Annals of Emergency Medicine
Volume 37, Issue 1 , Pages 61-62, January 2001

Continuous-flow nitrous oxide: Searching for the ideal procedural anxiolytic for toddlers☆

Division of Emergency Medicine, Children’s Hospital and Harvard Medical School, Boston, MA

Article Outline

Abstract 

[Krauss B. Continuous-flow nitrous oxide: searching for the ideal procedural anxiolytic for toddlers. Ann Emerg Med. January 2001;37:61-62.]

 

See related article, p. 20 .

Significant progress has been made in managing the acute pain associated with emergency department procedures in children.1 Emergency physicians have learned to effectively control the pain associated with procedures such as fracture reduction, abscess incision and drainage, arthrocentesis, lumbar puncture, thoracentesis, and bone marrow aspiration through the use of topical, local, and systemic analgesia. On the other hand, the anxiety associated with common and minimally painful procedures (eg, laceration repair, venipuncture, and intravenous cannulation) has proved challenging to effectively control, especially in young children. Parenteral routes of administration (intramuscular or intravenous) for these procedures, while effective, are either impractical because of the brief nature of the procedure or further exacerbate the high level of anxiety these children are already experiencing.

The ideal procedural anxiolytic for young children would be noninvasive, highly effective, with rapid onset and brief duration, and exhibit minimal adverse effects. Oral midazolam, ketamine, and fentanyl have been studied for this purpose2, 3, 4, 5, 6, 7, 8; however, each exhibits substantial limitations that distance them from this ideal. In 1995, while visiting France, I observed an anesthesiologist using nitrous oxide by a continuous-flow system for bone marrow aspiration in a 2-year-old.9 This system consisted of a small mask that was placed over the nose and mouth of the child and attached by tubing to a large tank of nitrous oxide that was wheeled from room to room with no scavenging device or electronic monitoring. I was intrigued by the efficacy and simplicity of this technique, and wondered whether such a free-flow system with appropriate monitoring and scavenging might bring us a step closer to the ideal procedural anxiolytic for toddlers.

In this issue of Annals , Luhmann et al10 describe the use of such a continuous-flow nitrous oxide system (50% nitrous/50% oxygen).11 The study compared, in a randomized fashion, the efficacy and complication profiles of nitrous oxide, oral midazolam, both, or neither for laceration repair in children ages 2 to 6. Nitrous oxide administered alone was found to be superior (shorter recovery times, greater suturer satisfaction, and fewer side effects) to the other groups. Interestingly, the nitrous-midazolam combination appeared to increase the side effect profile and offered no benefits over nitrous oxide alone.

Although Luhmann et al10 demonstrate the efficacy of this noninvasive drug delivery system in toddlers, 3 factors may prevent nitrous oxide from fulfilling the characteristics of an ideal procedural anxiolytic: (1) the labor-intensive personnel requirement of 2 physicians during the sedation/procedure (one to administer the nitrous oxide and the other to perform the procedure); (2) the relatively high emesis rate (5/51 [10%], 95% confidence interval 3% to 21%) in the setting of a mask tightly fit over the nose; and (3) the position of the mask limiting laceration repair in the perioral and nasal areas of the face. In addition, the cost and maintenance of the equipment and the training and personnel required to use it may limit its acceptance, especially in community hospital EDs with relatively low volumes of pediatric procedures.

There have been few prior studies of continuous-flow nitrous oxide for procedural sedation, especially in young children. Griffin et al12 administered nitrous oxide at an unspecified concentration for minor surgical procedures to “approximately” 3,000 “children and teenagers”; they noted emesis in 0.3%. Gamis et al13 compared 30% nitrous/70% oxygen with oxygen placebo for pediatric laceration repair. At this low concentration, they found an analgesic effect in children older than 8 years but not in children younger than 8 years, attributed to the inability of the younger children to cooperate with the mask. Burton et al14 compared continuous flow 50% nitrous/50% oxygen with oxygen placebo for laceration repair in children 2 to 7 years old, and noted a significant reduction in anxiety despite the small sample size (nitrous oxide n=17, placebo n=13). There were no serious adverse events in these studies.

There is more published experience using the demand valve delivery system (especially for fracture reduction)15, 16, 17; however, at these concentrations (50% nitrous/50% oxygen), the analgesic and amnestic effects of nitrous are variable. Although Wattenmaker et al15 reported that nitrous oxide was “a very effective analgesic agent for the reduction of fractures,” 19 of the 21 patients studied (all >4 years) were described as being in pain during the procedure, and 8 recalled having pain after the procedure. Hennrikus et al16 similarly studied 54 children (4 to 15 years) and found that 46% showed evidence of significant pain and only partial analgesia during the procedure and 9% appeared to obtain no analgesic effect. No serious adverse events were reported in any of these studies.

The continuous-flow systems, using nitrous oxide concentrations from 30% to 50%, appear more effective in younger children but have a higher predisposition toward emesis (6% to 10%10, 13, 14) than the demand-flow systems. It is unclear whether this is inherent to the continuous-flow system itself, or related to higher central nervous system concentrations and a deeper level of sedation.

Luhmann et al10 have succeeded in demonstrating that continuous-flow nitrous oxide exhibits 4 of the 5 characteristics of an ideal procedural anxiolytic in toddlers—painless administration, efficacy, rapid onset, and rapid recovery. Despite this contribution, their sample size is too small to reliably profile the incidence and severity of adverse events. Further research is needed to address the following questions: What is the adverse event profile in a large sample of administrations? Can the emesis associated with nitrous oxide delivered via continuous flow be prevented or minimized? Can continuous-flow nitrous oxide be used effectively for other procedures associated with high anxiety but a low level of pain (ie, intravenous cannulation, lumbar puncture, foreign body removal)? Because some mask leak from this technique is inevitable, is it possible to consistently avoid environmental contamination above accepted nitrous oxide exposure standards? Can the substantial logistical hurdle of a separate sedating physician be overcome through special nurse training in this technique? I hope that these investigators and others will address these issues.

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References 

  1. Krauss B, Green SM. Procedural sedation and analgesia in children. N Engl J Med. 2000;342:948–956
  2. Hennes HM, Wagner V, Bonadio WA, et al.  The effect of oral midazolam on anxiety of preschool children during laceration repair. Ann Emerg Med. 1990;19:1006–1009
  3. Sievers TD, Yee JD, Foley ME, et al.  Midazolam for conscious sedation during pediatric oncology procedures: safety and recovery parameters. Pediatrics. 1991;88:1172–1179
  4. Connors K, Terndrup TE. Nasal versus oral midazolam for sedation of anxious children undergoing laceration repair. Ann Emerg Med. 1994;24:1074–1079
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  8. Schechter NL, Weisman SJ, Rosenblum M, et al.  The use of oral transmucosal fentanyl citrate for painful procedures in children. Pediatrics. 1995;95:335–339
  9. Annequin D, Carbajal R, Chauvin P, et al.  Fixed 50% nitrous oxide oxygen mixture for painful procedures: a French survey. Pediatrics. 2000;105:e47
  10. Luhmann JD, Kennedy RM, Porter FL, et al.  A randomized clinical trial of continuous flow nitrous oxide and midazolam for sedation of young children during laceration repair. Ann Emerg Med. 2001;37:20–27
  11. Luhmann JD, Kennedy RM, Jaffe DM, et al.  Continuous flow delivery of nitrous oxide and oxygen: a safe and cost effective technique for inhalation and sedation of pediatric patients. Pediatr Emerg Care. 1999;15:388–392
  12. Griffin G, Campbell V, Jones RL. Nitrous oxide–oxygen sedation for minor surgery: experience in a pediatric setting. JAMA. 1983;245:2411–2413
  13. Gamis AS, Knapp JF, Glenski JA. Nitrous oxide analgesia in a pediatric emergency department. Ann Emerg Med. 1989;18:177–181
  14. Burton JH, Auble TE, Fuchs SM. Effectiveness of 50% nitrous oxide/50% oxygen during laceration repair in children. Acad Emerg Med. 1998;5:112–117
  15. Wattenmaker I, Kasser JR, McGravey A. Self-administered nitrous oxide for fracture reduction in children in an emergency room setting. J Orthop Trauma. 1990;4:35–38
  16. Hennrikus WL, Simpson RB, Klingelberger CE, et al.  Self-administered nitrous oxide analgesia for pediatric fracture reductions. J Pediatr Orthop. 1994;14:538–542
  17. Alexander AH, Alexander CE, Woodruff RE, et al.  Nitrous oxide analgesia for minor orthopaedic procedures. Orthopaedics. 1983;6:309–314

☆ Reprints not available from the author. Address for correspondence: Baruch Krauss, MD, EdM, Division of Emergency Medicine, Children’s Hospital, 300 Longwood Avenue, Boston, MA 02115; 617-355-4049, fax 617-355-6625; E-mail baruch.krauss@tch.harvard.edu.

PII: S0196-0644(01)34618-8

doi:10.1067/mem.2001.112004

Refers to article:

  • A randomized clinical trial of continuous-flow nitrous oxide and midazolam for sedation of young children during laceration repair

    Jan D. Luhmann, Robert M. Kennedy, Fran Lang Porter, J.Philip Miller, David M. Jaffe
    Annals of Emergency Medicine January 2001 (Vol. 37, Issue 1, Pages 20-27)

Annals of Emergency Medicine
Volume 37, Issue 1 , Pages 61-62, January 2001

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