Intranasal Fentanyl

Scenario
It's a summer afternoon and you're dispatched to a 9 year old male patient involved in an ATV accident. The nearest ALS engine company has been dispatched as well. Upon your arrival you find an ATV on its side, another ATV upright, and a crowd gathered on the porch of a nearby house. A paramedic from the engine is assessing a distraught young boy, sitting in his mother's lap, holding an obviously deformed right forearm. The officer on the engine informs you that the boy and his father were riding alongside the road, traveling at 20-30 miles per hour, when the boy lost control and was thrown from the ATV (his father insists he was wearing his helmet).

You introduce yourself to the child, assuring him you're here to help, and ask him what happened. The boy states that when he fell he put his arms out and he heard a loud pop when his right hand hit the ground. He denies passing out or any other injuries but says his arm, "really hurts". He reluctantly allows you to assess his radial pulse in the affected arm, which is rapid but easily palpable. There appears to be distal involvement of both the radius and ulna, however he does not tolerate any further assessment of the arm and screams if there is any movement. The remainder of your physical exam reveals only minor abrasions to exposed skin. The engine company reports tachypnea, tachycardia, and a normal blood pressure.

Discussion
It appears the child has suffered a Colles' Fracture of the right distal forearm. Appropriate treatment would include splinting, ice packs, and pharmacologic pain control. However, given the current state of the patient, it may not be possible to splint the extremity due to anxiety and pain. Traditional prehospital pain management would require intravenous access or intramuscular administration. Both of these routes are likely to cause increased anxiety in this patient, which is best avoided.

Pain management in the pre-hospital setting is fraught with problems. Most studies have found poor provider perception of pain, underutilization of analgesics, and a hesitance to treat pediatric pain (ThomasGreenwald). Often times, studies find that even if patients are provided analgesia, they do not feel their pain was managed adequately at all (Thomas). For pediatric patients, this problem is compounded as pre-hospital providers are often wary to provide pain management or may be unable to obtain invasive IV access to provide pain management (Greenwald). Moreover, pre-hospital providers are often placed in situations where access to patients is limited to provide pain-management, often times resulting in painful patient movements.

The addition of a noninvasive means of pain management would be an invaluable aid to pre-hospital providers and would remove a potential barrier to care. In pediatric populations, the importance of noninvasive pain management procedures is easy to grasp, as this patient population is often unable to comprehend the benefits of initially painful procedures. Improvements in "time to analgesia" will likely lead to and have a direct, positive impact on patient care and satisfaction.

Efficacy and Safety of Intranasal Fentanyl
The efficacy and safety of intranasal fentanyl (INF) has been the focus of multiple studies, both in-hospital and pre-hospital. Finn et al conducted an in-hospital randomized double-blind placebo controlled trial and found INF to have the same efficacy as oral morphine during procedural wound care in adult burn patients (n=26, 35.5 ± 12.4 years). The concentration of INF used in this study was 50 µg/mL, initial dosages of 1.48 ± 0.57 µg/kg, and no difference in the number of adverse events. Finn et al concluded that while patients receiving INF were more satisfied with their level of pain relief (p = 0.009) that overall only half of the patients in the trial reported they were "satisfied" or "very satisfied".

In a randomized, controlled, open-label study of pre-hospital INF versus IV morphine, Rickard et al found no significant difference in efficacy or safety (n=258, 42.3 ± 13.7 years). This study differs from Finn et al in that there were a multitude of chief complaints treated due to an "all-comers" design. Moreover, the doses used of INF was significantly higher at 180 µg divided evenly between the nares with up to two repeat dosages of 60 µg. Patients in the INF group received pain medication earlier than in the IV morphine group, likely owing to the simpler route of administration. Adverse effects were noted to occur more frequently in the INF group (relative risk 2.09, 95% CI 0.92-4.78, p = 0.07), however, the Rickard et al was not powered to adequately detect any statistical difference. One incidence of a significant adverse effect required a termination of the INF protocol, but it was unclear from the study if this was related to the treatment or the patient's condition. Rickard et al concluded that given the safety and efficacy of INF, it is a valuable option in patients where intravenous access is "undesirable or impossible".

Borland et al 2005 and Borland et al 2007 were inpatient randomized double-blind crossover studies evaluating the efficacy and safety of INF versus oral or IV morphine, respectively, in pediatric patients. Borland et al 2005 studied INF in pediatric burn patients requiring daily dressing changes and found no significant difference in outcomes (n=24, median 4.5 IQR 1.8-9.0 years). The INF dosage was calculated against the bioavailability of the IN route (listed as 70%) with 1.4 µg/kg fentanyl equating to an IV dosage of 1 µg/kg. There were no incidents of significant adverse events, although this was likely due to the study size. However, sedation scores recorded found that INF patients recovered earlier than their oral morphine counterparts. Overall, Borland et al 2005 found INF to be safe and efficacious, but more importantly well tolerated by pediatric patients.

Borland et al 2007 found INF to be comparable to intravenous morphine in pediatric patients presenting to the emergency department with acute long-bone fractures (n=67, 10.9 ± 2.4 years). The median total dose was 1.7 µg/kg fentanyl with repeat doses given PRN. The impetus of the study was to find alternative methods of analgesia to intravenous narcotics in the pediatric population. The study authors note that given the comparable efficacy, INF is invaluable as a means to decrease "time to analgesia" in the pediatric population with potential for pre-hospital adoption.

Mudd conducted a systematic review of the available literature for INF in the pediatric population and graded 12 studies with evidence qualities of four Level I/A, one II/A, two II/B, one III/A, and four at III/B. There was a wide variation in dosing of INF amongst the studies, with a common range of 1-2 µg/kg fentanyl. Differences in concentrations existed as well, owing to the fact that in the US fentanyl is commonly available at 50 µg/mL and is used IV/IM/IO/IN yet overseas it is often given IN with a more concentrated 100-150 µg/mL solution. No differences in significance in pain reduction were found between concentrations, only in the volume of medication delivered. While no studies found a significant difference in adverse effects, many studies had small sample sizes and no long-term studies have been completed on the action of fentanyl on the nasal mucosa. However, the evidence in the reviewed studies demonstrated three clear points: (1) that INF is as efficacious as IV/IM/PO morphine or IV fentanyl, (2) it has no difference in adverse effects, and (3) it decreases the time to analgesia administration and pain relief.

Intranasal Fentanyl Protocol
Based on the research available and the 2012 NC EMS protocols, an appropriate pain management protocol for the administration of intranasal fentanyl is given below:
  • Adult patients with indications for narcotic analgesia for whom intravenous access is not feasible, not available, or at the discretion of the lead Paramedic, an initial dose of 1-2 µg/kg fentanyl may be delivered intranasally. The total volume to be administered should be divided equally between the two nares (not to exceed 1 mL per nare).
    • If intravenous access is not available, repeat with 0.5-1 µg/kg fentanyl delivered intranasally every 5 minutes to a maximum total dose of 3 µg/kg.
  • Pediatric patients with indications for narcotic analgesia an initial dose of 1-2 µg/kg fentanyl may be delivered intranasally. The total volume to be administered should be divided equally between the two nares (not to exceed 0.5 mL per nare).
    • In order to decrease the anxiety of pediatric patients requiring analgesia and invasive procedures (such as intravenous access), it may be prudent to begin with intranasal fentanyl.
    • If intravenous access is not available, repeat with 0.5-1 µg/kg fentanyl delivered intranasally every 5 minutes to a maximum total dose of 3 µg/kg.
References
  • M. Borland, I. Jacobs and I. Rogers, Options in prehospital analgesia, Emerg Med (Freemantle) 14 (2002), pp. 77–84.
  • M. Borland, I. Jacobs and G. Geelhoed, Intranasal fentanyl reduces acute pain in children in the emergency department: a safety and efficacy study, Emerg Med (Freemantle) 14 (2002), pp. 275–280.
  • J. Finn, J. Wright, J. Fong, E. Mackenzie, F. Wood, G. Leslie and A. Gelavis, A randomized crossover trial of patient controlled intranasal fentanyl and oral morphine for procedural wound care in adult patients with burns, Burns 30 (3) (2004), pp. 262–268.
  • M. Borland, R. Bergesio and E.M. Pascoe et al., Intranasal fentanyl is an equivalent analgesic to oral morphine in paediatric burns patients for dressing changes: a randomised double blind crossover study, Burns 31 (2005), pp. 831–837.
  • M. Borland, I. Jacob and B. King et al., A randomized controlled trial comparing intranasal fentanyl to intravenous morphine for managing acute pain in the emergency department, Ann Emerg Med 49 (2007), pp. 335–340.
  • C. Rickard, P. O’Meara, M. McGrail, et al., A randomized controlled trial of intranasal fentanyl vs intravenous morphine for analgesia in the prehospital setting, Amer J Emerg Med 25 (2007), pp. 911-917.
  • S. Thomas, S. Shewakramani, Prehospital Trauma Analgesia, J Emerg Med 35 (2007), pp. 47-57.
  • M. Greenwald, Analgesia for the Pediatric Trauma Patient: Primum Non Nocere? Clin Pedi Emerg Med 11 (2010), pp. 28-40.
  • S. Mudd, Intranasal Fentanyl for Pain Management in Pediatrics: A Review of the Literature, J Pedi Health Care (2010), Article in Press. doi:10.1016/j.pedhc.2010.04.011.

No comments: