PHARMACOLOGY:
Inhalation Anesthetics
Lecture 8

Jeff Ko, DVM, MS, DACVA

Overall view

Commonly used inhalation anesthetics

• Isoflurane (mainly in small animals)
• Sevoflurane (both small and large animals)

Less commonly used inhalant anesthetics

• Methoxyflurane (not available in the US)
• Halothane (mainly used in large animals)
• Desflurane (phase out in human anesthesia)
• Nitrous oxide (not potent enough to be used in veterinary anesthesia)

Clinical considerations of selecting an inhalation agent

Metabolism

Anesthetic potency

• What is MAC ?
  • MAC is the minimum alveolar concentration of an anesthetic (in volume %) at which 50% of the patient will not respond to painful stimuli (eg, surgery-skin incision, tail clamp, or electrical stimulation).
  • MAC is used to compare inhalation anesthetic potency. (Similar to mg/kg for those of injectable anesthetics).
  • Clinically, achieving a surgical plane of anesthesia usually requires 1.2 to 1.5 times MAC to ensure 99.9% of the patient that will not respond to the surgical stimulation.
• The lower the MAC value, the more potent the anesthetic agent.
  • MAC values from the table below demonstrates that methoxyflurane is the most potent and nitrous oxide is the least potent inhalant anesthetics.  Halothane, isoflurane and sevoflurane are somewhere in between.  Sevoflurane is less potent than halothane and isoflurane.
  • The clinical implication of anesthetic potency is mainly related to the end-tidal inhalant anesthetic concentrations of the patient, and therefore, the dial setting of the vaporizer. The less potent the inhalant anesthetic, the higher the percentage of the inhalant anesthetic agent that will have to be used for anesthesia maintenance, and therefore the higher the dial setting of the vaporizer has to be set.

• Nitrous oxide is not commonly used in veterinary anesthesia for the following reasons:
  • Weak analgesic property when used alone in domestic animal species (MAC is roughly 200% - it is twice as potent in humans).
  • Its use together with a primary inhalant anesthetic (such as halothane, isoflurane) only reduces the amount of primary inhalation anesthetic by 25% to 30% of the control value (using halothane or isoflurane alone) at the most. This may not significantly reduce the amount of the primary anesthetic.
  • Because nitrous oxide is a weak analgesic agent and must be used in high concentrations, the inspired oxygen concentration is proportionally reduced.  This is not suitable for patients with pulmonary diseases that may require as much as 100% inspired oxygen to maintain acceptable blood oxygenation.
  • The use of nitrous oxide requires a higher fresh gas flow rate than would be used with oxygen alone.  Accordingly the total amount of the primary anesthetic that is vaporized is increased - more anesthetic is wasted, and therefore cost is increased.
  • Nitrous oxide diffuses rapidly into closed gas cavities within body, at a faster rate than nitrogen diffuses out of the cavity, resulting in either an increase in volume or pressure.  Patients with gastric or intestinal distension (colic, or GDV) or pneumothorax will suffer further.
  • Risk of diffusion (dilutional) hypoxia. This occurs at the time when the nitrous oxide is turned off and the patient is disconnected from the breathing circuit and starts to breathe room air (21% oxygen). Nitrous oxide is usually used in large volumes during anesthesia (> 50%), and when it is turned off its uptake is reversed and it moves from the blood to the alveoli. Thus, during the first 5 to 10 minutes after discontinuing the nitrous oxide, the volume moving into the lung is large and dilutes the oxygen concentration in the alveoli. If breathing room air, this may result in hypoxia. To avoid dilutional hypoxia, the animal should breathe 100% oxygen for the first 5-10 minutes after discontinuing nitrous oxide use.

Consideration of rate of induction, rate of change in anesthetic depth, and rate of recovery (blood/gas solubility)

• Rate of induction, change in anesthetic depth, and rate of recovery are related to the blood/gas solubility of each inhalant anesthetic.
• The higher the blood/gas solubility, the slower the induction and recovery rates.
• The higher the blood/gas solubility, the slower rate of change in depth of anesthesia.

• Based on the table above, induction, recovery and changes in anesthetic depth are relatively slow with methoxyflurane and relatively rapid with nitrous oxide and desflurane.
• Mask induction is impractical using methoxyflurane because of its high solubility and therefore very slow speed of induction. In addition, attempts to speed induction with high anesthetic concentration are limited by the maximum concentration achievable with methoxyflurane (approximately 3% - due to its low vapor pressure).  Clinically we use sevoflurane for mask induction. Sevoflurane possess several desirable properties for mask induction over other inhalant anesthetics. Sevoflurane 1) has a lower blood/gas solubility; 2) it does not irritate airway and stimulate excessive secretions; 3) it lacks of pungency and allows animal to accept the inhalant with ease, 4) the vaporizer of sevoflurane can be set as high as 7-8% to pressurize the inhalant into the patient’s lungs.
• Because of its low blood/gas solubility, nitrous oxide is used to facilitate the induction and rate of change in anesthetic depth when used together with one of the primary anesthetics such as halothane or isoflurane (this is called the 2nd gas effect).
• Because of its low blood/gas solubility, sevoflurane is now replacing isoflurane and used extensively in avian anesthesia for rapid induction and recovery. 

Cardiopulmonary consideration

Overall, all inhalant anesthetics depress cardiopulmonary function a dose-dependent manner as shown by the decreases cardiac output, blood pressure, respiratory rate and increase in partial pressure in CO2 concentrations. 

• Myocardial depression:

 Halothane > or = methoxyflurane > isoflurane = sevoflurane = desflurane > N₂O

• Reduction in cardiac output:

 Halothane > or = methoxyflurane > isoflurane = sevoflurane = desflurane > N₂O

• Reduction in systemic vascular resistance:

 Isoflurane = sevoflurane = desflurane > methoxyflurane > or = halothane > N₂O

• Respiratory depression:

 Isoflurane ≥ sevoflurane = desflurane > methoxyflurane > halothane > N₂O

Cost consideration

• Desflurane > sevoflurane > Isoflurane > halothane
• Methoxyflurane is relatively expensive due to lack of production (it is no longer being produced by the company that produced it for many years).
• Isoflurane has lost its patent and the cost has been relatively low.
• Sevoflurane is a newest inhalant agent and cost about 4-5 times more than isoflurane when compared on a ml/ml basis.
• Desflurane requires a special vaporizer (due to its high vapor pressure) that is only compatible with the newest human anesthetic machines - both the vaporizer and the anesthetic machines are very expensive. Desflurane vaporizer requires a plug in with an electrical outlet for external heat supply to the vaporizer. This design is not practical for most of veterinary anesthesia machine which designs to be more mobile utilization. Because of the equipment considerations, only sevoflurane is currently marketed in the veterinary medicine.

Clinical use of inhalant anesthetics

• Inhalant anesthetics are used for induction (one more alternative to those of intravenous injectable anesthetics) and maintenance of general anesthesia.
• Advantages of using inhalant anesthetics for induction of general anesthesia:
  • It offers the advantage of accurately controlling anesthetic depth during induction with the safety of being able to discontinue the administration of the inhalant anesthetic immediately if problem arise.
  • Furthermore, should problem arise the inhalant anesthetic (sevoflurane, or isoflurane) can be eliminated quickly through ventilation.
  • High-inspired oxygen is usually provided with inhalant anesthetic during the induction.
• Disadvantages of using inhalant anesthetic for induction include:
  • It is not suitable for healthy, unpremedicated hyperactive or aggressive large size dogs because of the relatively slow speed of induction via inhalant anesthetic. The induction is likely to accompany with vocalization, excitement, defecation, urination, and vigorous struggling.
  • The pungent smell of the isoflurane or halothane may prompt the animal to hold their breath during induction and therefore prevents the uptake of the inhalant anesthetic and slows the speed of induction.
  • Sevoflurane is superior to isoflurane and halothane for inhalant anesthetic induction…less irritation to the airway and faster speed of induction, and lack of pungency.  It has been the main inhalant anesthetic for using in human infants and children for mask induction.  At OSU, thousands of dogs, cats, birds, rodents and foals were mask induced with sevoflurane for anesthesia induction during the past 5 years.
  • Pollution of the work environment during induction. Waste inhalant anesthetic gas may cause headaches and other health problems. This can be taken care of by improve the ventilation at the working place. An electrical fan can be turned on during the induction to blow away the waste gas from the handlers.
• Advantages of using inhalation anesthetics for maintenance of general anesthesia:
  • Protection of the airway - since almost all patients anesthetized with inhalant anesthetic is intubated.
  • The depth of anesthesia during maintenance is easily controlled by adjusting the vaporizer output, ventilation pattern and the total flow rate.
  • High-inspired oxygen is usually provided with inhalant anesthetic during the maintenance.  This will augment the oxygen content of the blood. It is especially helpful to the patient with low oxygen-carrying capacity (patients with anemia or respiratory dysfunction).
  • Rapid recovery when compared to the injectable combinations. (Inhalant anesthetics are mostly eliminated through ventilation, whereas injectable anesthetics rely on the liver and kidney for metabolism/elimination).

Methods of inhalant anesthetic induction

Face-mask induction:

• Select a tight-fitting face mask (Figure 1) and place it on the face of the animal. Use the smallest mask possible to minimize dead space ventilation.
• Suitable in birds, rodents, neonate ruminants or foals, dogs or cats, or in healthy hyperactive dogs following profound premedication (acepromazine, opioids, or alpha-2 agents).
• Face mask induction is not practical in adult large animals (equine, bovine, porcine)
• Face mask induction usually begins with 4-5% of halothane, isoflurane, or 7-8% sevoflurane and continues until the animal is unconscious and able to be intubated.
• Using face mask induction in healthy animals with isoflurane without profound premedication usually results in excitement, vocalization, defecation, and struggling.
• Sevoflurane is markedly better for mask inductions than isoflurane.
• Using a non-rebreathing circuit (Modified Jackson Reeves, Bain, Norman Mask Elbow) for anesthesia induction is much faster than using a rebreathing circuit (see lecture note on breathing circuits). This is due to less volume barrier associated with a non-rebreathing circuit than a rebreathing circuit (in general, 200 ml vs several liters difference). 
• Debilitated patients (diseased dogs, cats, birds, other small ruminants or foals).
  • Mask induction usually begins with 2-3% of halothane, isoflurane, or 5-8% sevoflurane and continues until the patient is unconscious and ready for intubation. Sevoflurane induction usually takes less than 3 minutes. So be aware of the time frame and pay close attention to the patient when using high % for induction.
  • Debilitated patients are already depressed by the disease and they are more sensitive to the inhalation anesthetics, therefore reducing the inhalant anesthetic % is usually a good idea. If higher
  • Debilitated animals are less likely to become excited or struggle during induction.

Chamber induction:

• Suitable in small intractable animals (small dogs, cats, reptiles, and other small exotics).
• Provides a "hands free" induction with minimal physical restraint to the patients. Safe to the patient as well as personnel.
• Induction chambers are usually made of aquarium type of plastic box with various sizes (10-25 gallons).
• 5% isoflurane or 8% sevoflurane with high flow rates of oxygen (6+ liters per min) is used until the animal losses its righting reflex.  The animal is then taken out of the chamber, placed on a face mask, and anesthetic administration is continued until the patient is unconscious and ready for endotracheal intubation.
• To facilitate the speed of induction with chamber, use as high oxygen flow per min, as high vaporizer dial setting, and as small size of chamber as possible.

Nasotracheal intubation for anesthetic induction:

• Suitable in foals and calves.
• Most commonly done in foals up to 100 kg in body weight.
• Calves are more difficult to nasotracheally intubate than foals.
• Nasotracheal intubation is accomplished by passing a long endotracheal tube through the nose, while extending the head and neck to straighten the airway.
  • A small dose of xylazine, diazepam or midazolam may be used to sedate the patient if necessary (usually it is not needed)
  • Lubrication of the endotracheal tube with lidocaine gel may facilitate passage of the tube
  • If intubation proves difficult, administration of 2-3 mls of lidocaine down the endotracheal tube while the tip of the tube is in the pharynx may facilitate intubation.
• The animal is often pre-oxygenated for a few minutes with 100% oxygen before the anesthetic vaporizer is turned on for induction, if isoflurane is used.
• Isoflurane at 3-5% or sevoflurane at 7-8% is commonly employed.
• Nitrous oxide is often used (2nd gas effect) to facilitate the speed of induction for isoflurane, therefore minimizing excitement (Stage II of anesthesia). As soon as induction is completed, nitrous oxide is turned off. Sevoflurane does not require nitrous oxide to facilitate speed of induction due to its low blood/gas solubility.

 Second gas effect of nitrous oxide:

• Nitrous oxide has some physical characteristics that distinguish it from other inhalant anesthetics.  It has very low blood/gas solubility, so that its uptake and equilibration throughout the body is very rapid.  Because it is used in large volumes (usually more than 50%) and its uptake is rapid during the induction phase of anesthesia, it enhances the uptake of a second anesthetic gas, especially the more soluble inhalant anesthetics, such as isoflurane or halothane.

Maintenance of general anesthesia

• All major inhalant anesthetics (methoxyflurane, halothane, isoflurane and sevoflurane) are maintained with 1.2 to 1.5 times MAC for general anesthesia.
• Premedication of a tranquilizer or an opioid will reduce the maintenance concentration of inhalant anesthetics.
• In general inhalation anesthetics are maintained with following concentrations:
  • Methoxyflurane: 0.5 - 1.5%
  • Halothane: 0.75 - 2.0%
  • Isoflurane: 1 - 2.5 %
  • Sevoflurane: 2.5 - 4.0%

Factors affecting MAC

• Although all inhalant anesthetics are maintained with 1.2 to 1.5 times MAC for general anesthesia, factors that affect MAC have to be considered during the maintenance of general anesthesia.
• Factors that decrease MAC:
  • Hypotension
  • Anemia ( PCV < 13%).
  • Hypothermia
  • Metabolic acidosis
  • Extreme hypoxia (PaO2 < 38 mmHg)
  • Age: old animal require less anesthetic
  • Premedication (opioids, sedatives, tranquilizers)
  • Local anesthetics
  • Pregnancy
  • Hypothyroidism
  • Concurrent use of nitrous oxide
    • Clinical implications:
      • If you anesthetize an anemic patient – you will need less inhalant anesthetic to maintain this patient.
      • If your patient is losing blood intra-operatively – i.e., hypotensive, you will need less inhalant anesthetic to maintain this patient.
      • If you are anesthetizing a 15 years old dog or cat
      • If you premedicated your dog or cat with acepromazine, xylazine, or morphine etc. before anesthesia
      • If you anesthetize a pregnant mare
      • If you anesthetize a colic horse (with metabolic acidosis)
      • If your patient is getting too cold intra-operatively
• Factors increasing MAC
  • Increasing body temperature – increases cerebral metabolic rate of brain
  • Hyperthyroidism
  • Hypernatrimia
• Factors NOT affecting MAC
  • Type of stimulation
  • Duration of anesthesia
  • Species - MAC varies by only 10-20% from species to species
  • Gender
  • P_aCO₂ between range of 14-95 mmHg
  • Metabolic alkalosis
  • P_aO₂ between range of 38-500 mmHg
  • Hypertension
  • Potassium – no effect

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last updated October 19, 2007
Questions? Comments? Dr. Lyon Lee