Now that I have caught your attention it is only fair that I explain what I mean by such an absurd title. If you work with preterm infants, you have dealt with apnea of prematurity. If you have, then you also have had to manage such infants who seemingly are resistant to everything other than being ventilated. We have all seen them. Due to increasing events someone gives a load of methylxanthine and then starts maintenance. After a couple days a miniload is given and the dose increased with the cycle repeating itself until nCPAP or some other non-invasive modality is started. Finally, after admitting defeat due to persistent episodes of apnea and/or bradycardia, the patient is intubated. This, in the absence of some other cause for apnea such as sepsis or seizures is the methylxanthine resistant preterm infant. Seemingly no amount of treatment will amount to a reduction in events and then there is only so much that CPAP can do to help.
Other strategies have been attempted to deal with such infants but sadly none have really stood the test of time. Breathing carbon dioxide might make sense as we humans tend to breathe quickly to excrete rising CO2 but in neonates while such a response occurs it does not last and is inferior to methylxanthine therapy. Doxapram was used in the past and continues to be used in Europe but concerns over impacts on neurodevelopment have been a barrier in North America for some time. Stimulating infants through a variety of methods has been tried but the downside to using for example a vibrating mattress is that sleep could be interfered with and there are no doubt impacts to the preterm infant of having weeks of disturbed sleep states on developmental outcomes.
What if we could make our preterm infants walk?
This of course isn’t physically practical but two researchers have explored this question by using vibration at proprioceptors in the hand and foot. Such stimulation may simulate limb movement and trick the brain into thinking that the infant is walking or running. Why would we do this?. It has been known for 40 years that movement of limbs as in walking triggers a respiratory stimulatory effect by increasing breathing. This has been shown in adults but not in infants but this possibility is the basis of a study carried out in California entitled Neuromodulation of Limb Propriceptive Afferents Decreases Apnea of Prematurity and Accompanying Intermittent Hypoxia and Bradycardia. This was a small pilot study enrolling 19 patients of which 15 had analyzable data. The design was that of alternating individual preterm infants born between 23 – 35 weeks to receive either vibratory stimulation or nothing and measuring the number and extent of apnea and bradycardia over these four periods. In essence this was a proof of concept study.
The stimulation is likened to that felt when a cell phone vibrates as this was the size of device used to generate the sensation. The authors note that during the periods of stimulation the nurses noted no signs of any infant waking or seeming to be disturbed by the sensation. The results were quite interesting especially when noting that 80% of the infants were on caffeine during the time of the study so these were mostly babies already receiving some degree of stimulation
Should we run out and buy these?
The stimulation does appear to work but with any small study we need to be careful in saying with confidence that this would work in a much larger sample. Could there have been some other factor affecting the results? Absolutely but the results nonetheless do raise an eyebrow. One thing missing from the study that I hope would be done in a larger sample next time is an EEG. The authors are speculating that by placing the vibration over the hand and foot the brain is perceiving the signal as limb movement but it would have been nice to see the motor areas of the brain “lighting up” during such stimulation. As we don’t have that I am left wondering if the vibration was simply a form of mild noxious stimulus that led to these results. Of course in the end maybe it doesn’t matter if the results show improvement but an EEG could also inform us about the quality of sleep rather than relying on nursing report of how they thought the baby tolerated the stimulus. I know our nursing colleagues are phenomenal but can they really discern between quiet and active sleep cycles? Maybe some but I would guess most not. There will also be the naysayers out there that will question safety. While we may not perceive a gentle vibration as being harmful, with such a small number of patients can we say that with certainty? I am on the side of believing it is probably insignificant but then again I tend to see the world through rose coloured glasses.
Regardless of the filter through which you view this world of ours I have to say I am quite excited to see where this goes. Now we just have to figure out how to manage the “real estate” of our infant’s skin as we keep adding more and more probes that need a hand or a foot for placement!
The giant leaps in Neonatology may for the most part be over. So many outstanding research trials have brought us to where we are today. The major innovations of surfactant replacement, the discovery of nitric oxide and its later use to treat pulmonary hypertension, caffeine for apnea have all changed our field for the better. Cooling for HIE has certainly changed my practice in that I now truly have no idea what to tell parents after even some of the worst cases of asphyxia as our team has witnessed “miracles”after cooling. What will come next? My bet is that we are about to enter the era of Quality Improvement more and more. Think about the last study you read that had a major change in your practice or better yet made a substantial change in survival or neurodevelopmental outcome.
Tweaking care is where its at.
I like to think of it as fine tuning. As the era of the major leaps in care seems to be passing us by what I see more and more are studies looking at how to make further improvements on what we already know. In some cases such as using higher doses of caffeine may reduce the incidence of apnea further compared to standard dosing while cooling for 96 hours instead of 72 and at lower temperatures after asphyxia may not be such a good idea after all. There will be some studies that suggest a modification of practice and then others that suggest we should look elsewhere for further improvements. With all of this evidence coming out in hundreds if not thousands of journals every week it is difficult to keep up and it may be that our focus is in need of a change in direction or at least devoting members of the team to look at something different.
That Focus Is On Quality Improvement (QI)
Before I go on I don’t want to insinuate that I am something that I am not. I do not have any formal training in QI and consider myself an amateur but I do understand enough to undertake a PDSA cycle and see where it takes me. To me QI is about finding ways to actually make your best practices the best they can be. Take for example our units goal to minimize needle pokes by carefully examining the usefulness of common tests that we perform. Add to this the recent implementation of non invasive technology such as transcutaneous bilirubin metres which our evidence suggests can reliably replace a serum sample to screen for those in need of phototherapy. While I commonly like to praise our team for its ability to critically think about needed bloodwork it was only through the collection of data using audit tools that we discovered we had a problem. The problem was that the rate of CBC samples that were clotting were unacceptably high at over 30%. This was compared to another NICU in the same city that had a rate of less than 1/3 that. The initial reaction since it was trained lab personnel collecting at the low clotting site vs nursing at the high rate site was that the solution was simple. Just change back to lab personnel (as it used to be) at the high rate site! Ah but that would create another problem. Other evidence used to build a care plan for our preterm infants suggested that clustering of care was better for them than poking them at the usual run time of the lab techs so we had a conflict. How did we solve it? We resisted our urge for the quick fix and entered into a formal QI project.
How did we do it and what were the results?
It took us four rounds of PDSA cycles but in the end we found a solution that has lasted. As I write this I learned that one of our two units that had the high rates set a record low this past month of a 4.9% clotting rate even lower than the comparative site that began with a low clotting rate. It took work and was by no means easy but the dedication of our nurse educator to the task made all the difference. Fortunately, for those who don’t know where to begin an incredible resource is available from BMJ Quality Improvement who provide a step by step process to carry out your project. Moreover after using their template for publishing such work, we were able to publish our work which we hope may be of help for other centres that find themselves in a similar situation. Perhaps the solution might be the same or at least similar enough to try one of our interventions? The full paper can be found at the end of the post but the trend over time is so impressive that I felt obliged to show you the results.
Why should you care?
Teams spend so much time rolling out new evidence based initiatives. All the evidence in world won’t help if the intervention isn’t achieving the results you expect. How will you know unless you audit your results? You may be surprised to find that what you expected in terms of benefit you aren’t seeing. By applying the principals of QI you may find you don’t need to look for another treatment or device but rather you simply need to change your current practice. A little education and direction may be all that is needed. You may also find to your surprise that what you thought everyone was doing is not what they are doing at all.
Resist the quick solution and put in the time to find the right solution. As Carl Honore suggests slowing things down may be the best thing for all of us and more importantly the patients we care for.
Link to the full article:
- Mohammed S et al. High versus low-dose caffeine for apnea of prematurity: a randomized controlled trial. Eur J Pediatr 2015 Jul;174(7):949-56.
- Shankaran S et al. Effect of depth and duration of cooling on deaths in the NICU among neonates with hypoxic ischemic encephalopathy: a randomized clinical trial.JAMA 2014 Dec 24-31;312(24):2629-39
As the saying goes the devil is in the details. For some years now many centres worldwide have been publishing trials pertaining to high flow nasal cannulae (HFNC) particularly as a weaning strategy for extubation. The appeal is no doubt partly in the simplicity of the system and the perception that it is less invasive than CPAP. Add to this that many centres have found less nasal breakdown with the implementation of HFNC as standard care and you can see where the popularity for this device has come from.
This year a contact of mine Dominic Wilkinson on twitter (if you don’t follow him I would advise having a look!) published the following cochrane review, High flow nasal cannula for respiratory support in preterm infants. The review as with most cochrane systematic reviews is complete and comes to a variety of important conclusions based on 6 studies including 934 infants comparing use of HFNC to CPAP.
1. No differences in the primary outcomes of death (typical RR 0.77, 95% CI 0.43 to 1.36; 5 studies, 896 infants) or CLD.
2. After extubation to HFNC no difference in the rate of treatment failure (typical RR 1.21, 95% CI 0.95 to 1.55; 5 studies, 786 infants) or reintubation (typical RR 0.91, 95% CI 0.68 to 1.20; 6 studies, 934 infants).
3. Infants randomised to HFNC had reduced nasal trauma (typical RR 0.64, 95% CI 0.51 to 0.79; typical risk difference (RD) -0.14, 95% CI -0.20 to -0.08; 4 studies, 645 infants).
4. Small reduction in the rate of pneumothorax (typical RR 0.35, 95% CI 0.11 to 1.06; typical RD -0.02, 95% CI -0.03 to -0.00; 5 studies 896 infants) in infants treated with HFNC but the RR crosses one so this may be a trend at best.
If one was to do a quick search for the evidence and found this review with these findings it would be very tempting to jump on the bandwagon. Looking at the review a little closer though there is one line that I hope many do not miss and I was happy to see Dominic include it.
“Subgroup analysis found no difference in the rate of the primary outcomes between HFNC and CPAP in preterm infants in different gestational age subgroups, though there were only small numbers of extremely preterm and late preterm infants.”
In his conclusion he further states:
Further evidence is also required for evaluating the safety and efficacy of HFNC in extremely preterm and mildly preterm subgroups, and for comparing different HFNC devices.
With so few ELBW infants included and with these infants being at highest risk of mortality and BPD our centre has been reluctant to adopt this mode of respiratory support in the absence of solid evidence that it is equally effective to CPAP in these smallest infants. A big thank you to our Respiratory Therapy Clinical Specialist for harping on this point over the years as the temptation to adopt has been strong as other centres turn to this strategy.
Might Not Be So Safe After All
Now do not take what I am about to say as a slight against my twitter friend. The evidence to date points to exactly what he and his other coauthors concluded but with the release of an important paper in May by Taka DK et al, I believe caution is needed when it comes to our ELBW infants.
High Flow Nasal Cannula Use Is Associated with Increased Morbidity and Length of Hospitalization in Extremely Low Birth Weight Infants
This paper adds to the body of literature on the topic as it truly focuses on the outcome of infants < 1000g. While this study is retrospective in nature it does cover a five year period and examines important outcomes of interest to this population.
The primary outcome in this case was death or BPD and whether HFNC was used alone or with CPAP, this was more frequent than when CPAP was used alone. Other important findings were the need for multiple and longer courses of ventilation in those who received at least some HFNC. In these times of overburdened health care systems with goals of improving patient flow, it is also worth noting that there was a significant prolongation of length of stay with use of HFNC or HFNC and CPAP.
One interesting observation was that the group that fared the worst across the board was the combination of CPAP and HFNC rather than HFNC alone.
||HFNC +/- CPAP (1546)
|CPAP d (median, IQR)
|HFNC d (median, IQR)
|HFNC +/- CPAP
|BPD or death %
|Multiple ventiation courses
|More than 3 vent courses
|Ventilator d (median, IQR)
I believe the finding may be explained by the problem inherent with retrospective studies. This is not a study in which patients were randomized to either CPAP, HFNC or CPAP w/HFNC. If that were the case one would expect lung pathologies and severity of illness to even ou,t such that differences between groups might be explained by the difference in treatments. In this study though we are looking though the rearview mirror so to speak. How could we account for the combination being worse than the HFNC alone? I suspect it relates to the severity of lung disease. The babies who were placed on HFNC and did well on it might have had less severe chronic changes. What might be said about those that had the combination? Well, one could postulate that there might be some who were extubated to HFNC and collapsed needing escalation to CPAP and then failing that therapy were reintubated. Another explanation could be those babies who were placed on CPAP after extubation and transitioned before their lungs were ready to HFNC may have failed and lost FRC thereby going back to CPAP and possibly intubation. Exposure in either circumstance to HFNC would therefore put them at risk of further positive pressure ventilation and subsequent further lung injury. The babies who could tolerate transition to HFNC without CPAP might be intermediary in their outcomes (as they were found to be) as they lost FRC but were able to tolerate it but consumed more calories leaving less for growth and repair of damaged tissue leading to prolonged need for support.
Either way, the use of HFNC was found to lead to worse outcomes and in the ELBW infant should be avoided as routine practice pending the results of a prospective RCT on the subject.
Is it a total ban though?
As with many treatments that one should not consider standard of care there may be some situations where there may be benefit. The ELBW infant with nasal breakdown from CPAP that despite excellent nursing and RRT attention continues to demonstrate tissue damage is one patient that could be considered. The cosmetic implications and potential for surgical correction at a later date would be one reason to consider a trial of HFNC but only in the patient that was close to being able to come off CPAP. In the end I believe that if a ELBW infant needs non invasive pressure support then it should be with CPAP but as there saying goes there may be a right time and a place for even this modality.
It seems the expression “(insert a group) lives matter” is present everywhere these days so I thought I would join in after a moving experience I had today. For those of you who have been with the blog since the beginning you would have seen a number of posts that if you follow them in time, provide a glimpse into the transformation that Winnipeg has seen over the last year or so.
Prior to that point, 24 weeks was a cutoff for resuscitation that had been in place for some time and after a great amount of deliberation and thought was changed to 23 weeks. This did not come without a great deal of angst and a tremendous amount of education and teamwork that our nurse educators and clinical leads were so instrumental in helping to role out. The experience was outlined in a couple of posts that you may find interesting if you didn’t catch them the first time. The first was Winnipeg hospital now resuscitating all infants at 22 weeks! A media led case of broken telephone. and the second being Winnipeg Hospital About to Start Resuscitating Infants at 23 weeks!
Since these two posts we have certainly had our fair share of experience as we have seen far more babies than anticipated but the region has met the challenge head on and although the numbers are small we appear to have not only more survivors than expected but all but one infant had gone home without O2 and all have been demand feeding at discharge. While we await the 18 month outcomes, the results thus far appear reassuring.
A Special & Memorable Visit
Then today, a visit occurred from the first of such infants who is now just over a year of age. He was bright eyed, smiling, interactive and by his parent’s account, has normal tone and assessments thus far by physiotherapy. His presence in the NICU put smiles on faces and at least for myself made me think of the expression “Micropreemie Lives Matter”. He was a baby that everyone predicted would not survive and then when he did, that he would be grossly developmentally impaired which he does not appear to be in the least. His presence in the unit no doubt gives everyone who doubted the merits of moving down this path reason to pause.
Before you accuse me of wearing rose coloured glasses, make no mistake I know that he will not represent the outcome for everyone. In fact at one of our hospitals two of such infants have died while we await the 18 month outcomes for the other survivors. What his presence does though, is remind us or at least me that good outcomes are possible and in the case of our experience in Winnipeg may be more common that we thought they would be.
Black Swans and Human Nature
When I have spoken to audiences about the path forward when resuscitating such ELGANS I have often commented on the “Black Swan” effect. This was very nicely described by Nassim Taleb and described the human trait to react to unusual events with extreme reactions. An example is no one wanting to fly in the months after the world trade centre bombing when statistically this may have been the safest period in history to fly. Similarly, we as a team need to avoid the extreme reaction of saying that we should not be resuscitating such small infants when a bad outcome occurs. As I have told many people, we know these patients will not all survive, we know a significant number will have adverse development yet not all will and at least in our small sample thus far the babies would appear to be doing better overall than anticipated. If we know that bad outcomes will occur then why do we hear the questions come when they do such as “why are we doing this?”, “maybe we should rethink our position on 23 week infants”. It happens because we care and we hate seeing families and their babies go through such painful experiences. What we cannot do though for the sake of those such as our visitor today is react with a “Black Swan” reaction and steer the ship so to speak in the previous direction we were in. There are survivors and they may do well and that is why I say “Micropreemie Lives Matter”.
In the paper by Rysavy the overall finding at 23 weeks was that 1 out of 6 would survive without moderate or severe disability. What do we do as we increase our experience if the trend bears out that our outcomes are better? How will we counsel families? Will we continue to use the statistics from the paper or quote our own despite us being a medium sized centre?
The Big Questions
As our experience with such infants increases we will also no doubt see a change in our thoughts about infants at 24 weeks. I have seen this first hand already with a physician commenting today that 24 weeks is not such a big deal now! This brings me to the big question (which I will credit a nurse I work with for planting in my head in the last two weeks) which is for another time to answer as this post gets a little lengthy but is something to ponder. As our outcomes for 23 weeks improve and so do our results at 24 weeks (which is bound to happen with the more frequent team work in such situations) will our approach to infants at 24 weeks change. In our institution we generally follow the CPS guidelines for the management of infants at extremely low GA and offer the choice of resuscitation at 24 weeks. As outcomes improve at this GA will we continue to do so or will we reach a threshold where much like the case at 25 weeks we inform families that we will resuscitate their infant without providing the option of compassionate care?
It is too early to answer these questions conclusively but they are very deserving of some thought. Lastly, I would like to thank the parent who came by today for inspiring me and to all those who will follow afterwards.
I woke up this morning and as I do everyday, scanned the media outlets for news that would be of interest to you the reader. One such article today was about how breast milk may give babies a metabolic boost due to micro RNA present in the milk. This got me thinking about how natural a thing this breast milk is and how substances within interact with the baby receiving it. After that point I recalled writing about a challenge to the statement that breast milk is natural and thought you might like to see what I considered to be an outrageous piece of journalism from last year.
The premise of the article is that by reinforcing that breastfeeding is natural we may hamper initiatives to increase vaccination in many parts of the world and in particular North America I would think. The idea here is that if we firmly entrench in women’s heads that natural is better then this will strengthen the conviction that we should not vaccinate with these “man made” unnatural vaccines. I am sorry to be dramatic about this but I think the argument is ridiculous and in fact dangerous.
The Definition of Natural
“existing in nature and not made or caused by people : coming from nature”
From the Mirriam Webster dictionary
Breastfeeding satisfies this definition pure and simple and there is nothing that anyone should say to suggest otherwise no matter what the motive is. The shift from formula to breastfeeding has been predicated on this notion and a plethora of literature on the subject demonstrating reductions in such things as infections of many kinds, diarrhoea, atopic disease in the first year of life as examples. In my world of premature infants additional reductions in NEC, bloody stools, have been seen and more recently in some cases improved neurodevelopmental outcomes.
In this case of irresponsible journalism a better approach if you were wanting to use the natural argument with respect to vaccines is to promote just that.
Vaccines are Natural
Someone will no doubt challenge me on this point as it would be a fair comment to say that there are artificial substances added to vaccines but there is no question the organisms that we vaccinate against are natural.
Think about this for a moment. All of the vaccines out there are meant to protect us against organisms that exists in NATURE. These are all bacteria or viruses that have likely existed on this planet of ours for millions of years. They are found everywhere and in many cases what we are doing when we give such vaccines are providing parts of or weakened versions of these natural organisms in order for us the human to mount a protective response.
This protective response is NATURAL. If we didn’t vaccinate and came across the fully virulent pathogen in NATURE our bodies would do exactly what they do when a vaccine is given to us. Our immune system would mount a response to the organism and start producing protective antibodies. Unfortunately in many cases this will be too little too late as the bacteria or virus will cause it’s damage before we have a chance to rid ourselves of this natural organism.
This is the basis of vaccination. Allow our bodies a chance to have protection against an organism that we haven’t been exposed to yet so that when it comes we have a legion of antibodies just waiting to attach this natural organism.
CNN Didn’t Get It Right
In the article which is based on a paper entitled the Unintended Consequences of Invoking the “Natural” in Breastfeeding Promotion by
If the goal is to improve vaccination rates, focus on informing the public about how NATURAL vaccinations actually are and don’t drag breastfeeding down in order to achieve such goals. As a someone who writes themselves I am well aware of how personal biases creep into everything we write. I am aware of the irony of that statement since it is clear what side of the argument I sit on. While I peruse CNN myself almost daily I think the editors either missed the larger message in this piece or perhaps felt the same way. A disclosure that “the opinions of the author do not necessarily represent those of the network” does not cut it for what I would consider responsible journalism in this case.