N2O and Its Interaction with the Body
Upon completion of this chapter, the reader should be able to:
1. Identify the interaction of nitrous oxide with body systems.
2. Identify how nitrous oxide interacts with patients who have other health issues that could impact the sedation experience.
Nitrous oxide has been in continuous use as an anxiolytic drug because it is a safe drug. It is compatible with human physiology, and when administered with oxygen, it actually improves a patient’s perfusion while decreasing his or her anxiety. This chapter will explore how nitrous oxide interacts with specific body systems. Many instances necessitating the avoidance or postponement of its use are a reminder of the pharmacokinetic properties of the drug. In addition, basic knowledge of nitrous oxide is important to keep one aware of potential interactions with new drugs sure to find their way into the marketplace. Therefore, in today’s world of increasing human longevity, nitrous oxide finds its use across the spectrum from pediatric to geriatric and from healthy to medically-compromised patients.
A. N2O does not negatively affect the cardiovascular system to produce any significant physiologic changes.
1. The interaction of several cardiovascular functions, such as contractility, output, stroke volume, heart rate, and arrhythmias, with N2O have been researched in the past.1–5 Becker and Rosenberg state subanesthetic concentrations of nitrous oxide have minimal effect.6 Overall, N2O has proven to be slightly cardiotonic.
3. Blood flow to major organs is not significantly affected.3
4. Administration of N2O with O2 does not create adverse cardiovascular conditions. Conversely, it has a positive effect on myocardial ischemia by providing supplemental O2 and can be very helpful in myocardial infarction.7,8
5. Blood pressure effects from N2O may be dose related. In most instances, blood pressure is not affected by the N2O concentrations commonly used in ambulatory settings. Eger and colleagues1 found blood pressure readings to be lowered when N2O/O2 was used. This potential decrease in blood pressure is a result of relaxation, because N2O does not have any direct effect on the myocardium or voluntary skeletal muscle. It has also been stated that arterial blood pressure remains stable when lower amounts of nitrous oxide are administered, whereas venous tone is increased.6
6. Nitrous oxide has a minimal effect on heart rate.9 Similar to its effects on blood pressure, heart rate may decrease as anxiety is lowered.
B. Currently, no conditions involving the cardiovascular system should indicate medical consultation or postponement of N2O/O2 use.
A. When intended for minimal sedation, nitrous oxide does not depress ventilation.6
1. Because the route of administration is inhalation, airway patency is mandatory. Upper respiratory tract infections or conditions commonly compromise air exchange through the nose. If the patient is unable to breathe through the nose, insufficient amounts of N2O/O2 will enter the respiratory system.
a. Any type of common infection—such as a cold, cough, sinus infection, bronchitis, or allergy-related symptoms—may occlude the nasal passages such that adequate air exchange at the alveolar level will be incomplete.
b. In addition, if N2O/O2 is used for an individual with mild symptoms, the drying effect of the gases may create mucous plugs and negatively affect the pulmonary tree. Again, sedation may be incomplete and inadequate.
c. Sinus cavities represent rigid, noncompliant air spaces. The nonexpansive nature of these areas leads to an increase in pressure when N2O is administered. When sinusitis is present, the additional pressure may be uncomfortable for the patient.6
d. It is also problematic to administer effective inhalation sedation to patients with compromised airways because of anatomic variations.6
2. Although rare, silent regurgitation and subsequent aspiration need to be considered with N2O/O2 sedation. The concern regards whether pharyngeal-laryngeal reflexes remain intact. This problem can be avoided by not allowing a patient to pass into an unconscious state.10
b. Procedures performed in an ambulatory health setting may or may not be time intensive; however, patients may not have fasted before the procedure. Therefore, the potential for positive aspiration resulting from silent regurgitation does exist.
c. Because this is a potentially life-threatening situation, it is important to use the appropriate titration technique when administering N2O/O2 sedation to avoid oversedation. Continuous monitoring of the patient should always be performed.
3. Patients susceptible to hypoxia because of airway resistance, impaired function, or movement seem to be at a slight risk from N2O/O2 sedation but not more than from any other substance. Examples of conditions in this category are emphysema and chronic bronchitis.
a. There has never been a reported allergy to N2O. Its use is not contraindicated for asthma patients, because it is nonirritating to mucous membranes. In fact, the sedative nature of N2O/O2 has a positive influence on asthmatic patients, because anxiety can trigger an asthmatic episode.
b. For patients chronically debilitated with other respiratory conditions, N2O/O2 may be considered relatively contraindicated (Box 9-1).
i. Some of these patients may be on hypoxic drive. Although CO2 normally initiates respiration in healthy individuals, O2 may be the stimulus for those compromised with chronic obstructive pulmonary disease (COPD).6
ii. Patients with severe chronic respiratory diseases should receive medical consultation before undergoing any type of sedation. Any kind of sedation may risk further depression of their respiratory drive.
iii. In most cases, persons on hypoxemic drive are very ill. Some will not be able to be treated in an ambulatory setting; most represent an ASA 3 or 4 classification (see Chapter 10). Medical consultation is recommended before any treatment.
4. Patients with cystic fibrosis may incur bullae as a complication of this disease, again because of the expansive nature of the gas. N2O would be contraindicated in this case.13
5. The condition of pneumothorax (air or gas in the pleural cavity) may be complicated with N2O. The expansive quality of the gas causes increased expansion of the size of the pneumothorax. This condition demands medical attention. In general anesthesia, if 75% N2O is delivered, the volume of the space can be increased up to 300%.14 Even though much smaller dosages of N2O are used in the ambulatory setting, the pharmacodynamic nature of the gas is constant. N2O/O2 sedation should be avoided in this situation.
B. Nitrous oxide/oxygen sedation should be avoided for patients with pneumothorax or cystic fibrosis.
C. N2O/O2 sedation should be postponed for patients experiencing acute sinusitis or upper respiratory tract infections.
D. Medical consultation is advised for patients with any type of chronic obstructive pulmonary disease (COPD) (e.g., emphysema, chronic bronchitis).
A. N2O, like other anesthetics, has the ability to depress the CNS; however, the exact mechanism is unknown.4
1. N2O’s effects on cerebral blood flow, intracranial pressure, cerebral blood velocity, cerebral perfusion pressure, and O2 consumption have been compared with other anesthetics.15,16 Most effects seem to be less significant than those of other inhaled anesthetics.4,17 When nitrous oxide is used appropriately with oxygen in the ambulatory setting, these effects are not significant.
3. Because of the rapid replacement of N2 with N2O in air spaces, notable intracranial pressure increases were found in cases of pneumoencephalography. N2O should not be used for 1 week after this procedure.17
4. Evidence of injury to the nervous system has been shown in cases of chronic exposure to N2O. Numbness and weakness in the extremities are seen as symptoms, as is ataxic gait.2 This subject is discussed in detail in Chapter 17.
B. N2O/O2 sedation is contraindicated for patients having undergone recent pneumoencephalography or for patients who are abusers of nitrous oxide.
A. Megaloblastic bone marrow changes have been found in patients who have been exposed to high concentrations of N2O for an extended period.18 N2O has been implicated in the interference of the vitamin B12–dependent enzyme methionine synthase for many years. This enzyme is necessary for DNA synthesis and erythrocyte production.4,16
1. Impaired uptake of vitamin B12 is associated with cobalamin deficiency. Cobalamin is necessary for the conversion of homocysteine to methionine.9,19,20 Pernicious anemia and megaloblastic anemia are conditions that are associated with this vitamin deficiency. Animal studies focusing on cobalamin deficiencies show neurologic involvement.21 Myelopathy and neuropathy have also been cited in humans with cobalamin deficiencies.22 The studies citing hematologic effects associated with nitrous oxide are those when nitrous oxide is used as an anesthetic whe/>