Presentation for a lecture on_Anesthesia_part_2.pptx

Presentation for a lecture on_Basics of Anesthesia part 2

1. Anesthesiology. Inhaled & intravenous anesthetics Anesthesiology , Reanimatology & Intensive care Faculty with Ambulance/Paramed course. TSMU of RF Health ministry

2. What is anesthesia? Anesthesiology

3. Arrows indicate activation or potentiation, and Ts indicate inhibition or antagonism Anesthesiology A multisite model for anesthesia. Anesthetics are grouped according to similarity of mechanism

4. Anesthesiology GABA A Receptors

5. Anesthesiology N -Methyl-D-Aspartate Receptors

6. Inhaled Anesthetics Anesthesiology MECHANISM OF ACTION Inhaled anesthetics act through multiple complex mechanisms and pathways within the central nervous system (CNS). The agents act by binding to target sites in proteins to enhance inhibitory receptors (gamma-amino butyric acid (GABA), glycine and suppress excitatory transmission (block the action of glutamate at N-methyl D-aspartate (NMDA) receptors). Hypnosis/sedation and amnesia are produced through effect sites in the brain. Immobility is produced by actions within the spinal cord. Lipid solubility correlates to anesthetic potency (Meyer-Overton correlation). There is currently no comprehensive theory of volatile anesthetics, and our understanding of the sequence of events, networks, and mechanisms is limited. Nitrous oxide is an inhaled anesthetic that works primarily by NMDA receptor antagonism .

7. Amnesia: The partial or complete loss of memory. Usually anterograde (affecting recall of experiences after the onset of anesthesia), amnesia may also be retrograde (affecting recall of experiences that precede the onset of anesthesia). Hypnosis: Drug-induced impairment of cognitive functions required for responding appropriately to environmental stimuli, including attention and perception. For a patient in the awake state, administration of inhaled anesthetics can produce a wide range of hypnotic depths, from mild inattention to unresponsiveness to noxious stimuli. Sedation: There are various functional definitions of this term, which is sometimes used as a synonym for “hypnosis.” We use the term to connote drug induced hypnosis with anxiolysis, diminished motor activity, and decreased arousal. Inhaled Anesthetics Anesthesiology Glossary of Terms

8. Drug pharmacology is classically divided into Pharmacodynamics (what the drug does to the body) Pharmacokinetics (what the body does to a drug) Drug pharmacokinetics has four phases : Absorption (uptake), Distribution, Metabolism, Excretion (elimination). Inhaled Anesthetics Anesthesiology PHARMACOKINETIC PRINCIPLES

9. Endotracheal tube Inhaled Anesthetics Anesthesiology Face mask Laryngeal mask airway Administration of inhaled anesthetics

10. Gas Delivery Systems Inhaled Anesthetics Anesthesiology NON-REBREATHING SYSTEMS REBREATHING SYSTEMS PARTIAL REBREATHING WITHOUT CO 2 ABSORPTION Bain Coaxial Circuit Ayre's T-piece Jackson-Rees system

11. Gas Delivery Systems Inhaled Anesthetics Anesthesiology REBREATHING SYSTEMS CIRCLE SYSTEMS WITH CO2 ABSORPTION THE CARBON DIOXIDE ABSORBER

12. Delivery by anesthesia machine: ◦ The machine takes in fresh, pressurized gas. ◦ The gas passes through a hypoxic trap where a mixture of gasses is determined by the operator (e.g., anesthesiologist or certified registered nurse anesthetist). ◦ The gas is passed through a vaporizer where the anesthetic agent is mixed in with fresh gas, reaching the concentration determined by the anesthesiologist. ◦ The mixed gas flows into the common gas outlet and into the breathing circuit. Inhaled Anesthetics Anesthesiology Gas Delivery Systems

13. Inhaled Anesthetics Anesthesiology Inspired concentration (Fi) Increasing the concentration of the inhaled anesthetic increases F A , but also the rate of rise of F A /F i  via the concentration effect and the second gas effect Alveolar ventilation ↑ ventilation can ↓ uptake into circulation. The effect is greater with soluble agents, which are subject to greater uptake. Less pronounced with insoluble agents, where F A /F i  quickly reaches 1.0. Factors Affecting Anesthetic Delivery

14. Inhaled Anesthetics Anesthesiology Characteristics of anesthesia circuit Circuit volume: ↓ delivery with ↑ volume. Gas flow: ↑ delivery with ↑ flow. Solubility of agent into system components: ↓ delivery with ↑ absorption. Characteristics of pulmonary system Functional residual capacity (FRC): increased FRC will dilute the inspired gas due to a larger gas reservoir. Larger FRC → slower induction. V/Q mismatch: Factors Affecting Anesthetic Delivery

15. The goal of delivering inhaled anesthetics is to produce the anesthetic state by establishing a specific concentration (partial pressure) in the central nervous system (CNS). This is achieved by establishing the desired partial pressure in the lungs that ultimately equilibrates with the brain and spinal cord. At equilibrium, the CNS partial pressure equals the blood partial pressure, which equals alveolar partial pressure. The concentration of anesthetic in the target tissue depends on the partial pressure at equilibrium and the target tissue solubility. Because inhaled anesthetics are gases and because partial pressures of gases equilibrate throughout a system, monitoring the alveolar concentration (Fa) of inhaled anesthetics provides an index of their effects on the brain. Inhaled Anesthetics Anesthesiology

16. Inhaled Anesthetics Anesthesiology Distribution

17. Inhaled Anesthetics Anesthesiology Distribution Mapleson’s water analogue models. The levels illustrate the situation in the early part of maintenance

18. Tissue partial pressures of anesthetics. Results of a Gas Man simulation of a 70-kg patient administered sevoflurane for 10 minutes at 2.56 vol % in 8 L/min of 100% O2. Inhaled Anesthetics Anesthesiology Distribution Multicompartment model due to differing rates of uptake by tissue. Tissue uptake is determined by tissue solubility (tissue/blood coefficients), tissue perfusion, and partial pressure gradient (P a / P tissue ).

19. Minimum Alveolar Concentration MAC is the F A of an anesthetic at 1 atm and 37°C that prevents movement in response to a surgical stimulus in 50% of “normal” * patients (analogous to an ED50 for injected drugs). Clinical experience is that 1.2 to 1.3 MAC consistently prevents patient movement during surgical stimulation. Although these MAC levels do not absolutely ensure the defining criteria for brain anesthesia (absence of self-awareness and recall), it is unlikely for a patient to be aware of or to recall the surgical incision at these anesthetic concentrations unless other conditions exist so that MAC is increased. Selfawareness and recall are prevented by 0.4 to 0.5 MAC. HOW IS ANESTHESIA MEASURED? * “ normal ” (healthy, nonpregnant, adult) human subjects under standard conditions (normal body temperature, 1 atm, no other drugs) * F A – alveolar concentration Inhaled Anesthetics Anesthesiology

20. Inhaled Anesthetics Anesthesiology Glossary of Terms Median alveolar concentration awake (MAC-awake): The end-tidal concentration of inhaled anesthetic that prevents appropriate voluntary responses to spoken commands (e.g., to open one’s mouth or to raise a hand) in 50 percent of a test population. This end point measures perceptive awareness rather than memory. Median alveolar concentration for blunting autonomic responses (MAC-BAR): The end-tidal concentration of inhaled anesthetic that blocks changes in blood pressure and heart rate in response to surgical incision in 50 percent of a test population. Potency: A measure of relative drug activity that is inversely related to the concentration required to produce a standard effect. A volatile anesthetic that produces a behavioral effect at half the concentration of another anesthetic is said to be twice as potent.

21. Inhaled Anesthetics Anesthesiology

22. The second-gas effect is demonstrated in the lower lines in which the FA/FI ratio for halothane increases more rapidly when administered with 70% N2O than with 10% N2O. Inhaled Anesthetics Anesthesiology

23. Inhaled Anesthetics Anesthesiology Clinically useful minimal alveolar concentration (MAC) values. Inhalational anesthetic concentration for 1 MAC (Age 40)

24. Inhaled Anesthetics Anesthesiology Factors Affecting MAC Age: MAC increases by 30% from birth until 1-6 months of age and then decreases by 6-7% every decade after 20 years of age

25. Inhaled Anesthetics Anesthesiology HOW IS ANESTHESIA MEASURED?

26. Describe the ventilatory effects of volatile anesthetics. Delivery of anesthetic gases results in dose-dependent depression of ventilation mediated directly through medullary centers and indirectly through effects on intercostal muscle function. Minute volume decreases secondary to reductions in tidal volume, although rate usually appears to increase in a dose-dependent fashion. Respiratory drive in response to hypoxemia can be abolished at 1 MAC and significantly attenuated at lower MACs. Increased delivered anesthetic concentration also attenuates the ventilatory response to hypercarbia. 11. Do volatile anesthetics affect intracranial pressure? Yes. Volatile anesthetics increase intracranial blood flow and increase intracranial pressure (ICP). Cerebral metabolic rate will be decreased (except in the case of N2O) and autoregulation of cerebral blood flow impaired. Use of an intravenous anesthetic may be preferred to volatile anesthetics when elevated ICP may impair effective intracranial blood flow. 13. Which anesthetic agent is most associated with cardiac dysrhythmias? Halothane has been shown to increase the sensitivity of the myocardium to B1-adrenergic stimulation (i.e., epinephrine), resulting in premature ventricular contractions and tachydysrhythmias . The mechanism of arrythmogenesis may be related to the prolongation of conduction through the His-Purkinje system, thereby facilitating reentry. Compared with adults, children undergoing halothane anesthesia appear to be relatively resistant to this sensitizing effect. However, halothane has been shown to have a cholinergic, vagally induced bradycardic effect in children. Also of note, volatile anesthetics prolong the QT interval. 14. Do volatile anesthetics affect the renal system? Yes. All volatile anesthetics decrease renal blood flow, glomerular filtration rate, and urine output.

27. Inhaled Anesthetics Anesthesiology CLINICAL OVERVIEW OF CURRENT INHALED ANESTHETICS

28. Nitrous Oxide Inhalation of 75% nitrous oxide may expand a pneumothorax to double its size in 10 minutes. Accumulation of nitrous oxide in the middle ear may diminish hearing after surgery CLINICAL OVERVIEW OF CURRENT INHALED ANESTHETICS Inhaled Anesthetics Anesthesiology

29. Isoflurane CLINICAL OVERVIEW OF CURRENT INHALED ANESTHETICS Inhaled Anesthetics Anesthesiology

30. Desflurane Desflurane has the lowest blood/gas solubility of the potent volatile anesthetics permitting rapid emergence even with prolonged surgical procedures and in obese patients. CLINICAL OVERVIEW OF CURRENT INHALED ANESTHETICS Inhaled Anesthetics Anesthesiology

31. Sevoflurane CLINICAL OVERVIEW OF CURRENT INHALED ANESTHETICS Inhaled Anesthetics Anesthesiology

32. Xenon expensive (difficult to obtain) high minimum alveolar concentration (MAC) (71%) nonpungent Fast uptake and excretion No biotransformation Nonpungent does not produce myocardial depression or alter coronary blood flow Has analgesic properties CLINICAL OVERVIEW OF CURRENT INHALED ANESTHETICS Inhaled Anesthetics Anesthesiology

33. Inhaled Anesthetics Anesthesiology

34. Recovery and Elimination Inhaled Anesthetics Anesthesiology Exhalation from the lungs Transcutaneous and visceral losses Biodegradation

35. Diffusion Hypoxia Inhaled Anesthetics Anesthesiology

36. NEUROMUSCULAR SYSTEM AND MALIGNANT HYPERTHERMIA Inhaled Anesthetics Anesthesiology

37. Comparison of delivery of anesthetics by inhalation (upper panel) or intravenous infusion (lower panel) at the beginning of the total intravenous anesthesia era (circa 1995). Inhaled Anesthetics Anesthesiology

38. Intravenous Anesthetics Anesthesiology

39. Intravenous Anesthetics Anesthesiology

40. Ca + , Calcium ion; Cl − , chloride ion; GABA, gamma-aminobutyric acid type A; Mg 2 + , magnesium ion; NMDA, N-methyl-D-aspartate. Intravenous Anesthetics Anesthesiology

41. Anesthesiology Barbiturates Structures of clinically important barbiturates. Individual Agents

42. Individual Agents Barbiturates

43. Individual Agents Barbiturates

44. Intravenous Anesthetics Anesthesiology Benzodiazepines Benzodiazepines produce their effects by enhancing the binding of GABA to its receptor. Benzodiazepines bind the same set of receptors in the central nervous system as barbiturates but bind to a different site.

45. Intravenous Anesthetics Anesthesiology Benzodiazepines

46. Individual Agents Benzodiazepines Anesthesiology

47. Individual Agents Benzodiazepines Anesthesiology

48. Individual Agents Benzodiazepines Anesthesiology

49. Individual Agents KETAMINE Anesthesiology

50. Individual Agents KETAMINE Anesthesiology

51. Individual Agents KETAMINE Anesthesiology

52. High-resolution cryo-electron microscopy structure of the human α 1 β 3 γ 2 GABAA receptor in a lipid bilayer as viewed from within the plane of the membrane and (B) from the extracellular face looking down the chloride (Cl-) pore. PROPOFOL Anesthesiology Individual Agents

53. PROPOFOL Anesthesiology Individual Agents

54. PROPOFOL Anesthesiology Individual Agents

55. PROPOFOL Anesthesiology Individual Agents

56. Anesthesiology Individual Agents DEXMEDETOMIDINE Brand Names: Dexdor , Igalmi , Precedex

57. Individual Agents Anesthesiology DEXMEDETOMIDINE