Hydrogen Peroxide Production in Leukocytes during Cerebral Hypoxia and Reoxygenation with 100% or 21% Oxygen in Newborn Piglets

Kutzsche, Stefan; Ilves, Pilvi; Kirkeby, Ole J.; Saugstad, Ola Didrik

doi:10.1203/00006450-200106000-00020

Cited by 67 publications

(24 citation statements)

References 36 publications

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“…These results are in line with studies showing protective effects of HT (2-4,11-15) and with studies demonstrating harmful effects of hyperoxic reoxygenation (18)(19)(20)(21). The new and important knowledge added by this study is the effect of the combination of these two important interventions recommended by the International Liaison Committee on Resuscitation guidelines (10).…”

Section: Articlessupporting

confidence: 90%

“…Evidence from animal studies shows that supplemental oxygen during resuscitation causes significant hyperoxia in the newborn brain (16,17), with increased generation of reactive oxygen species (18), oxidative stress (19), inflammation (20), and cerebral injury (19,21,22). Clinical studies have shown that resuscitation with 100% oxygen has no advantage over air but causes increased mortality (23) and increased time to first breath and/ or cry (24)(25)(26).…”

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confidence: 99%

“…It is not known whether supplemental oxygen during resuscitation affects hypothermic neuroprotection, but resuscitation with oxygen and HT have opposite effects on important contributors in the cascades after hypoxia-ischemia (HI), such as the generation of reactive oxygen species (13,18) and the inflammatory response (15,20). We used an established neonatal rat model to study whether air or 100% oxygen during 30-min reoxygenation after HI would affect the development of hypoxic-ischemic brain injury, and whether supplemental oxygen during reoxygenation would influence the neuroprotective effect of postresuscitation HT.…”

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confidence: 99%

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Resuscitation with 100% oxygen increases injury and counteracts the neuroprotective effect of therapeutic hypothermia in the neonatal rat

et al. 2012

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IntroductIon: Mild therapeutic hypothermia (hT) reduces brain injury in survivors after perinatal asphyxia. Recent guidelines suggest that resuscitation of term infants should be started with air, but supplemental oxygen is still in use. It is not known whether supplemental oxygen during resuscitation affects the protection offered by subsequent hT. results: Wilcoxon median (95% confidence interval) hippocampal injury scores (range 0.0-4.0; 0 to ≥90% injury) were 21% O 2 normothermia (NT): 2.00 (1.25-2.50), 21% O 2 hT: 1.00 (0.50-1.50), 100% O 2 NT: 2.50 (1.50-3.25), and 100% O 2 hT: 2.00 (1.25-2.50). although hT significantly reduced hippocampal injury (B = -0.721, seM = 0.297, P = 0.018), reoxygenation with 100% O 2 increased injury (B = +0.647, seM = 0.297, P = 0.033). Regression constant B = 1.896, seM = 0.257 and normally distributed residuals. dIscussIon: We confirm an ~50% neuroprotective effect of therapeutic hT in the neonatal rat. Reoxygenation with 100% O 2 increased injury and worsened reflex performance. hT was neuroprotective whether applied after reoxygenation with air or 100% O 2 . however, hT after 100% O 2 gave no net neuroprotection. Methods: In an established neonatal rat model, hypoxiaischemia (hI) was followed by 30-min reoxygenation in either 21% O 2 or 100% O 2 before 5 h of NT (37 °c) or hT (32 °c). The effects of hT and 100% O 2 on histopathologic injury in the hippocampus, basal ganglia, and cortex, and on postural reflex performance 7 d after the insult, were estimated by linear regression.P erinatal asphyxia occurs in 1 to 6 per 1,000 term human births (1) and is an important cause of severe neurologic impairment and neonatal mortality. Therapeutic hypothermia (HT) has emerged as a neuroprotective therapy in both newborn animal models (2-4) and clinical trials (5-7). The collective evidence from these studies confirms that mild therapeutic HT improves outcome in hypoxic-ischemic encephalopathy, a condition in which ~50% of cooled infants normally die or have significant neurologic disability (8) as compared with before the advent of HT treatment when ~65% had poor outcome. In the UK, the National Institute for Health and Clinical Excellence has declared that HT should be used as standard of care after perinatal asphyxia (9). HT after perinatal asphyxia is also recommended by the recent 2010 International Resuscitation Guidelines (International Liaison Committee on Resuscitation) (10). HT suppresses many of the pathways that lead to delayed energy failure and cell death after hypoxia (11,12), including generation of reactive oxygen species (13), excitotoxicity (14), and the inflammatory response (15).Supplemental oxygen was previously recommended for resuscitation of the asphyxiated newborn infant, but after the changes in the 2010 International Liaison Committee on Resuscitation guidelines, it is now recommended that resuscitation of the term infant is best started with air, rather than pure oxygen (10). Evidence from animal studies shows that supplemental oxygen during resuscitation...

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Section: Articlessupporting

confidence: 90%

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confidence: 99%

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confidence: 99%

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Resuscitation with 100% oxygen increases injury and counteracts the neuroprotective effect of therapeutic hypothermia in the neonatal rat

et al. 2012

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“…In this and a series of subsequent experiments, we confirmed that 21% oxygen is as efficient as 100% oxygen for resuscitation. [10][11][12][13][14][15][16] The findings in the newborn piglet were consistent, and I realized that the time had come to test our hypothesis in a clinical study. Siddarth Ramji in New Delhi immediately agreed to participate, and the pilot clinical trial was carried out in India, enrolling 84 newborn infants randomized to room air or 100% oxygen resuscitation.…”

Section: Discovery Through a Failurementioning

confidence: 55%

Why are we still using oxygen to resuscitate term infants?

Saugstad

2010

J Perinatol

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This article summarizes the historical background for the use of oxygen during newborn resuscitation and describes some of the research and the process of changing the previous practice from a high-to a low-oxygen approach. Findings of a recent Cochrane review suggest that more than 100 000 newborn lives might be saved globally each year by changing from 100 to 21% oxygen for newborn resuscitation. This estimate represents one of the largest yields for a simple therapeutic approach to decrease neonatal mortality in the history of pediatric research. Available data also suggest that, for the very low birth weight infant, use of the low-oxygen approach should be considered with the understanding that some of the smallest and sickest preterm neonates will need some level of oxygen supplementation during the first minutes of postnatal life. As more data are needed for the very preterm population, creation of strict guidelines for these infants would be premature at present. However, it can be stated that term and late preterm infants in need of resuscitation should, in general, be started on 21% oxygen, and if resuscitation is not started with 21% oxygen, a blender should be available, enabling the administration of the lowest FiO 2 possible to keep heart rate and SaO 2 within the target range. For extremely low birth weight infants, initial FiO 2 could be between 0.21 and 0.30 and adjusted according to the response in SaO 2 and heart rate.

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“…An infant suffering severe perinatal asphyxia usually has poor color (cyanosis), perfusion, responsiveness, muscle tone, and respiratory effort, as reflected in a low 5 minute Apgar score. 3 Extreme degrees of asphyxia can cause cardiac arrest and death. If resuscitation is successful, the infant is usually transferred to a neonatal intensive care unit.…”

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confidence: 99%

Effect of hypothermia for perinatal asphyxia on childhood outcomes

Jose¹,

Ismael²

2017

Int J Contemp Pediatr

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Background: Perinatal asphyxia, neonatal asphyxia or birth asphyxia is the medical condition resulting from deprivation of oxygen to a new born infant that lasts long enough during the birth process to cause physical harm, usually to the brain. This study was performed to evaluate study population who were 6 to 8 years of age to determine whether the application of moderate hypothermia after perinatal asphyxia is associated with long term benefits.Methods: This study was a randomised, controlled trials which consisted of infants who were admitted with moderate and severe encephalopathy within 6 hours after birth after an acute perinatal event, with acidosis or resuscitation. Infants were assigned to undergo whole body hypothermia at 33ºC for 72 hours or to undergo usual care randomly.Results: All maternal baseline characteristics and Neonatal characteristics are non significant in both groups. APGAR score ≤5 is significant at 10mins in comparison. cerebral palsy were 18% and 25%, respectively, the rates of blindness were 1% and 4% the rates of hearing impairment (requiring aids) were 5.4% and 12.8%. There were no significant between-group differences in the level of disability among all survivors or in motor function among the 45 nondisabled children. Among children who had moderate or severe disability at 18 months, the corresponding rates at 6 to 7 years of age were 88% in the hypothermia group and 95% in the control group. All the children who had moderate-to-severe cerebral palsy at 18 months continued to be affected at 6 to 7 years in both groups. There was no significant between-group difference with respect to IQ scores that were measured on a continuous scale and other scores, with the exception of 1 of the 11 scores compared (attention and executive function, P=0.03). There were also no significant differences between groups in mean scores on the index of health care status derived from parental assessments or in parental scores for children’s strengths and difficulties and ADHD The mean difference in the academic achievement score favored the hypothermia group but was not significant.Conclusions: Moderate hypothermia after perinatal asphyxia resulted in improved neurocognitive outcomes in middle childhood.

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Hydrogen Peroxide Production in Leukocytes during Cerebral Hypoxia and Reoxygenation with 100% or 21% Oxygen in Newborn Piglets

Cited by 67 publications

References 36 publications

Resuscitation with 100% oxygen increases injury and counteracts the neuroprotective effect of therapeutic hypothermia in the neonatal rat

Resuscitation with 100% oxygen increases injury and counteracts the neuroprotective effect of therapeutic hypothermia in the neonatal rat

Why are we still using oxygen to resuscitate term infants?

Effect of hypothermia for perinatal asphyxia on childhood outcomes

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