Pain management and sedation/original research
Safety of Intranasal Fentanyl in the Out-of-Hospital Setting: A Prospective Observational Study

https://doi.org/10.1016/j.annemergmed.2013.10.025Get rights and content

Study objective

Initial out-of-hospital analgesia is sometimes hampered by difficulties in achieving intravenous access or lack of skills in administering intravenous opioids. We study the safety profile and apparent analgesic effect of intranasal fentanyl in the out-of-hospital setting.

Methods

In this prospective observational study, we administered intranasal fentanyl in the out-of-hospital setting to adults and children older than 8 years with severe pain resulting from orthopedic conditions, abdominal pain, or acute coronary syndrome refractory to nitroglycerin spray. Patients received 1 to 3 doses of either 50 or 100 μg, and the ambulance crew recorded adverse effects and numeric rating scale (0 to 10) pain scores before and after treatment.

Results

Our 903 evaluable patients received a mean cumulative fentanyl dose of 114 μg (range 50 to 300 μg). There were no serious adverse effects and no use of naloxone. Thirty-six patients (4%) experienced mild adverse effects: mild hypotension, nausea, vomiting, vertigo, abdominal pain, rash, or decrease of Glasgow Coma Scale score to 14. The median reduction in pain score was 3 (interquartile range 2 to 5) after fentanyl administration.

Conclusion

The out-of-hospital administration of intranasal fentanyl in doses of 50 to 100 μg is safe and appears effective.

Introduction

Due to difficulties in achieving successful intravenous cannulation in some out-of-hospital populations and lack of skills in administering intravenous opioids in a large part of the out-of-hospital workforce, both patients and the ambulance personnel are in need of an alternative analgesic that is safe, effective, noninvasive, easily administrable, and fast acting. A recent review suggests intranasal fentanyl as having some analgesic effect in the out-of-hospital setting.1 Adverse effects of fentanyl are most commonly respiratory depression, arterial hypotension, dizziness, fatigue, and nausea.2 Previous studies demonstrate adverse effects in 3.3% to 39% of patients treated with intranasal fentanyl,3, 4, 5 providing an ambiguous safety profile.

Editor's Capsule Summary

What is already known on this topic

Opioid therapy for out-of-hospital pain is often delayed by challenges with intravenous access.

What question this study addressed

Is intranasal fentanyl safe in the out-of-hospital setting?

What this study adds to our knowledge

In this prospective observational series, 903 adults and older children with severe pain received intranasal fentanyl in doses of either 50 or 100 μg. There were no serious adverse effects, and pain scores improved.

How this is relevant to clinical practice

Intranasal fentanyl was safe in this large series and represents a promising modality for rapid out-of-hospital analgesia.

Fentanyl is approximately 50 to 100 times more potent than morphine,6 which provides it with the capability of delivering a sufficient reduction in pain despite the volumetric limitation of intranasal application.7 Intranasal fentanyl has a bioavailability of 71% to 89%,8 and both maximal arterial blood concentration and onset of analgesia are reached in approximately 7 minutes.9, 10 Intranasal fentanyl in doses of 50, 100, and 200 μg are demonstrated as adequate analgesics in cancer patients with breakthrough pain.11

The Danish health care provision is divided into 5 regions with independent medical guidelines. In the region Zealand, only 25% of the ambulances in the Danish ambulance service Falck carry a paramedic or emergency medical technician (EMT) who is allowed to administer intravenous opioids.12 The remaining 75% are allowed to administer nitrous oxide, with mandatory requirement of special ventilation. If intranasal fentanyl were proven to be safe and well tolerated, it could provide ambulances a fast and easy way to administer opioids.

We wished to assess the safety profile and apparent analgesic effect of intranasal fentanyl in the out-of-hospital setting.

Section snippets

Study Design and Setting

We performed this prospective, observational, Strengthening the Reporting of Observational studies in Epidemiology–compliant13 study during a 2-year period, from June 27, 2011, to June 26, 2013, in the Danish region of Zealand. In this region, the Falck ambulance service responds to 55,000 emergencies yearly.12 The ambulance workforce amounts to 417 persons, of whom 189 are paramedics or EMTs. The regional Ethics Committee concluded that our study was not notifiable because intranasal fentanyl

Characteristics of Study Subjects

Participant flow is shown in the Figure, with 903 evaluable patients in the final analyses. The baseline pain score was less than 5 in 16 patients; however, to minimize the risk of selection bias we retained them in the analyses. The study sample included 414 male patients and 489 female patients, aged from 7 to 100 years, with a median of 58 years (interquartile range 39 to 72). Baseline variables are shown in Table 1. Patients received 1 (n=526), 2 (n=333), or 3 (n=44) doses of fentanyl, with

Limitations

Our study was not blinded, and therefore it is possible that adverse event recording was influenced by the perspectives of out-of-hospital personnel. However, we used objective thresholds for respiratory depression and hypotension, so any effect would likely be on the subjective, less serious adverse events. We recorded adverse effects according to patient observation and patient complaints; this may have resulted in a lower incidence than if we had actively questioned patients, using a lengthy

Discussion

We performed a large observational study of intranasal fentanyl in the out-of-hospital setting and found that just 36 patients (4%) experienced adverse effects, comparable to safety profiles reported elsewhere.3, 4 None of the adverse effects were serious or life threatening.

We did not observe respiratory depression (respiratory rate less than 11 breaths/min), GCS score reduction to 14 in 5 patients was transient, and there was no use of naloxone or mask ventilation. Ten patients (1%) had

References (20)

There are more references available in the full text version of this article.

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    We chose a dose, route of administration, and a specific opioid that that we thought were likely to improve the pain experience and not substantially impact workflow by requiring extra nursing time to place an intravenous catheter or unduly prolong ED length of stay. Intranasal fentanyl has been used successfully in the ED and prehospital setting, affording modest analgesia for a variety of indications (11–13). When compared with intravenous fentanyl, intranasal fentanyl offers slightly less and slightly delayed analgesia (14,15).

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    Using a lower concentration of fentanyl (50 μg·mL-1) with an emphasis on repeat dosing, as outlined in the Taos protocol, allows for titrating as well as standardizing IN and IV medications. The need for and success of progressive protocols that enable providers with less advanced certification to provide pain management has been demonstrated in a diverse range of rural and prehospital settings.6,8,20,24–26,31,45 Local protocols for non-EMS affiliated organizations often tightly restrict the ability of paramedics to provide an advanced level of care and pain management.

  • Atomized intranasal vs intravenous fentanyl in severe renal colic pain management: A randomized single-blinded clinical trial

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    In addition, intranasal administration of fentanyl is highly safe, and due to the non-invasive nature of the procedure, it can increase patient′s satisfaction. This is especially important in patients with anxiety, severe pain, or those who have inaccessible veins [20–24]. In a study by Fendter et al., intranasally administrated fentanyl was more effective than intravenous morphine in reducing pain in patients with renal colic [25].

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Supervising editor: Steven M. Green, MD

Author contributions: ST and JBD designed the study and obtained research funding. APHK and DMBP conducted the data collection. APHK analyzed data and drafted the article. JBD and MSH were the primary revisers, though all authors contributed substantially to the revision. JBD takes responsibility for the paper as a whole.

Funding and support: By Annals policy, all authors are required to disclose any and all commercial, financial, and other relationships in any way related to the subject of this article as per ICMJE conflict of interest guidelines (see www.icmje.org). APHK was funded by The Ambulance Company Falck. ST and DMBP were employed by Falck during the study period. The study is reported according to the Strengthening the Reporting of Observational studies in Epidemiology guidelines.

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