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General Anesthesia Dr. Israa General anesthesia • General anesthesia was not known until the mid1800’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 Modern Anesthesia • • It combines the following: 1. Analgesia 2. Sleep (loss of consciousness) 3. Skeletal Muscle relaxation 4. Amnesia 5. Abolition sensory & autonomic reflexes No single drug can produce all these effects Ideal anesthesia • 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) 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 Stages of anesthesia 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 Anesthesia protocols • For minor procedure, 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 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 General Anesthetics • 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 1. Inhaled Anesthetics • Include: – Nitrous oxide – Halothane – Enflurane – Isoflurane – Desflurane 2. Intravenous Anesthetics • Include: A. Barbiturates • Thiopental & Methohexital B. Opioids • Alfentanil, Meperidine, Fentanyl, Sufentanil (agonists) • Naloxone (antagonist) C. Benzodiazepines • Diazepam, Midazolam • Flumazenil (antagonist) Intravenous Anesthetics D. 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 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 μ and other subtypes • Ketamine antagonizes PCP site on NMDA receptors (prevent excitation) Intravenous agents Pharmacokinetics – Rapid induction = shorter acting – Duration of effect proportional to redistribution from brain to other tissue A. 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 Mechanism of action: • Potentiates GABA, decrease glutamate activity, increase chloride ion conductance Adverse reactions: • Decreased myocardial and respiratory activity B.OPIOIDS • Morphine and fentanyl are used in anesthesia regimens. • Respiratory depression due to these drugs may be reversed by naloxone. C. Benzodiazepines • Midazolam is widely used adjunctive with inhaled anesthetics and IV opioids • It has slow onset and longer duration of action if compared to thiopental. • Flumazenil is an antidote if respiratory depression occur. D. Miscellaneous Agents 1. 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 • Side effects – Myoclonus – Post-operative nausea and vomiting – Adrenal suppression if prolonged use. 2. 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 • Can cause increase intracranial pressure • Emergency reactions include disorientation, excitation and hallucination which can be reduced by preoperative administration of benzodiazepines Uses • Induction of anesthesia – in children – in severely hypovolemic patients Contraindications • Increased intracranial pressure • Ischemic heart disease • Psychological disorders 3.Propofol • Effects – Hypnosis , Antiemetic – Fast acting, short duration. – Fewer peripheral side effects compared to barbiturates • Uses – Induction and maintenance of anesthesia – As anesthetic agent at outpatient surgery – Also effective in producing prolong sedation in patient in critical care setting • Contraindications – Cardiovascular instability due to marked reduction in the peripheral resistance Preanaesthetic Medication GOOD LUCK