Epinephrine in Neonatal Resuscitation

Abstract

Epinephrine is the only medication recommended by the International Liaison Committee on Resuscitation for use in newborn resuscitation. Strong evidence from large clinical trials is lacking owing to the infrequent use of epinephrine during neonatal resuscitation. Current recommendations are weak as they are extrapolated from animal models or pediatric and adult studies that do not adequately depict the transitioning circulation and fluid-filled lungs of the newborn in the delivery room. Many gaps in knowledge including the optimal dosing, best route and timing of epinephrine administration warrant further studies. Experiments on a well-established ovine model of perinatal asphyxial cardiac arrest closely mimicking the newborn infant provide important information that can guide future clinical trials.

Keywords: epinephrine; intramuscular; intraosseous; intravenous; newborn; resuscitation.

Figure 1

Coronary perfusion pressure (CPP) and the mechanism of action of epinephrine. CPP is calculated as the difference between the aortic diastolic pressure and the right atrial pressure serves as a surrogate to coronary blood flow. In the premature infant, the effect of a left to right (from aorta into pulmonary artery) flow on coronary blood flow is unknown. Epinephrine’s effect on alpha-adrenergic receptors on peripheral vasculature leads to vessel contraction and a rise in systemic vascular resistance that can increase CPP. Epinephrine also exerts stimulation of beta-adrenergic receptors on myocytes that increase cardiac contractility. α: Alpha; β: Beta; LV: Left ventricle; PA: Pulmonary artery; PDA: Patent ductus arteriosus. Copyright Satyan Lakshminruismha.

Figure 2

Infographic showing alternative routes of epinephrine administrations. Advantages are shown in blue and disadvantages in red. ETT: Endotracheal tube; IM: Intramuscular; IO: Intraosseous; IV: Intravenous; UVC: Umbilical venous catheter. Copyright Satyan Lakshminrusimha.

Figure 3

Causes for poor bioavailability and efficacy of epinephrine administered through a low umbilical venous catheter (UVC). The internal volume of a 5 Fr UVC with a stopcock is 0.55 mL. A flush of 0.5–1 mL will clear the catheter and deposit epinephrine in the umbilical vein. In the presence of adequate pressure and flow into the umbilical vein, 40–50% of administered fluid passes through the ductus venosus [30]. In the absence of umbilical flow (as in cardiac arrest), the inlet of the ductus venosus narrows. The terminal portion of the inferior vena cava and ductus venosus do not have valves and backpressure from chest compressions can potentially cause back-flow. Epinephrine also increases portal venous resistance. The liver is also a major site of epinephrine breakdown. Right atrial delivery of a vasopressor can be enhanced by (a) catheter placement in the right atrium (not feasible in the delivery room); (b) quick flush with a mini-bolus to open up the ductus venosus and enhanced delivery to the heart in the absence of spontaneous circulation. Copyright Satyan Lakshminrusimha.

Figure 4

Endotracheal epinephrine. Asphyxia and acidosis decrease systemic vascular resistance by dilating the peripheral vascular bed, and high fetal pulmonary vascular resistance may lead to right to left shunting at the PDA limiting pulmonary blood flow. The presence of fetal lung liquid may dilute tracheal epinephrine, and absorption is further compromised by low pulmonary blood flow. The dashed green line represents the proposed path of intratracheal epinephrine. A higher dose of endotracheal epinephrine may compensate for dilution of lung liquid and overcome the diffusion barrier to achieve higher plasma concentrations. LV: Left ventricle; PA: Pulmonary artery; PDA: Patent ductus arteriosus; PVR: Pulmonary vascular resistance. Copyright Satyan Lakshminrusimha.

Figure 5

X-ray showing distribution following (A) low-lying umbilical venous catheter or (B) tibial IO administration of contrast in a perinatal cardiac arrested lamb model following 30 sec of chest compressions. Rapid distribution of contrast into the venous vasculature and heart can be appreciated following IO administration. IO: Intraossesus. Copyright Satyan Lakshminrusimha.

Figure 6

X-ray showing distribution of contrast following low- and high-volume flush through a low-lying umbilical venous catheter following 30 sec of chest compressions in term cardiac-arrested lambs. (A) Administration of 1 mL flush of Omnipaque shows the contrast remained in the portal venous system. (B) Increasing the Omipaque flush solution to 10 mL resulted in a much better distribution of contrast into the heart and great vessels. Copyright Satyan Lakshminrusimha.