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Specifics Concerning Nitrous Oxide and the Effects on the Human Body
Emily Anne Covington
University of Kansas Medical Center

Nitrous Oxide
Nitrous oxide is an inhalation anesthetic most commonly referred to as laughing gas.
Currently, anesthesia is administered generally, regionally, or locally. Although there are
numerous ways to give anesthesia, inhalation anesthesia evolved prior to all other methods
(Morgan, Mikhail, & Murray, 2006). The inhalation anesthetic nitrous oxide is used frequently in
the anesthesia community with numerous advantages and disadvantages when compared to other
Joseph Priestley produced nitrous oxide in 1772, but Humphry Davy first noted its
analgesic properties in 1800 (Morgan et al., 2006, p. 2). In the 1800s, nitrous oxide was disliked
due to its low potency and risk of causing asphyxia (Morgan et al., 2006). Therefore, in 1868
Edmund Andrews administered nitrous oxide in 20% oxygen, which helped to develop its
popular reputation (Morgan et al., 2006). During this time, many inhalants were created and
administered; however, of all the inhalation anesthetics originating during the 1800s, nitrous
oxide is the only agent still commonly used (Morgan et al., 2006).
Nitrous oxide is a colorless, odorless gas at room temperature (P. Patel, H. Patel, &
Roth, 2011, p. 546). It can be classified as a general anesthetic, inhalation anesthetic, or dental
gas (Donnelly, Barughman, Gonzales, Golembiewski, & Tomsik, 2008). There is a potential risk
for combustion when nitrous oxide interacts with a flammable anesthetic or material; however, in
most clinical situations nitrous oxide is neither flammable nor explosive (P. Patel et al., 2011).
Central nervous system depression is the basic mechanism of action for nitrous oxide
(Donnelly et al., 2008). Inhibiting action potentials by stabilizing axonal membranes may attain
sedation (Donnelly et al., 2008). Thus, nitrous oxide may also act on the opiate receptor system
causing analgesia (Donnelly et al., 2008). Nitrous oxide increases cerebral blood flow and
intracranial pressure while decreasing hepatic and renal blood flow (Donnelly et al., 2008, p.
According to P. Patel et al. (2011), when providing either analgesia or mild sedation in
the dental outpatient setting, nitrous oxide is administered at concentrations approximating 50%.
General anesthesia is delivered at a concentration of 40% to 70% via a mask or an endotracheal
tube (Donnelly et al., 2008). Nitrous oxide cannot be used at a concentration greater than 80%
because this limits the delivery of adequate oxygen (P. Patel et al., 2011). Furthermore, this
anesthetic is commonly used with various inhalational or intravenous anesthetics to prevent
deprivation of oxygen (P. Patel et al., 2011).
Nitrous oxide is insoluble in human blood and other human tissues resulting in balanced
alveolar anesthetic concentrations (P. Patel et al., 2011). Hence, this anesthetic demonstrates a
rapid initiation of anesthesia approximating less than five minutes (P. Patel et al., 2011).
Hastened induction and absorption occurs in the alveoli located in the lungs (Donnelly et al.,
2008). On discontinuation of nitrous oxide administration, nitrous oxide gas can diffuse from
blood to the alveoli, diluting oxygen in the lung (P. Patel et al., 2011, p. 546). Nitrous oxide has
a quick elimination half-life and is excreted mainly via respiration (Donnelly et al., 2008). The
primary portion of nitrous oxide not excreted through the lungs is diffused through the skin (P.
Patel et al., 2011). Moreover, due to the rapid elimination rate, less than 0.004% of nitrous oxide
is metabolized in the human body (Donnelly et al., 2008).
Nitrous oxide activates the central nervous system, resulting in an increased respiratory
rate (Banks & Hardman, 2005). Tracheal mucociliary flow and neutrophil chemotaxis is
depressed following administration of this anesthetic (Banks & Hardman, 2005). This may
increase the incidence of post-operative respiratory complications (Banks & Hardman, 2005, p.
146). Both, myocardial depression and constriction of the pulmonary vascular smooth muscles
are caused when nitrous oxide is administered, leading to an increase in right atrial pressure
(Banks & Hardman, 2005). Additionally, renal and hepatic blood flow is decreased as a result of
a rise in vascular resistance (Banks & Hardman, 2005). According to Hancock and Nathanson,
nitrous oxide increases cerebral blood flow, cerebral metabolism and intracranial pressure (as
cited in Banks & Hardman, 2005, p. 146). Interference in cerebral auto-regulation may result in
decreased cerebral perfusion (Banks & Hardman, 2005). Nitrous oxide has the potential to
increase skeletal muscle activity and less depressant activity at the neuromuscular junction than
other currently used inhalational anesthetic agents (Banks & Hardmann, 2005, p. 146).
Low potency prevents nitrous oxide from individual general anesthesia (Banks &
Hardmann, 2005). Its minimum alveolar concentration is 105% at 1 atmosphere pressure
(Banks & Hardmann, 2005, p. 146). Therefore, nitrous oxide administration is attractive in
combination with other current anesthetics (Banks & Hardmann, 2005). Nitrous oxide is found to
be nontoxic to the pregnant woman and fetus; and maternal complications may include nausea,
dizziness, paraesthesia, and dry mouth (Banks & Hardmann, 2005). The discomfort associated
with painful procedures may be lessened with the use of nitrous oxide. There are
contraindications to certain situations and repeated prolonged use (Banks & Hardmann, 2005).
Examples of conditions in which nitrous oxide might be hazardous include air embolism,
pneumothorax, acute intestinal obstruction, intracranial air, pulmonary air cyst, intraocular air
bubbles, and tympanic membrane grafting (Morgan et al., 2006, p. 166). Postoperative nausea
and vomiting are common side effects associated with nitrous oxide administration (Banks &
Hardman, 2005). Endotracheal tubes and laryngeal masks may experience an increase in cuff
pressure during administration of this inhalant anesthetic (Banks & Hardman, 2005).
Consequently, tracheal ischemia and mucosal injury may result (Banks & Hardman, 2005).
According to Sanders (2007), Nitrous oxide can oxidize the cobalt I form of vitamin B
, thereby preventing vitamin B
from acting as a co-factor for methionine synthetase (P.
Patel et al., 2011, p. 546). Subsequently, signs and symptoms of vitamin B
deficiency may be
presented (P. Patel et al., 2011). This is of particular concern in patients with malnutrition,
vitamin B
deficiency, or alcoholism (P. Patel et al., 2011, p. 547).
As per Myles et al., There is a plausible pathophysiologic rationale for increased long-
term cardiovascular morbidity and mortality in patients receiving significant exposure to nitrous
oxide (Leslie et al., 2011, p. 387). As previously mentioned, continuous use of nitrous oxide
may inactivate methionine synthase leading to an increase in plasma homocysteine (Leslie et al.,
2011). This increase may disrupt endothelial function, promote oxidative stress, and dislodge
plaque located in the coronary arteries (Leslie et al., 2011). This trial developed
pathophysiological reasoning linking to the relationship between administration of nitrous oxide
and myocardial infarction (Leslie et al., 2011). Postoperative plasma homocysteine and folate
concentrations were significantly increased in comparison with preoperative values in patients
who had a myocardial infarction (Leslie et al., 2011, p. 389). It was found that folate
supplementation and avoidance of nitrous oxide administration was proven to lessen the risk of
myocardial infarction (Leslie et al., 2011). In conclusion, the administration of nitrous oxide
was associated with increased long-term risk of myocardial infarction but not of death or stroke
in patients enrolled in the ENIGMA trial (Leslie et al., 2011, p. 392). This literature review
verified nitrous oxide could potentially increase the risk of myocardial infarction; however, it
suggests further research be completed to verify an exact relationship between nitrous oxide
administration and serious long-term adverse results (Leslie et al., 2011). Nitrous oxide was
found to be neither important, nor detrimental in this study.
Overall, nitrous oxide is an important aspect of the anesthetists armamentarium. This
inhalant anesthetic has been used for over a century. Like any other anesthetic, nitrous oxide has
numerous clinical advantages and adverse effects. There are various situations when nitrous
oxide is an unacceptable choice for anesthesia. Moreover, the concentration of this inhalant
anesthetic can be measured with exhalation (Banks & Hardman, 2011). The future of nitrous
oxide is not evident, and it could possibly become extinct; however, nitrous oxide presently has
no other gaseous alternative (Banks & Hardman, 2011).

Banks, A., & Hardman, J. G. (2005). Nitrous oxide. Continuing Education in Anaesthesia,
Critical Care and Pain, 5(5), 145-148. doi: 10.1093/bjaceaccp/mki039
Donnelly, A. J., Baughman, V. L., Gonzales, J. P., Golembiewski, J., & Tomsik, E. A. (2008).
Anesthesiology & critical care drug handbook (8
ed.). Hudson, OH: Lexi-Comp, Inc.
Leslie, K., Myles, P. S., Chan, M. T. V., Forbes, A., Paech, M. J., Peyton, P., Williamson, E.
(2011). Nitrous oxide and long-term morbidity and mortality in the ENIGMA trial.
Anesthesia & Analgesia, 112 (2), 387-393. doi: 10.1213/ANE.0b013e3181f7e2c4
Morgan, G. E., Jr., Mikhail M. S., & Murray M. J. (2006). The practice of anesthesiology. In M.
Strauss, H. Lebowitz, & P. J. Boyle (Eds.), Clinical anesthesiology (4
ed., pp. 1-16).
New York, NY: McGraw-Hill.
Morgan, G. E., Jr., Mikhail M. S., & Murray M. J. (2006). Inhalation anesthetics. In M. Strauss,
H. Lebowitz, & P. J. Boyle (Eds.), Clinical anesthesiology (4
ed., pp. 155-178). New
York, NY: McGraw-Hill.
Patel, P. M., Patel, H. H., & Roth, D. M. (2011). General anesthetics and therapeutic gases. In L.
L. Brunton, B. A. Chabner, & B. C. Knollmann (Eds.), Goodman & Gilmans the
pharmacological basis of therapeutics (12
ed., pp. 527-564). New York, NY: McGraw-