Morphine analgesia and gastrointestinal morbidity in preterm infants: secondary results from the NEOPAIN trial.
OBJECTIVE
To investigate the influence of morphine therapy and other factors on the attainment of full enteral feeds and on acquired gastrointestinal pathology in preterm infants.


METHODS
Secondary data analysis from a randomised, placebo controlled trial.


METHODS
16 neonatal intensive care units in USA, Sweden, France and UK.


METHODS
898 infants (treatment group 449, control 449). Gestation (median (range)): 27 (23-32) weeks; birth weight (median (range)): 985 (420-2440) g.


METHODS
Morphine (M) or placebo (Pl) given pre-emptively by intravenous loading dose (100 microg/kg of morphine) and infusion (10-30 microg/kg/h depending on gestation) while infants were ventilated, for up to 14 days. "Open-label" morphine (A) could be given if clinically indicated.


METHODS
Age at full enteral feeds and major acquired gastrointestinal pathology.


RESULTS
The group randomised to morphine was later in attaining full feeds (median days (quartiles): M 20 (13-29), Pl 17 (12-26); p = 0.003), and in starting feeds (median days (quartiles): M 5 (3-8), Pl 4 (2-7)). In a linear regression model, age at full feeds was independently associated with birth weight, a score of neonatal morbidities, neonatal dexamethasone use and cumulative morphine dose. There was no relationship between morphine use and acquired gastrointestinal pathology (M 9/449, Pl 8/449; chi2 p = 0.81).


CONCLUSIONS
Morphine delays the attainment of full enteral feeds, partly by delaying the start of feeding, but does not discernibly increase gastrointestinal complications. The attainment of full feeds is influenced by morphine dose, but other factors seem to be important, including birth weight and neonatal morbidity.
Menon
G
G
Department of Neonatology, Simpson Centre for Reproductive Health, Royal Infirmary of Edinburgh, 51 Little France Crescent, Old Dalkeith Road, Edinburgh EH16 4SA, Scotland, UK. gopi.menon@luht.scot.nhs.uk
Boyle
E M
EM
Bergqvist
L L
LL
McIntosh
N
N
Barton
B A
BA
Anand
K J S
KJ
D000701:Analgesics, Opioid / Q000627:therapeutic use*; D004750:Enteral Nutrition / Q000009:adverse effects*; D020345:Enterocolitis, Necrotizing / Q000139:chemically induced / Q000517:prevention & control*; D005260:Female; D041981:Gastrointestinal Tract / Q000187:drug effects / Q000503:physiopathology*; D006801:Humans; D007227:Infant Nutritional Physiological Phenomena / Q000502:physiology; D007231:Infant, Newborn; D007234:Infant, Premature; D007235:Infant, Premature, Diseases / Q000188:drug therapy; D015931:Intensive Care, Neonatal / Q000592:standards; D009020:Morphine / Q000627:therapeutic use*; D011247:Pregnancy; D016896:Treatment Outcome
D000701:Analgesics, Opioid; D009020:Morphine