What are the anesthetic gases？
Anesthetic gases (nitrous oxide, halothane, isoflurane, desflurane, sevoflurane), also known as inhaled anesthetics, are administered as primary therapy for preoperative sedation and adjunctive anesthesia maintenance to intravenous (IV) anesthetic agents (i.e., midazolam, propofol) in the perioperative setting. Inhaled anesthetics enjoy regular use in the clinical setting due to chemical properties that allow the rapid introduction of an agent into arterial blood via the pulmonary circulation compared to the more circuitous route of venous circulation.The significance of rapid therapeutic effects allows for efficient induction and discontinuation of sedation induced by these agents, providing proper amnesia, anesthesia, and a faster recovery period in postoperative care than IV agents.
Though indicated solely for the perioperative setting, these agents also have a significant off-label use within critical care to facilitate patient tolerance of endotracheal intubation, mechanical ventilation, and bedside procedures. Generally, for these cases, the recommended use of IV benzodiazepines (midazolam, lorazepam, diazepam) or propofol induces this level of sedation. However, more recent studies have explored the regular use of inhaled anesthetics, specifically the volatile anesthetics (halothane, isoflurane, desflurane, sevoflurane), as first-line agents for critical care sedation. Preliminary findings show shorter times to extubation and shorter lengths of stay in the ICU; however, there is a need for further study of these agents in this setting
FDA-label Indications
Preoperative sedation – primary or adjunctive; rapid induction of sedation, providing amnesia and anesthesia during surgical procedures.
Perioperative sedation maintenance – adjunctive; maintains anesthesia after sedation by IV benzodiazepines or propofol.
FDA-off-label Indications
ICU sedation – primary or adjunctive; facilitates tolerance of intubation, mechanical ventilation, bedside procedures.
Mechanism of Action
Inhaled anesthetics work to depress neurotransmission of excitatory paths involving acetylcholine (muscarinic and nicotinic receptors), glutamate (NMDA receptors), and serotonin (5-HT receptors) within the central nervous system (CNS) and augment inhibitory signals including chloride channels (GABA receptors) and potassium channels to provide an adequate level of sedation. These agents are sub-classified by both their chemical properties and believed mechanisms of action:
Non-volatile gases: nitrous oxide (N2O)
Volatile gases: halothane, isoflurane, desflurane, sevoflurane
The main distinction between the non-volatile and volatile gases originally stemmed from their specific chemical properties. Non-volatile anesthetics have high vapor pressures and low boiling points, meaning they are in gas form at room temperature, whereas volatile anesthetics have low vapor pressures and high boiling points, meaning they are liquids at room temperature and so require vaporizers during administration. Since these agents work on many different receptors, as described above, physiologically distinguishing these subclasses has proved to be more arduous. Current thought suggests non-volatile agents primarily inhibit NMDA receptors and glutamate signaling, whereas volatile agents augment GABA signaling
Administration
Administration of all anesthetic gases is via inhalation. As described above, N2O being the only non-volatile gas clinically administered at room temperature in its gaseous state, whereas the volatile gases of halothane, isoflurane, desflurane, and sevoflurane are liquids at room temperature requiring a vaporizer for administration. Compared to other agents in pharmacology, where the basis of the therapeutic index is the bioavailability of the agent within serum determined via the route of administration (IV, PO, IM, SC), inhaled anesthetics are unique in that they have one route of administration and multiple factors, listed below, that determine therapeutic index
Minimum alveolar concentration (MAC): used as a measure of potency, defined as the % gas concentration determined to produce immobility to noxious stimuli in 50% of patients. Essentially, the higher the MAC, the less the potency of the gas for sedative purposes.
Alveolar concentration (FA) to inspired concentration (FI): used to determine the speed of induction, works on a 0 to 1 scale where the FA/FI will approach 1 as the gas gets administered, 1 being equilibrium. The rate at which the above ratio approaches equilibrium represents the speed of induction.
Partition Coefficients: used to determine the solubility of the gas in both arterial blood (blood to gas) and perfused tissues (brain to blood). These coefficients represent the amount of gas that can enter the blood and the amount that must be reversed for equilibrium to be achieved, forming an inverse relationship with the speed of induction (FA/FI). The higher the partition coefficient, the higher concentration that can enter the blood or the brain, and the more that must flow backward along that gradient to reach equilibrium, which causes a slower rate of induction.
All agents have individualized aspects concerning administration:
N2O: greater than 100% MAC, blood to gas partition coefficient of 0.47, brain to blood partition coefficient of 1.1
Halothane: 0.75% MAC, blood to gas partition coefficient of 2.30, brain to blood partition coefficient of 2.9
Isoflurane: 1.4% MAC, blood to gas partition coefficient of 1.4, brain to blood partition coefficient of 2.6
Desflurane: 6 to 7% MAC, blood:gas partition coefficient of 0.42, brain:blood partition coefficient of 1.3
Sevoflurane: 2.0% MAC, blood:gas partition coefficient of 0.69, brain:blood partition coefficient of 1.7
