS OXIDE <ul><li>Humpry Davy …. 1800 first observed its analgesic effect …. Laughing gas </li></ul>
HORACE WELLS …. 1844 <ul><li>Used N 2 O to facilitate  </li></ul><ul><li>the extraction of a tooth </li></ul><ul><li>Unfor...
N 2 O USAGE IN THE INITIAL DAYS
PHYSICAL PROPERTIES <ul><li>Molecular weight : 44 </li></ul><ul><li>Boiling point : - 88°C </li></ul><ul><li>Colourless, s...
PHYSICAL PROPERTIES <ul><li>Blood gas partition coefficient … 0.42 </li></ul><ul><li>Metabolism … nil </li></ul><ul><li>Ex...
NITROUS OXIDE CYLINDERS <ul><li>Full cylinder at room temperature contains liquid  </li></ul><ul><li>The pressure in these...
ENTONOX <ul><li>Mixture of equal parts of N 2 O and O2. </li></ul><ul><li>Supplied in cylinders pressurized to 15000 kPa a...
 
PHARMACOKINETICS <ul><li>Low blood gas solubility … rapid equilibration of F a /F i  ratio. </li></ul><ul><li>Second gas e...
CONCENTRATION EFFECT <ul><li>Inspired anaesthetic concentration influences alveolar concentration that may be achieved and...
CONCENTRATION EFFECT <ul><li>The  F A  /  F I  ratio indicates the percent of anesthetic removed by uptake. </li></ul><ul>...
SECOND GAS EFFECT 19% oxygen 80% nitrous oxide 19% oxygen 40% nitrous oxide 32% nitrous oxide 1% second gas 7.6% oxygen 0....
SECOND GAS EFFECT <ul><li>Factors that govern concentration effect also influence the concentration of any gas given conco...
DIFFUSION HYPOXIA <ul><li>The uptake of large volumes of N 2 O into the alveoli during recovery. </li></ul><ul><li>Occuran...
PHARMACODYNAMICS VARIOUS ORGAN SYSTEM EFFECTS
CENTRAL NERVOUS SYSTEM <ul><li>Significantly increases CBF and ICP. </li></ul><ul><li>Minimally increases cerebral metabol...
RESPIRATORY SYSTEM <ul><li>Pleasant to inhale and not irritating to the airway </li></ul><ul><li>Increases the uptake of t...
RESPIRATORY SYSTEM <ul><li>Ventilatory response to CO2 …  no alteration </li></ul><ul><li>Ventilatory response to hypoxia ...
CARDIOVASCULAR EFFECTS <ul><li>Direct effect …. Myocardial depressant </li></ul><ul><li>This is offset by its stimulation ...
TOXICITY <ul><li>N2O interacts with Vit B 12 </li></ul><ul><li>… . Monovalent cobalt to bivalent cobalt which is no longer...
TOXICITY <ul><li>Exposure time : </li></ul><ul><li>< 30 min – no measurable change in methionine synthase activity. </li><...
CLINICAL USES <ul><li>Good analgesic </li></ul><ul><li>Labour analgesia </li></ul><ul><li>For anaesthesia used in combinat...
REFERENCES <ul><li>Miller ‘s Anesthesia – sixth edition </li></ul><ul><li>Stoelting‘s Pharmacology and physiology in anast...
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Inhalational anes

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Transcript of "Inhalational anes"

  1. 1. INHALATIONAL ANAESTHETICS PRESENTER: Dr. Karthick. D MODERATOR: Dr Anand H.Kulkarni
  2. 2. Topics Covered <ul><li>Comparison of commonly used inhalational anaesthetics, </li></ul><ul><li>- physical/chemical properties </li></ul><ul><li>- various organ system effects </li></ul><ul><li>- metabolism and toxicity </li></ul><ul><li>Nitrous oxide </li></ul>
  3. 3. ISOFLURANE SEVOFLURANE HALOTHANE
  4. 4. PHYSICAL AND CHEMICAL PROPERTIES OF INHALED ANAESTHETICS
  5. 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. 6. Implication <ul><li>Desflurane cannot be administered using standard vapourizer </li></ul>
  7. 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. 8. Implication <ul><li>In regard to negligible airway irritant activity sevoflurane followed by halothane are very suitable for inhalational induction </li></ul>
  9. 9. STRUCTURE <ul><li>Halothane: Halogenated alkane derivative </li></ul><ul><li>2 chloro, 2 bromo 1,1,1 trifluoroethane </li></ul><ul><li>Other halogenated agents: Halogenated ether derivatives </li></ul>
  10. 10. STRUCTURE <ul><li>Isoflurane </li></ul><ul><li>Sevoflurane </li></ul>ii H
  11. 11. Implication <ul><li>Effect on ozone layer </li></ul><ul><li>Sensitization of heart to epinephrine </li></ul><ul><li>Toxicity </li></ul>
  12. 12. BLOOD GAS PARTITION COEFFICIENT HALOTHANE 2.5 ISOFLURANE 1.4 SEVOFLURANE 0.69 DESFLURANE 0.42
  13. 14. Implication <ul><li>Lower the blood gas partition coefficient ……….. Rapid is the induction and recovery from anaesthesia </li></ul>
  14. 15. STABILITY HALOTHANE ISOFLURANE SEVOFLURANE ALKALI Some decomposition Stable Stable UV LIGHT Decomposes Stable Stable METAL May react Stable Stable
  15. 16. STABILITY <ul><li>Halothane - - - susceptible to decomposition to hydrochloric acid, chlorine, bromide and phosgene. </li></ul><ul><li>Stored in amber coloured bottles </li></ul><ul><li>Preservative - - - Thymol (0.01%) </li></ul>
  16. 17. METABOLISM <ul><li>Oxidative and Reductive metabolism </li></ul>HALOTHANE 20% ISOFLURANE 0.2% DESFLURANE 0.02% SEVOFLURANE 4%
  17. 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
  18. 19. EFFECTS ON VARIOUS ORGAN SYSTEM
  19. 20. CARDIOVASCULAR SYSTEM
  20. 21. MEAN ARTERIAL PRESSURE <ul><li>Halothane, Isoflurane, Desflurane, Sevoflurane ……… dose dependant decrease in MAP. </li></ul><ul><li>Halothane/ Enflurane ….. Decreases cardiac contractility </li></ul><ul><li>Isoflurane/Desflurane/Sevoflurane </li></ul><ul><li>……… .. principally decreases systemic vascular resistance </li></ul>
  21. 22. HEART RATE INHALATIONAL ANAESTHETIC HEART RATE HALOTHANE DECREASES ISOFLURANE/ENFLURANE/DESFLURANE/SEVOFLURANE INCREASES
  22. 23. CARDIAC OUTPUT AND STROKE VOLUME <ul><li>Halothane ……. Dose dependent decrease in cardiac output </li></ul><ul><li>Isofurane/Sevoflurane ….. Very minimal decrease </li></ul><ul><li>Nitrous oxide ……. Moderate increase </li></ul>
  23. 24. SYSTEMIC VASCULAR RESISTANCE ISOFLURANE/DESFLURANE/SEVOFLURANE Decrease HALOTHANE No net effect NITROUS OXIDE No effect
  24. 25. PULMONARY VASCULAR RESISTANCE <ul><li>Halogenated volatile anaesthetics ……. No predictable effect </li></ul><ul><li>Nitrous oxide …. Increases </li></ul>
  25. 26. CORONARY BLOOD FLOW <ul><li>Isoflurane ….. Most potent coronary vasodilator </li></ul><ul><li>… .. Small coronary vessels </li></ul><ul><li>… .. Coronary steal phenomenon </li></ul><ul><li>halothane/ Sevoflurane </li></ul><ul><li>… .. Cause coronary vasodilatation </li></ul>
  26. 27. EPINEPHRINE INDUCED ARRYTHMIAS <ul><li>Halothane precipitates arrhythmias in combination with epinephrine. </li></ul><ul><li>Epinephrine tolerated: micrograms/kg </li></ul><ul><li>Halothane: 1.5 </li></ul><ul><li>Isoflurane, sevoflurane,desflurane: 4.5 </li></ul><ul><li>When used at MAC levels. </li></ul>
  27. 28. RESPIRATORY SYSTEM
  28. 29. PATTERN OF BREATHING <ul><li>Halothane/ Desflurane/ Sevoflurane … dose dependant increase in the frequency of breathing </li></ul><ul><li>Isoflurane </li></ul><ul><li>… . Upto 1 MAC – dose dependant increase </li></ul><ul><li>> 1 MAC – no further increase </li></ul><ul><li>TIDAL VOLUME .. </li></ul><ul><li>all inhalational anaesthetics --- decrease </li></ul>
  29. 31. PATTERN OF BREATHING <ul><li>Net effect : </li></ul><ul><li>Rapid/ shallow pattern of breathing </li></ul><ul><li>Minute ventilation … ? </li></ul><ul><li>Decreases </li></ul>
  30. 32. MINUTE VENTILATION
  31. 33. VENTILATORY RESPONSE TO CO 2 <ul><li>All inhalational anaesthetics… decrease in ventilatory response to CO 2 </li></ul><ul><li>Mediated principally at the level of medulla. </li></ul><ul><li>N 2 O ----- doesn't increase PaCO 2 </li></ul>
  32. 34. VENTILATORY RESPONSE TO O 2 <ul><li>Volatile anaesthetics and N 2 O ….. Attenuate ventilatory response to hypoxemia in dose- dependant manner. </li></ul><ul><li>Peripheral chemoreceptors appear to be the major site of this inhibitory response. </li></ul>
  33. 35. AIRWAY RESISTANCE <ul><li>All volatile anaesthetics ---- potent bronchodilators </li></ul><ul><li>Halothane ….. Most potent </li></ul><ul><li>followed by isoflurane and sevoflurane. </li></ul>
  34. 36. AIRWAY RESISTANCE
  35. 37. AIRWAY IRRITABILITY <ul><li>Desflurane ----- most irritant </li></ul><ul><li>Enflurane/ Isoflurane ------ irritant </li></ul><ul><li>Halothane/ Sevoflurane ------ non – irritant </li></ul><ul><li>thus preferred for inhalational induction. </li></ul><ul><li>What if irritant agents are used for inhalational induction? </li></ul>
  36. 38. MUCOCILIARY FUNCTION <ul><li>Postoperative hypoxemia and atelectasis – common causes of postoperative morbidity </li></ul><ul><li>Halothane ---- dose dependant decrease in mucociliary function. </li></ul>
  37. 39. CENTRAL NERVOUS SYSTEM
  38. 40. CEREBRAL BLOOD FLOW <ul><li>Volatile anaesthetics administered during normocapnia in conc > 0.6 MAC </li></ul><ul><li>… . Cerebral vasodilatation </li></ul><ul><li>… . Decreased cerebral vascular resistance </li></ul><ul><li>… . Dose dependant increase in CBF </li></ul><ul><li>Greatest increase in CBF---- Halothane (200%) </li></ul><ul><li>Least increase ----- Isoflurane( minimal/no increase) </li></ul>
  39. 41. CEREBRAL BLOOD FLOW <ul><li>AUTOREGULATION: </li></ul>HALOTHANE ABOLISHED ISOFLURANE IMPAIRED SEVOFLURANE INTACT
  40. 42. CEREBRAL BLOOD FLOW
  41. 43. CEREBRAL METABOLIC OXYGEN REQUIREMENT <ul><li>All volatile anaesthetics …. Dose dependent decrease in CMRO 2 </li></ul><ul><li>Isoflurane = Desflurane = Sevoflurane > Halothane </li></ul>
  42. 44. CBF / CMR
  43. 45. CEREBROSPINAL FLUID CSF PRODUCTION ABSORPTION HALOTHANE ↓ (30%) ↓ ISOFLURANE -- ↑ ENFLURANE ↑ ↓
  44. 46. <ul><li>Increase in ICP parallels increase in CBF. </li></ul><ul><li>Enflurane …… increased incidence of epilepsy </li></ul><ul><li>Iso/Des/ Sevoflurane …. No evidence of convulsive activity on EEG. </li></ul><ul><li>N 2 O administration …. Increases motor activity with clonus and opisthotonus even in clinically used concentrations. </li></ul>
  45. 47. HEPATIC SYSTEM
  46. 48. HEPATIC BLOOD FLOW Desflurane/ Sevoflurane ……. Similar to isoflurane BLOOD FLOW HALOTHANE ISOFLURANE PORTAL VEIN ↓ ↓ HEPATIC ARTERY ↓ ↑ NET FLOW ↓ Maintained
  47. 49. HEPATIC BLOOD FLOW
  48. 50. DRUG EFFECTS <ul><li>Interference of drug clearance by volatile anaesthetics is due to, </li></ul><ul><li>1, decrease in hepatic blood flow </li></ul><ul><li>2, inhibition of drug metabolizing enzymes </li></ul><ul><li>Halothane … inhibits oxidative metabolism of drugs </li></ul>
  49. 51. HEPATOTOXICITY -- depends on the quantity of drug getting metabolised TFA (Trifluoro acetic acid) HALOTHANE Large amounts ISOFLURANE/ ENFLURANE/ DESFLURANE Minute quantities SEVOFLURANE Nil
  50. 52. RENAL SYSTEM
  51. 53. <ul><li>All volatile anaesthetics : dose related decrease in renal blood flow, glomerular filtration rate and urine output. </li></ul><ul><li>Reflects the effect of volatile anaesthetic on systolic B.P and cardiac output. </li></ul>
  52. 54. NEPHROTOXICITY <ul><li>Flouride induced nephrotoxicity </li></ul><ul><li>Methoxyflurane, Enflurane, Sevoflurane </li></ul><ul><li>Vinyl halide induced nephrotoxicity </li></ul><ul><li>Sevoflurane </li></ul>
  53. 55. FLOURIDE INDUCED NEPHROTOXICITY <ul><li>High output renal failure </li></ul><ul><li>Manifestations : polyuria, hypernatremia, hyperosmolarity, inability to conc. urine. </li></ul><ul><li>First observed after methoxyflurane administration </li></ul>
  54. 56. FLOURIDE INDUCED NEPHROTOXICITY <ul><li>Renal threshold limit of plasma flouride(toxicity) </li></ul><ul><li>…… 50 μ m/lit </li></ul><ul><li>Source of fluoride : </li></ul><ul><li>intrarenal production …. Methoxyflurane/ enflurane </li></ul><ul><li>hepatic metabolism …. sevoflurane </li></ul>
  55. 57. FLOURIDE INDUCED NEPHROTOXICITY
  56. 58. VINYL HALIDE NEPHROTOXICITY <ul><li>Reaction of CO 2 absorbents with sevoflurane. </li></ul><ul><li>Degradation products : Compound A – E </li></ul><ul><li>Compound A </li></ul><ul><li>… . Fluromethyl 2,2 difluoro 1 trifluro methyl vinyl ether. </li></ul><ul><li>… . Proximal renal tubular injury. </li></ul><ul><li>Precipitating factors </li></ul><ul><li>Degradation of compound A to reactive thiol. </li></ul>
  57. 59. SKELETAL MUSCLE EFFECTS
  58. 60. SKELETAL MUSCLE RELAXATION <ul><li>Sevoflurane/ Desflurane/ Isoflurane …. Two fold greater skeletal muscle relaxation than halothane. </li></ul><ul><li>N 2 0 …. No relaxation </li></ul><ul><li>> 1 MAC …. Skeletal muscle rigidity </li></ul>
  59. 61. INTERACTION WITH NEUROMUSCULAR BLOCKING AGENTS <ul><li>Dose dependant enhancement …. All volatile anaesthetics </li></ul><ul><li>Isoflurane / Desflurane/ Sevoflurane >= Halothane </li></ul><ul><li>N 2 O …. No significant potentiation </li></ul>
  60. 62. CARBONMONOXIDE TOXICITY <ul><li>Reflects degradation of volatile anaesthetics that contain a CHF 2 moiety ( desflurane, enflurane, isoflurane) by the strong bases present in carbondioxide absorbents. </li></ul><ul><li>Desflurane > Enflurane / Isoflurane </li></ul><ul><li>Halothane/ Sevoflurane…. No CO formation </li></ul>
  61. 63. NITROUS OXIDE
  62. 64. INTRODUCTION OF NITROUS OXIDE <ul><li>Humpry Davy …. 1800 first observed its analgesic effect …. Laughing gas </li></ul>
  63. 65. HORACE WELLS …. 1844 <ul><li>Used N 2 O to facilitate </li></ul><ul><li>the extraction of a tooth </li></ul><ul><li>Unfortunately, his first </li></ul><ul><li>public demonstration </li></ul><ul><li>was a failure. </li></ul>
  64. 66. N 2 O USAGE IN THE INITIAL DAYS
  65. 67. PHYSICAL PROPERTIES <ul><li>Molecular weight : 44 </li></ul><ul><li>Boiling point : - 88°C </li></ul><ul><li>Colourless, sweet smelling, non- inflammable and non – irritant gas. </li></ul><ul><li>MAC …. 105 % </li></ul>
  66. 68. PHYSICAL PROPERTIES <ul><li>Blood gas partition coefficient … 0.42 </li></ul><ul><li>Metabolism … nil </li></ul><ul><li>Excretion … lungs </li></ul><ul><li>Supply : </li></ul><ul><li>… . Pure nitrous oxide( 5000 kPa at 20°C) </li></ul><ul><li>… . Entonox (15000 kPa at 20°C) </li></ul>
  67. 69. NITROUS OXIDE CYLINDERS <ul><li>Full cylinder at room temperature contains liquid </li></ul><ul><li>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. </li></ul><ul><li>Critical temperature …. 36.5 °C </li></ul>
  68. 70. ENTONOX <ul><li>Mixture of equal parts of N 2 O and O2. </li></ul><ul><li>Supplied in cylinders pressurized to 15000 kPa at 20°C. </li></ul><ul><li>Pseudocritical temperature </li></ul><ul><li>Manufactured utilizing Poynting effect </li></ul><ul><li>Labour analgesia </li></ul>
  69. 72. PHARMACOKINETICS <ul><li>Low blood gas solubility … rapid equilibration of F a /F i ratio. </li></ul><ul><li>Second gas effect </li></ul><ul><li>Concentration effect </li></ul><ul><li>Diffusion hypoxia or Fink effect </li></ul><ul><li>N2O …. Enclosed gas – filled cavity within the body. </li></ul>
  70. 73. CONCENTRATION EFFECT <ul><li>Inspired anaesthetic concentration influences alveolar concentration that may be achieved and the rate at which that concentration may be attained </li></ul><ul><li>Concentration effect states that with higher inspired concentrations of an anesthetic, the rate of rise in arterial tension is greater </li></ul>
  71. 74. CONCENTRATION EFFECT <ul><li>The F A / F I ratio indicates the percent of anesthetic removed by uptake. </li></ul><ul><li>At 100% inspired concentration, uptake no longer limits the rise in F A / F I </li></ul>
  72. 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
  73. 76. SECOND GAS EFFECT <ul><li>Factors that govern concentration effect also influence the concentration of any gas given concomitantly with N 2 O </li></ul><ul><li>Loss of volume associated with the uptake of N 2 O concentrates the second gas </li></ul><ul><li>Replacement of the gas taken up by an increase in inspired ventilation augments the amount of second gas in the lung </li></ul>
  74. 77. DIFFUSION HYPOXIA <ul><li>The uptake of large volumes of N 2 O into the alveoli during recovery. </li></ul><ul><li>Occurance of hypoxia … 2 means </li></ul><ul><li>- directly affects oxygenation by displacing oxygen </li></ul><ul><li>- by diluting alveolar CO 2 , they may decrease respiratory drive and ventilation. </li></ul>
  75. 78. PHARMACODYNAMICS VARIOUS ORGAN SYSTEM EFFECTS
  76. 79. CENTRAL NERVOUS SYSTEM <ul><li>Significantly increases CBF and ICP. </li></ul><ul><li>Minimally increases cerebral metabolism </li></ul><ul><li>When used in neurosurgery … diffuses into air pockets left within the skull following closure of wound </li></ul><ul><li>Thus not recommended for neurosurgical cases. </li></ul>
  77. 80. RESPIRATORY SYSTEM <ul><li>Pleasant to inhale and not irritating to the airway </li></ul><ul><li>Increases the uptake of the accompanying agent in addition to reducing the MAC </li></ul><ul><li>Minimal effect on ventilation </li></ul>
  78. 81. RESPIRATORY SYSTEM <ul><li>Ventilatory response to CO2 … no alteration </li></ul><ul><li>Ventilatory response to hypoxia … significantly reduces </li></ul><ul><li>Risk of diffusion hypoxia </li></ul>
  79. 82. CARDIOVASCULAR EFFECTS <ul><li>Direct effect …. Myocardial depressant </li></ul><ul><li>This is offset by its stimulation of the sympathetic nervous system. </li></ul>
  80. 83. TOXICITY <ul><li>N2O interacts with Vit B 12 </li></ul><ul><li>… . Monovalent cobalt to bivalent cobalt which is no longer methyl group carrier. </li></ul><ul><li>Methionine synthesis / THFA synthesis affected. </li></ul>
  81. 84. TOXICITY <ul><li>Exposure time : </li></ul><ul><li>< 30 min – no measurable change in methionine synthase activity. </li></ul><ul><li>> 2 hrs – probably interferes with methionine synthase activity. </li></ul>
  82. 85. CLINICAL USES <ul><li>Good analgesic </li></ul><ul><li>Labour analgesia </li></ul><ul><li>For anaesthesia used in combination with a second agent. </li></ul><ul><li>-- reduces MAC of second agent. </li></ul><ul><li>-- increases rate of induction and recovery </li></ul>
  83. 86. REFERENCES <ul><li>Miller ‘s Anesthesia – sixth edition </li></ul><ul><li>Stoelting‘s Pharmacology and physiology in anasthetic practice </li></ul><ul><li>Prys – Roberts – International practice of anaesthesia 1 st edition </li></ul><ul><li>Wylie – text book of anaesthesia 7 th edition </li></ul><ul><li>Google images. </li></ul>
  84. 87. Thanks for your patient listening
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