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. This 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?
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.
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.
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.
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.
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.
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…
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.
It seems like a sensational title I know but it may not be as far fetched as you may think. The pendulum certainly has swung from the days of liberal post natal dexamethasone use in the 1990s to the near banishment of them from the clinical armamentarium after Keith Barrington published an article entitled The adverse neuro-developmental effects of postnatal steroids in the preterm infant: a systematic review of RCTs in BMC Pediatrics in 2011. This article heralded in the steroid free epoch of the first decade of the new millennium, as anyone caring for preterm infants became fearful of causing lifelong harm from steroid exposure. Like any scare though, with time fear subsides and people begin asking questions such as; was it the type of steroid, the dose, the duration or the type of patient that put the child at risk of adverse development? Moreover, when death from respiratory failure is the competing outcome it became difficult to look a parent in the eye when their child was dying and say “no there is nothing more we can do” when steroids were still out there.
Over the last decade or so, these questions in part have been studied in at least two important ways. The first was to ask whether we use a lower dose of dexamethasone for a shorter period to improve pulmonary outcomes without adverse neurodevelopment? The target population here were babies on their way to developing chronic lung disease as they were ventilated at a week of age. The main study to answer this question was the DART study. This study used a very low total dose of 8.9 mg/kg of dexamethasone given over ten days. While the study was stopped due to poor recruitment (it was surely difficult to recruit after the 2001 moratorium on steroids) they did show a benefit towards early extubation. This was followed up at 2 years with no difference in neurodevelopmental outcomes. Having said that the study was underpowered to detect any difference so while reassuring it did not prove lack of harm. Given the lack of evidence showing absolute safety practitioners have continued to use post natal steroids judiciously.
The second strategy was to determine whether one could take a prophylactic approach by providing hydrocortisone to preterm infants starting within the first 24 hours to prevent the development of CLD. The best study to examine this was by Kristi Watterberg in 2004 Prophylaxis of early adrenal insufficiency to prevent bronchopulmonary dysplasia: a multicenter trial. Strangely enough the same issue of early stoppage affected this study as an increased rate of spontaneous gastrointestinal perforation was noted leading to early closure. The most likely explanation is thought to be the combination of hydrocortisone and indomethacin prophylaxis which some centres were using at the same time. An interesting finding though was that in a subgroup analysis, infants with chorioamnionitis who received hydrocortisone had less incidence of chronic lung disease. (more on this later) Although this of course is subject to the possible bias of digging too deep with secondary analyses there is biologic plausibility here as hydrocortisone could indeed reduce the inflammatory cascade that would no doubt be present with such infants exposed to chorioamnionitis in utero.
Has the answer finally come?
The DART study at 360 patients was the largest study to date to look at prophylaxis as a strategy. That is until this past week. The results of the PREMILOC study have been published which is the long awaited trial examining a total dose of 8.5 mg/kg of hydrocortisone over 10 days. We can finally see the results of a trial without the complicating prophylactic indomethacin trials interfering with results. Surprisingly this study was also stopped early (a curse of such trials?!) due to financial reasons this time. Prior to stoppage though they managed to recruit 255 to hydrocortisone and 266 to control groups. All infants in this study were started on hydrocortisone within 24 hours of age and the primary outcome in this case was survival without BPD at 36 weeks of age.
All infants were less than 28 weeks at birth and therefore had a high risk of the combined outcome and despite the study being stopped early there was indeed a better outcome rate in the hydrocortisone group (60% vs 51%). Another way of looking at this is that to gain one more patient who survived without BPD you needed to treat 12 which is not bad at all. What is additionally interesting are some of the findings in the secondary analyses.
The lack of a difference in males may well reflect the biologic disadvantage that us males face overcoming any benefit from the hydrocortisone. In fact for the females studied the number needed to treat improves to 6 patients only! Short term outcomes of less ventilation are sure to please everyone especially parents. Lastly, a reduction in PDA ligation is most probably related to an antiprostaglandin effect of steroids and should be cause for joy all around. Lastly, a tip of the hat to Dr. Watterberg is in order as those infants who were exposed to chorioamnionitis once again show that this is where the real benefit may be.
But what about side effects?
The rate of NEC is quite high but is so for both groups but otherwise there is nothing much here to worry the reader. Once and for all we also see that by excluding concurrent treatment with indomethacin or ibuprofen the rate of GI perforation is no different this time around. Reassuring results indeed, but alas the big side effect, the one that would tip the scale towards us using or abandoning treatment has yet to be presented. Steroids no doubt can do great things but given the scare from 2001 we will need to see how this cohort of babies fares in the long run.
The follow-up is planned for these infants and the authors have done an incredible job of recruiting enough patients to make the results likely believable. I for one can’t wait to see what the future holds. If I was a betting man though I would say this ultra low dose of hydrocortisone may be just the thing to bring this therapy finally into the toolbox of neonatal units worldwide. We have been looking for the next big thing to help improve outcomes and good old hydrocortisone may be just what the doctor ordered.