A new guideline from the ATS has been published, which gives guidelines for home oxygen therapy for children, one large group of which is, of course, babies with bronchopulmonmary dysplasia. Hayes D, Jr., et al. Home Oxygen Therapy for Children. An Official American Thoracic Society Clinical Practice Guideline. Am J Respir Crit Care Med. 2019;199(3):e5-e23.
The overall recommendation is that children with chronic hypoxemia should receive home oxygen therapy.
It is hard to argue with a recommendation like that! The big question of course is, how to define chronic hypoxemia? It should, I would think, be defined by a a level of oxygenation which has been shown to have an adverse clinical impact on the child, on their growth or development or chronic illness.
You can only really determine that by performing controlled trials where children with various levels of oxygenation receive either home oxygen or no O2. You would have to start with relatively higher levels of saturation to ensure safety, and then test lower levels until you find a clinical impact.
Of course, we don’t have good sequential data like that, but what do we have?
The guidelines authors reviewed the literature and found 11 observational studies comparing outcomes of BPD kids who had home oxygen therapy (which they abbreviate as HOT). Ten of them were eliminated as being biased, so the only evidence they have to support their recommendations is from a 1996 study. (Moyer-Mileur LJ, et al. Eliminating sleep-associated hypoxemia improves growth in infants with bronchopulmonary dysplasia. Pediatrics. 1996;98(4 Pt 1):779-83).
In that study infants who were already home on oxygen were admitted overnight to a clinical research unit and taken off oxygen for at least 8 hours. They were then divided into 3 groups depending on their saturations.
Group 1 consisted of 11 infants whose Sao2 decreased to between 88% and 91 % for more than 1 hour of sleep. Group 2 consisted of 34 infants whose sustained minimum Sao2 was 92% or greater for the entire recording. Group 3 consisted of 18 infants whose sustained minimum Sao2 was less than 88% for more than 1 hour of sleep. [HOT] for infants in groups I and 2 was stopped, but it was continued for infants in group 3. After a subsequent prolonged slep Sao2 evaluation, all but 6 infants in group 3 graduated to groups I and 2, and [HOT] was stopped.
Which sound like a reasonable design for a prospective observational study, my main question being what was done about intermittent desaturations? Certainly at discharge many of our babies have baseline saturations in room air above 92%, but have multiple brief, or not so brief, desaturations to below 88%. This report only refers to sustained desaturations which make up 12.5% of the 8 hour sleep study.
The age at which the trial of stopping HOT was done varied between 4 months average in group 1, 6 months in group 2, and 9 months in the infants who were initially in group 3. The major outcome reported for the infants is their growth, although hospitalisations were recorded, they don’t appear to be reported.
The study showed that group 1 infants, those with sustained saturations for more than an hour below 92% when O2 was stopped during an overnight study, had a fairly dramatic falling off of their growth after HOT was discontinued by the time of their next clinical visit, 6 to 8 weeks later. Their energy intake was the same, but their weight gain dropped from 16 g/kg/d to 4 g/kg/d. There were a total of 14 babies in that group.
So I guess a reasonable recommendation, based only on this one study including 14 relevant babies, could be that, with not much confidence, after a few months of HOT, oxygen could be stopped if a prolonged sleep saturation recording did not have a sustained period of more than 1 hour of desaturation to below 92%, and that infants with lower sustained saturations (to between 88 and 92%) risk a short term period of reduced growth if HOT is stopped, but it should state that there is no information about how prolonged that growth reduction might be or any other health effects.
This is the recommendation:
For patients with BPD complicated by chronic hypoxemia, we recommend that HOT be prescribed (strong recommendation, very low-quality evidence). Chronic hypoxemia is defined as either 1) greater than or equal to 5% of recording time spent with an SpO2 less than or equal to 93% if measurements are obtained by continuous recording or 2) at least three separate findings of an SpO2 less than or equal to 93% if measurements are obtained intermittently.
The ATS guideline also gives an instructive interpretation of what they mean by a strong recommendation:
|A Strong Recommendation Conveys . . .||A Conditional Recommendation Conveys . . .|
|It is the right course of action for >95% of patients.||It is the right course of action for >50% of patients but may not be right for a sizable minority.|
|“Just do it. Don’t waste your time thinking about it, just do it.”||“Slow down, think about it, discuss it with the patient.”|
|You would be willing to tell a colleague that he or she did the wrong thing if he or she did not follow the recommendation.||You would NOT be willing to tell a colleague that he or she did the wrong thing if he or she did not follow the recommendation because there is clinical equipoise.|
|The recommended course of action may make a good performance metric.||The recommended course of action would NOT make a good performance metric.|
I find that table incredible!!
Based on very near to no data whatsoever, the ATS tell you that you should be like sheep and not even think about their recommendation, (“Just do it”: was this sponspored by NIKE?) and you should criticise your colleagues if they did something different. You are not supposed to even discuss starting O2 with the parents!! (Shared decision-making anyone?)
The recommendations are nothing like the only study that they use to support their recommendations! 5% of recording time at <94% is the recommendation based on a study which showed an impact (of questionable long term health significance) for children with a sustained saturation <92% for at least 1 hour, i.e. 12.5% of recording time.
This recommendation, if followed, will mandate thoughtless imposition of home oxygen therapy on tens of thousands of babies.
In addition (and of course I always find some additions) this is based on a single >20 year old observational study. By relying on this, if they followed their statement development guidelines, they imply that there are no randomized trials. But that is not the case, of course : Askie LM, et al. Oxygen-saturation targets and outcomes in extremely preterm infants. The New England journal of medicine. 2003;349(10):959-67.
In the first BOOST trial, 350 preterm babies with evolving lung disease born at less than 30 weeks were randomzied to higher or lower saturations if they still needed oxygen at 32 weeks. Saturations of either 95-98% or 91-94% were targeted, until the infant no longer needed oxygen. So this impacted on how many children went home on oxygen, what saturations they targeted at home, and how long they stayed on oxygen after discharge. 30% of the high sat target group went home on oxygen, compared to 17% of the low target group.
That study showed no health benefits of higher saturation targets, and no impact on growth. There was a hint of worse pulmonary outcomes with higher saturations. Of course, some babies in each group had acceptable saturations in no oxygen prior to discharge, but no clinical benefits were found in the overall study
In the STOP-ROP trial 650 very preterm babies with threshold retinopathy who needed oxygen were randomized to higher (96-99%) and lower (89-94%) saturation targets, which was continued until RoP was regressing, which was almost always by 3 months corrected age, by which time there were substantial numbers of babies still on oxygen, 47% vs 37%, mostly, but not all, at home (13% vs 7% remained hospitalized). During those 3 months there was no impact on growth.
Again in contrast to what is stated by the ATS guidelines, who claim that there are no adverse effects of home oxygen, infants in both of these trials note an increase in some adverse pulmonary outcomes. In BOOST there were more late pulmonary deaths, and in STOP-ROP there were more infants with “pneumonia/CLD events” in the group who had more prolonged oxygen and were more likely to go home of oxygen.
Proof of safety of the oxygen therapy thresholds mandated by the ATS (mandate is not too strong a word given their definition of what they mean by strong recommendation) does not exist. Lower thresholds might be safer, and would lead to fewer children needing home oxygen.
It is incoherent to have a strong recommendation which is supported by extremely low quality data, or indeed, as in this case, no data at all. A recommendation to discuss the possible pros and cons with parents, a clear outline of what those pros and cons might be, a more careful analysis of potential and proven impacts, positive and negative, and an outline of what data are needed to be able to provide evidence-based guidelines, and a commitment to fund such trials would serve our patients much better than this.
Of course some babies need and benefit from home oxygen, but providing HOT to many babies who might well not need it, and could potentially suffer adverse effects, is not the way to ensure that those who truly benefit will actually receive it.