Pulmonary hemodynamics and vascular reactivity in asphyxiated term lambs resuscitated with 21 and 100% oxygen

Abstract

An increase in oxygen tension is an important factor in decreasing pulmonary vascular resistance (PVR) at birth. Birth asphyxia results in acidosis and increased PVR. We determined the effect of resuscitation with 21 vs. 100% O(2) on pulmonary hemodynamics, pulmonary arterial (PA) reactivity, and oxidant stress in a lamb model of in utero asphyxia. Term fetal lambs were acutely asphyxiated by intrauterine umbilical cord occlusion for 10 min resulting in acidosis (pH 6.96 ± 0.05 and Pco(2) 103 ± 5 Torr), bradycardia, systemic hypotension, and increased PVR. Lambs were treated with 30 min of resuscitation with 21% or 100% O(2) (n = 6 each). Pa(O(2)) was significantly elevated with 100% O(2) resuscitation compared with 21% O(2) (430 ± 38 vs. 64 ± 8 Torr), but changes in pH and Pa(CO(2)) were similar. The 100% O(2) induced greater increase in pulmonary blood flow and decrease in PVR at 1 min of life, but subsequent values were similar to 21% O(2) group between 2 and 30 min of life. Oxygen uptake from the lung and systemic oxygen extraction was similar between the two groups. Pulmonary arteries showed increased staining for superoxide anions and increased contractility to norepinephrine following resuscitation with 100% O(2). The increased PA contractility induced by 100% O(2) was reversed by scavenging superoxide anions with superoxide dismutase and catalase. We conclude that resuscitation of asphyxiated lambs with 100% O(2) increases Pa(O(2)) but does not improve lung oxygen uptake, decrease PVR at 30 min, or increase systemic oxygen extraction ratios. Furthermore, 100% O(2) also induces oxidative stress and increases PA contractility. These findings support the new neonatal resuscitation guidelines recommending 21% O(2) for initial resuscitation of asphyxiated neonates.

Part 7: Neonatal Resuscitation

“…[216][217][218][219][220][221][222][223] 222 One demonstrated more rapid restoration of cerebral blood flow but no difference in histologic brain injury scores. 224 For the critical outcome of oxidative injury, we found 10 animal studies reported on oxidative injury with varying results 212,213,216,[219][220][221][222][223][225][226][227] (very-low-quality evidence, downgraded for potential bias, inconsistency, and indirectness).…”

“…For the critical outcome of ROSC, we found 8 animal studies (lambs/pigs/ rats) [216][217][218][219][220][221][222][223] all demonstrating no advantage to 100% over 21% during CPR (very-low-quality evidence, downgraded for bias and indirectness).…”

“…224 For the critical outcome of oxidative injury, we found 10 animal studies reported on oxidative injury with varying results 212,213,216,[219][220][221][222][223][225][226][227] (very-low-quality evidence, downgraded for potential bias, inconsistency, and indirectness). Six studies (pigs/mice) demonstrated no difference in various oxidative injury markers, 212,213,[219][220][221]224 3 (lambs/ rats) demonstrated more oxidative damage from using 100% O 2 including apoptosis, 216,222,226 and a pig study reported less striatal and hippocampal apoptosis with 100% O 2 compared with 21% O 2 . 227 …”

Part 13: Neonatal Resuscitation

“…Animal evidence shows no advantage to 100% oxygen during CPR. [179][180][181][182][183][184][185][186] However, by the time resuscitation of a newborn infant has reached the stage of chest compressions, efforts to achieve return of spontaneous circulation using effective ventilation with low-concentration oxygen should have been attempted. Thus, it would appear sensible to try increasing the supplementary oxygen concentration.…”

Hydrocortisone Normalizes Phosphodiesterase‐5 Activity in Pulmonary Artery Smooth Muscle Cells from Lambs with Persistent Pulmonary Hypertension of the Newborn

“…7,8 Although hypoxemia often prompts the administration of high concentrations of oxygen for infants with PPHN, a growing body of literature demonstrates that even brief periods of hyperoxia trigger oxidative stress as well as changes in enzyme activity and vascular reactivity. [9][10][11] Thus, new therapies are needed for newborns with PPHN.…”