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Randomised controlled trial evaluating effects of morphine on plasma adrenaline/noradrenaline concentrations in newborns
  1. S H P Simons1,3,
  2. M van Dijk1,
  3. R A van Lingen5,
  4. D Roofthooft3,
  5. F Boomsma4,
  6. J N van den Anker2,6,7,
  7. D Tibboel1
  1. 1Department of Paediatric Surgery, Erasmus MC-Sophia, Rotterdam, the Netherlands
  2. 2Department of Paediatrics, Erasmus MC-Sophia
  3. 3Division of Neonatology, Erasmus MC-Sophia
  4. 4Department of Internal Medicine, Erasmus MC
  5. 5Department of Paediatrics, Division of Neonatology, Isala Clinics, Zwolle, the Netherlands
  6. 6Division of Paediatric Clinical Pharmacology, Children’s National Medical Center, Washington DC, USA
  7. 7Department of Paediatrics and Pharmacology, George Washington University MC, Washington DC, USA
  1. Correspondence to:
    Dr Tibboel
    Department of Paediatric Surgery, Erasmus MC-Sophia, Dr Molewaterplein 60, 3015 GJ Rotterdam, the Netherlands;


Objectives: To determine the effects of continuous morphine infusion in ventilated newborns on plasma concentrations of adrenaline (epinephrine) and noradrenaline (norepinephrine) and their relation to clinical outcome.

Design: Blinded, randomised, placebo controlled trial.

Setting: Level III neonatal intensive care units in two centres.

Patients: A total of 126 ventilated neonates (inclusion criteria: postnatal age <3 days, duration of ventilation <8 hours, indwelling arterial catheter for clinical purposes; exclusion criteria: severe asphyxia, severe intraventricular haemorrhage, major congenital anomalies, neuromuscular blockers).

Interventions: Plasma adrenaline and noradrenaline concentrations were determined in patients during blinded morphine (n  =  60) and placebo (n  =  66) infusion (100 μg/kg plus 10 μg/kg/h).

Results: Plasma concentrations at baseline (nmol/l with interquartile range in parentheses) were comparable in infants treated with morphine (adrenaline, 0.22 (0.31); noradrenaline, 2.52 (2.99)) or placebo (adrenaline, 0.29 (0.46); noradrenaline, 2.44 (3.14)). During infusion, median adrenaline concentrations were 0.12 (0.28) and 0.18 (0.35) and median noradrenaline concentrations were 2.8 (3.7) and 3.8 (4.0) for the morphine and placebo treated infants respectively. Multivariate analyses showed that noradrenaline (p  =  0.029), but not adrenaline (p  =  0.18), concentrations were significantly lower in the morphine group than the placebo group. Furthermore, noradrenaline concentrations were related to the length of stay in the neonatal intensive care unit.

Conclusions: Continuous morphine infusion significantly decreased plasma noradrenaline concentrations in ventilated newborns compared with placebo treatment. The results of this study support the idea that routine morphine administration decreases stress responses in ventilated neonates.

  • NICU, neonatal intensive care unit
  • IVH, intraventricular haemorrhage
  • IQR, interquartile range
  • CI, confidence interval
  • morphine
  • randomised controlled trial
  • stress response
  • catecholamine
  • adrenaline

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  • Competing interests: none declared