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Inhaled Anesthetics

Inhaled anesthetics Anesthetics Agents that are capable of inducing a total or partial loss of sensation, especially tactile sensation and pain. They may act to induce general anesthesia, in which an unconscious state is achieved, or may act locally to induce numbness or lack of sensation at a targeted site. Anesthesiology: History and Basic Concepts are chemical compounds that can induce and maintain general anesthesia Anesthesia A state characterized by loss of feeling or sensation. This depression of nerve function is usually the result of pharmacologic action and is induced to allow performance of surgery or other painful procedures. Anesthesiology: History and Basic Concepts when delivered by inhalation. Inhaled anesthetics Anesthetics Agents that are capable of inducing a total or partial loss of sensation, especially tactile sensation and pain. They may act to induce general anesthesia, in which an unconscious state is achieved, or may act locally to induce numbness or lack of sensation at a targeted site. Anesthesiology: History and Basic Concepts can be divided into 2 groups: volatile anesthetics Anesthetics Agents that are capable of inducing a total or partial loss of sensation, especially tactile sensation and pain. They may act to induce general anesthesia, in which an unconscious state is achieved, or may act locally to induce numbness or lack of sensation at a targeted site. Anesthesiology: History and Basic Concepts and gases. Volatile anesthetics Anesthetics Agents that are capable of inducing a total or partial loss of sensation, especially tactile sensation and pain. They may act to induce general anesthesia, in which an unconscious state is achieved, or may act locally to induce numbness or lack of sensation at a targeted site. Anesthesiology: History and Basic Concepts include halothane, isoflurane, desflurane, and sevoflurane. Nitrous oxide (N2O) is the most common of the anesthetic gases; cyclopropane and xenon are less commonly used. While the exact mechanism of action of the inhaled anesthetics Anesthetics Agents that are capable of inducing a total or partial loss of sensation, especially tactile sensation and pain. They may act to induce general anesthesia, in which an unconscious state is achieved, or may act locally to induce numbness or lack of sensation at a targeted site. Anesthesiology: History and Basic Concepts is unknown, the drugs are believed to have variable Variable Variables represent information about something that can change. The design of the measurement scales, or of the methods for obtaining information, will determine the data gathered and the characteristics of that data. As a result, a variable can be qualitative or quantitative, and may be further classified into subgroups. Types of Variables effects on GABA GABA The most common inhibitory neurotransmitter in the central nervous system. Receptors and Neurotransmitters of the CNS, glycine Glycine A non-essential amino acid. It is found primarily in gelatin and silk fibroin and used therapeutically as a nutrient. It is also a fast inhibitory neurotransmitter. Synthesis of Nonessential Amino Acids, glutamate Glutamate Derivatives of glutamic acid. Included under this heading are a broad variety of acid forms, salts, esters, and amides that contain the 2-aminopentanedioic acid structure. Synthesis of Nonessential Amino Acids, and NMDA receptors Receptors Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors in the CNS. Inhaled anesthetics Anesthetics Agents that are capable of inducing a total or partial loss of sensation, especially tactile sensation and pain. They may act to induce general anesthesia, in which an unconscious state is achieved, or may act locally to induce numbness or lack of sensation at a targeted site. Anesthesiology: History and Basic Concepts have been used for medical purposes for the last 200 years.

Last updated: May 6, 2022

Editorial responsibility: Stanley Oiseth, Lindsay Jones, Evelin Maza

Chemistry and Pharmacodynamics

Table: Chemical characteristics of commonly used inhaled anesthetics Anesthetics Agents that are capable of inducing a total or partial loss of sensation, especially tactile sensation and pain. They may act to induce general anesthesia, in which an unconscious state is achieved, or may act locally to induce numbness or lack of sensation at a targeted site. Anesthesiology: History and Basic Concepts
Agent Characteristics Minimum alveolar concentration (MAC)
Nitrous oxide (N2O)
  • Naturally occurring nonvolatile gas
  • Can be artificially synthesized
  • Nonflammable
104%
Halothane
  • Hydrocarbon
  • Nonflammable
  • Halogenated
  • Volatile liquid
  • No longer commercially available in the United States
0.75%
Desflurane
  • Fluorinated ether
  • Clear and volatile liquid
6.6%
Sevoflurane
  • Fluorinated isopropyl ether
  • Volatile liquid
1.8%
Isoflurane
  • Fluorinated ether
  • Volatile liquid
1.2%

Mechanism of action

  • A single site of action is not shared by all inhaled anesthetics Anesthetics Agents that are capable of inducing a total or partial loss of sensation, especially tactile sensation and pain. They may act to induce general anesthesia, in which an unconscious state is achieved, or may act locally to induce numbness or lack of sensation at a targeted site. Anesthesiology: History and Basic Concepts.
  • The mechanism of action for most inhaled anesthetics Anesthetics Agents that are capable of inducing a total or partial loss of sensation, especially tactile sensation and pain. They may act to induce general anesthesia, in which an unconscious state is achieved, or may act locally to induce numbness or lack of sensation at a targeted site. Anesthesiology: History and Basic Concepts is poorly understood.
  • Inhaled anesthetics Anesthetics Agents that are capable of inducing a total or partial loss of sensation, especially tactile sensation and pain. They may act to induce general anesthesia, in which an unconscious state is achieved, or may act locally to induce numbness or lack of sensation at a targeted site. Anesthesiology: History and Basic Concepts work within the CNS:
    • Variable Variable Variables represent information about something that can change. The design of the measurement scales, or of the methods for obtaining information, will determine the data gathered and the characteristics of that data. As a result, a variable can be qualitative or quantitative, and may be further classified into subgroups. Types of Variables receptor Receptor Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors interaction:
      • Acetylcholine Acetylcholine A neurotransmitter found at neuromuscular junctions, autonomic ganglia, parasympathetic effector junctions, a subset of sympathetic effector junctions, and at many sites in the central nervous system. Receptors and Neurotransmitters of the CNS (nicotinic and muscarinic)
      • GABA GABA The most common inhibitory neurotransmitter in the central nervous system. Receptors and Neurotransmitters of the CNS
      • NMDA
      • Glutamate Glutamate Derivatives of glutamic acid. Included under this heading are a broad variety of acid forms, salts, esters, and amides that contain the 2-aminopentanedioic acid structure. Synthesis of Nonessential Amino Acids
      • Glycine Glycine A non-essential amino acid. It is found primarily in gelatin and silk fibroin and used therapeutically as a nutrient. It is also a fast inhibitory neurotransmitter. Synthesis of Nonessential Amino Acids
      • Serotonin Serotonin A biochemical messenger and regulator, synthesized from the essential amino acid l-tryptophan. In humans it is found primarily in the central nervous system, gastrointestinal tract, and blood platelets. Serotonin mediates several important physiological functions including neurotransmission, gastrointestinal motility, hemostasis, and cardiovascular integrity. Receptors and Neurotransmitters of the CNS (also known as 5-hydroxytryptamine 5-hydroxytryptamine A biochemical messenger and regulator, synthesized from the essential amino acid l-tryptophan. In humans it is found primarily in the central nervous system, gastrointestinal tract, and blood platelets. Serotonin mediates several important physiological functions including neurotransmission, gastrointestinal motility, hemostasis, and cardiovascular integrity. Receptors and Neurotransmitters of the CNS ( 5-HT 5-HT A biochemical messenger and regulator, synthesized from the essential amino acid l-tryptophan. In humans it is found primarily in the central nervous system, gastrointestinal tract, and blood platelets. Serotonin mediates several important physiological functions including neurotransmission, gastrointestinal motility, hemostasis, and cardiovascular integrity. Receptors and Neurotransmitters of the CNS))
    • Augment the physiology of receptor-related ion channels Channels The Cell: Cell Membrane:
      • K
      • Cl
    • Depression of neurotransmission Neurotransmission The communication from a neuron to a target (neuron, muscle, or secretory cell) across a synapse. In chemical synaptic transmission, the presynaptic neuron releases a neurotransmitter that diffuses across the synaptic cleft and binds to specific synaptic receptors, activating them. The activated receptors modulate specific ion channels and/or second-messenger systems in the postsynaptic cell. In electrical synaptic transmission, electrical signals are communicated as an ionic current flow across electrical synapses. Synapses and Neurotransmission pathways

Physiologic effects

General class effects (individual agents may have unique properties):

  • Desired therapeutic targets:
  • Cardiovascular effects:
    • Myocardial depression
    • ↓ Arterial blood pressure 
  • Respiratory effects:
  • Cerebral effects:
  • Renal effects:
    • ↑ Renovascular resistance Resistance Physiologically, the opposition to flow of air caused by the forces of friction. As a part of pulmonary function testing, it is the ratio of driving pressure to the rate of air flow. Ventilation: Mechanics of Breathing
    • Renal blood flow Renal blood flow The amount of the renal blood flow that is going to the functional renal tissue, i.e., parts of the kidney that are involved in production of urine. Glomerular Filtration
    • Urine Urine Liquid by-product of excretion produced in the kidneys, temporarily stored in the bladder until discharge through the urethra. Bowen Disease and Erythroplasia of Queyrat output

Pharmacokinetics

Administration of inhaled anesthetics Anesthetics Agents that are capable of inducing a total or partial loss of sensation, especially tactile sensation and pain. They may act to induce general anesthesia, in which an unconscious state is achieved, or may act locally to induce numbness or lack of sensation at a targeted site. Anesthesiology: History and Basic Concepts

Administration by inhalation:

Delivery by anesthesia Anesthesia A state characterized by loss of feeling or sensation. This depression of nerve function is usually the result of pharmacologic action and is induced to allow performance of surgery or other painful procedures. Anesthesiology: History and Basic Concepts machine:

  • The machine takes in fresh, pressurized gas.
  • The gas passes through a hypoxic trap where a mixture of gasses is determined by the operator (e.g., anesthesiologist or certified registered nurse anesthetist).
  • The gas is passed through a vaporizer where the anesthetic agent is mixed in with fresh gas, reaching the concentration determined by the anesthesiologist. 
  • The mixed gas flows into the common gas outlet and into the breathing circuit.

Inhaled anesthetic dosing:

  • Dosed in units of minimum alveolar concentration (MAC):
    • Gas concentration of 1 MAC is needed for 50% of recipients to not respond to noxious stimuli.
    • To achieve anesthetic goals, dose adjustments are made in increments of 1 standard deviation Standard deviation The standard deviation (SD) is a measure of how far each observed value is from the mean in a data set. Measures of Central Tendency and Dispersion (equal to 0.1 MAC).
  • Anesthetic goals:
    • Induction: transition from an awake state to an anesthetized state 
    • Anesthesia Anesthesia A state characterized by loss of feeling or sensation. This depression of nerve function is usually the result of pharmacologic action and is induced to allow performance of surgery or other painful procedures. Anesthesiology: History and Basic Concepts: absence of pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways perception Perception The process by which the nature and meaning of sensory stimuli are recognized and interpreted. Psychiatric Assessment
    • Immobility: absence of spontaneous movements and absence of movement in response to noxious stimuli
    • Amnesia: lack of recall for an event (i.e., surgery)
  • MAC of common agents at sea level:
    • Desflurane: 6.6%
    • Halothane: 0.75%
    • Isoflurane: 1.2%
    • Sevoflurane: 1.8%
    • Nitrous oxide: 104%
  • Factors affecting MAC:
    • Advancing age: ↓
    • Coadministration of other sedating drugs: ↓ 
    • Hypothermia Hypothermia Hypothermia can be defined as a drop in the core body temperature below 35°C (95°F) and is classified into mild, moderate, severe, and profound forms based on the degree of temperature decrease. Hypothermia: ↓
    • Hyperthermia: ↑
    • Chronic stimulant use: ↑
    • Chronic alcohol abuse: ↑
  • Agents with higher MAC need lower potency administration to achieve anesthetic goals.
  • Achieving and maintaining anesthetic goals requires monitoring and adjustment of respiratory parameters (usually performed with a mechanical ventilator):
Anesthesia machine

Anesthesia Anesthesia A state characterized by loss of feeling or sensation. This depression of nerve function is usually the result of pharmacologic action and is induced to allow performance of surgery or other painful procedures. Anesthesiology: History and Basic Concepts machine

Image: “Datex – Ohmeda” by Kitmondo Marketplace. License: CC BY 2.0

Pharmacokinetic principles of inhaled anesthetics Anesthetics Agents that are capable of inducing a total or partial loss of sensation, especially tactile sensation and pain. They may act to induce general anesthesia, in which an unconscious state is achieved, or may act locally to induce numbness or lack of sensation at a targeted site. Anesthesiology: History and Basic Concepts

Partition coefficient (Ostwald coefficient):

  • The ratio of the anesthetic concentration in the blood to the concentration in the gas
  • The more soluble the anesthetic is in blood:
    • The more the anesthetic binds to proteins Proteins Linear polypeptides that are synthesized on ribosomes and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of amino acids determines the shape the polypeptide will take, during protein folding, and the function of the protein. Energy Homeostasis in the blood
    • ↑ Blood-gas partition coefficient
  • The blood-gas partition coefficient is inversely related to the induction rate.

Inspiratory concentration (FI):

  • Depends mainly on:
    • Flow Flow Blood flows through the heart, arteries, capillaries, and veins in a closed, continuous circuit. Flow is the movement of volume per unit of time. Flow is affected by the pressure gradient and the resistance fluid encounters between 2 points. Vascular resistance is the opposition to flow, which is caused primarily by blood friction against vessel walls. Vascular Resistance, Flow, and Mean Arterial Pressure rate of fresh gas
    • Volume of the breathing system
    • Absorption Absorption Absorption involves the uptake of nutrient molecules and their transfer from the lumen of the GI tract across the enterocytes and into the interstitial space, where they can be taken up in the venous or lymphatic circulation. Digestion and Absorption by the breathing system
  • Directly proportional to the concentration of fresh gas

Alveolar concentration (FA):

  • Reflects pulmonary capillary uptake of gas:
    • The concentration of a gas is directly proportional to the partial pressure Partial pressure The pressure that would be exerted by one component of a mixture of gases if it were present alone in a container. Gas Exchange of the gas.
    • ↑ Capillary uptake equates to ↓ alveolar concentration.
  • The FA:FI ratio describes the relationship Relationship A connection, association, or involvement between 2 or more parties. Clinician–Patient Relationship of alveolar concentration to inspiratory concentration. 
  • Speed of induction: The rate at which the FA:FI ratio approaches 1.

Partial pressure Partial pressure The pressure that would be exerted by one component of a mixture of gases if it were present alone in a container. Gas Exchange:

  • Alveolar partial pressure Partial pressure The pressure that would be exerted by one component of a mixture of gases if it were present alone in a container. Gas Exchange determines the partial pressure Partial pressure The pressure that would be exerted by one component of a mixture of gases if it were present alone in a container. Gas Exchange of anesthetic in the blood. 
  • The partial pressure Partial pressure The pressure that would be exerted by one component of a mixture of gases if it were present alone in a container. Gas Exchange of anesthetic in the blood determines the concentration in the brain Brain The part of central nervous system that is contained within the skull (cranium). Arising from the neural tube, the embryonic brain is comprised of three major parts including prosencephalon (the forebrain); mesencephalon (the midbrain); and rhombencephalon (the hindbrain). The developed brain consists of cerebrum; cerebellum; and other structures in the brain stem. Nervous System: Anatomy, Structure, and Classification.

Effects of ventilation Ventilation The total volume of gas inspired or expired per unit of time, usually measured in liters per minute. Ventilation: Mechanics of Breathing rate:

  • The speed of induction is directly proportional to the ventilation Ventilation The total volume of gas inspired or expired per unit of time, usually measured in liters per minute. Ventilation: Mechanics of Breathing rate. 
  • Ventilation Ventilation The total volume of gas inspired or expired per unit of time, usually measured in liters per minute. Ventilation: Mechanics of Breathing maintains the partial pressure Partial pressure The pressure that would be exerted by one component of a mixture of gases if it were present alone in a container. Gas Exchange of anesthetic within the alveoli Alveoli Small polyhedral outpouchings along the walls of the alveolar sacs, alveolar ducts and terminal bronchioles through the walls of which gas exchange between alveolar air and pulmonary capillary blood takes place. Acute Respiratory Distress Syndrome (ARDS)

Effects of cardiac output Cardiac output The volume of blood passing through the heart per unit of time. It is usually expressed as liters (volume) per minute so as not to be confused with stroke volume (volume per beat). Cardiac Mechanics:

  • At the level of the alveolus, uptake is directly proportional to cardiac output Cardiac output The volume of blood passing through the heart per unit of time. It is usually expressed as liters (volume) per minute so as not to be confused with stroke volume (volume per beat). Cardiac Mechanics (CO): ↑ CO → ↑ alveolar blood flow Blood flow Blood flow refers to the movement of a certain volume of blood through the vasculature over a given unit of time (e.g., mL per minute). Vascular Resistance, Flow, and Mean Arterial Pressure → ↑ uptake from the lungs Lungs Lungs are the main organs of the respiratory system. Lungs are paired viscera located in the thoracic cavity and are composed of spongy tissue. The primary function of the lungs is to oxygenate blood and eliminate CO2. Lungs: Anatomy 
  • However, induction speed is inversely proportional to CO: ↑ uptake of gas → ↓ partial pressure Partial pressure The pressure that would be exerted by one component of a mixture of gases if it were present alone in a container. Gas Exchange of the anesthetic within the alveoli Alveoli Small polyhedral outpouchings along the walls of the alveolar sacs, alveolar ducts and terminal bronchioles through the walls of which gas exchange between alveolar air and pulmonary capillary blood takes place. Acute Respiratory Distress Syndrome (ARDS) → induction delay

Effects of pulmonary circulation Pulmonary circulation The circulation of the blood through the lungs. Systemic and Special Circulations

  • Uptake is also affected by the partial pressure Partial pressure The pressure that would be exerted by one component of a mixture of gases if it were present alone in a container. Gas Exchange gradient of the anesthetic between the alveoli Alveoli Small polyhedral outpouchings along the walls of the alveolar sacs, alveolar ducts and terminal bronchioles through the walls of which gas exchange between alveolar air and pulmonary capillary blood takes place. Acute Respiratory Distress Syndrome (ARDS) and venous blood.
  • Partial pressure Partial pressure The pressure that would be exerted by one component of a mixture of gases if it were present alone in a container. Gas Exchange of the anesthetic in venous blood → ↓ gradient between the blood and the alveoli Alveoli Small polyhedral outpouchings along the walls of the alveolar sacs, alveolar ducts and terminal bronchioles through the walls of which gas exchange between alveolar air and pulmonary capillary blood takes place. Acute Respiratory Distress Syndrome (ARDS) → ↓ uptake 
  • Indirectly indicates uptake by the peripheral tissues

Effects of concentration:

  • Speed of induction is directly proportional to the alveolar concentration.
  • ↑ Uptake → ↓ alveolar concentration → slows down induction
  • ↑ Concentration of the inhaled anesthetic → ↑ alveolar concentration → quicker induction 
  • Capacity = tissue/blood solubility × tissue volume

Summary of determinants of induction speed:

Table: Classification of tissues by solubility and blood flow Blood flow Blood flow refers to the movement of a certain volume of blood through the vasculature over a given unit of time (e.g., mL per minute). Vascular Resistance, Flow, and Mean Arterial Pressure
Group Organs Description
Vessel-rich group Brain Brain The part of central nervous system that is contained within the skull (cranium). Arising from the neural tube, the embryonic brain is comprised of three major parts including prosencephalon (the forebrain); mesencephalon (the midbrain); and rhombencephalon (the hindbrain). The developed brain consists of cerebrum; cerebellum; and other structures in the brain stem. Nervous System: Anatomy, Structure, and Classification, heart, liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy, kidney, and endocrine organs
  • Moderate solubility and small volume → limited capacity
  • Reaches steady state Steady state Enzyme Kinetics quickly (i.e., equalized arterial and tissue partial pressures)
Muscle group Skin Skin The skin, also referred to as the integumentary system, is the largest organ of the body. The skin is primarily composed of the epidermis (outer layer) and dermis (deep layer). The epidermis is primarily composed of keratinocytes that undergo rapid turnover, while the dermis contains dense layers of connective tissue. Skin: Structure and Functions and muscles
  • Larger volume → greater capacity → hours for uptake
Fat group Adipose tissue Adipose tissue Adipose tissue is a specialized type of connective tissue that has both structural and highly complex metabolic functions, including energy storage, glucose homeostasis, and a multitude of endocrine capabilities. There are three types of adipose tissue, white adipose tissue, brown adipose tissue, and beige or “brite” adipose tissue, which is a transitional form. Adipose Tissue: Histology
  • Similar perfusion to muscle group
  • Increased solubility of anesthetic → increased capacity
  • Days to reach a steady state Steady state Enzyme Kinetics
Vessel-poor group Bones, ligaments, teeth Teeth Normally, an adult has 32 teeth: 16 maxillary and 16 mandibular. These teeth are divided into 4 quadrants with 8 teeth each. Each quadrant consists of 2 incisors (dentes incisivi), 1 canine (dens caninus), 2 premolars (dentes premolares), and 3 molars (dentes molares). Teeth are composed of enamel, dentin, and dental cement. Teeth: Anatomy, hair, and cartilage Cartilage Cartilage is a type of connective tissue derived from embryonic mesenchyme that is responsible for structural support, resilience, and the smoothness of physical actions. Perichondrium (connective tissue membrane surrounding cartilage) compensates for the absence of vasculature in cartilage by providing nutrition and support. Cartilage: Histology
  • Insignificant uptake

Metabolism and excretion

Indications

  • Generally used in the operating room (FDA approved):
    • Induction of general anesthesia Anesthesia A state characterized by loss of feeling or sensation. This depression of nerve function is usually the result of pharmacologic action and is induced to allow performance of surgery or other painful procedures. Anesthesiology: History and Basic Concepts (faster onset of action than IV anesthetics Anesthetics Agents that are capable of inducing a total or partial loss of sensation, especially tactile sensation and pain. They may act to induce general anesthesia, in which an unconscious state is achieved, or may act locally to induce numbness or lack of sensation at a targeted site. Anesthesiology: History and Basic Concepts)
    • Maintenance of general anesthesia Anesthesia A state characterized by loss of feeling or sensation. This depression of nerve function is usually the result of pharmacologic action and is induced to allow performance of surgery or other painful procedures. Anesthesiology: History and Basic Concepts
  • Sometimes used in the ICU ICU Hospital units providing continuous surveillance and care to acutely ill patients. West Nile Virus (not FDA approved):
    • Sedation (e.g., ventilated individual, combative individual, or a bedside procedure)
    • Refractory bronchospasm Bronchospasm Asthma Drugs
    • Seizures Seizures A seizure is abnormal electrical activity of the neurons in the cerebral cortex that can manifest in numerous ways depending on the region of the brain affected. Seizures consist of a sudden imbalance that occurs between the excitatory and inhibitory signals in cortical neurons, creating a net excitation. The 2 major classes of seizures are focal and generalized. Seizures unresponsive to antiepileptics (i.e., status epilepticus Status Epilepticus A prolonged seizure or seizures repeated frequently enough to prevent recovery between episodes occurring over a period of 20-30 minutes. The most common subtype is generalized tonic-clonic status epilepticus, a potentially fatal condition associated with neuronal injury and respiratory and metabolic dysfunction. Nonconvulsive forms include petit mal status and complex partial status, which may manifest as behavioral disturbances. Simple partial status epilepticus consists of persistent motor, sensory, or autonomic seizures that do not impair cognition. Subclinical status epilepticus generally refers to seizures occurring in an unresponsive or comatose individual in the absence of overt signs of seizure activity. Seizures)
  • Often used in conjunction with IV anesthetics Anesthetics Agents that are capable of inducing a total or partial loss of sensation, especially tactile sensation and pain. They may act to induce general anesthesia, in which an unconscious state is achieved, or may act locally to induce numbness or lack of sensation at a targeted site. Anesthesiology: History and Basic Concepts:
    • Midazolam Midazolam A short-acting hypnotic-sedative drug with anxiolytic and amnestic properties. It is used in dentistry, cardiac surgery, endoscopic procedures, as preanesthetic medication, and as an adjunct to local anesthesia. The short duration and cardiorespiratory stability makes it useful in poor-risk, elderly, and cardiac patients. It is water-soluble at ph less than 4 and lipid-soluble at physiological pH. Benzodiazepines
    • Propofol Propofol An intravenous anesthetic agent which has the advantage of a very rapid onset after infusion or bolus injection plus a very short recovery period of a couple of minutes. Propofol has been used as anticonvulsants and antiemetics. Intravenous Anesthetics
Table: Advantages and disadvantages of inhaled anesthetics Anesthetics Agents that are capable of inducing a total or partial loss of sensation, especially tactile sensation and pain. They may act to induce general anesthesia, in which an unconscious state is achieved, or may act locally to induce numbness or lack of sensation at a targeted site. Anesthesiology: History and Basic Concepts
Agent Advantages Disadvantages
Nitrous oxide (N2O)
  • Rarely used as a solo agent (low potency)
  • Airspace expansion
  • Increased nausea Nausea An unpleasant sensation in the stomach usually accompanied by the urge to vomit. Common causes are early pregnancy, sea and motion sickness, emotional stress, intense pain, food poisoning, and various enteroviruses. Antiemetics and vomiting Vomiting The forcible expulsion of the contents of the stomach through the mouth. Hypokalemia
  • Inhibition of methionine synthase
  • Greenhouse gas
  • Supports combustion
Isoflurane
  • Good muscle relaxation
  • Bronchodilation
  • Stable heart rate Heart rate The number of times the heart ventricles contract per unit of time, usually per minute. Cardiac Physiology
  • Inexpensive
  • Slower uptake and elimination Elimination The initial damage and destruction of tumor cells by innate and adaptive immunity. Completion of the phase means no cancer growth. Cancer Immunotherapy
  • Strong odor → may cause airway Airway ABCDE Assessment irritation → poor choice for induction
Sevoflurane
  • The most common inhaled anesthetic
  • Fast uptake and excretion → rapid induction and recovery time
  • Bronchodilation
  • No pungency → no airway Airway ABCDE Assessment irritation → appropriate choice for induction
More expensive than isoflurane
Desflurane

Adverse Effects and Contraindications

Table: Adverse effects
Agent Adverse effects
Nitrous oxide (N2O)
  • Hypotension Hypotension Hypotension is defined as low blood pressure, specifically < 90/60 mm Hg, and is most commonly a physiologic response. Hypotension may be mild, serious, or life threatening, depending on the cause. Hypotension
  • Confusion
  • Dizziness Dizziness An imprecise term which may refer to a sense of spatial disorientation, motion of the environment, or lightheadedness. Lateral Medullary Syndrome (Wallenberg Syndrome)
  • Headache Headache The symptom of pain in the cranial region. It may be an isolated benign occurrence or manifestation of a wide variety of headache disorders. Brain Abscess
  • Nausea Nausea An unpleasant sensation in the stomach usually accompanied by the urge to vomit. Common causes are early pregnancy, sea and motion sickness, emotional stress, intense pain, food poisoning, and various enteroviruses. Antiemetics and vomiting Vomiting The forcible expulsion of the contents of the stomach through the mouth. Hypokalemia
  • Apnea
  • Potential neurotoxicity
Halothane
  • Fulminant hepatic necrosis Necrosis The death of cells in an organ or tissue due to disease, injury or failure of the blood supply. Ischemic Cell Damage
  • Arrhythmia (increased sensitivity Sensitivity Binary classification measures to assess test results. Sensitivity or recall rate is the proportion of true positives. Blotting Techniques to catecholamines Catecholamines A general class of ortho-dihydroxyphenylalkylamines derived from tyrosine. Adrenal Hormones)
  • Malignant hyperthermia Malignant hyperthermia An important complication of anesthesia is malignant hyperthermia, an autosomal dominant disorder of the regulation of calcium transport in the skeletal muscles resulting in a hypermetabolic crisis. Malignant hyperthermia is marked by high fever, muscle rigidity, rhabdomyolysis, and respiratory and metabolic acidosis. Malignant Hyperthermia
  • Potential neurotoxicity
Desflurane
  • Arrhythmia
  • Bradycardia Bradycardia Bradyarrhythmia is a rhythm in which the heart rate is less than 60/min. Bradyarrhythmia can be physiologic, without symptoms or hemodynamic change. Pathologic bradyarrhythmia results in reduced cardiac output and hemodynamic instability causing syncope, dizziness, or dyspnea. Bradyarrhythmias or tachycardia Tachycardia Abnormally rapid heartbeat, usually with a heart rate above 100 beats per minute for adults. Tachycardia accompanied by disturbance in the cardiac depolarization (cardiac arrhythmia) is called tachyarrhythmia. Sepsis in Children
  • Hypertension Hypertension Hypertension, or high blood pressure, is a common disease that manifests as elevated systemic arterial pressures. Hypertension is most often asymptomatic and is found incidentally as part of a routine physical examination or during triage for an unrelated medical encounter. Hypertension
  • Laryngospasm Laryngospasm Hypoparathyroidism
  • Malignant hyperthermia Malignant hyperthermia An important complication of anesthesia is malignant hyperthermia, an autosomal dominant disorder of the regulation of calcium transport in the skeletal muscles resulting in a hypermetabolic crisis. Malignant hyperthermia is marked by high fever, muscle rigidity, rhabdomyolysis, and respiratory and metabolic acidosis. Malignant Hyperthermia
  • Potential neurotoxicity
Sevoflurane
  • Hypotension Hypotension Hypotension is defined as low blood pressure, specifically < 90/60 mm Hg, and is most commonly a physiologic response. Hypotension may be mild, serious, or life threatening, depending on the cause. Hypotension
  • Agitation Agitation A feeling of restlessness associated with increased motor activity. This may occur as a manifestation of nervous system drug toxicity or other conditions. St. Louis Encephalitis Virus
  • Nausea Nausea An unpleasant sensation in the stomach usually accompanied by the urge to vomit. Common causes are early pregnancy, sea and motion sickness, emotional stress, intense pain, food poisoning, and various enteroviruses. Antiemetics and vomiting Vomiting The forcible expulsion of the contents of the stomach through the mouth. Hypokalemia
  • Sialorrhea
  • Malignant hyperthermia Malignant hyperthermia An important complication of anesthesia is malignant hyperthermia, an autosomal dominant disorder of the regulation of calcium transport in the skeletal muscles resulting in a hypermetabolic crisis. Malignant hyperthermia is marked by high fever, muscle rigidity, rhabdomyolysis, and respiratory and metabolic acidosis. Malignant Hyperthermia
  • Potential neurotoxicity
Isoflurane
  • Laryngospasm Laryngospasm Hypoparathyroidism
  • Malignant hyperthermia Malignant hyperthermia An important complication of anesthesia is malignant hyperthermia, an autosomal dominant disorder of the regulation of calcium transport in the skeletal muscles resulting in a hypermetabolic crisis. Malignant hyperthermia is marked by high fever, muscle rigidity, rhabdomyolysis, and respiratory and metabolic acidosis. Malignant Hyperthermia
  • Severe acute liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy injury
  • Potential neurotoxicity

Drug-drug interactions

  • N2O: ameliorates the circulatory and respiratory effects of other volatile anesthetics Anesthetics Agents that are capable of inducing a total or partial loss of sensation, especially tactile sensation and pain. They may act to induce general anesthesia, in which an unconscious state is achieved, or may act locally to induce numbness or lack of sensation at a targeted site. Anesthesiology: History and Basic Concepts when used together
  • Halothane:
    • Β-adrenergic blocking agents and calcium Calcium A basic element found in nearly all tissues. It is a member of the alkaline earth family of metals with the atomic symbol ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. Electrolytes channel blocking agents (myocardial depression)
    • Tricyclic antidepressants Tricyclic antidepressants Tricyclic antidepressants (TCAs) are a class of medications used in the management of mood disorders, primarily depression. These agents, named after their 3-ring chemical structure, act via reuptake inhibition of neurotransmitters (particularly norepinephrine and serotonin) in the brain. Tricyclic Antidepressants and monoamine oxidase Oxidase Neisseria (blood pressure fluctuations and arrhythmias)
  • Desflurane, sevoflurane, and isoflurane: potentiate neuromuscular blocking agents
Table: Contraindications Contraindications A condition or factor associated with a recipient that makes the use of a drug, procedure, or physical agent improper or inadvisable. Contraindications may be absolute (life threatening) or relative (higher risk of complications in which benefits may outweigh risks). Noninvasive Ventilation of commonly used inhaled anesthetics Anesthetics Agents that are capable of inducing a total or partial loss of sensation, especially tactile sensation and pain. They may act to induce general anesthesia, in which an unconscious state is achieved, or may act locally to induce numbness or lack of sensation at a targeted site. Anesthesiology: History and Basic Concepts
Agent Contraindications Contraindications A condition or factor associated with a recipient that makes the use of a drug, procedure, or physical agent improper or inadvisable. Contraindications may be absolute (life threatening) or relative (higher risk of complications in which benefits may outweigh risks). Noninvasive Ventilation
Nitrous oxide (N2O)
  • Air embolism Air embolism Blocking of a blood vessel by air bubbles that enter the circulatory system, usually after trauma; surgical procedures, or changes in atmospheric pressure. Nonthrombotic Embolism
  • Pneumothorax Pneumothorax A pneumothorax is a life-threatening condition in which air collects in the pleural space, causing partial or full collapse of the lung. A pneumothorax can be traumatic or spontaneous. Patients present with a sudden onset of sharp chest pain, dyspnea, and diminished breath sounds on exam. Pneumothorax
  • Bowel obstruction Bowel obstruction Any impairment, arrest, or reversal of the normal flow of intestinal contents toward the anal canal. Ascaris/Ascariasis
  • Pneumocephalus
  • Pulmonary air cysts Cysts Any fluid-filled closed cavity or sac that is lined by an epithelium. Cysts can be of normal, abnormal, non-neoplastic, or neoplastic tissues. Fibrocystic Change
  • Intraocular air bubbles
  • Tympanic membrane Tympanic membrane An oval semitransparent membrane separating the external ear canal from the tympanic cavity. It contains three layers: the skin of the external ear canal; the core of radially and circularly arranged collagen fibers; and the mucosa of the middle ear. Ear: Anatomy grafting
Halothane Unexplained liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy dysfunction after exposure Exposure ABCDE Assessment in a previous procedure
Desflurane
  • Severe hypovolemia Hypovolemia Sepsis in Children
  • Malignant hyperthermia Malignant hyperthermia An important complication of anesthesia is malignant hyperthermia, an autosomal dominant disorder of the regulation of calcium transport in the skeletal muscles resulting in a hypermetabolic crisis. Malignant hyperthermia is marked by high fever, muscle rigidity, rhabdomyolysis, and respiratory and metabolic acidosis. Malignant Hyperthermia
  • Intracranial hypertension Hypertension Hypertension, or high blood pressure, is a common disease that manifests as elevated systemic arterial pressures. Hypertension is most often asymptomatic and is found incidentally as part of a routine physical examination or during triage for an unrelated medical encounter. Hypertension
Sevoflurane
Isoflurane Severe hypovolemia Hypovolemia Sepsis in Children

References

  1. McKay, R. E. (2018). Inhaled Anesthetics. Pardo, M. C., & R. D. Miller, R. D. (Eds.) Basics of Anesthesia, 7e (pp. 83–103). https://www.elsevier.com/books/basics-ofanesthesia/pardo/978-0-323-40115-9
  2. National Center for Biotechnology Information (2021). PubChem Compound Summary for CID 948, Nitrous oxide. Retrieved June 11, 2021, from https://pubchem.ncbi.nlm.nih.gov/compound/Nitrous-oxide 
  3. Butterworth IV, J. F., Mackey, D. C., & Wasnick, J. D. (2018). Inhalation Anesthetics. In Morgan &amp; Mikhail’s Clinical Anesthesiology, 6e. McGraw-Hill Education. http://accessmedicine.mhmedical.com/content.aspx?aid=1161426360 
  4. Nizamuddin, J., & O’Connor, M. (2019). Anesthesia for surgical patients. Brunicardi F., & Andersen D. K., & Billiar T. R., & Dunn D. L., & Kao L. S., & Hunter J. G., & Matthews J. B., & Pollock R. E. (Eds.), Schwartz’s Principles of Surgery, 11e. McGraw-Hill. https://accessmedicine.mhmedical.com/content.aspx?bookid=2576&sectionid=216218112
  5. Miller, A. L., Theodore, D., & Widrich, J. (2021). Inhalational anesthetic. StatPearls (). Treasure Island (FL): StatPearls Publishing. Retrieved from http://www.ncbi.nlm.nih.gov/books/NBK554540/ 
  6. Clar, D. T., Patel, S., & Richards, J. R. (2021). Anesthetic gases. StatPearls. Treasure Island (FL): StatPearls Publishing. Retrieved from http://www.ncbi.nlm.nih.gov/books/NBK537013/ 
  7. National Center for Biotechnology Information (2021). PubChem Compound Summary for CID 3562, Halothane. Retrieved June 18, 2021, from https://pubchem.ncbi.nlm.nih.gov/compound/Halothane 
  8. National Center for Biotechnology Information (2021). PubChem Compound Summary for CID 4116, Methoxyflurane. Retrieved June 18, 2021, from https://pubchem.ncbi.nlm.nih.gov/compound/Methoxyflurane 
  9. National Center for Biotechnology Information (2021). PubChem Compound Summary for CID 3226, Enflurane. Retrieved June 18, 2021, from https://pubchem.ncbi.nlm.nih.gov/compound/Enflurane
  10. National Center for Biotechnology Information (2021). PubChem Compound Summary for CID 3763, Isoflurane. Retrieved June 18, 2021, from https://pubchem.ncbi.nlm.nih.gov/compound/Isoflurane
  11. National Center for Biotechnology Information (2021). PubChem Compound Summary for CID 42113, Desflurane. Retrieved June 20, 2021, from https://pubchem.ncbi.nlm.nih.gov/compound/Desflurane

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