When I think back to my early days as a medical student, one of the first lessons on the physical exam involves checking central and peripheral perfusion as part of the cardiac exam. In the newborn to assess the hemodynamic status I have often taught that while the blood pressure is a nice number to have it is important to remember that it is a number that is the product of two important factors; resistance and flow. It is possible then that a newborn with a low blood pressure could have good flow but poor vascular tone (warm shock) or poor flow and increased vascular tone (cardiogenic shock or hypovolemia). Similarly, the baby with good perfusion could be in septic shock and be vasodilated with good flow. In other words the use of capillary and blood pressure may not tell you what you really want to know.
Is there a better way?
As I have written about previously, point of care ultrasound is on the rise in Neonatology. As more trainees are being taught the skill and equipment more readily available opportunities abound for testing various hypotheses about the benefit of such technology. In addition to my role as a clinical Neonatologist I am also the Medical Director of the Child Health Transport Team and have pondered about a future where ultrasound is taken on retrievals to enhance patient assessment. I was delighted therefore to see a small but interesting study published on this very topic this past month. Browning Carmo KB and colleagues shared their experience in retrieving 44 infants in their paper Feasibility and utility of portable ultrasound during retrieval of sick preterm infants. The study amounted to a proof of concept and took 7 years to complete in large part due to the rare availability of staff who were trained in ultrasound to retrieve patients. These were mostly small higher risk patients (median birthweight, 1130 g (680–1960 g) and median gestation, 27 weeks (23–30)). Availability of a laptop based ultrasound device made this study possible now that there are nearly palm sized and tablet based ultrasound units this study would be even more feasible now (sometimes they were unable to send a three person team due to weight reasons when factoring in the ultrasound equipment). Without going into great detail the measurements included cardiac (structural and hemodynamic) & head ultrasounds. Bringing things full circle it is the hemodynamic assessment that I found the most interesting.
Can we rely on capillary refill?
From previous work normal values for SVC flow are >50 ml/kg/min and for Right ventricular output > 150 ml/kg/min. These thresholds if not met have been correlated with adverse long term outcomes and in the short term need for inotropic support. In the absence of these ultrasound measurements one would use capillary refill and blood pressure to determine the clinical status but how accurate is it?
First of all out of the 44 patients retrieved, assessment in the field demonstrated 27 (61%) had evidence using these parameters of low systemic blood flow. After admission to the NICU 8 had persistent low systemic blood flow with the patients shown below in the table. The striking finding (at least to me) is that 6 out of 8 had capillary refill times < 2 seconds. With respect to blood pressure 5/8 had mean blood pressures that would be considered normal or even elevated despite clearly compromised systemic blood flow. To answer the question I have posed in this section I think the answer is that capillary refill and I would also add blood pressure are not telling you the whole story. I suspect in these patients the numbers were masking the true status of the patient.
How safe is transport?
One other aspect of the study which I hope would provide some relief to those of us who transport patients long distance is that the head ultrasound findings before and after transport were unchanged. Transport with all of it’s movement to and fro and vibrations would not seem to put babies at risk of intracranial bleeding.
Where do we go from here?
Before we all jump on the bandwagon and spend a great deal of money buying such equipment it needs to be said “larger studies are needed” looking at such things as IVH. Although it is reassuring that patients with IVH did not have extension of such bleeding after transport, it needs to be recognized that with such a small study I am not comfortable saying that the case is closed. What I am concerned about though is the lack of correlation between SVC and RVO measurements and the findings we have used for ages to estimate hemodynamic status in patients.
There will be those who resist such change as it does require effort to acquire a new set of skills. I do see this happening though as we move forward if we want to have the most accurate assessment of clinical status in our patients. As equipment with high resolution becomes increasingly available at lower price points, how long can we afford not to adapt?
It is hard to be a Neonatologist who took the path through Pediatrics first and not use a Dr. Seuss quote from time to time. If your unit is anything like ours where you work I imagine you feel as if you are bursting at the seams. As the population grows so do our patient volumes. I often quote the number 10% as being the number of patients we see out of all deliveries each year in our units. When I am asked why our numbers are so high I counter that the answer is simple. For every extra 100 births we get 10 admissions. It is easy though to get lost in the chaos of managing a unit in such busy times and not take a moment to look back and see how far we have come. What did life look like 30 years ago or 25 years ago? In Winnipeg, we are preparing to make a big move into a beautiful new facility in 2018. This will see us unify three units into one which is no easy task but will mean a capacity of 60 beds compared to the 55 operational beds we have at the moment.
In 2017 we are routinely resuscitating infants as young as 23 weeks and now with weights under 500g at times. Whereas in the past anyone under 1000g was considered quite high risk, now the anticipated survival for a 28 week infant at 1000g is at or above 95%. Even in my short career which began in 1998 in terms of Pediatrics and then 2001 in Neonatology our approach in terms of comfort with the smallest infants has eased greatly. What inspired this post though was a series of newspaper clippings from 1986 and 1991 that made me take a moment to look up at the sky and mutter “huh”. When you take a trip down memory lane and read these posts I think you will agree we have come a LONG way and (in truth) in a very short time.
1986 – Opening of the New NICU at Children’s Hospital
This unit was built with 3.5 million dollars. Imagine how far that would go now…
The unit had a capacity of 18 beds but opened with only 12 and a nursing staff of 60 (compare that to 150 now!). They couldn’t open more beds due to the lack of available nurses with sufficient skills.
My favourite comment to provide some perspective was that 5 to 10 years before this time the estimated survival for infants under 1000g was 15%!
Have we ever come a long way in family centred care. Can you imagine having a baby born now at 695g whose family wouldn’t get to hold them till almost 3.5 months of age?! That is what happened in the case described in this article.
1991 – Opening of the new Intermediate Care Nursery
Did you know the old unit had 19 beds (was originally 9 babies) and expanded to 27 at this time?
It cost 3.1 million to build this unit.
The long and the short of it is that yes things are busy and in fact busier than they have ever been. Do not lose sight however wherever your practice is that you are part of a story for the ages. Things that were once thought impossible or miracles are now everyday events and you have been part of it. For those of you who read this post this will likely bring about a lot of nostalgia for you. Thirty years in medicine is not a long time and we have accomplished so much along the way. For those of you who are just starting out, imagine where we will be in 30 years from now. I for one can’t wait to read about it and wonder where we will have gone by then.
I don’t envy our nurses who care for babies withdrawing from various opiates and other substances. These assignments are definitely a challenge and require a great deal of patience and depending on the shrillness of an infant’s cry a good set of earplugs. Nonetheless we do our best with these infants to keep them calm and avoid as much stimulation as we can as we attempt to minimize the excitability of their nervous system.
Over 40 years ago the Finnegan Neonatal Abstinence scoring system was developed to assist medical teams by providing as objective a system as possible to compare one infant to another and determine when and if a patient should be treated pharmacologically. Unfortunately there is a problem inherent with this scoring system. It is the same problem that exists when you don’t have a blinded research trial. Imagine you are caring for an infant and you were given no history about drug exposure. How might you score a patient like that compared to one in which you are told has been exposed to illicit substances? Your senses are heightened and moreover if you were told this baby is “withdrawing terribly” or “is awful at night” you are biased. How are you likely to score such a patient when they are “on the edge” of being counted as a 1 or a 0 in a category? I bet in many cases, especially if you haven’t taken care of many such patients you err on the side of caution and score them on the high side. It is human nature. When the possible outcome of failing to recognize a withdrawing patient is a seizure, no one wants to be on when it happens having their scoring questioned. Have a look at the scoring tool though.
There is a lot of stuff in there to check off! What if it could be simpler?
The ESC Tool
In early May, news began to break of an abstract being presented at the Pediatric Academic Society meeting. The news story from the AAP can be found here. The ESC tool is a three question tool used to assess whether an infant requires treatment for withdrawal.
E – Eat (is an infant is able to eat 1 or more ounce per feeding)
S – Sleeping (sleep for an hour or longer undisturbed)
C – Console (Be consoled in 10 minutes or less.)
If all three criteria are met, the patient does not need treatment. If one or more criteria are not met the housestaff are notified and first non-pharmacologic and then pharmacologic means are employed if necessary to control symptoms.
The authors did something quite interesting. They looked at 50 patients with 201 hospital days with prenatal exposures to opiates and applied the ESC criteria to guide treatment. Concurrently they captured the Finnegan scores but did not use them to guide treatment.
The findings I hope you will agree are quite interesting!
“FNASS scores indicated starting morphine in 30 infants (60%). Morphine was actually started on only 6 patients (12%) (p< 0.0001) based on the ESC approach. The FNASS led protocol directed initiating or increasing meds on 24.6% of days compared to 2.7% of days using the ESC approach (p< 0.0001). The FNASS approach directed that morphine was either not started or decreased on 65.8% of days compared with 94.4% of days using the ESC approach (p< 0.0001). There were no readmissions or reported adverse events.
Pretty amazing but…
The ESC approach greatly reduced the need for treatment and as the authors state there were no readmissions or reported adverse events. What we don’t know and will be needed I suspect before anyone will adopt this strategy (which I have to say again is so much simpler that current approaches) is how these children do in the long run. If the system is undertreating withdrawal, could we see downstream impacts of a “kinder and gentler” approach? One outcome that will be reported soon in the next month is length of stay. I am eagerly awaiting further results as I for one think that a simpler approach to these patients may be just what the doctor ordered. I think the nurses might thank us as well but we will see just how appropriate it is!
The Abstract reporting these findings can be found below
Novel Approach to Evaluating and Treating Infants with Neonatal Abstinence Syndrome
I have often said that if this came to pass as a mandatory requirement that I would make an announcement shortly thereafter that I was moving on to another career. I think people thought I was kidding but I can put in writing for all to see that I am serious! The subject has been discussed for some time as I can recall such talks with colleagues both in my current position and in other centres. The gist of the argument for staying in-house is that continuity is improved over that period and efficiency gained by avoiding handovers twice a day . How many times have you heard at signover that extubation will be considered for the following morning or to keep the status quo for another issue such as feeding until the next day. No doubt this is influenced by a new set of eyes being in the unit and a change in approach to being one of “putting out fires” overnight. The question then is whether having one Neonatologist there for 24 hours leads to better consistency and with it better outcomes. With respect to PICUs the AAP has previously recommended that 24 hour in-house coverage by an intensivist be the standard so should Neonatology follow suit?
A Tale of Two Periods
My friends in Calgary, Alberta underwent a change in practice in 2001 in which they transitioned from having an in-house model of Neonatologist coverage for 24 hours a day to one similar to our own centres where the Neonatologist after handover late afternoon could take call from home. An article hot off the presses entitled Twenty-Four hour in-house neonatologist coverage and long-term neurodevelopmental outcomes of preterm infants seeks to help answer this question. The team undertook a retrospective analysis of 387 infants born at < 28 weeks gestational age during the periods of 1998-2000 (24 hour period, N=179 infants) vs 2002 – 2004 (day coverage, N= 208 infants) with the goal of looking at the big picture being follow-up for developmental outcome at 3 years. This is an important outcome as one can look at lots of short term outcomes (which they also did) but in the end what matters most is whether the infants survive and if they do are they any different in the long term.
As with any such study it is important to look at whether the infants in the two periods are comparable in terms of risk factors for adverse outcome. Some differences do exist that are worth noting.
Increased risk factors in the 24 hour group
- Maternal smoking
- Smaller birthweight (875 vs 922 g)
- Confirmed sepsis (23% vs 14%)
- Postnatal steroids (45% vs 8%) – but duration of ventilation longer in the day coverage group likely due to less postnatal steroids ( 31 vs 21 days)
All of these factors would predict a worse outcome for these infants but in the end for the primary outcome of neurodevelopmental impairment there was no difference. Even after controlling for postnatal steroids, birth weight, sex and 5 minute apgar score there was still no difference.
What might this mean?
Looking at this with a glass is half full view one might say that with all of the factors above predicting worse outcome for infants, the fact that the groups are not different in outcome may mean that the 24 hour model does indeed confer a benefit. Maybe having a Neonatologist around the clock means that care is made that much better to offset the effect of these other risk factors? On the other hand another explanation could also be that the reason there is no difference is that the sample just isn’t big enough to show a difference. In other words the size of the study might be underpowered to find a difference in developmental outcome.
One of the conclusions in this study is that the presence of a Neonatologist around the clock may have led to earlier extubation and account for the nearly 10 day difference in duration of ventilation. While I would love to believe that for personal reasons I don’t think we can ignore the fact that in the earlier epoch almost 50% of the babies received postnatal steroids compared to 8% in the later period. Postnatal steroids work and they do so by helping us get babies off ventilators. It is hard to ignore that point although I woudl like to take credit for such an achievement.
For now it would appear that I don’t feel compelled to stay overnight in the hospital unless it is necessary due to patient condition necessitating me having my eye on the patient. I am not sure where our field will go in the future but for now I don’t see the evidence being there for a change in practice. With that I will retire to my bedroom while I am on call and get some rest (I hope).
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.