Inhaled Anesthetics

Inhaled anesthetics are chemical compounds that can induce and maintain general anesthesia Anesthesia Anesthesiology is the field of medicine that focuses on interventions that bring a state of anesthesia upon an individual. General anesthesia is characterized by a reversible loss of consciousness along with analgesia, amnesia, and muscle relaxation. Anesthesiology: History and Basic Concepts when delivered by inhalation. Inhaled anesthetics can be divided into 2 groups: volatile anesthetics and gases. Volatile anesthetics 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 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, glycine, glutamate, and NMDA receptors in the CNS. Inhaled anesthetics have been used for medical purposes for the last 200 years.

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Editorial responsibility: Stanley Oiseth, Lindsay Jones, Evelin Maza

Table of Contents

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Chemistry and Pharmacodynamics

Table: Chemical characteristics of commonly used inhaled anesthetics
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.
  • The mechanism of action for most inhaled anesthetics is poorly understood.
  • Inhaled anesthetics work within the CNS:
    • Variable receptor interaction:
      • Acetylcholine (nicotinic and muscarinic)
      • GABA
      • NMDA
      • Glutamate
      • Glycine
      • Serotonin (also known as 5-hydroxytryptamine (5-HT))
    • Augment the physiology of receptor-related ion channels:
      • K
      • Cl
    • Depression of neurotransmission Neurotransmission The junction between 2 neurons is called a synapse. The synapse allows a neuron to pass an electrical or chemical signal to another neuron or target effector cell. The plasma membranes of the 2 neurons are placed very close together, and the space between the 2 neurons is called the synaptic cleft. The molecules that mediate the interaction are called neurotransmitters. Synapses and Neurotransmission pathways

Physiologic effects

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

  • Desired therapeutic targets:
    • Sedation (reversible loss of consciousness)
    • Analgesia
    • Amnesia
    • Skeletal muscle relaxation/immobility
  • Cardiovascular effects:
    • Myocardial depression
    • ↓ Arterial blood pressure 
  • Respiratory effects:
    • Respiratory depression
    • Tachypnea:
      • N2O
      • Desflurane
    • Bronchodilation:
      • Halothane
      • Sevoflurane
      • Isoflurane
    • Airway irritation:
      • Isoflurane
      • Desflurane
  • Cerebral effects:
    • ↓ Cerebral glucose utilization
    • ↑ Cerebral blood 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
    • ↑ Intracranial pressure ( ICP ICP Normal intracranial pressure (ICP) is defined as < 15 mm Hg, whereas pathologically increased ICP is any pressure ≥ 20 mm Hg. Increased ICP may result from several etiologies, including trauma, intracranial hemorrhage, mass lesions, cerebral edema, increased CSF production, and decreased CSF absorption. Increased Intracranial Pressure (ICP))
  • Renal effects:
    • ↑ Renovascular resistance
    • ↓ Renal blood 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
    • ↓ Urine output

Pharmacokinetics

Administration of inhaled anesthetics

Administration by inhalation:

  • Face mask
  • Laryngeal mask airway
  • Endotracheal tube

Delivery by anesthesia Anesthesia Anesthesiology is the field of medicine that focuses on interventions that bring a state of anesthesia upon an individual. General anesthesia is characterized by a reversible loss of consciousness along with analgesia, amnesia, and muscle relaxation. 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 (equal to 0.1 MAC).
  • Anesthetic goals:
    • Induction: transition from an awake state to an anesthetized state 
    • Anesthesia: absence of pain Pain Pain has accompanied humans since they first existed, first lamented as the curse of existence and later understood as an adaptive mechanism that ensures survival. Pain is the most common symptomatic complaint and the main reason why people seek medical care. Physiology of Pain perception
    • 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):
    • End-tidal CO2
    • Tidal volume
    • Respiratory rate
Anesthesia machine

Anesthesia machine

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

Pharmacokinetic principles of inhaled anesthetics

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 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 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 of alveolar concentration to inspiratory concentration. 
  • Speed of induction: The rate at which the FA:FI ratio approaches 1.

Partial pressure:

  • 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.

Effects of ventilation rate:

  • The speed of induction is directly proportional to the ventilation rate. 
  • ↑ Ventilation 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. 

Effects of cardiac output:

  • At the level of the alveolus, uptake is directly proportional to cardiac output (CO): ↑ CO → ↑ alveolar blood 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 → ↑ 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 
  • 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 → induction delay

Effects of pulmonary circulation: 

  • 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 and venous blood.
  • ↑ Partial pressure of the anesthetic in venous blood → ↓ gradient between the blood and the alveoli → ↓ 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:

  • Solubility of the anesthetic: ↑ solubility, the slower the induction
  • Inspired 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: ↑ 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, the faster the induction
  • Ventilation rate: ↑ ventilation rate, the faster the induction
  • Blood 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: ↑ blood 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, the slower the induction
  • Arteriovenous (AV) concentration gradient: ↑ AV gradient, the slower the induction
Table: Classification of tissues by solubility and blood 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
Group Organs Description
Vessel-rich group Brain, 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, kidney, and endocrine organs
  • Moderate solubility and small volume → limited capacity
  • Reaches steady state 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. Structure and Function of the Skin 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
  • Similar perfusion to muscle group
  • Increased solubility of anesthetic → increased capacity
  • Days to reach a steady state
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, 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
  • Insignificant uptake

Metabolism and excretion

  • < 5% of inhaled anesthetic is metabolized in the body.
  • Metabolism involves phase 1 and phase 2 reactions:
    • Phase 1 (catabolic reactions): hydrolysis and oxidation 
    • Phase 2 (anabolic reactions): the addition of a glucuronyl or methyl group to the metabolite
  • Excretion of the end product is through: 
    • Exhalation
    • Transcutaneous loss
    • Kidneys Kidneys The kidneys are a pair of bean-shaped organs located retroperitoneally against the posterior wall of the abdomen on either side of the spine. As part of the urinary tract, the kidneys are responsible for blood filtration and excretion of water-soluble waste in the urine. Kidneys
    • Hepatobiliary system 

Indications

  • Generally used in the operating room (FDA approved):
    • Induction of general anesthesia Anesthesia Anesthesiology is the field of medicine that focuses on interventions that bring a state of anesthesia upon an individual. General anesthesia is characterized by a reversible loss of consciousness along with analgesia, amnesia, and muscle relaxation. Anesthesiology: History and Basic Concepts (faster onset of action than IV anesthetics)
    • Maintenance of general anesthesia Anesthesia Anesthesiology is the field of medicine that focuses on interventions that bring a state of anesthesia upon an individual. General anesthesia is characterized by a reversible loss of consciousness along with analgesia, amnesia, and muscle relaxation. Anesthesiology: History and Basic Concepts
  • Sometimes used in the ICU (not FDA approved):
    • Sedation (e.g., ventilated individual, combative individual, or a bedside procedure)
    • Refractory bronchospasm
    • 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)
  • Often used in conjunction with IV anesthetics:
    • Midazolam
    • Propofol
Table: Advantages and disadvantages of inhaled anesthetics
Agent Advantages Disadvantages
Nitrous oxide (N2O)
  • Odorless
  • No taste or pungency
  • Fast uptake and excretion
  • Minimal cardiovascular depression
  • Minimal biotransformation
  • Inexpensive
  • Rarely used as a solo agent (low potency)
  • Airspace expansion
  • Increased nausea and vomiting
  • Inhibition of methionine synthase
  • Greenhouse gas
  • Supports combustion
Isoflurane
  • Good muscle relaxation
  • Bronchodilation
  • Stable heart rate
  • Inexpensive
  • Slower uptake and elimination
  • Strong odor → may cause airway 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 irritation → appropriate choice for induction
More expensive than isoflurane
Desflurane
  • Fast uptake and excretion
  • Minimal biotransformation
  • Strong odor → may cause airway irritation → poor choice for induction
  • Expensive

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
  • Headache
  • Nausea and vomiting
  • Apnea
  • Potential neurotoxicity
Halothane
  • Fulminant hepatic necrosis
  • Arrhythmia (increased sensitivity 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 or tachycardia
  • 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
  • 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
  • Nausea and vomiting
  • 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
  • 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 injury
  • Potential neurotoxicity

Drug-drug interactions

  • N2O: ameliorates the circulatory and respiratory effects of other volatile anesthetics when used together
  • Halothane:
    • Β-adrenergic blocking agents and calcium 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 (blood pressure fluctuations and arrhythmias)
  • Desflurane, sevoflurane, and isoflurane: potentiate neuromuscular blocking agents
Table: Contraindications of commonly used inhaled anesthetics
Agent Contraindications
Nitrous oxide (N2O)
  • Air 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
  • Pneumocephalus
  • Pulmonary air cysts
  • Intraocular air bubbles
  • Tympanic membrane 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 dysfunction after exposure in a previous procedure
Desflurane
  • Severe hypovolemia
  • 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
Sevoflurane
Isoflurane Severe hypovolemia

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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