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This document discusses general anesthetics used for inducing and maintaining anesthesia. It describes the two main types - inhalational anesthetics like isoflurane, sevoflurane, desflurane and nitrous oxide which are used for maintenance of anesthesia, and intravenous anesthetics like propofol, thiopental and ketamine which are used for induction of anesthesia. Key factors that determine the properties of inhalational anesthetics include their blood-gas partition coefficient, which impacts induction and recovery time, and oil-gas partition coefficient, which correlates with their potency. The document also provides details on the mechanisms, advantages and side effects of various commonly used general anesthetics.

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General anesthetics • Introduction & History • Principles of General anesthesia • General anesthetics 1. Inhalational anesthetics 2. Intravenous anesthetics
Anesthesiology • Anesthesia – is a reversible condition of comfort, quiescence and physiological stability in a patient before, during and after performance of a procedure. • Anesthesia – for surgical procedure to render the patient unaware / unresponsive to the painful stimuli.
Anesthesiology Original in the Royal College of Surgeons of England, London.
Ether Massachusetts General Hospital, 16th October, 1846.
Anesthesiology • Surgical stress evokes HPA axis and sympathetic system. • Tissue damage during surgery induces coagulation factors and activates platelets leading to hypercoagulability of blood. • Most anesthetics are associated with • decrease in systemic blood pressure – myocardial depression and direct vasodilatation. • reduce ventilatory drive and eliminate reflexes that maintain airway patency.
General anesthesia - principles • Goals of Balanced Anesthesia • Amnesia • Analgesia • Attenuation of autonomic reflexes • Immobility • Unconsciousness
General anesthesia - principles • Preanesthetic medications: It is the use of drugs prior to anesthesia to make it more safe and pleasant. • To relieve anxiety – benzodiazepines. • To prevent vomiting – antiemetics. • To supplement analgesia – opioids. • To prevent vagal stimulation and secretion – atropine.
General anesthesia - principles Stages of anesthesia: • Stage I : Analgesia • Stage II : Excitement, combative • behavior – dangerous state • Stage III : Surgical anesthesia • Stage IV : Medullary paralysis - respiratory and vasomotor control ceases.
General anesthetics - mechanism Molecular mechanism of the GA : • GABA –A : Potentiation by Halothane, Propofol, Etomidate • NMDA receptors : inhibited by Ketamine
General anesthetics There are two types of anesthetics : • Inhalational --- for maintenance • Intravenous --- for induction and short procedures • Inhalation anesthetics: • Advantage of controlling the depth of anesthesia. • Metabolism is very minimal. • Excreted by exhalation.
General anesthetics Inhalational anesthetics : • Nitrous oxide • Halothane • Enflurane – rarely used • Isoflurane – most commonly used • Desflurane • Sevoflurane • Methoxyflurane – not available in US because of concerns of nephrotoxicity.
General anesthetics
General anesthetics • The important characteristics of Inhalational anesthetics which govern the anesthesia are : • Solubility in the blood (blood : gas partition co-efficient) • Solubility in the fat (oil : gas partition co-efficient)
Inhalational anesthetics Blood : gas partition co-efficient: • It is a measure of solubility in the blood. • It determines the rate of induction and recovery of Inhalational anesthetics. • Lower the blood : gas co-efficient – faster the induction and recovery – Nitrous oxide. • Higher the blood : gas co-efficient – slower induction and recovery – Halothane.
BLOOD GAS PARTITION COEFFICIENT Agents with low solubility in blood quickly saturate the blood. The additional anesthetic molecules are then readily transferred to the brain
Inhalational anesthetics Blood gas partition co-efficient affecting rate of induction and recovery
Inhalational anesthetics Oil: gas partition co-efficient: • It is a measure of lipid solubility. • Lipid solubility - correlates strongly with the potency of the anesthetic. • Higher the lipid solubility – potent anesthetic. e.g., halothane
Inhalational anesthetics • MAC value is a measure of inhalational anesthetic potency. • It is defined as the minimum alveolar anesthetic concentration ( % of the inspired air) at which 50% of patients do not respond to a surgical stimulus. • MAC values are additive and lower in the presence of opioids.
OIL GAS PARTITION CO-EFFICIENT Higher the Oil: Gas Partition Co-efficient lower the MAC . E.g., Halothane 1.4 220 0.8
Inhalation Anesthetic MAC value % Oil: Gas partition Nitrous oxide >100 1.4 Desflurane 7.2 23 Sevoflurane 2.5 53 Isoflurane 1.3 91 Halothane 0.8 220
Clinical case • KJ is a 7-year-old, 20-kg boy who has been undergoing multidrug chemotherapy for aggressive osteosarcoma of his right femur. The time has now come for a surgical resection. • 8:00 PM (night before the operation): Dr. S, the anesthesiologist, provides reassurance and revisits the importance of fasting after midnight to prevent aspiration of gastric contents while under general anesthesia. • 6:30 AM: KJ clings to his mother and appears anxious, cachectic, and in some pain. His vital signs are stable with an elevated pulse of 120 and a blood pressure of 110/75.
Clinical case • An oral dose of midazolam is given to relieve anxiety and to allow KJ to separate from his parents. • 7:00 AM: Dr. S injects a small amount of lidocaine subcutaneously before inserting an intravenous catheter (which he carefully conceals from KJ until the last possible moment). Through the catheter, Dr. S delivers an infusion of morphine sulfate for analgesia.
Clinical case • 7:30 AM: Dr. S rapidly induces anesthesia with an intravenous bolus of 60 mg (3 mg/kg) of thiopental (a barbiturate; Within 45 seconds, KJ is in a deep anesthetic state. The doctor adds a dose of intravenous succinylcholine (a depolarizing muscle relaxant) to facilitate endotracheal intubation, and KJ is placed on artificial respiration. • 7:32 AM: A mixture of inhaled general anesthetics consisting of 2% isoflurane, 50% nitrous oxide, and 48% oxygen is provided through the ventilator to maintain the anesthetic state. • 7:50 AM: KJ shows no response, either through movement or increased sympathetic tone (e.g., increased heart rate, increased blood pressure), to the first surgical incision.
Clinical case • 12:35 PM: After a long surgery, Dr. S stops the isoflurane and nitrous oxide and turns on pure oxygen for a few minutes. • 12:45 PM: In less than 10 minutes, KJ is breathing spontaneously and is able to respond to questions, although he is still somewhat groggy. KJ's parents are relieved to find him awake and alert after more than 5 hours of anesthesia.
Questions 1. What determines the rate of induction and recovery from anesthesia? 2. What are the advantages of using a mixture of two anesthetics (in this example, nitrous oxide and isoflurane) instead of just one or the other? 3. Why did Dr. S give pure oxygen for a few minutes following the cessation of anesthetic administration?
Inhalational anesthetics Nitrous oxide: • Safest inhalational anesthetic. • Very weak anesthetic but a good analgesic. • No toxic effect on the heart, liver and kidney. • Administered with more potent anesthetics to hasten the uptake of the other agent(s)
Inhalational anesthetics Nitrous oxide • Commonly used for dental procedures • Quick induction and recovery. • Caution about diffusional hypoxia megaloblastic anemia.
Inhalational anesthetics Halothane: • It is a potent and pleasant anesthetic. • It sensitizes the heart to catecholamines. • It dilates bronchus – last resort in status asthmaticus. • It inhibits uterine contractions which can lead to severe bleeding – not used in labor. • Halothane hepatitis and malignant hyperthermia can occur.
Inhalational anesthesia Malignant Hyperthermia • Side effect of halogenated anesthetics • Fever of 110°F or more • Life threatening • Treatment: dantrolene (Dantrium) • Dantrolene is a muscle relaxant that acts by abolishing excitation-contraction coupling in muscle cells, probably by action on the ryanodine receptor.
Inhalational anesthetics Isoflurane: • It is commonly used with oxygen or nitrous oxide. • Its pungency can irritate the respiratory system. • No reports of hepatotoxicity.
Inhalational anesthetics Desflurane: • It is delivered through special vaporizer. • It is a popular anesthetic for day care surgery. • Induction can be troublesome and it can irritates the air passages producing cough and laryngospasm. • Recovery is fast as cognitive and motor impairment are short lived.
Inhalational anesthetics Sevoflurane: • Induction and recovery is fast. • It is an effective bronchodilator due to lack of pungency. • It is a good anesthetic in patients with myocardial ischemia. • Some concerns about nephrotoxicity.
Anesthetic B:G PC O:G PC Features Notes Halothane 2.3 220 PLEASANT Arrhythmia Hepatitis Hyperthermia Enflurane 1.9 98 PUNGENT Seizures Hyperthermia Isoflurane 1.4 91 PUNGENT Widely used Sevoflurane 0.62 53 PLEASANT Ideal Desflurane 0.42 23 IRRITANT Cough Nitrous 0.47 1.4 PLEASANT Anemia
Respiratory effects of inhalational anesthetics. Spontaneous ventilation with all of the halogenated inhalational anesthetics reduces minute volume of ventilation in a dose- dependent manner (lower panel). This results in an increased arterial carbon dioxide tension (top panel). Differences among agents are modest.
General anesthetics Parenteral anesthetics (IV): • These are used for induction of anesthesia. • Rapid onset of action. • Also reduce the amount of inhalation anesthetic for maintenance. • E.g., Thiopental, Midazolam Propofol, Etomidate, Ketamine.
Intravenous anesthetics Thiopental (Pentothal): • It is an ultra short acting barbiturates. • A typical induction dose produces duration of anesthesia of 5-8 minutes. • The principal mechanism limiting anesthetic duration after single dose is redistribution from brain to other tissues like skeletal muscle. • A single dose can produce psychomotor impairment for about 8 hrs.
Inhalational anesthetics Thiopental • It can be used for rapid control of seizures. • Thiopental (barbiturates) can induce fatal attacks of porphyria in patients with acute intermittent or variegate porphyria • Methohexital is another barbiturate which is preferred anesthetic in patients undergoing ECT because of its short duration of action.
Intravenous anesthetics Propofol (Diprivan): • Most commonly used IV anesthetic for both induction and maintenance. • Recovery is rapid and clearer than thiopenthal makes it best for day care surgery - residual impairment is less marked. • Anti-emetic in action.
Intravenous anesthetics Propofol • One of the most frequent side effects is pain on injection. • Rare and potentially fatal complication, propofol infusion syndrome (PRIS), after prolonged and high dose, which is characterized by acidosis and rhabdomyolosis.
Intravenous anesthetics Etomidate: • It is primarily used for anesthetic induction of patients at risk of hypotension. • It suppress the production of steroids from the adrenal gland and not for long term infusions. • It can cause seizures and nausea/vomiting. • CVS stability is the main advantage over anesthetics.
Intravenous anesthetics Ketamine : Dissociative anesthesia • Produce - profound analgesia, involuntary movements, amnesia and breathe spontaneously. • Acts by blocking NMDA receptors • Heart rate and BP are elevated due to sympathetic stimulation. • Best suited for children and in patients with asthma as respiration is not depressed.
Intravenous anesthetics Ketamine: • Emergence delirium, hallucinations and vivid dreams occurs in 50% cases during recovery. • It is useful for burn dressing and trauma surgery. • Dangerous for hypertensive and myocardial ischemia patients.
Intravenous anesthetics Analgesics: Opioids • Opioids are the primarily used analgesics during perioperative period. • The order of potency relative to morphine is: • Sufentanil (1000 X ) • Remifentanil (300 X) • Fentanyl (100 X), Meperidine ( 0.1 X) • Respiratory depression is a major adverse effect. • Antagonist naloxone (Narcan) reverse opioids overdose and actions.
Benzodiazepines • Used for short procedures and useful in controlling seizures. • Midazolam (Versed) • Fast action, potent and short half lifes are its salient features. • Flumazenil (Romazicon) can reverse overdose / actions of benzodiazepines.
Newer anesthetics i.v α-2 adrenergic agonists: Dexmedetomidine • It is FDA approved for short term sedation in non-intubated patients. • Activation of α-2 receptors produces sedation and analgesia. • It is a sedative-hypnotic that produce analgesia with little respiratory depression and mild drop in blood pressure.
Anesthetic I.V Duration mins Analgesia Muscle relaxation Others Thiopental 5 - 10 --- --- Respiratory depression Propofol 5-10 --- --- Respiratory depression Ketamine 5-10 +++ --- Hallucinations Midazolam 5-20 --- +++ Amnesia Fentanyl 5-10 +++ --- Respiratory depression