Original Article
Eva Malmros Olsson, Per-Arne Lönnqvist, Carl-Olav Stiller, Staffan Eksborg, Stefan Lundeberg. Rapid systemic uptake of naloxone after intranasal administration in children. Pediatric Anesthesia. 2021;31:631–636 PMID: 33687794
Drug administration using the intranasal (IN) route has intrigued and been used by pediatric anesthesiologists for more than 40 years. Dennis Fisher and colleagues first reported on the use of IN sufentanil as a painless, pre-induction med in 1988 (PMID: 2897172). Many of you probably use IN midazolam and dexmedetomidine alone or in combination as a premed. The IN route is faster than orally administered drugs and rivals IM and IV administration for speed of onset. How the IN route works is pretty amazing. The most obvious method is absorption of drug into the systemic circulation by diffusion across the highly vascular nasal mucosa. A less obvious method is rapid absorption directly into the CSF via the olfactory nerve and nasal cilia crossing the cribriform plate which bypasses the Blood Brain Barrier, so its speed of onset may rival or exceed direct IV administration.
IN naloxone is a very important method of resuscitation of opioid overdose outside of the hospital.1-4 Dispensed in 4 mg (and recently 8 mg) single use devices, they are simple to use and can be used by “civilians” with little training. These devices are so effective and safe, many have advocated that they be dispensed routinely with all opioid prescriptions and to families and friends of patients with, or at risk of, opioid use disorder.
This study is the first to formally look at IN naloxone pharmacokinetics in pediatrics. The authors did not use the commercially available products, fearing that the single, non-titratable 4 mg dose was too high. Rather, they used off the shelf 0.4 mg/mL ampules administered in syringes with an attached mucosal atomizing device, both of which are widely available in most ORs. The authors found that venous blood levels were quantifiable within 5 minutes (first blood draw) and maxed out at 10-20 minutes. They administered 20 mcg/kg doses divided into 0.1 mL aliquots administered into each nostril to a maximum of 0.4 mL. A major shortcoming of the paper is that the authors did not study the effectiveness of the absorbed dose at reversing opioid induced side effects, that is, a pharmacodynamic study.
This is an exciting development as an alternative method of naloxone administration when an IV in not available. To be honest, in an emergency I don’t think I’d have the presence of mind to divide the doses and would just give it all (0.4 mg/mL, or 0.5 mL (0.2 mg) into each nostril), knowing that not all of the drug would be absorbed nasally and some will overflow into the oral pharynx. For those with more steeley nerves, in an emergency the doses used in this study should hopefully be very effective in children. Obviously, a future pharmacodynamic to verify effectiveness in opioid overdose will be needed.
Myron Yaster MD
References
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Neale J, Brown C, Campbell ANC, Jones JD, Metz VE, Strang J, Comer SD: How competent are people who use opioids at responding to overdoses? Qualitative analyses of actions and decisions taken during overdose emergencies. Addiction 2019; 114: 708-718
McDonald R, Strang J: Are take-home naloxone programmes effective? Systematic review utilizing application of the Bradford Hill criteria. Addiction 2016; 111: 1177-87