Table 1.
Characteristics of included studies
| Study | Population | Intervention | Comparison | Outcomes |
|---|---|---|---|---|
| Studies comparing intranasal analgesia (IN) to intravenous (IV) administration | ||||
| Borland 2007 [29] | 67 children, 7–15 years, 20-50 kg, with clinically deformed closed long-bone fractures | IN fentanyl 1.2mcg/kg, 150mcg/ml + IV NaCl (n = 33). First dose at 0 min, additional doses every 5 min until relief, refusal or maximal dose (2–4 doses, weight dependent). Blinded | IV morphine 0.1 mg/kg, 10 mg/ml + IN NaCl (n = 34). First dose at 0 min, additional doses every 5 min until relief, refusal or maximal dose (2–4 doses, weight dependent). Blinded |
100 mm VAS at 0, 5, 10, 20, 30 min Adverse events for 30 min. Rescue medication. Verbal pain rating |
| Manjushree 2002 [30] | 32 children, 4–8 years, after elective surgical procedures of 1 to 1.5 h, ASA I-II, Hannallah score > / = 4 | IN fentanyl 0.5mcg/kg + IV NaCl (n = 16). Initial dose at 0 min, then every 5 min up to 30 min, pain relief or adverse events. Blinded | IV fentanyl 0.5mcg/kg + IN NaCl (n = 16). Initial dose at 0 min, then every 5 min up to 30 min, pain relief or adverse events. Blinded | Hannallah scale 10pt pain scores at 0, 5, 10, 15 min. Adverse events for 30 min. Dose requirements. Time to analgesia. Vitals |
| Tsze 2022 [31] | 59 children, 8–17 years, with migraine headache, with moderate to severe pain | IN ketorolac 1 mg/kg, 30 mg/ml, + IV NaCl 0.9%, single dose (n = 29). Blinded | IV ketorolac, 30 mg/ml + IN NaCl 0,9%, single dose (n = 30). Blinded | Faces Pain Scale – Revised (FPS-R) at 0, 10, 30, 60, 120 min. Adverse events. Rescue medication. Tolerability |
| Studies comparing intranasal analgesia (IN) to intramuscular (IM) administration | ||||
| Kendall 2001 [32] | 404 children, 3–16 years, with clinical fracture of a limb | IN diamorphine 0.1 mg/kg single dose (n = 207). Unblinded | IM morphine 0.2 mg/kg single dose (n = 209). Unblinded | Wong-Baker pain rating scale (WBFPS)/Visual analogue Scale (VAS) at 0, 5, 10, 20, 30 min, by parents, providers, and patients. Adverse events for 30 min. Acceptability for parents and providers. Patient prepared to have treatment again. Reaction to administration. Vitals |
| Wilson 1997 [34] | 58 children, 4–17 years, with clinically diagnosed limb fracture | IN diamorphine 0.1 mg/kg (n = 30), single dose. Unblinded | IM morphine 0.2 mg/kg (n = 28), single dose. Unblinded | WBFPS/6pt VAS at 0, 5, 10, 20, 30 min. Parental acceptability. Adverse events for 30 min. Rescue analgesia |
| Younge 1999 [33] | 47 children, 3–10 years, with clinical limb fracture | IN fentanyl 1.0mcg/kg (n = 24), 50mcg/ml, single dose. Unblinded | IM morphine 0.2 mg/kg (n = 23), 10 mg/ml, single dose. Unblinded | WBFPS 5pt pain score by patient and parents at 0, 5, 10, 20, 30 min. Tolerance 4pt score by parents at 0 min. Adverse events. Rescue analgesia. Vitals |
| Studies comparing intranasal analgesia (IN) agents | ||||
| Borland 2011 [35] | 199 children, 7-15 years, with clinically deformed closed long-bone fractures | IN fentanyl 50mcg/ml, 1.5mcg/kg (n = 102). First dose at 0 min, additional doses as required. Blinded | IN fentanyl 300mcg/ml, 1.5mcg/kg (n = 97). First dose at 0 min, additional doses as required. Blinded | 100 mm VAS or FPS-R at 0, 10, 20, 30 min. Adverse events for 30 min. Rescue analgesia. Vitals |
| Frey 2019 [37] | 90 children, 8–17 years, with acute extremity injury, with moderate to severe pain at presentation | IN ketamine 1.5 mg/kg, 50 mg/ml, single dose, max. 100 mg (n = 45). 4/44 (9%) had received ibuprofen and 1 (2%) paracetamol before coming to the ED. Blinded | IN fentanyl 2mcg/kg, 50mcg/ml, single dose, max. 100mcg (n = 45). 4/42 (10%) had received ibuprofen and 2 (5%) paracetamol before coming to the ED. Blinded | 100 mm VAS at 0, 15, 30, 60 min. Adverse events for 2 h, and at 30d. Rescue medication. Sedation, 5pt UMSS. Vital signs. Capnometry |
| Graudins 2015 [36] | 80 children, 3–13 years, < 50 kg, with isolated limb injury and moderate to severe pain at presentation | IN ketamine 1 mg/kg, 100 mg/ml, single dose (n = 36). 33/36 (92%) also received ibuprofen. Blinded | IN fentanyl 1.5mcg/kg, 50mcg/ml, single dose (n = 37). 33/37 (89%) also received ibuprofen. Blinded | FPS-R/100mmVAS at 0, 15, 30, 60 min. Adverse events. Rescue medication. Satisfaction. Sedation, 5pt UMSS |
| Quinn 2021 [40] | 22 children, 3–17 years, < 64 kg, with acute moderate to severe pain at presentation (extremity or abdominal) | IN ketamine 1 mg/kg, 100 mg/ml, single dose (n = 11). 2/11 (18%) had received ibuprofen and 2 (18%) paracetamol before the study drug. Blinded | IN fentanyl 1.5mcg/kg, 50mcg/ml, single dose (n = 11). Blinded. 2/11 (18%) had received ibuprofen and 2 (18%) paracetamol before the study drug. Blinded | NRS/WBFPS at 0, 10, 20, 30, 60 min. Adverse events. Sedation, 5pt University of Michigan Sedation Scale (UMSS). Rescue medication. Vitals |
| Reynolds 2017 [39] | 91 children, 4–17 years, < 70 kg, with a suspected single-extremity fracture and moderate to severe pain at presentation | IN ketamine 1 mg/kg, 50 mg/ml, at 0 min (n = 46); 2nd dose 0.5 mg/kg after 20 min as needed. Acetaminophen 15 mg/kg. 33/43 (79%) also received ibuprofen, 7 (16%) paracetamol, and 1 (2%) both. Blinded | IN fentanyl 1.5mcg/kg, 50mcg/ml, at 0 min (n = 45); 2nd dose 0.75mcg/kg after 20 min as needed. 35/44 (80%) also received ibuprofen, 5 (11%) paracetamol, and 3 (7%) both. Blinded | FPS-R/100 mm VAS at 0, 10, 20, 30, 60 min. Adverse events for 60 min. Required 2nd dose. Additional rescue analgesia |
| Fein 2017[38] | 49 children, 3–20 years, with Sickle Cell Disease with crisis | IN fentanyl 2mcg/kg, 50mcg/ml, single dose (n = 24). Max. 100mcg. Blinded. 1 (4%) had received paracetamol, 1 (4%) oxycodone, and 1 (4%) paracetamol + codeine within 2 h prior to study drug | IN NaCl 0.9%, single dose (n = 25). Blinded. 1 (4%) had received paracetamol + codeine, and 1 (4%) tramadol prior to study drug | WBFPS at 0, 10, 20, 30 min. Adverse events for 20 min. Hospitalisation, bouncebacks |