Anesthesia Lecture Notes PDF

Anesthesia Dr. Fatemah Alherz PHS 310 Week 10 1 Objectives of lecture 1 2 3 4 Explain basic Explain broad Study classification Describe major principles of mechanisms of...

Anesthesia Dr. Fatemah Alherz PHS 310 Week 10 1 Objectives of lecture 1 2 3 4 Explain basic Explain broad Study classification Describe major principles of mechanisms of of features of local general anesthesia action general anesthetics anesthetic drugs 2  Anesthesia For patients undergoing surgical or medical procedures, different levels of sedation can provide important benefits To facilitate procedural interventions. These levels of sedation range from anxiolysis to general anesthesia and can create: Sedation and reduced anxiety Lack of awareness and amnesia Skeletal muscle relaxation Suppression of undesirable reflexes Analgesia 3  General anesthesia General anesthesia is a reversible state of central nervous system (CNS) depression, causing loss of response and perception of all sensations. The anesthetic state includes loss of consciousness, amnesia, and immobility (a lack of response to noxious stimuli) but not necessarily complete analgesia. Because no single agent provides all desired objectives, several categories of drugs are combined to produce the optimum level of sedation required (adjunct agents) 4 Adjunct agents H2 blockers to reduce gastric acidity Benzodiazepines (e.g., diazepam) to relieve anxiety and facilitate amnesia Opioids (e.g., fentanyl) for analgesia Antihistamines to prevent allergic reactions Antiemetics to prevent aspiration of stomach contents and postsurgical nausea and Anticholinergics (e.g., atropine) to prevent bradycardia and secretion of fluids into the respiratory tract Neuromuscular blockers to provide muscle relaxation. Pre-medications facilitate smooth induction of anesthesia and lower required anesthetic doses. 5  Anesthesia General anesthetics Local anesthetics 1. Inhaled anesthetics 1. Amides Halothane Lidocaine Isoflurane Prilocaine (dental anesthetic) Desflurane Bupivacaine Sevoflurane Mepivacaine Nitric oxide Ropivacaine 2. IV 2. Esters Propofol Procaine Barbiturates (thiopental) Chloroprocaine Benzodiazepines Tetracaine Etomidate Ketamine Dexmedetomidine 6 General anesthesia Inhaled anesthetics Inhalation and/or (except for nitrous intravenous (IV) oxide) are injection halogenated hydrocarbons 7  General anesthetics distribute well to all body parts, becoming most concentrated in the fatty tissues. The CNS is the primary site of action of anesthetics. Most likely, loss of consciousness and amnesia Pharmacodynamic ensue from supraspinal action (i.e., action in the of anesthesia brainstem, midbrain, and cerebral cortex), While immobility in response to noxious stimuli is caused by depression of both supraspinal and spinal sensory and motor pathways. Different sites in the CNS are differentially affected by general anesthetics, giving rise to the classical stages observed with increasing anesthetic depth. 8  Stages of anesthesia General anesthesia has three stages: induction, maintenance, and recovery. Induction is the time from the administration of a potent anesthetic to the development of effective anesthesia (IV anesthetic) Maintenance provides sustained anesthesia (inhaled anesthetic) Recovery is the time from discontinuing anesthetic until consciousness and protective reflexes return. ✓Rapid induction and recovery are desirable. 9 Depth of anesthesia Depth of anesthesia is the degree to which the CNS is depressed 10 Inhalation anesthetics 11  Inhalation anesthetics Inhaled gases are used primarily for maintenance of anesthesia after administration of an IV agent Depth of anesthesia can be rapidly altered by changing the inhaled concentration. Inhalational agents have very sharp dose–response curves and very narrow therapeutic indices, so the difference in concentrations causing surgical anesthesia and severe cardiac and respiratory depression is small. Require close monitor No antagonists exist 12  Potency Measured by minimum alveolar concentration (MAC) MAC= concentration that prevents movement in 50% of patients in response to a noxious stimulus​ Expressed as the percentage of gas in a mixture required to achieve that effect Potency is inversely related to MAC​ (small for potent anesthetics) MAC decreases with increase age, pregnancy, and hypotension 13  Pharmacokinetics A. Anesthetic Uptake and Distribution The driving force for uptake of an inhaled anesthetic is the alveolar concentration. Two parameters that the anesthesiologist can control determine how quickly the alveolar concentration changes: (1) Inspired concentration or partial pressure (2) Alveolar ventilation B. Factors Controlling Uptake (1) Solubility (2) Cardiac output (3) Alveolar-to-venous partial pressure gradient 14  Anesthetic Uptake and Distribution 1. Inspired concentration or partial pressure The partial pressure of an anesthetic gas at the origin of the respiratory pathway is the driving force moving the anesthetic into the alveolar space and, thence, into the blood (Pblood), which delivers the drug to the brain and other body compartments. Because gases move from one body compartment to another according to partial pressure gradients, a steady state is achieved when the partial pressure in each compartment is equivalent to that in the inspired mixture. Palveoli = Pblood = Pbr “ steady state” The concentration of the inhaled anesthetic in the alveoli determines the rate of uptake. A higher inspired concentration results in faster uptake and induction 15  Anesthetic Uptake and Distribution 2. Alveolar Ventilation: An increase in pulmonary ventilation is accompanied by only a slight increase in arterial tension of an anesthetic with low blood solubility but can significantly increase the tension of agents with moderate to high blood solubility Thus, hyperventilation increases the speed of induction of anesthesia with inhaled anesthetics that would normally have a slow onset. Depression of respiration by opioid analgesics slows the onset of inhaled anesthetic anesthesia unless ventilation is manually or mechanically assisted. 16  Anesthetic uptake (removal to peripheral tissues other than the brain) 1-Solubility in blood One of the most important factors influencing the transfer of an anesthetic from the lungs to the arterial blood is its solubility characteristics. The blood: gas partition coefficient is a useful index of solubility and defines the relative affinity of an anesthetic for the blood compared with that of inspired gas. The solubility of inhaled anesthetics determines > the speed of induction and recovery ✓Anesthetic gas with low blood solubility (e.g. nitrous oxide) > diffuses from the alveoli into the circulation rapidly, and little anesthetic dissolves in the blood. Rapid induction and recovery ​Higher blood/gas partition coefficient (e.g. halothane) Slower induction and recovery 17 Solubility Desflurane and sevoflurane (newer agents) provide rapid onset and recovery due to low blood solubility. Isoflurane > higher blood solubility typically used only when cost is a factor. 18 Anesthetic uptake cont. 2- Cardiac output CO affects the removal of anesthetic from the lung to peripheral tissues, which are not the site of action (CNS). Cerebral blood flow is well regulated, and the increased cardiac output will therefore increase the delivery of anesthetic to other tissues and not the brain. For inhaled anesthetics, higher CO removes anesthetic from the alveoli faster (due to increased blood flow through the lungs) and thus slows the rate of rise in the alveolar concentration of gas. Therefore, it will take longer for the gas to reach equilibrium between the alveoli and the site of action in the brain. “For inhaled anesthetics, higher CO equals slower induction”. 19  Anesthetic uptake cont. 3. Alveolar-to-venous partial pressure gradient This gradient between the alveolar and returning venous gas partial pressure results from the tissue uptake from the arterial delivery. The arterial circulation distributes the anesthetic to various tissues, and tissue uptake depends on the blood flow, blood-to-tissue partial pressure difference, and blood-to-tissue solubility coefficient. As venous circulation returns to the lung blood with low or no dissolved anesthetic gas, this high gradient causes gas to move from the alveoli into the blood. If a large alveolar-to-venous partial pressure gradient persists, the peripheral tissue gas uptake must be high, and therefore, the induction time is longer In the case of volatile anesthetics with relatively high solubility in highly perfused tissues, venous blood concentration initially is very low, and equilibrium with the alveolar space is achieved slowly. 20 Washout –termination of anesthetic effect When an inhalation anesthetic gas is removed from the inspired admixture, the body becomes the repository of anesthetic gas to be circulated back to the alveolar compartment. The same factors that influence the uptake and equilibrium of the inspired anesthetic determine the time course of its exhalation from the body. 21 Mechanisms of action No specific receptor has been identified as the locus to create a state of general anesthesia. At clinically effective concentrations, general anesthetics increase the sensitivity of the γ- aminobutyric acid (GABAA) receptors to the inhibitory neurotransmitter GABA. This increases chloride ion influx and hyperpolarization of neurons. Postsynaptic neuronal excitability and, thus, CNS activity are diminished 22 Mechanisms of action Other mechanisms: 1. Inhibition of the N-methyl-d-aspartate (NMDA) receptors. Examples of general anesthetic work on NMDA receptor > nitrous oxide and ketamine 2. Inhibitory glycine receptors are found in the spinal motor neurons. volatile 3. Inhalation anesthetics block excitatory postsynaptic currents found on anesthetics nicotinic receptors. 23 Inhaled anesthetics 24  Halothane Prototype anesthetic It was an anesthetic of choice. However, it has been replaced in most countries > due to adverse effects and the availability of other anesthetics with fewer complications low MAC>>Providing high potency However, halothane also has a high blood/gas solubility, causing slow induction and recovery. MAC=Minimum alveolar concentration 25  Adverse effects Halothane toxic metabolites can result in fatal hepatotoxicity. A rare but potentially lethal adverse effect is malignant hyperthermia (MH). The susceptibility for this adverse reaction is inherited, typically as an autosomal dominant mutation in the sarcoplasmic reticulum Ca2+ channel Halothane causes uncontrolled calcium efflux from the sarcoplasmic reticulum, with subsequent tetany and heat production. Malignant hyperthermia is treated with dantrolene, an agent that blocks calcium release from the sarcoplasmic reticulum. 26 Isoflurane Little metabolism > not toxic to the liver or kidney. It has a pungent odor and stimulates respiratory reflexes (e.g., breath holding, salivation, coughing, laryngospasm) Thus, it is not used for inhalation induction. With higher blood solubility than desflurane and sevoflurane, isoflurane takes longer to reach equilibrium, making it less ideal for short procedures; however, its low cost makes it a good option for longer surgeries. 27 Desflurane It provides very rapid onset and recovery due to low blood solubility. Its degradation is minimal and tissue toxicity is rare. Required a special machine for delivery. It causes respiratory irritation > not used for inhalation induction. It is relatively expensive and thus rarely used for maintenance during extended anesthesia. 28 Sevoflurane It has low pungent odor, allowing rapid induction without irritating the airways. This makes it suitable for inhalation induction in pediatric patients. It has a rapid onset and recovery due to low blood solubility. Low hepatotoxicity. Compounds formed from reactions in the anesthesia circuit may be nephrotoxic 29 Characteristic of some inhaled anesthesia 30 Nitrous oxide Known as laughing gas Non-irritating Potent analgesic but a weak general anesthetic It is frequently used in dental clinics Low potency > combined with other more potent agents for surgical anesthesia Poor solubility in blood > rapid induction and recovery. 31 Nitrous oxide Does not depress respiration Moderate to no effect on the cardiovascular system The least hepatotoxic of the inhalation agents Therefore> it probably the safest of inhalation anesthetics 32 Intravenous anesthetics 33  Intravenous anesthetics IV anesthesia causes rapid induction in 1 minute or less. It is the most common way to induce anesthesia before maintenance of anesthesia with an inhalation agent. IV anesthetics may be used as single agents for short procedures or administered as infusions to help maintain anesthesia during longer surgeries. 34  Intravenous anesthetics Induction: After entering the blood, a percentage of the drug binds to plasma proteins, and the rest remains unbound or “free.” The degree of protein binding depends upon the physical characteristics of the drug, such as the degree of ionization and lipid solubility. The majority of CO flows to the brain, liver, and kidney (“vessel-rich organs”). Thus, a high proportion of the initial drug bolus is delivered to the cerebral circulation and then passes along a concentration gradient from the blood into the brain. The rate of this transfer is dependent on the arterial concentration of the unbound free drug, the lipid solubility of the drug, and the degree of ionization. 35  Intravenous anesthetics Recovery: Recovery from IV anesthetics is due to redistribution away from the CNS This initial redistribution of drug into other tissues leads to the rapid recovery seen after a single IV dose of induction agent. Metabolism and plasma clearance become important only following infusions and repeat doses of a drug. Adipose tissue makes little contribution to the early redistribution of free drug following a bolus, due to its poor blood supply. However, following repeat doses or infusions, equilibration with fat tissue forms a drug reservoir, often leading to delayed recovery. 36  When CO is reduced (for example, in certain types of shock, the elderly, cardiac disease), the Effect of body compensates by diverting more CO to the reduced cerebral circulation. cardiac A greater proportion of the IV anesthetic enters the cerebral circulation under these output on IV circumstances. anesthetics Therefore, the dose of the drug must be reduced. Further reduced CO causes prolonged circulation time, so it takes longer time for the induction drug to reach the brain and exert its effects. Slow titration of a reduced dose of IV anesthetic is key to a safe induction in patient with reduced CO. 37  Intravenous anesthetics Propofol: It is widely used as the first choice for induction of general anesthesia and sedation. No analgesic effects, so supplementation with narcotics is required. Induction is smooth and occurs 30 to 40 seconds after administration. Plasma levels decline rapidly as a result of redistribution, followed by a more prolonged period of hepatic metabolism and renal clearance. The initial redistribution half-life is 2 to 4 minutes. The pharmacokinetics of propofol are not altered by moderate hepatic or renal failure. 38  Intravenous anesthetics Propofol cont. it occasionally contributes to excitatory phenomena, such as muscle twitching, spontaneous movement, yawning, and hiccups. Transient pain at the injection site is common. Decreases blood pressure without significantly depressing the myocardium. It also reduces intracranial pressure due to decreased cerebral blood flow and oxygen consumption. Propofol is commonly infused in lower doses to provide sedation. The incidence of postoperative nausea and vomiting is very low, secondary to its antiemetic properties. 39 Intravenous anesthetics Etomidate: Benefit> little to no effect on the heart and circulation> usually only used for patients with coronary artery disease or cardiovascular dysfunction. Its adverse effects include decreased plasma cortisol and aldosterone levels 40  Intravenous anesthetics Ketamine: induces a dissociated state >patient is unconscious (but may appear to be awake) and does not feel pain. This dissociative anesthesia provides sedation, amnesia, and immobility. Stimulates sympathetic > increase increased blood pressure and bronchodilation Benefit> cardiogenic shock and in asthmatic patients. Contraindication > hypertensive and stroke patients. It may be used illegally > dream-like state and hallucinations. 41 Intravenous anesthetics Dexmedetomidine Mechanism of action: α2 receptor agonist > sympatholytic Blunts undesirable cardiovascular reflexes No respiratory depression Sedation of intubated and mechanically ventilated patients in the intensive care unit (ICU) and peri-procedural (or peri- operative) sedation of non-intubated patients 42 Summary 43 Local anesthetics 44 Local anesthetics Produce loss of sensation to pain in a specific area of the body without the loss of consciousness. Routes of administration: include topical administration, SQ, epidural. 45 Mechanism of Action Block nerve conduction of sensory impulses and from the periphery to the CNS. Voltage-gated Na+ channels are blocked to prevent the transient increase in permeability of the nerve membrane to Na+ that is required for an action potential 46  Local anesthetics Action: They cause vasodilation > rapid diffusion away from the site of action and shorter duration when these drugs are administered alone. By adding the vasoconstrictor epinephrine, the rate of local anesthetic absorption and diffusion is decreased. This minimizes systemic toxicity and increases the duration of action. 47 Local Anesthetics types 48  Esters: These include: Cocaine Procaine Tetracaine Chloroprocaine 49 Amides: These include: Lidocaine Mepivicaine Prilocaine Bupivacaine Etidocaine 50 Local anesthetics 51 local anesthetic Prila® cream is a local anesthetic (numbing medication) containing lidocaine and prilocaine 52 Local anesthetics Metabolism: Amides >primarily in the liver. -Prilocaine, a dental anesthetic, is also metabolized in the plasma and kidney, and one of its metabolites may lead to methemoglobinemia. Esters > by plasma pseudo-cholinesterase - Metabolite para-aminobenzoic acid (PABA)> may cause allergy in some patients 53 Local anesthetics Allergic reactions Common adverse effect May be due to epinephrine added to the local anesthetic Rare with amide anesthetics and common with esters Allergy to one ester > avoid others (all produce metabolite responsible for allergy) 54  Systemic toxicity Local anesthetic may cause systemic toxicity by : all systemic toxic reactions associated with local anesthetics are the result of over-dosage leading to high blood levels of the agent given. Neurotoxicity resulting from local effects produced by direct contact with neural elements. CNS toxicity: Initial imbalanced brain excitement (seizure) followed by generalized CNS depression (cardiac and respiratory depression) 55 Case An elderly man with type 2 diabetes mellitus and ischemic pain in the lower extremities is scheduled for femoral-to-popliteal bypass surgery. He has a history of hypertension and coronary artery disease with symptoms of stable angina and can walk only half a block before pain in his legs forces him to stop. He has a 50- pack-year smoking history but stopped 2 years ago. His medications include atenolol, atorvastatin, and hydrochlorothiazide. The nurse in the pre-operative holding area obtains the following vital signs: temperature 36.8°C (98.2°F), blood pressure 168/100 mm Hg, heart rate 78 bpm, oxygen saturation by pulse oximeter 96% while breathing room air, pain 5/10 in the right lower leg. What anesthetic agents will you choose and why? Does the choice of anesthetic make a difference? 56  This patient has significant underlying cardiac risk involving major stressful surgery. Balanced anesthesia would begin with intravenous agents that cause minimal changes in blood pressure and heart rate such as propofol or etomidate, combined with potent analgesics such as fentanyl (see Chapter 31) to block undesirable stimulation of autonomic reflexes. maintenance of anesthesia could incorporate inhaled anesthetics that ensure unconsciousness and amnesia, additional intra-venous agents to provide intraoperative and postoperative analgesia, and, if needed, neuromuscular blocking drugs (see Chapter 27) to induce muscle relaxation. The choice of inhaled agent(s) would be made based on the desire to maintain sufficient myocardial contractility, systemic blood pressure, and cardiac output for adequate perfusion of critical organs throughout the operation. Rapid emergence from the combined effects of the chosen anesthetic drugs would facilitate the patient ’s return to a baseline state of heart function, breathing, and mentation. 57 58