NEC & Anemia: Is the truth out there?

A debate broke out recently at one of our rounds when someone asked whether a recent case of NEC was possibly related to a transfusion that a baby received.  Much has been written about Transfusion Associated Necrotizing Enterocolitis (TANEC) with the pendulum swinging back and forth between it existing as a real entity or simply being an association that is not causative in the least.  Using one of my favourite sources, a retrospective analysis of the Canadian Neonatal Network database found no difference in mortality or morbidities for those who had a transfusion and NEC vs those without. Despite this we continue to see those who “hold feeds” for a few hours prior to transfusion and then resume them a few hours later.  Why does this happen?

Risk vs Benefit

Those who hold feeds argue that in Neonatology we hold feeds for far less.  Furthermore, what is the harm?  If a baby develops NEC within 24 hours of a transfusion and we held the feeds we feel we have done all we could.  If a baby is fed and develops NEC we are left asking “what if?”.  The purists out there would argue the contrary though, that the evidence is not strong enough to support the practice and may require the insertion of an IV which is a painful procedure and places the infant at risk of infection from one or more skin breaks.  Additionally, does the interruption of feeds potentially alter the microbiome of the patient and with it risk potential downstream consequences. In case you are wondering, I have tended to sit on the side of holding a feed although more often when I am asked about it than ordering it upfront.  The fact is I just don’t know.  The evidence has never been solid in this regard but it is hard to ignore the possibility when you have been bitten once or twice before (whether it was causative or not!).  I doubt it really exists but then again what if there is something there?

It May Not Be The Transfusion But Anemia Itself

A recent paper Association of Red Blood Cell Transfusion, Anemia, and Necrotizing Enterocolitis in Very Low-Birth-Weight Infants may have found a possible explanation to the ongoing debate.  Research papers associating transfusions with NEC may all have one thing in common in that they have not been able to prove causation.  When you have many papers finding the same thing it leads medical teams to begin to believe there is causation.  Something else may be at play at this paper suggests another association which again may not be causative but at least in my mind is perhaps biologically plausible.  It may be that those patients who are transfused when their hemoglobin is below a threshold of 80 g/L are at increased risk of developing NEC rather than all patients transfused.

This study was a secondary analysis of a prospective study on transfusion transmission of cytomegalovirus in preterm infants < 1500g.  The authors chose 80 g/L as a cutoff based on previous studies suggesting this threshold as an important one for transfusion practices. Forty eight out of 60 eligible infants developed NEC and it is from this 48 that multivariable analysis sought to identify factors predisposing to the outcome in question of NEC.  The factor with the greatest hazard risk for NEC was severe anemia in a given week with an approximate 6 fold risk (range 2 – 18) while receiving an RBC transfusion in a given week of life did not meet statistical significance.

What does this mean?

Before embracing the result and concluding we have the answer we have to acknowledge the authors have gone on a fishing expedition of sorts.  Any secondary analysis of a study that is done carries with it some words of warning.  There may be variables that were not controlled for that are affecting the results.  As well when looking at many many variables it could be by chance that something or several things come up by chance.  Lastly it may be that again there is nothing more than an association here at play.  Having said that, there is some biologic plausibility at least here.

  1. Delivery of oxygen to the tissues is dependent on HgB level. The oxygen content of blood is described by: O2 content = (gm Hbg)(1.34 ml O2/gm Hbg)(% sat) + 0.003(pO2) = ml O2/dL.
  2. Oxygen delivery = cardiac output X O2 concentration (or content)
  3. Could RBCs become less deformable and increase viscosity in low O2 environments? This could be the case when the HgB declines below 80 g/L.  Such changes to deformability have been demonstrated at mild levels of hypoxia as might exist in low pO2 conditions at the tissue level with anemia.

So imagine we have fewer RBCs carrying as much oxygen as they can but eventually you cross a threshold where there is not enough O2 being delivered at the tissue level and the RBCs become lodged or perhaps sluggish as they move through capillaries of the intestines. Add to this that NEC occurs in watershed areas most commonly and you have the potential setup for NEC.

Can we use the results of this study?

I suppose statistical purists out there will argue that it is merely an association.  The fact remains that there are many people who are holding feeds for varying amounts of time despite the lack of conclusive evidence that TANEC exists.  I wonder if a middle ground might be to be more cautious and restrict such practice to those with low HgB values below 80 g/L as the authors here have found.  To me at least there is biologic plausibility as outlined above.  It would seem to me that to hold feeds for all babies is excessive and likely without evidence but could the threshold actually matter which it comes to oxygen content.  Given that NEC is a condition related to ischemia, the authors here have provided another association that makes me at the very least scratch my head.

 

 

A Golden Opportunity For Your NICU Team!

I have written about respectful communication before in Kill them with kindness.

The importance of collaborating in a respectful manner cannot be overemphasized, as a calm and well prepared team can handle just about anything thrown their way.  This past week I finally had the opportunity to take the 7th ed NRP instructor course.  4865-NRP323_ProductWhat struck me most about the new version of the course was not the approach to the actual resuscitation but the preparation that was emphasized before you even start!  It only takes 30 seconds to establish who is doing what in a resuscitation and while it would seem logical to divide up the roles each will take on it is something that has not been consistently done (at least in our institution).  When a baby is born and responds to PPV quickly, this may not seem that important but in a situation where a team is performing chest compressions, placing an emergency UVC and moving on to epinephrine administration it certainly is nice to know in advance who is doing what.

The Golden Hour

We and many other centres have adopted this approach to resuscitation and at least here developed a checklist to ensure that everyone is prepared for a high risk delivery.  While teams may think they have all the bases covered, when heart rates are racing it may surprise you to see how many times crucial bits of information or planning is missed.  As I told you in another post I will be releasing a series of videos that I hope others will find useful.  The video in this case is of a team readying itself for the delivery of a preterm infant that they anticipate will have respiratory distress.  Ask yourself as you watch the film whether your team is preparing to this degree or not.  Preparing in such a fashion certainly reduces the risk of errors caused by assumptions about who is doing what or what risk factors are present.

As you can tell I am a big fan of simulation in helping to create high functioning teams!  More of these videos 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!

Donor Milk; Falling like DOMINOs?

The rise of donor milk banks and depots in recent years has been a welcome addition to the care of preterm infants.  We have known for many years that “breast is best” and advocate for mother’s own milk whenever possible.  When this is not possible we previously turned to formula but with the availability of pooled pasteurized donor milk many hospitals have focused on expanding the indications for use.  Through personal communications in Canada we are a bit all over the map in terms of indications with some centres restricting use based on birth weight while others taking into account, gestational age as the main criteria.  With respect to duration some centres use 2 weeks, others 4 and then others until a gestational age is reached which may mean up to 10 weeks of use for a baby born in that centre at 24 weeks.  While variation exists it is hard to find anyone who would suggest this is a bad thing to provide.

The main reason for pushing expansion of programs is the strong evidence that avoidance of bovine milk is associated with a reduction in the risk of NEC.  Many studies have been done in this regard and the Cochrane systematic review concluded that formula increased the risk of necrotising enterocolitis: typical risk ratio 2.77 (95% CI 1.40 to 5.46); risk difference 0.04 (95% CI 0.02 to 0.07).

While donor milk is a wonderful nutritional product for sure it does have one issue which is a lower protein content than mother’s own milk and as such dieticians will commonly increase the protein content from 0.9 g/dL to 1.2 g/dL by adding powder or more recently liquid protein supplements.  One might expect then that doing so would provide a reduction is NEC, and an optimal source of nutrition for the growing preterm brain.  Avoidance of NEC should reduce the risk of adverse neurodevelopmental outcome as the two have been linked before.

Enter the DOMINO Study

This Ontario, Canada based study utilized four NICUs to provide in a randomized fashion either donor human milk or formula with matching protein and caloric densities to 363 infants (181 donor milk, 182 formula).  All infants were preferentially fed mother’s own milk but supplemented with donor or formula if unavailable and planned to use one or the other for up to 90 days or discharge whichever came first.  The exposure to donor milk was quite long in comparison to our own units practice (1 month duration if born at < 1500g) .  The median number of days for donor milk was 65 (IQR, 41-90).  A significant risk to the results would be if there was a difference in amounts of mother’s own milk provided between the two groups but there was none. Exclusive feeding of mother’s own milk occurred in the Donor milk group (28.2%) and formula group (26.9%) respectively. Among infants requiring a supplement, there was no statistically significant difference between the donor milk and formula groups in the proportion of total enteral feeds for each infant consumed as mother’s milk (58.4% [IQR, 13.6%-96.0%] vs 63.3% [IQR, 9.6%-97.2%], respectively, P = .96).

Short term but not long term gains

Curiously (at least to me) I would have expected differences in some of the morbidities other than NEC but such was not the case. table-4-copy

The strength of using human milk though can not be understated as any reduction in NEC is an extremely important outcome regardless of whether long term neurodevelopment is affected positively or not.
in terms of the latter outcome no difference was observed between the two groups.  The Bayley III findings were quite similar at 18 months which on the surface may cause everyone’s shoulders to sag as the benefit everyone hoped for did not transpire.  Additionally, linear growth, head circumference and weight gain were not different between groups.  This may simply reflect that protein and caloric intakes were indeed matched between groups whereas in the past, the lack of protein fortification led to delays in growth in the donor milk groups.

At the risk of sounding like the end of a Cochrane review I am not sure this is the final word on donor milk and outcome.  Larger studies may be needed to get at the real truth.  This was not a pure sample of donor milk vs formula as a significant percentage (over 20% in both groups) received purely mother’s own milk.  Furthermore, in those that received supplements there was still a significant percentage that received some of mother’s own milk.  The authors suggest that a larger sample size would unlikely have detected a difference and that may be the case but is it so due to where the study was done.  What if the study were done in a centre with a very low rate of breastfeeding?  I am concerned that the lack of response in outcome may reflect a dilution of the impact of the strategy by having such a successful rate of providing mother’s own milk.

All Is Not Lost

Using a glass is half full view, I think it is worth pointing out that this study should also provide some comfort for those centres that use formula as a supplement.  Clearly the higher rate of NEC is not comforting to anyone but for those who survive to discharge the neurodevelopmental outcome is promising.  Formula in some circles has taken on a view as almost a toxic substance but I often remind residents and fellows that while we prefer breast milk, formula has been used in NICUs for decades and not every patient who receives it will develop NEC.  Yes it is a risk factor for NEC and when you don’t have an alternative it is an acceptable form of nutrition to use.  What I think may be lost in the DOMINO study is that if you are a centre that uses formula as there is no access to DBM this should help provide reassurance to the families you care for.  All is not lost after the DOMINO study.  Every cloud has a silver lining and fear not this will not be the last study to test this hypothesis.  At the moment it is just the best we have and this is not the last we will hear on this topic.

 

 

 

 

 

 

The Rugged Individualist Neonatal Blogger

Rather excited this week as Biomed Central picked up a blog post that I wrote on social media.  The post is found here.  It is based though on a larger version that I have included below and really delves into the impact of social media and how one uses it.  A big thank you to Kristy Wittmeier for all of her help in writing the post.

Original Piece

I read with great interest the article by Campbell et al entitled Social media use by physicians: a qualitative study of the new frontier of medicine.  The study interviewed 17 physician users of social media of which only one writer of a blog responded, but then declined to participate.  The four themes that emerged of Rugged Individualism, Uncertainty, Social Media as Media and Time Constraints certainly resonate with me as a blogger who also happens to be a Pediatrician but more specifically a Neonatologist.  The first theme truly resonates with me as I think back over the journey that has taken me to where I am now.  We in the medical social media world are certainly learning as we go.  Without clear paths drawn for us we explore and contemplate how we will make a positive difference far beyond the reach of the typical physician in a clinic, hospital or local community.  The commentary that follows explores the journey that I have taken with social media; engaging in largely unpaid work to bring information to others using these forums.

My own story as a Neonatal Blogger began in 2015 when my Minecraft-obsessed son asked me to help him start a blog about Minecraft.  minecraft-free-download-pc-macTwo very poorly read posts started my foray into blogging using WordPress as my blogging forum.  Around the same time, our family acquired a puppy and despite our best efforts over the next 18 months this new addition woke me between 4 – 5 AM daily.  After being awoken one morning at 4 AM I read an article on NICU size as it relates to outcomes and had a marked reaction to the conclusions of the paper.  On a whim on this early February morning, I chose to set up my own blog site, and All Things Neonatal was born.  I would like to say that there was a master plan at the inception but it was due to a visceral reaction to a paper perhaps enhanced by irritability and fatigue that led to me choosing to put my thoughts out there. And I was hooked. A year and a half later, I have produced a total of 139 publications on the site.

Knowing the benefit that I have received, and hopefully also imparted by engaging in social media as a healthcare professional has sparked my interest in encouraging others to consider doing the same. And for those interested in going beyond considering to doing, I would like to share some key learnings from my journey to inform yours.  To establish yourself in the realm of social media you need to utilize more than one platform, obtain your content in a time efficient manner and do not let your voice stay silent for too long.

Harnessing the combined power of multiple social media sites

When you begin blogging you come to realize that the method has its limitations in terms of reach.  As the paper suggests, the polling of social media users identifies multiple potential websites for both collecting and disseminating information (Facebook, Twitter, Tumblr, Linkedin, Google+ as examples).  Using them in combination can far enhance your reach. At the time of this writing the number of people who “follow” me on each site is quite disparate with Facebook by far leading the way in distribution power.

Table 1 – Variance in impact of commonly used social media websites

Site Number of Followers
Facebook 11859
Twitter 921
WordPress (my primary blogging platform) 393

Also in the article, concern is raised over the lack of feedback for social media users as it pertains to to data on interaction with their postings. With Facebook one cannot determine what was done with your post but on twitter there is some further delineation as one receives a tally of impressions, engagements and link clicks. When it comes to real metrics though, this is where the actual blogging site provides more useful data. I recommend embracing metrics, not only to understand your reach but perhaps just as importantly to give you the drive to continue your writings.  My most popular post, has received 5117 reads, meaning that this many took the time to open my blog post to hear what I had to say on the subject. If you were to share your thoughts on an article with colleagues via email, post a new guideline in an office or clinic or publish an article in a journal, how many people would actually see it?  The same information, if cited in a blog post and shared through Facebook can see a dramatic rise in exposure, along with your interpretation of the work.  The aforementioned post for example has had a reach on Facebook of 50934 people to date and was shared 58 times multiplying the distribution many fold.  If you published a journal article and were notified of such circulation I suspect you would be jubilant.

How to obtain content?

One of the greatest benefits to my own practice has been the necessity of using a wide net to capture potentially interesting content for my readers.  This habit facilitates the necessary practice of continuous learning through collecting articles from such sources as weekly automated pubmed searches, and various Child Health news websites. With time as your audience builds, postings on your own sites, tags on Facebook or mentions on Twitter draw your attention to content which your followers believe may be of interest to you.  Remember in most circumstances you are not being paid for these efforts and in between managing the rest of your workday and balancing the demands of a personal life this aspect of your life needs to be done in a very time efficient manner.

Do Not Let Your Voice Stay Silent For Too Long

If you want people to pay attention to what you are adding to the pool of knowledge, deposits must occur frequently.  Your followers are far more likely to mention you on various social media sites if they know you are likely to see and occasionally respond to their posts.  Without such a presence, the mentions, likes and shares slow, as will your growth and relevance in the social media world.  Future research should determine what the optimal frequency of posts to maximize reach would be.  I have long suspected that excessive posting may have the effect of diluting the important messages while posting too infrequently means you may be quickly forgotten.  Individuals must find the balance that works for them to keep their audience engaged while maintaining their motivation to continue the practice.

What Really Motivates Those Who Participate in Social Media?

I believe the motivation lies in the three qualities described by Malcolm Gladwell in his book The Tipping Point.tipping-point  He described three types of people that are needed for something to go from an idea to widespread adoption; connectors, mavens and salesmen.  The doctors out there on social media likely have a little bit of all these characteristics.  Gladwell said this about connectors; “They are people who “link us up with the world…people with a special gift for bringing the world together”.  With respect to mavens he characterized them as having the ability to “start “word-of-mouth epidemics” due to their knowledge, social skills, and ability to communicate”.  Lastly, salesmen in his view are “persuaders”.  These three traits aptly describe those that have waded into this field.  They must have the confidence to put their message out there with content that captures people’s attention and certainly have the goal of persuading people that it is worth considering what they have to say.  The fundamental drive though comes from a place of harnessing these traits to help people.  Whether writing original content or sharing what others have produced, the social media physician’s goal is generally pure and that is to share knowledge and generate discussion.  For example, if you have a new strategy for reducing infection, the active social media physician would ask “why not share this with the world” rather than limit it to your institution or city.

This frontier like field though does come with some caveats before you dip your feet into the collective pool of the various media sites.  As opposed to the more traditional medium of peer reviewed publications there is no one to assess your content prior to its release.  You are your own editor and therefore may miss the mark from time to time by missing a relevant publication that might influence your conclusions.  You must be prepared for the good and the bad.  One can easily appreciate the positive comments that often come but not all posts will be “home runs” and on some occasions the feedback (which will be public) may not be what you had hoped for.  You must constantly reflect on your own potential biases yet strive to improve base of knowledge; adding more ‘signal’ than ‘noise’. Respect for patient confidentiality is paramount and within Canada and elsewhere.  Organizations such as the Canadian Medical Association have set guidelines for conduct in this space that should be adhered to. [Ref 3] This new frontier for the Rugged Individualist is therefore not for the faint of heart.  It does however bring the world closer together and provide one with a post-publication form of peer review.  Once you enter into the fray it may surprise you how much information is in fact out there, that now flows to you through global connections.  It is an evolving form of communication and one that I am happy to part of. In fact, I am a better neonatologist for it. Is it right for you?

 

 

 

The New BPD That Matters

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.  image040As 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 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.

Benchmarking

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.

 

 

Healthy at risk infants failing the infant car seat challenge. Cause for concern?

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.

Conclusion

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?

 

Has permissive hypercapnia failed to deliver?

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 Low Target High Target
1-3 40-50 55-65
4-6 45-55 60-70
7-14 50-60 65-75

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.

You don’t plan to fail. You fail to plan

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. figure-1-the-thal-quick-chest-tube-set-including-introducer-needle-wire-guideIn 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!

 

Just how safe is feeding while on CPAP?

This is becoming “all the rage” as they say.  I first heard about the strategy of feeding while on CPAP from colleagues in Calgary.  They had created the SINC * (Safe Individualized Feeding Competence) program to provide an approach to safely introducing feeding to those who were still requiring CPAP.  As news of this approach spread a great deal of excitement ensued as one can only imagine that in these days when attainment of oral feeding is a common reason for delaying discharge, could getting an early start shorten hospital stay?  I could describe what they found with the implementation of this strategy but I couldn’t do it the same justice as the presenter of the data did at a recent conference in Winnipeg.  For the slide set you can find them here.  As you can imagine, in this experience out of Calgary though they did indeed find that wonderful accomplishment of shorter hospital stays in the SINC group.  We have been so impressed with the results and the sensibility of it all that we in fact have embraced the concept and introduced it here in both of our units.  The protocol for providing this approach is the following.eating-in-sinc-algorithm

I have to admit, while I have only experienced this approach for a short time the results do seem to be impressive.  Although anecdotal a parent even commented the other day that she felt that SINC was instrumental in getting her baby’s feeding going!  With all this excitement around this technique I was thrown a little off kilter when a paper came out suggesting we should put a full stop to feeding on CPAP!

Effect of nasal continuous positive airway pressure on the pharyngeal swallow in neonates

What caused my spirits to dampen? This study enrolled preterm infants who were still on CPAP at ≥ 34 weeks PMA and were taking over 50% of required feeding volumes by NG feeding.  The goal was to look at 15 patients who were being fed on CPAP +5 and with a mean FiO2 of 25% (21-37%) using video fluoroscopic swallowing studies to determine whether such patients aspirate when being fed.  The researchers became concerned when each of the first seven patients demonstrated abnormalities of swallowing function indicating varying degrees of aspiration.  As such they took each patient off CPAP in the radiology suite and replaced it with 1 l/min NP to achieve acceptable oxygen saturations and repeated the study again.  The results of the two swallow studies showed remarkable differences in risk to the patient and as such the recruitment of further patients was stopped due to concerns of safety and a firm recommendation of avoiding feeding while on CPAP was made.

Table 2. Percentage of all swallows identified with swallowing dysfunction
on-nCPAP off-nCPAP
Variable Mean ± s.d. Mean ± s.d. Median (q1–q3) Mean ± s.d. Median (q1–q3) P-value
Mild pen. % 20.1±16 20 (4.5–35) 15.4± 7.6 20 (9–20) 0.656
Deep pen. % 43.7±15.4 38.5 (30–59) 25.3± 8.8  25 (18.2–32) 0.031
Aspiration % 33.5±9.4 30 (27.3–44.4) 14.6± 7 15 (9.1–20) 0.016
Nasopharyngeal reflux   % 42.8±48.5 18.2 (0–100) 44.2± 45.4 18.2 (5–92) 0.875

Taking these results at face value it would seem that we should put an abrupt halt to feeding while on CPAP but as the saying goes the devil is in the details…

CPAP Using Ram Cannulae

Let me start off by saying that I don’t have any particular fight to pick with the RAM cannulae.  They serve a purpose and that is they allow CPAP to be delivered with a very simple set of prongs and avoid the hats, straps and such of more traditional CPAP devices. We have used them as temporary CPAP delivery when moving a patient from one area to another.  As the authors state the prongs are sized in order to ensure the presence of a leak.  This has to do with the need to provide a way for the patient to exhale when nasal breathing.  Prongs that are too loose have a large leak and may not deliver adequate pressure while those that are too tight may inadvertently deliver high pressure and therefore impose significant work of breathing on the patient.nonivasive-respiratory-support-niv-high-frequency-ventilation-hfv-63-638  Even with appropriate sizing these prongs do not allow one to exhale against a low pressure or flow as is seen with the “fluidic flip” employed with the infant flow interface. With the fluidic flip, exhalation occurs against very little resistance thereby reducing work of breathing which is not present with the use of the RAM cannula.

A comparison of the often used “bubble CPAP” to a variable flow device also showed lower work of breathing when variable flow is used.

The Bottom Line

Trying to feed an infant who is working against a constant flow as delivered by the RAM cannulae is bound to cause problems.  I don’t think it should be a surprise to find that trying to feed while struggling to breathe increases the risk of aspiration.  Similarly, under treating a patient by placing them on nasal prongs would lead to increased work of breathing as while you may provide the needed O2 it is at lower lung volumes.  Increasing work of breathing places infants at increased risk of aspiration.  That is what I would take from this study.  Interestingly, looking at the slide set from Calgary they did in fact use CPAP with the fluidic flip.  Smart people they are.  It would be too easy to embrace the results of this study and turn your nose to the SINC approach to feeding on CPAP.  Perhaps somewhere out there someone will read this and think twice about abandoning the SINC approach and a baby will be better for it.

* SINC algorithm and picture of the fluidic flip courtesy of Stacey Dalgleish and the continued work of Alberta Health Services

 

The Hidden Pathogen Of Late Onset Sepsis

If you work in the NICU then you have seen your fair share of septic workups for late onset sepsis.  Sepsis is such a common diagnosis that if I had to guess I would say that at least 50% of all discharge summaries would include this in a list of final diagnoses for any VLBW infant.  If you were to look through the chart though you would find that while workups are common, the recovery of a pathogenic bacterium is not as much.  This is in part due to the low threshold that many people have for doing such workups.  A little bit of temperature instability, a few more apneic events than normal or a rise in O2 requirements may all trigger such investigations.  When they come back negative we all feel good that we looked but we also are then quick to blame the etiology on something else.  Mild fluctuations in temperature are written off as overbundling, apnea due to outgrowth of caffeine and a rise in FiO2 to evolving CLD.  Maybe though the explanation at least in some cases is that there was a pathogen but we didn’t test for it.

Viruses are everywhere

Tis the season so to speak so everyone is on high alert for viruses in our homes, schools, malls etc but many of us consider the NICU to be mostly free of such pathogens.  The truth is we mostly are provided that we all wash our hands well, keep sick contacts from visiting and put on a mask when our coughing starts.  Alas, if you have done a handwashing audit as we have you would know that when looking at technique and duration of handwashing, we don’t always hit 100%.  These audits are for health care practitioners but I have often wondered what sort of results we would see were we to do the same for parents and visitors.  When we know the viruses are out there such as during outbreaks of RSV and influenza we can’t help but send off our samples for respiratory viruses more frequently but what if we did this with intention for every late onset septic workup?

Lucky For Us Someone Did Just That!

Back in 2014 the following study was published. Viral respiratory tract infections in the neonatal intensive care unit: the VIRIoN-I study.  This was a simple prospective and elegant study in which any infant in the NICU who had never been home and was greater than 72 hours had respiratory samples sent for viral panels within 72 hours of starting antibiotics for presumed late onset sepsis.  The findings were certainly interesting in that 6% of 135 sepsis evaluations tested positive for a virus.  In the analysis, the infants had the following characteristics:

  • tended to be older (41 vs 11 days; P = .007)
  • exposed to individuals with respiratory tract viral symptoms (37% vs 2%; P = .003)
  • lower total neutrophil counts (P = .02)
  • best predictor of viral infection was the caregivers’ clinical suspicion of viral infection (P = .006)

What interests me about these results are a couple things.  The first is that as I was once told, the sensitivity of asking if someone has been around sick people is low during peaks in viral outbreaks as who hasn’t?  Perhaps what this study tells us is that within the NICU environment we actually do a reasonable job of keeping such contacts away but when they slip through infections happen.  The second point worth mentioning is that a low neutrophil count is associated which is interesting given how often neutropenia is pointed to as a reason to start antibiotics.  These viruses are troublesome creatures indeed!

Further Evidence Arrives

At the end of last year a similar study was published by the same group Viral Respiratory Infections in Preterm Infants during and after Hospitalization.  They took a different approach this time out and took nasopharyngeal samples from 189 infants in the NICU (96 term and 93 preterm) within 7 days of birth and then sent samples weekly while in hospital followed by monthly for four months after discharge. In this collection of infants a mere 4 patients tested positive in NICU and all of them under 28 weeks of age at birth!  How do we account for the remarkable reduction in risk while in hospital?  To answer that you can read through the NICU environment in the full article if you have access.  In short, they had a very rigorous infection control set of precautions set up.  washing-hands-waterInterestingly only one of the infections was with RSV and the unit did not provide prophylaxis for infants in hospital.  Perhaps with precautions like theirs they felt it was unnecessary.  Once discharged a little over a third of patients acquired a viral infection in the first four months at home.  Given the potential risk for readmission and with that to a PICU this rate of viral infection is concerning.

Vision for the future!

Taken together we can state that viruses do make their way into the NICU but fortunately not as commonly as one might think.  What the last study in particular does remind us though is that we need to ensure that as part of discharge teaching parents take home many of the practices that we have used in the hospital with respect to hand hygiene, limiting visitors and not being afraid to holster some hand sanitizer for those times when soap and water are not so easy to come by.  To be sure viruses are out there but at least for the first few months after discharge for our most vulnerable babies a little paranoia about viruses could go a long way.