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GENERAL ANESTHESIA BY P R O F. D R . Y I E L D E Z B A S S I O U N I What is meant by general Anesthesia? General anesthesia is a controlled reversible state of: 1. Loss of sensation (analgesia) 2. Loss of consciousness 3. Skeletal muscle relaxation AIM OF ANESTHESIA Facilitates surgery Not therapeutic or diagnostic غير عالجية أو تشخيصية STAGES OF GENERAL ANESTHESIA Stage 1: Analgesia فقدان األلم Loss of sensation but patient is still alert and speaking Stage 2: Excitement إثارة CNS excitation+ BP (irregular) + respiratory rate Stage 3: Surgical Anesthesia التخدير الجراحي Regular respiration + relaxed skeletal muscles + eye movement stops and pupil is fixed Stage 4: Coma→→→ death MECHANISM OF ACTION Anesthetic agents may enhance action of inhibitory neurotrasmitters such as GABA and glycine as well as blocking excitatory NTM actions such as glutamic acid It is suggested that incorporation of the anesthetic drug into cell membrane phospholipids alters cell membrane fluidity Pre-anesthetic medications These are drugs used to facilitate smooth induction of anesthesia and help to lower the dose and side effects of anesthetic drugs Reduce postoperative pain Provide amnesia, decrease anxiety Decrease secretions Pre-anesthetic medications 1.Sedative hypnotics: BZs or barbiturates 2.Antihistaminics: H1 (anti-allergic) and H2 blockers (to reduce gastric acidity) 3.Anti-emetics: metoclopramide 4.Opioid analgesics: morphine or pethidine 5. Anti-cholinergics: scopolamine Classification of general anesthetic agents: 2) IV anesthetic drugs 1) Inhaled volatile agents IV anesthetic drugs • The term intravenous anesthetic agents means inducing anesthesia by drugs administered intravenously. Unbound, lipid soluble, unionized molecules cross the blood brain barrier the quickest. Advantages of IV anesthesia include: • rapid and smooth induction of anesthesia • little equipment requirement (syringes, needles, catheters) • easy administration of drugs PROPERTIES OF THE IDEAL INTRAVENOUS ANAESTHETIC AGENT o quick and smooth induction and recovery o high therapeutic index o no toxic metabolites & no emetic effects o No involuntary movements No emergence nightmares, No hang over effect o potent, so small volume is required for anesthetic induction/maintenance o compatible with other dugs ( muscle relaxants) o no cardiopulmonary depression , no pain on injection O No histamine release/hypersensitivity reactions INTRAVENOUS ANESTHETICS 1- Ultra- short acting barbituates -thiopental (Pentothal) -methohexital (Brevital) 2- Benzodiazepines (adjuvant ) -diazepam (Valium) -lorazepam (Ativan) -midazolam (Versed) 3- Etomidate (Amidate) 4- Propofol (Diprivan) INTRAVENOUS ANESTHETICS 5- Opioids -fentanyl (Duragesic, Sublimaze) -fentanyl- droperidol (neuroleptanalgesia) -Morphine 6- Dissociative anesthetics -ketamine (Ketalar) Sodium thiopental (pentothal) An IV dose of 3-5 mg/kg results in loss of consciousness ( 30-60 secs after administration). This is called the “arm brain” circulation time It has a short duration of action 5-10 min due to its redistribution away from the brain towards muscle and fat tissue If its concentration is low enough in the brain, consciousness returns It does not provide adequate skeletal muscle relaxation alone Sodium thiopental (pentothal) Disadvantages: 1- hypotension 2- respiratory depression: dose-dependent respiratory depression 3- tissue necrosis : following i.v. infusion 4- it does not provide analgesia 5- no skeletal muscle relaxation 6- laryngeal spasm 7- bronchospasm: unusual but may be precipitated in asthmatics pts Propofol (Diprivan® ) Advantages: *High lipophilicity; rapid and smooth onset and rapid recovery *Minimal nausea and vomiting * Amnestic and anti-emetic effects Disadvantages: Not water soluble-- painful (50%) Dose – related Respiratory depressant PROPOFOL & CVS Myocardial depression Propofol causes the most marked fall in blood pressure of all the induction drugs. This is mainly due to systemic vasodilatation. May be slight increase in heart rate. The fall in blood pressure is dosedependent and is most marked in the elderly and in shocked patients. Ketamine (Ketalar) * Structurally similar to phencyclidine * Dissociative anesthesia; the patient is unconscious but appears awake and doesn’t feel pain * Ketamine causes stimulation of the CVS. (increase HR, BP, CO) * Good analgesic • Ketamine acts by noncompetitive antagonism at the N-methyl-D aspartate (NMDA) receptor in the brain and spinal cord. Ketamine: advantages 1-Ketamine is a potent bronchodilator can be used as in asthmatic patients 2- Potent analgesic in sub-anesthetic doses 3- can be administered i.v., i.m., orally, nasally, rectally, and epidurally. 4- Suitable for shocked patients?? Ketamine: Disadvantages 1- The onset of action is slower than other induction drugs 2- ketamine increases cerebral blood flow, and intracranial pressure. Emergence can produce hallucination and unpleasant dreams (15 % esp. females & large dose of ketamine) usually be avoided by concomitant application of a sedative such as a BZ. 3- Generalized increase in the muscle tone and purposeful movements 4- It produces central sympathetic stimulation, which increases: arterial blood pressure, heart rate, and cardiac output Thiopental 1. IV barbiturate 2. Rapid induction 3. Short duration 4. Potent anesthetic but not analgesic Ketamine Propofol 1. Slower onset & 1. Rapid induction, rapid recovery 2. dissociative anesthesia pleasant recovery 2. No emesis 3. amnestic effect 3. Good analgesia 4. Bronchodilator 1. No analgesia 2. Little Sk.m. relaxation 1. sympathetic outflow 3. BP & bradycardia 2. cerebral blood 4. Laryngospasm, apnea, flow; postoperative cough, bronchospasm Hallucination, night mares 1. No analgesic action 2. Pain at injection site 3. Dose-related respiratory depression, 4. bradycardia, and hypotension Benzodiazepines They are used as adjuvant IV anesthetic agents for the following : 1 – amnesia 2 – minimal cardiac & respiratory depressant effect 3 – anticonvulsant activity 4 – low incidence of tolerance and dependence 5- availability of antagonist ‘ flumazenil’ Etomidate is a short acting iv anaesthetic agent used for the induction of general anesthesia for sedation for short procedures such as reduction of dislocated joints, tracheal intubation Rapid onset of action, usually within one minute. Duration of action 3-5 min. Etomidate causes the least cardiovascular depression of the IV anaesthetics Etomidate: Disadvantages Adrenal suppression: It supresses corticosteroid synthesis in the adrenal cortex (Reduced cortisol plasma levels) Do not use etomidate for critically ill patients ( increased mortality). Post operative vomiting is more common than with other induction agents. Pain on injection is common and there is a high rate of thrombophlebitis Etomidate has no analgesic activity Inhalational Anesthetics Inhalational Anesthetics Inhalational anesthesia refers to delivery of gases or vapors via the respiratory system to produce anesthesia 1- Gases like :Nitrous Oxide (N2O) cyclopropane and xenon by flowmeters 2-Volatile liquids are vaporized in a carrier gas (vaporizers). e.g. halothane, isoflurane, desflurane and sevoflurane O2 is bubbled in volatile Anesth. agnet blood Mixture vapor Diffuse across alveolar capillary membrane Anesthetic machine Lungs Brain Ideal Characteristics 1. pleasant to inhale, permitting a smooth induction and recovery 2. potent to allow the concomitant administration of high oxygen 3. Rapid induction and recovery (low solubility) 4. easily and cheaply prepared in a pure form 5. No CV or respiratory effects, non-toxic to organ systems 6. safe for exposure to operating room staff 7. not flammable, not metabolized. And nvironmentally safe 8. being liquid at room temperature, but evaporating easily for administration by inhalation Rate of induction and recovery Depends on Blood/Gas partition coefficient is the ratio of anesthetic concentration in blood compared to gas phase. Solubility in blood: •More soluble = slower induction (slow onset) e.g. Halothane •Less soluble = faster induction e.g. Nitrous oxide MINIMUM ALVEOLAR CONCENTRATION (MAC) Anesthetic potency is measured in MAC. It allows us to compare the potency of the various inhalational agents MAC is defined as the concentration of anesthetic that is required to produce immobility in 50% of patients exposed to a noxious stimulus (surgical incision) MAC VALUE Halothane = 0.75% Isoflurane = 1.16% Euflurane = 1.68% Sevoflurane = 2% N2O = 105% # Halothane is the most potent # N2O alone is unable to produce adequate anesthesia ( require high conc. ) NITROUS OXIDE Physical property: *Colorless, odorless, and nonflammable, laughing gas Pharmacology -Good analgesic -Low solubility (fast on/off) -Minimal effects on heart rate and BP - Weak anesthetic- MAC = 105% (Low potency) - it must be used as an adjunct anaesthetic, along with other agents HALOTHANE Halogenated hydrocarbon # Most potent inhalational anesthetic (MAC=0.75%) # has a pleasant, non-irritant smell # bronchodilator # drug of choice in children # Slow induction & slow recovery # Hepatotoxicity # Myocardial depressant # Sensitizes myocardium to effects of exogenous catecholamines ( ventricular arrhythmias) ISOFLURANE Advantages - Rapid induction and recovery - Little risk of hepatic or renal toxicity - Cardiovascular stability - Muscle relaxation - Few side effects Disadvantages - Pungent odor الذعcough, breath holding Halothane Isoflurane Nitrous oxide 1956 1984 1799 Potency High High weak Induction& Slow Rapid Very rapid 1. risk No risk No risk No risk No risk -drug of choice 1. Good muscle 1. Rapid onset & in relaxation. recovery 2. Rapid recovery 2. Good recovery Arrhythmia 2. sensitivity to catecholamines Hepatotoxicity risk ( not in children) Therapeutic advantages children - Good for asthmatic bronchodilataion 3. No sensitization to catecholamines analgesia SEVOFLURANE Advantages 1. Well tolerated (non-irritant, sweet odor), even at high concentrations, making this the agent of choice for inhalational induction 2. Rapid induction and recovery 3. Does not sensitize the myocardium to catecholamines as much as halothane 4. Bronchodilator SEVOFLURANE Disadvantages 1. Less potent than similar halogenated agents 2. Risk of renal toxicity ( about 5% is metabolized and serum fluoride level is elevated) Thank You