Intranasal Fentanyl to Reduce Pain and Improve Oral Intake in the Management of Children With Painful Infectious Mouth Lesions

Abstract

Objectives: Painful infectious mouth conditions such as herpangina, hand-foot-and-mouth disease, and herpetic gingivostomatitis can cause pain, dehydration, and hospitalization in young children. Treatment for these conditions is generally supportive and directed toward pain relief from ulcerative lesions, thus facilitating oral intake, and preventing dehydration. Attempts at oral therapy at home and in the emergency department are often refused and immediately spit back out. This study evaluated the efficacy of intranasal fentanyl (INF) compared with a commonly used oral (PO) acetaminophen/hydrocodone formulation for the treatment of children with painful infectious mouth conditions.Methods: This study was a prospective, nonblinded, randomized controlled noninferiority trial conducted in an academic tertiary care pediatric emergency department. The study enrolled children between the ages of 6 months and 18 years with painful infectious mouth lesions and poor oral intake. Patients were randomized to receive either INF (1.5 μg/kg, intervention) or PO acetaminophen/hydrocodone (0.15 mg/kg, control) based on the dose of hydrocodone. The primary outcome was volume of fluid intake per body weight (in milliliters per kilogram) 60 minutes after analgesic administration. Secondary outcomes included pain scores using a validated visual assessment scale (VAS; 1, no pain; 10, worst pain), hydration score (VAS; 1, well hydrated; 4, very dehydrated), admission rate and overall satisfaction score (VAS; 1, worst; 7, best). A priori power analysis indicated that 34 patients would achieve an 81% power with an α value of 0.05. Results:Of the 34 patients enrolled, 17 were randomized to INF and 17 to PO. The demographics between both groups were similar in age, weight, sex, and race. There were no significant differences in parental perception of pain ( P = 0.69) or hydration status ( P = 0.78). Oral fluid intake at 60 minutes was 20 mL/kg for INF versus 18 mL/kg for PO ( P = 0.53). Pain scores at 15 and 30 minutes were 1.7 versus 2.9 ( P = 0.09) and 0.6 versus 1.6 ( P = 0.59). Parental perceptions of pain and hydration status at 60 minutes were 2.2 versus 2.4 ( P = 0.77) and 1.7 versus 1.5 ( P = 0.37). Overall parental satisfaction was 6.4 for INF versus 6.5 for PO ( P = 0.71), and admission rate was 0 vs 12% ( P = 0.49). There were no adverse events such as respiratory, cardiac, or central nervous system depression in either group.Conclusions: Intranasal fentanyl seems to be a safe and effective alternative to acetaminophen with hydrocodone in reducing pain and improving hydration status in children with painful infectious mouth lesions and poor oral intake.

Intranasal Fentanyl for Acute Pain Management in Children, Adults and Elderly Patients in the Prehospital Emergency Service and in the Emergency Department: A Systematic Review

“…Out of 23 studies included, 18 studies were conducted in children: 1 PS in the PHES (Murphy et al, 2017 [ 38 ]), 9 observational studies (Akinsola et al, 2018 [ 39 ], Anderson et al, 2022 [ 40 ], Cole et al, 2009 [ 41 ], Crelin et al, 2010 [ 42 ], Finn et al, 2010 [ 43 ], Kelly et al, 2018 [ 44 ], Nemeth et al, 2019 [ 45 ], Saunders et al, 2010 [ 46 ], Schaefer et al, 2015 [ 47 ]) and 8 RCTs (Borland et al, 2011 [ 48 ], Fein et al, 2017 [ 49 ], Frey et al, 2019 [ 50 ], Graudins et al, 2015 [ 51 ], Quinn et al, 2021 [ 52 ], Reynolds et al, 2017 [ 53 ], Ruffin et al, 2022 [ 54 ], Younge et al, 1999 [ 30 ]) in the ED; 5 studies were conducted in the adult population: 1 observational study in the PHES setting (Tanguay et al, 2020 [ 55 ]), 2 observational studies (Assad et al, 2023 [ 56 ], Belkouch et al, 2015 [ 57 ]) and 2 RCTs (Nasr Isfahani et al, 2022 [ 58 ], Nazemian et al, 2020 [ 59 ]) in the ED setting; one subgroup analysis of an observational study reported data on the elderly patients in the PHES (Tanguay et al, 2020 [ 55 ]). A total of 10,280 patients were included: 1203 in the PHES setting (94 children, 729 adults and 380 elderly) and 9077 in the ED setting (8714 children and 363 adults).…”

“…Four studies reported INF to be effective in reducing pain at different time points (Cole et al, 2009 at 10 and 30 min [ 41 ]; Crellin et al, 2010 [ 42 ]; Finn et al, [ 43 ] at 5 and 30 min; Saunders et al, 10, 20 and 30 min [ 46 ]). Two studies [ 44 , 45 ] and six RCTs reported INF to be equally effective as comparators [ 48 , 50 , 51 , 52 , 53 , 54 ]. Two RCTs demonstrated INF to be more effective in reducing pain: Fein et al, 2017, compared INF to the “standard of care” (more effective at 20 min after administration, no differences at 10 and 30 min) [ 49 ] and Younge et al, 1999, compared IM 0.2 mg/kg morphine (more effective at 10 min, no difference at 20 and 30 min) [ 30 ].…”

“…One PS also reported a reduced ED length of stay and admission rate in the INF group [ 39 ]. One RCT reported no change in overall satisfaction or pain score at 60 min [ 54 ] and one RCT reported higher tolerance to INF compared with IM morphine [ 30 ].…”

“…According to the Cochrane R.o.B. 2.0 tool, in children, six of the eight RCTs conducted in the ED setting were rated as low risk of bias [ 48 , 49 , 50 , 51 , 52 , 53 ], while two RCTs were rated as high risk of bias [ 30 , 54 ].…”

“…A total of 23 studies have shown INF to be safe and effective in children in both the PHES setting [ 38 ] and the ED setting [ 39 , 42 , 45 , 46 ], including children aged 1–3 years [ 40 ] and at higher doses administered [ 39 ], with no difference in efficacy between the standard 50 µg/mL concentration and the higher concentration [ 48 ]. Furthermore, INF is as effective as orally administered paracetamol and hydrocodone [ 54 ], as effective with a lower rate of adverse events and discomfort than IN ketamine [ 50 , 51 , 52 , 53 ] and IM morphine [ 30 ] and more effective than standard treatment plus IN placebo at 20 min after drug administration [ 48 ], improving the time to opioid administration [ 39 , 44 , 47 ]. In adults, one study in the PHES setting showed INF to be effective, feasible and safe, particularly in older people.…”