Adrenaline for prevention of morbidity and mortality in preterm infants with cardiovascular compromise

Abstract

Inotropes are widely used in preterm infants to treat cardiovascular compromise, which may result from early adaptive problems of the transitional circulation, perinatal asphyxia or sepsis. Sustained hypotension and poor organ blood flow are associated with brain injury including peri/intraventricular haemorrhage and subsequent poor neurodevelopmental outcomes. Adrenaline (epinephrine) infusions are used in preterm infants with clinical cardiovascular compromise. To determine the effectiveness and safety of adrenaline compared to no treatment or other inotropes in reducing mortality and morbidity in preterm infants with cardiovascular compromise. Randomised controlled trials were identified by searching MEDLINE (1966-August 2003), The Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 3, 2003) and EMBASE (1980 - 2003), supplemented with searches of reference lists of published trials and abstracts of conference proceedings. Randomised controlled trials of preterm newborn infants that compared adrenaline to no treatment or other inotropic agents (including dopamine, dobutamine, noradrenaline or isoprenaline). Data were extracted and analysed independently by two reviewers. Treatment effects on the following outcomes were to be determined: mortality in the newborn period, long term neurodevelopmental outcomes, radiological evidence of brain injury, short term haemodynamic changes, adverse drug effects and short term neonatal outcomes. Study authors were contacted for additional information. Studies were analysed for methodological quality using the criteria of the Cochrane Neonatal Review Group. One ongoing study (Pellicer 2003) was identified. One study comparing adrenaline with dopamine infusion was included but was published in abstract form only (Phillipos 1996). It enrolled hypotensive, predominantly preterm infants in the first 24 hours. Only infants >1750g are included in this review (report for infants <=1750g appears incomplete). The study was reported as being randomised and double blinded, but methods were not reported. Both adrenaline and dopamine significantly increased heart rate and mean BP, with no statistically significant effect on left or right ventricular outputs. No other clinical outcomes were reported. No studies were identified that compared adrenaline to other inotropes, placebo or no treatment. There are insufficient data on the use of adrenaline infusions in preterm infants with cardiovascular compromise to make recommendations for practice. There is a need for larger trials to determine whether adrenaline is effective in reducing morbidity and mortality in preterm infants with cardiovascular compromise.