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About this blog

I am a Neonatologist trained in Winnipeg, Manitoba and Edmonton, Alberta.  My current position is Section Head of Neonatology in Manitoba and over my career my interests have meandered from time to time.  I have been a past Program Director of Neonatology and Medical Director for a level II Intensive Care Unit prior to relocating to Winnipeg become a Section Head.

Welcome to my blog which I hope will provide a forum for discussion on topics that are of interest to Neonatologists, trainees, all health care professionals and in some cases parents of those we care for.  My intent is to post opinions and analysis on both items from the media and literature that pertain to neonates.  While I have many interests, my particular motivation is to find ways to reduce discomfort for the patients that we care for.  Whether it is through the use of non-invasive testing or finding a way to improve the patient experience this is where I find myself most energized.

I chose the picture for this site as since the inception of this site there is hardly a country that has not had an individual or many people view posts.  Moreover I have received comments from many people from so many different countries that have inspired me to think not just about the impact of these posts in North America but more globally as well.

If you like what you see and would like updates to be sent to you as they are published feel free to follow the site by clicking the follow button on the sidebar to the bottom right.  You can also follow both my Twitter (@NICU_Musings) and Facebook feeds for additional content and discussion by clicking the additional links found there.

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Entries in this blog

AllThingsNeonatal
Can a chest x-ray predict the future?

If you work in Neonatology then chances are you have ordered or assisted with obtaining many chest x-rays in your time.  If you look at home many chest x-rays some of our patients get, especially the ones who are with us the longest it can be in the hundreds. I am happy to say the tide though is changing as we move more and more to using other imaging modalities such as ultrasound to replace some instances in which we would have ordered a chest x-ray.  This has been covered before on this site a few times; see Point of Care Ultrasound in the NICU, Reducing Radiation Exposure in Neonates: Replacing Radiographs With Bedside Ultrasound. and Point of Care Ultrasound: Changing Practice For The Better in NICU.This post though is about something altogether different.

If you do a test then know what you will do with the result before you order it.

If there is one thing I tend to harp on with students it is to think about every test you do before you order it.  If the result is positive how will this help you and if negative what does it tell you as well.  In essence the question is how will this change your current management. If you really can’t think of a good answer to that question then perhaps you should spare the infant the poke or radiation exposure depending on what is being investigated.  When it comes to the baby born before 30 weeks these infants are the ones with the highest risk of developing chronic lung disease.  So many x-rays are done through their course in hospital but usually in response to an event such as an increase in oxygen requirements or a new tube with a position that needs to be identified.  This is all reactionary but what if you could do one x-ray and take action based on the result in a prospective fashion?

What an x-ray at 7 days may tell you

How many times have you caught yourself looking at an x-ray and saying out loud “looks like evolving chronic lung disease”.  It turns out that Kim et al in their publication Interstitial pneumonia pattern on day 7 chest radiograph predicts bronchopulmonary dysplasia in preterm infants.believe that we can maybe do something proactively with such information.

In this study they looked retrospectively at 336 preterm infants weighing less than 1500g and less than 32 weeks at birth.  Armed with the knowledge that many infants who have an early abnormal x-ray early in life who go on to develop BPD, this group decided to test the hypothesis that an x-ray demonstrating a pneumonia like pattern at day 7 of life predicts development of BPD.  Screenshot-2017-10-10-21.43.36-copy-300xThe patterns they were looking at are demonstrated in this figure from the paper.  Essentially what the authors noted was that having the worst pattern of the lot predicted the development of later BPD.  The odds ratio was 4.0 with a confidence interval of 1.1 – 14.4 for this marker of BPD.  Moreover, birthweight below 1000g, gestational age < 28 weeks and need for invasive ventilation at 7 days were also linked to the development of the interstitial pneumonia pattern.

What do we do with such information?

I suppose the paper tells us something that we have really already known for awhile.  Bad lungs early on predict bad lungs at a later date and in particular at 36 weeks giving a diagnosis of BPD.  What this study adds if anything is that one can tell quite early whether they are destined to develop this condition or not.  The issue then is what to do with such information.  The authors suggest that by knowing the x-ray findings this early we can do something about it to perhaps modify the course.  What exactly is that though?  I guess it is possible that we can use steroids postnatally in this cohort and target such infants as this. I am not sure how far ahead this would get us though as if I had to guess I would say that these are the same infants that more often than not are current recipients of dexamethasone.

Would another dose of surfactant help?  The evidence for late surfactant isn’t so hot itself so that isn’t likely to offer much in the way of benefit either.

In the end the truth is I am not sure if knowing concretely that a patient will develop BPD really offers much in the way of options to modify the outcome at this point.  Having said that the future may well bring the use of stem cells for the treatment of BPD and that is where I think such information might truly be helpful.  Perhaps a screening x-ray at 7 days might help us choose in the future which babies should receive stem cell therapy (should it be proven to work) and which should not.  I am proud to say I had a chance to work with a pioneer in this field of research who may one day cure BPD.  Dr. Thebaud has written many papers of the subject and if you are looking for recent review here is one Stem cell biology and regenerative medicine for neonatal lung diseases.Do I think that this one paper is going to help us eradicate BPD?  I do not but one day this strategy in combination with work such as Dr. Thebaud is doing may lead us to talk about BPD at some point using phrases like “remember when we used to see bad BPD”.  One can only hope.

 

AllThingsNeonatal

 

 

Automated control of FiO2; one step closer

It has been over two years since I have written on this subject and it continues to be something that I get excited about whenever a publication comes my way on the topic.  The last time I looked at this topic it was after the publication of a randomized trial comparing in which one arm was provided automated FiO2 adjustments while on ventilatory support and the other by manual change.  Automated adjustments of FiO2. Ready for prime time? In this post I concluded that the technology was promising but like many new strategies needed to be proven in the real world. The study that the post was based on examined a 24 hour period and while the results were indeed impressive it left one wondering whether longer periods of use would demonstrate the same results.  Moreover, one also has to be wary of the Hawthorne Effect whereby the results during a study may be improved simply by being part of a study.

The Real World Demonstration

So the same group decided to look at this again but in this case did a before and after comparison.  The study looked at a group of preterm infants under 30 weeks gestational age born from May – August 2015 and compared them to August to January 2016.  The change in practice with the implementation of the CLiO2 system with the Avea ventilator occurred in August which allowed two groups to be looked at over a relatively short period of time with staff that would have seen little change before and after.  The study in question is by Van Zanten HA The effect of implementing an automated oxygen control on oxygen saturation in preterm infants. For the study the target range of FiO2 for both time periods was 90 – 95% and the primary outcome was the percentage of time spent in this range.  Secondary outcomes included time with FiO2 at > 95% (Hyperoxemia) and < 90, <85 and < 80% (hypoxemia). Data were collected when infants received respiratory support by the AVEA and onlyincluded for analysis when supplemental oxygen was given, until the infants reached a GA of 32 weeks

As you might expect since a computer was controlling the FiO2 using a feedback loop from the saturation monitor it would be a little more accurate and immediate in manipulating FiO2 than a bedside nurse who has many other tasks to manage during the care of an infant.  As such the median saturation was right in the middle of the range at 93% when automated and 94% when manual control was used. Not much difference there but as was seen in the shorter 24 hour study, the distribution around the median was tighter with automation.  Specifically with respect to ranges, hyperoxemia and hypoxemia the following was noted (first number is manual and second comparison automated in each case).

Time spent in target range: 48.4 (41.5–56.4)% vs 61.9 (48.5–72.3)%; p<0.01

Hyperoxemia  >95%: 41.9 (30.6–49.4)% vs 19.3 (11.5–24.5)%; p<0.001

< 90%: 8.6 (7.2–11.7)% vs 15.1 (14.0–21.1)%;p<0.0001

< 85%: 2.7 (1.4–4.0)% vs 3.2 (1.8–5.1)%; ns

Hypoxemia < 80%: 1.1 (0.4–1.7)% vs 0.9 (0.5–2.1)%; ns

What does it all mean?

I find it quite interesting that while hyperoxemia is reduced, the incidence of saturations under 90% is increased with automation.  I suspect the answer to this lies in the algorithmic control of the FiO2. With manual control the person at the bedside may turn up a patient (and leave them there a little while) who in particular has quite labile saturations which might explain the tendency towards higher oxygen saturations.  This would have the effect of shifting the curve upwards and likely explains in part why the oxygen saturation median is slightly higher with manual control.  With the algorithm in the CLiO2 there is likely a tendency to respond more gradually to changes in oxygen saturation so as not to overshoot and hyperoxygenate the patient.  For a patient with labile oxygen saturations this would have a similar effect on the bottom end of the range such that patients might be expected to drift a little lower then the target of 90% as the automation corrects for the downward trend.  This is supported by the fact that when you look at what is causing the increase in percentage of time below 90% it really is the category of 85-89%.

Is this safe? There will no doubt be people reading this that see the last line and immediately have flashbacks to the SUPPORT trial which created a great deal of stress in the scientific community when the patients in the 85-89% arm of the trial experienced higher than expected mortality.  It remains unclear what the cause of this increased mortality was and in truth in our own unit we accept 88 – 92% as an acceptable range.  I have no doubt there are units that in an attempt to lessen the rate of ROP may allow saturations to drop as low as 85% so I continue to think this strategy of using automation is a viable one.

For now the issue is one of a ventilator that is capable of doing this.  If not for the ventilated patient at least for patients on CPAP.  In our centre we don’t use the Avea model so that system is out.  With the system we use for ventilation there is also no option.  We are anxiously awaiting the availability of an automated system for our CPAP device.  I hope to be able to share our own experience positively when that comes to the market.  From my standpoint there is enough to do at the bedside.  Having a reliable system to control the FiO2 and minimize oxidative stress is something that may make a real difference for the babies we care for and is something I am eager to see.

AllThingsNeonatal

 

 

Maybe we shouldn’t be in such a rush to stop caffeine.

Given that many preterm infants as they near term equivalent age are ready to go home it is common practice to discontinue caffeine sometime between 33-34 weeks PMA.  We do this as we try to time the readiness for discharge in terms of feeding, to the desire to see how infants fare off caffeine.  In general, most units I believe try to send babies home without caffeine so we do our best to judge the right timing in stopping this medication.  After a period of 5-7 days we generally declare the infant safe to be off caffeine and then move on to other issues preventing them from going home to their families.  This strategy generally works well for those infants who are born at later gestations but as Rhein LM et al demonstrated in their paper Effects of caffeine on intermittent hypoxia in infants born prematurely: a randomized clinical trial., after caffeine is stopped, the number of intermittent hypoxic (IH) events are not trivial between 35-39 weeks.  Caffeine it would seem may still offer some benefit to those infants who seem otherwise ready to discontinue the medication.  What the authors noted in this randomized controlled trial was that the difference caffeine made when continued past 34 weeks was limited to reducing these IH events only from 35-36 weeks but the effect didn’t last past that.  Why might that have been?  Well it could be that the babies after 36 weeks don’t have enough events to really show a difference or it could be that the dose of caffeine isn’t enough by that point.  The latter may well be the case as the metabolism of caffeine ramps up during later gestations and changes from a half life greater than a day in the smallest infants to many hours closer to term.  Maybe the caffeine just clears faster?

Follow-up Study attempts to answer that very question.

Recognizing the possibility that levels of caffeine were falling too low after 36 weeks the authors of the previous study begun anew to ask the same question but this time looking at caffeine levels in saliva to ensure that sufficient levels were obtained to demonstrate a difference in the outcome of frequency of IH.  In this study, they compared the original cohort of patients who did not receive caffeine after planned discontinuation (N=53) to 27 infants who were randomized to one of two caffeine treatments once the decision to stop caffeine was made.  Until 36 weeks PMA each patient was given a standard 10 mg/kg of caffeine case and then randomized to two different strategies.  The two dosing strategies were 14 mg/kg of caffeine citrate (equals 7 mg/kg of caffeine base) vs 20 mg/kg (10 mg/kg caffeine base) which both started once the patient reached 36 weeks in anticipation of increased clearance.  Salivary caffeine levels were measured just prior to stopping the usual dose of caffeine and then one week after starting 10 mg/kg dosing and then at 37 and 38 weeks respectively on the higher dosing.  Adequate serum levels are understood to be > 20 mcg/ml and salivary and plasma concentrations have been shown to have a high level of agreement previously so salivary measurement seems like a good approach.  Given that it was a small study it is work noting that the average age of the group that did not receive caffeine was 29.1 weeks compared to the caffeine groups at 27.9 weeks.  This becomes important in the context of the results in that earlier gestational age patients would be expected to have more apnea which is not what was observed suggesting a beneficial effect of caffeine even at this later gestational age.  Each patient was to be monitored with an oximeter until 40 weeks as per unit guidelines.

So does caffeine make a difference once term gestation is reached?

A total of 32 infants were enrolled with 12 infants receiving the 14 mg/kg and 14 the 20 mg/kg dosing.  All infants irrespective of assigned group had caffeine concentrations above 20 mcg/mL ensuring that a therapeutic dose had been received.  The intent had been to look at babies out to 40 weeks with pulse oximetry even when discharged but owing to drop off in compliance with monitoring for a minimum of 10 hours per PMA week the analysis was restricted to infants at 37 and 38 weeks which still meant extension past 36 weeks as had been looked at already in the previous study.  The design of this study then compared infants receiving known therapeutic dosing at this GA range with a previous cohort from the last study that did not receive caffeine after clinicians had determined it was no longer needed.

The outcomes here were measured in seconds per 24 hours of intermittent hypoxia (An IH event was defined as a decrease in SaO2 by ⩾ 10% from baseline and lasting for ⩾5 s).  For graphical purposes the authors chose to display the number of seconds oxygen saturation fell below 90% per day and grouped the two caffeine patients together given that the salivary levels in both were therapeutic.  As shown a significant difference in events was seen at all gestational ages.

Putting it into context

The scale used I find interesting and I can’t help but wonder if it was done intentionally to provide impact.  The outcome here is measured in seconds and when you are speaking about a mean of 1200 vs 600 seconds it sounds very dramatic but changing that into minutes you are talking about 20 vs 10 minutes a day.  Even allowing for the interquartile ranges it really is not more than 50 minutes of saturation less than 90% at 36 weeks.  The difference of course as you increase in gestation becomes less as well.  When looking at the amount of time spent under 80% for the groups at the three different gestational ages there is still a difference but the amount of time at 36, 27 and 38 weeks was 229, 118 and 84 seconds respectively without caffeine (about 4, 2 and 1 minute per day respectively) vs 83, 41, and 22 seconds in the caffeine groups. I can’t help but think this is a case of statistical significance with questionable clinical significance.  The authors don’t indicate that any patients were readmitted with “blue spells” who were being monitored at home which then leaves the sole question in my mind being “Do these brief periods of hypoxemia matter?”  In the absence of a long-term follow-up study I would have to say I don’t know but while I have always been a fan of caffeine I am just not sure.

Should we be in a rush to stop caffeine?  Well, given that the long term results of the CAP study suggest the drug is safe in the preterm population I would suggest there is no reason to be concerned about continuing caffeine a little longer. If the goal is getting patients home and discharging on caffeine is something you are comfortable with then continuing past 35 weeks is something that may have clinical impact.  At the very least I remain comfortable in my own practice of not being in a rush to stop this medication and on occasion sending a patient home with it as well.

 

 

AllThingsNeonatal
A Magic Bullet to Reduce Duration of Treatment and Hospital Stays for Newborns With NAS

As someone with an interest in neonatal abstinence (NAS) I am surprised that I missed this study back in May.  Anyone who says they aren’t interested in NAS research must be turning a blind eye to the North American epidemic of patients filling neonatal units or postpartum wards in need of treatment for the same.  News feeds such as CNN have covered this story many times with concerning articles such as this published “Opioid Crisis Fast Facts” even the Trump White House has  officially declared it as an emergency at this pointScreenshot-2017-09-21-07.18.58-300x152.pWith NICU resources stretched and care providers fatigue levels wearing thin (these patients are typically very challenging to take care of due to the crying and agitation with neurological excitability that is at the core of the symptoms, something needs to be done. The vast majority of neonatal care providers treat such patients with an approach that promotes first non pharmacologic strategies such as keeping mom and baby together when possible, breast feeding and disturbing these infants as little as possible to name a few points.  For those patients though who require pharmacologic support though, the mainstay has been oral morphine.  At least in our units though once a patient is admitted and undergoes treatment we are still looking at anywhere from 3-4 weeks on average that they will occupy a hospital bed.  If only there was a better way.

Could Buprenorphine do the trick?

While morphine is widely used to treat NAS symptoms unresponsive to other non pharmacologic methods of control, buprenorphine has a similar profile as an opioid but has less risk of respiratory depression as a partial agonist. A small but important trial has been published directly comparing the use of morphine to buprenorphine for treatment of NAS symptoms with the primary outcome being days of treatment and the second important point being length of stay.  The trial, Buprenorphine for the Treatment of the Neonatal Abstinence Syndrome.by Kraft WK et al was entitled the BBORN trial for short.  This was a single centre trial in which a double blind/double dummy approach was used.  By double dummy this meant that after randomization those babies randomized to morphine received morphine plus a buprenorphine placebo and the other arm received a buprenorphine dose and a morphine placebo.  In total 33 infants were randomized to buprenorphine and 30 to morphine (hence my comment about this being a small study).  Their power calculation had called for 40 infants per arm to detect a 28% difference in the primary end point of duration of treatment but in the end that didn’t matter so much as they found a significant difference exceeding their estimate anyway.  A lack of power would have become important mind you had they not found a difference as they wouldn’t have actually had the numbers to do so.

A strength of the study up front was that all care providers scored NAS symptoms the same way (need to take into account there is some subjectivity in scoring altogether though) and escalations and decreases of medication were done following a strict protocol both ways.  In both arms, once a maximal dose of 60 mcg/kg of body weight for  buprenorphine and 1.2 mg/kg for morphine was reached phenobarbital was added.  When comparing the two groups at the outset there were no significant differences in characteristics so two generally similar populations of infants were being treated.

The Results Were Indeed Impressive

Before launching into the table, there were 21 babies in both groups that were bottle fed and 12 in the burprenorphine group and 9 in the morphine group that breastfed.

Outcome Buprenorphine Morphine p
Median days of treatment 15 (3-67) 28 (13-67) <0.001
Bottle feeding 15 (3-67) 28 (13-67)  
Breast feeding 20 (3-55) 28 (16-52)  
       
Hospital stay in days 21 (7-71) 33 (18-70) <0.001
Bottle feeding 21 (7-71) 33 (18-70)  
Breast feeding 26 (7-58) 32 (20-58)  

No difference was seen in those who needed phenobarbital.  Looking at the table, a couple things really stand out to me.  They were looking for a 28% reduction in days of treatment.  The results came in far excess of that at a 46% reduction.  Curiously, breastfeeding which has classically been associated with a reduction in scores and therefore faster weaning due to less symptoms seemed to have the opposite effect here.  Does this imply that breastfeeding slows down both duration of treatment and length of stay as a result?  With a study this small it is difficult to say with so few breastfed babies but if I had to guess I would suggest those mothers that worked at breastfeeding may have had longer stays.

Should we all jump on the buprenorphine train?

For now I would give this a big maybe.  One of the concerns about burprenorphine is that it comes as a solution of 30% alcohol.  Giving multiple doses (3 per day in this study) of such a solution could in part contribute to these results of lower NAS symptoms.  Is giving alcohol to reduce symptoms a good idea here?  Not sure if there are any long term effects and moreover if the cumulative dose of this medication would be of a concern.  Definitely something to check with your local pharmacist before rolling this out.  On the other hand if the dose of alcohol provided was truly significant I might have expected the burprenorphine group to be poorer feeders due to intoxication which we certainly did not see.

With increasing volumes of newborns afflicted with symptoms of NAS we do need to find a way to stem the tide.  Ideally, primary preventative strategies would be best but until that solution is found could burprenorphine be the next step in tackling this epidemic?

AllThingsNeonatal

 

 

Is  expired CO2 the key to making sustained inflation a standard in resuscitation?

We can always learn and we can always do better.  At least that is something that I believe in.  In our approach to resuscitating newborns one simple rule is clear.  Fluid must be replaced by air after birth and the way to oxygenate and remove CO2 is to establish a functional residual capacity.  2000px-Lungvolumes.svgThe functional residual capacity is the volume of air left in the lung after a tidal volume of air is expelled in a spontaneously breathing infant and is shown in the figure. Traditionally, to establish this volume in a newborn who is apneic, you begin PPV or in the spontaneously breathing baby with respiratory distress provide CPAP to help inflate the lungs and establish FRC.

Is there another way?

Something that has been discussed now for some time and was commented on in the most recent version of NRP was the concept of using sustained inflation (SI) to achieve FRC. I have written about this topic previously and came to a conclusion that it wasn’t quite ready for prime time yet in the piece Is It Time To Use Sustained Lung Inflation In NRP?

The conclusion as well in the NRP textbook was the following:

“There are insufficient data regarding short and long-term safety and the most appropriate duration and pressure of inflation to support routine application of sustained inflation of greater than 5 seconds’ duration to the transitioning newborn (Class IIb, LOE B-R). Further studies using carefully designed protocols are needed”

So what now could be causing me to revisit this concept?   I will be frank and admit that whenever I see research out of my old unit in Edmonton I feel compelled to read it and this time was no different.  The Edmonton group continues to do wonderful work in the area of resuscitation and expand the body of literature in such areas as sustained inflation.

Can you predict how much of a sustained inflation is needed?

This is the crux of a recent study using end tidal CO2 measurement to determine whether the lung has indeed established an FRC or not.  Dr. Schmolzer’s group in their paper (Using exhaled CO2 to guide initial respiratory support at birth: a randomised controlled trial) used end tidal CO2 levels above 20 mmHg to indicate that FRC had been established.  If you have less CO2 being released the concept would be that the lung is actually not open.  There are some important numbers in this study that need to be acknowledged.  The first is the population that they looked at which were infants under 32 6/7 weeks and the second is the incidence of BPD (need for O2 or respiratory support at 36 weeks) which in their unit was 49%.  This is a BIG number as in comparison for infants under 1500g our own local incidence is about 11%.  If you were to add larger infants closer to 33 weeks our number would be lower due to dilution.  With such a large number though in Edmonton it allowed them to shoot for a 40% reduction in BPD (50% down to 30%).  To accomplish this they needed 93 infants in each group to show a difference this big.

So what did they do?

For this study they divided the groups in two when the infant wouldn’t breathe in the delivery room.  The SI group received a PIP of 24 using a T-piece resuscitator for an initial 20 seconds.  If the pCO2 as measured by the ETCO2 remained less than 20 they received an additional 10 seconds of SI.  In the PPV group after 30 seconds of PPV the infants received an increase of PIP if pCO2 remained below 20 or a decrease in PIP if above 20.  In both arms after this phase of the study NRP was then followed as per usual guidelines.

The results though just didn’t come through for the primary outcome although ventilation did show a difference.

Outcome SI PPV p
BPD 23% 33% 0.09
Duration of mechanical ventilation (hrs) 63 204 0.045

The reduction in hours of ventilation was impressive although no difference in BPD was seen.  The problem though with all of this is what happened after recruitment into the study.  Although they started with many more patients than they needed, by the end they had only 76 in the SI group and 86 in the PPV group.  Why is this a problem?  If you have less patients than you needed based on the power calculation then you actually didn’t have enough patients enrolled to show a difference.  The additional compounding fact here is that of the Hawthorne Effect. Simply put, patients who are in a study tend to do better by being in a study.  The observed rate of BPD was 33% during the study.  If the observed rate is lower than expected when the power calculation was done it means that the number needed to show a difference was even larger than the amount they originally thought was needed.  In the end they just didn’t have the numbers to show a difference so there isn’t much to conclude.

What I do like though

I have a feeling or a hunch that with a larger sample size there could be something here.  Using end tidal pCO2 to determine if the lung is open is in and of itself I believe a strategy to consider whether giving PPV or one day SI.  We already use colorimetric devices to determine ETT placement but using a quantitative measure to ascertain the extent of open lung seems promising to me.  I for one look forward to the continued work of the Neonatal Resuscitation–Stabilization–Triage team (RST team) and congratulate them on the great work that they continue doing.

AllThingsNeonatal
Is our approach to ventilation really harming babies?

A grenade was thrown this week with the publication of the Australian experience comparing three epochs of 1991-92, 1997 and 2005 in terms of long term respiratory outcomes. The paper was published in the prestigious New England Journal of Medicine; Ventilation in Extremely Preterm Infants and Respiratory Function at 8 Years. This journal alone gives “street cred” to any publication and it didn’t take long for other news agencies to notice such as Med Page Today. The claim of the paper is that the modern cohort has fared worse in the long run. This has got to be alarming for anyone reading this! As the authors point out, over the years that are being compared rates of antenatal steroid use increased, surfactant was introduced and its use became more widespread and a trend to using non-invasive ventilation began. All of these things have been associated with better short term outcomes. Another trend was declining use of post-natal steroids after 2001 when alarms were raised about the potential harm of administering such treatments.

Where then does this leave us?

I suppose the first thing to do is to look at the study and see if they were on the mark. To evaluate lung function the study looked at markers of obstructive lung disease at 8 years of age in survivors from these time periods. All babies recruited were born between 22-27 completed weeks so were clearly at risk of long term injury. Measurements included FEV1, FVC, FVC:FEV1 and FEF 25-75%. Of the babies measured the only two significant findings were in the FEV1 and ratio of FEV1:FVC. The former showed a drop off comparing 1997 to 2005 while the latter was worse in 2005 than both epochs.

Variable 1991-92 1997 2005
%predicted value N=183 N=112 N=123
FEV1 87.9+/-13.4 92.0+/-15.7 85.4+/-14.4
FEV1:FVC 98.3+/-10 96.8+/-10.1 93.4+/-9.2

This should indeed cause alarm. Babies born in a later period when we thought that we were doing the right things fared worse. The authors wonder if perhaps a strategy of using more CPAP may be a possible issue. Could the avoidance of intubation and dependence on CPAP for longer periods actually contribute to injury in some way? An alternative explanation might be that the use of continuous oximetry is to blame. Might the use of nasal cannulae with temporary rises in O2 expose the infant to oxygen toxicity?

There may be a problem here though

Despite everyone’s best efforts survival and/or BPD as an outcome has not changed much over the years. That might be due to a shift from more children dying to more children living with BPD. Certainly in our own centre we have seen changes in BPD at 36 weeks over time and I suspect other centres have as well. With concerted efforts many centres report better survival of the smallest infants and with that they may survive with BPD. The other significant factor here is after the extreme fear of the early 2000s, use of postnatal steroids fell off substantially. This study was no different in that comparing the epochs, postnatal glucocorticoid use fell from 40 and 46% to 23%. One can’t ignore the possibility that the sickest of the infants in the 2005 cohort would have spent much more time on the ventilator that their earlier counterparts and this could have an impact on the long term lung function.

Another question that I don’t think was answered in the paper is the distribution of babies at each gestational age. Although all babies were born between 22-27 weeks gestational age, do we know if there was a skewing of babies who survived to more of the earlier gestations as more survived? We know that in the survivors the GA was not different so that is reassuring but did the sickest possible die more frequently leaving healthier kids in the early cohorts?

This bigger issue interestingly is not mentioned in the paper. Looking at the original cohorts there were 438 in the first two year cohort of which 203 died yielding a survival of 54% while in 1997 survival increased to 70% and in 2005 it was 65%. I can’t help but wonder if the drop in survival may have reflected a few more babies at less than 24 weeks being born and in addition the holding of post natal steroids leading to a few more deaths. Either way, there are enough questions about the cohorts not really being the same that I think we have to take the conclusions of this paper with a grain of salt.

It is a sensational suggestion and one that I think may garner some press indeed. I for one believe strongly though as I see our rates of BPD falling with the strategies we are using that when my patients return at 8 years for a visit they will be better off due to the strategies we are using in the current era. Having said that we do have so much more to learn and I look forward to better outcomes with time!

AllThingsNeonatal

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Exclusive human milk (EHM) diets using either mother’s own milk or donor milk plus a human based human milk fortifier have been the subject of many papers over the last few years. Such papers have demonstrated reductions is such outcomes as NEC, length of stay, days of TPN and number of times feedings are held due to feeding intolerance to name just a few outcomes. There is little argument that a diet for a human child composed of human milk makes a great deal of sense. Although we have come to rely on bovine sources of both milk and fortifier when human milk is unavailable I am often reminded that bovine or cow’s milk is for baby cows.

Challenges with using an exclusive human milk diet.

While it makes intuitive sense to strive for an exclusive human milk diet, there are barriers to the same. Low rates of maternal breastfeeding coupled with limited or no exposure to donor breast milk programs are a clear impediment. Even if you have those first two issues minimized through excellent rates of breast milk provision, there remains the issue of whether one has access to a human based fortifier to achieve the “exclusive” human milk diet.

The “exclusive” approach is one that in the perfect world we would all strive for but in times of fiscal constraint there is no question that any and all programs will be questioned from a cost-benefit standpoint. The issue of cost has been addressed previously by Ganapathy et al in their paper Costs of Necrotizing Enterocolitis and Cost-Effectiveness of Exclusively Human Milk-Based Products in Feeding Extremely Premature Infants. The authors were able to demonstrate that choosing an exclusive human milk diet is cost effective in addition to the benefits observed clinically from such a diet. In Canada where direct costs are more difficult to visualize and a reduction in nursing staff per shift brings about the most direct savings, such an argument becomes more difficult to achieve.

Detractors from the EHM diet argue that we have been using bovine fortification from many years and the vast majority of infants regardless of gestational age have little challenge with it. Growth rates of 15-20 g/kg/d are achievable using such fortification so why would you need to treat all patients with an EHM diet?

A Rescue Approach

In our own centre we were faced with these exact questions and developed a rescue approach. The rescue was designed to identify those infants who seemed to have a clear intolerance to bovine fortifier as all of the patients we care for under 1250g receive either mother’s own or donor milk. The approach used was as follows:

A. < 27 weeks 0 days or < 1250 g
a. 2 episode of intolerance to HMF
b. Continue for 2 weeks

This month we published our results from using this targeted rescue approach in Winnipeg, Human Based Human Milk Fortifier as Rescue Therapy in Very Low Birth Weight Infants Demonstrating Intolerance to Bovine Based Human Milk Fortifier with Dr. Sandhu being the primary author (who wrote this as a medical student with myself and others. We are thrilled to share our experience and describe the cases we have experienced in detail in the paper. Suffice to say though that we have identified value in such an approach and have now modified our current approach based on this experience to the following protocol for using human derived human milk fortifier in our centre to the current:
A. < 27 weeks 0 days or < 1250 g
a. 1 episode of intolerance to HMF
b. Continue for 4 weeks
B. ≥ 27 week 0 days or ≥ 750g
a. 2 episodes of intolerance to HMF
b. Continue for 4 weeks or to 32 weeks 0 days whichever comes sooner

We believe given our current contraints, this approach will reduce the risk of NEC, feeding intolerance and ultimately length of stay while being fiscally prudent in these challenging times. Given the interest at least in Canada with what we have been doing here in Winnipeg and with the publication of our results it seemed like the right time to share this with you.

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It’s possible! Resuscitation with volume ventilation after delivery.

I know how to bag a baby.  At least I think I do.  Providing PPV with a bag-valve mask is something that you are taught in NRP and is likely one of the first skills you learned in the NICU.  We are told to squeeze the bag at a rate of 40-60 breaths a minute.  According to the Laerdal website, the volume of the preterm silicone bag that we typically use is 240 mL.  Imagine then that you are wanting to ventilate a baby who is 1 kg.  How much should you compress the bag if you wish to delivery 5 mL/kg.  Five ml out of a 240 mL bag is not a lot of squeeze is it?  Think about that the next time you find yourself squeezing one.  You might then say but what about a t-piece resuscitator?  A good choice option as well but how much volume are you delivering if you set the initial pressures at 20/5 for example?  That would depend on the compliance of the lung of course.  The greater the compliance the more volume would go in. Would it be 5 mL, 10 ml or even 2.5 mL based on the initial setting?  Hard to say as it really depends on your seal and the compliance of the lung at the pressure you have chosen.  If only we had a device that could deliver a preset volume just like on a ventilator with a volume guarantee setting!

Why is this holy grail so important?

It has been over 30 years since the importance of volutrauma was demonstrated in a rabbit model. Hernandez LA et al published Chest wall restriction limits high airway pressure-induced lung injury in young rabbits. The study used three models to demonstrate the impact of volume as opposed to pressure on injuring the lung of preterm rabbits.  Group 1 were rabbit ventilated at pressures of 15/30/45 cm H2O for one hour, group 2 rabbits with a cast around their thorax to limit volume expansion and group 3 sets of excised lungs with no restriction to distension based on the applied pressures.  As you might expect, limitation of over distension by the plaster cast led the greatest reduction in injury (measured as microvascular permeability) with the excised lungs being the worst.  In doing this study the authors demonstrated the importance of over distension and made the case for controlling volume more than pressure when delivering breaths to avoid excessive tidal volume and resultant lung injury.

The “Next Step” Volume Ventilator BVM

Perhaps I am becoming a fan of the Edmonton group.  In 2015 they published A Novel Prototype Neonatal Resuscitator That Controls Tidal Volume and Ventilation Rate: A Comparative Study of Mask Ventilation in a Newborn Manikin.  The device is tablet based and as described, rather than setting a PIP to deliver a Vt, a rate is set along with a volume to be delivered with a peep in this case set at +5.  fped-04-00129-g002_figure2This study compared 5 different methods of delivering PPV to a 1 kg preterm manikin.  The first was a standard self inflating bag, the next three different t-piece resuscitators and then the Next Step.  For the first four the goal was to deliver a pressure of 20/5 at a rate of 40-60 breaths per minute.  A test lung was connected to the manikin such that each device was used for a one minute period at three different levels of compliance (0.5 ml/cmH2O, 1.0 ml/cmH2O and then 2.0 ml/cm H2O representing increasing compliance.  The goal of the study was to compare the methods in terms of delivering a volume of 5 mL to this 1 kg model lung.  The order in which the devices were used was randomized for the 25 participants in the study who were all certified in NRP and included some Neonatologists.

Some Concerning Findings

As I said at the beginning, we all like to think we know how to ventilate a newborn with BVM.  The results though suggest that as compliance increases our ability to control how much volume we deliver to a lung based on a best guess for pressures needed is lacking.  One caveat here is that the pressures set on the t-piece resucitators were unchanged during the 1 minute trials but then again how often during one minute would we change settings from a starting point of 20/5?

    Vt (mL)  
  0.5 mL/cmH20 1.0 mL/cmH20 2.0mL/cmH20
Self inflating 11.4 17.6 23.5
Neo-Tee 5.6 11.2 19.3
Neopuff 6.1 10 21.3
Giraffe 5.7 10.9 19.8
Next Step 3.7 4.9 4.5

Without putting in all the confidence intervals I can tell you that the Next Step was the tightest.  What you notice immediately (or at least I did) was that no matter what the compliance, the self inflating bag delivers quite an excessive volume even in experienced hands regardless of compliance.  At low compliance the t-piece resuscitators do an admirable job as 5-6 ml/kg of delivered Vt is reasonable but as compliance improves the volumes increase substantially.  It is worth pointing out that at low compliance the Next Step was unable to deliver the prescribed Vt but knowing that if you had a baby who wasn’t responding to ventilation I would imagine you would then try a setting of 6 ml/kg to compensate much like you would increase the pressure on a typical device. How might these devices do in a 29 week infant for example with better compliance than say a 24 week infant?  You can’t help but wonder how many babies are given minutes of excessive Vt after birth during PPV with the traditional pressure limited BVM setup and then down the road how many have BPD in part because of that exposure.

I wanted to share this piece as I think volume resuscitation will be the future.  This is just a prototype or at least back then it was.  Interestingly in terms of satisfaction of use, the Next Step was rated by the participants in the study as being the easiest and most comfortable to use of all the devices studied.  Adding this finding to the accuracy of the delivered volume and I think we could have a winner.

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Is this for real?!

I would consider myself fairly open minded when it comes to care in the NICU.  I wouldn’t call myself a maverick or careless but I certainly am open to new techniques or technologies that may offer a better level of care for the babies in our unit.  When it comes to “non-Western” concepts though such as therapeutic touch, chiropractic manipulations of infants and acupuncture (needle or otherwise) I have generally been a skeptic.  I have written about such topics before with the most popular post being Laser acupuncture for neonatal abstinence syndrome.  My conclusion there was that I was not a fan of the strategy but perhaps I could be more open to non traditional therapies.

Magnetic Acupuncture

This would appear to be the newest and perhaps strangest (to me at least) approach to pain relief that I have seen.  I do love name of this study; the MAGNIFIC trial consisted of a pilot study on the use of auricular magnetic acupuncture to alleviate pain in the NICU from heel lances.  The study was published in Acta Paediatrica this month; Magnetic Non-Invasive Acupuncture for Infant Comfort (MAGNIFIC) – A single-blinded randomized controlled pilot trial.  The goal here was to measure pain scores using the PIPP scoring system for pain in the neonate before during and after a painful experience (heel lance) in the NICU.  Being a pilot study it was small with only 20 needed per arm based on the power calculation to detect a 20% difference in scores.  The intervention used small magnets placed at specific locations on the ear of the infant at least two hours before the heel lance was to occur.  Before I get into the results, the authors of the study provide references to explain how the therapy works. 600pcs-Magnetic-Therapy-Ear-Seeds-Sticke Looking at the references I have to admit I was not able to obtain complete papers but the evidence is generally it would appear from adult patients.  The explanation has to do with the magnetic field increasing blood flow to the area the magnet is applied to and in addition another reference suggests that there are affects the orbitofrontal and limbic regions which then impacts neurohormonal responses as seen in functional MRI.  The evidence to support this is I would have thought would be pretty sparse but I was surprised to find a literature review on the subject that looked at 42 studies on the topic.  The finding was that 88% of the studies reported a therapeutic effect.  The conclusion though of the review was that the quality of the included studies was a bit sketchy for the most part so was not able to find that this should be a recommended therapy.

So what were the results?

Despite my clear skepticism what this study did well was that aside from the magnets, the intervention was the same.  Twenty one babies received the magnetic treatments vs 19 placebo.  There was a difference in the gestational ages of the babies with the magnet treated infants being about two weeks older (35 vs 33 weeks).  What difference that might in and of itself have on the PIPPs scoring I am not sure.  The stickers were applied to the ears with and without magnets in a randomized fashion and the nurses instructed to score them using the PIPP scoring system.  Interestingly, as per their unit policy all babies received sucrose as well before the intervention of a heel lance so I suppose the information gleaned here would be the use of magnets as an adjunctive treatment.  No difference was noted in the two groups before and after the heel lance but during the procedure the magnet treated infants had a difference in means (SD): 5.9 (3.7) v 8.3 (4.7), p=0.04).  No differences were found in secondary measures such as HR or saturation and no adverse effects were noted.  The authors conclusions were that it was feasible and appears safe and as with most pilot studies warrants further larger studies to verify the results.

Should we run out and buy it?

One of the issues I have with the study is that in the introduction they mention that this treatment might be useful where kangaroo care (KC) is not such as a critically ill infant.  Having placed infants who are quite sick in KC and watched wonderful stability arise I am not sure if the unit in question under utilizes this important modality for comfort.

The second and perhaps biggest issue I have here is that although the primary outcome was reached it does seem that there was some fishing going on here.  By that I mean there were three PIPP scores examined (before, during and after) and one barely reached statistical significance.  My hunch is that indeed this was reached by chance rather than it being a real difference.

The last concern is that while the intervention was done in a blinded and randomized fashion, the evidence supporting the use of this in the first place is not strong.  Taking this into account and adding the previous concern in as well and I have strong doubts that this is indeed “for real”.  I doubt this will be the last we will hear about it and while my skepticism continues I have to admit if a larger study is produced I will be willing and interested to read it.

AllThingsNeonatal

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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.

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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?

AllThingsNeonatal

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Things aren’t the way they used to be.  When I was training, opportunities abounded for opportunities to intubate infants.  Then we did away with intubating vigourous infants born through meconium and now won’t be electively intubating them at all.  Then you can add in the move towards use of non-invasive respiratory support instead of intubating and giving surfactant and voila…you have the perfect barrier for training residents and others how to intubate.  On top of all of this the competition for learning has increased as the skill that was once the domain of the physician has now spread (quite rightly) to respiratory therapists, nurses in some places and with the growth of residency programs (ours is now 2.5X larger than when I trained) the scarce chances are divided among many.

Enter the Video Laryngoscope

To be clear this isn’t a post to promote a product but rather an examination of the effectiveness of a tool.  I am putting this out there recognizing the possibility that someone out there might have heard of or have been contemplating purchasing one of these items.  3467268_rdax_80Those that are quite proficient at intubation (likely trained in the “good old days”) would likely question the need for such a device but I believe the device isn’t really aimed at that group except to use perhaps as a teaching tool.  It really is targeted (at least I think) for those who don’t perform the skill often.

Does use of the video laryngoscope improve success rates at intubation?

This question has had an attempt now at being answered by Parmekar S et al in their paper Mind the gap: can videolaryngoscopy bridge the competency gap in neonatal endotracheal intubation among pediatric trainees? a randomized controlled study.  The study involved taking 100 pediatric residents and randomizing them into two groups.  The first would use the videolaryngoscope (VL group) and then intubate using the standard technique of direct laryngoscopy (DL group).  The second group started with DL and then changed to VL. Both groups took part in a training session on intubation and then participated in three simulation scenarios from NRP.

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The findings demonstrated a couple interesting things.  The first as shown in the graph was that the group that started with the laryngoscope had a near 90% success rate compared to about 60% for the traditional approach.  When the groups swapped though they were both equal in effectiveness. This suggests that by visualizing the airway with the VL students were able to identify structures better after doing so such that success was improved simply by having used the device.

The other finding worth mentioning was that when the times to intubation were looked at, there was no difference between the two groups at all.  If the intubation success is no different, why might the times be the same?  Having used the video laryngoscope myself it does take some getting used to.  Rather than looking directly at the airway you find yourself looking off to the side and adjusting the approach that is in front of you to place the ETT.  No doubt this does take some getting used to.

What I would have liked to see is a repeat assessment a week later after using a few more trials with the VL as I suspect once you are used to it the speed of intubation would improve as well.  I suppose though we will have to wait a little while until someone does such work but as a means of improving success in intubation I believe this tool has something to add.

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I had the pleasure of meeting the author of a paper I am about to comment on this week while at the 99 NICU conference in Stockholm.  Dr. Ohlin from Orebro University in Sweden presented very interesting work on their unit’s “scrub the hub” campaign. As he pointed out, many places attempt to reduce coagulase negative staphylococcal infections by introducing central line bundles but seldom is there one thing that is changed in a bundle that allows for a before and after comparison like his team was able to do.  I was so impressed by this work and at the same time concerned about another strategy to reduce infection that I felt compelled to make a comment here.

Scrub the hub!

Dr. Ohlin and the first author Dr. Bjorkman published Scrubbing the hub of intravenous catheters with an alcohol wipe for 15 sec reduced neonatal sepsis back in 2015.  They compared a 16.5 month period in their unit when they rolled out a CLABI reduction bundle to a period of 8.5 months afterwards when they made one change.  Nurses as is done in the units I work in were commonly scrubbing the hub before they injected the line with a medication but in the second epoch the standard changed to be a specified 15 second scrub instead of being left up to the individual nurse.  With permission from Dr. Ohlin here is a picture of the hubs highlighting bacterial growth without scrubbing, then for a duration less than 15 seconds and then with 15 seconds.

In the first epoch they had 9 confirmed CLABSIs and 0 confirmed in the second after their intervention.  The rate of CLABSI then in the first epoch was 1.5% vs 0% in the second group.  As with any study looking at sepsis, definitions are important and while they didn’t do paired cultures to rule out contamination (one positive and one negative as is the definition in our hospitals) they did refer each patient to a senior Neonatologist to help determine whether each case should be considered a true positive or not.  Given that they made no changes to practice or other definitions in diagnosing infections during that time perhaps the results were indeed real.  Presumably if they had missed an infection and not treated it in the second epoch the patient would have declared themselves so I think it is reasonable to say that 8.5 months without a CLABSI after their intervention is a success.  As Dr. Ohlin points out the scrub duration may also help due to the abrasion of the hub surface removing a bacterial film.  Regardless of the reason, perhaps a 15 second scrub is a good idea for all?

The lazy person’s solution – the SwabCap

One way to get around human nature or people being distracted might be to cover each luer lock with a cap containing 70% isopropyl alcohol.  In this way when you go to access the line there should be no bacteria or labour required to scrub anything since the entry of the line is bathed in alcohol already.  This was the subject of a systematic review from the Netherlands entitled Antiseptic barrier cap effective in reducing central line-associated bloodstream infections: A systematic review and meta-analysis.  The reviews ultimately examined 9 articles that met their inclusion criteria and found the following; use of the antiseptic barrier cap was effective in reducing CLABSIs (IRR = 0.59, 95% CI = 0.45–0.77, P < 0.001). Moreover, they concluded that this was an intervention worth adding to central-line maintenance bundles. Having said that, the studies were mostly adult and therefore the question of whether minute quantities of isopropyl alcohol might be injected with medications was not a concern when they made their conclusion.

What about using such caps in ELBW infants

Sauron et al in St. Justine Hospital in Montreal chose to look at these caps more carefully after they were implemented in their NICU.  The reason for taking a look at them was due to several luer valves malfunctioning.  The authors created an in-vitro model to answer this question by creating a closed system in which they could put a cap on the end of a line with a luer lock and then inject a flush, followed by a simulated medication (saline) and then a flush and collect the injected materials in a glass vial that was sealed to prevent evaporative loss of any isopropyl alcohol.  They further estimated the safe amount of isopropyl alcohol from Pediatric studies would be 1% of the critical threshold of this alcohol and using a 500g infant’s volume of distribution came up with a threshold of 14 mmol/L.  The study then compared using the SwabCap over two different valve leur lock systems they had in their units (SmartSite and CARESITE valves) vs. using the strategy of “scrub the hub”.

The results were quite concerning and are shown below.

Circuit Type Temperature Sample 1 Sample 2 Sample 3 Mean
SwabCap on Smart Site Valve Room 49.5 58.4 46.8 51.6
  Incubator 35 degrees 45.16 94.7 77.9 72.6
SwabCap on CARESITE valve Room 14.1 5.7 5.2 8.34
  Incubator 35 degrees 7.0 8.1 5.9 7.0
Isopropyl alcohol pad on CARESITE Valve Room 0 0 0 0

 

Certainly, the Smart Site valve allowed considerable amounts of isopropyl alcohol to enter the line but the CARESITE while better still allowed entry compared to the control arm which allowed none.  Beyond the introduction of the alcohol into the system in all cases considerable clouding of the valves occurred with repeated capping of the system with new caps as was done with each med injection since each was single use.  In lines that were not accessed contact with the cap was left for 96 hours as per recommendations from the manufacturer and these changes occurred as well.

Conclusion

While a reduction in CLABSI is something we all need to strive to obtain, it is better to take the more difficult path and “scrub the hub” and by that for 15 seconds which incidentally is the same recommended duration for hand hygiene in both of our units.  Perhaps in larger term infant’s seepage of isopropyl alcohol into the lines would not be as concerning as their larger volume of distribution would lead to lower levels but I would ask the question “should any isopropyl alcohol be injected into any baby?”.  I think not and perhaps by reading this post you will ask the same thing if your unit is using these caps.

  • Thank you to Örebro University Hospital for their permission in using the photo for the post
AllThingsNeonatal

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Look around you.  Technology is increasingly becoming pervasive in our everyday lives both at home and at work.  The promise of technology in the home is to make our lives easier.  Automating tasks such as when the lights turn on or what music plays while you eat dinner (all scripted) are offered by several competitors.  In the workplace, technology offers hopes of reducing medical error and thereby enhancing safety and accuracy of patient care.  The electronic health record while being a nuisance to some does offer protection against incorrect order writing since the algorithms embedded in the software warn you any time you stray.  What follows is a bit of a story if you will of an emerging technology that has caught my eye and starts like many tales as a creative idea for one purpose that may actually have benefits in other situations.

Meet Stethocloud

In 2012 students in Australia rose to the challenge and designed a digital stethoscope that could be paired with a smartphone.  The stethoscope was able to send the audio it was receiving to the smartphone for analysis and provide an interpretation.  The goal here was to help diagnose childhood pneumonia with a stethoscope that would be affordable to the masses, even “Dr. Mom” as the following video documents.  Imagine before calling your health line in your city having this $20 tool in your hands that had already told you your child had breath sounds compatible with pneumonia.  Might help with moving you up the triage queue in your local emergency department.

 

Shifting the goal to helping with newborns

Of course breath sounds are not the only audio captured in a stethoscope.  Heart sounds are captured as well and the speed of the beats could offer another method of confirming the heart is actually beating.  Now we have ECG, pulse oximetry, auscultation and palpation of the umbilical stump to utilize as well so why do you need another tool?  It comes down to accuracy.  When our own heart rates are running high, how confident are we in what we feel at the stump (is that our own pulse we are feeling?).  In a review on measurement of HR by Phillipos E et al from Edmonton, Alberta, auscultation was found to take an average of 17 seconds to produce a number and in 1/3 of situations was incorrect.  The error in many cases would have led to changes in management during resuscitation.  Palpation of the umbilical cord is far worse.  In one study “cord pulsations were impalpable at the time of assessment in 5 (19%) infants, and clinical assessment underestimated the ECG HR with a mean (SD) difference between auscultation and palpation and ECG HR of − 14 (21) and − 21 (21) beats min –1″.  In another study, 55% of the time providers were incorrect when they thought the HR was under 100 BPM.  This leaves the door open for something else.  Might that something be the digital stethoscope?

How does the digital stethoscope fare?

Kevac AC et al decided to look at the use of the Stethocloud to measure HR after birth in infants >26 weeks gestational age at birth. The opted to use the ECG leads as the gold standard which arguably is the most accurate method we have for detecting HR.   The good news was that the time to signal acquisition was pretty impressive.  The median time to first heart rate with the stethoscope was 2 secs (IQR 1-7 seconds).  In comparison the time for a pulse oximeter to pick up HR is variable but may be as long as one minute.  In low perfusion states it may be even longer or unable to pick up a good signal.  The bad news was the accuracy as shown in the Bland Altman plot.  Screenshot 2017-06-04 17.32.59The tendency of the stethoscope was to underestimate the EKG HR by about 7 BPM. Two standard deviations though had it underestimate by almost 60 BPM or overestimate by about 50 BPM.  For the purposes of resuscitation, this range is far to great.  The mean is acceptable but the precision around that mean is to wide.  The other issue noted was the frequent missing data from loss of contact with the patient.  Could you imagine for example having a baby who has a heart rate of 50 by the stethoscope but by EKG 100? Big difference in approach, especially if you didn’t have EKG leads on to confirm.  The authors note that the accuracy is not sufficient and felt that an improvement in the software algorithms might help.

Another go at it

So as suggested the same group after having a new version with improved software decided to go at it again.  This time Gaertner VD et al restricted the study to term infants. Forty four infants went through the same process again with the stethoscope output being compared to EKG lead results.  This time around the results are far more impressive.  StethoscopeThere was virtually no difference between the ECG and the stethoscope with a 95% confidence interval as shown in the graphs with A being for all recordings and B being those without crying (which would interfere with the acquiring of HR).  A maximal difference of +/- 18 BPM for all infants is better than what one gets with auscultation or palpation in terms of accuracy and let’s not forget the 2 second acquisition time!

 

Should you buy one?

I think this story is evolving and it wouldn’t surprise me if we do see something like this in our future.  It certainly removes the element of human error from measuring.  It is faster to get a signal than even the time it takes to get your leads on.  Where I think it may have a role though is for the patient who has truly no pulse. In such a case you can have an EKG HR but the patient could be in pulseless electrical activity.  Typically in this case people struggle to feel a pulse with the accuracy being poor in such situations.  Using a device that relies on an actual heart contraction to make a sound provides the team with real information.  Concurrent with this technology is also the rise of point of care ultrasound which could look at actual cardiac contractions but this requires training that makes it less generalizable.  Putting a stethoscope on a chest is something we all learn to do regardless of our training background.

I think they could be on to something here but perhaps a little more evidence and in particular a study in the preterm infant would be helpful to demonstrate similar accuracy.

AllThingsNeonatal
 

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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.

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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

AllThingsNeonatal

 

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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

  1. Chorioamnionitis
  2. Maternal smoking
  3. Smaller birthweight (875 vs 922 g)
  4. Confirmed sepsis (23% vs 14%)
  5. 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).

AllThingsNeonatal
Posted on May 7, 2017 by winnineo

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In our journey as Neonatologists and interdisciplinary teams we are forever seeking to rid or at least reduce the plague of BPD in the patients we care for.  The PREMILOC trial was a double-blind, multicenter, randomized, placebo-controlled trial designed to test just that concept by introducing a low dose of hydrocortisone within 24 hours of birth. They   enrolled infants born between 24 – 26+6 weeks of gestation  and assigned them to receive either placebo or low-dose hydrocortisone 0.5mg/kg twice per day for 7 days, followed by 0.5 mg/kg per day for 3 days.  The trial has been the subject of a previous post A Shocking Change in Position. Postnatal steroids for ALL microprems?  Although the trial was stopped early due to financial concerns the authors demonstrated a 9% reduction in BPD using this strategy.  The theory here in part is that the presence of hydrocortisone reduces inflammation and that this in turn may allow for better growth of lungs with time.

Why Not Adopt The Results Based on These Fantastic Results?

Steroids in preterm infants have a bad name.  As discussed in previous posts on the topic the concern in all trials has been the potential impact of such medications on the developing brain. A nice summary of these concerns can be found in a paper in the CMAJ by the other “Canadian Neonatal Blogger” from 2001 in which he quoted the risk of cerebral palsy increasing from about 1 in 6 babies to 1 in 3 if babies born at < 28 weeks were exposed to postnatal steroids.  Neurodevelopmental impairment overall would change from 1 in 4 to 1 in 3 if such exposure occurred.  This paper and others expressing concerns over the effect of postnatal steroids led to a change in practice from more ubiquitous use to one restrained to only in those cases where the patient was nearing the end of all other options.  This meant holding out for such therapy until such patients were at 90% or more O2 and on high mean airway pressures.  Although not formally studied I was very concerned at the time with using this approach as I felt it was a “fait de complet” that they would either die or have significant developmental impairment should they survive due to the complications of having such severe BPD.  It is critical to note though that the outcomes from these long term studies were in infants exposed to much longer courses of dexamethasone and at high doses that are used today.

Over the years with the development of the DART protocol and other more gentle approaches to steroids we as a group relaxed and certainly rescue courses of lower dose steroids have crept into practice when patients seem to be “stuck” on the ventilator.

Drumroll Please…

The results of the PREMILOC follow-up study are now here and in short they look good.  Patients were followed up at an average age of 22 months and included a medical history, anthropometric measures, respiratory status, standardized neurological examination based on specific definitions of disabilities, and quantitative neurodevelopmental assessment using the revised Brunet-L.zine (RBL) scale.  Follow-up was 93% in the hydrocortisone and 90% in the placebo arm which is important as we need not worry about the missed patients influencing the results to a significant degree if they had been included.  Although some post-hoc analyses were done what I am most interested in is the primary outcome which is shown below.

premiloc followup

There was no difference in either neurodevelopment overall or any of the subcategories.  This provides a great deal of reassurance to those who provide steroids this way.  There will be those however that argue the study is too small.  While a larger study might be better able to address whether there is a small difference in outcome I don’t think we will see one anytime soon.  It is one of the challenges we face in Neonatology.  Unlike the adult world with studies of thousands of patients, due to the small number of patients born at <28 weeks it is always a challenge to recruit into such large volume trials.  We can compare trials by doing meta analyses or systematic reviews and perhaps that is where we will head with this study although given that different steroids will have been used (thinking dexamethasone as in the DART study) this will always be left open to question.

Is it worth it?

I suppose the real question here is the following for a parent to consider. “Would you like your baby to receive hydrocortisone shortly after birth with a 7% reduction in the risk of BPD at 36 weeks bearing in mind that although we don’t think there is an impact on long term development we aren’t certain yet”.  

I guess to answer this question you need to think about the first part of the question.  Is BPD at 36 weeks a good outcome to look at for benefit?  The Canadian Neonatal Network has recently called for a rethink on this The New BPD That Matters.  It turns out that it is 40 weeks and not 36 weeks that has the greatest prediction for respiratory morbidity after discharge.  If you were to move the goal post to 40 weeks from 36 I strongly suspect one would see the 9% reduction in BPD as shown in the PREMILOC trial vanish.  If that is the case, would a slightly earlier extubation time be enough to motivate families to take the plunge?

Although I often cringe at the expression “more trials are needed”, I think at least a combination of studies to achieve greater confidence in outcome may be needed.  Barring that, we might just have to sit tight and accept that while there may be a little bit to be gained with the use of the PREMILOC protocol it may just not be enough to be clinically warranted at this time.  May want to wait for the next big thing to tackle BPD…

AllThingsNeonatal

 

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I think my first training in resuscitation began with the principles outlined in the NRP 3rd edition program.  As we have moved through subsequent editions with the current edition being number 7, I can’t help but think about how many changes have occurred over that time.  One such change has been the approach to using medications as part of a resuscitation.  Gone are such things as calcium gluconate, naloxone and sodium bicarbonate but something that has stood the test of time is epinephrine.  The dosing and recommendations for administering epinephrine have changed over time as well with the dose of endotracheal medication increasing from 0.01 to 0.03 and now to 0.05 – 0.1 mg/kg.  While this dosing has increased, that of IV administration has remained the same at 0.01 to 0.03 mg/kg.  The change in dosing for the ETT route was due to an increasing awareness that this route just isn’t as effective as IV.  Having said that with only 0.1% of resuscitations requiring such support the experience with either route is fairly limited.

What is the concern?

Giving a medication directly via the IV route ensures the dose reaches the heart in the amount desired.  In the case of ETT administration there are a few potential issues along the way.  The first is that one needs to push the dose down the ETT and this presumes the ETT is actually in the trachea (could have become dislodged).  Secondly, if the medication is sent to the lung what effect does the liquid component in the airways have in terms of dilution and distribution of the medication?  Lastly, even if you get the epinephrine to the lung it must be picked up at the capillary level and then returned to the left side of the heart.  In the absence of significant forward pulmonary blood flow this is not assured.

What is the evidence?

In terms of human clinical research it remains fairly limited.  Barber published a retrospective review of 47 newborns who received epinephrine via the endotracheal route.  The study Use and efficacy of endotracheal versus intravenous epinephrine during neonatal cardiopulmonary resuscitation in the delivery room found that spontaneous circulation was restored in 32% of this cohort.  Following the first dose, a subsequent dose of intravenous epinephrine restored circulation in 77%.  This study provided the first suggestion that the IV route may be better than endotracheal.  Keep in mind though that this study was retrospective and as the authors conclude in the end, prospective studies are needed to confirm these findings.  The question really is what is the likelihood of restoring circulation if the first dose is given IV?

Eleven years later we have a second study that attempts to answer this question although once again it is retrospective. Efficacy of Intravenous and Endotracheal Epinephrine during NeonatalCardiopulmonary Resuscitation in the Delivery Room by Halling et al. This study really was designed to answer two questions.  The study group looked at the period from July 2006 to July 2014.  During this period the dose of IV epinephrine remained unchanged as per NRP recommendations but the dose of endotracheal epinephrine increased from 0.01 to 0.03 and then to 0.05 mg/kg endotracheally.  The increase was in response to both NRP and site observations that the lower doses were not achieving the effect they were hoping for.

The Results

  ETT epinephrine IV Epinephrine
Number 30 20
Return of circulation 23 15
1 dose 6 4
2 dose 5 8
3 doses 9 0
4 doses 3 3

In the ETT group all doses except for 3 after the first dose were given as IV.  There was no difference in the response rate over time suggesting that higher doses do not truly increase the chance of a better response.  The authors noted that the effectiveness of the two arms were not that different despite a significantly higher dose of epinephrine being administered to the group receiving ETT epinephrine first which is not surprising given the higher recommended dosages.

What I find interesting though is that giving the first dose of epinephrine was given IV in 20 of the paitents, if it is indeed the better route one might expect a better response than in the ETT group.  The response from one dose of ETT epi was 20% while that from the IV first group was in fact also only 20%!  We do indeed need to be careful here with small numbers but the results at least to me do not suggest strongly that giving IV epi first ensures success. What the study suggests to me is that two doses of epinephrine may be needed to restore circulation.  If you choose to start with IV it certainly does not seem unwise but if you have any delays I don’t see any reason to avoid ETT epinephrine as your first line.

The reality is that for many individuals a UVC is a procedure that while they may have learned in an NRP class they may have never actually placed one.  Having an ETT in place though seems like a good place to start.  I doubt we will ever see a randomized trial of ETT vs IV epinephrine in Neonatology at this point given the stance by the NRP so these sorts of studies I suspect will be the best we get.

For now, based on what is out there I suggest use the route that you can get first but expect to need additional doses at least one more time to achieve success.  Lastly remember that even if you do everything correct there will be some that cannot be brought back.  Rest assured though that if the first dose was given via ETT you have still done your best if that was the route you had.

AllThingsNeonatal

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The human body truly is a wondrous thing.  Molecules made from one organ, tissue or cell can have far reaching effects as the products take their journey throughout the body.   As a medical student I remember well the many lectures on the kidney.  How one organ could control elimination of waste, regulate salt and water metabolism, blood pressure and RBC counts was truly thought provoking.  At the turn of the century (last one and not 1999 – 2000) Medical school was about a year in length and as the pool of knowledge grew was expanded into the three or four year program that now exists.  Where will we be in another 100 years as new findings add to the ever growing volume of data that we need to process?  A good example of the hidden duties of a molecule is erythropoetin (Epo) the same one responsible from stimulating red blood cell production.

Double Duty Molecule

In saying that I am simplifying it as there are likely many processes this one hormone influences in the body but I would like to focus on its potential role in neuroprotection. In 1999 Bernaudin Et al performed an animal study in mice to test this hypothesis.  In this elegant study, strokes were induced in mice and the amount of Epo and Epo receptors measured in injured tissues.  Levels of both increased in the following way “endothelial cells (1 day), microglia/macrophage-like cells (3 days), and reactive astrocytes (7 days after occlusion)”.  To test the hypothesis that the tissues were trying to protect themselves the authors then administered recombinant human Epo (rhEpo) to mice prior to inducing stroke and the injury was clearly reduced.  This established Epo as a potential neuroprotectant.  Other animal studies then followed demonstrating similar findings.

A Human Trial

When you think about hypoxic ischemic encephalopathy (HIE) you can’t help but think of whole body cooling.  The evidence is pretty clear at this point that cooling in this setting reduces the combined outcome of death or neurodevelopmental disability at 18 months with a number needed to treat of 7.  The risk reduction is about 25% compared to not those not cooled so in other words there is room to improve. Roughly 30-40% of infants who are cooled with moderate to severe HIE will still have this outome which leaves room for improvement.  This was the motivation behind a trial called High-Dose Erythropoietin and Hypothermia for Hypoxic-Ischemic Encephalopathy: A Phase II Trial. This was a small trial comparing 50 patients (24 treated with rhEpo and cooling to 26 given placebo) who were treated with 1000 U of rEpo on days 1,2,3,5 and 7. Primary outcome was neurodevelopment at 12 months assessed by the Alberta Infant Motor Scale (AIMS)and Warner Initial Developmental Evaluation. A significant improvement in a subset of mobility on the latter was found and a significant difference in the AIMS overall.   An additional finding giving support for a difference was that blinded reviews of MRI scans demonstrated a singificant improvement in brain tissue in those who received rhEPO. One curious finding in this study was that the mean timing of administration of rhEPO was 16.5 hours of life.  Knowing that the benefit of cooling is best when done before 6 hours of age one can only wonder what impact earlier administration of a neuroprotective agent might have. This suggests that the addition of rEPO to cooling has additional impact but of course being a small study further research is needed to corroborate these findings.

The Next Step

This past week Malla et al published an interesting paper to add to the pool of knowledge in this area; Erythropoietin monotherapy in perinatal asphyxia with moderate to severe encephalopathy: a randomized placebo-controlled trial.  This study was done from the perspective of asking if rhEPO by itself in resource poor settings without access to cooling in and of itself could make a difference in outcome for patients with HIE.  This was a larger study with 100 Hundred term neonates (37 weeks or greater) with moderate or severe HIE. Fifty were randomized by random permuted block algorithm to receive either rhEPO 500 U kg− 1 per dose IV on alternate days for a total of five doses with the first dose given by 6 h of age (treatment group) or 2 ml of normal saline (50 neonates) similarly for a total of five doses (placebo group) in a double-blind study. The primary outcome was combined end point of death or moderate or severe disability at mean age of 19 months and the results of this and other important outcomes are shown below.

Outcome Treatment Placebo p
Death/disability (mod/severe HIE) 40% 70% 0.003
Death/disability (mod HIE only) 21% 61% 0.004
Cerebral Palsy 23% 45% 0.04
MRI abnormalities 40% 60% 0.04
Seizures treatment at 19 months 19% 43% 0.03

To say that these results are impressive is an understatement.  The results are on par with those of cooling’s effect on reduction of injury and improvement in outcome.  When looking at the primary outcome alone the result in dramatic when put in perspective of looking at number needed to treat which is 4! This is significant and I can’t help but wonder if the impact of this medication is at least in part related to starting the dosing within the same window of effectiveness of therapeutic hypothermia.  Importantly there were no adverse effects noted in the study and given that rhEpo has been used to treat anemia of prematurity in many studies and not found to be associated with any significant side effects I would say this is a fairly safe therapy to use in this setting.

Next Steps

I find this puts us in a challenging position.  The academic purists out there will call for larger and well designed studies to test the combination of rhEPO and cooling both initiated within 6 hours of age.  While it takes years to get these results might we be missing an opportunity to enhance our outcomes with this combination that is right in front of us.  The medication in question other than raising your RBC count has little if any side effects especially when given for such a short duration and by itself and possibly with cooling increases the rate of neuroprotection already.  I don’t know about you but I at least will be bringing this forward as a question for my team.  The fundamental question is “can we afford to wait?”

AllThingsNeonatal

This post rings in another new video to add to the series on the All Things Neonatal YouTube channel.  I hope that you have gotten something out of the ones posted so far and that this adds something further to your approach to neonatal care.

The Golden Hour Revisited

In the last post to the video selections the main thrust of the video was on the use of the Golden Hour approach to starting a baby on CPAP.  Having a standardized checklist based approach to providing care to high risk newborns improves team functioning for sure.  What do you do though when you need to hand off a patient to another team?  Depending on where you work this may not be an issue if the team performing the resuscitation is the team providing the care for the patient in the NICU.  Perhaps you work in a centre similar to our own where the team performing resuscitation is not the same as the one who will ultimately admit the patient.  You may also be in a location where there are no babies born on site but rather all patients are transferred in so in each case the patient is new to everyone on the receiving team.  How do you ensure that a complete hand over is done.

Out with the old and in with the new!

By no means do I want to imply that it is not possible to transfer information outside of the way that we demonstrate in this video.  What I do believe though is that with telehealth being available in more and more settings or without a formal support for the same, the use of smartphones make video conferencing a reality for almost everyone.  In most centres handovers have followed the practice of like communicating with like.  Nurses give report to nurses, respiratory therapists to each other and MDs to MDs.  What if there was another way though?  In the video below we demonstrate another approach.  Would it work for your team?

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!

AllThingsNeonatal

 

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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.

AllThingsNeonatal

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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.  What 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!

AllThingsNeonatal

 

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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.

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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.  Two 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 twitterthere 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?

AllThingsNeonatal

 

 

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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?

AllThingsNeonatal

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.

 

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