Evidence on Adrenaline Use in Resuscitation and Its Relevance to Newborn Infants: A Non-Systematic Review

Abstract

Aim: Guidelines for newborn resuscitation state that if the heart rate does not increase despite adequate ventilation and chest compressions, adrenaline administration should be considered. However, controversy exists around the safety and effectiveness of adrenaline in newborn resuscitation. The aim of this review was to summarise a selection of the current knowledge about adrenaline during resuscitation and evaluate its relevance to newborn infants. Methods: A search in PubMed, Embase, and Google Scholar until September 1, 2015, using search terms including adrenaline/epinephrine, cardiopulmonary resuscitation, death, severe brain injury, necrotizing enterocolitis, bronchopulmonary dysplasia, and adrenaline versus vasopressin/placebo. Results: Adult data indicate that adrenaline improves the return of spontaneous circulation (ROSC) but not survival to hospital discharge. Newborn animal studies reported that adrenaline might be needed to achieve ROSC. Intravenous administration (10-30 μg/kg) is recommended; however, if there is no intravenous access, a higher endotracheal dose (50-100 μg/kg) is needed. The safety and effectiveness of intraosseous adrenaline remain undetermined. Early and frequent dosing does not seem to be beneficial. In fact, negative hemodynamic effects have been observed, especially with doses ≥30 μg/kg intravenously. Little is known about adrenaline in birth asphyxia and in preterm infants, but observations indicate that hemodynamics and neurological outcomes may be impaired by adrenaline administration in these conditions. However, a causal relationship between adrenaline administration and outcomes cannot be established from the few available retrospective studies. Alternative vasoconstrictors have been investigated, but the evidence is scarce. Conclusion: More research is needed on the benefits and risks of adrenaline in asphyxia-induced bradycardia or cardiac arrest during perinatal transition.

Epinephrine Use during Newborn Resuscitation

“…Through β 2 receptor stimulation, it causes vascular smooth muscle relaxation and increased myocardial contractility, but these effects are usually minor. In vivo effects of epinephrine depend on the dose of epinephrine, number of receptors available on target tissues, the affinity of these receptors, and local target tissue environments (23). …”

“…No studies in term or preterm newborns or animal models with newborn transition physiology have investigated the mechanism of action of epinephrine during CPR. The distribution and maturation of α and β receptors in term and preterm newborns remain unknown (23). …”

“…ET epinephrine efficacy may be limited in the newly born due to dilution by non-mobilized lung fluid. Elevated pulmonary arterial pressure in the presence of patent ductus arteriosus could result in right-sided cardiac output bypassing the lungs and thus limiting epinephrine absorption from the lung (23, 25). Based on this evidence, guidelines recommended an increase in ET epinephrine dosing from 0.01 to 0.03 to 0.05 to 0.1 mg/kg (1, 9).…”

Effects of epinephrine on hemodynamic changes during cardiopulmonary resuscitation in a neonatal piglet model

“…Severe asphyxia presents with bradycardia or asystole at birth. Current resuscitation guidelines recommend chest compressions (CC) if the heart rate remains o60/min despite adequate ventilation with supplementary oxygen for 30 s 3 . Further, once CC are given, a vascular access should be established for epinephrine administration 3 .…”

Optimal Chest Compression Rate and Compression to Ventilation Ratio in Delivery Room Resuscitation: Evidence from Newborn Piglets and Neonatal Manikins

“…The focus of CC research has been on systemic and coronary hemodynamics with the primary endpoint often being ROSC. Even though neurological adverse effects of epinephrine in preterm infants have been described (43, 44), less attention has been given to the effects of CC alone on cerebral circulation in asphyxiated term infants.…”