Development of an Artificial Placenta IV

Abstract

An extracorporeal artificial placenta would change the paradigm of treating extremely premature infants. We hypothesized that a venovenous extracorporeal life support (VV-ECLS) artificial placenta would maintain fetal circulation, hemodynamic stability, and adequate gas exchange for 24 hours. A near-term neonatal lamb model (130 days; term = 145 days) was used (n = 9). The right jugular vein was cannulated for VV-ECLS outflow, and an umbilical vein was used for inflow. The circuit included a peristaltic roller pump and a 0.5 m(2) hollow fiber oxygenator. Lambs were maintained on VV-ECLS in an "amniotic bath" for up to 24 hours. Five of nine fetuses survived for 24 hours. In the survivors, average mean arterial pressure was 69 ± 10 mm Hg for the first 4 hours and 36 ± 8 mm Hg for the remaining 20 hours. The mean fetal heart rate was 202 ± 30. Mean VV-ECLS flow was 94 ± 20 ml/kg/min. Using a gas mixture of 50% O(2)/3% CO(2) and sweep flow of 1-2 L/min, the mean pH was 7.27 ± 0.09, with Po(2) of 35 ± 12 mm Hg and Pco(2) of 48 ± 12 mm Hg. Necropsy revealed a patent ductus arteriosus in all cases, and there was no gross or microscopic intracranial hemorrhage. Complications in failed attempts included technically difficult cannulation and multisystem organ failure. Future studies will enhance stability and address the factors necessary for long-term support.

An extracorporeal artificial placenta supports extremely premature lambs for 1week

“…Despite cannulation of the aorta via the umbilical artery, we could not solve the problem of persistent hypotension. We transitioned to a model of venovenous (VV) ECLS with jugular drainage and umbilical reinfusion and supported lambs for up to 92 hours [13, 16]. We found that this model of an AP provided adequate perfusion to the brain despite the ligation of one carotid artery for monitoring line placement [17].…”

Development of an artificial placenta V: 70h veno-venous extracorporeal life support after ventilatory failure in premature lambs

“…We found that the AP stabilized hemodynamics and gas exchange, maintained fetal circulation, and provided cerebral perfusion for over 70h of support. This is a significant step forward from our previous series of five 24h survivors on TAPS and another advance towards clinical translation of this technology [10]. …”

“…The most successful study described 3 week AV-ECLS support of 2 goat fetuses in 1993, but these results have not been reproduced nor have there been significant advances leading to clinical translation [8]. Despite limited initial success in our laboratory with AV-ECLS AP models, we made greater strides after transitioning to a pump-driven VV (venovenous)-ECLS AP preparation [9,10]. We reported a series of 5 near-term premature sheep that maintained hemodynamic stability and fetal gas exchange parameters for 24h using a VV-ECLS AP [10].…”

“…Despite limited initial success in our laboratory with AV-ECLS AP models, we made greater strides after transitioning to a pump-driven VV (venovenous)-ECLS AP preparation [9,10]. We reported a series of 5 near-term premature sheep that maintained hemodynamic stability and fetal gas exchange parameters for 24h using a VV-ECLS AP [10]. No animal studies to date, however, have mimicked the clinical scenario of initiating AP support after ventilatory failure in a premature animal model.…”

A paradigm shift in the treatment of extreme prematurity

“…[46**] During these experiments sheep were delivered prematurely by Caesarean section and cannulated while on native placental support. Initially they were maintained in an artificial amniotic bath, but it was noted to become easily infected causing sepsis in sheep who lived >24hrs.…”