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Intranasal fentanyl and high-concentration inhaled nitrous oxide for procedural sedation: A prospective observational pilot study of adverse events and depth of sedation

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Literature Review

Intranasal Fentanyl and High-concentration Inhaled Nitrous Oxide for Procedural Sedation: A prospective observational pilot study of adverse events and depth of sedation

Reviewed by Daniel Tsze, MD and Joseph Cravero, MD

Seigh R, Theophilos T, Babl F.  Acad Emerg Med.  2012;19(1):31-36.

Nitrous oxide (N­2O) is a titratable, inhaled agent that can be useful in providing sedation and analgesia.  However, the degree of analgesia provided by N2O alone is often insufficient for painful procedures, such as fracture reduction.  Intranasal fentanyl (INF) is an effective, non-parenteral means of providing analgesia.  This study tested the hypothesis that the addition of INF to N2O could provide a more effective regimen for procedural sedation than either agent alone. In addition, the authors sought to delineate the incidence of adverse events when this combination was used for procedural sedation.

A prospective, observational pilot study was conducted in 41 children, all of whom received INF 1.5 mcg/kg, and 98% received 70% N2O (one patient received 50%) for procedural sedation.  Depth of sedation was measured using the University of Michigan Sedation Scale (UMSS)1. Adverse events were defined in nine categories as per the Consensus Panel on Sedation Research of Pediatric Emergency Research Canada (PERC) and the Pediatric Emergency Care Applied Research Network (PECARN)2.  The majority of procedures were orthopedic (80.5%), with 61% of those procedures being fracture reduction.

UMSS data revealed that 43.9% were moderately sedated (somnolent/sleeping, easily roused with light tactile stimulation or simple verbal command); 36.9% were miminally sedated (may appear tired/sleepy, responds to verbal conversation and/or sounds); and only 14.6% were deeply sedated (deep sleep, rousable only with deep or significant stimuli).  No patients were unarousable.

There were no serious adverse events (i.e. hypoxia, required assisted ventilation; or had clinically apparent pulmonary aspiration, laryngospasm, cardiovascular events, or permanent complications).  The most common mild and self-resolving adverse event was vomiting in 19.5% of the patients.

The depth of sedation achieved by N2O and INF appears to be deeper than that achieved by N2O alone as per prior studies from the same institution (deep sedation achieved by 14.6% vs. 2.5%, respectively)3.  Unfortunately, the outcomes reported by the authors did not reveal whether or not the addition of fentanyl led to adequate conditions during significantly painful procedures. The authors failed to include a measure of intraprocedural distress or pain that would have been helpful in elucidating whether there is a significant analgesic benefit gained by adding INF.  This is especially important in light of any higher incidence of adverse events.

Analysis of adverse events revealed a higher rate of vomiting when combining N2O and INF compared to when N2O was given alone (19.5% vs. 5.7%)3.  This incidence is remarkable, especially in light of the fact that they did not follow up with patients after discharge, during which time patients may still vomit.  The sample size of this pilot study is too small to comment on incidence of serious adverse events, but the observation of increased vomiting in itself indicates the need for  increased vigilance and potentially implementing additional strategies to decrease emesis when combining N2O and INF.  The authors have suggested strategies such as giving the INF between 30 to 60 minutes before commencing N2O so that the peak emetic effect of INF does not coincide with administering N2O, which itself is pro-emetic. They also suggest premedicating with an antiemetic such as ondansetron.

In summary, the study documents that a greater proportion of children achieved deep sedation when N2O was used in conjunction with INF, than when N2O was used alone.  There was a clear trend toward increased vomiting with the combination. The study does not clearly resolve whether or not INF provides a significant amount of additional intraprocedural analgesia.  Future studies should evaluate alternative methods for decreasing emesis associated with this combination.  In addition, this combination should be compared in cotrolled studies to other combinations such as N2O combined with local anesthetic or ketamine.


  1. Malviya S et al.  Depth of sedation in children undergoing computed tomography: validity and reliability of the University of Michigan Sedation Scale (UMSS).  Br J Anaesth. 2002;88;241-5.
  2. Bhatt et al.  Consensus-based recommendations for standardizing terminology and reporting adverse events for emergency department procedural sedation and analgesia in children.  Ann Emerg Med. 2009;53’426-36.
  3. Babl et al.  High-concentration nitrous oxide for procedural sedation in children: adverse events and depth of sedation.  Pediatrics. 2008; 121:e528-32.
  4. Luhmann JD, et al.  A randomized comparison of nitrous oxide plus hematoma block versus ketamine plus midazolam for emergency department forearm fracture reduction in children.  Pediatrics. 2006;118:e1078-86.

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