Can a chest x-ray predict the future?

Can a chest x-ray predict the future?

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

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

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

What an x-ray at 7 days may tell you

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

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

What do we do with such information?

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

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

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

 

Is our approach to ventilation really harming babies?

Is our approach to ventilation really harming babies?

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

Where then does this leave us?

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

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

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

There may be a problem here though

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

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

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

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

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

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

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

Why is this holy grail so important?

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

The “Next Step” Volume Ventilator BVM

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

Some Concerning Findings

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

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

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

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

 

Magnetic acupuncture coming to an NICU near you?

Magnetic acupuncture coming to an NICU near you?

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

Magnetic Acupuncture

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

So what were the results?

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

Should we run out and buy it?

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

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

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

 

Free parking to increase parental visitation

Free parking to increase parental visitation

This is a title that I hope caught your eye.  In the nearly twenty years I have been in the field of Pediatrics the topic of parking being a barrier to parental visitation has come up again and again.  A few years ago the concern about the cost of parking was so great that I was asked if I could find a pool of donors to purchase parking passes to offset the burden to the family.  The theory of course is based on the idea that if parking were free in the NICU parents would visit more.  If parents visit more they will be more involved in the care of their baby, more likely to breastfeed and with both of these situations in play the infant should be discharged earlier than other infants whose parents don’t visit.  Try as I might it was a tough sell for donors who tend to prefer buying something more tangible that may bear their name or at least something they can look at and say “I bought that”.  This is quite tough when it comes to a parking stall and as such I am still looking for that elusive donor.  Having said that, is there any basis to believe that free parking is the solution that will deliver us from minimal visitation by some parents?

A Study May Help Answer The Question

Northrup TF et al published an article that was sent my way and to be honest I couldn’t wait to read it.  A free parking trial to increase visitation and improve extremely low birth weight infant outcomes. This is like the holy grail of studies.  A study that gets right to the point and attempts to answer the exact question I and others have been asking for some time.  The study took place in Houston, Texas and was set up as an RCT in which families were randomized into two groups.  Inclusion criteria were birth weight ⩽1000 g, age 7 to 14 days and deemed likely to survive.  Seventy two patients were enrolled in the free parking group while 66 were placed in the usual care.  Interestingly the power calculation determined that they would need 140 to show a difference so while 138 is close it wasn’t enough to truly show a difference but let’s see what they found.

The Results

Free parking made absolutely no difference for the whole group. Specifically there was no difference in the primary outcome of length of stay or hours spent per visit.  Some interesting information though that may not be that surprising was found to be of importance in the table below.  table-1

It may not seem like a surprise but the patients who were more affluent and those who had less children tended to visit more.  The latter makes a lot of sense as what are many people to do when they have one or more other children to care for at home especially in the face of little support?  Would free parking make one iota of difference if the barrier has nothing to do with the out of pocket cost?

The conclusion was that the strategy didn’t work that well but as you may have picked up I think the study was flawed.  By applying the strategy to all they were perhaps affected by choosing the wrong inclusion criteria.  Taken to an extreme, would a 50 million dollar Powerball winner care one bit about parking vouchers?  It wouldn’t make any difference to whether they were going to come or not.  Similarly a single mother with 5 other kids who lives below the poverty line and has little support is not going to come more frequently whether they have a voucher or not.

What if the study were redone?

I see a need to redo this study again but with different parameters.  What if you randomized people with a car or access to one who lived below a certain income level and had a committed support person who could assure that team that they could care for any other children the family had when called upon?  Or one could look at families with no other children and see if offering free parking led to more frequent visitation and then from there higher rates of Kangaroo Care and breastfeeding.  I for one haven’t given up on the idea and while I was truly excited to be sent this article and sadly initially dismayed on first read, I am hopeful that this story has not seen it’s end.

It is intuitive to me that for some parents parking is a barrier to visiting. Finding the right population to prove this though is the key to providing the evidence to arm our teams with evidence to gain support from hospital administrations.  Without it we truly face an uphill battle to get this type of support for families.  Stay tuned…