Oxymetazoline (Afrin™)

Myron Yaster MD, Lynne Maxwell, John Fiadjoe, Debnath Chatterjee MD

Although hard to believe, it’s been six months since Ron Litman’s untimely death. Yesterday was his birthday. In his role at the FDA, Ron was very much involved in pediatric drug labeling for new and old drugs, therapeutic interventions and vaccines (see PAAD: “why are children always last”?).  As you all know, many drugs used in our daily practice are used “off-label”, that is, they aren’t tested or approved by the FDA for use in children. The lack of labeling doesn’t mean we can’t use them but puts the onus of complications and liability on us, the practitioners, rather than the company producing the drug. Today’s PAAD is about the over-the-counter topical nasal decongestant, oxymetazoline (Afrin™), which is used almost every day in the pediatric operating rooms and yet is FDA approved only for patients > 6 years of age.  Is it safe? Are we administering it correctly?  Today’s PAAD is a position paper by the Section on Anesthesiology and Pain Medicine and the Section on Otolaryngology–Head and Neck Surgery of the American Academy of Pediatrics and was submitted to the PAAD by Dr. Debnath Chatterjee.  Dabe should be well known to many of you because he is the Chair elect of the AAP’s Anesthesia section and in his role in OpenAnesthesia. So, I asked him to join us in this review.  The position paper presents some information that really surprised us and wanted to share with you. And this information and lack of FDA labeling would have been right up Ron’s alley. So, this one’s for you Ron and all of us who miss you and still can’t believe you are gone.  Myron Yaster MD Lynne Maxwell MD and John Fiadjoe

Original article

Cartabuke R, Tobias JD, Jatana KR; Section on Anesthesiology and Pain Medicine, Section on Otolaryngology–Head And Neck Surgery, American Academy of Pediatrics.  Topical Nasal Decongestant Oxymetazoline: Safety Considerations for Perioperative Pediatric Use. Pediatrics. 2021 Oct 4:e2021054271. PMID: 34607935

Oxymetazoline (Afrin™) is “is an α-adrenergic agonist with greater activity at the α2 versus α1 adrenergic receptor.  Its action at the peripheral α2-adrenergic receptor on the smooth muscle of the vasculature results in vasoconstriction, from which its clinical utility emanates as both a decongestant and a topical hemostatic agent. It is used off label in the operating room to prepare the nasal passages during nasal intubation and during ear, nose, and throat (ENT) surgery to improve visualization of the airway and to minimize intraoperative or postoperative bleeding”.  Its effect is as good or better than phenylephrine or cocaine.1,2  However, rapid absorption across the nasal mucosa is always possible whenever drugs are administered topically or by spray in the nose.  That’s why nasal naloxone and dexmedetomidine are so effective.  Because we know so little about the pharmacokinetics and dynamics of oxymetazoline when it’s administered nasally to children in the operating room3 serious adverse effects like hypertension, bradycardia, respiratory depression and sedation are possible.  Indeed, this has been reported.4

What we found most startling in this position paper concerned the variable dosing that occurs relative to the method of oxymetazoline’s administration.  It turns out that the spray bottle is designed to be administered only to patients in an upright position.  Inverting the bottle, as we do in a supine patient in the operating room, can produce a 75-fold increase in the volume of medication administered!4  This increased dose also occurs when soaked surgical pledgets are used as well! WOW!

Afrin’s package insert recommends 2-3 sprays in each nostril with the bottle in the upright position, which translates to about 180 mL of oxymetazoline, which is far less than the 1000 mL with a single spray when using the bottle in the inverted position or a single afrin soaked pledget.4

To be honest, we are not sure how to make use of this information. With the widespread use of oxymetazoline, if this drug is as dangerous as the position paper suggests, we should be seeing many more case reports of serious cardiovascular complications with Afrin use in small children. Sooooo, is this really a problem? Further, should we pre-spray the patient’s nose in the upright position in preop? In small children, should we be drawing up oxymetazoline in a 1-cc syringe and spraying it using a mucosal atomization device, like nasal dexmedetomidine administration? Should we lift the head and spray the nose without inverting the bottle in the OR? Should surgeons dilute the concentration of oxymetazoline when using pledgets?  We don’t know.  Clearly, this is an area that needs more research and we think would be an ideal project for young investigators.

Debnath Chatterjee, MD, FAAP, Lynne Maxwell, MD, FAAP, Myron Yaster MD

References

1.           Riegle EV, Gunter JB, Lusk RP, Muntz HR, Weiss KL: Comparison of vasoconstrictors for functional endoscopic sinus surgery in children. Laryngoscope 1992; 102: 820-3

2.           Higgins TS, Hwang PH, Kingdom TT, Orlandi RR, Stammberger H, Han JK: Systematic review of topical vasoconstrictors in endoscopic sinus surgery. Laryngoscope 2011; 121: 422-32

3.           Cartabuke RS, Anderson BJ, Elmaraghy C, Rice J, Tumin D, Tobias JD: Hemodynamic and pharmacokinetic analysis of oxymetazoline use during nasal surgery in children. Laryngoscope 2019; 129: 2775-2781

4.           Latham GJ, Jardine DS: Oxymetazoline and hypertensive crisis in a child: can we prevent it? Paediatr Anaesth 2013; 23: 952-6