Reoxygenation with 100 or 21% Oxygen after Cerebral Hypoxemia-Ischemia-Hypercapnia in Newborn Piglets

Solås, Anne-Beate; Kalous, P; Saugstad, Ola Didrik

doi:10.1159/000074966

Cited by 48 publications

(22 citation statements)

References 28 publications

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“…This result is consistent with the report by A. Solas and co-authors who demonstrated that 30 min of Re-O 2 was superior to Re-Air in restoration of microcirculation in cerebral cortex of piglets following HI-insult (20). This was associated with significant reduction of excitatory amino acids level in the striatum suggestive of more favorable neurologic outcome in Re-O 2 HI-piglets (5).…”

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confidence: 92%

Reoxygenation with 100% Oxygen Versus Room Air: Late Neuroanatomical and Neurofunctional Outcome in Neonatal Mice with Hypoxic-Ischemic Brain Injury

et al. 2006

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Study investigated neuroutcome in mice subjected at 7-8 d of life to hypoxic-ischemic brain injury (HI) followed by 30 min of reoxygenation with 100% O 2 (Re-O 2 ) or room air (Re-Air). At 24 h of recovery, mouse reflexes were tested. At 7 wks after HI spatial orientation and memory were assessed in the same mice. Mortality rate was recorded at 24 h and at 7 wks of recovery. In separate cohort of mice, changes in cerebral blood flow (CBF) during HI-insult and reoxygenation were recorded. T he resuscitation of asphyxiated neonates is aimed to reestablish tissue oxygen delivery by restoring blood flow and increasing the arterial oxygen content. Use of 100% O 2 during neonatal resuscitation is currently recommended (1). However, Re-O 2 compared with Re-Air significantly exacerbates an oxidative stress in asphyxiated neonates (2), which is one of the mechanisms of HI-brain injury (3). To avoid hyperoxia-induced oxidative stress, the efficacy of resuscitation with room air (RA) instead of 100% O 2 is being extensively studied. To date, results of these studies are conflicting. For instance, it was reported that in asphyxiated pigs the Re-O 2 restored CBF significantly faster and more complete compared with Re-Air (4). Significantly higher levels of excitatory amino acids were found in the striatum of newborn HI-piglets Re-Air compared with Re-O 2 piglets which may be indicative of less favorable neurologic prognosis for Re-Air animals (5). However, Liu. Y and co-authors, using a canine model of cardiac arrest, demonstrated that Re-O 2 versus ReAir resulted in greater neurologic impairment assessed at 24 h of recovery (6). In contrast, the postischemic use of hyperbaric oxygenation, which produces substantial oxidative stress (7), significantly improved neurologic score following focal cerebral ischemia in adult rats and HI in neonatal rats (8,9). Hyperbaric oxygenation used as a mode of resuscitation from experimental heatstroke in rats was shown to be significantly neuroprotective (10). Meier and co-authors reported that hyperoxic ventilation significantly reduced short-term (6 h) mortality due to systemic ischemia following an acute hemorrhagic shock in pigs (11). The most recent meta-analysis indicates that there are not enough data to challenge current recommendation of using of pure O 2 during resuscitation (12).The assessment of long-term neurologic handicap following HI is of paramount clinical value to define the ultimate efficacy of Re-O2 versus Re-Air in an asphyxiated subject. There are no reports on late neurologic outcome and reoxygenation strategy following asphyxia. This work was undertaken to provide experimental data on short-and long-term neuropathological and neurofunctional outcomes in HIaffected mice re-oxygenated with either 100% O 2 or RA immediately following the index event. MATERIALS AND METHODSMurine model of HI. Three day old (p3) C57/BL6J mice of both genders were purchased from Jackson Laboratories (Bar Harbor, ME) with their birth mothers. All research was conducted according ...

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confidence: 92%

Reoxygenation with 100% Oxygen Versus Room Air: Late Neuroanatomical and Neurofunctional Outcome in Neonatal Mice with Hypoxic-Ischemic Brain Injury

et al. 2006

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“…One major difference between birth asphyxia and the present model is that in the former the partial carbon dioxide tension of arterial blood (PaCO 2 ) is elevated. Restoration of cerebral blood flow during reoxygenation differs whether it starts out with a high or as in the present study a relatively low PaCO 2 (16). In resuscitated newborns infants, we also know that the time of reoxygenation often does not last more than a few minutes.…”

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confidence: 47%

Newborn resuscitation: should we oxygenate or not?

Saugstad¹

2008

American Journal of Physiology-Heart and Circulatory Physiology

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HOW SHOULD WE OXYGENATE newborn and infants suffering from hypoxia and ischemia? Is it harmful to use 100% O 2 ? It may seem odd to question a practice that has been carried out for so long, seemingly without any adverse effects. The case is, however, that after the practice of routinely using 100% O 2 for newborn resuscitation was examined, many serious potentially harmful effects have to date been described (for review, see Ref. 13).Fabian et al.(1) add new information to the topic of how asphyxiated newborns should be reoxygenated (1). By inducing unilateral brain ischemia and hypoxia in newborn (7 day) rats, they showed that cerebral blood flow in the ischemic cortex declined following resuscitation with 100% O 2 but not with ambient air. These findings in hyperoxic animals were accompanied by a reduction in perivascular production of nitric oxide (NO). Intraperitoneal injection with tetrahydrobiopterin (BH 4 ) increased cerebral blood flow during hyperoxic resuscitation. This was followed by increased perivascular NO and reduced perivascular O 2 Ϫ . The authors suggest that hyperoxia uncouples perivascular NO synthase (NOS), probably endothelial NOS, leading to a reduced NO and increased O 2 Ϫ production. An injection of apocyanin, which is an inhibitor of NADPH oxidase, also increased NO and reduced O 2 Ϫ , indicating that an oxidative burst may be of importance in neonatal hypoxic-ischemic brain injury.This study confirms that a hyperoxic resuscitation of newborns may reduce the restoration of cerebral blood flow and therefore may be detrimental. But it also indicates that BH 4 and perhaps also apocyanin should be interesting agents to test out in similar models to prevent such potentially harmful effects.For many reasons one should be careful drawing firm conclusions from newborn rats to newborn human infants. One major difference between birth asphyxia and the present model is that in the former the partial carbon dioxide tension of arterial blood (PaCO 2 ) is elevated. Restoration of cerebral blood flow during reoxygenation differs whether it starts out with a high or as in the present study a relatively low PaCO 2 (16). In resuscitated newborns infants, we also know that the time of reoxygenation often does not last more than a few minutes. A reoxygenation time of 2 h as in the study of Fabian et al. (1) therefore may not be relevant for newborns. On the other hand, such a long exposure to hyperoxia is not rare in the intensive care of children outside the immediate newborn period. A recent study by Koch et al. (8) showed that postischemic and posthypoxic hyperoxic exposure may have shocking effects on the brain. These authors found a dramatic augmented cerebral injury in 2-wk-old mice exposed to unilateral carotid ligation and hypoxia already after 30 min of hyperoxic-reoxygenation compared with reoxygenation with ambient air.

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“…Birth asphyxia is associated with fluctuations in CBF in the early post-resuscitation period [21]. Monitoring PCO 2 is not only important to avoid fluctuations in CBF and but also to maintain moderately elevated PaCO 2 during the first minutes of resuscitation to restore CBF [22,23]. In addition elevated PCO 2 may be beneficial and is associated with higher 5 minute apgar scores after moderate acidemia [24].…”

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confidence: 99%

Continuous End-Tidal Carbon Dioxide Monitoring during Resuscitation of Asphyxiated Term Lambs

et al. 2016

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Background: The Neonatal Resuscitation Program (NRP) recommends close monitoring of oxygenation during the resuscitation of newborns using a pulse oximeter. However, there are no guidelines for monitoring carbon dioxide (CO₂) to assess ventilation. Considering that cerebral blood flow (CBF) correlates directly with PaCO₂, continuous capnography monitoring of end-tidal CO₂ (ETCO₂) may limit fluctuations in PaCO₂ and, therefore, CBF during resuscitation of asphyxiated infants. Objective: To evaluate whether continuous monitoring of ETCO₂ with capnography during resuscitation of asphyxiated term lambs with meconium aspiration will prevent fluctuations in PaCO₂ and carotid arterial blood flow (CABF). Methods: Fifty-four asphyxiated term lambs with meconium aspiration syndrome were mechanically ventilated from birth to 60 min of age. Ventilatory parameters were adjusted based on clinical observation (chest excursion) and frequent arterial blood gas analysis in 24 lambs (control group) and 30 lambs (capnography group) received additional continuous ETCO₂ monitoring. Left CABF was monitored. We aimed to maintain PaCO₂ between 35 and 50 mm Hg and ETCO₂ between 30 and 45 mm Hg. Results: There was a significant correlation between ETCO₂ and PaCO₂ (R = 0.7, p < 0.001), between PaCO₂ and carotid flow (R = 0.52, p < 0.001) and between ETCO₂ and carotid flow (R = 0.5, p < 0.001). PaCO₂ and CABF during the first 60 min of age showed significantly higher fluctuation in the control group compared to the capnography group. Conclusion: Continuous monitoring of ETCO₂ using capnography with mechanical ventilation during and after resuscitation in asphyxiated term lambs with meconium aspiration limits fluctuations in PaCO₂ and CABF and may potentially limit brain injury.

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Reoxygenation with 100 or 21% Oxygen after Cerebral Hypoxemia-Ischemia-Hypercapnia in Newborn Piglets

Cited by 48 publications

References 28 publications

Reoxygenation with 100% Oxygen Versus Room Air: Late Neuroanatomical and Neurofunctional Outcome in Neonatal Mice with Hypoxic-Ischemic Brain Injury

Reoxygenation with 100% Oxygen Versus Room Air: Late Neuroanatomical and Neurofunctional Outcome in Neonatal Mice with Hypoxic-Ischemic Brain Injury

Newborn resuscitation: should we oxygenate or not?

Continuous End-Tidal Carbon Dioxide Monitoring during Resuscitation of Asphyxiated Term Lambs

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