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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.

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Entries in this blog

 

Scrub but don’t cap the hub to reduce infections in the NICU

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

AllThingsNeonatal

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Could a digital stethoscope revolutionize resuscitation of the newborn?

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.  The 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.  There 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

AllThingsNeonatal

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Is it time to (ESC)ape from Neonatal Abstinence

I don’t envy our nurses who care for babies withdrawing from various opiates and other substances.  These assignments are definitely a challenge and require a great deal of patience and depending on the shrillness of an infant’s cry a good set of earplugs. Nonetheless we do our best with these infants to keep them calm and avoid as much stimulation as we can as we attempt to minimize the excitability of their nervous system. Over 40 years ago the Finnegan Neonatal Abstinence scoring system was developed to assist medical teams by providing as objective a system as possible to compare one infant to another and determine when and if a patient should be treated pharmacologically.  Unfortunately there is a problem inherent with this scoring system.  It is the same problem that exists when you don’t have a blinded research trial.  Imagine you are caring for an infant and you were given no history about drug exposure.  How might you score a patient like that compared to one in which you are told has been exposed to illicit substances?  Your senses are heightened and moreover if you were told this baby is “withdrawing terribly” or “is awful at night” you are biased. How are you likely to score such a patient when they are “on the edge” of being counted as a 1 or a 0 in a category?  I bet in many cases, especially if you haven’t taken care of many such patients you err on the side of caution and score them on the high side.  It is human nature.  When the possible outcome of failing to recognize a withdrawing patient is a seizure, no one wants to be on when it happens having their scoring questioned.  Have a look at the scoring tool though. There is a lot of stuff in there to check off!  What if it could be simpler? The ESC Tool In early May, news began to break of an abstract being presented at the Pediatric Academic Society meeting.  The news story from the AAP can be found here.  The ESC tool is a three question tool used to assess whether an infant requires treatment for withdrawal. E – Eat (is an infant is able to eat 1 or more ounce per feeding) S – Sleeping (sleep for an hour or longer undisturbed) C – Console (Be consoled in 10 minutes or less.) If all three criteria are met, the patient does not need treatment.  If one or more criteria are not met the housestaff are notified and first non-pharmacologic and then pharmacologic means are employed if necessary to control symptoms. The authors did something quite interesting.  They looked at 50 patients with 201 hospital days with prenatal exposures to opiates and applied the ESC criteria to guide treatment.  Concurrently they captured the Finnegan scores but did not use them to guide treatment. The findings I hope you will agree are quite interesting! “FNASS scores indicated starting morphine in 30 infants (60%). Morphine was actually started on only 6 patients (12%) (p< 0.0001) based on the ESC approach. The FNASS led protocol directed initiating or increasing meds on 24.6% of days compared to 2.7% of days using the ESC approach (p< 0.0001). The FNASS approach directed that morphine was either not started or decreased on 65.8% of days compared with 94.4% of days using the ESC approach (p< 0.0001). There were no readmissions or reported adverse events. Pretty amazing but… The ESC approach greatly reduced the need for treatment and as the authors state there were no readmissions or reported adverse events.  What we don’t know and will be needed I suspect before anyone will adopt this strategy (which I have to say again is so much simpler that current approaches) is how these children do in the long run.  If the system is undertreating withdrawal, could we see downstream impacts of a “kinder and gentler” approach?  One outcome that will be reported soon in the next month is length of stay.  I am eagerly awaiting further results as I for one think that a simpler approach to these patients may be just what the doctor ordered.  I think the nurses might thank us as well but we will see just how appropriate it is! The Abstract reporting these findings can be found below Novel Approach to Evaluating and Treating Infants with Neonatal Abstinence Syndrome
AllThingsNeonatal

AllThingsNeonatal

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Should 24 hour Neonatologist In-House Coverage Be The Rule ?

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 Chorioamnionitis Maternal smoking Smaller birthweight (875 vs 922 g) Confirmed sepsis (23% vs 14%) Postnatal steroids (45% vs 8%) – but duration of ventilation longer in the day coverage group likely due to less postnatal steroids ( 31 vs 21 days) All of these factors would predict a worse outcome for these infants but in the end for the primary outcome of neurodevelopmental impairment there was no difference.  Even after controlling for postnatal steroids, birth weight, sex and 5 minute apgar score there was still no difference. What might this mean? Looking at this with a glass is half full view one might say that with all of the factors above predicting worse outcome for infants, the fact that the groups are not different in outcome may mean that the 24 hour model does indeed confer a benefit.  Maybe having a Neonatologist around the clock means that care is made that much better to offset the effect of these other risk factors?  On the other hand another explanation could also be that the reason there is no difference is that the sample just isn’t big enough to show a difference.  In other words the size of the study might be underpowered to find a difference in developmental outcome. One of the conclusions in this study is that the presence of a Neonatologist around the clock may have led to earlier extubation and account for the nearly 10 day difference in duration of ventilation.  While I would love to believe that for personal reasons I don’t think we can ignore the fact that in the earlier epoch almost 50% of the babies received postnatal steroids compared to 8% in the later period.  Postnatal steroids work and they do so by helping us get babies off ventilators.  It is hard to ignore that point although I woudl like to take credit for such an achievement. For now it would appear that I don’t feel compelled to stay overnight in the hospital unless it is necessary due to patient condition necessitating me having my eye on the patient.  I am not sure where our field will go in the future but for now I don’t see the evidence being there for a change in practice.  With that I will retire to my bedroom while I am on call and get some rest (I hope).
AllThingsNeonatal

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Early Hydrocortisone: Short term gain without long term pain.

Posted on May 7, 2017 by winnineo 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. 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…
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Why does ETT epinephrine get such a bad rap?

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

AllThingsNeonatal

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A Leap Forward in the Treatment of HIE?

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?”
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Rethinking how teams hand over. A better way

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!
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NEC & Anemia: Is the truth out there?

A debate broke out recently at one of our rounds when someone asked whether a recent case of NEC was possibly related to a transfusion that a baby received.  Much has been written about Transfusion Associated Necrotizing Enterocolitis (TANEC) with the pendulum swinging back and forth between it existing as a real entity or simply being an association that is not causative in the least.  Using one of my favourite sources, a retrospective analysis of the Canadian Neonatal Network database found no difference in mortality or morbidities for those who had a transfusion and NEC vs those without. Despite this we continue to see those who “hold feeds” for a few hours prior to transfusion and then resume them a few hours later.  Why does this happen? Risk vs Benefit Those who hold feeds argue that in Neonatology we hold feeds for far less.  Furthermore, what is the harm?  If a baby develops NEC within 24 hours of a transfusion and we held the feeds we feel we have done all we could.  If a baby is fed and develops NEC we are left asking “what if?”.  The purists out there would argue the contrary though, that the evidence is not strong enough to support the practice and may require the insertion of an IV which is a painful procedure and places the infant at risk of infection from one or more skin breaks.  Additionally, does the interruption of feeds potentially alter the microbiome of the patient and with it risk potential downstream consequences. In case you are wondering, I have tended to sit on the side of holding a feed although more often when I am asked about it than ordering it upfront.  The fact is I just don’t know.  The evidence has never been solid in this regard but it is hard to ignore the possibility when you have been bitten once or twice before (whether it was causative or not!).  I doubt it really exists but then again what if there is something there? It May Not Be The Transfusion But Anemia Itself A recent paper Association of Red Blood Cell Transfusion, Anemia, and Necrotizing Enterocolitis in Very Low-Birth-Weight Infants may have found a possible explanation to the ongoing debate.  Research papers associating transfusions with NEC may all have one thing in common in that they have not been able to prove causation.  When you have many papers finding the same thing it leads medical teams to begin to believe there is causation.  Something else may be at play at this paper suggests another association which again may not be causative but at least in my mind is perhaps biologically plausible.  It may be that those patients who are transfused when their hemoglobin is below a threshold of 80 g/L are at increased risk of developing NEC rather than all patients transfused. This study was a secondary analysis of a prospective study on transfusion transmission of cytomegalovirus in preterm infants < 1500g.  The authors chose 80 g/L as a cutoff based on previous studies suggesting this threshold as an important one for transfusion practices. Forty eight out of 60 eligible infants developed NEC and it is from this 48 that multivariable analysis sought to identify factors predisposing to the outcome in question of NEC.  The factor with the greatest hazard risk for NEC was severe anemia in a given week with an approximate 6 fold risk (range 2 – 18) while receiving an RBC transfusion in a given week of life did not meet statistical significance. What does this mean? Before embracing the result and concluding we have the answer we have to acknowledge the authors have gone on a fishing expedition of sorts.  Any secondary analysis of a study that is done carries with it some words of warning.  There may be variables that were not controlled for that are affecting the results.  As well when looking at many many variables it could be by chance that something or several things come up by chance.  Lastly it may be that again there is nothing more than an association here at play.  Having said that, there is some biologic plausibility at least here. 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. Oxygen delivery = cardiac output X O2 concentration (or content) 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.
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A Golden Opportunity For Your NICU Team!

I have written about respectful communication before in Kill them with kindness. The importance of collaborating in a respectful manner cannot be overemphasized, as a calm and well prepared team can handle just about anything thrown their way.  This past week I finally had the opportunity to take the 7th ed NRP instructor course.  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!
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Donor Milk; Falling like DOMINOs?

The rise of donor milk banks and depots in recent years has been a welcome addition to the care of preterm infants.  We have known for many years that “breast is best” and advocate for mother’s own milk whenever possible.  When this is not possible we previously turned to formula but with the availability of pooled pasteurized donor milk many hospitals have focused on expanding the indications for use.  Through personal communications in Canada we are a bit all over the map in terms of indications with some centres restricting use based on birth weight while others taking into account, gestational age as the main criteria.  With respect to duration some centres use 2 weeks, others 4 and then others until a gestational age is reached which may mean up to 10 weeks of use for a baby born in that centre at 24 weeks.  While variation exists it is hard to find anyone who would suggest this is a bad thing to provide. The main reason for pushing expansion of programs is the strong evidence that avoidance of bovine milk is associated with a reduction in the risk of NEC.  Many studies have been done in this regard and the Cochrane systematic review concluded that formula increased the risk of necrotising enterocolitis: typical risk ratio 2.77 (95% CI 1.40 to 5.46); risk difference 0.04 (95% CI 0.02 to 0.07). While donor milk is a wonderful nutritional product for sure it does have one issue which is a lower protein content than mother’s own milk and as such dieticians will commonly increase the protein content from 0.9 g/dL to 1.2 g/dL by adding powder or more recently liquid protein supplements.  One might expect then that doing so would provide a reduction is NEC, and an optimal source of nutrition for the growing preterm brain.  Avoidance of NEC should reduce the risk of adverse neurodevelopmental outcome as the two have been linked before. Enter the DOMINO Study This Ontario, Canada based study utilized four NICUs to provide in a randomized fashion either donor human milk or formula with matching protein and caloric densities to 363 infants (181 donor milk, 182 formula).  All infants were preferentially fed mother’s own milk but supplemented with donor or formula if unavailable and planned to use one or the other for up to 90 days or discharge whichever came first.  The exposure to donor milk was quite long in comparison to our own units practice (1 month duration if born at < 1500g) .  The median number of days for donor milk was 65 (IQR, 41-90).  A significant risk to the results would be if there was a difference in amounts of mother’s own milk provided between the two groups but there was none. Exclusive feeding of mother’s own milk occurred in the Donor milk group (28.2%) and formula group (26.9%) respectively. Among infants requiring a supplement, there was no statistically significant difference between the donor milk and formula groups in the proportion of total enteral feeds for each infant consumed as mother’s milk (58.4% [IQR, 13.6%-96.0%] vs 63.3% [IQR, 9.6%-97.2%], respectively, P = .96). Short term but not long term gains Curiously (at least to me) I would have expected differences in some of the morbidities other than NEC but such was not the case.  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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The Rugged Individualist Neonatal Blogger

Rather excited this week as Biomed Central picked up a blog post that I wrote on social media.  The post is found here.  It is based though on a larger version that I have included below and really delves into the impact of social media and how one uses it.  A big thank you to Kristy Wittmeier for all of her help in writing the post. Original Piece I read with great interest the article by Campbell et al entitled Social media use by physicians: a qualitative study of the new frontier of medicine.  The study interviewed 17 physician users of social media of which only one writer of a blog responded, but then declined to participate.  The four themes that emerged of Rugged Individualism, Uncertainty, Social Media as Media and Time Constraints certainly resonate with me as a blogger who also happens to be a Pediatrician but more specifically a Neonatologist.  The first theme truly resonates with me as I think back over the journey that has taken me to where I am now.  We in the medical social media world are certainly learning as we go.  Without clear paths drawn for us we explore and contemplate how we will make a positive difference far beyond the reach of the typical physician in a clinic, hospital or local community.  The commentary that follows explores the journey that I have taken with social media; engaging in largely unpaid work to bring information to others using these forums. My own story as a Neonatal Blogger began in 2015 when my Minecraft-obsessed son asked me to help him start a blog about Minecraft.  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.  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?
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Healthy at risk infants failing the infant car seat challenge. Cause for concern?

The infant car seat challenge(ICSC) is a test which most definitely fits the definition of a battleground issue in Neonatology.  After publishing the Canadian Pediatric Practice point on the same topic I received interesting feedback through the various social media forums that I frequent.  While some were celebrating the consensus of the statement as verification that a centres’ non practice of the test was acceptable, others seriously questioned the validity of the position.  The naysayers would point out that extremely infrequent events unless intentionally tracked may be difficult to pick up.  In the case of the ICSC, if a few patients were to suffer a hypoxic event leading to an ALTE or worse after discharge, could the ICSC have picked out these babies and prevented the outcome?  The evidence for adverse events associated with the use of car seats as discussed in the position statement is poor when using autopsy records over decades but when many clinicians can point to a failed ICSC picking up events, the thought goes that they “caught one”.  Does catching one make a difference though? The Well Appearing Infant Shah et al in their recent paper Clinical Outcomes Associated with a Failed Infant Car Seat Challenge attempt to address this very point.  They performed a retrospective study of 148 patients who were either <37 weeks GA or < 2500g at birth.  The study was made possible by the fact that all such infants in their hospital admitted to a well newborn area meeting these criteria by policy must have an ICSC prior to discharge.  Keep in mind that these were all infants who were on the well newborn service since they were asymptomatic.  The definition of an event in this group was one or more of pulse oximeter saturation ≤ 85% for > 10 seconds, apnea > 20 seconds, bradycardia < 80 bpm for > 10 seconds, or an apnea or bradycardia event requiring stimulation.  The failure rate was 4.5% which is very similar to other reported studies. Why did they “fail”? Failure of the ICSC was owing to desaturation 59% Bradycardia 37% Tachypnea 4% Combination of 2 in 11% What is interesting about these results is what happened to these infants after admission to the NICU in that 39% were identified with apnea (48% in preterm vs 17% in term infants).  These events were in the supine position which is a curious finding since the ICSC was designed to find risk of cardiorespiratory stability in a semi-recumbent position.  This has been shown previously though. What does it all mean? The infants in this study ultimately had more NG feeding, prolonged length of stay and septic workups after failing the ICSC that comparable infants who passed.  At first blush one would read this article and immediately question the validity of the CPS position but then the real question is what has this added to the “pool of knowledge”.  That infants may fail an ICSC at a rate of 4.5% is already known.  That such infants may demonstrate apneic events has also been shown before and a study like this may help to support those clinicians who feel it is still imperative to find these infants in order to achieve a safe discharge.  I think it is important to put these findings in the context of what would have happened if such a unit did not routinely test these types of babies.  As all were seemingly well and I presume feeding with their families, they would have been discharged after 24-48 hours to home.  We have no evidence (since they have not compared this sample to a group who did not have such testing) that if these babies were discharged they would have faired poorly. The supporters of the ICSC would point to all the support these babies received by admitting them for 6-8 days, providing NG feeding and ruling out sepsis that they were unsafe for discharge.  The other possible way to look at it was that the infants were subjected to interventions that we have no evidence helped them.  Whether any of these infants had a positive blood culture justifying antibiotics or needed methylxanthine support is not mentioned.  Judging however by the short length of stay I suspect that none or few of these infants needed such medication as I would expect they would have stayed much longer had they needed medical treatment for apnea. Conclusion I do commend the authors for completing the study and while it does raise some eyebrows, I don’t see it changing at least my position on the ICSC.  While they have described a cohort of patients who failed the ICSC nicely, the fundamental question has been left unanswered.  Does any of this matter?  If you look well, are feeding well and free of any clinically recognizable events but are late preterm or IUGR can the ICSC prevent harm?  This has not been answered here and perhaps the next step would be for a centre that has abandoned the ICSC to follow their patients after discharge prospectively and see whether any adverse outcomes do indeed occur.  Any takers?
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The New BPD That Matters

As a Neonatologist I doubt there are many topics discussed over coffee more than BPD.  It is our metric by which we tend to judge our performance as a team and centre possibly more than any other.  This shouldn't be that surprising.  The dawn of Neonatology was exemplified by the development of ventilators capable of allowing those with RDS to have a chance at survival.  As John F Kennedy discovered when his son Patrick was born at 34 weeks, without such technology available there just wasn't much that one could do.  As premature survival became more and more common and the gestational age at which this was possible younger and younger survivors began to emerge.  These survivors had a condition with Northway described in 1967 as classical BPD.  This fibrocystic disease which would cripple infants gave way with modern ventilation to the "new bpd". The 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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Has permissive hypercapnia failed to deliver?

Positive pressure ventilation puts infants at risk of developing chronic lung disease (CLD). Chronic lung disease in turn has been linked many times over, as a risk for long term impacts on development.  So if one could reduce the amount of positive pressure breaths administered to a neonate over the course of their hospital stay, that should reduce the risk of CLD and by extension developmental impairment.  At least that is the theory.  Around the start of my career in Neonatology one publication that carried a lot of weight in academic circles was the Randomized Trial of Permissive Hypercapnia in Preterm Infants which randomized 49 surfactant treated infants to either a low (35-45) or high (45-55) PCO2 target with the thought being that allowing for a higher pCO2 should mean that lower settings can be used.  Lower settings on a ventilator would lead to less lung damage and therefore less CLD and in turn better outcomes.  The study in question did show that the primary outcome was indeed different with almost a 75% reduction in days of ventilation and with that the era of permissive hypercapnia was born. The Cochrane Weigh in In 2001 a systematic review including this and another study concluded that there was insufficient evidence to support the strategy in terms of a benefit to death or chronic lung disease. Despite this lack of evidence and a recommendation from the Cochrane group that permissive hypercapnia be used only in the context of well designed trials the practice persisted and does so to this day in many places.  A little lost in this discussion is that while the end point above was not different there may still be a benefit of shorter term ventilation. A modern cohort It would be unwise to ignore at this point that the babies of the late 90s are different that the ones in the current era.  Surfactant and antenatal steroid use are much more prevalent now.  Ventilation strategies have shifted to volume as opposed to pressure modes in many centres with a shift to early use of modalities such as high frequency ventilation to spare infants the potential harm of either baro or volutrauma.  Back in 2015 the results of the PHELBI trial were reported Permissive hypercapnia in extremely low birthweight infants (PHELBI): a randomised controlled multicentre trial. This large trial of 359 patients randomized to a high or low target pCO2 again failed to show any difference in outcomes in terms of the big ones “death or BPD, mortality alone, ROP, or severe IVH”.  What was interesting about this study was that they did not pick one unified target for pCO2 but rather set different targets as time went on reflecting that with time HCO3 rises so what matters more is maintaining a minimum pH rather than targeting a pCO2 alone which als0 reflects at least our own centre’s practice. There is a fly in the ointment here though and that is that the control group has a fault (at least in my eyes) Day of life Low Target High Target 1-3 40-50 55-65 4-6 45-55 60-70 7-14 50-60 65-75 In the original studies of permissive hypercapnia the comparison was of a persistent attempt to keep normal pCO2 vs allowing the pCO2 to drift higher.  Although I may get some argument on this point, what was done in this study was to compare two permissive hypercapnia ranges to each other.  If it is generally accepted that a normal pCO2 is 35-45 mmHg then none of these ranges in the low target were that at all. How did these babies do in the long run? The two year follow-up for this study was published in the last month; Neurodevelopmental outcomes of extremely low birthweight infants randomised to different PCO2 targets: the PHELBI follow-up study. At the risk of sounding repetitive the results of Bayley III developmental testing found no benefit to developmental outcome.  So what can we say?  There is no difference between two strategies of permissive hypercapnia with one using a higher and the other a lower threshold for pCO2.  It doesn’t however address the issue well of whether targeting a normal pCO2 is better or worse although the authors conclude that it is the short term outcomes of shorter number of days on ventilation that may matter the most. The Truth is Out There I want to believe that permissive hypercapnia makes a difference.  I have been using the strategy for 15 or so years already and I would like to think it wasn’t poor strategy.  I continue to think it makes sense but have to admit that the impact for the average baby is likely not what it once was.  Except for the smallest of infants many babies these days born at 27 or more weeks of gestation due to the benefits of antenatal steroids, surfactant and modern ventilation techniques spend few hours to days on the ventilator.  Meanwhile the number of factors such chorioamniotitis, early and late onset sepsis and genetic predisposition affect the risks for CLD to a great degree in the modern era.  Not that they weren’t at play before but their influence in a period of more gentle ventilation may have a greater impact now.  That so many factors contribute to the development of CLD the actual effect of permissive hypercapnia may in fact not be what it once was. What is not disputed though is that the amount of time on a ventilator when needed is less when the strategy is used.  Let us not discount the impact of that benefit as ask any parent if that outcome is of importance to them and you will have your answer. So has permissive hypercapnia failed to deliver?  The answer in terms of the long term outcomes that hospitals use to benchmark against one and other may be yes.  The answer from the perspective of the baby and family and at least this Neonatologist is no.  
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You don’t plan to fail. You fail to plan

I am fortunate to work with a group of inter-professionals who strive for perfection.  When you connect such people with those with skills in multimedia you create the opportunity for education.  I can’t say enough about the power of education and moreover the ability to improve patient outcomes when it is done well. With this post I am going to be starting to share a collection of videos that I will release from time to time.  The hope with any release like this is that you the reader wherever you are may find some use from these short clips.  My thanks to the team that put these together as the quality is beyond compare and the HD quality is great for viewing on any device. Placing A Chest Tube Can Be A Difficult Thing As I said to a colleague in training the other day, a chest tube may seem daunting but once you see how it is done it loses some of its intimidation.  Having said that, once you see it placed it can be a long time between opportunities for you to view another.  That is where having a repository of videos comes in that you can watch prior to the next opportunity.  These very short clips are easy to access when needed and may calm the nerves the next time you are called to place a chest tube. A Word About Chest Tubes The videos in question demonstrate how to place a Thal quick chest tube. In case this looks foreign to you it may be because you are using the older generation style of chest tubes that come equipped with a trocar.  Even without the use of the trocar, these rigid tubes carry a significant risk of lung laceration or other tissue injury.  For a review of such complications related to chest tube insertion see Thoracostomy tubes: A comprehensive review of complications and related topics. The jury as they say is still out with respect to the use of these softer chest tube sets.  There is no question that they are easier to place than the traditional thoracostomy tube.  Their pliability though does carry a significant risk of kinking or blockage as we have seen in some patients when the Thal chest tube set is used to drain fluid in particular.  Less of an issue with air leaks. Start of a series This post I suppose marks a slightly new direction for the blog.  While I thoroughly enjoy educating you with the posts about topics of interest I see an opportunity to help those who are more visual in their learning.  The videos will be posted over the next while with accompanying written posts such as this.  They can be accessed on my Youtube channel at All Things Neonatal YouTube To receive regular updates as new videos are added feel free to subscribe! Lastly a big thank you to NS, RH and GS without whom none of this would have been possible!
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Just how safe is feeding while on CPAP?

This is becoming “all the rage” as they say.  I first heard about the strategy of feeding while on CPAP from colleagues in Calgary.  They had created the SINC (Safe Individualized Feeding Competence) program to provide an approach to safely introducing feeding to those who were still requiring CPAP.  As news of this approach spread a great deal of excitement ensued as one can only imagine that in these days when attainment of oral feeding is a common reason for delaying discharge, could getting an early start shorten hospital stay?  I could describe what they found with the implementation of this strategy but I couldn’t do it the same justice as the presenter of the data did at a recent conference in Winnipeg.  For the slide set you can find them here.  As you can imagine, in this experience out of Calgary though they did indeed find that wonderful accomplishment of shorter hospital stays in the SINC group.  We have been so impressed with the results and the sensibility of it all that we in fact have embraced the concept and introduced it here in both of our units.  The protocol for providing this approach is the following. I have to admit, while I have only experienced this approach for a short time the results do seem to be impressive.  Although anecdotal a parent even commented the other day that she felt that SINC was instrumental in getting her baby’s feeding going!  With all this excitement around this technique I was thrown a little off kilter when a paper came out suggesting we should put a full stop to feeding on CPAP! Effect of nasal continuous positive airway pressure on the pharyngeal swallow in neonates What caused my spirits to dampen? This study enrolled preterm infants who were still on CPAP at ≥ 34 weeks PMA and were taking over 50% of required feeding volumes by NG feeding.  The goal was to look at 15 patients who were being fed on CPAP +5 and with a mean FiO2 of 25% (21-37%) using video fluoroscopic swallowing studies to determine whether such patients aspirate when being fed.  The researchers became concerned when each of the first seven patients demonstrated abnormalities of swallowing function indicating varying degrees of aspiration.  As such they took each patient off CPAP in the radiology suite and replaced it with 1 l/min NP to achieve acceptable oxygen saturations and repeated the study again.  The results of the two swallow studies showed remarkable differences in risk to the patient and as such the recruitment of further patients was stopped due to concerns of safety and a firm recommendation of avoiding feeding while on CPAP was made. Table 2. Percentage of all swallows identified with swallowing dysfunction     on-nCPAP off-nCPAP   Variable Mean ± s.d. Mean ± s.d. Median (q1–q3) Mean ± s.d. Median (q1–q3) P-value Mild pen. % 20.1±16 20 (4.5–35) 15.4± 7.6 20 (9–20) 0.656 Deep pen. % 43.7±15.4 38.5 (30–59) 25.3± 8.8  25 (18.2–32) 0.031 Aspiration % 33.5±9.4 30 (27.3–44.4) 14.6± 7 15 (9.1–20) 0.016 Nasopharyngeal reflux   % 42.8±48.5 18.2 (0–100) 44.2± 45.4 18.2 (5–92) 0.875   Taking these results at face value it would seem that we should put an abrupt halt to feeding while on CPAP but as the saying goes the devil is in the details… CPAP Using Ram Cannulae Let me start off by saying that I don’t have any particular fight to pick with the RAM cannulae.  They serve a purpose and that is they allow CPAP to be delivered with a very simple set of prongs and avoid the hats, straps and such of more traditional CPAP devices. We have used them as temporary CPAP delivery when moving a patient from one area to another.  As the authors state the prongs are sized in order to ensure the presence of a leak.  This has to do with the need to provide a way for the patient to exhale when nasal breathing.  Prongs that are too tight have a large leak and may not deliver adequate pressure while those that are too tight may inadvertently deliver high pressure and therefore impose significant work of breathing on the patient.  Even with appropriate sizing these prongs do not allow one to exhale against a low pressure or flow as is seen with the “fluidic flip” employed with the infant flow interface. With the fluidic flip, exhalation occurs against very little resistance thereby reducing work of breathing which is not present with the use of the RAM cannula. A comparison of the often used “bubble CPAP” to a variable flow device also showed lower work of breathing when variable flow is used. The Bottom Line Trying to feed an infant who is working against a constant flow as delivered by the RAM cannulae is bound to cause problems.  I don’t think it should be a surprise to find that trying to feed while struggling to breathe increases the risk of aspiration.  Similarly, under treating a patient by placing them on nasal prongs would lead to increased work of breathing as while you may provide the needed O2 it is at lower lung volumes.  Increasing work of breathing places infants at increased risk of aspiration.  That is what I would take from this study.  Interestingly, looking at the slide set from Calgary they did in fact use CPAP with the fluidic flip.  Smart people they are.  It would be too easy to embrace the results of this study and turn your nose to the SINC approach to feeding on CPAP.  Perhaps somewhere out there someone will read this and think twice about abandoning the SINC approach and a baby will be better for it.
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The Hidden Pathogen Of Late Onset Sepsis

If you work in the NICU then you have seen your fair share of septic workups for late onset sepsis.  Sepsis is such a common diagnosis that if I had to guess I would say that at least 50% of all discharge summaries would include this in a list of final diagnoses for any VLBW infant.  If you were to look through the chart though you would find that while workups are common, the recovery of a pathogenic bacterium is not as much.  This is in part due to the low threshold that many people have for doing such workups.  A little bit of temperature instability, a few more apneic events than normal or a rise in O2 requirements may all trigger such investigations.  When they come back negative we all feel good that we looked but we also are then quick to blame the etiology on something else.  Mild fluctuations in temperature are written off as overbundling, apnea due to outgrowth of caffeine and a rise in FiO2 to evolving CLD.  Maybe though the explanation at least in some cases is that there was a pathogen but we didn’t test for it. Viruses are everywhere Tis the season so to speak so everyone is on high alert for viruses in our homes, schools, malls etc but many of us consider the NICU to be mostly free of such pathogens.  The truth is we mostly are provided that we all wash our hands well, keep sick contacts from visiting and put on a mask when our coughing starts.  Alas, if you have done a handwashing audit as we have you would know that when looking at technique and duration of handwashing, we don’t always hit 100%.  These audits are for health care practitioners but I have often wondered what sort of results we would see were we to do the same for parents and visitors.  When we know the viruses are out there such as during outbreaks of RSV and influenza we can’t help but send off our samples for respiratory viruses more frequently but what if we did this with intention for every late onset septic workup? Lucky For Us Someone Did Just That! Back in 2014 the following study was published. Viral respiratory tract infections in the neonatal intensive care unit: the VIRIoN-I study.  This was a simple prospective and elegant study in which any infant in the NICU who had never been home and was greater than 72 hours had respiratory samples sent for viral panels within 72 hours of starting antibiotics for presumed late onset sepsis.  The findings were certainly interesting in that 6% of 135 sepsis evaluations tested positive for a virus.  In the analysis, the infants had the following characteristics: tended to be older (41 vs 11 days; P = .007) exposed to individuals with respiratory tract viral symptoms (37% vs 2%; P = .003) lower total neutrophil counts (P = .02) best predictor of viral infection was the caregivers’ clinical suspicion of viral infection (P = .006) What interests me about these results are a couple things.  The first is that as I was once told, the sensitivity of asking if someone has been around sick people is low during peaks in viral outbreaks as who hasn’t?  Perhaps what this study tells us is that within the NICU environment we actually do a reasonable job of keeping such contacts away but when they slip through infections happen.  The second point worth mentioning is that a low neutrophil count is associated which is interesting given how often neutropenia is pointed to as a reason to start antibiotics.  These viruses are troublesome creatures indeed! Further Evidence Arrives At the end of last year a similar study was published by the same group Viral Respiratory Infections in Preterm Infants during and after Hospitalization.  They took a different approach this time out and took nasopharyngeal samples from 189 infants in the NICU (96 term and 93 preterm) within 7 days of birth and then sent samples weekly while in hospital followed by monthly for four months after discharge. In this collection of infants a mere 4 patients tested positive in NICU and all of them under 28 weeks of age at birth!  How do we account for the remarkable reduction in risk while in hospital?  To answer that you can read through the NICU environment in the full article if you have access.  In short, they had a very rigorous infection control set of precautions set up.  Interestingly only one of the infections was with RSV and the unit did not provide prophylaxis for infants in hospital.  Perhaps with precautions like theirs they felt it was unnecessary.  Once discharged a little over a third of patients acquired a viral infection in the first four months at home.  Given the potential risk for readmission and with that to a PICU this rate of viral infection is concerning. Vision for the future! Taken together we can state that viruses do make their way into the NICU but fortunately not as commonly as one might think.  What the last study in particular does remind us though is that we need to ensure that as part of discharge teaching parents take home many of the practices that we have used in the hospital with respect to hand hygiene, limiting visitors and not being afraid to holster some hand sanitizer for those times when soap and water are not so easy to come by.  To be sure viruses are out there but at least for the first few months after discharge for our most vulnerable babies a little paranoia about viruses could go a long way.
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Too Small To Extubate?

This is something that I continue to hear from time to time even in 2016 and I imagine I will continue to hear rumblings about this in 2017.  Certainly, there are physical limitations when a baby is born at less than 500g.  Have you tried fitting a mask to deliver NIPPV or CPAP to a baby this small?  I have and it didn’t work.  The mask was simply too big to provide a seal and while I am all for INSURE and emerging minimally invasive surfactant techniques they still require transitioning to a form of non invasive positive pressure ventilation to allow extubation success.  Certainly though above the 500g barrier it may be that the greatest impediment to extubation is our own bias. If this sounds a little familiar it is because I have written about this topic before Extubation failure is not a failure itself.  The reason for bringing the topic up again though is that aside from needing to address our own fears there is a new systematic review that acts somewhat of a how to guide to optimizing your chance at a successful extubation.  The review encompasses findings from 50 studies with successful extubation as defined as no need for reintubation within 7 days.  Before getting into the details of the optimal approach it is worth reminding people that failure of extubation in even our smallest babies is not a failure itself.  Such babies who “fail” up to 5 times do not suffer any long term consequences and may wind up with less risk of BPD than those who are kept intubated due to fear of failure. So After Reviewing The Evidence What Are the Recipes To Success? Continuous positive airway pressure Reduced extubation failure in comparison with head-box oxygen (risk ratio [RR], 0.59;95%CI, 0.48-0.72; number needed to treat [NNT], 6; 95%CI, 3-9). If you aren’t extubating to nCPAP then chances are I would bet your success rates are quite low.  Head boxes certainly can tell you how much O2 a patient requires but do nothing to help inflate alveolar spaces. Nasal intermittent positive pressure ventilation (NIPPV) vs. CPAP Higher prevention of extubation failure (RR, 0.70; 95%CI, 0.60-0.81; NNT, 8; 95%CI, 5-13).  This one is of particular interest to me.  The evidence has suggested this for some time and with a number needed to treat of 8 it would seem illogical to use anything else at the outset, especially in the smallest of infants.  The issue here though is that at least here in Canada the options for delivering such NIPPV are currently quite limited.  At the moment we are limited to use of ventilator NIPPV and the stability of the CPAP offered from such devices and the imposed work of breathing are most likely inferior to that found in variable flow devices which at this point have been pulled from the market. See Comparison of nasal continuous positive airway pressure delivered by seven ventilators using simulated neonatal breathing.  What I hope 2017 brings is a comparison of the effectiveness of extubation success using new variable flow devices capable of generating previously unreachable CPAP pressures above 9 or 10 cm H2O.  Will these attain similar effectiveness to the NIPPV devices? Methylxanthines reduced extubation failure (RR, 0.48; 95%CI, 0.32-0.71; NNT, 4; 95%CI, 2-7) compared with placebo or no treatment. Ok, pretty much anyone working in Neonatology would assume this but what really is at the crux of the discussion in 2016 and beyond is “what dose?” It has been pretty clear during my career thus far that there are some preterm infants that just don’t respond to conventional doses of caffeine base from 2.5  – 5 mg/kg/d.  In our own units we have increased doses to 6, 7 or 8 mg/kg/d to achieve some degree of respiratory stimulation and usually been limited by tachycardia in determining how high we can go.  Given the sparse literature regarding safety on this topic we are relegated to ask ourselves what is worse, leaving a baby on a ventilator or using higher doses of caffeine? I have given some thoughts on this before as well Are we overdosing preemies on caffeine?   Doxapram did not aid successful extubation (RR, 0.80; 95% CI, 0.22-2.97). For selfish reasons I have to admit I was happy to see this.  We can’t access this medication very easily here in Canada so hearing that it doesn’t seem to work to enhance the likelihood of a successful extubation is somewhat of a relief. A Cautionary Note While I applaud the authors of the systematic review for performing such a thorough job I do feel the need to raise one concern with the analysis.  It is not a major concern but one that I just feel the need to mention.  Success if the studies was defined as not requiring reintubation within 7 days of extubation.  My concern is that having such a lengthy time frame leaves the possibility that the decision to reintubate had nothing to do with the patient in fact not being ready.  Seven days is a long time and much can happen in the life of a preterm infant in an NICU that triggers a reintubation.  What if a patient needed to be transferred to a different NICU and for safe air transport it was deemed safest to replace the ETT?  How many patients could have developed NEC or sepsis in the seven days? What if a PDA was being semi-electively ligated after a failed NSAID course? In the end the impact of such conditions could be minimal but I am less convinced that a patient failed extubation when up to 7 days have passed.  I would be very interested to see a similar study looking at a period of 24 or 48 hours after extubation and seeing how many stay that way.  Would the predictors of success stay the same?  Probably but I suspect the number safely extubated would rise as well. featured image from the March of Dimes
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What do body builders and preemies have in common?

A strange title perhaps but not when you consider that both are in much need of increasing muscle mass.  Muscle takes protein to build and a global market exists in the adult world to achieve this goal.  For the preterm infant human milk fortifiers provide added protein and when the amounts remain suboptimal there are either powdered or liquid protein fortifiers that can be added to the strategy to achieve growth.  When it comes to the preterm infant we rely on nutritional science to guide us. How much is enough?  The European Society For Pediatric Gastroenterology, Hepatology and Nutrition published recommendations in 2010 based on consensus and concluded: “We therefore recommend aiming at 4.0 to 4.5 g/kg/day protein intake for infants up to 1000 g, and 3.5 to 4.0 g/kg/day for infants from 1000 to 1800 g that will meet the needs of most preterm infants. Protein intake can be reduced towards discharge if the infant’s growth pattern allows for this. The recommended range of protein intake is therefore 3.5 to 4.5 g/kg/day.” These recommendations are from six years ago though and are based on evidence that preceded their working group so one would hope that the evidence still supports such practice.  It may not be as concrete though as one would hope. Let’s Jump To 2012 Miller et al published an RCT on the subject entitled Effect of increasing protein content of human milk fortifier on growth in preterm infants born at <31 wk gestation: a randomized controlled trial.  This trial is quite relevant in that it involved 92 infants (mean GA 27-28 weeks and about 1000g on average at the start), 43 of whom received a standard amount of protein 3.6 g/kg/day vs 4.2 g/kg/d in the high protein group. This was commenced once fortification was started and carried through till discharge with energy intakes and volume of feeds being the same in both groups.  The authors used a milk analyzer to ensure consistency in the total content of nutrition given the known variability in human milk nutritional content.  The results didn’t show much to write home about.  There were no differences in weight gain or any measurements but the weight at discharge was a little higher in the high protein group.  The length of stay trended towards a higher number of days in the high protein group so that may account for some of the difference.  All in all though 3.6 or 4.2 g/kg/d of protein didn’t seem to do much to enhance growth. Now let’s jump to 2016 This past month Maas C et al published an interesting trial on protein supplementation entitled Effect of Increased Enteral Protein Intake on Growth in Human Milk-Fed Preterm Infants: A Randomized Clinical Trial.  This modern day study had an interesting question to answer.  How would growth compare if infants who were fed human milk were supplemented with one of three protein contents based on current recommendations.  The first group of 30 infants all < 32 weeks received standard protein intake of 3.5 g/kg/d while the second group of 30 were given an average intake of 4.1 g/kg/d.  The second group of 30 were divided though into an empiric group in which the protein content of maternal or donor milk was assumed to be a standard amount while the second 15 had their protein additive customized based on an analysis of the human milk being provided.  Whether the higher intake group was estimated or customized resulted in no difference in protein intake on average although variability between infants in actual intake was reduced. Importantly, energy intake was no different between the high and low groups so if any difference in growth was found it would presumably be related to the added protein. Does it make a difference? The results of this study failed to show any benefit to head circumference, length or weight between the two groups.  The authors in their discussion postulate that there is a ceiling effect when it comes to protein and I would tend to agree.  There is no question that if one removes protein from the diet an infant cannot grow as they would begin to break down muscle to survive.  At some point the minimum threshold is met and as one increases protein and energy intake desired growth rates ensue.  What this study suggests though is that there comes a point where more protein does not equal more growth.  It is possible to increase energy intakes further as well but then we run the risk of increasing adiposity in these patients. I suppose it would be a good time to express what I am not saying!  Protein is needed for the growing preterm infant so I am not jumping on the bandwagon of suggesting that we should question the use of protein fortification.  I believe though that the “ceiling” for protein use lies somewhere between 3.5 – 4 g/kg/d of protein intake.  We don’t really know if it is at 3.5, 3.7, 3.8 or 3.9 but it likely is sitting somewhere in those numbers.  It seems reasonable to me to aim for this range but follow urea (something outside of renal failure I have personally not paid much attention to).  If the urea begins rising at a higher protein intake approaching 4 g/kg/d perhaps that is the bodies way of saying enough! Lastly this study also raises a question in my mind about the utility of milk analyzers.  At least for protein content knowing precisely how much is in breastmilk may not be that important in the end.  Then again that raises the whole question of the accuracy of such devices but I imagine that could be the source of a post for another day.
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Mother’s milk and BPD; Every Drop Counts

Producing milk for your newborn and perhaps even more so when you have had a very preterm infant with all the added stress is not easy.  The benefits of human milk have been documented many times over for preterm infants.  In a cochrane review from 2014 use of donor human milk instead of formula was associated with a reduction in necrotizing enterocolitis.  More recently similar reductions have been seen in retinopathy of prematurity. Interestingly with respect to the latter it would appear that any amount of breast milk leads to a reduction in ROP.  Knowing this finding we should celebrate every millilitre of milk that a mother brings to the bedside and support them when it does not flow as easily as they wish.  While it would be wonderful for all mothers to supply enough for their infant and even more so that excess could be donated for those who can’t themselves we know this not to be the case.  What we can do is minimize stress around the issue by informing parents that every drop counts and to celebrate it as such! Why Is Breast Milk So Protective Whether the outcome is necrotizing enterocolitis or ROP the common pathway is one of inflammation.  Mother’s own milk contains many anti-inflammatory properties and has been demonstrated to be superior to formula in that regard by Friel and no difference exists between preterm and term versions.  Aside from the anti-inflammatory protection there may be other factors at work such as constituents of milk like lactoferrin that may have a protective effect as well although a recent trial would not be supportive of this claim. Could Mother’s Own Milk Have a Dose Response Effect in Reducing The Risk of BPD? This is what is being proposed by a study published in early November entitled Influence of own mother’s milk on bronchopulmonary dysplasia and costs.  What is special about this study and is the reason I chose to write this post is that the study is unusual in that it didn’t look at the effect of an exclusive human milk diet but rather attempted to isolate the role of mother’s own milk as it pertains to BPD.  Patients in this trial were enrolled prospectively in a non randomized fashion with the key difference being the quantity of mothers own milk consumed in terms of a percentage of oral intake.  Although donor breast milk existed in this unit, the patients included in this particular cohort only received mother’s own milk versus formula.  All told, 254 infants were enrolled in the study. As with many studies looking at risks for BPD the usual culprits were found with male sex being a risk along with smaller and less mature babies and receipt of more fluid in the first 7 days of age.  What also came up and turned out after adjusting for other risk factors to be significant as well in terms of contribution was the percentage of mother’s own milk received in the diet. Every ↑ of 10% = reduction in risk of BPD at 36 weeks PMA by 9.5% That is a really big effect! Now what about a reduction in costs due to milk?  That was difficult to show an independent difference but consider this.  Each case of BPD had an additional cost in the US health care system of $41929! What Lesson Can be Learned Here? Donor breast milk programs are a very important addition to the toolkit in the NICU.  Minimizing the reliance on formula for our infants particularly those below 1500g has reaped many benefits as mentioned above.  The availability of such sources though should not deter us from supporting the mothers of these infants in the NICU from striving to produce as much as they can for their infants.  Every drop counts!  A mother for example who produces only 20% of the needed volume of milk from birth to 36 weeks corrected age may reduce the risk of her baby developing BPD by almost 20%.  That number is astounding in terms of effect size.  What it also means is that every drop should be celebrated and every mother congratulated for producing what they can.  We should encourage more production but rejoice in every 10% milestone. What it also means in terms of cost is that the provision of lactation consultants in the NICU may be worth their weight in gold.  I don’t know what someone performing such services earns in different institutions but if you could avoid two cases of BPD a year in the US I would suspect that nearly $84000 in cost savings would go a long way towards paying for such extra support. Lastly, it is worth noting that with the NICU environment being as busy as it is sometimes the question “are you planning on breastfeeding?” may be missed.  As teams we should not assume that the question was discussed on admission.  We need to ask with intention whether a mother is planning on breastfeeding and take the time if the answer is “no” to discuss why it may be worth reconsidering.  Results like these are worth the extra effort!
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Parents,What Are You Worried About?

Throughout my career one thing has been consistently true.  That is that wherever I was working and regardless of the role I have been an educator.  I imagine the blog to a great extent is related to my interest in this aspect of my work.  In the last few years much has been said about care by parents whether it be a general approach for family centred care or in formalized approaches such as FiCare which has also been formally studied in the research setting.  When we speak of family centred care, one thing that I am constantly reminded of is that the focus of all of our efforts must be on the family and the patient.  As I said recently to a colleague when discussing what was presented as a difficult discussion with another colleague due to a disagreement about the direction of management, when you put the patient first the discussion really isn’t difficult at all.  It’s not about you or a colleagues ego but about the patient and if the management is not up to par then change direction and worry about managing egos later. What We Know And What They Know Another aspect that needs to be addressed is the difference in power that we have through knowledge.  I am not talking about us exerting authority over families but from the perspective of us having the knowledge from years of experience in the field as to what is significant and what is not in terms of events in the NICU.  The evidence for example with respect to neurodevelopmental outcome from apnea and bradycardia should give us reason to be optimistic the majority of the time.  While in Edmonton I learned a great deal from one of my colleagues who  was the lead author in a paper entitled Early childhood neurodevelopment in very low birth weight infants with predischarge apnea.  While frequent apnea may be associated with mild motor impairments in their paper, the predictive value of these predischarge recordings is very limited when you take away those kids without severe IVH.  I think about all of the parents we see who have their eyes glued to the monitors while they attend at the bedside and what they must be thinking.  To us it is just a matter of time but I wonder for them how agonizing a time it really is!  It isn’t just those infants who are nearing discharge and having apnea either as the CAP study  at 5 years of age showed no difference in survival without disability in those infants who received caffeine vs those who did not.  More frequent events may not be that detrimental after all.  I am not suggesting we not treat patients as one never knows where the threshold lies to cause injury but these preemies are certainly made of some tough stuff. Identifying Stress and Preparing Parents For it The first step in dealing with this issue is to know it is there.  Recognizing this, Melnyk and others performed an educational intervention targeting behaviour of families in their study Reducing premature infants’ length of stay and improving parents’ mental health outcomes with the Creating Opportunities for Parent Empowerment (COPE) neonatal intensive care unit program: a randomized, controlled trial.  The group of parents who went through the program had better mental health outcomes compared to the control groups.  The issue here and really is at the crux of the goal in writing all of this is that the stress that parents feel may not be overtly present.  The squeaky wheel as the saying goes gets the grease and the parents that are demonstrating signs of poor coping are the first to draw the referrals to social work or engage in a deeper conversation with nursing at the bedside.  All parents experience stress at least to a certain degree and it is all of our jobs to tease it out.  On the other hand employing standardized approaches such as the COPE program for all parents might be another way of helping those who are in need but not clearly wearing a sign on their foreheads that say “help me”. Don’t Underestimate the Power of Reassurance So we know that much of what we see on the monitors will not lead to long term harm, transient central cyanosis during feeds will not damage the brain and apnea of prematurity is a distinct entity from SIDS.  The parents on the other hand commonly make these links and additionally in case no one has mentioned it to you, those babies with TTN may one day develop asthma and those with hypoglycemia may have diabetes (we know both not to be true but I have been asked about this many times).  This is why I believe it is our duty to explain why we are not worried about things that come up in the unit.  Saying “don’t worry” or “that is normal preterm behaviour” may not be enough.  Ask a parent what it is they are worried about and you may be surprised to find out the links that they have made in their heads, some of which may be valid but some completely false.  I am not meaning to trivialize their concerns but rather validate them as real worries.  If we have the knowledge and it is power as I said before then shouldn’t we use that power to help reduce their stress? Engaging Families Can Reap Huge Dividends The movement towards family centred care and more specifically care by parent will have a dramatic impact on this issue.  As more and more centres move to engaging families to be part of rounds and not just listen and then ask questions but to take some degree of control and provide some of the reporting stress will be reduced.  It is only logical.  The more a family comes to understand what is significant and what is not in terms of reporting concerns the more confident they will be.  Moreover, spending more time at the bedside leads to more skin to skin care and with that shorter hospital stays due to better cardiorespiratory stability.  We aren’t there yet but we are headed in the right direction.  In the meantime, take the time to ask a simple question “what are you worried about” to parents no matter how confident and strong they appear and you may find yourself with an opportunity to harness the power of education you have a make a real difference to a family in need.  
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Towards better and safer intubation

We are the victims of our own success.  Over the last decade, the approach to respiratory support of the newborn with respiratory distress has tiled heavily towards non-invasive support with CPAP.  In our own units when we look at our year over year rates of ventilation hours they are decreasing and those for CPAP dramatically increasing.  Make no mistake about it, this is a good thing.  Seeming to overlap this trend is a large increase in demand by learners as we see the numbers of residents, subspecialty trainees, nurse practitioners on the rise.  The combined effect is a reduction is the experience trainees can possibly hope to obtain when these rarer and rarer opportunities arise.  The result of all of this is that at least by my eyes (although we haven’t documented it) the number of attempts for intubations seems to be much higher than it once was.  It is not uncommon to see 3-4 attempts or sometimes more whereas in days gone by 1-2 attempts was the norm.  We do our best to deal with these shortages using simulation as an example but nothing quite compares to dealing with the real thing even if it comes close. The Less Practice You Get The More Adverse Events You Can Expect This is just the way it is.  Perfect practice makes perfect and it has been well documented that intubations can lead to many complications such as desaturation, bradycardia, bleeding, airway edema from multiple attempts and a host of other issues.  Hatch and colleagues first described their experience with 162 intubations in which they found adverse events in 107 (39%) with 35% being classified as non-severe and severe events in 8.8%.  Not surprisingly one of the factors associated with adverse events was the need for multiple intubation attempts.  Based on this initial experience they determined that as a unit they could do better and soon after undertook a series of PDSA Quality Improvement cycles to see if they could reduce these events and that they did.  What follows are the lessons learned from their QI project and it is my hope that some or all of these ideas may help others elsewhere who are experiencing similar frustrating rates. Steps To A Better Intubation The findings of their QI study were published last month in Pediatrics in their paper Interventions to Improve Patient Safety During Intubation in the Neonatal Intensive Care Unit.  The strategies they used were threefold. Standardized checklist before intubation – This used a “do-confirm” approach in which the individuals on the team “do” what they need to prepare and then confirm with the group that they are done.  An example might be an RRT who states “I have three sizes of ETT ready with a stylet already inserted, surfactant is thawed and the ventilator is set with settings of … if needed etc”.  Another critical part of the checklist includes ensuring that everyone knows in advance their roles and who is responsible for what. Premedication algorithm – Prior to this project the use of premedication was inconsistent, drug selection was highly varied and muscle relaxation was almost non-existent.  The team identified from the literature that a standard approach to premedication had been associated with reductions in adverse events in other centres so adopted the same here using fentanyl with atropine if preterm and muscle relaxation optional. Computerized order set for intubation – interestingly the order set included prompts to nursing to make sure intervention 1 and 2 were done as well. The results of there before and after comparison were numerous but I have summarized some of the more important findings in the table below. Outcome Period 1 (273 intubations) Period 2 (236 intubations) p Any AE 46.2% 36.0% 0.02 Severe events 8.8% 6.4% 0.04 Bradycardia 24.2% 9.3% <0.001 Hypoxemia 44.3% 33.1% 0.006 Esophageal intubation 21.3% 14.4% 0.05 # attempts 2 2 NS <10 intubations experience 15.1% 25.5% 0.001 The median number of attempts were no different but the level of experience in the second epoch was less.  One would expect with less experienced intubators this would predict higher risk for adverse events.  What was seen though was a statistically significant reduction in many important outcomes as listed in the table.  I can only speculate what the results might have been if the experience of the intubators was similar in the first and second periods but I suspect the results would have been even more impressive.  The results seem even more impressive in fact when you factor in that the checklist was used despite all of the education and order set 73% of the time and muscle relaxation was hardly used at all.  I believe though what can be taken out of these results is that taking the time to plan each intubation and having a standard approach so that all staff practice in the same way reaps benefits.  If you already do this in your unit then congratulations but if you don’t then perhaps this may be of use to you! What About Intubation For INSURE? We are in the process of looking in our own centre at the utility of providing premedication when planning to give surfactant via the INSURE technique.  I couldn’t help but notice that this paper also looked at that very issue.  Their findings in 17 patients all of whom were provided premedication were that only one could not be extubated right after surfactant.  The one who was not extubated however was kept intubated for several hours without any reasoning provided in the records so it may well be that the infant could have been electively kept ventilated when they may have indeed been ready for extubation.  The lesson here though is that we likely do not need to exclude such patients from premedication it will reduce the likelihood of complications without prolonging the time receiving positive pressure ventilation. Whatever your thoughts may be at this time one of the first questions you should ask is what is our local rate of complications?  If you don’t know then do an audit and find out.  Whatever the result, shouldn’t we all strive to lower that number if we can?
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Congratulations On The Birth Of Your Preterm Infant! Now Pay It Forward?

It’s World Prematurity Day today and if you are a parent or are caring for a baby who has just entered this world before 37 weeks GA you are now part of a membership that counts 15 million new babies each year according to the WHO’s data.  As I tell most new parents who have a baby admitted to our unit “It’s ok to take some time to adjust to this.  You didn’t plan on being here”.  That is true for most who go into spontaneous labour but of course those who are electively delivered due to maternal or fetal indications that have been followed closely often have time to prepare for the journey to the NICU.  Many of these parents will have had the opportunity to visit the NICU or even connect with other parents before the anticipated birth of their child to at least get a glimpse into what life is like in the NICU.  Much has been written about parental stress and methods to reduce it and I find that a piece that appeared in the Huffington Post offers some good pointers to helping parents manage the transition from pregnancy to NICU.  The piece is entitled 5 Things Never To Say To Parents Of Preemies (And What To Say Instead).  It is well worth a read but the one thing that stuck out in my mind is one very important thing to say. Congratulations on the birth of your baby There is no doubt that the family who gives birth to a preterm infant is experiencing stress.  What may be lost in the first few days of surfactant, central lines and looking for sepsis among other things is that a new member of the 15 million strong has entered this world.  They have a new child and just like anyone else should receive a congratulations.  No one needs to tell them to be worried.  They already are and likely view many of the possibilities more pessimistically than you do.  Taking a moment to say congratulations though may go a long way to reminding them that amidst all this stress there is something to rejoice in and look to the future.  If we aren’t supportive then I have no doubt the subconscious message is that they shouldn’t have hope either.  I am not suggesting that we sugarcoat what is really going on but one can be honest about likely outcomes and still celebrate the arrival of a new baby.  Much has also been written recently about a number of strategies to reduce stress in the NICU such as skin to skin care, integration of families more closely into the patient care team and forming parent support groups just to name a few.  What else can be done to improve the quality of life for parents going through this journey? Enrol Your Baby In A Research Study I work in an academic centre and given the volume of research projects at any given time there is a need to approach families and sometimes quite soon after delivery.  interestingly, I have heard from time to time that individuals have been hesitant to approach families due to a feeling that they are overwhelmed and won’t be receptive to being approached in this fragile state.  I am guilty of the same thoughts from time to time but maybe it is time I reconsider.  Nordheim T et al just published an interesting study on this topic entitled Quality of life in parents of preterm infants in a randomized nutritional intervention trial.  This study was actually a study of parents within a study that called the PreNu trial that involved an intervention of a energy and protein supplemental strategy to enhance weight at discharge.  The trial was an RCT and unfortunately although well intentioned was stopped when the intervention group was found to have an unexpected increase in sepsis rates.  Although this study did not ultimately find a positive outcome there were additional analyses performed of quality of life and parental stress at two time points the first being during the hospital stay and the second at 3.5 years of age.  The patients were all treated the same aside from the nutritional intake and in the end 30 intervention parents and 31 single parents not enrolled in a study (many in couples) participated in the study.  In followup a little less than 70% completed the stress measures at 3.5 years.  The results are found below. How Do We Interpret This The parents in this study who were part of the intervention group were about 3 years older so perhaps with more life experience may have developed some better coping strategies but during the hospital stay those who participated in research had better measures of quality of life and at three years better reports of sleep and energy levels.  The study is quite small so we need to take all of this with a grain of salt with respect to the 3.5 year outcomes as there are so many variables that could happen along the way to explain this difference but I think it may be fair to acknowledge the quality of life measure during the stay. Why might parents report these findings? The finding of better quality of life is especially interesting given that more patients in this study had sepsis which one would think would make for a worse result. Here are a few thoughts.  Involvement in research may have increased their knowledge base as they learned about nutrition and expected weight gain in the NICU. Frequent interaction with researchers may have given them more attention and with it more education. Some parents may have simply felt better about knowing they were helping others who would come after them.  I have heard this comment myself many times and suspect that it would be attributable at least to a certain extent. A better understanding of the issues facing their infants through education may have reduced stress levels due to avoiding “fear of the unknown”. Regardless of the exact reason behind the findings what stands out in my mind is that participation in research likely provides comfort for parents who are in the midst of tremendous stress.  Is it the altruistic desire to help others or being able to find something good in the face of a guarded outlook?  I don’t know but I do believe that what this study tells us is that we shouldn’t be afraid to approach families. After first congratulating them give them a little time to absorb their new reality and then offer them the chance to improve the care for the next 15 million that will come this time next year for World Prematurity Day 2017.
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A Cure For Neonatal Hypoglycemia

I have probably received more requests for our glucose gel protocol than any other question since I started writing on this blog.  Dextrose gel has been used more and more often for treatment of hypoglycemia such that it is now a key strategy in the management of low blood sugar in ours and many other institutions.  If you are interested in the past analyses of the supporting trials they can be found in these posts; Glucose gel For Managing Hypoglycemia. Can We Afford Not To Use It? and Dextrose gel for hypoglycemia: Safe in the long run?  As you can tell from these posts I am a fan of dextrose gel and eagerly await our own analysis of the impact of using gel on NICU admission rates for one! But What If You Could Prevent Hypoglycemia Rather Than Treating It? This is the question that the same group who has conducted the other trials sought to answer in their dose finding study entitled Prophylactic Oral Dextrose Gel for Newborn Babies at Risk of Neonatal Hypoglycaemia: A Randomised Controlled Dose-Finding Trial (the Pre-hPOD Study).  I suppose it was only a matter of time that someone asked the question; “What if we prophylactically gave at risk babies dextrose gel?  Could we prevent them from becoming hypoglycemic and reduce admissions and improve breastfeeding rates as has been seen with treatment of established hypoglycemia?”  That is what they went out and did.  The group selected at risk patients such as those born to mothers with any type of diabetes, late preterm infants, SGA and others typically classified as being at risk but who did not require NICU admission at 1 hour of age when treatment was provided.  The primary outcome was hypoglcyemia (<2.6 mmol/L) in the first 48 hours.  Secondary outcomes included NICU admissions, breastfeeding rates in hospital and after discharge as well as formula intake at various time points. The study sought really to serve as a pilot whose goal was to determine when compared to placebo whether several different regimens could prevent development of hypoglycemia.  The groups were (with the first dose in each case given at 1 hour of age): Single dose of 40% dextrose gel – 0.5 mL/kg Single dose of 40% dextrose gel – 1 ml/kg Four doses of 0.5 mL/kg given every three hours with breastfeeding A single dose of 1 mL/kg then 3 X 0.5 mL/kg given q3h before each breastfeed. In total 412 patients were randomized into 8 different groups (4 treatment and 4 placebo).   As The Saying Goes, Less Is More The only dose of dextrose that reduced the risk of hypoglycemia in the first 48 hours was 0.5 mL/kg which provides 200 mg/kg of dextrose which is the same as a bolus of IV dextrose when giving 2 mL/kg of D10W.  Curiously using a higher dose or using multiple doses had no effect on reducing the risk.  Based on a difference of 14% between placebo and this group you would need to treat roughly 7 patients with dextrose gel once to prevent one episode of hypoglycemia.  Also worth noting is that admission to NICU was no different but if one restricted the reason for admission to hypoglycemia the difference was significant (13% vs 2% risk; p = 0.04).  What was not seen here was a difference in rates of breastfeeding and much effect on use of formula. Why Might These Results Have Occurred? Insulin levels were not measured in this study but I truly wonder if the reason for hypoglycemia in the other groups may have been transient hyperinsulinemia from essentially receiving either a very large load of glucose (1 mL/kg groups) or effectively 4 boluses of glucose in the first 12 hours of feeding.  Rebound hypoglycemia from IV boluses is a known phenomenon as insulin levels surge to deal with the large dextrose load and I can’t help but wonder if that is the reason that all but the single dose regimen had an effect.  It is also worth commenting that with so many secondary outcomes in this study the p values needed to reach significance are likely much smaller than 0.05 so I would take the reduction in NICU admissions for hypoglycemia with a grain of salt although at least the trend is encouraging. I wouldn’t change my practice yet and the authors do acknowledge in the article that a much larger study is now being done using the single dose of 0.5 mL/kg to look at outcomes and until that is published I don’t think a practice change is in order.  What this study does reinforce though is that providing multiple doses of dextrose gel may yield diminishing returns.  While the goal here was prophylaxis, I can’t help but think about the patients who are symptomatic and receive two or three gels and still wind up with an IV.  Could it be the same rebound hypoglycemia at play? We also have to acknowledge that even if this is an effective preventative strategy, is it in the best interests of the babies to all receive such treatment when at least in 6 babies they wouldn’t have needed any?  Could such treatment simply be reserved as has been done for those who develop hypoglycemia?  Those who question the safety of the ingredients such as dyes that are found in the product may want some long term safety data before this becomes routine in at risk babies but it won’t surprise me if such strategies become commonplace pending the results of the larger trial on the way.
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