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Morphine in ventilated neonates: its effects on arterial blood pressure

¹ Department of Paediatric Surgery, Erasmus MC-Sophia Children’s Hospital, Rotterdam, The Netherlands
² Division of Neonatology, Department of Paediatrics, Erasmus MC-Sophia Children’s Hospital
³ Department of Paediatrics, Division of Neonatology, Isala Clinics, Zwolle, The Netherlands
⁴ Department of Medical Psychology and Psychotherapy, Erasmus MC, Rotterdam
⁵ Departments of Pediatrics and Pharmacology, George Washington University Medical Center/Children’s National Medical Center, Washington DC, USA

Correspondence to:
Correspondence to:
Dr Tibboel
Department of Paediatric Surgery, Erasmus MC-Sophia Children’s Hospital, Dr Molewaterplein 60, 3015 GJ Rotterdam, The Netherlands; j.illsley{at}erasmusmc.nl

Objective: To study the effects of continuous morphine infusion on arterial blood pressure in ventilated neonates.

Design: Blinded randomised placebo controlled trial.

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

Patients: A total of 144 ventilated neonates. Inclusion criteria were postnatal age <3 days, ventilation <8 hours, and indwelling arterial line. Exclusion criteria were severe asphyxia, severe intraventricular haemorrhage, major congenital anomalies, neuromuscular blockers.

Intervention: Arterial blood pressure was measured before the start and during the first 48 hours of masked infusion of drug (morphine/placebo; 100 µg/kg + 10 µg/kg/h).

Outcome measures: Arterial blood pressure and blood pressure variability.

Results: There were no significant differences in overall mean arterial blood pressure between the morphine group (median (interquartile range) 36 mm Hg (6) and the placebo group (38 mm Hg (6)) (p = 0.11). Although significantly more morphine treated patients (70%) showed hypotension than the placebo group (47%) (p = 0.004), the use of volume expanders and vasopressor drugs was not significantly different (morphine group, 44%; placebo group, 48%; p = 0.87), indicating the limited clinical significance of this side effect. Blood pressure variability was not influenced by routine morphine analgesia (p = 0.81) or additional morphine (p = 0.80). Patients with and without intraventricular haemorrhage showed no differences in blood pressure (Mann-Whitney U test 1953; p = 0.14) or incidence of hypotension (² test 1.16; df 1; p = 0.28).

Conclusions: Overall arterial blood pressure, use of inotropes, and blood pressure variability were not influenced by morphine infusion. Therefore the clinical impact of hypotension as a side effect of low dose morphine treatment in neonates is negligible.

Abbreviations: CBF, cerebral blood flow; IVH, intraventricular haemorrhage; MAP, mean arterial blood pressure

Keywords: randomised controlled trial; opioids; preterm/term infants; hypotension; blood pressure variability