ABSTRACT
BACKGROUND: Intranasal diamorphine is a potential treatment for breakthrough pain but few paediatric data are available to assist dose estimation. AIM: To determine an intranasal diamorphine dose in children through an understanding of pharmacokinetics. DESIGN: A systematic review of the literature was undertaken to seek diamorphine pharmacokinetic parameters in neonates, children and adults. Parenteral and enteral diamorphine bioavailability were reviewed with respect to formation of the major metabolite, morphine. Clinical data quantifying equianalgesic effects of diamorphine and morphine were reviewed. REVIEW SOURCES: PubMed (1960-2020); EMBASE (1980-2020); IPA (1973-2020) and original human research studies that reported diacetylmorphine and metabolite after any dose or route of administration. RESULTS: The systematic review identified 19 studies: 16 in adults and 1 in children and 2 neonatal reports. Details of study participants were extracted. Age ranged from premature neonates to 67 years and weight 1.4-88 kg. Intranasal diamorphine bioavailability was predicted as 50%. The equianalgesic intravenous conversion ratio of morphine:diamorphine was 2:1. There was heterogeneity between pharmacokinetic parameter estimates attributed to routes of administration, lack of size standardisation, methodology and pharmacokinetic analysis. Estimates of the pharmacokinetic parameters clearance and volume of distribution were reduced in neonates. There were insufficient paediatric data to characterise clearance or volume maturation of either diamorphine or its metabolites. CONCLUSIONS: We estimate equianalgesic ratios of intravenous morphine:diamorphine 2:1, intravenous morphine:intranasal diamorphine 1:1 and oral morphine:intranasal diamorphine of 1:3. These ratios are based on adult literature, but are reasonable for deciding on an initial dose of 0.1 mg/kg in children 4-13 years.
ABSTRACT
The management of pain in pediatric palliative care (PPC) is essential. Whilst the field of pain management has developed over the years, much of what is done in PPC is based on anecdotal evidence or adult studies. This review explores recent developments in pain management in PPC, in particular the WHO guidelines on the pharmacological treatment of persisting pain in children with medical illnesses. Key issues discussed include the definition, assessment, pharmacological and integrative management of pain, availability of medications, education and research. Whilst advances have been made, including publication of the guidelines, significant gaps exist in terms of the evidence base, education and access to essential medications and both interdisciplinary and international collaboration are required to meet these gaps.
