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Nitrous Oxide : Neurotoxicity
Case Synopsis
A 7-week-old infant underwent a Kasai procedure for the diagnosis of biliary atresia. The patient received isoflurane and nitrous oxide, and the operation was uneventful. Five days after the surgery, the patient developed hypotonia, hyporeflexia, and apnea. Computed tomography showed severe cerebral atrophy, and homocysteine was detected in the infant’s urine.
Problem Analysis
Definition
Nitrous oxide (N 2 O), also known as laughing gas, was first discovered in 1772 by John Priestly. In 1798 the Pneumatic Institute was founded by Thomas Beddoes, which aimed to study the use of gases in medicine. Humphry Davy, who worked as an assistant in the institute, noticed the reduction in pain that was caused by an eruption of a wisdom tooth after inhaling N 2 O. He later published a book on N 2 O in which he stated, “As nitrous oxide in its extensive operation appears capable of destroying physical pain, it may probably be used with advantage during surgical operations where too great an effusion of blood does not take place.” However, his discovery was not widely accepted at that time. Later, Horace Wells, an American dental surgeon, also noticed the anesthetic effect of N 2 O as he saw that Gardner Quincy Colton injured his leg without feeling any pain while receiving the gas. Wells later requested to get his tooth removed while inhaling N 2 O, in which he reported that the surgery was a painless experience. Nonetheless, Wells failed to show the same effect during a demonstration at Massachusetts General Hospital. Hence, it was not until about 20 years later that Colton reintroduced the use of N 2 O with the improved apparatus, and since then it has become popular.
Recognition
N 2 O is a colorless, sweet-smelling gas, which has been used for more than 150 years as an anesthetic ( Table 93.1 ). It is considered to be the least potent inhalational anesthetic in current practice, with 104% of minimal alveolar concentration. Because of its low potency, N 2 O is often used as an additional inhalation agent to augment the effect of the anesthesia. For example, evidence has shown that pretreatment of N 2 O with 50% oxygen enhances the speed of induction of sevoflurane. N 2 O has a relatively low partition coefficient of only 0.47, which allows rapid equilibrium between the partial pressures of blood and gas. For this reason, the speed of onset and offset of N 2 O is relatively quick. Furthermore, N 2 O gives a “second gas effect” in which it increases the speed of onset of other gaseous anesthetics. For instance, the speed of onset of desflurane is increased by the concurrent administration of N 2 O. This “second gas effect” is due to the lower lipid solubility of N 2 O than nitrogen, which allows rapid diffusion of N 2 O into blood. This causes an increased concentration of the volatile anesthetics in the alveolar space and thus the increased speed of onset. N 2 O is also transported freely in the blood as it does not bind to hemoglobin. The elimination of this inhalation agent is therefore rapid.
TABLE 93.1
Physical and Chemical Properties of Nitrous Oxide
Data from Brown SM, Sneyd JR: Nitrous oxide in modern anesthetic practice. BJA Educ 16(3):87-91, 2015; Becker DE, Rosenberg M: Nitrous oxide and the inhalation anesthetics. Anesth Prog 55(4):124-131, 2008.
| Boiling point | −88°C |
| Molecular weight | 44 |
| Minimal alveolar concentration | 104% |
| Blood:gas partition coefficient | 0.47 |
| Fat:blood partition coefficient | 2.3 |
| Color | Colorless |
| Smell | Sweet smelling |
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