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Nitrous oxide is one of the oldest inorganic inhalation anesthetics still used in practice today to achieve unconsciousness. This odorless gas, which can support combustion, is most commonly administered in a concentration of 50%–75% in oxygen. Because it has a minimum alveolar concentration (MAC) value of 104%, nitrous oxide is a weak anesthetic that is typically used as part of a balanced technique with a potent volatile inhalation agent and opioids. Due to the second gas effect, giving high concentrations of nitrous oxide will help increase the alveolar concentration of a second, simultaneously given volatile agent. The solubility of N2O in blood is very low (blood/gas partition coefficient of 0.47), resulting in faster equilibration of partial pressures between blood and alveolus and rapid induction and emergence.

Compared to other inhalation agents, nitrous oxide has unique physiologic effects. It is neither a vasodilator, nor does it cause hypotension. It is actually sympathomimetic and increases both cardiac output and systemic vascular resistance. In the lungs, nitrous oxide does not inhibit hypoxic pulmonary vasoconstriction, so there may be an increase in pulmonary vascular resistance, especially in patients with known pulmonary hypertension. Unlike other inhalation agents, nitrous oxide has no known effect on uterine contractility and does not cause skeletal muscle relaxation. It has been shown to increase the risk of postoperative nausea and vomiting. It also has mild analgesic properties, with about 30% nitrous oxide by face mask producing the equivalent of 10–15 mg morphine. Prolonged use of nitrous oxide can lead to a megaloblastic anemia. This is because nitrous oxide can oxidize the cobalt atom within vitamin B12, therefore inhibiting vitamin B12-dependent enzymes such as methionine synthetase, which are important for DNA synthesis.

If nitrous oxide is included as part of a balanced general anesthetic, a significant amount can enter closed gas spaces within the body. This assumes that the patient is receiving an inspired anesthetic gas mixture consisting of 70% nitrous oxide/30% oxygen. Preoxygenation and denitrogenation of the alveoli will not necessarily remove all the nitrogen molecules from preexisting pockets of air (21% oxygen, 78% nitrogen) in the patient, such as in an obstructed small bowel. Nitrogen is highly insoluble (blood/gas partition coefficient 0.015) and, therefore, is “trapped” in these gas compartments and does not pass easily from gas to blood. Based on a blood/gas coefficient of 0.47, nitrous oxide, therefore, is roughly 34 times more soluble than nitrogen. Nitrous oxide will quickly and readily transfer across membranes and enter these closed gas-filled spaces more than 30 times faster than nitrogen will diffuse out of the space proportionally. The transfer of nitrous oxide into these closed air spaces does not influence how quickly it achieves its alveolar partial pressure (FA/FI).

Since the entrance of nitrous oxide into the closed air space is not balanced by an equal loss of nitrogen, a significant increase in volume may result ...

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