Physical Properties and Pharmacokinetics/Pharmacodynamics of N₂O

The conscientious healthcare provider offering N₂O/O₂ sedation to patients must be knowledgeable about the physical properties as well as the pharmacokinetics and pharmacodynamics of any drug he or she administers. Pharmacokinetics is defined as “the activity or fate of drugs in the body over a period of time, including the processes of absorption, distribution, localization in tissues, biotransformation, and excretion.”¹ The definition of pharmacodynamics is “the study of the biochemical and physiological effects of drugs and the mechanisms of their actions, including the correlation of actions and effects of drugs with their chemical structure, and the effects on the actions of a drug or drugs.”¹ N₂O has many favorable attributes related to pharmacokinetics and pharmacodynamics, which prove noteworthy in the ambulatory setting. Although there may be disagreement about whether N₂O deserves the “ideal” label, many agree that its role in healthcare is fundamental.

1 Physical and Chemical Properties of N₂O

A. Dinitrogen monoxide (N₂O) is a stable, linear compound that is chemically diagrammed as N ≡ N = O. It is a slightly sweet-smelling colorless gas.

B. The boiling point of N₂O, which is − 88.5° C (− 127° F), indicates that it is a gas at room temperature. When compressed into a cylinder, N₂O becomes a liquid.

C. The U.S. Department of Transportation classifies nitrous oxide as nonflammable²; however, N₂O supports combustion. If the gas comes in contact with a combustible substance or flame, decomposition of the gas will occur. If the decomposition occurs at high temperature (650° C/1202° F) and elevated pressure (inside a cylinder or high-pressure pipeline), a violent chemical reaction such as an explosion will occur. If N₂O is present near an open flame, the flame will burn brighter.

D. Because N₂O, like O₂, is an oxidizing gas, no hydrocarbon compounds, such as lubricants, grease, or oil, should be used on any N₂O storage, distribution, or dispensing equipment. Of further concern is the operation of such equipment in a manner that increases the temperature of the N₂O. The most common example is the quick opening of valves, which causes a rapid pressure increase. The phenomenon known as the heat of compression can increase the temperature of the metal to a level that ignites any hydrocarbon contaminants and causes a chemical reaction resulting in fire or explosion. This reaction can occur with any organic contaminant acting as a fuel.

E. The molecular weight of N₂O is 44. Its specific gravity (sp gr) is 1.53, which indicates that it is heavier than nitrogen/air (sp gr = 1) or pure O₂ (sp gr = 1.1).

F. N₂O is found in minimal concentrations (322 to 323 parts per billion [ppb]) in the atmosphere.³ The Compressed Gas Association states the emission of nitrous oxide derived from commercial production is approximately 1% of total emissions.⁴ Anesthetic N₂O contributes insignificantly to that total amount. Several natural and man-made methods release N₂O into the atmosphere (e.g., burning of pine wood). The U.S. Environmental Protection Agency (EPA) and others suggest that N₂O enters the environment through rivers and ocean currents, soil denitrification, synthetic and manure fertilizers, livestock manure, wastewater treatment, fossil fuel combustion, plants and trees, and adipic acid (nylon) and nitric acid production.^3–8 Concentrations of this naturally occurring greenhouse gas have increased 19% from 1750, a preindustrial time period, to 2010, whereas carbon dioxide (CO₂) and methane (CH₄) concentrations have increased 39.2% and 158%, respectively.³ As ultraviolet (UV) light combines with N₂O and O₂, free radicals (i.e., nitric oxide) are produced, which can also affect the ozone.³

G. There are several applications for nitrous oxide. Besides its use in healthcare, it is used in food processing, semiconductor manufacturing, autoracing, and analytical chemistry.^2,9

H. A Safety Data Sheet (SDS) for nitrous oxide is provided as a reference in Appendix A.

2 Physical and Chemical Properties of O₂

A. Discovery

1. Many early scientists, such as Bayen, Borch, and Scheele (1772), prepared O₂ but did not recognize the significance of their findings.¹⁰

2. Joseph Priestley in England was credited with discovering not only N₂O but also O₂, carbon monoxide, sulfur dioxide, and ammonia. Priestley, a British chemist, is considered one of the founders of modern chemistry because of his contributions to the field of science.

B. Preparation

1. O₂ is primarily prepared by fractional evaporation of liquid air or by heating potassium chlorate using manganese dioxide as a catalyst. Air separation manufacturing facilities make 99% of the gas. O₂ costs approximately 5 cents per cubic foot for small quantities.¹⁰

2. Air is cooled and compressed until it liquefies. O₂ compresses to a pale blue liquid at − 183° C.

3. Nitrogen (N) and other elements evaporate, leaving liquid O₂.

4. Oxygen is also produced by plants during photosynthesis.

C. Characteristics

1. In a gaseous state, O₂ is odorless, colorless, and tasteless.

2. Oxygen comprises approximately 21% of the earth’s atmosphere and 49.2% of the earth’s crust. The human body is 61% oxygen and 90% of water is oxygen. Oxygen is the third most abundant element in the sun and is thought to be part of its energy source.¹⁰

3. The molecular weight of O₂ is 32; its specific gravity is 1.1 (sp gr air = 1) and its atomic weight is 15.9. The atomic weight of oxygen was used as the standard for comparison of other elements until carbon-12 replaced it as the standard in 1961.¹⁰

4. Like N₂O, O₂ supports combustion but is not itself flammable. It reacts similarly to N₂O when it contacts a combustible material such as oils, grease, or flammable materials.

5. O₂ is a compressed gas in cylinders. The dial in the regulator gauge accurately depicts the O₂ content in the cylinder. As the gas is consumed, the dial changes proportionally.

6. Oxygen is highly reactive and combines with most elements. It is a component within hundreds of thousands of organic compounds.

D. Uses

1. There are many uses for O₂. The steel industry is one of the largest consumers of O₂. O₂ is also used for welding and lighting and as a propellant in rockets. It is widely used in the medical field for performing surgical procedures and for treating anaerobic infections and hypoxia.

2. Commercially, O₂ consumption is estimated at 20 million short tons per year in the United States.¹⁰

3. O₂ is the required component of N₂O when N₂O is used for sedation. Current sedation equipment guarantees a minimum O₂ delivery of 30%. This provides an amount of O₂ greater than that found naturally in atmospheric air, which is significant for patient safety during N₂O/O₂ administration. It is common to use approximately 2.5 tanks of O₂ to every 1 tank of N₂O during sedation procedures.

4. The oxygen molecule does not separate from the nitrogen molecule in N₂O and is therefore unavailable as an oxygen source.

5. Oxygen is inhaled recreationally and is often sold at an “oxygen bar.” Flavoring and coloring agents are often mixed with the gas to enhance its appeal (