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# ANESTÉSICOS GERAIS INALATÓRIOS

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• 1. ANESTÉSICOS INALATÓRIOS Carlos Darcy A. Bersot
• 2. Anestesiologia - Dados Históricos 1842 1846
• 3. PK Inalatória
• 4. PK Inalatória  Captação  FA  FI  FA/FI
• 5. Dalton’s law:  partial pressure of each component gas is directly related to its concentration  P total = P1 + P2 + P3 + .......Pn  The Partial Pressure is defined as the pressure of a single gas in the mixture as if that gas alone occupied the container
• 6. Henry’s law:  The quantity of gas that will dissolve in a liquid is proportional to the partial pressure of that gas in contact with the liquid, or the partial pressure of the gas in the gas phase
• 7. Partition coefficient:  An expression of the relative solubility of a substance in two immiscible phases. It compares the amount of gas present in the first phase when one part dissolves in the second phase.
• 8. Partition coefficient:  An expression of the relative solubility of a substance in two immiscible phases. It compares the amount of gas present in the first phase when one part dissolves in the second phase.
• 9. PK Inalatória
• 10. PK Inalatória
• 11. PK Inalatória
• 12. PK Inalatória
• 13. 300 Isoflurane Enflurane Halothane 250 200 Tempo(seg) 150 100 50 0 INDUCTION RECOVERY Bersot,CD UFRJ 2006 in mice
• 14. Concentration/Second Gas Effects As you  anesthetic concentration, you  alveolar concentration. As you  1st anesthetic concentration, you  alveolar concentration of 2nd anesthetic .
• 15. A B 1% of 1.7 % second gas of second gas 19 % O2 31.7 % O2 Uptake of half of the N2O 66.7 % N2O 80% N2O
• 16. Minimum alveolar concentration (MAC)  Alveolar concentration required to prevent movement in 50% of subjects  standard stimulus – originally incision  represents +/- brain concentration  additive
• 17. MAC Values (%)
• 18. PROPRIEDADES FISICOQUÍNICAS DOS ANESTÉSICOS INALATÓRIOS   Sevoflurano Desflurano Isoflurano Enflurano Halotano N2O Ponto de ebulição (°C) 59 24 49 57 50 –88 Pressão de vapor a 20°C (mm Hg) 157 669 238 172 243 38.770 Peso molecular (g) 200 168 184 184 197 44 Coeficiente de partição óleo:gás 47 19 91 97 224 1.4 Coeficiente de partição sangue:gás 0,65 0,42 1,46 1,9 2,50 0,46 Solubilidade cérebro:sangue 1,7 1,3 1,6 1,4 1,9 1,1 Solubilidade gordura:sangue 47,5 27,2 44,9 36 51,1 2,3 Solubilidade músculo:sangue 3,1 2,0 2,9 1,7 3,4 1,2 CAM em O , 30-60 a, 37°C P 760 (%) 2 B 1,8 6,6 1,17 1,63 0,75 104 CAM em 60–70% N O (%) 2 0,66 2,38 0,56 0,57 0,29   CAM >65 a (%) 1,45 5,17 1,0 1,55 0,64 — Preservativo Não Não Não Não Timol Não Estável em absorvedor CO úmido2 Não Sim Sim Sim Não Sim Inflamabilidade (%) (N O/O 70/30%) 2 2 10 17 7 5,8 4,8   Recuperado como metabólitos(%) 2–5 0,02 0,2 2,4 20
• 19. NEUROSCIENCE OF GENERAL ANAESTHESIA
• 20. Molecular Mechanism of Action: Two Ideas 1. Meyer-Overton Theory lipid soluble drug increases volume of lipid membranes which, in turn, distorts membrane proteins 2. Protein Receptor Hypothesis inhaled agent binds directly to hydrophobic part of membrane protein
• 21. The GABA/Cl channel complex  GABAA / GABAB  ↑GABA effects vs direct Cl- action  ↑Channel open-time  Bicuculline = GABAA antagonist (NB bicuculline doesn’t reverse general anaesthesia!!!)
• 22. Subcortical vs Cortical  Cortex is more sensitive than thalamus/ reticular activating system (Steriade, Electro Clin Neurophys 1994;90:1), (Tomoda, BJA 1993;71:383), (Angel, Exp Phys 1991;76:1), (Dougherty, J. Neurophys 1997;77:1375)
• 23. The Pathways of MAC/Rousability Actual State Potential response
• 24. “Functional Disconnection of cortico-thalamic circuits” White & Alkire, Neuroimage 2003;19:402
• 25. Halothane and K Channels + (IKAn) (Winegar -Anesth 1996;85:889)  Hyperpolarization is minor and NOT proportional to Spike Rate (MacIvor & Kendig, Anesthesiology, 1991;74:83)  May be important in EEG phenomena of Deep Anaesthesia
• 26. Nitrous Oxide  Simple linear compound  Not metabolized  Only anesthetic agent that is inorganic
• 27. Nitrous Oxide  Low potency  MAC value is 105%  Weak anesthetic, powerful analgesic  Needs other agents for surgical anesthesia  Low blood solubility (quick recovery)
• 28. Nitrous Oxide Systemic Effects  Minimal effects on heart rate and blood pressure  May cause myocardial depression  Little effect on respiration  Safe, efficacious agent
• 29. Nitrous Oxide Side Effects  Beginning of case: second gas effect  End of case: diffusion hypoxia  Diffusion into closed spaces
• 30. Nitrous Oxide Side Effects  Inhibits methionine synthetase (precursor to DNA synthesis)  Inhibits vitamin B-12 metabolism  Dentists, OR personnel, abusers at risk
• 31. Halothane  Synthesized in 1956 by Suckling  Halogen substituted ethane  Volatile liquid easily vaporized, stable, and nonflammable
• 32. Halothane  Most potent inhalational anesthetic  MAC of 0.75%  Efficacious in depressing consciousness  Very soluble in blood and adipose  Prolonged emergence
• 33. Halothane Systemic Effects  Inhibits sympathetic response to painful stimuli  Inhibits sympathetic driven baroreflex response (hypovolemia)  Sensitizes myocardium to effects of exogenous catecholamines-- ventricular arrhythmias
• 34. Halothane Systemic Effects  Decreases respiratory drive-- central response to CO2 and peripheral to O2  Depresses myocardium-- lowers BP and slows conduction  Mild peripheral vasodilation
• 35. Halothane Side Effects  “Halothane Hepatitis” -- 1/10,000 cases  fever, hepatic necrosis, death  metabolic breakdown products are hapten-protein conjugates  immunologically mediated assault  exposure dependent
• 36. Halothane Side Effects  Malignant Hyperthermia-- 1/60,000 with succinylcholine to 1/260,000 without  halothane in 60%, succinylcholine in 77%  Classic-- rapid rise in body temperature, muscle rigidity, tachycardia, rhabdomyolysis, acidosis, hyperkalemia, DIC
• 37. Enflurane  Developed in 1963 by Terrell, released for use in 1972  Stable, nonflammable liquid  Pungent odor  MAC 1.68%
• 38. Enflurane Systemic Effects  Potent inotropic and chronotropic depressant and decreases systemic vascular resistance-- lowers blood pressure and conduction dramatically  Inhibits sympathetic baroreflex response  Sensitizes myocardium to effects of exogenous catecholamines-- arrhythmias
• 39. Enflurane Side Effects  Metabolism one-tenth that of halothane-- does not release quantity of hepatotoxic metabolites  Metabolism releases fluoride ion-- renal toxicity  Epileptiform EEG patterns
• 40. Isoflurane  Synthesized in 1965 by Terrell, introduced into practice in 1984  Not carcinogenic  Nonflammable,pungent  Less soluble than halothane or enflurane  MAC of 1.30 %
• 41. Isoflurane Systemic Effects  Depresses respiratory drive and ventilatory responses-- less than enflurane  Myocardial depressant-- less than enflurane  Inhibits sympathetic baroreflex response-- less than enflurane  Sensitizes myocardium to catecholamines -- less than halothane or enflurane
• 42. Isoflurane Systemic Effects  Produces most significant reduction in systemic vascular resistance-- coronary steal syndrome, increased ICP  Excellent muscle relaxant-- potentiates effects of neuromuscular blockers
• 43. Isoflurane Side Effects  Little metabolism (0.2%) -- low potential of organotoxic metabolites  Bronchoirritating, laryngospasm
• 44. Sevoflurane and Desflurane  Low solubility in blood-- produces rapid induction and emergence  Minimal systemic effects-- mild respiratory and cardiac suppression  Few side effects  Expensive  Differences
• 45. Sistema Nervoso Central
• 46. Silêncio ao EEG: Iso, Sevo e Desflurano: em torno de 2 CAM Halotano: acima de 3,5 CAM Enflurano: não há silêncio Proteção cerebral: Isoflurano: semelhante ao tiopental, até silêncio Atividade convulsivante: Enflurano > 2 CAM
• 47. Fluxo Sangüíneo Cerebral Stoelting Isoflurano preserva auto-regulação Halotano não preserva
• 48. Liquor Produção Absorção Efeito na PIC Enflurano + - + Isoflurano = + N 2O =
• 49. Sistema Nervoso Autônomo Barash Stoelting
• 50. Índice Cardíaco, PVC, RVS RVS Contra- RVS PA tilidade Halot - + - I, S, D = - -
• 51. Freqüência Cardíaca e Pressão Arterial Pressão Arterial FC: H - I,S,D + Mecanismos: depressão de reflexo baro-r, depressão NSA
• 52. Arritmias
• 53. Parâmetros Respiratórios Mecanismo da depressão: depressão dos centros medulares alteração da função dos músculos intercostais Barash
• 54. Resposta à hipoxemia 0,1 CAM diminui 50-70% Resposta Ventilatória ao CO2 Stoelting
• 55. Broncodilatação Barash É difícil demonstrar efeito broncodilatador na ausência de broncoconstricção
• 56. Vasoconstricção Hipóxica A inibição da vasoconstricção pulmonar hipóxica pelos anestésicos inalatórios não prejudica a oxigenação na ventilação monopulmonar. Barash
• 57. Músculos Esqueléticos Hipertermia Maligna Todos os halogenados podem desencadear Aumento das contraturas induzidas por cafeína no sartório do sapo N 2O Iso Enfl Hal 1,3 3 4 11