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%
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?
Throughout my career one thing has been consistently true. That is that wherever I was working and regardless of the role I have been an educator. I imagine the blog to a great extent is related to my interest in this aspect of my work. In the last few years much has been said about care by parents whether it be a general approach for family centred care or in formalized approaches such as FiCare which has also been formally studied in the research setting. When we speak of family centred care, one thing that I am constantly reminded of is that the focus of all of our efforts must be on the family and the patient. As I said recently to a colleague when discussing what was presented as a difficult discussion with another colleague due to a disagreement about the direction of management, when you put the patient first the discussion really isn’t difficult at all. It’s not about you or a colleagues ego but about the patient and if the management is not up to par then change direction and worry about managing egos later.
What We Know And What They Know
Another aspect that needs to be addressed is the difference in power that we have through knowledge. I am not talking about us exerting authority over families but from the perspective of us having the knowledge from years of experience in the field as to what is significant and what is not in terms of events in the NICU. The evidence for example with respect to neurodevelopmental outcome from apnea and bradycardia should give us reason to be optimistic the majority of the time. While in Edmonton I learned a great deal from one of my colleagues who was the lead author in a paper entitled Early childhood neurodevelopment in very low birth weight infants with predischarge apnea. While frequent apnea may be associated with mild motor impairments in their paper, the predictive value of these predischarge recordings is very limited when you take away those kids without severe IVH. I think about all of the parents we see who have their eyes glued to the monitors while they attend at the bedside and what they must be thinking. To us it is just a matter of time but I wonder for them how agonizing a time it really is! It isn’t just those infants who are nearing discharge and having apnea either as the CAP study at 5 years of age showed no difference in survival without disability in those infants who received caffeine vs those who did not. More frequent events may not be that detrimental after all. I am not suggesting we not treat patients as one never knows where the threshold lies to cause injury but these preemies are certainly made of some tough stuff.
Identifying Stress and Preparing Parents For it
The first step in dealing with this issue is to know it is there. Recognizing this, Melnyk and others performed an educational intervention targeting behaviour of families in their study Reducing premature infants’ length of stay and improving parents’ mental health outcomes with the Creating Opportunities for Parent Empowerment (COPE) neonatal intensive care unit program: a randomized, controlled trial. The group of parents who went through the program had better mental health outcomes compared to the control groups. The issue here and really is at the crux of the goal in writing all of this is that the stress that parents feel may not be overtly present. The squeaky wheel as the saying goes gets the grease and the parents that are demonstrating signs of poor coping are the first to draw the referrals to social work or engage in a deeper conversation with nursing at the bedside. All parents experience stress at least to a certain degree and it is all of our jobs to tease it out. On the other hand employing standardized approaches such as the COPE program for all parents might be another way of helping those who are in need but not clearly wearing a sign on their foreheads that say “help me”.
Don’t Underestimate the Power of Reassurance
So we know that much of what we see on the monitors will not lead to long term harm, transient central cyanosis during feeds will not damage the brain and apnea of prematurity is a distinct entity from SIDS. The parents on the other hand commonly make these links and additionally in case no one has mentioned it to you, those babies with TTN may one day develop asthma and those with hypoglycemia may have diabetes (we know both not to be true but I have been asked about this many times). This is why I believe it is our duty to explain why we are not worried about things that come up in the unit. Saying “don’t worry” or “that is normal preterm behaviour” may not be enough. Ask a parent what it is they are worried about and you may be surprised to find out the links that they have made in their heads, some of which may be valid but some completely false. I am not meaning to trivialize their concerns but rather validate them as real worries. If we have the knowledge and it is power as I said before then shouldn’t we use that power to help reduce their stress?
Engaging Families Can Reap Huge Dividends
The movement towards family centred care and more specifically care by parent will have a dramatic impact on this issue. As more and more centres move to engaging families to be part of rounds and not just listen and then ask questions but to take some degree of control and provide some of the reporting stress will be reduced. It is only logical. The more a family comes to understand what is significant and what is not in terms of reporting concerns the more confident they will be. Moreover, spending more time at the bedside leads to more skin to skin care and with that shorter hospital stays due to better cardiorespiratory stability. We aren’t there yet but we are headed in the right direction. In the meantime, take the time to ask a simple question “what are you worried about” to parents no matter how confident and strong they appear and you may find yourself with an opportunity to harness the power of education you have a make a real difference to a family in need.
We are the victims of our own success. Over the last decade, the approach to respiratory support of the newborn with respiratory distress has tiled heavily towards non-invasive support with CPAP. In our own units when we look at our year over year rates of ventilation hours they are decreasing and those for CPAP dramatically increasing. Make no mistake about it, this is a good thing. Seeming to overlap this trend is a large increase in demand by learners as we see the numbers of residents, subspecialty trainees, nurse practitioners on the rise. The combined effect is a reduction is the experience trainees can possibly hope to obtain when these rarer and rarer opportunities arise. The result of all of this is that at least by my eyes (although we haven’t documented it) the number of attempts for intubations seems to be much higher than it once was. It is not uncommon to see 3-4 attempts or sometimes more whereas in days gone by 1-2 attempts was the norm. We do our best to deal with these shortages using simulation as an example but nothing quite compares to dealing with the real thing even if it comes close.
The Less Practice You Get The More Adverse Events You Can Expect
This is just the way it is. Perfect practice makes perfect and it has been well documented that intubations can lead to many complications such as desaturation, bradycardia, bleeding, airway edema from multiple attempts and a host of other issues. Hatch and colleagues first described their experience with 162 intubations in which they found adverse events in 107 (39%) with 35% being classified as non-severe and severe events in 8.8%. Not surprisingly one of the factors associated with adverse events was the need for multiple intubation attempts. Based on this initial experience they determined that as a unit they could do better and soon after undertook a series of PDSA Quality Improvement cycles to see if they could reduce these events and that they did. What follows are the lessons learned from their QI project and it is my hope that some or all of these ideas may help others elsewhere who are experiencing similar frustrating rates.
Standardized checklist before intubation – This used a “do-confirm” approach in which the individuals on the team “do” what they need to prepare and then confirm with the group that they are done. An example might be an RRT who states “I have three sizes of ETT ready with a stylet already inserted, surfactant is thawed and the ventilator is set with settings of … if needed etc”. Another critical part of the checklist includes ensuring that everyone knows in advance their roles and who is responsible for what.
Premedication algorithm – Prior to this project the use of premedication was inconsistent, drug selection was highly varied and muscle relaxation was almost non-existent. The team identified from the literature that a standard approach to premedication had been associated with reductions in adverse events in other centres so adopted the same here using fentanyl with atropine if preterm and muscle relaxation optional.
Computerized order set for intubation – interestingly the order set included prompts to nursing to make sure intervention 1 and 2 were done as well.
The results of there before and after comparison were numerous but I have summarized some of the more important findings in the table below.
Period 1 (273 intubations)
Period 2 (236 intubations)
<10 intubations experience
The median number of attempts were no different but the level of experience in the second epoch was less. One would expect with less experienced intubators this would predict higher risk for adverse events. What was seen though was a statistically significant reduction in many important outcomes as listed in the table. I can only speculate what the results might have been if the experience of the intubators was similar in the first and second periods but I suspect the results would have been even more impressive. The results seem even more impressive in fact when you factor in that the checklist was used despite all of the education and order set 73% of the time and muscle relaxation was hardly used at all. I believe though what can be taken out of these results is that taking the time to plan each intubation and having a standard approach so that all staff practice in the same way reaps benefits. If you already do this in your unit then congratulations but if you don’t then perhaps this may be of use to you!
What About Intubation For INSURE?
We are in the process of looking in our own centre at the utility of providing premedication when planning to give surfactant via the INSURE technique. I couldn’t help but notice that this paper also looked at that very issue. Their findings in 17 patients all of whom were provided premedication were that only one could not be extubated right after surfactant. The one who was not extubated however was kept intubated for several hours without any reasoning provided in the records so it may well be that the infant could have been electively kept ventilated when they may have indeed been ready for extubation. The lesson here though is that we likely do not need to exclude such patients from premedication it will reduce the likelihood of complications without prolonging the time receiving positive pressure ventilation.
Whatever your thoughts may be at this time one of the first questions you should ask is what is our local rate of complications? If you don’t know then do an audit and find out. Whatever the result, shouldn’t we all strive to lower that number if we can?
I have probably received more requests for our glucose gel protocol than any other question since I started writing on this blog. Dextrose gel has been used more and more often for treatment of hypoglycemia such that it is now a key strategy in the management of low blood sugar in ours and many other institutions. If you are interested in the past analyses of the supporting trials they can be found in these posts; Glucose gel For Managing Hypoglycemia. Can We Afford Not To Use It? and Dextrose gel for hypoglycemia: Safe in the long run? As you can tell from these posts I am a fan of dextrose gel and eagerly await our own analysis of the impact of using gel on NICU admission rates for one!
But What If You Could Prevent Hypoglycemia Rather Than Treating It?
This is the question that the same group who has conducted the other trials sought to answer in their dose finding study entitled Prophylactic Oral Dextrose Gel for Newborn Babies at Risk of Neonatal Hypoglycaemia: A Randomised Controlled Dose-Finding Trial (the Pre-hPOD Study). I suppose it was only a matter of time that someone asked the question; “What if we prophylactically gave at risk babies dextrose gel? Could we prevent them from becoming hypoglycemic and reduce admissions and improve breastfeeding rates as has been seen with treatment of established hypoglycemia?” That is what they went out and did. The group selected at risk patients such as those born to mothers with any type of diabetes, late preterm infants, SGA and others typically classified as being at risk but who did not require NICU admission at 1 hour of age when treatment was provided. The primary outcome was hypoglcyemia (<2.6 mmol/L) in the first 48 hours. Secondary outcomes included NICU admissions, breastfeeding rates in hospital and after discharge as well as formula intake at various time points.
The study sought really to serve as a pilot whose goal was to determine when compared to placebo whether several different regimens could prevent development of hypoglycemia. The groups were (with the first dose in each case given at 1 hour of age):
Single dose of 40% dextrose gel – 0.5 mL/kg
Single dose of 40% dextrose gel – 1 ml/kg
Four doses of 0.5 mL/kg given every three hours with breastfeeding
A single dose of 1 mL/kg then 3 X 0.5 mL/kg given q3h before each breastfeed.
In total 412 patients were randomized into 8 different groups (4 treatment and 4 placebo).
As The Saying Goes, Less Is More
The only dose of dextrose that reduced the risk of hypoglycemia in the first 48 hours was 0.5 mL/kg which provides 200 mg/kg of dextrose which is the same as a bolus of IV dextrose when giving 2 mL/kg of D10W. Curiously using a higher dose or using multiple doses had no effect on reducing the risk. Based on a difference of 14% between placebo and this group you would need to treat roughly 7 patients with dextrose gel once to prevent one episode of hypoglycemia. Also worth noting is that admission to NICU was no different but if one restricted the reason for admission to hypoglycemia the difference was significant (13% vs 2% risk; p = 0.04). What was not seen here was a difference in rates of breastfeeding and much effect on use of formula.
Why Might These Results Have Occurred?
Insulin levels were not measured in this study but I truly wonder if the reason for hypoglycemia in the other groups may have been transient hyperinsulinemia from essentially receiving either a very large load of glucose (1 mL/kg groups) or effectively 4 boluses of glucose in the first 12 hours of feeding. Rebound hypoglycemia from IV boluses is a known phenomenon as insulin levels surge to deal with the large dextrose load and I can’t help but wonder if that is the reason that all but the single dose regimen had an effect. It is also worth commenting that with so many secondary outcomes in this study the p values needed to reach significance are likely much smaller than 0.05 so I would take the reduction in NICU admissions for hypoglycemia with a grain of salt although at least the trend is encouraging.
I wouldn’t change my practice yet and the authors do acknowledge in the article that a much larger study is now being done using the single dose of 0.5 mL/kg to look at outcomes and until that is published I don’t think a practice change is in order. What this study does reinforce though is that providing multiple doses of dextrose gel may yield diminishing returns. While the goal here was prophylaxis, I can’t help but think about the patients who are symptomatic and receive two or three gels and still wind up with an IV. Could it be the same rebound hypoglycemia at play?
We also have to acknowledge that even if this is an effective preventative strategy, is it in the best interests of the babies to all receive such treatment when at least in 6 babies they wouldn’t have needed any? Could such treatment simply be reserved as has been done for those who develop hypoglycemia? Those who question the safety of the ingredients such as dyes that are found in the product may want some long term safety data before this becomes routine in at risk babies but it won’t surprise me if such strategies become commonplace pending the results of the larger trial on the way.