Inhalant Anesthesia and Inhalant Anesthetics

“O sleep! O gentle sleep! Nature’s soft nurse, how have I frightened thee, That thou no more will weigh my eyelids down and steep my senses in forgetfulness?”

WILLIAM SHAKESPEARE

Overview

Inhalant anesthetic drugs (inhalants) act at the brain and spinal cord to produce general anesthesia. They are suitable for use in all species including reptiles, birds, fish, and zoo animals. Their safe use requires knowledge of their pharmacologic effects and physical and chemical properties. Anesthetic doses produce unconsciousness (hypnosis), immobilization (muscle relaxation, hyporeflexia), and analgesia. Inhalant anesthetics provide optimal control of anesthesia, rapid induction and recovery from anesthesia, and have minimal carryover (“hangover”) effects. Adjuncts to anesthesia (tranquilizers, analgesics) are frequently used in conjunction with inhalants to augment the quality of anesthesia and reduce the amount of inhalant anesthetic required to maintain anesthesia, thereby decreasing cardiorespiratory depression.

General Considerations

I Inhalant anesthetics are vapors or gases that are inhaled directly into the respiratory system

II To produce anesthesia, inhalant anesthetics must be absorbed from the alveoli into the bloodstream and carried by the blood to the central nervous system (CNS)

III Inhalant anesthetics are primarily eliminated by the lungs

A Some metabolism occurs in the liver

IV The uptake and elimination of inhalant anesthetic drugs are relatively rapid, thus the depth of anesthesia can be controlled effectively, but constant monitoring is required

V The classical stages and planes of anesthesia (Fig. 9-1) were developed by Guedel for ether anesthesia and continue to be loosely applied to most inhalant anesthetics

FIG. 9-1 Increasing “depth” of anesthesia produces characteristic changes in ocular, motor reflex, respiratory, and cardiovascular responses. These effects were originally described for ether by Guedel as the stages and planes of anesthesia. Although not perfect, they are useful for determining inhalant anesthetic (isoflurane, sevoflurane) effects. Moderate (medium) levels of inhalant anesthesia (stage III) are ideal for most invasive surgical procedures. Minimal (light) levels of stage III anesthesia can be administered for minor surgical procedures (biopsy, laceration repair) if analgesia is supplemented by local anesthetics or opioids.

A Stage I: analgesia (from the beginning of induction to the loss of consciousness)

1. Disorientation, with normal reflexes or hyperreflexia, is the most common feature

2. Anxiety, increased heart rate, and rapid respirations may occur

3. Excessive salivation may occur

B Stage II: delirium or excitement, which represents the period of early loss of consciousness

1. Potential hazards of stage II include struggling, physical injury, and increased sympathetic tone

2. Voluntary centers in the brain become depressed; the patient becomes unaware of its surroundings

3. During light anesthesia, the animal may react to stimuli (e.g., sound) with exaggerated struggling

4. Respirations are generally irregular in depth and rate, and breath holding may occur

5. The eyelids are widely open, and the pupils are dilated because of sympathetic stimulation

6. Reflex vomiting may occur unless food has been withheld; defecation and urination may occur

7. The duration of stage II can be decreased or eliminated by preanesthetic medication

C Stage III

1. Plane I: marked by more regular respiration

a. Carbon dioxide (CO₂) retention during the preceding stages may double tidal volume for the first few minutes

b. Preanesthetic medication directly affects the rate and volume of respiration

c. Responses to pain, although depressed, are still present

d. Cardiovascular function is only minimally affected

2. Plane II: respiratory rate may be increased or decreased and respiratory volume (tidal volume) is decreased; cardiovascular function is mildly depressed

3. Plane III: loss of intercostal muscle activity

a. Respiratory depression is significant

b. Cardiovascular function is noticeably depressed

4. Plane IV: complete paralysis of muscles needed for breathing

a. Cessation of all respiratory effort and dilation of the pupils

b. Cardiovascular function is generally impaired, resulting in vasodilation leading to hypotension

D Stage IV: respiratory arrest followed by circulatory collapse; death ensues within 1 to 5 minutes

Desirable Properties of Inhalant Anesthetic Drugs

I Nonirritating and free from disagreeable odors

II Easily controlled, producing rapid induction and recovery from anesthesia

III Muscular relaxation; hyporeflexia

IV Analgesia

V Minimal side effects

VI Nontoxic to the animal or the environment

VII Not flammable or explosive (stable during storage)

VIII Compatible with other drugs

Factors Controlling the Brain Tension of Inhalant Anesthetic Drugs

I Physical and chemical properties of the drug (See Table 9-1)

TABLE 9-1

Boiling Points, Vapor Pressures, and Vaporization of Inhalant Anesthetic Drugs

Drug	Boiling Point (°C)	Vapor pressure at 20° C (mm Hg)	Maximum Concentration of Vapor (%) Delivered by Saturation Vaporizer at 20° C	Useful Ranges of Concentration (agent used alone)
Drug	Boiling Point (°C)	Vapor pressure at 20° C (mm Hg)		Induction (%)	Maintenance (%)
VOLATILE ANESTHETIC DRUGS
Desflurane	23.5	664	87.4	8-15	5-9
Sevoflurane	59	160	22	4-5	2.0-3.5
Isoflurane	48	252	33	2-6	1-3
Halothane	50	243	32	1-4	0.5-2.0
ANESTHETIC GAS
Nitrous oxide*	-89	39,500 (50 atm)

^*Nitrous oxide is a gas at room temperature.

A Vapor pressure of the inhalant determines its volatility

1. Volatility determines the design of the vaporizer used to deliver clinically relevant concentrations of inhalants (see Chapter 12)

B Boiling points (other than for nitrous oxide [N₂O] and desflurane) are higher than room temperature (70° F or 27° C)

1. N₂O is a gas at room temperatures. Its delivery is controlled using a flow meter

2. Desflurane is delivered using an electrically heated vaporizer to deliver consistent concentrations

II Anesthetic system

A The concentration of inhalant delivered to the animal is determined by the type of vaporizer, the vaporizer setting, the fresh gas flow rate, and the type of anesthetic circuit (Chapter 12)

B Frequent inspection and maintenance of inhalant anesthetic equipment is necessary to prevent malfunctions such as leaks and sticky one-way valves

III Ventilation and uptake: The partial pressure of inhalant anesthetic in the brain and spinal cord depends on the alveolar partial pressure; the alveolar partial pressure of an inhalant anesthetic is the result of the inspired concentration, the alveolar ventilation, and uptake from the lungs. Rapidity of uptake of inhalants is determined by their blood-gas partition coefficients, the cardiac output or lung blood flow, and the alveolar-to-venous partial pressure difference.

A Inspired concentration

1. Concentration effect: the greater the inspired concentration (vaporizer setting), the more rapid the rate of rise of the alveolar concentration

2. Second-gas effect

a. A 50% to 70% inspired concentration of N₂O initially augments the inflow and rate of uptake of a second gas (sevoflurane, isoflurane) in the inspired mixture

B Alveolar ventilation

1. Generally, the greater the ventilation (minute volume), the more rapid the approach of the alveolar gas concentration of any inhalant to its inspired gas concentration, but excessive hyperventilation may slow induction by reducing cerebral blood flow

2. The rate of rise of the inhalant concentration in the alveoli may be delayed in the presence of large lung volumes because of the increased functional residual capacity (volume of gas in the lungs at the end of expiration)

3. Factors affecting ventilation

a. Respiratory rate

b. Tidal volume

c. Increased dead space (anatomic and physiologic) that develops during anesthesia results in decreased effective alveolar ventilation; tidal volume (V_T) = dead space volume (V_D) + alveolar ventilation (V_A): V_T = V_D + V_A

d. Effective alveolar ventilation requires a patent airway

e. Preanesthetic and induction drugs may cause respiratory depression, slowing the onset of action of inhalant anesthesia

C Uptake of inhalant anesthetic from the lungs

1. Solubility: describes how much of a substance can be dissolved in a gas, liquid, or solid (e.g., fat); the relative solubility of inhalants is usually expressed as a partition coefficient; how an inhalant is distributed between two phases (e.g., between blood and gas, between tissue and blood); Ostwald’s partition coefficient expresses the solubility of an inhalant between blood and gas. An inhalant with a blood-gas partition coefficient of 2 has one volume in the alveoli per two volumes in the blood at equilibrium.

Blood-Gas Partitioning

Agent	Blood-Gas Partition Coefficient (Ostwald’s coefficient)
Halothane	2.36
Isoflurane	1.41
Sevoflurane	0.69
Nitrous oxide	0.49
Desflurane	0.42

a. An inhalant’s blood-gas partition coefficient and potency determine its rapidity of onset of effect

b. The greater the blood-gas partition coefficient, the greater the solubility of the inhalant in blood; the tension of the inhalant in arterial blood rises slowly for drugs that are highly soluble in blood (high blood-gas coefficient); onset of the clinical effect is contingent on the tension of the inhalant developed in the blood

c. Inhalants that are more soluble in blood have longer induction and recovery times because large amounts of inhalant must be taken into the blood before their tension (partial pressure) rises sufficiently to produce anesthesia; clinically, slow induction may be overcome by raising the inspired concentration of the inhalant anesthetic to values above those necessary to maintain anesthesia (anesthesia overpressure)

d. The lower the blood-gas partition coefficient, the less soluble the inhalant is in blood (only small quantities are carried in the blood); both alveolar concentration and tension will rise rapidly and blood inhalant anesthetic tension (partial pressure) increases rapidly (Fig. 9-2); less soluble inhalants: N₂O, isoflurane, and sevoflurane have comparatively short induction and short recovery times

FIG. 9-2 The blood-gas solubility coefficient is a determinant of the rate of rise (rate of increase) of the alveolar inhalant concentration. The lower the blood gas solubility coefficient, the faster the increase in alveolar inhalant concentration and the faster induction and recovery from anesthesia (ex. sevoflurane faster than isoflurane).

2. Cardiac output: blood carries the inhalant anesthetic away from the lungs; the greater the cardiac output, the slower the rate of rise of alveolar concentration and the lower the partial pressure of the inhalant anesthetic in the lung and blood

a. Excited, stressed animals generally have an elevated cardiac output and a slower rate of induction because of the slower rate of rise of alveolar concentration and lower partial pressure of the inhalant anesthetic in the lungs; animals with a decreased cardiac output are induced to anesthesia very rapidly

3. Alveolar-venous anesthetic tension difference: during induction, tissues remove nearly all the inhalant brought to them because of the high tissue solubility of most inhalant anesthetics; venous blood returning to the lungs contains little inhalant; as time passes, increasing tissue saturation raises the venous blood concentration; therefore, less inhalant is taken up in the lungs; inhalant uptake is a continuous process towards a steady state (plateau) concentration

4. Other

a. Right-to-left intracardiac or intrapulmonary shunts (e.g., Fallot’s tetralogy) delay induction

b. Left-to-right shunts can speed the rate of induction by increasing the rate of rise of the alveolar concentration and the partial pressure of the inhalant anesthetic in the lung; this occurs very rapidly if the cardiac output is low

c. Pathologic changes in alveoli: if the alveolar membranes are affected by disease resulting in exudate, transudate, emphysema, or pulmonary fibrosis, diffusion may be impaired, and the uptake of the inhalant slowed

IV Factors governing brain and tissue uptake of inhalants

A The factors are the same as those determining uptake from the lungs

1. Solubility (blood versus tissue)

2. Tissue blood flow

3. Arterial blood to tissue inhalant tension difference

B The uptake by tissue is dependent on anesthetic tension in the blood, blood flow, and tissue capillary density

1. Tissues can be categorized into four groups according to blood supply (Fig. 9-3)

FIG. 9-3 Anesthetic delivery to tissues is dependent on blood flow. Lung, brain, heart, and major organs (liver, kidney) have a relatively high blood flow (vessel-rich group [VRG]) compared with muscle and fat and are more susceptible to anesthetic drug-related effects.

a. Vessel-rich group (VRG): 75% of cardiac output (e.g., brain, heart, intestines, liver, kidneys, spleen)

b. Vessel-moderate group, or muscle group (MG): 15% to 20% of cardiac output (e.g., muscle, skin)

c. Fat group (FG): 5% of cardiac output (e.g., adipose tissue)

d. Vessel-poor group: 1% to 2% of cardiac output (e.g., bone, tendons, cartilage)

Blood Flow Groups

Group	Examples	Principal points
VRG: vessel-rich group	Brain, heart, liver	Equilibration of an inhalant anesthetic drug is complete in 5-20 minutes
MG: vessel-moderate group/muscle group	Muscle, skin	Equilibration of an inhalant anesthetic drug is complete in 1.5-4 hours
FG: neutral fat group	Adipose tissue	May affect recovery time after prolonged anesthesia