Anesthesia PDF

ANESTHESIA I. Overview of General Anesthesia General anesthesia induces a reversible central nervous system (CNS) depression, causing loss of consciousness and perception of stimuli, which is crucial for various medical or surgical procedures. Key benefits include: 1. Sedation and Reduced Anx...

ANESTHESIA I. Overview of General Anesthesia General anesthesia induces a reversible central nervous system (CNS) depression, causing loss of consciousness and perception of stimuli, which is crucial for various medical or surgical procedures. Key benefits include: 1. Sedation and Reduced Anxiety: Helps calm the patient. 2. Amnesia: Patients lack awareness or memory of the procedure. 3. Muscle Relaxation: Eases surgical manipulation. 4. Reflex Suppression: Reduces involuntary reflexes. 5. Analgesia: Provides pain relief. Since no single drug achieves all these effects, multiple agents are combined for effective anesthesia. These can include: Preanesthetics: Calm patients, provide analgesia, and prevent potential side effects. Neuromuscular Blockers: Aid in tracheal intubation and facilitate surgery. Inhaled Anesthetics: Most are volatile halogenated hydrocarbons, with nitrous oxide as a non-volatile exception. IV Anesthetics: A diverse group used for rapid anesthesia induction. II. Patient Factors in Anesthesia Selection Choosing the right anesthetic agents involves assessing the patient's medical status, including organ function, concurrent medical conditions, and medications to ensure safe, efficient anesthesia. A. Status of Organ Systems 1. Cardiovascular System: ○ Anesthetic agents often depress cardiovascular function. ○ Patients with conditions like coronary artery disease, heart failure, or dysrhythmias are at increased risk. ○ Hypotension may occur, leading to reduced blood flow and tissue injury. ○ Vasoactive drugs may be needed, and agents like halothane can make the heart more susceptible to arrhythmias with sympathomimetic drugs. 2. Respiratory System: ○ Respiratory health is critical, particularly in patients with asthma or ventilation abnormalities. ○ Inhaled anesthetics tend to depress respiration but may also provide bronchodilation. ○ IV anesthetics and opioids can significantly suppress breathing, potentially complicating ventilation and oxygenation. 3. Liver and Kidney: ○ These organs play essential roles in the distribution and elimination of anesthetics. ○ Metabolites from halogenated hydrocarbons (e.g., fluoride and bromide) can accumulate and harm the liver and kidneys, especially with repeated use. 4. Nervous System: ○ Neurologic conditions, such as epilepsy or neuromuscular disorders, influence anesthetic selection. 5. Pregnancy: ○ Pregnancy requires careful anesthetic management due to fetal organogenesis risks, especially in early pregnancy. ○ Nitrous oxide use is limited to avoid fetal aplastic anemia risk, and benzodiazepines are avoided to prevent birth defects and complications like hypotonia in the newborn. B. Concomitant Drug Use 1. Multiple Adjunct Agents: ○ Common preanesthetic medications include: H2 blockers (e.g., famotidine) to reduce gastric acidity. Benzodiazepines (e.g., midazolam) for anxiety relief and amnesia. Analgesics, such as opioids (e.g., fentanyl) or non-opioids (e.g., acetaminophen). Antihistamines (e.g., diphenhydramine) to prevent allergic responses. Antiemetics (e.g., ondansetron) to control nausea. Anticholinergics (e.g., glycopyrrolate) to prevent bradycardia and secretion buildup. ○ These agents support smooth anesthesia induction and help reduce required anesthetic doses but may intensify side effects like hypoventilation. 2. Concurrent Use of Other Drugs: ○ Pre-existing medications or substance abuse can alter anesthetic effects. ○ For instance, patients with alcohol dependence may have increased liver enzymes, accelerating anesthetic metabolism, while drug abusers may have developed tolerance to opioids. III. Stages and Depth of Anesthesia General anesthesia consists of three main stages—induction, maintenance, and recovery. These stages ensure that anesthesia is administered smoothly and safely. 1. Induction: ○ This is the phase from anesthetic administration to the onset of effective anesthesia. ○ IV Agents (e.g., propofol) are typically used in adults for rapid induction, achieving unconsciousness in 30–40 seconds. ○ Inhaled Agents (e.g., sevoflurane) are used for children without IV access due to their non-pungent nature. ○ Often, an IV neuromuscular blocker (e.g., rocuronium, vecuronium, or succinylcholine) is also administered to facilitate tracheal intubation and ensure muscle relaxation. 2. Maintenance: ○ This stage sustains the depth of anesthesia. ○ Continuous monitoring of vital signs and response to stimuli helps balance the anesthetic levels. ○ Volatile anesthetics are typically used here, allowing precise control over the anesthesia depth. ○ Opioids (e.g., fentanyl) are added for pain relief, as inhaled anesthetics are weak analgesics. ○ IV infusions may also be administered to support anesthesia during this stage. 3. Recovery: ○ This stage begins when the anesthetic agents are withdrawn. ○ The patient is monitored closely as they regain consciousness and protective reflexes. ○ Recovery mirrors induction but in reverse, as the anesthetic diffuses away from the brain rather than being metabolized. ○ If neuromuscular blockers are still active, reversal agents may be administered to aid muscle function. ○ Monitoring continues until the patient shows normal physiological responses: regular respiration, stable blood pressure and heart rate, restored reflexes, and absence of delayed effects like respiratory depression. 4. Depth of Anesthesia 1.Stage I — Analgesia: ○ Characteristics: Pain sensation decreases due to interference with sensory transmission (spinothalamic tract). ○ The patient is initially conscious and conversational, progressing to a drowsy state. ○ Additional Effects: Amnesia and reduced awareness of pain begin as the patient moves toward Stage II. 2.Stage II — Excitement: ○ Characteristics: Delirium and potentially combative behavior may appear. ○ Physiological Changes: Blood pressure and respiration often become elevated and irregular; there’s also a risk of laryngospasm. ○ Management: Rapid-acting IV agents are typically administered before inhaled anesthetics to reduce this stage’s duration. 3. Stage III — Surgical Anesthesia: ○ Characteristics: Muscle tone and reflexes diminish as CNS depression deepens, leading to muscle relaxation and loss of spontaneous movement. ○ Physiological Changes: Breathing becomes regular; skeletal muscle relaxation makes this stage optimal for surgery. ○ Caution: Careful monitoring is essential to prevent unintentional transition into Stage IV. 4. Stage IV — Medullary Paralysis: ○ Characteristics: This is a critical stage, with extreme depression of respiratory and vasomotor centers. ○ Risks: Without immediate support for ventilation and circulation, there is a high risk of fatality.IV. Inhalation Anesthetics Inhalation anesthetics are primarily used during the maintenance phase of anesthesia following initial induction by an IV agent. Their potency and rapid adjustability make them ideal for sustaining anesthesia throughout a procedure. A. Common Features of Inhalation Anesthetics Modern inhalation anesthetics, like nitrous oxide and halogenated volatile agents, are nonflammable and nonexplosive. These agents decrease cerebrovascular resistance, increasing brain perfusion, and they cause bronchodilation. However, they also reduce spontaneous ventilation and suppress hypoxic pulmonary vasoconstriction, which can affect oxygenation in under-ventilated lung areas. The movement of inhaled anesthetics from the lungs into various body tissues depends on: ○ Solubility in blood and tissues. ○ Blood flow through these compartments. These factors directly influence both induction and recovery from anesthesia. B. Potency Potency of inhalation anesthetics is defined by the Minimum Alveolar Concentration (MAC): ○ MAC represents the concentration of an anesthetic gas in the alveoli that prevents movement in response to a surgical stimulus in 50% of patients. It serves as a median effective dose (ED50). ○ A lower MAC value indicates a higher potency (e.g., sevoflurane is potent with a low MAC), while a higher MAC (e.g., nitrous oxide) signifies lower potency. Factors influencing MAC: ○ Increase MAC (lower sensitivity): Hyperthermia, CNS-stimulating drugs, chronic alcohol use. ○ Decrease MAC (higher sensitivity): Aging, hypothermia, pregnancy, sepsis, acute intoxication, concurrent IV anesthetics, and α₂-adrenergic agonists like clonidine. C. Uptake and Distribution of Inhalation Anesthetics The goal of inhalation anesthesia is to achieve a steady, optimal brain partial pressure (Pbr) of the anesthetic. This is accomplished by ensuring equilibrium between alveolar (Palv), arterial (Pa), and brain (Pbr) partial pressures. ○ Alveolar pressure (Palv) drives anesthetic movement into the bloodstream, which then transports it to the brain and other tissues. ○ Equilibrium (Palv = Pa = Pbr) signifies that the partial pressure is equal across all compartments, maintaining the desired anesthetic effect. 1. Alveolar Wash-In Alveolar wash-in is the initial process in which inspired anesthetic gas replaces normal lung gases, filling the functional residual capacity (FRC) of the lungs. ○ Time dependence: This wash-in process is faster with increased ventilatory rate and smaller lung volume. ○ Independence from gas properties: Wash-in speed doesn’t rely on the gas’s physical characteristics but on lung and breathing dynamics. 2. Anesthetic Uptake (Peripheral Distribution) Following wash-in, anesthetic uptake depends on blood flow to peripheral tissues and the gas’s solubility in blood. ○ a. Solubility in Blood: Measured by the blood/gas partition coefficient, determining how well the anesthetic dissolves in blood. Low solubility (e.g., nitrous oxide): Reaches equilibrium quickly, leading to rapid induction and recovery. High solubility (e.g., halothane): Dissolves more extensively in blood, slowing induction and recovery as more anesthetic molecules are needed to reach therapeutic levels in the brain. ○ b. Cardiac Output (CO): Higher CO increases anesthetic removal from the alveoli, slowing induction by delaying equilibrium between alveoli and the brain. Low CO can accelerate the rise of alveolar concentration and quicken the onset of anesthesia. ○ c. Alveolar-Venous Partial Pressure Gradient: The difference between alveolar and venous anesthetic levels drives gas uptake. Greater gradient means faster uptake, while smaller gradients slow the rate of induction. 3. Effect of Tissue Types on Anesthetic Uptake The time needed for anesthetic to reach equilibrium in a tissue depends on blood flow to that tissue and the tissue's ability to store anesthetic. a. Highly Perfused Organs (brain, heart, liver): Reach steady-state quickly. b. Skeletal Muscle: Low perfusion and large volume cause slower equilibration. c. Fat: Slow delivery but high lipid solubility creates a large storage capacity, delaying equilibrium. d. Bone and Cartilage: Minimal anesthetic uptake due to low perfusion and storage capacity. 4. Washout (Clearance of Anesthetic) When anesthesia is discontinued, the body drives the anesthetic out toward the alveoli, influenced by the same factors affecting uptake. ○ Nitrous oxide is cleared faster than halothane due to lower blood and tissue solubility. D. Mechanism of Action Receptor interactions: General anesthetics act primarily by enhancing GABA_A receptor sensitivity to GABA, the brain’s main inhibitory neurotransmitter. ○ Result: Increased chloride ion influx causes neuron hyperpolarization, reducing excitability and overall CNS activity. Alternative Mechanisms: Nitrous oxide and ketamine primarily inhibit NMDA receptors (glutamate receptors), modulating excitatory transmission without major effects on GABA_A receptors. Additional effects: Volatile anesthetics also enhance glycine receptor activity in spinal motor neurons and inhibit postsynaptic nicotinic receptors. E. Halothane Therapeutic Uses: Known for its potent anesthetic effects, halothane is a weak analgesic and often combined with nitrous oxide or opioids for pain relief. It can be used in obstetrics to relax uterine muscles and is suitable for pediatric inhalation induction (although sevoflurane is now preferred). Pharmacokinetics: Halothane undergoes oxidative metabolism, producing potentially toxic metabolites that may lead to liver toxicity in adults (but not typically in children). Adverse Effects: ○ Cardiac Effects: Can cause bradycardia and arrhythmias, especially with catecholamines. ○ Malignant Hyperthermia (MH): In rare cases, MH can be triggered by halogenated anesthetics like halothane. Dantrolene is the antidote, used to manage muscle contractions and prevent complications. F. Isoflurane Characteristics: Isoflurane has minimal metabolism, making it liver and kidney-safe. It does not cause arrhythmias or catecholamine sensitization. However, its pungent odor limits its use for inhalation induction, and it can trigger respiratory reflexes (e.g., coughing). Use Cases: Due to higher blood solubility than desflurane and sevoflurane, isoflurane is more cost-effective, though its onset and recovery times are slower. G. Desflurane Characteristics: Desflurane has low blood solubility, allowing for rapid onset and recovery, which is ideal for outpatient procedures. It requires a special heated vaporizer and is rarely used for prolonged anesthesia due to its high cost and low volatility. Respiratory Impact: Like isoflurane, it can trigger respiratory reflexes and is not used for inhalation induction. H. Sevoflurane Characteristics: With low pungency and high volatility, sevoflurane enables rapid induction and recovery, making it suitable for pediatric use. However, its liver metabolism can create nephrotoxic compounds in low gas flow circuits. I. Nitrous Oxide (N₂O) Properties and Uses: Nitrous oxide, commonly known as “laughing gas,” is a nonirritating, highly effective analgesic but a weak anesthetic. It’s commonly administered at 30–50% concentration with oxygen, especially for pain relief in dental procedures. Due to its weak anesthetic properties, nitrous oxide is often combined with more potent anesthetics for surgical anesthesia. Pharmacokinetics: Nitrous oxide is poorly soluble in blood and tissues, which allows for rapid movement in and out of the body. This characteristic leads to quick onset and recovery times. However, in closed body spaces (such as a pneumothorax or sinuses), nitrous oxide can cause volume or pressure increases, as it displaces nitrogen faster than nitrogen can escape. Adverse Effects: ○ Diffusion Hypoxia: During recovery, the rapid outflow of nitrous oxide can displace oxygen in the lungs, leading to diffusion hypoxia. This can be prevented by administering high concentrations of oxygen during recovery. ○ Respiratory and Cardiovascular Effects: Nitrous oxide does not depress respiration, induce muscle relaxation, or significantly affect cardiovascular function, making it relatively safe. ○ Hepatotoxicity: It is the least hepatotoxic of inhaled anesthetics, adding to its safety profile. Overall Safety: Nitrous oxide is considered one of the safest inhalation anesthetics due to its minimal impact on the cardiovascular and respiratory systems, provided it is used with adequate oxygen. V. Intravenous Anesthetics Intravenous (IV) anesthetics are known for their rapid onset, allowing for quick induction of anesthesia, typically occurring within the time it takes for the drug to travel from the injection site to the brain (known as "arm-brain circulation time"). These anesthetics can be used alone for short procedures or in combination with inhaled agents for longer surgeries. Additionally, they can be administered at lower doses for sedation. A. Induction  Mechanism: Upon entering the bloodstream, a portion of the drug binds to plasma proteins while the remainder remains unbound or "free." The degree of protein binding is influenced by the drug’s characteristics, including its ionization and lipid solubility. The drug is transported through venous blood to the right heart, then to the pulmonary circulation, and finally to systemic circulation. Target Areas: The highest initial concentrations of the drug are delivered to vessel-rich organs, particularly the brain, where the drug crosses from blood into the brain based on concentration gradients. Factors affecting this transfer include the arterial concentration of unbound drug, lipid solubility, and ionization. Nonionized, lipid-soluble molecules cross the blood-brain barrier most rapidly. Action: The exact mode of action for IV anesthetics is still not fully understood, similar to inhalation anesthetics. B. Recovery Redistribution: Recovery from IV anesthetics occurs primarily due to redistribution from the CNS. After the drug floods the CNS and other highly perfused tissues, it begins to diffuse into tissues with lower blood supply. This diffusion lowers plasma drug concentrations, allowing the drug to exit the CNS via a reverse concentration gradient. Early Recovery: The initial redistribution leads to rapid recovery following a single bolus of an induction agent. Metabolism: Metabolism and clearance of the drug from the plasma become more significant during infusions or repeated doses. Adipose Tissue: Adipose tissue has minimal impact on early drug redistribution but can become a reservoir with repeated dosing, contributing to delayed recovery. C. Effect of Reduced Cardiac Output on IV Anesthetics Increased Cerebral Distribution: In situations of reduced cardiac output (e.g., shock, elderly patients, cardiac disease), more cardiac output is directed to the cerebral circulation, resulting in a higher proportion of the IV anesthetic reaching the brain. Dosing Considerations: Due to these dynamics, a reduced dose of anesthetic is often necessary. The slower circulation time means that the onset of effects from induction agents is prolonged, necessitating careful titration of doses for safe induction in patients with compromised cardiac output. D. Propofol Overview: Propofol is a widely used IV sedative/hypnotic that serves as the primary choice for the induction and maintenance of anesthesia, having largely replaced thiopental. Formulation: Due to its poor water solubility, propofol is formulated as an emulsion containing soybean oil and egg phospholipid, giving it a milky appearance. 1. Onset: Induction occurs smoothly within 30 to 40 seconds after administration. Following a bolus, there’s rapid equilibration between plasma and brain tissue, with plasma levels declining quickly due to redistribution. The initial redistribution half-life is approximately 2 to 4 minutes. Propofol’s pharmacokinetics remain stable even with moderate hepatic or renal impairment. 2. Actions: ○ CNS Effects: While propofol depresses the CNS, it can also elicit excitatory effects like muscle twitching and yawning. ○ Cardiovascular Effects: It decreases blood pressure without significantly affecting myocardial contractility and reduces intracranial pressure mainly through systemic vasodilation. ○ Neurosurgical Monitoring: Propofol has less impact on CNS-evoked potentials, making it suitable for procedures requiring spinal cord monitoring. ○ Analgesia: It does not provide analgesia, so it is often used alongside narcotics. ○ Side Effects: Common issues include transient pain at the injection site and a low incidence of postoperative nausea and vomiting, due to its antiemetic properties. E. Barbiturates Thiopental: Thiopental is an ultra-short-acting barbiturate known for its high lipid solubility, making it a potent anesthetic, though it has weak analgesic properties. As such, supplementary analgesics are necessary during anesthesia. Mechanism: Upon intravenous administration, thiopental and similar agents like methohexital rapidly enter the central nervous system (CNS) and induce anesthesia, often within 1 minute. The rapid onset is coupled with equally fast diffusion out of the brain due to redistribution to other tissues. Metabolism: While thiopental has a quick redistribution phase, it remains in the body for an extended period, as only about 15% of a dose is metabolized by the liver each hour. Consequently, thiopental's metabolism is slower than its redistribution. Cardiovascular Effects: Thiopental has minimal effects on a normal cardiovascular system but can lead to severe hypotension in patients experiencing hypovolemia or shock. Adverse Effects: All barbiturates carry risks such as apnea, coughing, and bronchospasm, making them a concern for patients with asthma. Due to these issues and the development of better-tolerated alternatives, thiopental is no longer available in many countries, including the United States. F. Benzodiazepines Usage: Benzodiazepines are often used in conjunction with other anesthetics for sedation. The most commonly used benzodiazepine is midazolam, while diazepam and lorazepam serve as alternatives. Mechanism: These agents facilitate amnesia while inducing sedation by enhancing the inhibitory effects of neurotransmitters, particularly gamma-aminobutyric acid (GABA). Effects: Benzodiazepines typically exhibit minimal cardiovascular depressant effects, but they can be respiratory depressants, especially with IV administration. They undergo liver metabolism with variable elimination half-lives, and co-administration with erythromycin may prolong their effects. Amnesia: Benzodiazepines can cause a temporary form of anterograde amnesia, wherein patients retain memories of past events but do not remember new information. Important treatment information should be repeated to the patient after the drug's effects wear off. G. Opioids Analgesic Properties: Opioids are frequently combined with other anesthetics due to their strong analgesic effects. The choice of opioid depends on the required duration of action. Common Agents: The most commonly used opioids in anesthesia include fentanyl, sufentanil, and remifentanil, which provide rapid analgesia compared to morphine. They can be administered through various routes, including intravenously, epidurally, or intrathecally. Limitations: Although opioids are effective analgesics, they do not offer significant amnesic effects and can lead to hypotension, respiratory depression, and muscle rigidity. Postanesthetic nausea and vomiting are also common side effects. Their effects can be reversed with the opioid antagonist naloxone. H. Etomidate  Characteristics: Etomidate is a hypnotic agent used for anesthesia induction; however, it lacks analgesic properties. Its poor water solubility necessitates formulation in a propylene glycol solution. Induction and Effects: Induction with etomidate is rapid, and the drug is short-acting. It has minimal impact on cardiovascular function, making it suitable for patients with coronary artery disease or cardiovascular issues. Adverse Effects: Etomidate can lead to decreased plasma cortisol and aldosterone levels, effects that can persist for up to 8 hours. It should not be infused for extended periods due to the risk of prolonged hormonal suppression. Common side effects include injection site reactions and involuntary skeletal muscle movements, which may be managed with benzodiazepines or opioids. I. Ketamine Overview: Ketamine is a short-acting, nonbarbiturate anesthetic that induces a dissociated state where the patient may appear unconscious but is unaware of pain. This dissociative anesthesia results in sedation, amnesia, and immobility. Physiological Effects: Ketamine stimulates central sympathetic outflow, leading to increased heart rate, blood pressure, and cardiac output. It also acts as a potent bronchodilator, making it advantageous for patients in shock or with asthma, but it is contraindicated in hypertensive or stroke patients. Redistribution: Similar to barbiturates, ketamine quickly redistributes to other tissues. It is primarily used in pediatric and elderly populations for short procedures but is less common due to the potential for increased cerebral blood flow and hallucinations, especially in young adults. Additionally, ketamine has potential for illicit use due to its ability to induce dream-like states. J. Dexmedetomidine Usage: Dexmedetomidine is a sedative used mainly in intensive care and surgical settings. Its unique ability to provide sedation without causing respiratory depression sets it apart. Mechanism: As an α2 receptor agonist, dexmedetomidine produces sedative, analgesic, sympatholytic, and anxiolytic effects. It can reduce the need for volatile anesthetics, sedatives, and analgesics without significantly impacting respiratory function. Clinical Considerations: The therapeutic advantages and disadvantages of various anesthetic agents, including dexmedetomidine, are summarized in a comparative figure in the referenced material (Figure 13.11). VI. Neuromuscular Blockers Neuromuscular blockers are essential agents in anesthesia used primarily to facilitate tracheal intubation and provide muscle relaxation during surgical procedures.. VII. LOCAL ANESTHETICS Overview: Local anesthetics block nerve conduction of sensory (and in higher doses, motor) impulses from reaching the CNS by inhibiting Na+ ion channels. This prevents the necessary Na+ permeability for action potential formation, stopping sensation from reaching the brain. Delivery methods include: Topical Infiltration Peripheral nerve blocks Neuraxial blocks (spinal, epidural, caudal) Most Common Local Anesthetics: Bupivacaine (noted for cardiotoxicity if injected IV; liposomal form lasts 24+ hrs) Lidocaine Mepivacaine (avoid in obstetric anesthesia due to neonatal toxicity) Procaine Ropivacaine Tetracaine A. Metabolism Amides: Metabolized mainly in the liver (e.g., prilocaine also in plasma & kidney; can cause methemoglobinemia). Esters: Broken down by plasma cholinesterase. Slow metabolism in patients with pseudocholinesterase deficiency. Reduced liver function may increase toxicity risk. B. Onset and Duration Influencing Factors: Tissue pH, nerve morphology, drug concentration, pKa, and lipid solubility. Mechanism: Ionized form at physiological pH binds Na+ channels. Lower pH (e.g., in infected sites) can delay/prevent onset. Concentration & Lipid Solubility: Higher levels can improve onset. Duration depends on proximity to nerves for Na+ channel blocking. C. Actions Vasodilation: Speeds up diffusion away from the site, reducing duration. Adding epinephrine slows absorption, extending duration and minimizing toxicity. Other Uses: Lidocaine serves as an antiarrhythmic when administered IV. D. Allergic Reactions Often due to side effects of epinephrine or psychogenic responses rather than true allergy. True Allergies: ○ Ester Anesthetics: More likely to cause true allergies due to para-aminobenzoic acid metabolite. ○ Amide Anesthetics: Rare to cause allergy; if allergic to one, others may still be safe. ○ Allergies can also be to preservatives in multi-dose vials. E. Use in Children and Elderly Children: Calculate maximum dose by weight to avoid overdose. Elderly: Lower doses are advised, especially of epinephrine, due to potential liver/cardiovascular compromise. F. Systemic Toxicity May arise from repeated or accidental IV injection. Symptoms: Variable; may include altered mental status or cardiovascular issues. CNS signs (excitation or depression) may be subtle or absent. Treatment: Support airway, circulation, control seizures, possibly CPR, and lipid emulsion therapy (lipid rescue).