As I said in another post on this topic I have been a huge advocate of RSV prophylaxis since my days as a Pediatric resident. When I started my residency we were not using Palivizumab (Synagis) and I recall admitting 10+ patients per day at times with bronchiolitis. With the use of passive immunization this rate dropped dramatically in Manitoba although rates in other areas of the country may have not seen such significant impacts. Manitoba may be somewhat different from many areas due to the communities in Nunavut being so impacted when RSV enters these areas and can infect many of the children due to crowded living conditions and inability to really isolate kids from one and other. The lack of benefit in other areas though, has no doubt led to controversy among practitioners who often wonder if giving 5 IM injections during the RSV season is indeed worth it. The real question has not necessarily been does it work but to whom should it be given so that you get the most benefit.
In preterm infants without CLD born before 30 + 0 weeks’ GA who are <6 months of age at the start of RSV season, it is reasonable (but not essential) to offer palivizumab. Infants born after 30 + 0 weeks’ GA have RSV admission rates that are consistently ≤7% (Figure 3), yielding a minimum number needed to treat of 18 (90 doses of palivizumab to prevent one RSV admission) if one assumes 80% efficacy and five doses per infant. Therefore, palivizumab should not be prescribed for this group.
Gone are recommendations for treating those from 30 – 32 weeks and moreover 33- 35 weeks if meeting certain conditions. There is a provision for those in Northern communities to expand these criteria to 36 0/7 weeks if such infants would require medical transport to receive care for bronchiolitis. What is not really clear though is what is meant by Northern communities in terms of criteria to determine suitability exactly.
“The burden of RSV disease and costs associated with transport from remote locations may result in a broader use of palivizumab for RSV prevention in Alaska Native populations and possibly in selected other American Indian populations.”
The American guideline also states that it is for those infants who are “well” and under 29 weeks that RSV prophylaxis is appropriate but from 29 – 32 weeks use should be restricted to those babies who are on oxygen at 28 days of life.
The authors of this study found that while during the RSV season admission for RSV bronchiolitis was lower from 29 – 32 weeks in those infants who had received Synagis. This would argue that it should be given in this group except for the fact that as the authors state it was a “wash” since hospitalization for non-RSV bronchiolitis in the same population was increased by a similar amount. In essence if you didn’t get RSV you wound up getting something else that still put you in hospital. The conclusion here is that the decision to drop the criterion for prophylaxis to under 29 weeks is supported since from 29 – 32 weeks you can’t prevent hospitalization from viruses that take the place of RSV.
A Few Thoughts Though Before We Conclude It Has No Place
As I stated upfront I am not totally free of bias having seen a very large impact up here in Manitoba. What I worry about though is that we have in medicine a tendency to try and capture the “gist” of a guideline rather than committing it in its entirety to memory. We can’t help ourselves as the volume of information we are asked to remember is growing daily. What this may lead to however is changes to our practice that may expose vulnerable infants. The AAP guideline was designed to recommend changes for the otherwise healthy infant under 29 weeks. What I think we are really talking about are the truly exceptional babies. In our institution babies born at less than 29 weeks and certainly those closer to 24 weeks often spend as much as a month on CPAP. At 28 days even if the patient were on room air it might only be due to the fact that they were on distending pressure. Put them on nasal prongs and they would qualify.
Another important consideration is the remote location point. Here in Canada the majority of the population lives along the border with the US. Take a look though at our population density and you can see that for our Aboriginal (Indian) and Inuit populations as well as all those living in the north we have a significant need to protect them. Living conditions in these places involve overcrowding and high smoking levels both ideal breeding grounds for transmission of RSV and an intolerance to handling the inflammation in your bronchioles. The same is likely true of many parts of Alaska for my US readers.
It would be too easy to simply state “I only need to give Synagis to those babies under 29 weeks now” but that would do a disservice to the populations in our remote communities both here and in the US.
In case you are wondering, I am not employed by the makers of Synagis here or in the US nor do I have any financial or conflicts otherwise. I am someone I suppose who has seen the difference of before and after and while I will let others debate the merits of giving Synagis from 29 – 32 weeks and above, I wrote this as a reminder that not all populations are the same and therefore we should not paint all susceptible patients with one brush.
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.
I don’t know about your place of work but our centre is busy and by busy I mean our resources and staff are almost always working at full capacity. There is a shift afoot though in modern Neonatal care to shift some of the responsibility for care to the parents. You might say it always should have been this way but as with any speciality we grow, learn and evolve over time.
The most recent stage of evolution is the development of the FiCare philosophy. This is not the first time (and likely not the last) that I will reference this strategy. For more information on what it is and what it takes to practice this concept you can click on the FiCare website from Mt. Sinai Hospital in Toronto here. The gist of it though is that with education and support from nursing in particular some of the traditional functions that are carried out by health care staff can be transferred to the parents. Something as basic as identifying their baby can be a start with progression to providing part of the daily report, participating in handling of their infant during times of stress and performing skin to skin care for many hours a day. The parents are asked to commit to a significant number of hours per day to make this work and the benefits of having close contact are obvious as well.
Can Physiotherapy Be Taught To Parents?
As someone who has been involved in the FiCare project I took particular interest in an article this past month which in essence is related to the teachings of FiCare. T. Ustad from Norway and colleagues published the following Early Parent-Administered Physical Therapy for Preterm Infants: A Randomized Controlled Trial. As someone who values the contribution of our physiotherapists I was curious as to what could be transferred given the demands on an individual PT’s time. Add to this that during surges when many babies under 29 weeks are born and the number of patients they need to see may become overwhelming. What if parents though could take over some of this workload? Well that is what they did in three centres in Norway in a RCT single blinded intervention.
What did they do?
All babies were born < 32 weeks and underwent the intervention between 34 – 36 weeks with final evaluation at 37 week. Parents were taught to perform 10 minutes of manipulation with the goal of improving postural control, head control, and midline orientation. Teaching was done through videos, photos, booklets and direct teaching by the PT on day 1 and then on day 2 return demonstration with correction by the PT occurred.
It was single blinded in that the parent and the PT who did the teaching knew of course which baby received what treatment but the PT doing the standardized evaluation after the two week period was over was blind to treatment assignment. The authors used the TIMP scoring system for spontaneous movements which as it can take up to 30 minutes in some cases may stress the infants so for those a scoring system consisting of half the items was developed called the TIMPSI. This has beee shown previously to correlate well with the larger more involved test.
Sample size calculations were based on finding a difference at 2 years of 0.5 SD between groups which meant they needed 63 infants to show such a difference. They enrolled 153 but after some withdrew the groups were 63 in the intervention and 76 in conventional care.
On to the results
Just so we are clear, this was only designed to be a two week intervention but it was meant to be twice daily for ten minutes at a time. Graphically, using the z-scores for the TIMP scores we have the following graph. Clicking on the highlighted link will tell you more about z-scores but it measures simply how many standard deviations above or below a population mean a score is.
So in this case the absolute difference after the two week period with evaluation one week later is 0.42. This falls short of the 0.5 at two years the sample size calculation was looking for. As with many differences in outcome the results tend to improve with time. Think about the CAP study as an example in which those babies who received caffeine initially had better developmental outcome measures than those who did not but by school age there was no longer a differenced. If the difference is less then one needs many more patients to show a difference than the original sample size would allow. In the end one also needs to think about whether the difference in scores is of statistical interest or if it has true clinical impact.
Some things to consider though
The parents in the intervention group did keep a journal and what they actually did was not what was designed in the study. The average number of sessions per day was only 1.3 with a length of 9 minutes per session. The goals again were 2 for 10 minutes each. The second thing to think about is that by looking at the difference in results from this short intervention it is an exciting mental exercise to think about a couple things. The first is what might the differences look like if the families had been able to do two sessions each per day instead of being closer to 1. The extra minute may not have made such a difference but the extra session might have.
The next thing to consider is how short a time period this really was. What if the plan had been rather than only two weeks, providing the intervention till discharge which for some born at 24 weeks might have been a corrected age at 40 – 44 weeks when they finally went home. Would a much longer exposure have made a bigger difference?
It is always fun to speculate and while I cautioned that the difference seen at two years may narrow further I wonder what the impact on the families will be after the intervention and post discharge. They were taught a new set of techniques to support motor development. Would they simply revert back to the control group afterwards or informally continue on which is what I suspect to some degree they would. The log book doesn’t count the impact of these “extra sessions”. The authors plan an interim analysis along the way so that will be interesting to see.
What the study does show though and what I think is exciting is that it is not just nursing that can transfer some functions to parents. Clearly the parents in this study learned something about handling of patients from the perspective of a PT. I would hope that this study might inspire PTs and other disciplines as the FiCARE approach widens to consider equipping parents with some of their skills sets that are traditionally owned by those specialties alone. What we are discovering with time is that parents are capable of doing more than we have had them do in the past. To make it family centred care truly make them part of the team!
There may be nothing that is harder in medicine. We are trained to respond to changes in patients condition with a response that more often than not suggests a new treatment or change in management. Sometimes the best thing for the patient is in fact to do nothing or at least resist a dramatic response to the issue in front of you. This may be the most common issue facing the new trainee who is undoubtedly biased towards doing something. Take for instance the situation in which the trainee who is new to the service finding out that their 26 week infant has a PDA. Their mind races as they digest this information from morning signover. There is less than 2 hours until they come face to face with their attending who no doubt will ask them the dreaded question. “What are you going to do about it?”. When having to choose a path, if they state “I want to sit tight and watch” they fear the thought of the attending thinking they don’t know what to do. Conversely they could stick their neck out and choose to treat with a variety of approaches but then might they be seen as too aggressive?! The likely path is suggesting treatment but in fact the more I think about it the option of benign neglect may be the best approach or at least one in which if you treat and it doesn’t work the first time you just shrug your shoulders and say “I’ll deal with it till it closes on it’s own”.
This post really is a follow-up to a previous one entitled The Pesky PDA. A Puzzle After All These Years. What triggered this writing was another before and after comparison of two periods in which the management of PDAs for a unit took a 180 degree turn.
Know When to Hold Em And No When to Fold Em
This is the essence of the issue for one unit. Sung SI et al published a paper this month entitled Mandatory Closure Versus Nonintervention for Patent Ductus Arteriosus in Very Preterm Infants. They describe a before and after comparison of 81 infants from 2009-11 and 97 infants from 2012-14. All babies were born between 23-26 weeks gestational age. In the first time period their unit had a mandatory PDA closure policy. That is they gave one course of indomethacin and if possible a second course followed by surgical ligation. A significant PDA was defined as one that had a left to right shunt and was at least 2 mm in diameter and the patient had to be ventilated. Any patient who had been extubated regardless of need for CPAP did not have to have their PDA closed. In the second time period the group attempted to avoid indomethacin and ligation at all costs and in fact in this cohort none received either.
So What Happened?
In the first time period 52 (64%) received indomethacin but only 29% responded and a full 37/52 (71%) went on to receive surgical ligation. Of the 29 that did not receive indomethacin due to contraindications they underwent primary ligation for a total of 82% receiving surgical ligation. The average day of closure for period 1 was 12.9 days.
In period 2 a number of interesting findings occurred. The average day of closure was at 44.2 days. Five infants were discharged with a PDA with 3 experiencing spontaneous closure after discharge and the remaining infants undergoing transcatheter occlusion. In period 2 there were more diuretics and fluid restriction employed. Comparing the two periods for a number of other outcomes reveals some other intriguing findings.
Even with such differing approaches there is no difference in mortality, severe IVH, ROP, PVL, NEC or sepsis. What is different though is the diagnosis of BPD yet there is no difference in total ventilation. In period 2 there is a shift towards more of this ventilation being HFOV less CPAP use at the same time.
What Might It All Mean?
It is retrospective and therefore we cannot be certain that there are not other variables that are not affecting the results that would have had a better chance of being evened out in an RCT. Having said that it is intriguing that having a PDA has been associated with BPD in the past but in this study having a PDA for a longer time is associated with a reduction in BPD. We know that longer periods of invasive mechanical ventilation increase the risk of developing BPD so it is intriguing that that there is no difference in mechanical ventilation yet there is more BPD when you are aggressive with the PDA. You might postulate that the need for surgery leads to greater need for ventilatory support and therefore damages the lungs but the needs for HFOV was higher in the second phase which at least hints that in terms of aggressiveness, Period 2 infants had a tougher go.
The culprit may be the heart. In period 1 there was a significantly increased rate of myocardial dysfunction and need for inotropes following ligation. It could well be that left ventricular dysfunction led to pulmonary edema such that in the 24-28 hours after the surgery ventilator requirements were increased and damaged the lung. The lack of a difference in overall ventilation days supports this possibility. Looking at the other common risk factors for BPD such as chorioamnionitis and lack of antenatal steroids these are no different between groups. Although not statistically significant there are more male infants in period 2 which would usually tip the scales towards worse outcome as well. It does need to be stressed as well that the rate of surgical ligation is higher than any study I have come across so the contribution of the surgery itself to the disparate outcome needs to be seriously considered.
What would I do?
Despite this study and some others that have preceded it I am not at the point of saying we shouldn’t treat at all. Our own approach is to give prophylactic indomethacin to such babies and then for the most part if a PDA remains treat one more time but at all costs try and avoid ligation. An RCT sounds like it is in the works though comparing the two approaches so that will certainly be interesting to see. It is tough to say what the future holds but to any young trainees who are reading this, the next time you are asked what to do about a PDA you are well within your rights to suggest “Maybe we should do nothing”!