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General anesthesia

General anesthesia. General anesthesia was not known until the mid-1800’s Diethylether was the first general anesthetic used for surgery General Anesthetics are divided into two classes: Inhaled anesthetics (usually halogenated compounds) Intravenous anesthetics or induction agents.

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General anesthesia

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  1. General anesthesia • General anesthesia was not known until the mid-1800’s • Diethylether was the first general anesthetic used for surgery • General Anesthetics are divided into two classes: • Inhaled anesthetics (usually halogenated compounds) • Intravenous anesthetics or induction agents

  2. Modern Anesthesia • It combines the following: • Analgesia • Sleep (loss of consciousness) • Skeletal Muscle relaxation • amnesia • Abolition sensory & autonomic reflexes • No single drug can produce all these effects

  3. Ideal anesthesia is • Induce loss of consciousness smoothly and rapidly • Allow for prompt recovery of cognitive function after its administration is discontinued • Possess wide margin of safety • Have no side effects • No single drug can produce all these effects

  4. Stages of anesthesia • Stage 1:analgesia Decreased pain awareness, sometimes with amnesia ,conscious may be impaired but not lost • Stage 2:disinhibition Delirium, excitation, amnesia, enhanced reflexes, irregular respiration and incontinence • Stage 3:surgical anesthesia Unconsciousness ,no pain reflex, regular respiration and maintained blood pressure • Stage 4:medullary depression Severe CVS and respiratory depression and the patient require pharmacological and ventilatory support

  5. Anesthesia protocols • For minor procedure, conscious sedation conscious sedation techniques that combine IV agent with local anesthetics are often used ;these can provide profound analgesia, with retention of the patient ability to maintain a patent airway and response to verbal commands • For extensive surgical procedure protocol commonly includes IV drug for induction, inhaled agent(with or without IV)for maintenance and neuromuscular junction blockers to cause muscle relaxation

  6. General Anesthetics • Absence of sensation associated with a reversible loss of consciousness, skeletal muscle relaxation, and loss of reflexes. • Drugs used for anesthesia are CNS depressants with action that can be induced and terminated more rabidly than conventional sedative and hypnotics • Most sensitive site of action for general anesthetics is the reticular activating system of the brainstem (RAS) • Anesthetic dose: does not cause depression of cardiac, vasomotor or respiratory centers • Has a small margin of safety

  7. Inhaled Anesthetics • Include: Nitrous oxide Halothane Enflurane Isoflurane Desflurane

  8. Intravenous Anesthetics • Include: • Barbiturates • Thiopental & Methohexital • Opioids • Alfentanil, Meperidine, Fentanyl, Sufentanil (agonists) • Naloxone (antagonist) • Benzodiazepines • Diazepam, Midazolam • Flumazenil (antagonist)

  9. Intravenous Anesthetics • Miscellaneous Agents • Etomidate – non-barbiturate hypnotic agent without analgesic properties • Droperidol - Neuroleptic (similar to Haloperidol) - combined with Fentanyl and is used for neuroleptanalgesia (state of analgesia and amnesia) • Ketamine - dissociative anesthetic • Propofol

  10. General Uses of IV Anesthetics • Primary Use = induction of general anesthesia • Supplement general anesthesia • maintain general anesthesia • provide sedation • control Blood Pressure

  11. Intravenous agents • Mechanism of action • Act at cell surface receptors • Barbiturates and benzodiazepine act at GABA-A receptors to increase Cl- influx • Opioids act on m and other subtypes • Ketamine antagonizes PCP site on NMDA receptors (prevent excitation) • Pharmacokinetics • Rapid induction = shorter acting • Duration of effect proportional to redistribution from brain to other tissue

  12. Barbiturates: Thiopentone • Ultra-short acting hypnotic with no analgesic action • High lipid solubility promotes rapid entry to the brain • Eliminated by the liver • Has rapid onset of action and recovery • M.O.A.= potentiates GABA, decrease glutamate activity, increase chloride ion conductance Adverse reactions: decreased myocardial and respiratory activity

  13. Etomidate • Imidazole derivative that provide induction with minimal change in cardiac function and respiratory rate and has short duration of action • It is not analgesic , and its primary advantage is in anesthesia for patient with limited respiratory and cardiac reserve • Activates GABA receptors • Uses • Induction of anesthesia • Side effects • Myoclonus • Post-operative nausea and vomiting

  14. Ketamine • This drug produce dissociative state in which the patient is patient remains conscious but has marked catatonia, analgesia, and amnesia • It is a chemical congener of the psychotomimetic agent, phencyclidine (PCP) • It is a cardiovascular stimulant drug and this action may cause increase ICP • Emergency reactions include disorientation ,excitation and hallucination which can be reduced by preoperative administration of benzodiazepines

  15. Uses- Induction of anesthesia • in children • in severely hypovolemic patients • Contraindications • Increased intracranial pressure • Ischemic heart disease • Psychological disorders • Effects • Analgesic with dissociative anesth. properties • Dreaming in children

  16. Propofol • Uses • Induction and maintenance of anesthesia • As anesthetic agent at outpatient surgery • Also effective in producing prolog sedation in patient in critical care setting • Contraindications • Cardiovascular instability due to marked reduction in the peripheral resistance • Effects • Hypnosis ,Antiemetic • Fast acting, short duration. Fewer peripheral side effects compared to barbiturates

  17. Opiates • Potent analgesics • Fentanyl -Potency 50-100X >Morph • Alfentanil -Potency 25-30X > Morph • Sufentanil -Potency 5-10X >Fentanyl • Meperidine • Uses • Supplementation of general anesthesia or analgesia • Effects • respiratory depression • nausea and vomiting • muscle rigidity

  18. INHALATION ANESTHETICS

  19. MAC(minimal alveolar concentration) • MAC of anaesthetic measures potency of anaesthetic vapour. High MAC means low potency • Defined as the concentration of anesthetic that prevents movement induced by a painful stimulus in 50 % of subjects.

  20. Mechanism of Action • Potency is correlated with lipid solubility • Olive oil:gas partition coefficient • The greater the number, the more potent the anesthetic Methoxyflurane>halothane>isoflurane etc.

  21. Theories for Mechanism of Action • Theory #1 • Gas movement into lipid membrane disrupting ion channels and action potential propagation • Increased Atmospheric pressure will reverse effects • Theory #2 • Binding theory = anesthetics bind to hydrophobic portion of the ion channel • Theory #3 • Neuromodulator theory = anesthetics bind to cell-surface receptors. • increased Cl- flux (possible GABA mediation)

  22. Pharmacokinetics of Inhaled Anesthetics • Factors influencing the effects of inhaled anesthetics • Amount that reaches the brain • Indicated by oil:gas ratio (lipid solubility) • Partial pressure of anesthetic • 5% anesthetic = 38 mmHg (10% =76 mmHg) • Solubility of gas into blood • The lower the blood:gas ratio, the more anesthetic will arrive at the brain • Cardiac Output • Increased CO = greater Induction time

  23. Rate of Entry into the Brain: Influence of Blood and Lipid Solubility

  24. General Actions of Inhaled Anesthetics • Respiration • Depressed respiration • Kidney • Depression of renal blood flow and urine output • Muscle • High enough concentrations will relax skeletal muscle

  25. General Actions of Inhaled Anesthetics • Cardiovascular System • Generalized reduction in arterial pressure and peripheral vascular resistance. Isoflurane maintains CO and coronary function better than other agents • Central Nervous System • Increased cerebral blood flow and decreased cerebral metabolism

  26. Toxicity and Side Effects • Depression of respiratory drive • Depressed cardiovascular drive • Fluoride-ion toxicity from methoxyflurane • Metabolized in liver = release of Fluoride ions • Decreased renal function allows fluoride to accumulate = nephrotoxicity • Malignant hyperthermia • To treat this, rapidly cool the individual and administer Dantrolene to block release of Calcium from muscle sarcoplasmic reticulum

  27. Advantages and Disadvantages of Selected Inhaled Anesthetics • Isoflurane • Cardiac output is maintained • Arrhythmias are uncommon • Potentiates the actions of muscle relaxants • Minimally metabolized and no reports of heptato- or nephrotoxicity • most widely used agent • MAY CAUSE MALIGNANT HYPERTHERMIA

  28. Advantages and Disadvantages of Selected Inhaled Anesthetics • Desflurane • More irritating to airways than other agents • Rapid recovery • No reports of malignant hyperthermia

  29. Preanaesthetic Medication

  30. Focus Points • Induction of anesthesia is through use of any of the IV agents (Barbiturates: Thiopental, Opiate: Fentanyl, Benzodiazepines: Midazolam, Dissociative: Ketamine, Others: Propofol, Etomidate and Droperidol) • Majntenance of anesthesia is through use of any of the ihalation agents -N2O (70% in oxygen) is not suitable alone - N2O is usually combined with another inhalation agent or with opioids e.g. fentanyl

  31. A comparison halothane N2O Speed of induction intermediate fast Potency v.potent weak MAC=2% MAC 80% Muscle relaxation some none Cardiac arrhythmia yes no Liver damage yes no Recovery slow rapid

  32. NOTES: • Enflurane releases flouride ions which may cause renal failure • All inhalation anesthetics can cause resp. depression, myocardial depression, cardiac arrhythmias, hypotension and PONV • A mixture of N2O(50-70%) and haothane 1% is usually used in anesthesia.

  33. Nitrous Oxide • Characterized by inert nature with minimal metabolism • Colorless, odorless, tasteless, and does not burn

  34. Simple linear compound • Only anesthetic agent that is inorganic • Major difference is low potency • MAC value is 80 - 105% • Weak anesthetic, powerful analgesic • Needs other agents for surgical anesthesia • Low blood solubility (quick recovery)

  35. GOOD LUCK

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