General Veterinary Anesthesia

1. General Veterinary Anesthesia S. HabibianDehkordi D.V.M, Ph.D, Postdoctral Research Assistant in Neuropharmacology, Postdoctral Research Associate in Neuroscience

2. Anesthetics • Anesthesia means without sensation • Anesthetics interfere with the conduction of nerve impulses • Anesthetics produce loss of sensation and muscle relaxation, and may cause loss of consciousness • General anesthetics affect the CNS, produce loss of sensation with partial or complete loss of consciousness • Local anesthetics block nerve transmission in the area of application with no loss of consciousness

3. Categories of Anesthetics • General anesthetics • Central nervous system (CNS) depressants used to produce loss of pain sensation and consciousness • Local anesthetics • Used to cause loss of pain sensation and feeling in a designated area of the body • Does not produce the systemic effects associated with severe CNS depression

4. Important difference between general and local anesthetic are as fallows

5. An ideal General Anaesthetic………. Unconsciousness, Amnesia and Analgesia AND Muscle relaxant properties Fast Acting Rapid Recovery Low Toxicity Wide Safety Margin (large Therapeutic Index)

6. Outline • History of Anesthesia • Methods of Administration • Mechanisms of Action • Companion Animal Drugs

7. Timeline

9. Goals of General Anesthetics • Analgesia • Loss of pain perception • Unconsciousness • Loss of awareness of one’s surroundings • Amnesia • Inability to recall what took place

10. Basic Principles of Anesthesia • Anesthesia defined as the abolition of sensation • Analgesia defined as the abolition of pain • “Triad of General Anesthesia” • need for unconsciousness • need for analgesia • need for muscle relaxation

11. Methods of Administration Common: Inhalation Intravenous Intramuscular Less Common: Rectal Oral Nasal Intraperitoneal

12. Mechanism of Action • Hyperpolarize neurons • Anticholingeric: suppresses nervous system communication • Alpha-2 adrenergic receptor agonist/antagonist: suppress norepinephrine binding/release to receptor • Cardiovascular depressant • Respiratory depressant

13. Action Potentials: Overview • Ach is a main neurotransmitter of the autonomic NS of PNS • In the CNS, excitatory actions

14. Stages of General Anaesthesia (based on observations of patients undergoing induction with ether) Stages of Anesthesia • Stage 1: The analgesia stage • Stage 2: The excitement stage • Stage 3: Surgical anesthesia • Stage 4: Medullary paralysis

15. Stage 1: Analgesia Start from beginning of anesthetic inhalation and lasts upto the loss of consciousness. Pain is progressively abolished during these stage patient remains abolished during this stage. Patient remains conscious, can hear and see, and fees a dream like state. Reflexes and respiration remain normal. Though some minor and even major operation can be carried out during this stage, it is rather difficult to maintain-use is limited to short procedure. Still conscious All Reflexes

16. Stage 2: Delirium and Excitation From loss of consciousness to beginning of regular respiration. Excitement is seen-patient may shout, struggle and hold his breath; muscle tone increases, jaw are tightly closed, breathing is jerkey; vomiting, involuntary micturition or defecation may occur. Heart rate and BP may rise and pupils dilate due to sympathetic stimulation. No stimulus should be applied or operative procedure carried out during this stage. Vomiting, Salivation Coughing Increased muscle tone Increased BP and HR Depression of Palpebral {eyelash} reflex.

17. Stage 3: Surgical anesthesia : Extends from onset of regular respiration to cessation of spontaneous breathing. This has been divided into 4 planes Plane 1 & 2 : Regular breathing rhythm. Progressive reduction in tidal volume Pupils progressively larger in diameter Depression of vomiting reflex, withdrawal reflex, corneal reflex Plane 3 (for surgical anaesthesia): Regular breathing rhythm. Small tidal volume Pupils dilated (3/4 diameter) Depression of laryngeal (gag) reflex Plane 4: Irregular, diaphragmatic shallow breathing Pupils fully dilated Depression of Carinal and anal sphincter reflex

18. Stage 3 : Surgical Anaesthesia (Four Planes) Plane 1 & 2 : Regular breathing rhythm. Progressive reduction in tidal volume Pupils progressively larger in diameter Depression of vomiting reflex, withdrawal reflex, corneal reflex Plane 3 (for surgical anaesthesia): Regular breathing rhythm. Small tidal volume Pupils dilated (3/4 diameter) Depression of laryngeal (gag) reflex Plane 4: Irregular, diaphragmatic shallow breathing Pupils fully dilated Depression of Carinal and anal sphincter reflex

19. Stage 4: Medullary Paralysis Cessation of breathing to failure of circulation and death. Pupil is widely dilated, muscles are totally flabby, pulse is thready or imperceptible and BP is very low. Respiratory failure, Cardiovascular failure Lack of pupillary reflex

20. Adjuvants to Anaesthesia Drugs that are given with the anaesthetic before, during and after anaesthesia They are NOT anaesthetics Pre-anaesthetic Adjuvants Benzodiazepines: Relieves anxiety produces some amnesia Analgesics: Relieves anxiety provides post op. analgesia Antimuscarinics: Reduce bronchial and salivary secretions also gives some amnesia Most of the above drug types POTENTIATE the action of the anaesthetic (Lab III)

21. Adjuvants during Anaesthesia Neuromuscular blockers: Produce muscle relaxation AND allow for intubation for artificial ventilation during surgery Pressor or Depressor’s: Increase or decrease Blood Pressure during surgery. Adjuvants post operatively Analgesics: To relieve post operative pain Cholinergic agonist: To reverse Anti Muscarinic side effects (urinary retention and constipation) Anticholinesterases: Reverse neuromuscular blockers and if spontaneous breathing does not recommence

22. Agents Involved in Balanced Anesthesia • Preoperative medications • Sedative–hypnotics • Antiemetics • Antihistamines • Narcotics

23. CHARACTERSITICS OF AN IDEAL ANAESTHETIC • Rapid and pleasant induction • Rapid changes in the depth of anesthesia • Adequate Muscle Relaxation • Wide margin of safety • Absence of toxic/adverse effects

24. Risk Factors Associated With General Anesthetics • CNS factors • Cardiovascular factors • Respiratory factors • Renal and hepatic function

25. GENERAL ANAESTHETICS CLASSIFICATION Inhalation agents:NEWER AGENTS OLDER DRUGS Halothane Chloroform Enflurane Ether Volatile liquids: IsofluraneEthylchloride DesfluraneTrichlorethylene Sevoflurane Gases:Nitrous oxide Cyclopropane Ethylene Intravenous agents: Thiopentone Benzodiazepines Etomidate Ketamine Propofol

26. Mechanism of Action • We don’t know… much, but let me tell you about what we do know…

27. Inhalation Anaesthetics How they work (pharmacodynamics) Lipid theory/Membrane Theory Inhalation anaesthetics are ‘lipophyllic’ (lipo = lipids phyllic = love) Cross the Blood Brain Barrier Enter the plasma membrane and disrupt sodium channel structure Decrease neuronal excitability (increased threshold)

28. Membrane Hypotheses • Some membrane channels behavior is changed by anesthetic agents • Some channels slowed • Some channels sped up • Different channels different effect with different agents • Postulated that lipid bilayer may be site of action • Lipid permeability is changed • Synaptic vesicles behavior changes • Thickness of lipid bilayer is changed - thicker

29. Receptor Theory • Inhaled anesthetic agents interact with many neuronal cell surface proteins • GABA receptor is thought to be a likely target • GABAA sub-unit is thought to be area of interest – not all GABAA are the same • GABA receptors containing alpha-5 sub-unit are also implicated • GABA receptors outside the synapse are also thought to be implicated • .

30. Inhalation Anesthetics • Diethyl ether, nitrous oxide, chloroform • Halothane • Isoflurane • Sevoflurane

31. Pharmacokinetics of inhalation anesthetics: • Inhalation anesthetics are gases or vapors that diffuse rapidly across pulmonary alveoli and tissue barriers. the depth of anesthesia depend on the agent (MAC is an index of potency) and its partial pressure(PP) in the brain, while the induction and recovery depend on the rate of change of PP in the brain. • Transfer of anesthetics between lung and brain depends on a series of tension gradient which may be as Alveoli Blood Brain

32. Elimination • When anesthetic administration is discontinued, gradient are reversed and the channel of absorption (pulmonary epithelium) becomes the channel of ellimination. • Most of general anesthetics are eliminated unchanged. metabolism is significant only for halothane. Other are practically not metabolized

33. Diethyl ether • First anesthetic discovered • Nontoxic to organs • Unpleasant smell • Decreases possibility of action potential by decreasing rate of rise to an end-plate potential

34. Chloroform CH(Cl)3 • Colorless and odorless • Hepatotoxin • Severe CV depressant • Cardiac arrhythemia • Aka Sudden Sniffer’s Death • Blocks flow of K+ out of the cell www.inchem.org/documents/ehc/ehc/ehc163.htm

35. Halogenated hydrocarbons anesthetics

36. MAC • Minimum Alveolar Concentration = MAC • Anesthetic potency is measured in MAC • 1 MAC is the Minimum Alveolar Concentration at which 50% of humans have no response (movement) to surgical stimulus (skin incision) • MACawake is the alveolar concentration when 50% of persons will awake to vocal stimulus • MAC is directly proportional to the partial pressure of the anesthetic agent in the CNS • MAC is consistent within a species and between species • MAC is different for each inhaled agent

37. MAC

38. MAC

39. MAC • MAC decreases with decreasing body temperature • MAC increases with increasing pressure • more anesthetic agent required higher pressures to achieve same MAC • Ion concentrations in CNS alter MAC • Na – MAC increases with concentration • K – no effect • Ca – no effect • Mg – inversely proportional increase with concentration • MAC decreases with age (greatest at 6 months) • MAC is altered by other drugs • MAC decreases as patient medical condition deteriorates

40. MAC

41. Nitrous Oxide • Prepared by Priestly in 1776 • Anesthetic properties described by Davy in 1799 • Characterized by inert nature with minimal metabolism • Colorless, odorless, tasteless, and does not burn. • Simple linear compound • Not metabolized • Only anesthetic agent that is inorganic

42. General Anesthetics/Analgesics • Nitrous oxide: • Inhalant analgesic that diffuses rapidly throughout the body • Can enter gas-filled body compartments (increases pressure in these compartments) • Contraindicated in cases of gastric dilatation, pneumothorax, and twisted intestines • Leave animals on 100% oxygen following surgery to prevent diffusion hypoxia • Inhalant general analgesics (cont.): • Nitrous oxide: • Inhalant analgesic that diffuses rapidly throughout the body • Can enter gas-filled body compartments (increases pressure in these compartments) • Contraindicated in cases of gastric dilatation, pneumothorax, and twisted intestines • Leave animals on 100% oxygen following surgery to prevent diffusion hypoxia

43. NITROUS OXIDE: Di nitrogen monoxide • Odorless gas • Stored in blue cylinders in liquid form • Currently used as an adjuvant with other agents. • MAC-105% • Higher concentrations promote hypoxia. • Ideally used as: • Induction by I/ V agent • Muscle relaxation by NMBA (Neuromuscular Blocking Agents) • Analgesia by Nitrous oxide

44. NITROUS OXIDE When used with other inhalational agents, reduces their MAC. ADVANTAGES • Non-Inflammable • Non-Irritant • Powerful analgesic • Rapid onset and recovery • Little or no toxicity • Reduces dose of other agents • Ideal for dental procedures and first stage of parturition • DISADVANTAGES • Weak agent • No muscle relaxant activity • Causes hypoxia • Air pockets in closed spacesmay expand in abdomen, chest, skull. • Inhibits methionine synthetase (precursor to DNA synthesis) • Inhibits vitamin B-12 metabolism

45. General Anesthetics/Analgesics • Inhalant general anesthetics: Inhalant anesthetics are halogenated hydrocarbons • Halothane: • Nonflammatory, inhalant anesthetic administered via a precision vaporizer • Can cause hepatic problems, malignant hyperthermia, cardiac problems, and tachypnea

46. HALOTHANE • First in series of drugs used commonly • Standard to compare other agents • Potent General Anesthetic • Causes smooth rapid loss of consciousness

47. HALOTHANE PHARMACOLOGICAL EFFECTS: ADVANTAGES DISADVANTAGES Non-Inflammable Low analgesia Rapid induction Hypoxia Recovery rapid Hypotension Smooth induction Arrythmogenic Relaxes uterus Respiratory depressant Useful in C.S Hepatic necrosis

48. Malignant Hyperthermia (continued) • treatment--early detection, d/c agents, hyperventilate, bicarb, IV dantrolene (2.5 mg/kg), ice packs/cooling blankets, lasix/mannitol/fluids. ICU monitoring • Susceptible patients-- preop with IV dantrolene, keep away inhalational agents and succinylcholine

49. General Anesthetics/Analgesics • Inhalant general anesthetics (cont.): • Isoflurane: • Nonflammatory, inhalant anesthetic administered via a precision vaporizer • Causes rapid induction of anesthesia and short recoveries following anesthetic procedures • Does not cause the cardiac arrhythmia problems of halothane • Vigilant monitoring is needed because the animal can change anesthetic planes quickly • Masking of animals with isoflurane is difficult because it irritates the respiratory system • Side effects include respiratory depression and malignant hyperthermia

50. ISOFLURANE • Isomer of Enflurane • Similar Chemical properties • Low blood gas solubility coefficient • Low doses required • Induction in less than 10 minutes With 3% concentration • Maintenance with 1.5- 2.5% • Dose reduced if adjuvant used