As a Neonatologist I doubt there are many topics discussed over coffee more than BPD. It is our metric by which we tend to judge our performance as a team and centre possibly more than any other. This shouldn’t be that surprising. The dawn of Neonatology was exemplified by the development of ventilators capable of allowing those with RDS to have a chance at survival. As John F Kennedy discovered when his son Patrick was born at 34 weeks, without such technology available there just wasn’t much that one could do. As premature survival became more and more common and the gestational age at which this was possible younger and younger survivors began to emerge. These survivors had a condition with Northway described in 1967 as classical BPD. This fibrocystic disease which would cripple infants gave way with modern ventilation to the “new bpd”.
The disease has changed to one where many factors such as oxygen and chorioamnionitis combine to cause arrest of alveolar development along with abnormal branching and thickening of the pulmonary vasculature to create insufficient air/blood interfaces +/- pulmonary hypertension. This new form is prevalent in units across the world and generally appears as hazy lungs minus the cystic change for the most part seen previously. Defining when to diagnose BPD has been a challenge. Is it oxygen at 28 days, 36 weeks PMA, x-ray compatible change or something else? The 2000 NIH workshop on this topic created a new approach to defining BPD which underwent validation towards predicting downstream pulmonary morbidity in follow-up in 2005. That was over a decade ago and the question is whether this remains relevant today.
I don’t wish to make light of the need to track our rates of BPD but at times I have found myself asking “is this really important?” There are a number of reasons for saying this. A baby who comes off oxygen at 36 weeks and 1 day is classified as having BPD while the baby who comes off at 35 6/7 does not. Are they really that different? Is it BPD that is keeping our smallest babies in hospital these days? For the most part no. Even after they come off oxygen and other supports it is often the need to establish feeding or adequate weight prior to discharge that delays things these days. Given that many of our smallest infants also have apnea long past 36 weeks PMA we have all seen babies who are free of oxygen at 38 weeks who continue to have events that keep them in hospital. In short while we need to be careful to minimize lung injury and the consequences that may follow the same, does it matter if a baby comes off O2 at 36, 37 or 38 weeks if they aren’t being discharged due to apnea or feeding issues? It does matter for benchmarking purposes as one unit will use this marker to compare themselves against another in terms of performance. Is there something more though that we can hope to obtain?
When does BPD matter?
The real goal in preventing BPD or at least minimizing respiratory morbidity of any kind is to ensure that after discharge from the NICU we are sending out the healthiest babies we can into the community. Does a baby at 36 weeks and one day free of O2 and other support have a high risk of coming back to the hospital after discharge or might it be that those that are even older when they free of such treatments may be worse off after discharge. The longer it takes to come off support one would think, the more fragile you might be. This was the goal of an important study just published entitled Revisiting the Definition of Bronchopulmonary Dysplasia: Effect of Changing Panoply of Respiratory Support for Preterm Neonates. This work is yet another contribution to the pool of knowledge from the Canadian Neonatal Network. In short this was a retrospective cohort study of 1503 babies born at <29 weeks GA who were assessed at 18-21 months of age. The outcomes were serious respiratory morbidity defined as one of:
(1) 3 or more rehospitalizations after NICU discharge owing to respiratory problems (infectious or noninfectious);
(2) having a tracheostomy
(3) using respiratory monitoring or support devices at home such as an apnea monitor
or pulse oximeter
(4) being on home oxygen or continuous positive airway pressure at the time of assessment
While neurosensory impairment being one of:
(1) moderate to severe cerebral palsy (Gross Motor Function Classification System ≥3)
(2) severe developmental delay (Bayley Scales of Infant and Toddler
Development Third Edition [Bayley III] composite score <70 in either cognitive, language, or motor domains)
3) hearing aid or cochlear implant use
(4) bilateral severe visual impairment
What did they find?
The authors looked at 6 definitions of BPD and applied examined how predictive they were of these two outcomes. The combination of oxygen and/or respiratory support at 36 weeks PMA had the greatest capacity to predict this composite outcome. It was the secondary analysis though that peaked my interest. Once the authors identified the best predictor of adverse outcome they sought to examine the same combination of respiratory support and/oxygen at gestational ages from 34 -44 weeks PMA. The question here was whether the use of an arbitrary time point of 36 weeks is actually the best number to use when looking at these longer term outcomes. Great for benchmarking but is it great for predicting outcome?
It turns out the point in time with the greatest likelihood of predicting occurrence of serious respiratory morbidity is 40 weeks and not 36 weeks. Curiously, beyond 40 weeks it becomes less predictive. With respect to neurosensory impairment there is no real difference at any gestational age from 34-44 weeks PMA.
From the perspective of what we tell parents these results have some significance. If they are to be believed (and this is a very large sample) then the infant who remains on O2 at 37 weeks but is off by 38 or 39 weeks will likely fair better than the baby who remains on O2 or support at 40 weeks. It also means that the risk of neurosensory impairment is largely set in place if the infant born at < 29 weeks remains on O2 or support beyond 33 weeks. Should this surprise us? Maybe not. A baby who is on such support for over 5 weeks is sick and as a result the damage to the developing brain from O2 free radical damage and/or exposure to chorioamnionitis or sepsis is done.
It will be interesting to see how this study shapes the way we think about BPD. From a neurosensory standpoint striving to remove the need for support by 34 weeks may be a goal worth striving for. Failure to do so though may mean that we at least have some time to reduce the risk of serious respiratory morbidity after discharge.
Thank you to the CNN for putting out what I am sure will be a much discussed paper in the months to come.
The infant car seat challenge(ICSC) is a test which most definitely fits the definition of a battleground issue in Neonatology. After publishing the Canadian Pediatric Practice point on the same topic I received interesting feedback through the various social media forums that I frequent. While some were celebrating the consensus of the statement as verification that a centres’ non practice of the test was acceptable, others seriously questioned the validity of the position. The naysayers would point out that extremely infrequent events unless intentionally tracked may be difficult to pick up. In the case of the ICSC, if a few patients were to suffer a hypoxic event leading to an ALTE or worse after discharge, could the ICSC have picked out these babies and prevented the outcome? The evidence for adverse events associated with the use of car seats as discussed in the position statement is poor when using autopsy records over decades but when many clinicians can point to a failed ICSC picking up events, the thought goes that they “caught one”. Does catching one make a difference though?
The Well Appearing Infant
Shah et al in their recent paper Clinical Outcomes Associated with a Failed Infant Car Seat Challenge attempt to address this very point. They performed a retrospective study of 148 patients who were either <37 weeks GA or < 2500g at birth. The study was made possible by the fact that all such infants in their hospital admitted to a well newborn area meeting these criteria by policy must have an ICSC prior to discharge. Keep in mind that these were all infants who were on the well newborn service since they were asymptomatic. The definition of an event in this group was one or more of pulse oximeter saturation ≤ 85% for > 10 seconds, apnea > 20 seconds, bradycardia < 80 bpm for > 10 seconds, or an apnea or bradycardia event requiring stimulation. The failure rate was 4.5% which is very similar to other reported studies.
Why did they “fail”?
- Failure of the ICSC was owing to desaturation 59%
- Bradycardia 37%
- Tachypnea 4%
- Combination of 2 in 11%
What is interesting about these results is what happened to these infants after admission to the NICU in that 39% were identified with apnea (48% in preterm vs 17% in term infants). These events were in the supine position which is a curious finding since the ICSC was designed to find risk of cardiorespiratory stability in a semi-recumbent position. This has been shown previously though.
What does it all mean?
The infants in this study ultimately had more NG feeding, prolonged length of stay and septic workups after failing the ICSC that comparable infants who passed. At first blush one would read this article and immediately question the validity of the CPS position but then the real question is what has this added to the “pool of knowledge”. That infants may fail an ICSC at a rate of 4.5% is already known. That such infants may demonstrate apneic events has also been shown before and a study like this may help to support those clinicians who feel it is still imperative to find these infants in order to achieve a safe discharge. I think it is important to put these findings in the context of what would have happened if such a unit did not routinely test these types of babies. As all were seemingly well and I presume feeding with their families, they would have been discharged after 24-48 hours to home. We have no evidence (since they have not compared this sample to a group who did not have such testing) that if these babies were discharged they would have faired poorly.
The supporters of the ICSC would point to all the support these babies received by admitting them for 6-8 days, providing NG feeding and ruling out sepsis that they were unsafe for discharge. The other possible way to look at it was that the infants were subjected to interventions that we have no evidence helped them. Whether any of these infants had a positive blood culture justifying antibiotics or needed methylxanthine support is not mentioned. Judging however by the short length of stay I suspect that none or few of these infants needed such medication as I would expect they would have stayed much longer had they needed medical treatment for apnea.
I do commend the authors for completing the study and while it does raise some eyebrows, I don’t see it changing at least my position on the ICSC. While they have described a cohort of patients who failed the ICSC nicely, the fundamental question has been left unanswered. Does any of this matter? If you look well, are feeding well and free of any clinically recognizable events but are late preterm or IUGR can the ICSC prevent harm? This has not been answered here and perhaps the next step would be for a centre that has abandoned the ICSC to follow their patients after discharge prospectively and see whether any adverse outcomes do indeed occur. Any takers?
Positive pressure ventilation puts infants at risk of developing chronic lung disease (CLD). Chronic lung disease in turn has been linked many times over, as a risk for long term impacts on development. So if one could reduce the amount of positive pressure breaths administered to a neonate over the course of their hospital stay, that should reduce the risk of CLD and by extension developmental impairment. At least that is the theory. Around the start of my career in Neonatology one publication that carried a lot of weight in academic circles was the Randomized Trial of Permissive Hypercapnia in Preterm Infants which randomized 49 surfactant treated infants to either a low (35-45) or high (45-55) PCO2 target with the thought being that allowing for a higher pCO2 should mean that lower settings can be used. Lower settings on a ventilator would lead to less lung damage and therefore less CLD and in turn better outcomes. The study in question did show that the primary outcome was indeed different with almost a 75% reduction in days of ventilation and with that the era of permissive hypercapnia was born.
The Cochrane Weigh in
In 2001 a systematic review including this and another study concluded that there was insufficient evidence to support the strategy in terms of a benefit to death or chronic lung disease. Despite this lack of evidence and a recommendation from the Cochrane group that permissive hypercapnia be used only in the context of well designed trials the practice persisted and does so to this day in many places. A little lost in this discussion is that while the end point above was not different there may still be a benefit of shorter term ventilation.
A modern cohort
It would be unwise to ignore at this point that the babies of the late 90s are different that the ones in the current era. Surfactant and antenatal steroid use are much more prevalent now. Ventilation strategies have shifted to volume as opposed to pressure modes in many centres with a shift to early use of modalities such as high frequency ventilation to spare infants the potential harm of either baro or volutrauma. Back in 2015 the results of the PHELBI trial were reported Permissive hypercapnia in extremely low birthweight infants (PHELBI): a randomised controlled multicentre trial. This large trial of 359 patients randomized to a high or low target pCO2 again failed to show any difference in outcomes in terms of the big ones “death or BPD, mortality alone, ROP, or severe IVH”. What was interesting about this study was that they did not pick one unified target for pCO2 but rather set different targets as time went on reflecting that with time HCO3 rises so what matters more is maintaining a minimum pH rather than targeting a pCO2 alone which als0 reflects at least our own centre’s practice. There is a fly in the ointment here though and that is that the control group has a fault (at least in my eyes)
|Day of life
In the original studies of permissive hypercapnia the comparison was of a persistent attempt to keep normal pCO2 vs allowing the pCO2 to drift higher. Although I may get some argument on this point, what was done in this study was to compare two permissive hypercapnia ranges to each other. If it is generally accepted that a normal pCO2 is 35-45 mmHg then none of these ranges in the low target were that at all.
How did these babies do in the long run?
The two year follow-up for this study was published in the last month; Neurodevelopmental outcomes of extremely low birthweight infants randomised to different PCO2 targets: the PHELBI follow-up study. At the risk of sounding repetitive the results of Bayley III developmental testing found no benefit to developmental outcome. So what can we say? There is no difference between two strategies of permissive hypercapnia with one using a higher and the other a lower threshold for pCO2. It doesn’t however address the issue well of whether targeting a normal pCO2 is better or worse although the authors conclude that it is the short term outcomes of shorter number of days on ventilation that may matter the most.
The Truth is Out There
I want to believe that permissive hypercapnia makes a difference. I have been using the strategy for 15 or so years already and I would like to think it wasn’t poor strategy. I continue to think it makes sense but have to admit that the impact for the average baby is likely not what it once was. Except for the smallest of infants many babies these days born at 27 or more weeks of gestation due to the benefits of antenatal steroids, surfactant and modern ventilation techniques spend few hours to days on the ventilator. Meanwhile the number of factors such chorioamniotitis, early and late onset sepsis and genetic predisposition affect the risks for CLD to a great degree in the modern era. Not that they weren’t at play before but their influence in a period of more gentle ventilation may have a greater impact now. That so many factors contribute to the development of CLD the actual effect of permissive hypercapnia may in fact not be what it once was.
What is not disputed though is that the amount of time on a ventilator when needed is less when the strategy is used. Let us not discount the impact of that benefit as ask any parent if that outcome is of importance to them and you will have your answer.
So has permissive hypercapnia failed to deliver? The answer in terms of the long term outcomes that hospitals use to benchmark against one and other may be yes. The answer from the perspective of the baby and family and at least this Neonatologist is no.
I am fortunate to work with a group of inter-professionals who strive for perfection. When you connect such people with those with skills in multimedia you create the opportunity for education. I can’t say enough about the power of education and moreover the ability to improve patient outcomes when it is done well.
With this post I am going to be starting to share a collection of videos that I will release from time to time. The hope with any release like this is that you the reader wherever you are may find some use from these short clips. My thanks to the team that put these together as the quality is beyond compare and the HD quality is great for viewing on any device.
Placing A Chest Tube Can Be A Difficult Thing
As I said to a colleague in training the other day, a chest tube may seem daunting but once you see how it is done it loses some of its intimidation. Having said that, once you see it placed it can be a long time between opportunities for you to view another. That is where having a repository of videos comes in that you can watch prior to the next opportunity. These very short clips are easy to access when needed and may calm the nerves the next time you are called to place a chest tube.
A Word About Chest Tubes
The videos in question demonstrate how to place a Thal quick chest tube. In case this looks foreign to you it may be because you are using the older generation style of chest tubes that come equipped with a trocar. Even without the use of the trocar, these rigid tubes carry a significant risk of lung laceration or other tissue injury. For a review of such complications related to chest tube insertion see Thoracostomy tubes: A comprehensive review of complications and related topics.
The jury as they say is still out with respect to the use of these softer chest tube sets. There is no question that they are easier to place than the traditional thoracostomy tube. Their pliability though does carry a significant risk of kinking or blockage as we have seen in some patients when the Thal chest tube set is used to drain fluid in particular. Less of an issue with air leaks.
Start of a series
This post I suppose marks a slightly new direction for the blog. While I thoroughly enjoy educating you with the posts about topics of interest I see an opportunity to help those who are more visual in their learning. The videos will be posted over the next while with accompanying written posts such as this. They can be accessed on my Youtube channel at
All Things Neonatal YouTube
To receive regular updates as new videos are added feel free to subscribe!
Lastly a big thank you to NS, RH and GS without whom none of this would have been possible!