Inhalation anesthetic agents: Properties and delivery

INTRODUCTION — This topic will review the properties, pharmacokinetics, and delivery of inhalation anesthetics, including the potent volatile agents (sevoflurane, desflurane, isoflurane [and in some countries, halothane]) and nitrous oxide (N₂O).

Use of anesthesia machines for delivery of these inhalation anesthetics is reviewed separately. (See "Anesthesia machines: Prevention, diagnosis, and management of malfunctions".)

Clinical effects and specific uses for each of the inhalation anesthetic agents are reviewed separately. (See "Inhalation anesthetic agents: Clinical effects and uses".)

Potential environmental impact of anesthetic agents is reviewed separately. (See "Environmental impact of perioperative care", section on 'Managing use of anesthetic inhalation agents'.)

MECHANISMS OF ACTION — The precise mechanisms whereby inhalation agents induce general anesthesia are not known, and no single proposed mechanism of action fully explains their clinical effects (see "Inhalation anesthetic agents: Clinical effects and uses", section on 'Clinical effects'). Various ion channels including gamma-aminobutyric acid_A (GABA_A), glycine, and glutamate receptors located in the central nervous system (ie, brain and spinal cord) are affected by the volatile inhalation anesthetics (sevoflurane, desflurane, and isoflurane) [1-4]. Nitrous oxide (N₂O) is thought to act both by agonism of GABA_A receptors and by antagonism of N-methyl-D-aspartate (NMDA) receptors [5,6].

Similarly, the mechanisms by which various intravenous agents are able to induce general anesthesia are not fully understood. (See "General anesthesia: Intravenous induction agents" and "Maintenance of general anesthesia: Overview", section on 'Total intravenous anesthesia'.)

PHARMACOKINETICS

General concepts — Inhalation agents are unique in their method of delivery via the lungs as a volume percent of inspired gas, rather than as a dose by weight as with intravenous (IV) or oral medications. Inhalation agents are delivered via specialized airway circuits that are connected to an anesthesia machine, with scavenging of exhaled gases to prevent environmental contamination of the operating room or interventional suite [7]. Bottled volatile anesthetic liquids (sevoflurane, desflurane, isoflurane, halothane) are delivered as gases via vaporizers on the anesthesia machine. Nitrous oxide (N₂O) is supplied as a pressurized gas in equilibrium with its liquid phase in a cylinder, then delivered as a gas via flow meter (similar to delivery of other gases such as medical air or oxygen). (See "Anesthesia machines: Prevention, diagnosis, and management of malfunctions".)

Uptake of an agent with onset of anesthetic effect, changes in anesthetic depth, and clearance of the agent with termination of anesthetic effect depend on pulmonary gas exchange via the lungs, and on the rate of change of the inhalation anesthetic's concentration in alveoli. The pharmacokinetic parameters for each agent (ie, what the body does to the drug) describe differences between them in their uptake, redistribution, metabolism, and clearance.

Uptake — Inhalation agents must pass from inspired gas into the blood of the alveolar capillary network (ie, uptake), then from circulating blood into the central nervous system (CNS; ie, redistribution) in order to exert anesthetic effects [7].

Speed of uptake and of onset of anesthetic effect depends in large part on the inspired concentration of the inhalation agent (figure 1). Also, the blood:gas partition coefficient for each agent (ie, the ratio of its solubility in blood to its solubility in gas) determines how quickly its concentration in pulmonary capillary blood reaches equilibrium with its concentration in alveolar gas (see 'Blood:gas partition coefficient' below). Furthermore, uptake also depends on the patient's minute ventilation (the volume of gas exchanged in the respiratory system per unit of time) (see 'Respiratory factors' below), and on the patient's pulmonary blood flow (ie, the volume of blood passing through the pulmonary circulation per unit of time) [8] (see 'Cardiovascular factors' below). These factors determine the speed of equilibration of the concentration gradient of the inhalation agent between alveoli and pulmonary capillary blood, and thus influence the speed of anesthetic induction or emergence.

Redistribution — Redistribution of the inhaled agent depends in part on the tissue:blood partition coefficient (ie, the ratio of the agent's solubility in tissue to its solubility in blood) for each perfused tissue bed (see 'Brain:blood partition coefficient' below), and also depends on the blood flow to these tissue compartments (see 'Cardiovascular factors' below). Specifically, production of the inhalation agent's primary effect in the brain (sedation progressing to general anesthesia) depends on the agent's brain:blood partition coefficient (ie, the ratio of its solubility in brain to its solubility in blood). Overall redistribution depends on blood flow to the brain and also to other perfused tissue compartments (see 'Cardiovascular factors' below). These factors determine the speed of equilibration of concentration of the agent between arterial blood, brain, and other tissues, thereby influencing speed of anesthetic induction or emergence.

Metabolism

●Sevoflurane, desflurane, isoflurane, nitrous oxide – Sevoflurane, desflurane, isoflurane, and N₂O undergo negligible biotransformation and metabolism, thus these agents are primarily exhaled unchanged.

●Halothane – Up to 50 percent of halothane is metabolized in the liver, while 50 percent or more is exhaled unchanged. Hepatic metabolism of halothane to hepatotoxic intermediates, particularly trifluoroacetic acid, is thought to be largely responsible for the transient, usually mild hepatic injury seen in approximately 25 percent of patients after halothane administration (halothane hepatotoxicity). Notably, an autoimmune hepatitis is thought to be responsible for so-called halothane hepatitis, a severe and occasionally fatal hepatic injury that occurs in 1 in 1000 to 1 in 10,000 patients after halothane administration. (See "Anesthesia for the patient with liver disease", section on 'Effects of anesthetics on the liver'.)

Clearance — Clearance of inhalation agents with termination of anesthetic and other effects depends on the same factors that influence uptake. Specifically, redistribution out of the CNS depends on the presence of a concentration gradient favoring clearance from brain to blood, then from blood to alveoli (from which the agent is exhaled from the body). For each agent, speed of clearance by exhalation thus depends on its brain:blood partition coefficient (ie, the ratio of its solubility in brain to its solubility in blood) (see 'Brain:blood partition coefficient' below), and on its blood:gas partition coefficient (ie, the ratio of its solubility in blood to its solubility in gas) (see 'Partition coefficients and potency' below). Clearance also depends on the patient's minute ventilation (see 'Respiratory factors' below), and on pulmonary blood flow [8] (see 'Cardiovascular factors' below). Notably, most inhalation agents (with the exception of halothane) are exhaled unchanged because of minimal hepatic metabolism or renal excretion. (See 'Metabolism' above.)

FACTORS AFFECTING INHALATION ANESTHETIC DELIVERY

Partition coefficients and potency — Ideal inhalation anesthetics would have low blood and tissue solubility and high potency, promoting rapid induction of general anesthesia, rapid changes in anesthetic depth, and rapid recovery. Actual solubility and potency of currently available inhalation anesthetics vary considerably (table 1).

Blood:gas partition coefficient — The blood:gas partition coefficient of an inhalation agent (ie, the ratio of its solubility in blood to its solubility in gas) is a major determinant of speed of anesthetic onset because this determines the rate at which concentration of the agent in inspired gas reaches equilibrium with concentration in circulating blood (see 'Uptake' above), and subsequently in the brain [7]. A lower blood:gas partition coefficient means that the inhalation agent is relatively insoluble in blood. Less agent is therefore required to saturate the blood compartment, allowing concentration of the inhalation agent in alveolar gas to reach equilibrium with its concentration in pulmonary capillary blood more quickly, thereby promoting more rapid induction and emergence. A higher blood:gas partition coefficient means that the inhalation agent is relatively soluble in blood. More agent is therefore required to saturate the blood compartment, causing concentration of the inhalation agent in alveolar gas to reach equilibrium with its concentration in pulmonary capillary blood more slowly, promoting less rapid induction and emergence.

Blood:gas partition coefficients from lowest to highest (ie, fastest to slowest with regard to speed of induction of general anesthesia) are (table 1):

Note that because of its very low potency, N₂O alone is inadequate to induce general anesthesia at physiologic temperature and pressure. (See 'Oil:gas partition coefficient/potency' below.)

Brain:blood partition coefficient — The brain:blood partition coefficient (ie, the ratio of agent solubility in brain to its solubility in blood) determines the speed at which the agent reaches equilibrium in the brain to cause its anesthetic effect [7]. As with the blood:gas partition coefficient, a lower brain:blood partition coefficient means that the inhalation agent is relatively insoluble in brain. Less agent is therefore required to saturate the brain compartment, allowing concentration of the inhalation agent in the central nervous system (CNS) to reach equilibrium with its concentration in circulating blood more quickly, promoting more rapid induction and emergence. A higher brain:blood partition coefficient means that the inhalation agent is relatively soluble in brain. More agent is therefore required to saturate the brain compartment, causing concentration of the inhalation agent in the CNS to reach equilibrium with its concentration in circulating blood more slowly, promoting less rapid induction and emergence.

Brain:blood partition coefficients of modern inhalation agents are similar and close to 1.0 (table 1).

From lowest to highest (ie, fastest to slowest with regard to speed of induction of general anesthesia), brain:blood partition coefficients are:

Note that because of its very low potency, N₂O alone is inadequate to induce general anesthesia at physiologic temperature and pressure. (See 'Oil:gas partition coefficient/potency' below.)

Tissue:blood partition coefficient — Tissue:blood partition coefficients (ie, the ratio of agent solubility in tissue to its solubility in blood) are a primary determinant of the speed of redistribution of each inhalation agent. (See 'Redistribution' above.)

The speed with which tissue:blood equilibrium is reached in the brain and other tissues also depends in large part on blood flow to each perfused tissue compartment (ie, the fraction of overall cardiac output received by the compartment [7] (see 'Cardiovascular factors' below)). Since blood flow to the brain is high, equilibrium between the concentration of an inhalation agent in the blood and the brain is achieved quickly. Thus, in practice, tissue:blood partition coefficients have relatively little effect on speed of anesthetic induction.

As with the blood:gas and blood:brain partition coefficients, redistribution of an agent out of the tissues into the blood is faster if it has a low tissue:blood partition coefficient [9].

Oil:gas partition coefficient/potency — The oil:gas partition coefficient of an inhalation agent is the ratio of its solubility in oil (conventionally olive oil) to its solubility in gas (conventionally air) at physiologic temperature and pressure (ie, 37°C and 1 atmosphere). An inverse linear relationship exists for most inhalation agents between their solubility in oil and their anesthetic potency measured as their minimum alveolar concentration (MAC) [10]. (See "Inhalation anesthetic agents: Clinical effects and uses", section on 'MAC and MAC-awake values for inhalation agents'.)

Oil:gas partition coefficients from highest to lowest (ie, most to least potent) are (table 1):

Note that because of its very low potency, N₂O alone is inadequate to induce general anesthesia at physiologic temperature and pressure.

Although MAC for an inhalation agent may be estimated by dividing its oil:gas partition coefficient by a constant (typically, 150), this coefficient is not a direct measure of potency for any clinical effect or physiologic state such as sedation or general anesthesia.

Patient-related considerations

Respiratory factors — Respiratory factors that speed uptake and clearance of inhalation agents include increased minute ventilation (ie, the volume of gas exchanged in the respiratory system per unit of time), which depends on the patient's tidal volume and respiratory rate [8,11,12]. Conversely, decreased minute ventilation or the presence of a large ventilation/perfusion (V/Q) mismatch or volume of dead space slows the speed of uptake and clearance. Although general anesthesia increases alveolar dead space and increases alveolar to arterial partial pressure gradients (ie, A-a gradients) for all gases, these effects are much greater for inhalation anesthetic agents than for carbon dioxide (CO₂), and appear related to the blood solubility of these agents [13].

Cardiovascular factors

●Induction – Somewhat counterintuitively, decreased cardiac output (CO) actually speeds anesthetic induction. Decreased CO is associated with decreased pulmonary blood flow and decreased uptake of inhalation agent, so that the alveolar concentration of the agent is maintained, allowing for more rapid equilibrium between the concentration of inhalation agent in alveoli and that in pulmonary capillary blood, thereby speeding induction [8,11,12]. Thus, anesthetic overdose is more likely in patients with low CO.

In contrast, increased CO actually slows anesthetic induction [8,11,12]. Increased CO is associated with increased pulmonary blood flow and increased uptake of anesthetic agent from the alveoli, delaying establishment of equilibrium between agent concentrations in alveoli and pulmonary capillary blood, thereby slowing induction.

After uptake of an inhalation agent from the alveoli, the relatively high percent of blood flow directed to the brain promotes rapid uptake of inhalation agent from circulating blood into the brain. Notably, the greater the solubility of an inhalation agent (ie, the higher its blood:gas partition coefficient), the greater the effect of CO on speed of induction.

●Emergence – The overall effect of CO on clearance of an inhalation agent and speed of emergence is thus more difficult to predict. The effect of CO on clearance of an inhalation agent and speed of emergence is more complex, given the interplay between tissue washout and pulmonary clearance of inhalation agent accumulated in tissue stores during the anesthetic. For example:

•Decreased CO during emergence is associated with decreased pulmonary blood flow, which allows for more rapid equilibrium between the concentration of inhalation agent in alveoli and that in pulmonary capillary blood. However, decreased pulmonary blood flow decreases overall delivery of inhalation agent to the pulmonary circulation for clearance.

•Decreased CO during emergence similarly allows for more rapid equilibrium between the concentration of inhalation agent in tissue versus blood, and in blood versus alveolus. This effect is more pronounced with increasing solubility of the inhalational agent. As with induction, this would be expected to speed emergence, although this effect is offset by delayed washout of inhalational agent accumulated in various tissue compartments. In clinical practice, the overall effect of decreased CO during emergence may be difficult to predict.

•The greater the solubility of an inhalation agent (ie, the higher its blood:gas partition coefficient), the greater the effect of CO on equilibrium between agent concentration in alveoli and pulmonary capillary blood, and the greater the likelihood that decreased CO will speed emergence. However, the greater the tissue:blood partition coefficient of an inhalation agent, the greater the accumulation of tissue stores of the agent, particularly during a prolonged anesthetic, and the greater the likelihood that decreased CO will delay emergence.

●Considerations with congenital heart disease – In certain types of congenital heart disease, significant right-to-left shunt reduces pulmonary blood flow relative to systemic blood flow (ie, pulmonary-to-systemic flow ratio [Q_P/Q_S] is <1). Since this shunted blood bypasses the pulmonary circulation, the concentration of an inhalation agent in systemic arterial blood represents a mixture of the concentration in the pulmonary capillary blood and that in shunted blood. This mixing slows the rate at which the concentration of an inhalation agent in systemic arterial blood reaches equilibrium with the concentration in inspired gas, with consequent slowing of uptake or clearance of the inhalation agent, and slower anesthetic induction or emergence [14,15]. Although left-to-right shunt with relatively increased pulmonary blood flow (ie, a pulmonary-to-systemic flow ratio [Q_P/Q_S] that is >1) might be expected to increase uptake or clearance of inhalation agent, speeding anesthetic induction or emergence, such an effect is not predicted by computer modeling and has not been demonstrated in clinical practice [14,15].

Technique-related considerations — Modified administration techniques can speed or slow induction and emergence.

Fresh gas flow rate — In the semi-closed circle system of an anesthesia machine, fresh gas flow rates at or above minute ventilation prevent rebreathing; in this setting, the concentration of inhalation agent delivered to the patient is indicated by the setting on the vaporizer (for volatile inhalation anesthetics) or flow meter (for N₂O). Increasing the fresh gas flow rate to be higher than minute ventilation will have no further effect on uptake and clearance, and will not influence speed of induction or emergence. Decreasing the fresh gas flow rate during maintenance of inhalation anesthesia results in reduced consumption of anesthetic agents with consequent cost savings, and also reduces the environmental impact of these greenhouse gases [16,17]. However, if the fresh gas flow rate is less than the patient's minute ventilation, rebreathing occurs necessitating absorption of CO₂ by CO₂ absorbent [18], and the inhaled delivered anesthetic concentration will actually be a mixture of the concentration in the exhaled gas as well as the concentration in the fresh gas flow indicated on the vaporizer and/or flow meter settings. (See "Anesthesia machines: Prevention, diagnosis, and management of malfunctions".)

Concentration effect — A higher inhaled concentration of anesthetic agent results in faster onset of anesthetic effect [7,19]. Higher inhaled concentration of inhalation agent promotes more rapid rise in alveolar concentration, resulting in a concentration gradient favoring transfer of agent from alveoli to blood. However, the concentration of volatile anesthetic agent (eg, sevoflurane) is often increased gradually during inhalation induction of anesthesia to avoid unpleasant pungency and increased risk of airway irritation (laryngospasm, bronchospasm) that can occur with rapid introduction of high concentrations [7] (see "Inhalation anesthetic agents: Clinical effects and uses", section on 'Inhalation induction (sevoflurane, halothane, nitrous oxide)'). Notably, desflurane and, to a lesser extent, isoflurane are not suitable for inhalation induction due to their high degree of airway irritation [20,21]. (See "Inhalation anesthetic agents: Clinical effects and uses", section on 'Disadvantages and adverse effects'.)

Similarly, clearance and termination of anesthetic effect is fastest if the inhaled concentration of the agent is zero, resulting in a concentration gradient favoring transfer of agent from blood to alveoli, with subsequent elimination via exhalation.

Overpressurization — Modified techniques such as overpressurization of inspired concentration of volatile anesthetic may be used to speed loss of consciousness during induction of general anesthesia [7]. For example, the breathing circuit may be primed with a high sevoflurane concentration (eg, 8 percent) plus N₂O. The patient is then instructed to take a vital capacity breath (defined as a complete expiration followed by a complete inspiration), followed by a period of apnea with inflated lungs (ie, "breath-holding") [22]. Typically, this primed-circuit technique achieves the 2 percent alveolar sevoflurane concentration required to tolerate a painful intervention such as a surgical incision in approximately 60 seconds, similar to the speed of intravenous induction with propofol [23].

Second gas effect — A volatile anesthetic agent is often coadministered with N₂O to speed induction by concentrating the volatile agent and increasing its rate of rise in alveoli, a phenomenon known as the "second gas" effect. Because of its very low blood:gas partition coefficient (table 1), during induction, bulk transfer of N₂O gas out of the alveoli lowers alveolar concentration of N₂O, obligatorily increasing the concentration of other alveolar gases including the volatile anesthetic agent. This effect increases the concentration gradient between alveolar gas and pulmonary capillary blood, promoting uptake of volatile anesthetic and thereby speeding induction. Administration of N₂O gas during and after induction also rapidly increases anesthetic depth and reduces the concentration of volatile anesthetic agent required for adequate anesthesia.

Second gas effects of N₂O are more pronounced with coadministration of highly soluble volatile anesthetics (ie, agents with a higher blood:gas partition coefficient such as halothane or isoflurane) since alveolar concentrations of these agents change more slowly compared with less soluble volatile anesthetics (ie, agents with a lower blood:gas partition coefficient such as sevoflurane and desflurane) (table 1). Furthermore, second gas effects of N₂O are more pronounced in patients with increased ventilation-perfusion (V/Q) mismatch due to increased blood concentration of the volatile anesthetic, although end-tidal measurements are likely to underestimate the blood concentration in such patients [24].

Although coadministration of N₂O with volatile anesthetic to take advantage of this second gas effect is most commonly employed to speed induction, coadministration may also speed emergence by diluting the alveolar concentration of volatile anesthetic, thereby increasing its rate of decline in alveoli. Because of its low blood:gas partition coefficient, upon discontinuation of N₂O administration, bulk transfer of N₂O gas into the alveolus increases alveolar concentration of N₂O, obligatorily decreasing the concentration of other alveolar gases including the volatile anesthetic. Decreased alveolar concentration of volatile anesthetic increases the concentration gradient between pulmonary capillary blood and alveolar gas, promoting elimination of the volatile anesthetic and thereby speeding emergence [25].

Notably, bulk transfer of N₂O gas into alveoli during emergence also decreases alveolar oxygen concentration, potentially inducing desaturation, a process known as "diffusion hypoxia." Diffusion hypoxia may be prevented by delivery of high inspired oxygen concentration for several minutes before and after discontinuing N₂O. (See "Inhalation anesthetic agents: Clinical effects and uses", section on 'Disadvantages and adverse effects'.)

Use of extracorporeal circulation — Inhalation agents may also be delivered or eliminated via a cardiopulmonary bypass (CPB) or extracorporeal membrane oxygenation (ECMO) circuit. (See "Management of cardiopulmonary bypass", section on 'Maintenance of anesthesia and neuromuscular blockade'.)

ENVIRONMENTAL IMPACT OF INHALATION ANESTHETICS — All the volatile inhalation anesthetic agents are potent greenhouse gases (GHGs), and nitrous oxide (N₂O) gas is also destructive to the ozone layer. Sevoflurane, desflurane, isoflurane, and N₂O undergo negligible biotransformation and metabolism; thus, these agents are primarily exhaled unchanged (see 'Metabolism' above). Then, scavenging of exhaled gases to prevent environmental contamination of the operating room or interventional suite vents these gases directly to the atmosphere. Potential mitigation strategies include minimizing or avoiding inhalation anesthetic agents (particularly desflurane and N₂O), although this is not always feasible or appropriate; using low fresh gas flows during anesthetic administration (even sevoflurane [26]); and recycling and reusing inhalation anesthetic agents. These issues are discussed in a separate topic. (See "Environmental impact of perioperative care", section on 'Managing use of anesthetic inhalation agents'.)

SUMMARY AND RECOMMENDATIONS

●General considerations – Inhalation agents are unique in their method of delivery via the lungs as a volume percent of inspired gas, rather than as a dose by weight as with intravenous (IV) or oral medications. These agents are delivered via specialized airway circuits connected to an anesthesia machine, with scavenging of exhaled gases to prevent environmental contamination. Bottled volatile anesthetic liquids (sevoflurane, desflurane, isoflurane, halothane) are delivered as gases via vaporizers on the anesthesia machine, while nitrous oxide (N_2O) is supplied as a pressurized gas in a cylinder via a flow meter (similar to delivery of other gases such as medical air or oxygen). (See 'General concepts' above.)

●Uptake, redistribution, metabolism, and clearance of inhalation agents – Uptake of the inhalation anesthetic during onset of anesthesia, changes in anesthetic depth, and clearance of the agent during termination of anesthetic effect depend on pulmonary gas exchange via the lungs and the rate of change in the inhalation anesthetic's concentration in alveoli. Metabolism and biotransformation are negligible for all inhalation anesthetic agents (sevoflurane, desflurane, isoflurane, N₂O), with the exception of halothane. (See 'Pharmacokinetics' above.)

●Factors affecting speed of anesthetic delivery or elimination

•Blood and tissue solubility (see 'Partition coefficients and potency' above):

-A lower blood:gas partition coefficient (ie, the ratio of an agent's solubility in blood to its solubility in gas) promotes more rapid equilibrium between alveolar and blood concentrations of inhalation agent, with associated faster onset (or termination) of anesthetic effect. Blood:gas partition coefficients from lowest to highest (ie, fastest to slowest with regard to speed of induction and emergence) are (table 1):

Because of its very low potency, N₂O alone is inadequate to induce general anesthesia at physiologic temperature and pressure. (See 'Oil:gas partition coefficient/potency' above.)

-A lower brain:blood partition coefficient (ie, the ratio of an agent's solubility in brain to its solubility in blood) permits faster redistribution of an inhalation agent (equilibration between concentrations in blood and brain), with associated faster onset (or termination) of anesthetic effect. Brain:blood partition coefficients from lowest to highest (ie, fastest to slowest with regard to speed of induction of general anesthesia) are (table 1):

Because of its very low potency, N₂O alone is inadequate to induce general anesthesia at physiologic temperature and pressure. (See 'Oil:gas partition coefficient/potency' above.)

-The oil:gas partition coefficient (ie, the ratio of an agent's solubility in oil to its solubility in gas) provides an estimate of its anesthetic potency. Oil:gas partition coefficients from highest to lowest (ie, most to least potent) are (table 1):

Because of its very low potency, N₂O alone is inadequate to induce general anesthesia at physiologic temperature and pressure. (See 'Oil:gas partition coefficient/potency' above.)

•Patient-related considerations (see 'Patient-related considerations' above):

-Respiratory factors – Increased minute ventilation speeds uptake of inhalation agents. Conversely, decreased minute ventilation or the presence of ventilation/perfusion (V/Q) mismatch or dead space slows uptake and clearance. (See 'Respiratory factors' above.)

-Cardiovascular factors – Somewhat counterintuitively, decreased cardiac output actually speeds uptake and anesthetic induction because reduced blood flow through the pulmonary vasculature promotes faster equilibration between concentration of inhalation agent in alveoli and blood. Conversely, increased cardiac output slows uptake and anesthetic induction. (See 'Cardiovascular factors' above.)

•Technique-related considerations – A high inhaled concentration of the selected volatile agent (overpressurization) and coadministration of N₂O ("second gas" effect) will speed anesthetic induction by augmenting the agent's rate of rise in alveoli. (See 'Technique-related considerations' above.)

●Environmental impact – The environmental impact of inhalation anesthetic agents is discussed separately. (See "Environmental impact of perioperative care", section on 'Managing use of anesthetic inhalation agents'.)