Published online August 1, 2006
PEDIATRICS Vol. 118 No. 2 August 2006, pp. 789-792 (doi:10.1542/peds.2006-0832)

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COMMENTARY

Oxygen for Newborn Resuscitation: How Much Is Enough?

Ola Didrik Saugstad, MD, PhD^a, Siddarth Ramji, MD^b and Max Vento, MD, PhD^c

^a Department of Pediatric Research, Rikshospitalet University Hospital, Oslo, Norway
^b Department of Pediatrics, Maulana Azad Medical College, New Delhi, India
^c Servicio de Neonatologia, Hospital Universitario Materno-Infantil La Fe, Valencia, Spain

Abbreviations: AHA, American Heart Association • ILCOR, International Liaison Committee on Resuscitation

The new guidelines for newborn resuscitation from the American Heart Association (AHA), the International Liaison Committee on Resuscitation (ILCOR), and the European Resuscitation Council are based on the International Consensus Conference on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations of 2005.^1,2 Since the publication of the previous guidelines from the ILCOR and AHA in 1999 and 2000,^3,4 controversial issues within neonatal resuscitation have been identified, and a consensus was reached on (1) the role of supplementary oxygen, (2) peripartum management of meconium, (3) ventilation strategies, (4) devices to confirm placement of an advanced airway, (5) medications, (6) maintenance of body temperature, (7) postresuscitation management, and (8) considerations for withholding and discontinuing resuscitation. In this commentary we discuss the use of supplementary oxygen only.

When considering the guidelines provided by the AHA in 1992, the change in attitude regarding use of supplementary oxygen has been substantial. In 1992 it was clearly stated that resuscitation should be conducted with oxygen and that such a brief exposure of pure oxygen is not harmful: "Hypoxia is nearly always present in the newborn requiring resuscitation at birth. Therefore, if cyanosis, bradycardia, or other signs of neonatal distress are noted in a breathing newborn during stabilization, early administration of 100% oxygen is important."⁵ In addition: "The hazards of administering too much oxygen during the brief period required for resuscitation should not be a concern."⁵ In the AHA guidelines from 2000 it still was stated that 100% oxygen should be used if ventilation is needed: "If assisted ventilation is required, 100% oxygen should be delivered by positive pressure ventilation" and "[i]f supplemental oxygen is not available, resuscitation of the newly born infant should be initiated with positive pressure ventilation and room air."⁴ At that time it was argued that more data were needed before a change in practice using less oxygen than 100% could be recommended. However, if oxygen was not available, it was acceptable to use room air. This represented an important change in attitude since 1992.

According to the AHA 2000 guidelines, 5 questions should be asked and answered at every delivery: Is the amniotic fluid clear of meconium? Is the infant breathing or crying? Is there good muscle tone? Is the color pink? Was the infant born at term? If the answer to any of these questions is no, resuscitation should be considered. In 2005 the question of whether the infant is pink was taken out. The AHA clearly understood that it was unfortunate to mention pink color, because we now know that newly born infants are not supposed to be pink in the first minutes of life.⁶ Still, the AHA in 2005 maintained that "supplementary oxygen is recommended whenever positive-pressure ventilation is indicated for resuscitation; free flow oxygen should be administered to infants who are breathing but have central cyanosis (Class indeterminate)."¹ This is somewhat modified in the next sentence: "The standard approach to resuscitation is to use 100%, and some may start with no supplementary oxygen (ie, room air). There is evidence that employing either of these practices during resuscitation of neonates is reasonable."¹

The substantial international change in attitude toward use of less oxygen for resuscitation of the newly born infant is perhaps demonstrated clearer in the conclusion of the new guidelines as published by the ILCOR: "there is currently insufficient evidence to specify the concentration of oxygen to be used at initiation of resuscitation."² Emphasis is instead put on establishing adequate ventilation: "Once adequate ventilation is established, if the heart rate remains low, there is no evidence to support or refute a change in the oxygen concentration that was initiated."² It may add to an uncertainty because the AHA and ILCOR versions may seem contradictive to some extent. A contradiction may also be found because the ILCOR does not recommend change of the oxygen concentration initiated, whereas the AHA recommends that "oxygen is available to use if there is no appreciable improvement within 90 seconds after birth."^1,2

As far as we understand, both versions leave the choice to the clinician or individual institution of choosing the initial concentration of supplementary oxygen.

Provided it is correct that the optimal oxygen concentration for newly born infants is not known, these guidelines, and especially the ILCOR version, are at the present stage appropriate and wisely phrased. The clinician is now given freedom to choose an oxygen concentration that meets the patient's individual needs.

However, it can be questioned whether it is correct to state that there is currently insufficient evidence to specify the concentration of oxygen to be used at initiation of resuscitation. Regarding the issue of 100% vs 21% O₂, it was concluded in a Cochrane review that uncertainty exists.⁷ Such a review should be based on clinical data only; the same authors felt that addition of experimental data so strongly demonstrates the ill effects of pure oxygen that they (in another article) recommended to start out with room air and provide extra oxygen after 90 seconds if needed.⁸

In our opinion, there are now sufficient data to state that pure oxygen should be avoided at the initiation of newborn resuscitation. Clinical data have demonstrated that 100% oxygen compared with room air for newborn resuscitation

• increases neonatal mortality (40% also in developed countries)⁹;
  
• increases oxidative stress at least 4 weeks after birth¹⁰;
  
• increases myocardial and kidney injury¹¹;
  
• delays recovery (significantly lower 5-minute Apgar score and heart rate, prolonged time to first cry and breath)⁹;
  
• increases time in need of resuscitation and oxygen¹⁰; and
  
• is associated with a higher risk for childhood leukemia and cancer.^12,13
  Animal studies have shown that 100% oxygen compared with room air
  • increases neurologic injury and brain injury^14,15;
    
  • induces inflammation in the lung, heart, and brain^16–19;
    
  • increases pulmonary resistance and reactivity²⁰;
    
  • increases oxidative stress^21–23; and
    
  • activates transcription factors.²⁴
    
  
  

Some animal studies have shown that microcirculation in the brain and normalization of metabolic markers as glutamate are restored faster with 100% than 21% O₂.²⁵ This study was performed with normocapnia. In other animal studies, such differences were not found,^26–28 and it seems that moderate hypercapnia reduces any such difference.²⁹

In total, 6 clinical studies including >1800 infants enrolled in either a room-air or 100%-oxygen arm have now been published,^10,30–34 and meta-analyses show a dramatic reduction in neonatal mortality in the infants resuscitated with room air.^7–9 Therefore, most available data strongly and clearly point in one direction: pure oxygen is toxic even for a brief (minutes) period of time postpartum and should be avoided if possible. For this reason, in a recent editorial Paneth³⁵ gave a warning for initiating resuscitation with pure oxygen and instead recommended the use of room air.

We conclude that it has been demonstrated that initiation of resuscitation of the newborn infant can be conducted with room air, and, in most cases, it should not be started with 100% O₂. Whether any oxygen concentration between 21% and 100% is more optimal is not known. However, 10 years of practice in Sweden (in which initiation with 40% oxygen has been recommended the last 10 years) has demonstrated that 40% is safe. In Europe, more and more centers are now starting with an oxygen concentration between 21% and 40%. This requires oxygen blenders, which should be installed in all 5000 delivery units in the United States. We recommend that oxygen always be available if possible as a backup and that we switch to oxygen after 90 seconds if there is poor response, as recommended by the AHA. This is despite the fact that nonresponders have a poor prognosis regardless of whether they are resuscitated with 21% or 100% O₂ as the first choice.⁶

There are still a number of unanswered questions in this field. We may not know the optimal oxygen saturation and, consequently, the optimal fraction of inspired oxygen in the first minutes of life. We do not know if the normal development in arterial oxygen saturation, which now is well defined for the first 10 minutes after birth, is the optimal aim, and even less is known regarding premature infants. Therefore, there is still substantial need for research in this field. Since 1992 our understanding of the ill effects of brief oxygen exposure at birth has been increased significantly. This is reflected in the quite dramatic changes in attitudes and recommendations in the use of oxygen for resuscitation of the newly born infant from 1992–2005. Within the next 5 years and before new guidelines are published around 2010, this issue should be penetrated in even more depth. Until then, much freedom is given for the individual clinician and institution to choose the initial oxygen concentration. From what is known, we strongly warn against starting out with 100% O₂ provided the infant's lungs are healthy. If supplementary oxygen is used, blenders should be installed in every delivery unit so that oxygen can be reduced to the lowest level needed as fast as possible.

	FOOTNOTES

 
Accepted Mar 21, 2006.

Address correspondence to Ola Didrik Saugstad, MD, PhD, Department of Pediatric Research, Rikshospitalet University Hospital, 0027 Oslo, Norway. E-mail: o.d.saugstad{at}medisin.uio.no

The authors have indicated they have no financial relationships relevant to this article to disclose.

Opinions expressed in these commentaries are those of the authors and not necessarily those of the American Academy of Pediatrics or its Committees.

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