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

Abstract

Purpose An artificial placenta would change the paradigm of treating extremely premature infants. We hypothesized that using a veno-venous extracorporeal life support (VV-ECLS) artificial placenta after ventilatory failure would stabilize premature lambs and maintain normal fetal physiologic parameters for 70h. Methods A near-term neonatal lamb model (130 days; term=145) was used. The right jugular vein (drainage) and umbilical vein (reinfusion) were cannulated with 10–12 Fr cannulas. Lambs were then transitioned to an infant ventilator. After respiratory failure, the endotracheal tube was filled with amniotic fluid, and VV-ECLS total artificial placenta support (TAPS) was initiated. Lambs were maintained on TAPS for 70h. Results Six of seven lambs survived for 70h. Mean ventilation time was 57±22min. During ventilation, mean MAP was 51±14mmHg, compared to 44±14mmHg during TAPS (p=0.001). Mean pH and lactate during ventilation were 7.06±0.15 and 5.7±2.3mmol/L, compared to 7.33±0.07 and 2.0±1.8mmol/L during TAPS (p<0.001 for both). pO2 and pCO2 remained within normal fetal parameters during TAPS, and mean carotid blood flow was 25±7.5mL/kg/min. Necropsy showed a patent ductus arteriosus and no intracranial hemorrhage in all animals. Conclusions The artificial placenta stabilized premature lambs after ventilatory failure and maintained fetal circulation, hemodynamic stability, gas exchange, and cerebral perfusion for 70h.

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].…”

“…Research in our laboratory initially involved a pumpless arteriovenous system and a pump-driven venoarterial system [12]. Our current model involves pump-driven venovenous ECLS; we previously reported its use to support near-term fetal lambs for 70 hours after initial failure of conventional mechanical ventilation [13]. The purpose of this study was to examine the AP's efficacy a) in providing prolonged support up to one week, b) in supporting extremely premature lambs that more closely model the human ELGAN, and c) as compared to the current standard of care in neonatal intensive care units.…”

A paradigm shift in the treatment of extreme prematurity

“…In premature lambs, mechanical ventilation failed within one hour and subsequently 6 of 7 lambs were then successfully transitioned to the AP and survived for 24 hours. [47**] Subsequent work has focused on sheep models of extreme prematurity (equivalent to a 24 week human), lung development, brain function, development of nonthrombogenic surfaces, and survival after weaning from the AP. While much progress has been made, many challenges remain to model development and clinical translation (Table 2).…”

Artificial Placenta: A Novel Approach for Preterm Neonates: Review of Literature

“…The first attempts to develop an artificial placenta as an effective alternation to provide respiratory support for newborns, especially preterm were made in mid-20th century [2]. Since, then for many decades it has fascinated the imaginations of researchers as an alternative approach to help extremely preterm infants (EPIs) born less than 28 weeks of gestation to overcome respiratory insufficiency [3,4].…”

“…Even conventional extracorporeal life support or extracorporeal membrane oxygenation (ECLS/ECMO) causes severe damage to immature lungs, and is contraindicated in extremely low gestational age newborns (ELGANs) [24]. Hence, the best way to save such neonates is through use of artificial placenta that helps in maintaining fetal circulation and bypassing lungs, thus obviating the need for mechanical ventilation and allowing the lungs to mature [4]. …”