Intranasal fentanyl for the treatment of children in acute pain

Background

Pain is the most common reason why patients are seen in emergency departments (EDs). The challenging nature of treating children in acute severe pain is reflected in the medical literature by poor pain management in this population. We reviewed evidence on the effect of intranasal fentanyl (INF) (a strong pain relief drug, similar to morphine) compared with any other pain-relieving technique for treatment of children in acute severe pain.

Study characteristics

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.

Key results

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

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.

Authors' conclusions: 

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.

Read the full abstract...
Background: 

Pain is the most common symptom in the emergency setting; however, timely management of acute pain in children continues to be suboptimal. Intranasal drug delivery has emerged as an alternative method of achieving quicker drug delivery without adding to the distress of a child by inserting an intravenous cannula.

Objectives: 

We identified and evaluated all randomized controlled trials (RCTs) and quasi-randomized trials to assess the effects of intranasal fentanyl (INF) versus alternative analgesic interventions in children with acute pain, with respect to reduction in pain score, occurrence of adverse events, patient tolerability, use of "rescue analgesia," patient/parental satisfaction and patient mortality.

Search strategy: 

We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (2014, Issue 1); MEDLINE (Ovid SP, from 1995 to January 2014); EMBASE (Ovid SP, from 1995 to January 2014); the Cumulative Index to Nursing and Allied Health Literature (CINAHL) (EBSCO Host, from 1995 to January 2014); the Latin American and Caribbean Health Science Information Database (LILACS) (BIREME, from 1995 to January 2014); Commonwealth Agricultural Bureaux (CAB) Abstracts (from 1995 to January 2014); the Institute for Scientific Information (ISI) Web of Science (from 1995 to January 2014); BIOSIS Previews (from 1995 to January 2014); the China National Knowledge Infrastructure (CNKI) (from 1995 to January 2014); International Standard Randomized Controlled Trial Number (ISRCTN) (from 1995 to January 2014); ClinicalTrials.gov (from 1995 to January 2014); and the International Clinical Trials Registry Platform (ICTRP) (to January 2014).

Selection criteria: 

We included RCTs comparing INF versus any other pharmacological/non-pharmacological intervention for the treatment of children in acute pain (aged < 18 years).

Data collection and analysis: 

Two independent review authors assessed each title and abstract for relevance. Full copies of all studies that met the inclusion criteria were retrieved for further assessment. Mean difference (MD), odds ratio (OR) and 95% confidence interval (CI) were used to measure effect sizes. Two review authors independently assessed and rated the methodological quality of each trial using the tool of The Cochrane Collaboration to assess risk of bias, as per Chapter 8 of the Cochrane Handbook for Systematic Reviews of Interventions.

Main results: 

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.

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