Comparison of morphine concentration–time profiles following intravenous and intranasal diamorphine in children

Background: Current best practice for treating acute severe pain in children is to administer intravenous or intranasal opioid. Intranasal diamorphine offers less traumatic analgesia than the potentially difficult and distressing intravenous route. However, there has been no direct comparison of intranasal and intravenous diamorphine nor are there pharmacokinetic data for intranasal diamorphine in children. Objective: To compare plasma morphine concentration–time profiles following intranasal and intravenous diamorphine administration. Design: Observational. Setting: A&E department in a city-centre paediatric teaching hospital. Patients: Children, aged 3–13 years, with isolated limb fracture. Interventions: An intravenous catheter was sited and baseline blood taken. The first 12 children received intravenous diamorphine (0.1 mg/kg), and the subsequent 12 intranasal diamorphine (0.1 mg/kg) in 0.2 ml sterile water drops. Subsequent samples were taken at 2, 5, 10, 20, 30 and 60 min. Measurements: Plasma morphine radioimmunoassay. Results: Peak plasma morphine concentrations were higher (median 109 vs 36 nmol/l), and occurred earlier (median 2 vs 10 min), with greater area under the curve (3761 vs 1794 nmol/l/h) following intravenous compared to intranasal diamorphine (all p<0.001, Mann–Whitney U test). Higher plasma concentrations at 60 min (47 vs 32 nmol/l) were also observed following intravenous diamorphine (p = 0.01, Mann–Whitney U test). Conclusions: Our evidence supports the wider use of diamorphine administration by nasal drops in children, as it shows that adequate plasma levels of morphine are usually achieved. However, we demonstrated significantly attenuated and delayed peak plasma morphine levels with lower levels at 1 h with intranasal compared with intravenous diamorphine.