ABSTRACT:The optimal inhaled oxygen fraction for newborn resuscitation is still not settled. We hypothesized that short-lasting oxygen ventilation after intrauterine asphyxia would not cause arterial or cerebral hyperoxia, and therefore be innocuous. The umbilical cord of fetal sheep was clamped and 10 min later, after delivery, ventilation with air (n ϭ 7) or with 100% oxygen for 3 (n ϭ 6) or 30 min (n ϭ 5), followed by air, was started. Among the 11 lambs given 100% oxygen, oxygen tension (P O2 ) was 10.7 (1.8 -56) kPa [median (range)] in arterial samples taken after 2.5 min of ventilation. In those ventilated with 100% oxygen for 30 min, brain tissue P O2 (Pbt O2 ) increased from less than 0.1 kPa in each lamb to individual maxima of 56 (30 -61) kPa, whereas in those given oxygen for just 3 min, Pbt O2 peaked at 4.2 (2.9 -46) kPa. The maximal Pbt O2 in airventilated lambs was 2.9 (0.8 -5.4) kPa. Heart rate and blood pressure increased equally fast in the three groups. Thus, prolonged ventilation with 100% oxygen caused an increase in Pbt O2 of a magnitude previously only reported under hyperbaric conditions. Reducing the time of 100% oxygen ventilation to 3 min did not consistently avert systemic hyperoxia. (Pediatr Res 65: 57-61, 2009) C urrent guidelines from the International Liaison Committee on Resuscitation breathe considerable uncertainty as to how much supplementary oxygen should be given during resuscitation of newborn asphyxiated infants (1). Previous recommendations were to be generous with oxygen, but recent guidelines from a number of countries, e.g. Australia, Canada, Finland, the Netherlands, Sweden, and the United Kingdom recommend initial ventilation with air, because of the results from several experimental (2-5) and clinical (6 -13) studies indicating that resuscitation with 100% oxygen is harmful. In the clinical studies, the time of exposure to 100% oxygen was typically 5-7 min (8,13), whereas only one animal study (5) has investigated an exposure time to oxygen less than 15 min.We speculated that very short times of exposure might not allow systemic hyperoxia to develop and so be harmless to the newborn infant, except for a possible negative effect on the lungs. In fact, the pulse oximetric saturation at 3 min after birth is usually below 80% (14,15) in the normal air-breathing infant, suggesting the presence of cardiac or pulmonary rightto-left shunts. One might expect that such shunts would delay the appearance of arterial hyperoxemia in the infant breathing pure oxygen. However, this has been studied neither in normal nor in asphyxiated subjects.We used a sheep model of term intrauterine asphyxia with postnatal resuscitation, and hypothesized that hyperoxia of arterial blood and of brain tissue could be prevented by limiting the period of ventilation with 100% oxygen to 3 min. We also investigated whether the speed of circulatory recovery, as reflected by the heart rate (HR) and mean arterial blood pressure (MAP) responses, and the speed of recovery of brain oxygenation, as reflected ...
Inhaled NO (iNO) has an established role in the treatment of pulmonary hypertension (PH) in the newborn. However, costs and potential toxicity associated with iNO have generated interest in alternative inhaled selective pulmonary vasodilators such as iloprost. In a preterm lamb model of respiratory distress syndrome, we studied effects of increasing doses of iloprost followed by iNO on right ventricular pressure (RVP) and circulation including cerebral oxygenation. Fetal sheep were randomized to three doses (0.2-4 mg/kg) of iloprost (n ϭ 9) or saline (n ϭ 10), administered as 15-min inhalations with 15-min intervals after a 60-min postnatal stabilization. No differences were found in RVP, arterial PO 2 , or cardiac index according to treatment. The cerebral oxygenation, measured with near-infrared spectroscopy, deteriorated in control lambs, but not in iloprost lambs. Iloprost treatment followed by iNO resulted in a larger decrease (p ϭ 0.007) in RVP than saline treatment followed by iNO. In conclusion, iloprost stabilized cerebral oxygenation and when followed by iNO had a larger effect on RVP than iNO alone. Although species differences may be relevant, these results suggest that iloprost should be studied in newborn infants for the treatment of PH. circulation, the pulmonary vascular resistance decreases rapidly. The vascular tone in pulmonary arteries is regulated by a balance of vasoconstrictors and vasodilators. Endothelin, hypoxemia, and acidemia have strong constrictor effects on pulmonary arterioles (1). The main endogenous vasodilators are the endothelial-derived substances NO and prostacyclin, which increase endothelial cell production of cGMP and cAMP, respectively (1). When the transition is disturbed, the pulmonary arterial resistance remains elevated resulting in considerable hypoxemia and low-oxygen delivery to tissue. As arterial O 2 tension does not necessarily reflect the oxygen delivery to tissue because of low perfusion or extraction, near-infrared spectroscopy (NIRS) has been applied to monitoring tissue oxygenation (2).Inhaled NO (iNO) exerts a rapid pulmonary vasodilatation and is an established treatment of pulmonary hypertension (PH) in newborn infants (3). iNO has, however, several disadvantages, such as unpredictable and nonsustained effect, and rebound PH after withdrawal (4). The toxic NO product peroxynitrite inhibits prostacyclin synthase (5), the key enzyme of prostacyclin synthesis. Further, NO causes an increased endothelin-1 release (6). Thus, other effective agents with fewer side effects are sought for the treatment of PH in the newborn.Prostanoids have been administered in the clinical setting mainly in adults as i.v. infusions of prostacyclin, s.c. infusion of treprostinil, and inhalations of iloprost (7). I.v. prostacyclin causes severe systemic hypotension in newborns (8). Inhaled prostacyclin decreases pulmonary vascular resistance without decreasing systemic blood pressure. The prostacyclin analogue iloprost has a longer half-life (almost 30 min) than prostac...
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