IInhalation anesthetics are widely used for the anesthetic management of animals. The most common inhalant anesthetics currently available in veterinary medicine are halothane and isoflurane—both of which are volatile liquids at room temperature.

The inhalant anesthetics are unique among the anesthetic drugs because they are administered, and in large part removed from the body, via the lungs. The primary advantage of their use arises because their pharmacokinetic characteristics favor predictable and rapid adjustment of the anesthetic depth of the patient.

One disadvantage of their use is the requirement of a special apparatus (i.e. an anesthetic vaporizer) to deliver a controlled amount of the anesthetic drug to the patient. Precision anesthetic vaporizers are calibrated in percentage of agent (i.e. in vol %) and are only accurate for delivery of the specific agent for which they have been calibrated.

The change in state of an inhalant anesthetic from a liquid to a gas phase is known as vaporization. In a closed container (that is kept at constant temperature), the dynamic process of vaporization eventually reaches an equilibrium---at which point the gas phase of the volatile anesthetic liquid is saturated. Within a closed container, molecules of a vapor exert a force (i.e. pressure) per unit area. The saturated vapor pressure represents a maximum concentration of molecules, in the vapor state, that can exist for a given liquid at a specific temperature. The greater the vapor pressure of a specific inhalant anesthetic, the greater the concentration of the drug deliverable to the patient.

The low saturated vapor pressure of the inhalant anesthetic, methoxyflurane (no longer available), provided users with a "range of safety" in the "open drop jar" anesthetic delivery system (as used for rodents). With higher saturated vapor pressures, halothane and isoflurane attain a concentration (using an "open drop jar") that is above the range of concentrations that are needed for safe clinical anesthetic management. Herein lies the reason these agents should be used in a precision vaporizer. The purpose of the precision anesthetic vaporizer is to dilute the vapor generated from the liquid anesthetic with oxygen to produce a more controlled inspired anesthetic concentration.

Anesthetic gases and vapors dissolve in liquids and solids. The solubility of an anesthetic in blood and body tissues is a primary factor in the rate of uptake of the drug, and its distribution, within the body.

Solubility of inhalation anesthetics is most commonly measured and expressed as a partition coefficient (PC). The PC is the concentration ratio of an anesthetic in the solvent and gas phases (e.g. blood and gas) or between two tissue solvents (e.g. brain and blood).

One of the most important PCs used in describing an inhalant anesthetic is the blood/gas PC. This measurement provides a means for predicting the speed of anesthetic induction, recovery, and change of anesthetic depth. For example, an inhalant anesthestic that has a PC value of 15 will have a blood concentration that will be 15 times greater at equilibrium than that in alveolar gas. Alternatively, an inhalant anesthetic with a PC value of 1.4 (at equilibrium) will have a concentration in blood that is only 1.4 times greater than alveolar air.

The inhalant anesthetic with the higher PC value (as compared to the one with the lower PC value) will require a longer time of administration to attain a partial pressure in the body for a particular end point (such as anesthetic induction). Likewise, the anesthetic with the higher PC value will have more anesthetic (at equilibrium) to be eliminated from blood---thus, requiring a longer anesthetic recovery period.

The goal in administering an inhalation anesthetic to a patient is to achieve an adequate partial pressure or tension of anesthetic (Panes) in the brain to cause a desired level of CNS depression commensurate with the definition of general anesthesia. The rate of change of anesthetic depth is dependent upon the rate of change in anesthetic tensions in the various "media" in which the anesthetic is contained before reaching the brain.

Inhalation anesthetics move down a series of partial pressure gradients (from regions of higher tension to those of lower tension) until equilibrium (i.e. equal pressure throughout the anesthetic delivery equipment and body tissues) is established. The alveolar partial pressure (PA), of an anesthetic, is a balance between anesthetic input (i.e. anesthetic delivery to the alveoli) and loss (uptake of the anesthetic by blood and body tissues) from the lungs.

A rapid rise in the PA of an anesthetic is associated with a rapid anesthetic induction or change in anesthetic depth. Factors that contribute to a rapid change in the PA of an anesthetic are those related to anything that increases inspired anesthetic concentration, anything that increases alveolar ventilation, and/or anything that decreases removal of the anesthetic from the alveoli.

The uptake of an inhalant anesthetic by blood is related to three factors: solubility (the blood/gas PC), cardiac output (CO), and the difference in the anesthetic partial pressure between the alveolus and venous blood returning to the lungs. The blood serves as a conduit for drug delivery to the brain and, as such, can be visualized as a pharmacologically inactive reservoir that is interposed between the lungs and the agent’s site of desired pharmacologic activity (i.e. the brain).

For inhalant anesthetics with a high blood/gas PC, the blood acts like a large "reservoir" into which the anesthetic is poured and, accordingly, blood is "reluctant" to give up the agent to other tissues. The greater the CO, the more blood passes through the lungs carrying away anesthetic from the alveoli. This has the same effect as an increased anesthetic agent blood solubility.

The magnitude of difference in anesthetic partial pressure between the alveoli and venous blood is related to the amount of uptake of anesthetic by tissues. The largest pressure difference gradient occurs during induction. Once the tissues no longer absorb anesthetic (i.e. equilibrium is reached) there is no longer any uptake of anesthetic from the lungs. Recovery from inhalation anesthesia results from the elimination of anesthetic from the brain and is essentially a reverse of the induction process. The same three factors are important in anesthesia recovery.

Inhalation anesthetics are not chemically inert. They undergo varying degrees of metabolism—primarily in the liver, but also (to lesser degrees) in the lung, kidney, and intestinal tract. In a limited way, metabolism may facilitate anesthetic recovery. There is also the potential for acute and chronic toxicities by intermediary or end-metabolites of inhalation agents, especially on kidneys, liver, and reproductive organs. The magnitude of metabolism of inhalation anesthetic agents is determined by a variety of factors including the chemical structure of the agent, hepatic enzyme activity, blood concentration of the anesthetic, disease states of the patient, and genetic factors of the patient.

The term potency refers to the quantity of an inhalant anesthetic that must be administered to cause a desired effect (i.e. general anesthesia). The standard quantitative index of anesthetic potency for inhalation anesthetics is inversely related to the "minimum alveolar concentration" (MAC).

MAC is defined as the minimum alveolar concentration of an anesthetic, at one atmosphere pressure, that produces immobility in 50% of the subjects exposed to a supramaximal noxious stimulus. Thus, MAC corresponds to the effective dose that anesthetized half of the subjects (i.e. ED50).

MAC is determined in healthy animals, under laboratory conditions, in the absence of other drugs/circumstances that may modify the requirements for anesthesia. Rarely is this the case with research animals. Therefore, the expected MAC in research animals may be modified by experimental status, research stressors, or other stimuli.

Anesthetic dose (of a specific inhalant anesthetic) can be expressed as multiples of MAC. This is directly related to the measure of the inhalation anesthetic potency and serves as a means of assessing the effects of increasing anesthetic depths on physiologic processes. In a single species, the variability in MAC (for a specific agent) is generally small. Even between species the variability in MAC, for a given agent, is usually not large. Equipotent doses (i.e. equivalent concentrations of different anesthetics at MAC) are useful for comparing effects of inhalation anesthetics on vital organs.

Pharmacodynamic action of the two inhalant anesthetics, halothane and isoflurane, on various body systems include:

• induces a reversible, generalized, central nervous system depression

• depresses respiratory system function i.e. progressive decrease of spontaneous ventilation

• decrease of tidal volume

• decrease in minute volume

• increase in dead space ventilation

• increase PaCO2

• decrease PaO2

• decreases cardiac output (due to a decrease in stroke volume as a result of depression in myocardial contractility)

• dose-dependent decrease in arterial blood pressure (partially related to decrease in stroke volume)

• may increase the automaticity of the myocardium (i.e. sensitize the heart to arrhythmogenic effects of catecholamines; most prominent with halothane)

• dose-related reduction in renal blood flow and glomerular filtration rate

• depresses hepatic function and may cause hepatocellular damage (direct or indirect action; transient or permanent effect; primarily related to reduced hepatic blood flow)

• may cause rapid rise in body temperature (most commonly occurs in swine; most potent triggering agent is halothane)

This method is well-suited for use in rodent quarantine and sentinel programs because the bag can be used once, resealed and discarded in an appropriate manner after the anesthetic procedure is finished and the mouse is removed. The piece of cotton enclosed in a histopathology cassette technique can also be used in more traditional induction chambers (e.g., desiccation chambers, bell jars, jars with screw top lids) for vaporization of isoflurane or halothane while protecting the animal from the gas in liquid form. In one author’s experience, the use of 0.1-0.2) ml of either agent per liter of induction chamber volume gives a gas concentration of two to four percent, which is sufficient to induce anesthesia in a mouse in less than 60 seconds. The other authors have found that 0.6 ml isoflurane per liter of chamber works safely in providing deep anesthesia of reasonable duration to obtain a blood sample. However, owing to the high volatility of these agents, the lid should be kept on the induction chamber constantly or the volume of gas will be rapidly exhausted. For rapid and effective induction, we have found that the liquid form of the anesthetic gas must be replenished on the piece of cotton approximately every three batches. Also, maintenance or supplemental anesthesia during the procedure can be provided by placing 0.05-0.1 ml of isoflurane in cotton at the tip of an Eppendorf tube used as a nose cone.

For more information, see articles:

• Inhalant Anesthesia -Patient Considerations

• Inhalant Anesthesia - Specific Agents