In veterinary practice, maintenance of anaesthesia with inhalation agents is standard practice because of the simplicity, reliability, predictability, and good recovery quality even after long procedures. Their pharmacological characteristics and administration via the lungs, which act as a damping reservoir, means that microprocessor controlled administration with problem recognition and management is achievable in the near future.

In the early to mid-19th century, inhalation agents were used by people experimenting with "gases at public inhalations for ladies and gentlemen!" Nitrous oxide failed as a sole anaesthetic agent, although veterinary anaesthesia using it was attempted by Sir Humphrey Davy and his students conducting narcosis experiments on dogs and chickens 25 years before human anaesthesia was "discovered." The first administration of general anaesthesia is credited to Dr. Crawford Long of Jefferson County, Georgia, USA in March 1842 using ether. Chloroform was initially used in the UK to provide pain relief during birth, such as by Dr. John Snow for Queen Victoria. However there were high levels of patient mortality with ether or chloroform anaesthesia due to limitations of the agents, crude equipment, and lack of use of oxygen. Many of the early anaesthetists became addicted to the drugs they used, possibly due to chronically high levels of occupational pollution from open face masks.

Inhalation anaesthetics no longer used include chloroform, cyclopropane, ether and Trilene. Over the last 25 years we have seen the decline in use of methoxyflurane, enflurane, nitrous oxide, and more recently halothane, although methoxyflurane is again being used in humans to provide immediate analgesia post trauma.

Veterinary anaesthesia has a high risk of mortality compared to human anaesthesia. Despite large improvements in anaesthetic outcome of animals, in part due to better anaesthetic agents, mortality rates in veterinary anaesthesia today are still high: 100 to 500 deaths per 100,000 anaesthetics for cats and dogs; 350 deaths per 100,000 anaesthetised horses as compared to 1 death per 100,000 to 300,000 anaesthetised humans. Recovery from anaesthesia accounts for up to 50% of deaths in veterinary anaesthesia which should be of concern.

Isoflurane, Sevoflurane and Desflurane

These newer agents have faster inductions and recoveries, less metabolism, less cardiac depression, higher heart rates, lower ventricular arrhythmogenicity, better tissue perfusion, minimal liver metabolism and renal excretion. There is better tolerance of deep anaesthesia, lower morbidity and mortality, and reduced occupational health considerations from exposure to waste anaesthetic gas. The downside includes agent cost, equipment cost, and managing volatility (requiring more accurate vaporizers).

Table 1. Properties of inhalation anaesthetics

Solubility = speed of uptake and onset of action.

Sevoflurane is half as soluble in blood as isoflurane, which is approximately half as soluble in blood as halothane (Table 1 & Graph). Desflurane is slightly less soluble than sevoflurane. The more insoluble an anaesthetic, the faster its anaesthetic induction, the more rapid the changes in depth and the faster is anaesthesia recovery. The speed of a mask induction using sevoflurane or desflurane is faster compared to halothane and to a lesser extent isoflurane. However both humans and animals tend to breathe sevoflurane better than isoflurane or desflurane resulting in a smoother and more even induction.

Wake-up after induction: thiopentone, propofol, Alfaxan®, fentanyl and to a lesser extent ketamine are commonly used for induction of anaesthesia but their rapid redistribution and elimination often result in animals "waking up" before a stable level of inhalation anaesthesia is achieved. Subtle differences between inhalation anaesthetics including speed of onset, as well as the efficiency of the delivery equipment, becomes more important to prevent "wake up" typically observed 5 minutes after induction (Graph). These differences also affect the ease of controlling anaesthetic depth during surgery, although provision of good preemptive analgesia will also dampen the response to surgical stimulation.

Graph

Circulatory Function

All inhalation anaesthetics cause a dose-dependent reduction in mean arterial pressure which is caused by a dose-dependent decrease in cardiac output and stroke volume. There is a tendency for less cardiac depression with isoflurane, sevoflurane, and desflurane at deep levels of anaesthesia (2.5 to 3.0 MAC). The cardiovascular system seems to be more tolerant of changes in anaesthetic depth with isoflurane or sevoflurane compared to halothane. It should be noted that these cardiovascular differences are affected by the degree of hypoventilation (i.e., increasing arterial PaCO₂ causes sympathetic stimulation) so comparisons are typically made under positive pressure ventilation to a normal, awake PaCO₂.

The arrhythmogenic potential for halothane is much greater than that for isoflurane, sevoflurane, or desflurane. This is especially important for any patient with cardiac disease manifested by an arrhythmia. In such patients (e.g., heart disease, post blunt chest trauma, or gastric dilatation) halothane may be contraindicated.

Tissue perfusion is better with isoflurane, sevoflurane, or desflurane at normal arterial PaCO₂ levels when compared to halothane. This is an important benefit for geriatric animals with reduced hepatic or renal function. Better blood flow helps maintain tissue oxygenation, hepatic metabolism, renal excretory function, and is directly correlated to blood flow. However, it is important to remember that hypocapnoea (a rising PaCO₂) causes vasoconstriction which reduces tissue perfusion. Positive pressure ventilation can reduce this effect but causes a decrease in cardiac output, virtually negating any benefit to tissue perfusion. Therefore inhalation anaesthetics that cause less respiratory depression such as sevoflurane will result in better overall tissue blood flow (see apnoeic index below).

Provision of adequate additional analgesia before painful stimulation will reduce circulating catecholamines which cause vasoconstriction, therefore reducing peripheral perfusion.

Respiratory Function

All inhalation anaesthetics cause a dose-dependent respiratory depression, as evidenced by a rise in arterial carbon dioxide tension with increasing anaesthetic dose. In canine patients, isoflurane and desflurane cause more respiratory depression when compared to sevoflurane. In cats, isoflurane has been shown to cause less respiratory depression when compared to halothane (there is no comparative data for sevoflurane or desflurane).

Apnoeic index is the anaesthetic concentration at which spontaneous ventilation ceases and is used as a measure to compare respiratory depression. The apnoeic index for sevoflurane in dogs is approximately 1/3 higher than for halothane or isoflurane indicating it's lower respiratory depression (Table 1).

Animals that breathe better during anaesthesia have two benefits:

 Anaesthetic depth tends to be more constant and depth is more easily adjusted.

 Extreme hypocapnoea causes cardiovascular depression, reduces tissue perfusion, and increases ICP, possibly leading to depression in recovery (slower or rougher recoveries).

Metabolism

Traditionally, it was thought that the inhalation anaesthetics were entirely taken up and eliminated by the lungs. However, of that portion of the anaesthetic taken up by the body's tissue, 25% of halothane is metabolized, compared to 3% of sevoflurane and virtually 0% for isoflurane or desflurane (Table 1). This becomes particularly important for neonatal animals and animals with liver or renal impairment.

In addition, metabolism of inhalation anaesthetics is an important concern from an occupational health aspect. Since metabolism of isoflurane, desflurane, and sevoflurane is minimal, there are less potential risks associated with chronic occupational health exposure. In veterinary practices with good waste anaesthetic gas management, occupational exposure still occurs at the time of disconnection, during recovery, and when servicing equipment, specially filling vaporisers!

Recovery Considerations

Speed of recovery from sevoflurane or desflurane is faster compared to halothane and to a lesser extent isoflurane. The speed of recovery from newer agents can be clinically observed - animals are more alert and owners notice this difference. These differences are possibly greater in geriatric, sick, or debilitated patients. Speed of recovery is also an important consideration for neonates (C-sections) and patients undergoing long anaesthesia.

The quality of recovery from anaesthesia is not necessarily related to the speed of recovery. Provision of analgesia positively influences the quality of recovery, but may prolong recovery. In large species such as horses this effect is clearly observed. Recent work in small animal anaesthesia suggests that hypothermia is an important factor affecting both duration and quality of recovery. Hypothermia occurs in 80% of anaesthetized small animals. There are a number areas where inhalation anaesthesia can influence the development of hypothermia including breathing circuits; and therefore, fresh O₂ flows used, the level of cardio-pulmonary depression, and the return of skeletal muscle function to enable the animal to generate heat by shivering.

Occupational Safety

Generally less than 20% of the fresh gas supplied to a circle breathing system is used by the animal, (less than 5% for non-rebreathing systems). The excess oxygen and anaesthetic agent (waste anaesthetic gas or WAG) is vented via the "pop-off valve" to avoid pressure build up in the breathing system which would cause breath-holding, reduce blood flow through the lungs, and could result in death. Waste anaesthetic gas should be either ducted out of the room to the atmosphere or absorbed by activated charcoal. Another major source of work-place WAG pollution is from the animal during recovery from anaesthesia, when the anaesthetic agent absorbed into the body is exhaled into the recovery room. Therefore, recovery rooms should be larger, well-ventilated rooms.

Many studies of the short- and long-term health effects of exposure to WAG have examined incidence of developmental defects, spontaneous abortion, neurological dysfunction, and cancer. The evidence supporting toxicity from WAG exposure is only suggestive but some things are clear: inhaled anaesthetics can be metabolized to varying levels (Table 1) producing fluoride ions that can alter cellular biochemical function; newer agents have minimal metabolism; chronic nitrous oxide exposure can cause hepatic and neurological dysfunction; and there is an increased incidence of spontaneous abortion in pregnant women working in the anaesthesia environment, although this may be caused by other environmental factors. For these reasons, there are occupational safety guidelines outlining the acceptable levels of WAG exposure, which should be minimised in the work environment.

Environmental Pollution

All the inhalation anaesthetic agents used eventually end up in the atmosphere. Waste anaesthetic gas bound to charcoal deposited in a land-fill is vaporized with heat and sunlight exposure. Inhalation agents have a 10 to 30 year life in the atmosphere and are ozone depleting. Nitrous oxide is a green-house gas. Simply reducing oxygen fresh gas flows to reasonable levels (30 ml/kg/min for circle breathing systems), reducing usage of high flow non-rebreathing circuits (use 200 ml/kg/min or higher fresh gas flows), and eliminating use of nitrous oxide could reduce atmospheric pollution by up to 90%. Newer technology will enable animals as small as 2 kg to be anaesthetized using circle breathing systems. This will be discussed in the lecture on anaesthesia breathing circuits for practice (Circuits for Inhalation Anaesthesia).

Cost of Inhalation Anaesthesia

Inhalation anaesthesia cost is based on the cost of the agent itself; the fresh gas flow rate (oxygen ± nitrous oxide), which is dependent on the type of breathing circuit and size of the animal; and the vaporizer setting which is affected by the level of painful stimulation and other parenteral analgesics and anaesthetics administered. Other costs not considered in the table below include the cost of CO₂ absorbent, oxygen, charcoal, cost/depreciation of equipment, and service of the machine or vaporizer.

Table 2

Table 3. Cost of inhalation anaesthetic agent