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

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.  Screenshot 2017-06-04 17.32.59The tendency of the stethoscope was to underestimate the EKG HR by about 7 BPM. Two standard deviations though had it underestimate by almost 60 BPM or overestimate by about 50 BPM.  For the purposes of resuscitation, this range is far to great.  The mean is acceptable but the precision around that mean is to wide.  The other issue noted was the frequent missing data from loss of contact with the patient.  Could you imagine for example having a baby who has a heart rate of 50 by the stethoscope but by EKG 100? Big difference in approach, especially if you didn’t have EKG leads on to confirm.  The authors note that the accuracy is not sufficient and felt that an improvement in the software algorithms might help.

Another go at it

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

Should you buy one?

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

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

 

 

 

 

 

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.

973235-978492-156

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

Communication is certainly key

If there is one thing that keeps coming back as a lesson again and again in life it is the importance of communication.  Whether it be in the home or at work, too many of our “problems” in the workplace come down to whether or not our teams talk to one another effectively.

A tremendous source of stress of course is the unknown. When a baby is born in the field we can only rely on the information being presented to us via telephone contact.  In the melee that occurs on arrival of a potentially sick patient, details can be missed.

The following video illustrates such a situation and I believe aptly provides a good example of how to communicate in such a way that the stress of the situation is relieved. If we can all strive to slow things down just a little we may find that communication eliminates much of the tension in such a situation.

If you are looking to “slow” down your life and improve things such as communication style you may want to have a look at the book “In Praise of Slow” as we head into the weekend.  It’s all about slowing things down to actually improve efficiency.  51giI-ZIOtL._SX332_BO1,204,203,200_The world is moving pretty quickly these days and couldn’t we all do with a little more efficiency and less wasted time?  In Neonatology we are confronted with surprises every day, often with little notice.  If we can slow things down and pass on the needed information to the right people at the right time we will help to reduce errors if we can just get it right the first time!

 

 

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!

 

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

  1. Chorioamnionitis
  2. Maternal smoking
  3. Smaller birthweight (875 vs 922 g)
  4. Confirmed sepsis (23% vs 14%)
  5. Postnatal steroids (45% vs 8%) – but duration of ventilation longer in the day coverage group likely due to less postnatal steroids ( 31 vs 21 days)

All of these factors would predict a worse outcome for these infants but in the end for the primary outcome of neurodevelopmental impairment there was no difference.  Even after controlling for postnatal steroids, birth weight, sex and 5 minute apgar score there was still no difference.

What might this mean?

Looking at this with a glass is half full view one might say that with all of the factors above predicting worse outcome for infants, the fact that the groups are not different in outcome may mean that the 24 hour model does indeed confer a benefit.  Maybe having a Neonatologist around the clock means that care is made that much better to offset the effect of these other risk factors?  On the other hand another explanation could also be that the reason there is no difference is that the sample just isn’t big enough to show a difference.  In other words the size of the study might be underpowered to find a difference in developmental outcome.

One of the conclusions in this study is that the presence of a Neonatologist around the clock may have led to earlier extubation and account for the nearly 10 day difference in duration of ventilation.  While I would love to believe that for personal reasons I don’t think we can ignore the fact that in the earlier epoch almost 50% of the babies received postnatal steroids compared to 8% in the later period.  Postnatal steroids work and they do so by helping us get babies off ventilators.  It is hard to ignore that point although I woudl like to take credit for such an achievement.

For now it would appear that I don’t feel compelled to stay overnight in the hospital unless it is necessary due to patient condition necessitating me having my eye on the patient.  I am not sure where our field will go in the future but for now I don’t see the evidence being there for a change in practice.  With that I will retire to my bedroom while I am on call and get some rest (I hope).

Isn’t it time for a little Kangaroo in your NICU?

Aside from me donning the costume in the above picture for the Kangaroo Challenge 2017 I learned something new today.  Before I get into what I learned, let me say that I had the opportunity to put so many smiles on parents faces by walking around in this full body costume that I am grateful to Diane for finding this costume and Sue (you both know who you are) for purchasing it.  Handing out cookies to the parents and children at the bedside and seeing them smile while knowing that they were under significant stress gave me the opportunity to interact with parents in a very different way than I am accustomed to as a Neonatologist so I am so thankful to have had that experience and yes if called upon I will do it again!

We even made the local news! CTV newscast

I posted the above picture on my Facebook page and to my surprise many of the comments led me to believe that Kangaroo Care is still something that needs a little nudging to get the word out about.  I found this actually quite surprising given how immersed we are in Winnipeg with this strategy.  When I think about new interventions in Neonatology it is synonymous in virtually all cases with an influx of dollars to achieve usher in the new program.  Here is a program that is virtually free but only requires a commitment from families to spend the time at the bedside with their baby in the NICU.

I have been asked by many of my nursing colleagues to write something about Kangaroo care on this site and so here it is…

What is it?

You have likely heard of Kangaroo Care and you may have even seen some children receiving it in your hospital.  Why is this so important?

Kangaroo Care (KC) or Skin to Skin Care (STS) is an ideal method of involving parents in the care of their premature infant.  It fosters bonding between parents and their hospitalized infant, encourages the family to be with their child and thereby exposes them to other elements of neonatal care that they can take part in.  While we know that many units are practising Kangaroo Care there is a big difference between having KC in your unit and doing everything you can to maximize the opportunity that your families have to participate.

There is much more to KC than simply holding a baby against your chest.  For a demonstration of KC please watch the accompanying video and show it to any one in your units that may need a visual demonstration.  This excellent video is from Nationwide Children’s Hospital and walks you through all of the important steps to get it right and maximize benefit.

Kangaroo Care Video

Before you reach the conclusion that KC only serves to enhance the parental experience it does so much more than that.  The practice began in Bogota Columbia in 1979 in order to deal with a shortage of incubators and associated rampant hospital infections.  The results of their intervention were dramatic and lead to the spread of this strategy worldwide.  The person credited with helping to spread the word and establish KC as a standard of care in many NICUs is Nils Bergman and his story and commentary can be found here http://bit.ly/1cqIXlm

The effects of KC are dramatic and effective to reduce many important morbidities and conclusively has led to a reduction in death arguably the most important outcome.  An analysis of effect has been the subject of several Cochrane Collaboration reviews with the most recent one being found here.

To summarize though, the use of KC or STS care has resulted in the following overall benefits to premature infants at discharge or 40 – 41 weeks’ postmenstrual age:

Reduction in

mortality  (typical RR 0.68, 95% CI 0.48 to 0.96)

nosocomial infection/sepsis  (typical RR 0.57, 95% CI 0.40 to 0.80)

hypothermia (typical RR 0.23, 95% CI 0.10 to 0.55)

Increase in

KMC was found to increase some measures of infant growth, breastfeeding, and mother-infant attachment

To put this in perspective, medicine is littered with great medications that never achieved such impact as simply putting your child against your chest.  This is another shining example of doing more with less.  This is not to say that modern medicine and technology does not have its place in the NICU but KC is simply too powerful a strategy not to use and promote routinely in the NICU.

Please join me in championing this wonderful technique and make a difference to all of our babies!

A sample of our parent letter to promote KC is found in the link below.

Parent letter II

Early Hydrocortisone: Short term gain without long term pain.

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

Why Not Adopt The Results Based on These Fantastic Results?

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

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

Drumroll Please…

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

premiloc followup

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

Is it worth it?

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

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

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

 

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.

 

 

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?”

 

 

Improving information transfer. A team approach.

 

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 entitled A Golden Opportunity For Your NICU Team! 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

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Lastly a big thank you to NS, RH and GS without whom none of this would have been possible!