Naloxone can be administered via multiple routes, with nebulization gaining popularity in the past decade. A previous ALiEM Trick of the Trade presented this unique method of administration. In order for nebulized naloxone to be effective patients need to have some level of respiratory effort. It should not be used in patients in respiratory arrest or impending respiratory arrest. It may be a more gentle way to wake up patients to confirm the diagnosis of opioid toxicity and to gather a history. Theoretically, if the patient arouses enough to start experiencing mild withdrawal, they can ‘self-titrate’ and remove the nebulizer mask.

How is it prepared?

Mix 2 mg naloxone (5 mL of  naloxone 0.4 mg/mL) with 3 mL of 0.9% sodium chloride for inhalation in a nebulizer cup.


Anecdotal reports tout the benefits of nebulized naloxone, but what does the literature say?

  • Case report of a 46 y/o female with an initial oxygen saturation of 61%. Naloxone 2 mg was administered via nebulization and within 5 mins her oxygen saturation was 100% and mental status was normal [1].
  • Retrospective analysis of prehospital administration in 105 patients with suspected opioid overdose. Following nebulized naloxone,  22% had a “complete response” and 59% had a “partial response.” It’s important to note that the initial respiratory rate was already 14 bpm with GCS of 12 for patients that responded to treatment [2].
  • Prospective analysis of 26 patients with suspected opioid intoxication treated at an inner-city, academic ED. Pre-naloxone the mean respiratory rate was 13 with a median GCS of 11. Following treatment, the mean respiratory rate improved to 16 with a median GCS of 13. Three patients (12%) experienced moderate-to-severe agitation and 2 (8%) became diaphoretic, suggesting precipitation of acute withdrawal [3].
  • Case report of a 20 y/o female with initial oxygen saturation of 62% (respiratory rate not reported). She improved following administration of nebulized naloxone and clinical efficacy corresponded with serum naloxone concentrations [4].


Importantly, aside from the two case reports, the above studies both primarily included patients without severe respiratory depression. As far as the safety of nebulized naloxone, Baumann et al. reported 5 patients (out of 26) who seemed to have mild-to-moderate symptoms of withdrawal following administration [3]. So this raises a question that must be answered on a patient specific basis: Does the benefit of this therapy outweigh the risk in patients who may not require naloxone to begin with? An alternative approach, if IV access is established, is to try low-dose diluted IV naloxone.


Bottom Line

Many of the studied patients may not have needed naloxone in the first place as they had an initial respiratory rate 13-14, with a few developing withdrawal symptoms. Nebulized naloxone may have a role in the “not-too-sick” opioid overdose in whom you want to prove your diagnosis and wake the patient up enough to obtain a history. It is not a therapy for an apneic patient with suspected opioid overdose.



  1. Mycyk MB, Szyszko AL, Aks SE. Nebulized naloxone gently and effectively reverses methadone intoxication. J Emerg Med. 2003;24(2):185-187. doi: 10.1016/s0736-4679(02)00723-0. PMID: 12609650.
  2. Weber JM, Tataris KL, Hoffman JD, Aks SE, Mycyk MB. Can nebulized naloxone be used safely and effectively by emergency medical services for suspected opioid overdose? Prehosp Emerg Care. 2012;16(2):289-292. doi: 10.3109/10903127.2011.640763. PMID: 22191727.
  3. Baumann BM, Patterson RA, Parone DA, et al. Use and efficacy of nebulized naloxone in patients with suspected opioid intoxication. Am J Emerg Med. 2013;31(3):585-588. doi: 10.1016/j.ajem.2012.10.004. PMID: 23347721.
  4. Minhaj FS, Schult RF, Fields A, Wiegand TJ. A case of nebulized naloxone use with confirmatory serum naloxone concentrations. Ann Pharmacother. 2018;52(5):495-496. doi: 10.1177/1060028017752428. PMID: 29319329.
Bryan D. Hayes, PharmD, DABAT, FAACT, FASHP

Bryan D. Hayes, PharmD, DABAT, FAACT, FASHP

Leadership Team, ALiEM
Creator and Lead Editor, Capsules and EM Pharm Pearls Series
Attending Pharmacist, EM and Toxicology, MGH
Associate Professor of EM, Division of Medical Toxicology, Harvard Medical School
Bryan D. Hayes, PharmD, DABAT, FAACT, FASHP


EM Pharmacist & Toxicologist @MassGeneralEM | Asst Prof @HarvardMed/@EMRES_MGHBWH | @ALiEMteam leadership | Capsules creator, ALiEMU | President, ABAT | #FOAMed