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Rescue morphine in mechanically ventilated newborns associated with combined OPRM1 and COMT genotype

    Maja Matic

    Department of Clinical Chemistry, Erasmus MC – University Medical Center Rotterdam, The Netherlands

    Department of Pediatric Surgery, Erasmus MC – University Medical Center Rotterdam, Sophia Children’s Hospital, Rotterdam, The Netherlands

    ,
    Sinno HP Simons

    Department of Pediatrics, Division of Neonatology, Erasmus MC – University Medical Center Rotterdam, Sophia Children’s Hospital, Rotterdam, The Netherlands

    ,
    Richard A van Lingen

    Princess Amalia Department of Pediatrics, Division of Neonatology, Isala Clinics, Zwolle, The Netherlands

    ,
    Joost van Rosmalen

    Department of Biostatistics, Erasmus MC – University Medical Center Rotterdam, The Netherlands

    ,
    Laure Elens

    Louvain Centre for Toxicology & Applied Pharmacology (LTAP) Institut de Recherche Expérimentale et Clinique (IREC)4, Université Catholique de Louvain (UCL), Brussels, Belgium

    ,
    Saskia N de Wildt

    Department of Pediatric Surgery, Erasmus MC – University Medical Center Rotterdam, Sophia Children’s Hospital, Rotterdam, The Netherlands

    ,
    Dick Tibboel

    Department of Pediatric Surgery, Erasmus MC – University Medical Center Rotterdam, Sophia Children’s Hospital, Rotterdam, The Netherlands

    &
    Ron HN van Schaik

    *Author for correspondence:

    E-mail Address: r.vanschaik@erasmusmc.nl

    Department of Clinical Chemistry, Erasmus MC – University Medical Center Rotterdam, The Netherlands

    Published Online:https://doi.org/10.2217/pgs.14.100

    Aim: Determine whether SNPs of OPRM1 118A>G (asn40asp), COMT 472G>A (val158met) and ARRB2 8622C>T are associated with morphine rescue in newborns on mechanical ventilation. Materials & methods: This is a pharmacogenetic analysis of a randomized controlled trial in (pre)term newborns (n = 64) at a level III Neonatal Intensive Care Unit (NICU) who received placebo infusion and for whom need and dose for rescue morphine was documented. Results: For OPRM1 and COMT separately, the expected risk for rescue morphine or morphine dose was not significantly increased. However, the combined OPRM1/COMT ‘high-risk’ genotype lead to a significant association with the need for rescue (OR: 5.12; 95% CI: 1.12–23.3; p = 0.035). No association was found between OPRM1/COMT ‘high-risk’ genotype and total morphine dose administered. Conclusion: Combined OPRM1 118A>G and COMT 472G>A genotype might serve as a predictor for the need of rescue morphine in premature and term newborns on mechanical ventilation.

    Original submitted 21 January 2014; Revision submitted 20 June 2014

    Papers of special note have been highlighted as: • of interest; •• of considerable interest

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