Home oxygen therapy: the jury is still in session.

Abstract

In the last issue of The Journal of Perinatology (2004;24:36–40), Ellsbury and colleagues ask a controversial question about oxygen therapy for infants with chronic lung disease: Just how much is appropriate and which infants should be treated? After polling the Vermont Oxford Network participants, the authors report that 43% of those responding would not choose to initiate home oxygen therapy in discharged preterm infants until oxygen saturations were less than 90%. Furthermore, once home oxygen therapy was initiated, oxygen saturation levels targeted by respondents varied between >84 and >98%. Even if there was no variability in treatment regimens of the infant in neonatal units, this article demonstrates that target oxygen saturation goals for the preterm headed home are very disparate. This discrepancy alone could potentially result in very different outcomes for graduates of neonatal units. The findings of Ellsbury et al. underscore the need to assess what we know about the risks and benefits of oxygen therapy for the former preterm graduate of the neonatal unit. However, it is equally important to focus on the limitations of the available data in order to determine the goals of future research efforts. A large percentage of the Vermont Oxford Network participants chose to reserve oxygen therapy for infants with oxygen saturations less than 90%, and for many, the initiation level was less than 88%. There may be some reluctance to consider an infant now ‘‘oxygen dependent’’ when prior saturation goals immediately after birth were lower due to the increased risk of retinal disease. Recent controlled trials might lead the practitioner to keep oxygen saturation goals low permanently, if cautious interpretation of those studies is not performed. For instance, in the Australian ‘‘BOOST’’ trial (Benefits of Oxygen Saturation Targeting), there were patients in a low oxygen saturation group (91 to 94% targets) and a high saturation group (95 to 98%) with no significant outcome differences in growth or major developmental handicaps. Patients in both experimental arms were sent home on oxygen with saturation targets of greater than or equal to 91%. The effect of oxygen saturation levels below 91% on long-term growth or development cannot therefore be inferred from that study. The former premature 2-month-old infant now has a new disease compared to the same infant at birth. Due to cancelled fetal growth, combined with development that has altered its trajectory, the disease risks and profiles for the ex-premature infant are dramatically different. Diminished lung volumes cause dramatic ventilation/perfusion mismatches with simple colds. Infants with bronchopulmonary dysplasia have unexpected episodes of significant oxygen saturation reductions while sleeping or feeding. We are now faced with critical questions concerning proper oxygen saturation targets for these former premature infants. What saturation level should be targeted to meet respiratory and cognitive requirements while not compromising tissue development? Should oxygen saturation goals be increased in the older developing preterm graduate of the neonatal unit? There may be significant risks to oxygen therapy as outlined below. Unfortunately, the threshold oxygen saturation that increases each risk is unknown. As demonstrated in animal studies, possible permanent blunting of ventilatory responses to hypoxia develops after exposure to high oxygen saturations at a critical developmental period. Theoretical problems resulting from a blunted response could lead to increased sleep disordered breathing, hypoxia with illness, or could contribute to a risk of death. The existence of this critical period, or its age of occurrence, in humans remains to be determined. Infants on high oxygen levels (target saturation1⁄4 95 to 99%) in the controlled ‘‘STOPROP’’ trial, which followed 649 preterm infants after 35 weeks postmenstrual age, demonstrated some retinal benefits after the development of the second phase of retinopathy of prematurity (ROP). On the down side, there was an increased incidence of pulmonary issues in that group compared to the lower oxygen target. In contrast, the BOOST trial that had an upper limit cutoff of 98% in the high oxygen saturation group did not see significant abnormal pulmonary outcomes in the two treatment arms. The preterm infant, cut off from protective placental factors, may demonstrate specific regulatory abnormalities of tissue development when exposed to the toxicity of hyperoxia. For example, the mechanism proposed for hyperoxia-induced tissue Johns Hopkins Hospital Department of Pediatrics, Pediatric Pulmonology, Baltimore, USA; Euloweod Division of Pediatric Respiratory Sciences, John Hopkins University, Baltimore, Maryland, USA.