Table 2.
Summary of findings
|
Comparison 1a: Intranasal analgesia (IN) vs intravenous administration (IV): Single dose IN fentanyl vs IV morphine in children aged 7–15 with acute fractures | ||||||
| Outcomes | Absolute effect (95% CI) | Relative effect | No of participants (studies) | Certainty of the evidence (GRADE) | What happens | |
| Risk with IV morphine | Risk with IN fentanyl | |||||
| Pain 10 min | Mean pain score: 41 mm |
Mean 5 mm higher (7 lower to 16 higher) |
65 (1 RCT) [29] |
Lowa | Children receiving intranasal fentanyl may achieve similar reductions in pain scores at 10 and 30 min as those receiving intravenous morphine | |
| Pain 30 min | Mean pain score: 33 mm |
Mean 4 mm higher (8 lower to 16 higher) |
65 (1 RCT) [29] |
Lowa | ||
| Rescue medication | 59 per 1000 children |
61 per 1000 children (9 to 405) |
RR 1.03 (0.15 – 6.89) |
67 (1 RCT)32 |
Lowa | |
| Mild adverse events | 29 per 1,000 children |
91 per 1,000 children (10 to 830) |
RR 3.091 (0.338 to 28.281) |
67 (1 RCT) [29] |
Lowa,b | |
|
Comparison 1b: Intranasal analgesia (IN) vs intravenous administration (IV): Multiple doses IN fentanyl vs IV fentanyl in children aged 4–8 with postoperative pain | ||||||
| Outcomes | Absolute effect (95% CI) | Relative effect | No of participants (studies) | Certainty of the evidence (GRADE) | What happens | |
| Risk with IV fentanyl | Risk with IN fentanyl | |||||
| Pain 10 min (Hannallah score) |
MD -0.47 (-1.51 – 0.37) |
32 (1 RCT)33 |
Lowa | Patients receiving intranasal fentanyl may achieve similar reductions in pain scores at 10 and 15 min as those receiving intravenous fentanyl | ||
|
Pain 15 min (Hannallah score) |
MD 0 (-0.35 – 0.35) |
32 (1 RCT)33 |
Lowa | |||
| Mild adverse events | 125 per 1000 children | 187.5 per 1000 children |
RR 1.50 (0.29 – 7.81) |
32 (1 RCT)33 |
Lowa | |
|
Comparison 1c: Intranasal analgesia (IN) vs intravenous administration (IV): Single dose IN ketorolac vs IV ketorolac in children aged migraine headache with migraine | ||||||
| Outcomes | Absolute effect (95% CI) | Relative effect | No of participants (studies) | Certainty of the evidence (GRADE) | What happens | |
| Risk with IV ketorolac | Risk with IN ketorolac | |||||
| Pain 10 min |
MD 0.9 (-0.4 – 2.2) |
56 (1 RCT)31 |
Lowa | Patients receiving intranasal ketorolac may achieve similar reductions in pain scores at 10 and 30 min as those receiving intravenous ketorolac | ||
| Pain 30 min |
MD 0.8 (-0.4 – 1.9) |
56 (1 RCT)31 |
Lowa | |||
| Rescue medication | 170 of 1,000 children | 220 per 1,000 children |
RR 1.29 (0.44 – 3.73) |
56 (1 RCT)31 |
Lowa | |
| Mild adverse events | 207 per 1,000 children | 148 per 1,000 children |
RR 0.716 (0.23 – 2.26) |
56 (1 RCT)31 |
Lowa | |
| Acceptability (child) | 955 per 1,000 children | 792 per 1,000 children |
RR 0.83 (0.66 – 1.04) |
46 (1 RCT)31 |
Lowa | |
|
a – single study, no published protocol b – underpowered to find differences in uncommon, but serious adverse events | ||||||
|
Comparison 2: Intranasal analgesia (IN) vs intramuscular administration (IM) IN fentanyl or IN diamorphine vs IN morphine in children aged 3–17 with acute moderate to severe pain | ||||||
| Outcomes | Absolute effect (95% CI) | Relative effect | No of participants (studies) | Certainty | What happens | |
| Risk with IM morphine | Risk with IN fentanyl/diamorphine | |||||
| Pain 10 min |
Kendall 2001 found lower mean pain scores in the IN diamorphine group than in the IM morphine group (MD 0.35, 95%CI -0.01, 0.71); Wilson 1997 found no difference in median pain scores between the IN diamorphine group and the IM morphine group (MD 0, 95%CI -0.24, 0.24) Younge 1999 found a 1-point lower median pain score in the IN fentanyl group than in the IM morphine group |
490 (3 RCTs) [32–34] | Moderatea | Patients receiving intranasal fentanyl or diamorphine probably experience similar or more pain reduction at 10 and 30 min than those receiving intramuscular morphine. Any difference is unlikely to be clinically relevant | ||
| Pain 30 min |
Kendall 2001 found lower mean pain scores in the IN diamorphine group than in the IM morphine group (MD 0.43, 95%CI 0.08, 0.78) Wilson 1997 found no difference in median pain scores between the IN diamorphine group and the IM morphine group (MD 0, 95% CI -0.55, 0.55) Younge 1999 found no difference in median pain score between the IN fentanyl group and the IM morphine group |
483 |
Moderatea | |||
| Rescue medication | 45 per 1,000 children |
50 per 1,000 children (23 – 108 children per 1,000) |
RR 1.11 (0.51 – 2.40) |
503 (3 RCTs) 28–30 |
Lowa,b | Patients receiving intranasal fentanyl or diamorphine may experience similar risk of requiring rescue analgesia, as those receiving intramuscular morphine |
| Adverse events | Kendall 2001 reported total adverse events 49/203 (24%) in the IN diamorphine group, and 37/200 (18.5%) in the IM morphine group. All events were mild, except one case of vomiting in the IN diamorphine group; and over halt the events were local irritation at the site of administration. Neither Kendall 2001, Wilson 1997 or Younge 1999 found a difference in pulse, respiratory rate or GCS, or clinically significant in O2-saturations, but a high dropout rate in the IM morphine group |
502 (3 RCTs) |
Lowa, b | Patients receiving intranasal fentanyl or diamorphine may experience similar risk of adverse events, as those receiving intramuscular morphine | ||
| Acceptability (child): uncooperative / negative reaction | 505 per 1,000 children |
31 per 1,000 children (15 to 65 per 1,000 children) |
RR 0.0611 (0.0291 to 0.1282) |
449 |
Highd | Children are less likely to be uncooperative or have a negative reaction to intranasal analgesia than intramuscular morphine |
| Acceptability (child) | 588 per 1,000 children |
941 per 1,000 children (835 to 1,000 children) |
RR 1.60 (1.42 to 1.81) |
402 (1 RCT) [32] |
Moderatec | Children probably find intranasal diamorphine more acceptable than intramuscular morphine |
| Acceptability (parents) | 721 per 1,000 chilrden | 966 per 1,000 children (887 to 1,000 children) |
RR 1.34 (1.23 to 1.47) |
389 (1 RCT) [32] |
Moderatec | Parents probably find intranasal diamorphine more acceptable than intramuscular morphine |
| Acceptability (providers) | 322 per 1,000 children |
981 per 1,000 children (801 to 1,000 children) |
RR 3.05 (2.49 to 3.73) |
402 (1 RCT) [32] |
Highd | Providers find intranasal diamorphine more acceptable than intramuscular morphine |
|
a – Wilson 1997 had high risk of bias, and some concerns in Kendall 2001 and Younge 1999 b – Imprecision: underpowered to find differences in uncommon events including rescue medication and adverse events c – Imprecision—single study d – Single study/only two studies, but upgraded because of large effect size | ||||||
|
Comparison 3a: Comparison of different intranasal (IN) agents IN ketamine vs IN fentanyl in children aged 3–17 with acute moderate to severe pain | ||||||
| Outcomes | Absolute effect (95% CI) | Relative effect | No of participants (studies) | Certainty | What happens | |
| Risk with IN fentanyl | Risk with IN ketamine | |||||
| Pain 10–15 min |
SMD 0.05 (-0.19 to 0.28) |
263 |
High | Patients receiving intranasal ketamine achieve similar pain reduction at 10–15 min, as those receiving intranasal fentanyl | ||
| Pain 30 min |
SMD 0.05 (-0.20 to 0.29) |
254 |
High | Patients receiving intranasal ketamine achieve similar pain reduction at 30 min as those receiving intranasal fentanyl | ||
| Rescue medication | 396 of 1,000 children |
336 per 1,000 children (245 – 461 of 1,000 children) |
RR 0.85 (0.62 – 1.17) |
268 (4 RCTs) 36–39 |
Moderatea | Patients receiving intranasal ketamine probably experience a similar risk of requiring rescue analgesia as those receiving intranasal fentanyl |
| Mild adverse events | 389 per 1,000 children |
841 per 1,000 children (670 to 1,000 children) |
RR 2.16 (1.72 to 2.71) |
263 (4 RCTs) |
High | Patients receiving intranasal ketamine probably experience a higher risk of adverse events than those receiving intranasal fentanyl |
| Adverse events – Sedation | 315 per 1,000 children |
550 per 1,000 children (408 to 740 per 1000 children) |
RR 1.74* (1.30 to 2.35) |
261 (4 RCTs) |
High | Patients receiving intranasal ketamine experience a higher risk of sedation than those receiving intranasal fentanyl |
| Acceptability (child) | 722 per 1,000 children | 829 per 1,000 children (644 to 1,000 children) | RR 1.15 (0.89 to 1.48) |
71 (1 RCT) [36] |
Lowb | Children may find intranasal ketamine equally acceptable to intranasal fentanyl |
|
Comparison 3b: Comparison of different intranasal (IN) agents IN fentanyl vs IN placebo in children aged 3–20 with vaso-occlusive crisis of sickle cell disease | ||||||
| Outcomes | Absolute effect (95% CI) | Relative effect | No of participants (studies) | Certainty | What happens | |
| Risk with IN placebo | Risk with IN fentanyl | |||||
| Pain 10 min |
Mean pain reduction 1.0 (SD 2.0) |
Mean pain reduction 2.2 (SD 2.6) |
49 (1 RCT)34 |
Lowb | Children receiving IN fentanyl may experience a 2 point greater reduction in pain than those receiving placebo at 10 min. This difference represents an appreciable change | |
| Pain 30 min |
Mean pain reduction 1.8 (SD 2.5) |
Mean pain reduction 2.3 (SD 2.8) |
49 (1 RCT)34 |
Lowb | Children receiving IN fentanyl may experience no difference in reduction of pain compared to those receiving placebo at 30 min | |
| Adverse events (in VOC) | There were no differences in serious adverse events. Two subjects in either group had hypotension that resolved spontaneously, and three in the intranasal fentanyl group had transient hypoxia |
49 (1 RCT)34 |
Lowb | There may be little or nor difference in adverse events between intranasal fentanyl and placebo in vaso-occlusive crises | ||
|
Comparison 3c: Comparison of different intranasal (IN) agents Standard concentration IN fentanyl vs high concentration IN fentanyl in children aged 7–15 with fractures | ||||||
| Outcomes | Absolute effect (95% CI) | Relative effect | No of participants (studies) | Certainty | What happens | |
| Risk with high concentration IN fentanyl | Risk with standard concentration IN fentanyl | |||||
| Pain 10 min |
Median pain reduction 20 mm |
Median pain reduction 20 mm |
Median difference 0 (-5.2 – 5.2 mm) |
189 (1 RCT)35 |
Lowb | Patients receiving standard concentration (50mcg/ml) intranasal fentanyl may achieve similar pain relief at 10 min, as those receiving high concentration (300mcg/ml) intranasal fentanyl |
| Rescue medication | 275 per 1,000 children |
429 of 1,000 children (286 – 642 per 1,000 children) |
RR 1.56 (1.04 – 2.34) |
189 (1 RCT)35 |
Lowa | Patients receiving standard concentration (50mcg/ml) intranasal fentanyl may experience a higher risk of requiring rescue analgesia than those receiving high concentration (300mcg/ml) intranasal fentanyl |
| Adverse events | 320 per 1,000 children | 225 per 1,000 children | RR 0.76 (0.47 – 1.23) |
189 (1 RCT)35 |
Lowa | Patients receiving standard concentration (50mcg/ml) intranasal fentanyl may experience similar risk of adverse events, as those receiving high concentration (300mcg/ml) intranasal fentanyl |
|
a – Imprecision: underpowered to find differences in uncommon events, including rescue medication and serious adverse events b – Imprecision: single study | ||||||