Nitrous oxide has a long history of utilization and experimentation over the last 2 centuries. The first documented medical application of a nitrous oxide–oxygen combination was to facilitate a dental extraction in 1840 (1). Nitrous oxide is now widely used for sedation in a variety of clinical settings.

The advantages offered by nitrous oxide are a quick onset of action, a low incidence of complications, and the rapid return of the patient’s baseline level of consciousness. For the pediatric population, perhaps the greatest advantage is that nitrous oxide can be administered without inflicting the pain of an intravenous line insertion or intramuscular injection. The primary disadvantage of nitrous oxide administration is that its clinical effects are somewhat unpredictable; that is, the degree of anxiolysis and analgesia experienced can be variable. Furthermore, effective delivery of the gas is predicated on the patient’s acceptance of the mask and willingness to inhale the gas mixture. Lack of interest and/or cooperation often results in inadequate administration of nitrous oxide and a poor clinical response.

Several investigations have described nitrous oxide utilization for procedural sedation and analgesia in pediatric patients (2,3,4,5,6,7,8,9,10,11,12). At least two relatively large studies in children have shown good efficacy and a low rate of complications when nitrous oxide is used to facilitate minor procedures (2,3). In most reports, nitrous oxide concentrations of 33% to 60% delivered by mask have led to clinically important relief of pain and anxiety in pediatric patients. While vomiting and respiratory events (e.g., desaturation, apnea) are typically cited as the most serious complications encountered, both are infrequent (less than 1% for respiratory complications) and resolve with cessation of nitrous oxide administration. Among the procedures that nitrous oxide has been used to facilitate in children are laceration repair, venous cannulation, incision and débridement of wounds, and fracture reduction.

Although most published studies have focused on the self-administered delivery of nitrous oxide, physician-assisted delivery of gas to pediatric patients also has proven to be safe and effective (2,3,4,5,6,7,8,9). As described below, this method allows the operator to provide sedation and analgesia to younger children, typically between the ages of 2 and 5 years, who might not otherwise understand or cooperate with self-administration. Using nitrous oxide sedation for children under 2 years of age is uncommon, primarily because it is often difficult or impossible to convince a younger child to accept the mask apparatus. Administration of a nitrous oxide–oxygen mixture to pediatric patients requires skill and experience with airway management procedures and a thorough familiarity with the delivery apparatus and the physiologic effects of the gas.

The unique aspect of nitrous oxide that distinguishes it from other agents used for procedural sedation and analgesia outside the operating room is that it is a gas. Although a daily activity for the anesthesiologist, the use of gaseous agents by most other practitioners is less common. Consequently, an understanding of the physiologic mechanisms governing the uptake, distribution, and excretion of an administered gas is important when using nitrous oxide.

Inhaled medications must be transferred from a respiratory circuit to the patient’s lungs, taken up by the pulmonary vasculature, and distributed to the tissues where it will have an effect, primarily the central nervous system. Several qualities of both the gas and the patient will govern the uptake and elimination of an inhaled medication. The most important physical property of the gas is its solubility. An insoluble gas is taken up in the lungs much more rapidly than a highly soluble gas. Nitrous oxide is the most insoluble gas used in
anesthesia; as a result, a high concentration develops in the alveoli, favoring a large concentration gradient to the blood, which in turn causes rapid uptake. A more soluble agent is continually washed out of the lung and therefore produces a lower concentration gradient.

Once the gas is in the lung, the patient’s minute ventilation will determine the rate of delivery of the gas to the blood. The cardiac output will determine the rate of uptake of the gas. A high minute ventilation (which is normal in children) increases the uptake of the gas. However, this effect is partially offset by a high cardiac output, which will delay gas uptake. This occurs because the gas is washed out of the lung, producing a lower concentration gradient from the alveoli to the blood. Despite these competing effects, the nitrous oxide onset of action for a pediatric patient is rapid (2 to 3 minutes) as a result of the low solubility of the gas and a high minute ventilation.

Elimination of a gas (off-loading) occurs in a manner that is essentially the reverse of uptake. Off-loading occurs as a concentration gradient develops from the blood to the alveoli when gas delivery is discontinued and the agent is excreted each time the patient exhales. Several factors contribute to the rapid off-loading of nitrous oxide, which normally takes 2 to 5 minutes (13). For one thing, nitrous oxide is not metabolized before excretion, so elimination begins immediately. Nitrous oxide also is lipid insoluble, and therefore uptake by the muscle, fat, and solid organs is minimal. This lowers the total body stores and makes the gas rapidly available for excretion. Finally, nitrous oxide is not significantly protein bound, which enhances the diffusion of the gas from the blood to the alveoli.

The mechanism of action of nitrous oxide is poorly understood, although it does appear to act directly on the endogenous opioid system (14,15). This finding in part accounts for its analgesic properties. Nitrous oxide also acts as an anxiolytic, but the mechanism of this effect is unknown. Despite being a potent CNS depressant, nitrous oxide has been shown to have minimal effects on the normal protective airway reflexes in children (16). As mentioned previously, patients can have a wide range of clinical responses using this agent. Anxiolysis, a sense of detachment, and euphoria are most commonly observed. In addition, the patient is usually amnestic after the procedure. This profile of sedation, analgesia, and amnesia is one of the primary reasons that nitrous oxide is an excellent choice in selected cases for pediatric conscious sedation.

The typical pediatric candidate for nitrous oxide use is the child who requires a short duration of sedation and/or analgesia during a painful or anxiety-provoking procedure. Nitrous oxide provides a low to moderate depth of sedation in the majority of patients. Specific clinical circumstances in which nitrous oxide might be chosen include foreign body removal, intravenous access with an anxious child, laceration repair, fracture reduction, minor joint relocation, incision and drainage of an abscess, and burn débridement. However, almost any minor pediatric procedure can be facilitated by nitrous oxide administration.

As with any procedure, if the level of procedural sedation and analgesia proves to be inadequate, another method should be used. One point worth emphasizing is that nitrous oxide should not be used as a replacement for local anesthesia during painful wound management procedures. As with virtually all forms of procedural sedation and analgesia, a local anesthetic should be administered intradermally or topically whenever possible. Otherwise, the goal of using nitrous oxide becomes not only sedation and analgesia but the complete elimination of any perception of pain—an unrealistic expectation that makes a successful sedation far less likely.

Contraindications to using a nitrous oxide–oxygen mixture are relatively few. One important concern with this agent is the property of expansion within closed spaces. Nitrous oxide readily diffuses across biologic membranes. This diffusion theoretically continues until equilibrium is reached for the gases contained within any space. Consequently, the volume of gas within a closed space will increase as diffusion of nitrous oxide continues, eventually leading to excessively high pressures. Any known or suspected gaseous pocket in the body has the potential for expansion during the use of nitrous oxide. Nitrous oxide is therefore contraindicated in patients with suspected pneumothorax, bowel obstruction, or otitis media, a particularly common pediatric problem. Examining the ears and eliciting any history of otalgia is therefore especially important before using nitrous oxide with children. Potential adverse consequences include tension pneumothorax, bowel perforation, and tympanic membrane rupture (see also “Complications”).

Another contraindication to using nitrous oxide is impairment of the patient’s level of consciousness. Because safe and effective use of this agent requires significant cooperation, the patient with mental status changes who requires sedation would likely be better managed with an intravenous regimen. For example, the child with a minor head injury who has postconcussive agitation or lethargy would not be an appropriate candidate for nitrous oxide sedation (e.g., to repair a complex facial laceration or to reduce a displaced fracture). In such situations, the patient is unlikely to provide the degree of cooperation necessary to use nitrous oxide appropriately.