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Editorial Indian Pediatrics 2003; 40:507-509 |
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Oxygen Therapy During Neonatal Resuscitation - Too Little or Too Much? |
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The use of 100% oxygen in resuscitation is intuitively appealing and was based on the logic that by maximising the gradient driving oxygen into hypoxic cells may speed recovery. However, we now know that most of the damaging effect following hypoxic injury occurs during period of hyperoxia and mediated through oxygen-derived free radicals. Indeed, experimental resuscitation with 100% oxygen has been noted to be associated with a variety of adverse reactions including increased generation of free radicals, decreased central nervous system sodium potassium ATPase function and decreased dopamine metabolism. There is also experimental animal evidence which suggests that, given a healthy pulmonary system, only 15% to 18% oxygen is needed for a successful resuscitation. This may explain the success of the age old practice of mouth to mouth resuscitation, and lends credence to the notion of using room air (21%) for resuscitation. There are a number of other theoretical considerations too. Babies grow perfectly well in-utero with arterial blood that is only 70 - 80% saturated. Why then do we persist in trying to keep their oxygen saturation after birth above 90%? Children with cyanotic congenital heart disease make the transition to the extra-uterine level without difficulty despite all we know about the effect that oxygen has on pulmonary vasculature and ductal tone. Why then do we fear that mild desaturation could dangerously compromise that transition?(2) Moreover, the physiological range of oxygen saturation in the umbilical cord of newborn infant is wide and skewed. In a recent study of cord blood samplings from 1281 vigorous newborn infants, the median umbilical arterial saturation was only 24.3% and the 2.5th centile was as low as 2.7%(3). Yet we started using oxygen for resuscitation because it seemed like a good idea, and now we use it because we always have. This is despite there being no evidence of a role for oxygen concentration above 21% during resuscitation of the newborn if the lungs were functioning adequately. Because newborn infants, especially preterms, have red blood cells that have a high oxygen affinity, the knowledge of the P90 (the partial pressure of oxygen, PaO2, required for 90% saturation of haemoglobin) provides useful information about optimal oxygenation. In a previous study, it was shown that mean P50 was 18.3 ± 0.9 mmHg (2.5 ± 0.3 kpa) and the P90 was 40.8 ± 3.6 mmHg (5.4 ± 0.5 kpa). This shows that when treating very low birth weight newborns with oxygen, a PaO2 of 41 mmHg (5.5 kpa) is enough to saturate 90% of hemoglobin at a physiological pH(4). Despite earlier suggestion that most newborn infants in need of resuscitation at birth could be resuscitated equally efficiently with room air as with 100% oxygen, the American Academy of Paediatrics along with American Heart Association and International Liaison Committee for Resuscitation (ILCOR) still recommended use of 100% oxygen in their last consensus statement published in 2000(5). The recommendation for 100% oxygen was based on logic and experience but more so because there were not enough published data to justify change in practice. Considerable progress has been made since then and sufficient evidence, both direct and indirect, are now available from recent clinical studies suggesting that keeping the oxygen therapy to an ‘acceptable’ minimum in newborn babies does not do any harm and may be even advantageous(6-10). In this issue of the Indian Paediatrics, Ramji and colleagues present the findings of a large trial in which they have compared the short term efficacy of room air versus 100% oxygen for resuscitation of asphyxiated newborns at birth(11). This was a multicentric quasi randomised controlled trial on a large sample size which would be more than sufficient to detect a difference in the primary outcome measure between the two groups with 95% power. The treatment allocation was not blinded because of practical reasons but both groups of infants were comparable and they are all accounted for. The study was approved by the participating institutions’ ethics committee and informed consent was obtained from parents prior to enrolment. The results of this study shows that there was no significant difference either in the primary or secondary outcome measures whether resuscitated with room air or 100% oxygen. Both groups had similar incidence of treatment failure according to a pre-defined criteria. Overall mortality was numerically higher in babies resuscitated with 100% oxygen but this difference was statistically not significant. The observations of the present study are similar to that of the previously reported studies(12-14) but provide further impetus for change in resuscitation guidelines for newborns. It will be a gross under-statement that these findings are relevant only for developing countries where oxygen may not be routinely available for resuscitation. Fetal asphyxia occurs globally, albeit less frequently in developed countries, but the biochemical cascade producing post-asphyxial damage remains the same. It seems that resuscitation of newborn still is more of an ‘art’ than ‘science’ and requires continuing research both at the level of basic science and clinical applications. Evaluation of innovative approaches to neonatal resuscitation, gained from diverse global perspectives, may also result in improvement of outcome in areas such as neurodevelopmental, after perinatal hypoxic-ischaemic injury which have proven refractory to current interventions. Continued co-operation on an international scale should help in ensuring that infants around the world can rapidly benefit from advances in neonatal resuscitation. It is not surprising that despite the recommendations made in 2000 by ILCOR that 100% oxygen continued to be used, it appears as if many have already changed their practises to some degree. Preliminary results from a recent international survey of a sample of academic centres disclosed that approximately 50% of the neonatologists responding from 13 countries reported that they already had begun to modify the percentage of oxygen used during neonatal resuscitation in their institutions(15). Purists will argue that we need further randomised controlled trial of as many as 7000 asphyxiated babies in order to achieve adequate statistical power to determine with confidence which of these oxygen concentrations (21% vs 100%) is most appropriate for resuscitation of newborns. Such a trial is possible through a collaborative, multicentric and possibly international effort but perhaps, we will be testing the wrong hypothesis(16). Sunil Sinha, |
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