Resuscitation of newborn infants with 100% oxygen or air: A systematic review and meta-analysis

Article Outline

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Davis PG, Tan A, O'Donnell CP, Schulze A. Lancet 2004;364:1329-33.

Context International consensus statements for resuscitation of newborn infants recommend provision of 100% oxygen with positive pressure if assisted ventilation is required. However, 100% oxygen exacerbates reperfusion injury in animals and reduces cerebral perfusion in newborn babies.

Objectives To establish whether resuscitation with air decreased mortality rates or neurologic disability in newborn infants compared with 100% oxygen.

Design Systematic review and meta-analysis of trials that compared resuscitation with air versus 100% oxygen, combining data for similar outcomes in the analysis using a fixed-effects model.

Main outcome measures Failure to intubate and death.

Study identification Using methods of the Cochrane Collaboration, the authors' initial search identified 350 potentially eligible clinical trials and 12 review articles.

Studies reviewed Ten full-text articles were reviewed and five trials (two masked and three unmasked), totaling 1302 infants, fulfilled inclusion criteria.

Results Most babies were born at or near term in developing countries. In the three unmasked studies, infants resuscitated with room air who remained cyanotic and bradycardic were switched to 100% oxygen at 90 seconds. The masked studies allowed crossover to the other gas during the first minutes of life. Although no individual trial showed a difference in mortality rates, the pooled analysis showed a significant benefit for infants resuscitated with air (relative risk, 0.71 [95% CI, 0.54 to 0.94]; risk difference, −0.05 [−0.08 to −0.01]). The effect on long-term development could not be reliably determined because of methodologic limitations in the one study that followed up infants beyond 12 months of age.

Conclusions For term and near-term infants, the authors reasonably conclude that air should be used initially, with oxygen as backup if initial resuscitation fails. The effect of intermediate concentrations of oxygen at resuscitation needs to be investigated. Future trials should include and stratify for premature infants.

Comment In this systematic review, Davis et al conclude that for every 20 babies resuscitated with 100% oxygen, one additional baby will die. This number should give all who resuscitate infants reason to pause. If this number needed to treat is even close to true, then every pediatrician who cares for or has cared for a newborn infant has contributed to excessive mortality rates in newborn infants. For the individual, the easiest way out of this uncomfortable feeling is to invoke the “not in my nursery” excuse. Evidence-based medicine provides us with a structured way of examining possible reasons for invoking this excuse. In asking a good question, one defines a population. Davis describes seemingly simple and straightforward general inclusion criteria that include newborn infants with apnea, bradycardia, or both. Two of the studies also use “unresponsive to stimulation” as additional criteria, suggesting that many of these newborn infants are in “secondary” apnea. The infants are described by Davis et al as “moderately asphyxiated,” with a mean pH>7.02. These inclusion criteria describe infants that one might expect to encounter regularly in large delivery centers. However, further insight into the population is gained by looking at the results, where we find 13.8% (1/7) of all infants entered into the study died. If one accepts the “moderately asphyxiated” definition and the 1/7 mortality rate, one must accept that there is something else about these infants or the care these infants received that is fundamentally different from the experience in most modern intensive care units. Another curiosity noted is that although death was more common in infants resuscitated in 100% oxygen, all measures of morbidity were not different between the groups. This absence of covariance seems counterintuitive. In most modern intensive care units, it is unusual for a moderately asphyxiated infant to die. If these studies are replicated in nurseries in developed nations, will we find changes in morbidity but not mortality (ie, a shift from excessive death to excessive morbidity)? Is our ability to prevent death masking an outcome that will be difficult to measure (long-term outcome)? In this systematic review, the difference in primary outcome (death) is compelling. Similar studies should be replicated outside of the developing world. Until then, we should be worried about what is the proper means of resuscitating an infant. This worry should prompt reflection and more attention to the way each individual infant is resuscitated.