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Troubleshooting Drug Shortages – Alternatives to Fentanyl

Dr. BurgerBy Becky Burger, MD
Section Editor

We have all become accustomed these days to our pharmacists informing us that “(fill in the blank)” is on shortage or not available at all, the most recent of which is fentanyl.  Fentanyl and midazolam (Versed™) are often used for moderate sedation in the intravenous or intranasal forms or as adjuncts during rapid sequence intubation. With the current fentanyl shortage, we will have to turn to other drugs with which we may not be as familiar.  Here is a review of several alternatives to fentanyl.

Two well known alternatives to fentanyl are morphine and hydromorphone (Dilaudid™).  Proceed with caution when using these opioid alternatives in combination with midazolam for sedation as their effects can last much longer than fentanyl, thereby requiring a longer post-procedural observation period.   Fentanyl has an almost immediate onset when given IV and lasts between 30 to 60 minutes (1).  Comparatively, morphine’s onset is approximately five minutes when given IV and lasts between 3 to 5 hours; hydromorphone’s onset is within five minutes when given IV and lasts between 3 to 5 hours (1).  Neither morphine nor hydromorphone are available in intranasal forms.  Intranasal diamorphine has been shown to be more, or as effective, as respectively IM (2) and IV (3) morphine in clinical studies, however diamoprhine is not widely available in the United States.

Fentanyl is a commonly used adjunct to propofol for deep sedation in painful procedures.   An alternative to fentanyl in this setting is a sub-dissociative dose (0.5-1 mg/kg) of ketamine (“ketofol”).  Ketamine is a wonderful analgesic at low doses and in combination with propofol, the adverse effects of these two drugs balance out (4).

Other non-opioid alternatives include using intranasal midazolam alone for mild to moderate sedation.  Intranasal midazolam has an onset of action of 5 to 10 minutes and lasts between 30 and 60 minutes (1).  The recommended intranasal midazolam dosage is 0.2-0.5 mg/kg (1); the maximum dose is 10 mg when using the 5 mg/ml concentration because the maximum volume per nostril is 1 ml.  Intranasal midazolam is a good choice for simple procedures that do not require placing an IV.  Proceed with caution when using midazolam, however, as it can cause paradoxical agitation, especially in young children.  Intranasal delivery can cause irritation of the nasal mucosa.  Chiaretti, et. al. showed that giving intranasal lidocaine spray prior to intranasal midazolam prevented nasal burning and irritation (5). 

Inhaled nitrous oxide (50% to 70% concentration) is effective at providing mild sedation for non-painful procedures.  When attempting more painful procedures, use local/topical anesthesia if feasible, or consider adding additional agents for analgesia (with increased monitoring, since adding additional agents increases the likelihood of achieving deeper levels of sedation and nausea/vomiting) (6).  The onset of action of nitrous oxide is 2 to 5 minutes (1).  Nitrous oxide is absorbed quickly in the lungs.  Once the mask delivering nitrous oxide is removed from the patient’s face, the sedating effects wear off very quickly.  The recovery time from nitrous oxide is almost immediate making it a very attractive mode of sedation.  For more details about nitrous oxide and its use in pediatric procedural sedation, see Tobias’ article in Pediatric Emergency Care (7).

Finally, child life or distraction must always be considered when performing procedures that are non-painful or quick as the risks of sedation may outweigh the benefits.  While any of the above listed drugs used for sedation will likely allow you to complete the procedure needing to be done, always consider the risks involved and what is best for the patient.


  1. Lexicomp (
  2. Kendall JM, Reeves BC, Latter VS; Nasal Diamorphine Trial Group.  Multicentre randomized controlled trial of nasal diamorphine for analgesia in children and teenagers with clinical fractures.  BMJ.  2001 Feb 3; 322(7821): 261-5.
  3. Regan L, Chapman AR, Celnik A, Lumsden L, et al.  Nose and vein, speed and pain: comparing the use of intranasal diamorphine and intravenous morphine in a Scottish paediatric emergency department.  Emerg Med J.  2013 Jan; 30(1):49-52.
  4. Alletag M, Auerbach MA, Baum CR.  Ketamine, Propofol, and Ketofol Use for Pediatric Sedation.  Pediatr Emerg Care.  2012 Dec; 28(12): 1391-5.
  5. Chiaretti A, Barone G, Rigante D, Ruggiero A, et al.  Intranasal lidocaine and midazolam for procedural sedation in children.  Arch Dis Child.  2011; 96(2): 160-3.
  6. Seith RW, Theophilos T, Babl FE.  Intranasal fentanyl and high-concentration inhaled nitrous oxide for procedural sedation: A prospective observational pilot study of adverse events and depth of sedation.  Academic Emerg Med.  2012 Jan; 19(1):31-36.
  7. Tobias, Joseph D.  Applications of nitrous oxide for procedural sedation in the pediatric population.  Pediatr Emerg Care.  2013 Feb; 29(2): 245-65.

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