Abstract: Three studies (313 participants) met the inclusion criteria. One study compared INF versus intramuscular morphine (IMM); another study compared INF versus intravenous morphine (IVM); and another study compared standard concentration INF (SINF) versus high concentration INF (HINF). All three studies reported a reduction in pain score following INF administration. INF produced a greater reduction in pain score at 10 minutes post administration when compared with IMM (INF group pain score: 1/5 vs IMM group pain score: 2/5; P value 0.014). No other statistically significant differences in pain scores were reported at any other time point. When INF was compared with IVM and HINF, no statistically significant differences in pain scores were noted between treatment arms, before analgesia or at 5, 10, 20 and 30 minutes post analgesia. Specifically, when INF was compared with IVM, both agents were seen to produce a statistically significant reduction in pain score up to 20 minutes post analgesia. No further reduction in pain score was noted after this time. When SINF was compared with HINF, a statistically and clinically significant reduction in pain scores over study time was observed (median decrease for both groups 40 mm, P value 0.000). No adverse events (e.g. opiate toxicity, death) were reported in any study following INF administration. One study described better patient tolerance to INF compared with IMM, which achieved statistical significance. The other studies described reports of a “bad taste” and vomiting with INF. Overall the risk of bias in all studies was considered low. INF may be an effective analgesic for the treatment of patients with acute moderate to severe pain, and its administration appears to cause minimal distress to children. However, this review of published studies does not allow any definitive conclusions regarding whether INF is superior, non-inferior or equivalent to intramuscular or intravenous morphine. Limitations of this review include the following: few eligible studies for inclusion (three); no study examined the use of INF in children younger than three years of age; no study included children with pain from a "medical" cause (e.g. abdominal pain seen in appendicitis); and all eligible studies were conducted in Australia. Consequently, the findings may not be generalizable to other healthcare settings, to children younger than three years of age and to those with pain from a "medical" cause.

Plain-language summary: We included studies with children (younger than 18 years of age) suffering from acute severe pain as a result of injury or medical illness. The target intervention was INF administered for pain relief compared with any other drug intervention for pain relief (e.g. intravenous morphine) or non-drug intervention (e.g. limb splinting, wound dressing) provided in the emergency setting. The evidence is current to January 2014. We identified three studies that included 313 children with acute severe pain resulting from broken bones of the upper and lower limbs. These trials compared INF versus morphine administered by a needle into a muscle (intramuscular morphine) or via a drip into a vein (intravenous morphine), as well as standard concentration INF versus high concentration INF. The collective study population in these trials consisted of children three to 15 years of age. Males accounted for approximately two-thirds of the overall study population. The review concluded that INF may be an effective analgesic for the treatment of children in acute moderate to severe pain, and its administration appears to cause minimal distress to children; however, the evidence is insufficient to permit judgement of the effects of INF compared with intramuscular or intravenous morphine. No serious adverse events (e.g. opiate toxicity, death) were reported. Limitations of this review include the following: Few studies (three) were eligible for inclusion; no study examined the use of INF in children younger than three years of age; no study included children with pain resulting from a "medical" cause (e.g. abdominal pain seen in appendicitis); and all eligible studies were conducted in Australia. Consequently, the findings may not be generalizable to other healthcare settings, to children younger than three years of age and to those with pain from a "medical" cause.