General Anesthetics PDF Lecture Notes - Batterjee Medical College 2024

General Anesthetics Dr. Ahmed Mohammed Saaduddin Sapri Assistant Professor and Consultant of OMFS Batterjee Medical College – Jeddah Monday 11 March 2024 Lecture Content: ꟷ ꟷ ꟷ ꟷ ꟷ ꟷ ꟷ ꟷ Definition Balanced Anesthesia. History of General Anesthesia. General Anesthesia in Dentistry. Classification of...

General Anesthetics Dr. Ahmed Mohammed Saaduddin Sapri Assistant Professor and Consultant of OMFS Batterjee Medical College – Jeddah Monday 11 March 2024 Lecture Content: ꟷ ꟷ ꟷ ꟷ ꟷ ꟷ ꟷ ꟷ Definition Balanced Anesthesia. History of General Anesthesia. General Anesthesia in Dentistry. Classification of General Anesthetics. Phases of General Anesthesia. Properties of Ideal Anesthetic Agent. Inhalational Anesthetics. Introduction Introduction What is the General Anesthesia (GA)?! General anesthesia refers to drug-induced (anesthetics) reversible loss of sensation and a complete loss consciousness “awareness” that feels like a very deep sleep. GA Analgesia Lack of Awareness & Amnesia Skeletal Muscle Relaxation Suppression of Undesirable Reflexes Sedation & Anxyolysis Introduction What are the five important benefits of the GA? 1) Analgesia [loss of pain sensation] 2) Lack of awareness [consciousness] 3) Amnesia [memory loss] 4) Sedation and reduced anxiety 5) Skeletal muscle relaxation and Suppression of undesirable reflexes GA Analgesia Lack of Awareness & Amnesia Skeletal Muscle Relaxation Suppression of Undesirable Reflexes Sedation & Anxiolysis Introduction Balanced Anesthesia: Since it is not possible to achieve ideal anesthesia with a single drug as there is no single anaesthetic agent that can produce all the desired anesthetic features. Accordingly, the anaesthetic protocol includes the use of multiple drugs (IV-anesthetics for induction, inhalational anesthetics for maintenance, sedative hypnotics, opioids “analgesics”, neuromuscular blocking drugs) to minimize the adverse effects of using single anesthetic agent. GA Analgesia Lack of Awareness & Amnesia Skeletal Muscle Relaxation Suppression of Undesirable Reflexes Sedation & Anxiolysis History History Hanaoka Seishu; 1804 The first reliable documentation of an operation to be performed under general anesthesia was conducted by the Japanese surgeon “Hanaoka Seishu”, in 1804 who performed a partial mastectomy for breast cancer on a 60-year-old woman. He also used it to remove cancers of the oropharynx, to remove necrotic bone, and to perform amputations of the extremities in Japan. History Over several decades, Oral and maxillofacial surgeons have been at the forefront of anesthesia and pain control among all dental specialties and have been providing safe outpatient anesthesia. Dr. Horace Wells; 1844: He is the pioneer of the modern surgical anesthesia. He demonstrated the use of nitrous oxide gas “laughing gas” in the prevention of pain during surgery. Dr. William Morton; 1864: He was credited for the first anesthetic (known as Ether Day) and he solidified the foundation for the use of anesthetics in dental practice. He demonstrated the use of Ether vapors for the removal of a jaw tumor. History Dr. Greene Vardeman Black; 1883: The father of modern dentistry, founding dean of Northwestern School of Dentistry, and general anesthesia educator. He developed the carious lesion classification system used by dentists to this day. Also, he lectured on the “Introduction of Bromide of Ethyl as an Anesthetic for Dental Purposes or Any Very Short Operation” in1883. Dr. Charles Teeter; 1902: He introduced the first anesthesia machine capable of delivering N2O/O2, ether, and chloroform. History Dr. John Lundy ;1926: He introduced the concept of the balanced anesthesia. Dr. Adrian Hubbell; 1970: He pioneered and popularized the intravenous office-based outpatient general anesthesia among OMFS by administering barbiturates. He also advocated the utility and safety of recovering patients on their side or abdomen postoperatively to prevent aspiration of vomitus. John Lytle; 1980s: He authored many early OMS anesthesia safety articles in the professional literature. General Anesthesia in Dentistry Indications for General Anesthesia in Dentistry In dental practice, need for general anesthesia is determined on an individual basis. It is indicated in: 1) Mentally challenged patients: In these patients, conduct of dental procedures safely under local anesthesia could be difficult. 2) Children: In small children where attempts to use local anesthesia alone or with conscious sedation has been unsuccessful or the child does not cooperate, dental procedures need to be carried out under general anesthesia. 3) Patients allergic to local anaesthetic. 4) Prolonged traumatic procedures. 5) Inability to safely inject the local anesthesia (e.g., severe trismus) General Anesthesia in Dentistry Depending on the health status of the individual and nature of dental procedure to be undertaken, general anesthesia when indicated can be administered on: 1) Dental chair anesthesia “Office based anesthesia” on outpatient basis. 2) Day care anesthesia (patient is admitted and discharged on the same day) for oral surgical procedures lasting not more than one hour. 3) Inpatient an anesthesia for extensive procedures. Classification Classification Phases of General Anesthesia Phases of General Anesthesia Before Surgery (Premedication) Before the surgery the anesthesiologist During Surgery 1) will meet the patient and evaluate his Induction usually by an IV-anesthetic (propofol or thiopental), After Surgery (Recovery) The patient is introduced to the recovery room to be under close medical condition and he may 2) Neuromuscular blocker (NMB), supervision until his consciousness and prescribe to the patient an Anxiolytic 3) Maintenance usually by inhalational the protective reflexes are restored with &/or Metoclopramide to hasten gastric evacuation. anesthetics. stable respiration and circulation. Steps of General Anesthesia INTUBATION INDUCTION IV-Induction ▪ MAINTENANCE Inhalational induction General anesthesia in adults is normally induced with an IV agent like propofol, producing unconsciousness in 30 to 40 seconds. ▪ Additional inhalation and/or IV drugs may be given to produce the desired depth of anesthesia and this often includes an IV neuromuscular blocker such as rocuronium, or succinylcholine to facilitate tracheal intubation and muscle relaxation. ▪ Endotracheal intubation is done to: ▪ Maintenance is commonly provided with Keep the airway open in order to volatile anesthetics which offer good give oxygen in association with the control over the depth of anesthesia. inhalational anesthetics. ▪ Opioids (e.g., Fentanyl) are used for analgesia along with inhalation agents, as the latter are not good analgesics. Properties of Ideal Anesthetic Agent Properties of an Ideal Anesthetic Agent: 1) Inexpensive, 2) Environmentally safe, 3) Doesn’t react with other compounds (e.g., plastic pipes and metal tubes or cylinders), 4) Non-flammable (non-explosive and doesn't support combustion), 5) Long shelf life (i.e., stable over a range of temperatures, doesn’t degraded by light and doesn’t require a preservative), 6) Pleasant (non-pungent) and non-irritant (non-painful), 7) Easy and controllable administration (titratability), 8) Potent at low concentration, 9) Provide adequate sedation, analgesia, muscle relaxation and amnesia; 10) Wide margin of safety, 11) Smooth induction and recovery, 12) Minimal effects on cardiovascular functions (cardiostability) and bronchodilator. Inhalational Anesthetics Defintion Definition: Inhalational anesthetics are anesthetics which are administered in a gaseous form. They are used primarily for maintenance of anesthesia after administration of an IV agent. General Characteristics General Characteristics: 1) Easy administration with the ability to change the depth of anesthesia by changing the inhaled concentration, 2) Nonflammable and nonexplosive agents. 3) They have very steep dose–response curves 4) They have a very narrow therapeutic indices (i.e., the difference in concentrations causing surgical anesthesia and severe cardiac and respiratory depression is small). General Characteristics: 6) They have no antagonists. 7) They are delivered in a recirculation system containing absorbents that remove carbon dioxide and allow rebreathing of the agents in order to minimize waste of the potent inhaled agents and decrease cost. Potent inhaled anesthetic agents are delivered in a circle absorption system containing absorbents that remove carbon dioxide and allow re-breathing of the inhaled anesthetic Classification Types Volatile Liquids (Halogenated Gases) 1) Halothane 2) Isoflurane 3) Enflurane 4) Desflurane 5) Sevoflurane Nonvolatile Anesthetic (Exist as a gas at room temperature) 1) Nitrous Oxide 2) Nobel Gases (any of the seven chemical elements that make up Group 18 (VIIIa) of the periodic table. ) a) Xenon b) Helium Mechanism of Action ▪ Old Theory Lipid Solubility ; Mayer-Overton Theory Modern Theories ▪ ▪ ▪ Activation of Gamma-aminobutyric acid (GABA) receptors Opening the two pore potassium channels Inhibition of N-methyl-D-aspartate (NMDA) receptors Mechanism of Action: Old Theory ▪ Lipid Solubility ; Mayer-Overton Theory Modern Theories ▪ ▪ ▪ Activation of Gamma-aminobutyric acid (GABA) receptors Opening the two pore potassium channels Inhibition of N-methyl-D-aspartate (NMDA) receptors Mechanism of Action: Old Theory (Lipid Solubility ; Mayer-Overton Theory) ▪ Assumption: - Anesthetic agents are highly lipid soluble molecules that can penetrate and spreads the neuronal cell membrane and affect the membrane fluidity and physical properties of the ion channels in the cell membrane.. - The anesthetic potency is correlated to the degree of lipid solubility. - Not all highly lipid soluble substances are anesthetics - Some potent anesthetics are not lipid soluble. ▪ Refutation: Meyer (left) & Overton (right) Mechanism of Action: 1) Activation of Gamma-aminobutyric acid (GABA) Receptors ▪ The GABA receptor is an ionotropic receptor activated by the inhibitory neurotransmitter γ-aminobutyric acid (GABA). ▪ Activation of the GABA receptor leads to influx of chloride ions, which causes hyperpolarization of the neuronal membranes. ▪ Anesthetic agents directly and indirectly facilitate a GABA-mediated increase in chloride conductance to hyperpolarize and inhibit neuronal membrane activity. ▪ The GABAA receptor has been identified as the main target of: - Intravenous anesthetics (e.g., propofol and etomidate) - Inhalational anesthetics (e.g., halothane, isoflurane and enflurane) Mechanism of Action: 2) Opening the Two Pore Potassium Channels Some general anaesthetic promote the opening of some of these channels, increasing the potassium conductance and hyperpolarize the neuronal membrane and thus producing a reduction in neuronal excitability that contributes to the transition to unconsciousness. Mechanism of Action: 3) Inhibition of N-methyl-D-aspartate (NMDA) Receptors ▪ The N-methyl-D-aspartate (NMDA) receptor is a receptor of glutamate, the primary excitatory neurotransmitter in the human brain. ▪ It plays an integral role in the a neuronal mechanism associated with memory formation. ▪ Certain anesthetics (e.g., nitrous oxide, xenon and ketamine) inhibit excitatory glutamate gated ion channels. Pharmacokinetics of Inhaled Anesthetics Pharmacokinetics of Inhaled Anesthetics ▪ Inhaled anesthetics have a unique “inhalation” route of administration, it provides a rapid increase in the lung concentration and access to the blood stream without necessitating intravenous access. ▪ Diffusion of the inhaled anesthetic gas from the lung alveoli to blood depends on: 1) The partial pressure between the alveoli (air) and blood. 2) The partition coefficient between tissues. 3) Cardiac output to pulmonary and cerebral blood vessels. ▪ Elimination: - Inhalational anesthetics are eliminated unchanged by the lungs via expiration - Agents which are soluble in fat and tissues require longer time for elimination and therefore recovery is slower Potency of Inhaled Anesthetics Minimum Alveolar Concentration (MAC) Potency is defined quantitatively as the minimum alveolar concentration (MAC) MAC is the minimum concentration of an anaesthetic in alveoli required to produce immobility in response to a painful stimulus (e.g., incision) in 50% patients. MAC is the median effective dose of the anesthetic (ED50), expressed as the percentage of gas in a mixture required to achieve that effect. The lower the MAC value, the more potent the agent (i.e., Isoflurane is more potent than Sevoflurane). MAC is independent of gender and weight. Factors affecting the MAC: - Factors that reduce the MAC (make the patient more sensitive): Increased age (>40y), Pregnancy, hypothermia and Hypotension. - Factors that increase the MAC (make the patient less sensitive): Hyperthermia and chronic alcoholism Anesthetics Halothane “1956” It is the prototype to which newer inhalation anesthetics are compared. Properties: It is a noninflammable, colorless volatile liquid with a sweet smell that is unstable in light (decompose to hydrogen fluoride, hydrogen chloride & hydrogen bromide). It has a direct myocadiac depressant It is a potent bronchodilator. It is a skeletal muscles relaxant. It reduces renal blood flow and GFR Advantages: 1. It is a potent anesthetic 2. It has a rapid induction and recovery. 3. It has a pleasant non-irritant odor (formerly it was the anesthetic of choice for inhalation induction in pediatrics) Disadvantages: 1. It is a weak analgesic and usually coadministered with opioids or local anesthetics. 2. It has an arrhythmogenic effect with adrenaline 3. Hepatotoxic (postoperative liver failure) in 1:50,000 patients 4. Malignant hyperthermia Enflurane “1973” ▪ It is a colorless, noninflammable, volatile liquid with a sweety smell and light sensitive gas. ▪ It is similar to halothane except that: - It has no arrhythmogenic effect with adrenaline (i.e., Does not sensitize the heart to adrenaline). - It is metabolized to a lesser extent than halothane and therefore safer regarding the liver toxicity. - It may precipitate seizures in epileptics and should be avoided in them. Isoflurane “1981” ▪ It is colorless, nonflammable, volatile liquid with pungent odor. ▪ It is commonly used now because: - It is more potent than halothane - It has no arrhythmogenic effect with adrenaline (i.e., Does not sensitize the heart to adrenaline). - It has a negligible metabolism and therefore safer regarding the liver toxicity - It does not provoke seizures - It is the preferred anesthetic in neurosurgical procedures because it causes milder cerebral vasodilation and less increase in intracranial pressure than other anesthetics. Desflurane “1992” ▪ It is a colorless nonflammable, volatile liquid with a pungent odor. ▪ It is the most popular anesthetic for outpatient procedures as it has a very rapid onset and recovery due to low blood solubility. ▪ It has a low volatility, requiring administration via a special heated vaporizer. ▪ It stimulates respiratory reflexes (so, it is not used for inhalation induction). ▪ It is relatively expensive and thus rarely used for maintenance during extended anesthesia. ▪ Its degradation is minimal and tissue toxicity is rare. Sevoflurane “1994” ▪ It is a colorless nonflammable liquid with a non-pungent odor that makes it an ideal inhalational induction agent in pediatric patients. ▪ It has a potency similar to enflurane. ▪ It has a rapid onset and recovery due to low blood solubility. ▪ Its vapor pressures allow for the use of a conventional vaporizer. ▪ It is metabolized in liver but its metabolites formed in the liver may cause renal damage (so it should be avoided in renal patients). Xenon ▪ It is a potent anesthetic ▪ It has a rapid induction and recovery as t is insoluble in blood and tissues ▪ It has no effect on hepatic, renal or pulmonary functions ▪ It provides a stable intraoperative blood pressure. ▪ It is not metabolized in the body. ▪ It is expensive as it is not manufactured but extracted from air and administered in hyperbaric conditions (impractical in surgery). Nitrous Oxide ▪ It produces light anesthesia (low potency) and it is a weak muscle relaxant but it is a strong analgesic. ▪ It has a rapid and smooth induction and recovery ▪ It is a non-inflammable gas with a slightly sweetish non-irritating odor. ▪ It has insignificant postoperative nausea ▪ It has a little effect on cardiovascular or respiratory functions and it is quickly removed unchanged from lungs. ▪ It is non-toxic to liver, kidney and brain. ▪ Its repeated use can depress the bone marrow and precipitate anemia. HALOTHANE Use ENFLURANE It is a weak analgesic Cardiac Arrhythmogenic effect with adrenaline SEVOFLURANE (1) It is the most popular anesthetic for short procedures due to very rapid onset & recovery. (2) Requires administration via a special heated vaporizer (High Cost) Contraindicated in epileptic patients as it precipitate seizures Vascular Liver DESFLURANE Not used today due to its arrhythmic effect and hepatotoxicity Brain Respiratory ISOFLURANE Preferred anesthetic in neurosurgical procedures because it causes mild cerebral vasodilation and less increase in intracranial pressure No arrhythmogenic effect with adrenaline DECREASE BLOOD PRESSURE Potent bronchodilator Hepatotoxic They have a pungent odor that stimulates respiratory reflexes (salivation, coughing, laryngospasm), so it is not used for inhalation induction Nontoxic Has low pungency and hence low respiratory irritation that makes it useful for inhalation induction, especially with pediatric patients who do not tolerate IV placement Adverse Effects of Inhaled Anesthetics Central Nervous System (CNS): Cardiovascular Effects(CNS): - Desflurane is a pulmonary irritant and can cause bronchospasm. Liver Effects: - Halothane causes Cardiac Arrhythmia (inconsistent heartbeat pattern) Respiratory Effects: - They vasodilate the cerebral blood vessels and rise the intracranial blood pressure. Halothane can cause acute liver injury (halothane hepatitis). Postoperative Nausea and Vomiting: - All inhaled anesthetics are emetogenic and can induce postoperative nausea and vomiting (PONV). Adverse Effects of Inhaled Anesthetics Malignant Hyperthermia (MH): o Definition: A life-threatening hypermetabolic disorder of skeletal muscle that occurs secondary to exposure to halogenated anesthetics (especially Halothane) or the neuromuscular blocker Succinylcholine. o Incidence: It is a rare (1:20000) o Cause: - Genetic abnormality in calcium channel in Ryanodine Receptors in sarcoplasm reticulum (SR) of muscle cells, leading to massive influx of calcium following exposure to inhaled anesthetics or succinylcholine. - Increased susceptibility to MH is suspected in burn victims, individuals with muscular dystrophy & osteogenesis imperfecta. o Pathophysiology: - MH causes an uncontrolled increase in skeletal muscle oxidative metabolism, overwhelming the body’s capacity to supply oxygen, remove carbon dioxide, and regulate temperature. o Symptoms: Muscle spasm, Hyperthermia, Tachycardia and Hypertension. o Treatment: - Administration of Dantrolene (a muscle relaxant that blocks calcium ion release from calcium ion channels) - Cooling the patient. Adverse Effects of Inhaled Anesthetics Malignant Hyperthermia (MH): Intravenous Anesthetics Propofol – Thiopental – Etomidate – Ketamine - Midazolam Intravenous Anesthetics: ▪ They are commonly used for rapid induction of anesthesia. ▪ They are highly lipophilic drugs, upon administration, they rapidly distribute in the highly vascular tissues including the brain causing rapid induction of anesthesia. ▪ Termination of anesthesia is due to rapid redistribution of the drug from nervous tissues to other tissues such as muscles, viscera and adipose tissue. TOTAL INTRAVENOUS ANESTHESIA [TIVA] ▪ It is a technique of general anesthesia that uses only intravenous anesthetic agents given exclusively without the use of inhalational agents. ▪ The prolonged administration of intravenous anesthetics saturate the adipose tissue and slow down the redistribution from the brain with subsequent prolonged anesthesia. Propofol (Diprivan) ▪ It is the most commonly used IV-agent for induction of anesthesia ▪ It is administered as an oil-in-water emulsion that cause pain at the injection site. ▪ Fospropofol is a water-soluble derivative that is less painful and converted to propofol in the body. ▪ Advantages 1. Rapid and pleasant induction with rapid recovery and clarity of mental status. ▪ Disadvantages 1. Pain at the injection site. 2. Respiratory center depressant. 3. Markedly decreases the blood pressure. 4. Propofol related infusion syndrome (PRIS): - It occurs with prolonged infusion. - It consists of fever, severe metabolic acidosis, skeletal muscle necrosis (rhabidomyoloisis), hyperkalamia, lipemia, renal failure, arrhythmia and cardiovascular collapse. Thiopental ▪ It is the only remaining barbiturate in common use as an IV-agent for induction of anesthesia ▪ It is only used for induction of anesthesia (not for maintenance) ▪ It has a very rapid and pleasant induction within 20 seconds and its anesthetic effect lasts for 5 – 15 minutes. ▪ It is highly alkaline solution ▪ Adverse effects: 1. SC or IM injection causes local tissue necrosis and ulceration. 2. Respiratory center depressant. 3. High dose can cause hypotension 4. Myocardial depressant. 5. Like other barbiturates, it is hepatic microsomal enzyme inducer. Etomidate ▪ It is very similar to thiopental but is less hypotensive and less myocardial depressant. ▪ Adverse Effects 1. It suppress the production of adrenal steroids, an effect that is associated with increase in mortality rate in severely ill patients (e.g., sepsis) 2. Postoperative nausea and vomiting. Ketamine (Ketalar) ▪ The characteristic state observed after an induction dose of ketamine is known as “dissociative anesthesia” wherein the patient’s eyes remain open with slaw nystagmic gaze. ▪ Mechanism of action: inhibition of the NMDA-receptors. ▪ It is the preferred IV-agent in pediatric due to low rate of adverse effects. ▪ It differs from other IV-anesthetic agents in: 1. It produce significant analgesia 2. It raises the blood pressure 3. Doesn’t affect the respiratory center ▪ Adverse Effects 1. Hallucinations and psychiatric disturbance in recovery. Midazolam ▪ It is a very short acting Benzodiazpines that has a rapid onset and short duration. ▪ It is commonly used in dentistry ▪ Its action can be reversed with Flumazenil. Thank You