We heard the patient coming down the hall to the operating room before we saw her- a crying toddler in the nurse's arms, the first tonsillectomy of several today. Dutifully my trainee initiated the flow of nitrous oxide and oxygen and applied the mask, swiftly adding sevoflurane to curtail the crying. After several breaths of high-concentration sevoflurane, the child's chest continued moving, but gas exchange had ceased despite all airway maneuvers. In the grips of a laryngospasm, the child began to desaturate quickly. The diminishing tone of the pulse oximeter echoed as a code was called, an intravenous catheter was frantically attempted, and the child's heart rate began to decrease.

This toddler's situation usually resolves without any long-term sequelae, even in extreme circumstances requiring chest compressions. But in the aftermath of an acute emergency, we wonder what we might do differently to avoid this situation in the future. While we can mitigate some circumstances that increase the likelihood of laryngospasm or other airway complications during mask induction, we cannot omit the risk entirely. If there had been more time between the laryngospasm and the desaturation, it would likely have been a more stable situation with the possibility of maintained oxygen saturation during airway maneuvers and IV placement.

1 INTRODUCTION

Induction of anesthesia in adults, even perfectly healthy adults, is always preceded by preoxygenation/denitrogenation to maximize the time to desaturation in the event of an airway complication. If a trainee were to forego preoxygenation prior to inducing anesthesia in a healthy adult, they would be sternly educated about the importance of preoxygenation and the roles of functional residual capacity (FRC) and oxygen metabolism in determining apnea time before desaturation.

The benefits of preoxygenation/denitrogenation prior to induction of anesthesia are unquestioned in adult anesthesia practice. Likewise indisputable is the more rapid desaturation of children versus adults during apnea and the role of gas composition in a child's lungs on the duration of maintained oxygen saturation during apnea.^{1, 2} Given the rigid expectation of preoxygenation/denitrogenation in adults undergoing intravenous induction of anesthesia as well as the growing concern regarding the environmental impact of nitrous oxide, it is appropriate and it is the goal of this Perspectives essay to challenge the dogma of routinely using nitrous oxide for mask induction of anesthesia in children. It is indeed well-established dogma: a small survey of Society for Pediatric Anesthesia members found that 77% of respondents use at least 50% nitrous oxide in oxygen for pediatric mask induction.³ Herein we address each of several frequently cited reasons for using nitrous oxide for pediatric mask inductions, counter each reason with evidence, and propose alternatives that in our clinical experience result in a safer, equally pleasant, and less environmentally-impactful induction experience.

2 REASON: BECAUSE WE HAVE ALWAYS DONE IT THIS WAY

If the reason cited to use nitrous oxide is “because we've always done it this way,” it is appropriate to consider that the conditions of anesthetizing children are dynamic, and so is the environment in which we practice. Although anesthesia practice varies, anecdotally there are many institutions whereby the vast majority of pediatric patients are induced with N₂O regardless of patient comorbidities and risk factors. Poor air quality during wildfire season (and not just in forested areas, as evidenced by the dangerous air quality seen in cities on the United States' East coast due to Canadian wildfires in June 2023) has joined previously-recognized risk factors for airway complications in children undergoing anesthesia⁴ and with the ongoing drought in many large forested areas, the incidence and severity of large wildfires is predicted to increase. Additionally, childhood obesity in the United States has tripled in the past 30 years,⁵ further increasing the risk of upper airway obstruction in the pediatric population. Preoxygenation prior to induction is a basic tenet of anesthesia practice used to increase the margin of safety for patients in our care. The importance of maintaining adequate oxygenation during airway management is unquestioned and is explicitly stated in Gregory's Pediatric Anesthesia textbook.⁶ Compared to adults, children undergoing mask induction of anesthesia have proportionally less FRC, higher oxygen consumption per kilogram, an elevated risk of laryngospasm, and are without intravenous access. Because of these factors, a laryngospasm that occurs in the presence of 70% nitrous oxide will cause a more rapid and profound desaturation² than if the child had been pre-oxygenated during induction. The additional time prior to desaturation and bradycardia afforded by preoxygenating the patient increases the likelihood that airway maneuvers, IV placement, or administered intramuscular medication will relieve the laryngospasm prior to a severe desaturation event.

3 REASON: I TURN OFF THE NITROUS OXIDE ONCE THE CHILD IS UNRESPONSIVE

If the defense of using laughing gas is, “I turn off the nitrous oxide once the child is asleep,” we must ponder whether that method provides increased time before desaturation in the event of a laryngospasm compared to ceasing the flow of nitrous oxide when a laryngospasm occurs. The optimal condition in which to manage a laryngospasm during pediatric mask induction is that of a fully preoxygenated child. Adequate preoxygenation and denitrogenation has been defined as exhaled oxygen concentration (F_EO₂) >90% prior to the (intravenous) induction of anesthesia, a process that in adults takes at least 1 min (but can take up to 3 min) of breathing 100% oxygen through a well-fitting mask.⁷ Preoxygenation occurs more quickly in children but may still require 1–2 min.⁸ If nitrous oxide is turned off “once a child is asleep”, a nebulous parameter at best, it's unlikely that even one full minute of breathing 100% oxygen will be completed prior to a laryngospasm, should one occur. The interval between a child “falling asleep” and entering Stage 2, when laryngospasm is most likely to occur, is unlikely to be of a long enough duration to allow preoxygenation and the subsequent benefit of prolonged maintenance of oxygen saturation during airway occlusion. As a significant proportion of pediatric perioperative cardiac arrests are due to airway complications, most commonly laryngospasm, it is the anesthesiologist's duty to anticipate and take precautions against that scenario by providing as much time as possible to manage any airway complication.

4 REASON: WHY FIX SOMETHING THAT IS NOT BROKEN

If the reason cited to use nitrous oxide is, “It's just nitrous oxide, what's the big deal?” consider that the National Institute for Occupational Safety and Health has raised concerns about occupational exposure to nitrous oxide and established an exposure threshold⁹ due to studies in workers exposed to nitrous oxide finding reduced fertility,¹⁰ increased risk of spontaneous abortions, and neurologic, renal, and liver disease.¹¹ There may be additional risks for anesthesiologists and anesthetists with B12 deficiency due to known inactivation of methionine synthetase by nitrous oxide. Additionally, multiple recent studies have shown that 75%–95% of purchased nitrous oxide leaks out of the nitrous oxide central pipeline prior to even being available for clinical use.^12-14 This is concerning for occupational exposures and is, in any case, a profligate use of resources. Utilizing E-cylinders for delivery of nitrous oxide, rather than the central pipeline, reduces the leak substantially.¹² Nitrous oxide is a potent greenhouse gas with a Global Warming Potential 265 times that of carbon dioxide,¹² and nitrous oxide is now the leading cause of ozone depletion worldwide.¹⁵ Nitrous oxide persists in the environment for more than 100 years, and its impact is heightened due to the high concentrations required for clinical use. A 1-h anesthetic at 1 MAC Sevoflurane (maintenance FGF 0.7 Lpm) preceded by mask induction comprised of 70% nitrous oxide with total fresh gas flow of 5 Lpm for 5 min has 3.5× the total emissions as the same anesthetic without nitrous oxide.¹⁶

5 REASON: TO ALLOW A CHILD TO HAVE A NON-TRAUMATIC INDUCTION EXPERIENCE

If the reason cited to use nitrous oxide is: “To help a nervous child have a non-traumatic induction experience,” let us first agree that patient experience is very important and that there are many ways to help a child have a pleasant induction experience. Recall that the onset to euphoria with nitrous oxide, while not well-studied in children, is at least 30 s in adults inhaling deeply four times with a good mask fit in controlled settings.¹⁷ Administering nitrous oxide without a mask (e.g., with one's hand holding the circuit near a child's face) requires high flows of nitrous oxide and oxygen for far longer than would be required through a mask and results in occupational exposure of the anesthesia staff and anyone else nearby (e.g., the circulating nurse). The administration of nitrous oxide through a loosely-fitting mask (or a cupped hand), even at concentrations as high as 70%, will still have a delay prior to the onset of euphoria, and will not prevent an uncooperative child from experiencing distress during mask induction. However, factors that do influence mask acceptance include premedication, baseline patient and parent anxiety,¹⁸ preoperative preparation,¹⁹ selective use of parental presence,²⁰ and distraction techniques.^{21, 22} In a study of 832 pediatric patients undergoing mask induction with sevoflurane and nitrous oxide,¹⁹ while 57% of the patients had “perfect” compliance, the other 43% had “moderate” or “poor” compliance as indicated by adverse behaviors such as crying, refusing the mask, hysterical screaming, or kicking. Importantly, midazolam administration rates did not differ among the compliance groups. These results indicate that the use of nitrous oxide during mask induction does not guarantee a pleasant patient experience.

6 REASON: TO EASE THE TRANSITION TO BREATHING SEVOFLURANE

If the reason cited to use nitrous oxide is “To assist the transition to breathing sevoflurane without causing the child distress,” we must expose the impatience of our profession and openly admit, since it has not been studied, that most anesthesiologists do not wait for nitrous oxide-induced euphoria to occur before initiating the administration of sevoflurane. Early pediatric anesthesia textbooks do not specify the duration of nitrous oxide inhalation that should precede the addition of a volatile agent; the first edition of Smith to specify induction guidelines²³ recommends 1–2 min—that is, an eternity—of high-concentration nitrous oxide prior to adding halothane to the mask. Without accepted definitions of euphoria or consensus guidelines in practice, many anesthesiologists initiate sevoflurane into the circuit very soon after the start of the induction with nitrous oxide, all the while telling the child they “may smell something bad” or similar language. If we are using nitrous oxide to induce indifference to the smell of sevoflurane, why do we feel the need to warn the child about the smell? Prior to the ubiquitous presence of screens in everyday life, pediatric anesthesiologists enjoyed distracting children with jokes or stories or conversation. However, current practice often (and likely more effectively) involves a screen with a child's distraction-of-choice displayed during entry to the operating room, monitor placement, and mask placement—usually with consistent indifference or even tranquility from the child.²¹

7 REASON: BECAUSE THE SECOND-GAS EFFECT SPEEDS UP MASK INDUCTION

If the reason cited to use nitrous oxide is “To speed up induction via the second-gas effect,” we note that the second-gas effect was studied extensively for wash-in of halothane in intubated adults prior to the availability of sevoflurane, which has much lower blood solubility—and thus its relevance in pediatric mask induction is questionable at best. The uptake of sevoflurane (ratio of F_A/F_I) occurs at the same rate in children whether nitrous oxide is present in small (15%) or large (65%) inspired fractions except for a brief effect at 3 min into induction²⁴ and this study concluded that the second-gas effect contributed little to increasing the alveolar anesthetic concentration. Additionally, clinically the presence of nitrous oxide during pediatric mask induction did not decrease the time to loss of lash reflex or time to incision.²⁵ This study did note a longer time to intubation in the sevoflurane-only group compared to the sevoflurane with 66% nitrous oxide group (6.2 ± 1.8 min vs. 5.1 ± 1.9 min), though the criteria for determining appropriate depth for intubation were not specified and intravenous adjuncts were not given prior to intubation. The reasons for the second-gas effect not having clinical relevance in pediatric mask induction are multifactorial, including that children have increased alveolar ventilation relative to their FRC as well as having a higher proportion of their cardiac output dedicated to the vessel-rich group.

8 CONCLUSION

Why would we continue a practice that is less safe for children, potentially harmful to ourselves, and assuredly more harmful to the atmosphere—without any evidence of benefit for our patients? The answer cannot be “because we’ve always done it this way.” It’s time we put to use the arsenal of effective tools we have at our disposal: preoperative preparation of children, use of preoperative anxiety scores, use of effective premedication, and ubiquitous distraction technology to assure that the operating room personnel (ourselves included) experience less occupational exposure, that our environment is polluted with fewer damaging gases and most importantly that our pediatric patients have a safe and pleasant induction experience.

CONFLICT OF INTEREST STATEMENT

Dr. Chatterjee serves as a Section Editor for Pediatric Anesthesia. Dr. McGain has received grant funding from the NHMRC (National Health and Medical Research Council) and colleges of anesthesia and intensive care (ANZCA, CICM). Dr. McGain also receives royalties for a co-invented patient isolation hood. None of Dr. McGain's funding or royalties were used or pertain to this manuscript. Dr. Gordon has no conflicts of interest to disclose. No patient information or data is used in this publication. No permissions are needed for publication as there are no figures or direct quotes from published work in the manuscript.