Cardiopulmonary Resuscitation of Asystolic Newborn Lambs Prior to Umbilical Cord Clamping; the Timing of Cord Clamping Matters!

Abstract

Background: Current guidelines recommend immediate umbilical cord clamping (UCC) for newborns requiring chest compressions (CCs). Physiological-based cord clamping (PBCC), defined as delaying UCC until after lung aeration, has advantages over immediate UCC in mildly asphyxiated newborns, but its efficacy in asystolic newborns requiring CC is unknown. The aim of this study was to compare the cardiovascular response to CCs given prior to or after UCC in asystolic near-term lambs. Methods: Umbilical, carotid, pulmonary, and femoral arterial flows and pressures as well as systemic and cerebral oxygenation were measured in near-term sheep fetuses [139 ± 2 (SD) days gestation]. Fetal asphyxia was induced until asystole ensued, whereupon lambs received ventilation and CC before (PBCC; n = 16) or after (n = 12) UCC. Epinephrine was administered 1 min after ventilation onset and in 3-min intervals thereafter. The PBCC group was further separated into UCC at either 1 min (PBCC 1 , n = 8) or 10 min (PBCC 10 , n = 8) after return of spontaneous circulation (ROSC). Lambs were maintained for a further 30 min after ROSC. Results: The duration of CCs received and number of epinephrine doses required to obtain ROSC were similar between groups. After ROSC, we found no physiological benefits if UCC was delayed for 1 min compared to immediate cord clamping (ICC). However, if UCC was delayed for 10 min after ROSC, we found significant reductions in post-asphyxial rebound hypertension, cerebral blood flow, and cerebral oxygenation. The prevention of the post-asphyxial rebound hypertension in the PBCC 10 group occurred due to the contribution of the placental circulation to a low peripheral resistance. As a result, left and right ventricular outputs continued to perfuse the placenta and were evidenced by reduced mean pulmonary blood flow, persistence of right-to-left shunting across the ductus arteriosus, and persistence of umbilical arterial and venous blood flows.

Sustained Inflation Reduces Pulmonary Blood Flow during Resuscitation with an Intact Cord

“…DCC for 15 min restored cardiac output and oxygenation and mitigated post-asphyxial rebound hypertension after resuscitation in a non-arrest ovine model of perinatal asphyxia induced by maternal iliac artery ligation [ 13 ]. In lambs with asphyxial arrest, DCC for 10 min caused significant reductions in post-asphyxial rebound hypertension, cerebral blood flow and oxygenation [ 20 ]. These studies indicate improved hemodynamics with a longer DCC duration, and along with a difference in methodology of induced asphyxia (cord occlusion vs. maternal iliac artery ligation), may explain lack of sustained benefits in our study.…”

Single versus continuous sustained inflations during chest compressions and physiological-based cord clamping in asystolic lambs

“…Pregnant Border-Leicester ewes ( Ovis aries ) at 139±2 days’ gestation (term ~148 days) were anaesthetised by intravenous injection of thiopentone sodium (20 mg/kg; Jurox, NSW, Australia), followed by tracheal intubation and delivery of inhaled anaesthesia (isofluorane 1.5%–2.5% in oxygenated air; Bomac Animal Health, NSW, Australia). Fetal surgery and instrumentation have been described in detail previously 10 12. Briefly, ultrasonic flow transducers (Transonic Systems, Ithaca, NY, USA) were placed around the left main pulmonary artery and left carotid artery, and catheters were inserted into a carotid artery and jugular vein 10 12 13.…”

“…Fetal surgery and instrumentation have been described in detail previously 10 12. Briefly, ultrasonic flow transducers (Transonic Systems, Ithaca, NY, USA) were placed around the left main pulmonary artery and left carotid artery, and catheters were inserted into a carotid artery and jugular vein 10 12 13. Arterial pressures and blood flows were digitally recorded in real time (1 kHz, Powerlab; ADInstruments, NSW, Australia) 10.…”

“…Current neonatal resuscitation guidelines recommend immediate cord clamping (ICC) for infants requiring CC 2–4. We have recently demonstrated that ventilation and CC while attached to the umbilical cord in newborn lambs, termed physiological-based cord clamping (PBCC), does not impede the ability or increase the time taken to achieve ROSC 10. However, it is unclear whether ICC or PBCC influences the outcomes following different respiratory support techniques during CCs.…”

How to Provide Motherside Neonatal Resuscitation with Intact Placental Circulation?

“…One approach would be to perform resuscitation while the cord is still intact. Several studies have demonstrated improvements in physiological outcomes, such as higher Apgar scores or oxygen levels in the first few minutes of birth with resuscitation with an intact cord compared to early cord clamping [ 6 , 7 , 8 , 9 , 10 , 11 ]. Another challenge, however, is implementation of this practice.…”