Appendix B

Nitrous Oxide

Nitrous oxide (N2O) is a colorless, nonflammable gas with a pleasant odor that has been used in human patients since the mid 1800s to provide anesthesia and analgesia. It is not sufficiently potent to induce general anesthesia when used alone, but when used in combination with halogenated inhalant anesthetics, speeds induction and recovery, provides additional analgesia, and decreases the necessary dose and adverse effects of concurrently used agents.

PHYSICAL PROPERTIES OF NITROUS OXIDE

Because N2O is a gas at room temperature, it is stored in blue compressed gas cylinders and does not require a vaporizer for delivery. It is delivered via a gas specific flow meter, mixed with O2 in the anesthetic machine and then delivered to the patient as a part of the carrier gas flow.

The property that limits the use of N2O in veterinary anesthesia is its lack of potency (that is, a high minimum alveolar concentration [MAC]) in domestic animal species. The MAC of N2O in humans is approximately 100%, whereas the MAC in dogs and horses is close to 200% and in the cat is approximately 250%. Consequently, it is impossible to achieve surgical anesthesia in a healthy domestic animal using N2O alone.

Other properties of N2O can be summarized as follows:

• N2O reduces the MAC (and therefore the vaporizer setting) of other anesthetics by 20% to 30%. This reduces adverse effects and results in faster recoveries. N2O also has been shown to speed the uptake of other anesthetic gases into the bloodstream by the second gas effect when used at high concentrations (50% to 70% of the total gas flow). The second gas effect is an increase in the concentration of a gas in the alveoli resulting from the absorption of a second gas into the bloodstream. The absorption of N2O causes the concentration of the inhalant anesthetic gas in the alveoli to increase more rapidly than it would otherwise. This effect results in more rapid inductions.

• N2O has an extremely low solubility coefficient and by itself is associated with rapid induction and recovery rates. It is therefore a helpful addition to slow-acting agents such as methoxyflurane. It does little to enhance induction with rapid-acting agents such as isoflurane and sevoflurane, however.

EFFECTS OF NITROUS OXIDE ON MAJOR ORGAN SYSTEMS

Central Nervous System

N2O has a mild anesthetic effect, insufficient to produce general anesthesia when used alone, but does provide good analgesia.

Cardiovascular System

N2O usually has little effect on heart rate (HR), cardiac output (CO), and arterial blood pressure (BP), although there is a potential for tachycardia. It is considered to have a wide margin of safety.

Respiratory System

N2O causes minimal respiratory depression, although it will displace oxygen in the breathing circuit and the patient’s lungs, leading to hypoxemia when used in concentrations of over 70% of total carrier gas flow. It is nonirritating to the respiratory system.

OTHER EFFECTS

• N2O may accumulate within the gastrointestinal tract, causing distension and ileus.

• N2O crosses the placental barrier and may cause neonatal hypoxemia.

• N2O is not a muscle relaxant.

Despite the relative safety and advantages of N2O, over the past several decades, its popularity has gradually decreased to the point that it is seldom used in general practices in North America. One reason is the increased cost of N2O anesthesia, compared with anesthesia with an inhalation agent alone. Another reason is the increased use of isoflurane and sevoflurane, which provide rapid inductions and recoveries even without the concurrent use of N2O. Finally, the availability of good injectable analgesics has made the analgesic properties of N2O less advantageous.

NITROUS OXIDE RISKS

The use of N2O is associated with several potential problems, including those described in the following paragraphs.

Fire Hazard

N2O is not flammable, but like O2 it supports combustion.

Risk of Hypoxemia

The use of N2O in an anesthetic machine limits the amount of O2 that is delivered to the patient to the extent that N2O replaces O2 in the circuit. Because the minimal amount of N2O necessary to achieve analgesic effects is 50% (and values of 60% to 67% are recommended), the use of this agent decreases the amount of O2 delivered to the patient by the same amount (50% to 67%). Therefore the patient breathing N2O should be monitored closely for adequate oxygenation with a pulse oximeter or blood gas analysis. Patients should also be monitored closely for cyanosis and cardiac arrhythmias. Because of the risk of hypoxemia, animals with preexisting lung disease are poor candidates for N2O anesthesia. For all patients, care should also be taken when adjusting the flow meter of the anesthetic machine to avoid confusing O2 controls with those for N2O.

Diffusion into Air Pockets

Because of its low solubility coefficient, N2O is able to diffuse into trapped air pockets within the body. This diffusion may result in an increase in the amount of gas within an organ and consequent distension of the organ containing trapped gas. For this reason, the use of N2O is contraindicated in animals with intestinal obstruction, gastric torsion, pneumothorax, or diaphragmatic hernia. As there is normally a large amount of gas in the equine gut, N2O may cause undesirable dilation of the intestines in this species.

Use in Closed (Total) Rebreathing Systems

N2O should never be used in a closed rebreathing system (that is, one with low O2 flow rates) unless the anesthetist uses a monitor to determine O2 levels in the inspired gas. Because O2 is removed from a closed system by the animal’s metabolism, the level of N2O in the circuit may increase to dangerous levels, resulting in hypoxemia.

Diffusion Hypoxia

During recovery from anesthesia, N2O will readily exit from the body via the respiratory system. Because of the rapid outpouring of N2O into the lungs, a state of diffusion hypoxia may occur. In this condition, O2 molecules normally found in the alveoli are displaced by the large numbers of N2O molecules exiting the blood. Diffusion hypoxia can be prevented by keeping the animal on high O2 flow rates for at least 5 minutes after the N2O has been turned off and ensuring that the animal is frequently bagged with pure O2.

Waste Anesthetic Gas Hazards

Exposure of operating room personnel to waste N2O has been linked to several health disorders (see Chapter 13).

Nitrous Oxide Storage

Some anesthetic machines are designed to deliver N2O gas in addition to O2. N2O is contained in a compressed gas cylinder that is blue in color. As with O2, this may be a large freestanding tank or a smaller tank attached to the machine. The pressure in a full N2O tank (745 psi or about 5140 kPa) is considerably less than the pressure in a full O2 tank. This is because, unlike O2, N2O is present in both the liquid and gas states within the pressurized tank.

The tank pressure gauge indicates the pressure of the gas within the tank but not that of the liquid and therefore does not indicate how full the tank is. As the gas leaves the tank, more liquid evaporates and enters the gas state. As a result, the pressure of the gas within the tank will not change until all of the liquid has evaporated, at which point the tank is nearly empty (5 to 10 minutes left, depending on the flow rate). The anesthetist therefore should not expect the N2O tank gauge reading to change, even after several hours of anesthesia, unless the tank is close to empty.

The amount of N2O in the tank can be determined only by weighing the tank before use. The full and empty weights are normally stamped on the outside of each cylinder. An E cylinder of N2O weighs approximately 8 kg (18 lb) when full and about 6.4 kg (14 lb) when empty. Because weighing the cylinder is not always an option, especially during a procedure, the anesthetist should change the tank as soon as the tank pressure gauge starts to drop below 745 psi.

NITROUS OXIDE DELIVERY

As with O2, N2O is delivered to the patient by a flow meter. So when this gas is used on a machine, there will be a flow meter for each gas (see Figure 4-25). These flow meters allow the anesthetist to accurately control the relative amounts of O2 and N2O delivered. If the N2O flow meter is set to deliver 2 L/min and the O2 flow meter is adjusted to deliver 1 L/min, the resulting mixture will be a 2:1 ratio of N2O to O2. (This represents approximately 67% N2O and 33% O2.)

Some machines automatically set the O2 and N2O proportions, and an adjustment of the flow rate of one gas will automatically change the flow rate of the other. Some also have a device that discontinues N2O administration to the patient if the O2 flow is cut off. This mechanism prevents inadvertent asphyxiation of the patient, which could occur if the patient breathed N2O in the absence of O2.

NITROUS OXIDE USE

When using N2O, the anesthetist should ensure that the N2O/O2 ratio never exceeds 2:1, or the patient will receive insufficient O2 and asphyxiation may result. It is also imperative to deliver a minimum O2 flow of 10 to 15 mL/kg/min for large animal patients and 30 mL/kg/min for small animal patients receiving a mixture of N2O and O2. Total flow rates less than 500 mL/min should be avoided.

For example, if a total carrier gas flow of 1 L/min is required, the 1 L may consist of pure O2 or some combination of N2O and O2. For example, 600 mL of N2O per minute and 400 mL of O2 per minute (a ratio of 1.5:1) would be appropriate.

Oxygen Depletion and Nitrous Oxide Accumulation

During any procedure, O2 is gradually depleted as the patient breathes the circulating gas. This is normally compensated for by fresh O2 entering the circuit. In a closed rebreathing system, the O2 flow rate is low and the amount of fresh O2 added to the circuit may not entirely compensate for this loss. This is particularly serious if N2O is used in addition to O2, because the relative amount of N2O in the circuit may increase as the amount of O2 decreases. As a result, the patient may breathe dangerously high levels of N2O gas. This effect is less likely to occur in a semiclosed rebreathing system, in which N2O escapes through the pop-off valve and O2 flow rates are higher. The use of an O2 flow above the minimum levels mentioned prevents N2O buildup, but this flow rate is not possible in a closed rebreathing system. Closed rebreathing systems therefore are not recommended if N2O is part of the anesthetic protocol, unless a monitor is used to measure inspired O2.