An Intranasal Diamorphine Spray for Acute Pain in Children
An Intranasal Diamorphine Spray for Acute Pain in Children
The DIASAFE study was designed with sufficient sample size to ensure (with 95% probability) that at least one child would experience any particular AE, if the underlying event rate was at least 2%. As with other opiates, the main adverse effects of diamorphine include respiratory depression, sedation, nausea and vomiting, constipation and sweating. In this study, there was no evidence of clinically significant respiratory depression, and only minor reductions in the level of consciousness in children. The incidence of vomiting was as expected and considered to be acceptable.
A potential concern of IND is local (nasal) tolerability. No incidence of swelling or tenderness was seen, although a small number of children reported mild itching (with one moderate itching) or mild sneezing. Nasal irritation does not appear to be directly related to the volume administered per se, but just due to exposure to the product in those sensitive to the drug, excipients or nasal administration in general. The severity of irritation has been mild only, except for one moderately severe report, and one report which was not graded, but no sequelae were reported.
The incidence of AEs in the DIASAFE study (26.5%) is similar to the Kendall study (24.5%) which compared safety and efficacy of IND with intramuscular morphine sulfate; specific attribution of events was not recorded in this earlier study. The incidence of AEs related to nasal irritation, however, was higher in the DIASAFE study compared to the Kendall study (20.4% patients vs 13.2%). This was expected, because nasal irritation was systematically evaluated in the DIASAFE study in line with study objectives. In the Kendall study, nasal irritation was assessed by staff at the time of treatment administration, and thereafter evaluated ad hoc by asking patients if they had irritation rather than specifically assessing the site of administration.
The DIASAFE study was carried out in Teaching and District General Hospital EDs, some of which had dedicated paediatric EDs, with varying local population catchment areas and characteristics. Thus, children in this trial are representative of those presenting to EDs throughout the UK. Our studies were unable to evaluate rare AEs due to the limited sample size.
Discussion
The DIASAFE study was designed with sufficient sample size to ensure (with 95% probability) that at least one child would experience any particular AE, if the underlying event rate was at least 2%. As with other opiates, the main adverse effects of diamorphine include respiratory depression, sedation, nausea and vomiting, constipation and sweating. In this study, there was no evidence of clinically significant respiratory depression, and only minor reductions in the level of consciousness in children. The incidence of vomiting was as expected and considered to be acceptable.
A potential concern of IND is local (nasal) tolerability. No incidence of swelling or tenderness was seen, although a small number of children reported mild itching (with one moderate itching) or mild sneezing. Nasal irritation does not appear to be directly related to the volume administered per se, but just due to exposure to the product in those sensitive to the drug, excipients or nasal administration in general. The severity of irritation has been mild only, except for one moderately severe report, and one report which was not graded, but no sequelae were reported.
The incidence of AEs in the DIASAFE study (26.5%) is similar to the Kendall study (24.5%) which compared safety and efficacy of IND with intramuscular morphine sulfate; specific attribution of events was not recorded in this earlier study. The incidence of AEs related to nasal irritation, however, was higher in the DIASAFE study compared to the Kendall study (20.4% patients vs 13.2%). This was expected, because nasal irritation was systematically evaluated in the DIASAFE study in line with study objectives. In the Kendall study, nasal irritation was assessed by staff at the time of treatment administration, and thereafter evaluated ad hoc by asking patients if they had irritation rather than specifically assessing the site of administration.
The DIASAFE study was carried out in Teaching and District General Hospital EDs, some of which had dedicated paediatric EDs, with varying local population catchment areas and characteristics. Thus, children in this trial are representative of those presenting to EDs throughout the UK. Our studies were unable to evaluate rare AEs due to the limited sample size.
