Adrian Joseph Anthony Ziino, Mark W Davies, Peter G Davis

Epinephrine is a cardiac stimulant with complex effects on the heart and blood vessels. It has been used for decades in all age groups to treat cardiac arrest and bradycardia. Despite formal guidelines for the use of epinephrine in neonatal resuscitation, the evidence for these recommendations has not yet been rigorously scrutinised. While it is understood that this evidence is in large part derived from animal models and the adult human population, the contribution from work in the neonatal population remains unclear. In particular, it remains to be determined if any randomised studies in neonates have helped to establish if the administration of epinephrine in the context of apparent stillbirth or extreme bradycardia might influence mortality and morbidity. ~bullet~To determine if the administration of epinephrine to apparently stillborn and extremely bradycardic newborns reduces mortality and morbidity Secondary objectives: ~bullet~To determine the effect of intravenous versus endotracheal administration on mortality and morbidity ~bullet~To determine the effect of high dose versus standard dose epinephrine on mortality and morbidity, where high dose is defined as any dose greater than the current recommended standard dose of 0.1 to 0.3ml/kg of a 1:10,000 solution of epinephrine ~bullet~To determine whether the effect of epinephrine on mortality and morbidity varies with gestational age, i.e. term (greater than or equal to 37 weeks) versus pre-term (less than 37 weeks) Searches were made of Medline from 1966 to December 2002, CINAHL (from 1982), Current Contents (from 1988), EMBASE, and the Cochrane Controlled Trials Register (2002, issue 4). Bibliographies of conference proceedings were reviewed and unpublished studies were sought by hand searching the conference proceedings of the Society for Pediatric Research and the European Society for Pediatric Research from 1993 to 2002. Randomised and quasi-randomised controlled trials of newborns, both pre-term and term, receiving epinephrine for unexpected apparent stillbirth or extreme bradycardia. No studies were found meeting the criteria for inclusion in this review No studies were found meeting the criteria for inclusion in this review. We found no randomised, controlled trials evaluating the administration of epinephrine to the apparently stillborn or extremely bradycardic newborn infant. Similarly, we found no randomised, controlled trials which addressed the issues of optimum dosage and route of administration of epinephrine. Current recommendations for the use of epinephrine in newborn infants are based only on evidence derived from animal models and the human adult literature. Randomised trials in neonates are urgently required to determine the role of epinephrine in this population.