Miniaturization: The Clue to Clinical Application of the Artificial Placenta

Abstract

The artificial placenta as a fascinating treatment alternative for neonatal lung failure has been the subject of clinical research for over 50 years. Pumpless systems have been in use since 1986. However, inappropriate dimensioning of commercially available oxygenators has wasted some of the theoretical advantages of this concept. Disproportional shunt fractions can cause congestive heart failure. Blood priming of large oxygenators and circuits dilutes fetal hemoglobin (as the superior oxygen carrier), is potentially infectious, and causes inflammatory reactions. Flow demands of large extracorporeal circuits require cannula sizes that are not appropriate for use in preterm infants. NeonatOx, a tailored low-volume oxygenator for this purpose, has proven the feasibility of this principle before. We now report the advances in biological performance of a refined version of this specialized oxygenator.

An extra-uterine system to physiologically support the extreme premature lamb

“…A pumpless circuit powered by the fetal heart is not a new concept and has been the initial approach taken by many investigators232425444546. The advantages include simplicity, absence of pump-induced haemolysis and the potential for at least some autoregulation of circuit blood flow.…”

“…The disadvantages of pumpless systems include cardiac failure due to afterload imbalance if the circuit/oxygenator has supraphysiologic resistance, or the potential for high-output cardiac failure if the oxygenator has subphysiologic resistance. Most attempts have been limited by subphysiologic circuit flows and rapid haemodynamic decompensation despite the use of vasopressor support and other measures24254446. Recently, Miura et al 45.…”

“…In addition, all other access sites require an operative procedure on the fetus for both insertion and removal of cannulas, require stabilization of cannulas to avoid catastrophic decannulation events and raise concern for compromise of blood flow to the brain or other structures, depending upon the vessel utilized. While many investigators have utilized the umbilical vessels, most have placed their cannulas into the central vasculature to avoid umbilical vascular spasm7811121314152324254546. This is possible in sheep or goats, but not possible and would likely be hazardous for arterial cannula placement in the human fetus due to the tortuous course of the umbilical arteries and the large cannulas required.…”

Umbilical cannulation optimizes circuit flows in premature lambs supported by the EXTra‐uterine Environment for Neonatal Development (EXTEND)

“…Although the umbilical arteries comprise the most physiological conduit for extracorporeal support of the preterm neonate, attempts to cannulate the umbilical vessels for 'artificial placenta' inflow over the past 50 years have produced limited and progressively declining driving pressures and inadequate circuit flows. Researchers have employed several strategies aiming to circumvent the inherent spasticity of umbilical vessels, such as using continuous paralytics to minimize flow-limiting movement, inserting umbilical cannulas to the depth of the abdominal aorta and incorporating pumps to augment flow, often avoiding the umbilical arteries altogether (Callaghan et al 1965;Alexander et al 1968;Zapol et al 1969;Unno et al 1993;Awad et al 1995;Sakata et al 1998;Pak et al 2002;Reoma et al 2009;Miura et al 2012;Schoberer et al 2014;Bryner et al 2015;Miura et al 2015). Although many of these approaches have supported long-term extra-uterine runs in premature animal models, none have achieved physiological 'placental' flows.…”

“…Over the past 50 years, vascular access has been an obstacle for groups developing 'artificial placenta' technology, with long-term support generally limited by insufficient circuit flows and, ultimately, subphysiological oxygen delivery (Callaghan et al 1965;Alexander et al 1968;Zapol et al 1969;Unno et al 1993;Awad et al 1995;Sakata et al 1998;Pak et al 2002;Reoma et al 2009;Miura et al 2012;Schoberer et al 2014;Bryner et al 2015;Miura et al 2015). As our system evolved, we experimented with three distinct AV cannulation strategies: carotid artery/jugular vein (CA/JV), carotid artery/umbilical vein (CA/UV) and umbilical artery (×2)/umbilical vein (UA/UV).…”