1 Södertälje, Sweden 2 Belfast, UK
EditorWhile we share the interest of Long and colleagues1 in topical anaesthesia for procedural pain in neonates and applaud their initiative to evaluate a potential new agent, some of their statements are incorrect or outdated. When commenting on one case of methaemoglobinaemia reported in 1995 after injection of prilocaine for circumcision in a neonate,2 Long and colleagues write this means that EMLA cream is contraindicated in infants of less than 3 months of age. The authors of the case report also concluded that in particular, prilocaine injections should be avoided in the newborn,2 a statement with which we agree. However, EMLA cream and EMLA patches have been well studied for the treatment of acute pain in neonates.39 Although the use of large doses of prilocaine-containing formulations may cause an increase in the methaemoglobin (MetHb) concentration in infants and neonates, safe doses of EMLA in these age groups have been established. The application of a 1 g dose of EMLA cream to the prepuce for 1 h before circumcision in full-term neonates during their first week of life resulted in similar MetHb concentrations (mean 1.3%, monitored for 18 h) to placebo.4 In a similar study, using the same dosage of EMLA cream for circumcision, the upper 99% confidence interval for the post-treatment MetHb concentrations remained within the normal range.3 In their systematic review of 12 studies, Taddio and colleagues5 concluded that single doses of EMLA ranging from 0.5 to 2 g do not cause methaemoglobinaemia in neonates. Subsequently, Brisman and colleagues7 reported that a 1 g dose of EMLA applied to two skin sites (0.5 g each) for 1 h resulted in a mean MetHb concentration of 1.17% (range 0.502.53), which was slightly higher than placebo-treated neonates, 0.96% (range 0.501.53). In all patients, the MetHb values, which were monitored for 18 h, were well below potentially harmful concentrations. Normal physiological MetHb levels are <2%. In neonates, elevated MetHb concentrations up to 56% are considered to be of no clinical significance.3 5 10
Based on a wealth of available clinical data on the use of EMLA in neonates, infants and children, maximum dosage recommendations can be made (Table 1). These dosages are approved by regulatory agencies in a number of countries including most of the European Union member states and the USA (although not yet the UK).
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For many medicines, data in children particularly in neonates are sparse, but in the case of EMLA clinical studies have enabled the identification of adequate doses for a number of painful procedures in these age groups.
S. Lillieborg
I. Otterbom
K. Ahlen
Södertälje, Sweden
EditorI would like to thank the research team at AstraZeneca R&D for their interest in this study and to respond to the points they have raised about our article.1
The statement this means that EMLA cream is contraindicated in infants of less than 3 months of age made by my colleagues and me is indeed now outdated, as the new British National Formulary states Infant 112 months [unlicensed use] single application on intact skin under specialist supervision, under 1 month not recommended (risk of methaemoglobinaemia).12 Although the novel tetracaine anaesthetic patch has been specifically designed for application to neonatal infants including preterm babies, the risk of percutaneous systemic absorption must be considered as significantly increased.13 14 In their correspondence, Lillieborg and colleagues have presented a number of studies pertaining to the safe use of EMLA in infants <3 months old, but they also state the use of EMLA in premature infants with a gestational age less than 37 weeks need further study. One of the main issues that the introduction of our article1 stressed was that the use of tetracaine as an active ingredient would negate any possible risk of increased MetHb after application to neonatal skin.
C. Long
Belfast, UK
References
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