Randomised double-blind controlled trial of effect of morphine on catecholamine concentrations in ventilated pre-term babies

Lancet. 1993 Aug 7;342(8867):324-7. doi: 10.1016/0140-6736(93)91472-x.


A sick premature baby who requires intensive care will undergo many uncomfortable procedures. It is now accepted that such babies perceive pain and need adequate analgesia, but little is known about the effects of sedation in these patients. We investigated the use of morphine to provide analgesia and sedation for ventilated preterm babies in a randomised, double-blind, placebo-controlled trial. 41 mechanically ventilated babies who had been treated with surfactant (Curosurf) for hyaline membrane disease were randomly assigned morphine in 5% dextrose (100 micrograms/kg per h for 2 h followed by 25 micrograms/kg per h continuous infusion) or 5% dextrose (placebo). Plasma catecholamine concentrations were measured 1 h after the first dose of surfactant and 24 h later. Blood pressure was measured at study entry and after 6 h. The morphine and placebo groups showed no differences in method of delivery, Apgar scores, birthweight, gestation, or catecholamine concentrations at baseline. Morphine-treated babies showed a significant reduction in adrenaline concentrations during the first 24 h (median change -0.4 [95% CI -1.1 to -0.3] nmol/L p < 0.001), which was not seen in the placebo group (median change 0.2 [-0.6 to 0.6] nmol/L, p = 0.79). There was a non-significant reduction in noradrenaline concentration in the morphine group. Blood pressure showed a slight but non-significant fall (median -4 mm Hg) in morphine-treated babies. The incidence of intraventricular haemorrhage, patent ductus arteriosus, and pneumothorax, the number of ventilator days, and the numbers of deaths did not differ significantly between the groups. Morphine, in the dose regimen we used, is safe and effective in reducing adrenaline concentrations in preterm ventilated babies.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analgesia / methods*
  • Apgar Score
  • Biological Products*
  • Blood Pressure
  • Catecholamines / blood*
  • Double-Blind Method
  • Epinephrine / blood
  • Humans
  • Hyaline Membrane Disease / blood
  • Hyaline Membrane Disease / physiopathology
  • Hyaline Membrane Disease / therapy*
  • Infant, Newborn
  • Morphine / administration & dosage
  • Morphine / pharmacology*
  • Phospholipids*
  • Pulmonary Surfactants / therapeutic use
  • Respiration, Artificial*
  • Stress, Physiological / blood*


  • Biological Products
  • Catecholamines
  • Phospholipids
  • Pulmonary Surfactants
  • Morphine
  • poractant alfa
  • Epinephrine