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

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

(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

General Anesthetics 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

1. Inhaled Anesthetics Include: Nitrous oxide Halothane Enflurane Isoflurane Desflurane

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

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

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 depends on 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, 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 Activates GABA receptors It is not analgesic , and its primary advantage is in anesthesia for patient with limited respiratory and cardiac reserve 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

Anesthesia protocols Induction and maintenance for general anesthesia: For extensive surgical procedure The protocol commonly includes IV drug for induction, inhaled agent (with or without IV) for maintenance and neuromuscular junction blockers to cause muscle relaxation Conscious sedation techniques: For minor procedure, that combine IV agent with local anesthetics These can provide profound analgesia, with retention of the patient ability to maintain a patent airway and response to verbal commands

Neuroleptanalgesia: combine a major neuroleptic (droperidol) and a potent opioid analgesic (fentanyl) to produce a detached, pain-free state. (state of analgesia and amnesia) Dissociative anesthetic Produced by ketamine The patient is patient remains conscious but has marked catatonia, analgesia, and amnesia

GOOD LUCK