Will the edge of viability be redefined before long?

Will the edge of viability be redefined before long?

I couldn’t think of a better topic for World Prematurity Day 2021 than what constitutes the edge of viability. Thinking back over my career, when I was a resident and fellow infants born at 25 and 26 weeks were deemed about as low as “we should” go but we certainly resuscitated infants at 24 weeks but this was considered heroic. Jump ahead to the last decade and we began caring for infants at birth at 23 weeks so commonly that the thought of offering comfort care only to infants at 24 weeks became almost unthinkable for many health care providers. Before I get jumped on, let me say that I am not saying I agree or disagree with that sentiment but it is something that is felt by many.

The Shared Decision Model

In the last few years a rethink again has occurred whereby the concept of the treating team knowing best has been replaced by the “shared decision model”. In this line of thinking, it is not up to us as health care providers to “tell the parents” what to do but rather come to a shared decision based on an assessment of the wishes and values of the parents in conjunction with hearing about both short and long term problems their infants may face if resuscitated. This concept was central to the statement by the Canadian Pediatric Society that I am proud to have been part of with respect to its development. The statement for those that are interested is Counselling and management for anticipated extremely preterm birth

What’s next? Going below 22 weeks?

The challenge of the shared decision model is that there comes a point where the answer is simply “no”. If for example a family at 19 weeks gestation demanded an attempt at resuscitation I would have to inform them that survival is not possible (assuming ultrasound confirmed anthropometric measurements consistent with that age). The question though becomes a little more difficult to answer at 21 weeks and was the subject of a recent article in the New York Times about a survivor at 21 weeks gestation.

Even with the best gestational age dating the estimate can be off by up to 5 days so it’s possible that the infant in this story was closer to 22 weeks or even midpoint between 22 and 23 weeks in reality. Regardless it does raise the question about what to do at 21 weeks and I suspect we will begin to see more stories about this now that the glass ceiling of 22 weeks has been breached. What about below 21 weeks? Sounds impossible I know but with research that remains at the stage of animal studies this may become possible. Maybe not in the next 5-10 years but it could happen in my lifetime in this chosen field.

The Artificial Placenta

This made headlines a few years ago with the news that the Children’s Hospital of Philadelphia had successfully kept a lamb alive for a period of 4 weeks using an artificial placenta and amniotic fluid.

You might think that this was a one-off experiment that will never see the light of day but similar work is being done in Toronto, Canada where they have been able to do similar work with preterm piglets in their paper Achieving sustained extrauterine life: Challenges of an artificial placenta in fetal pigs as a model of the preterm human fetus. Incidentally as my colleague Dr. Ayman Sheta worked on this project while in Toronto I am particularly pleased to share this research. Similar to the experience in CHOP the team in Toronto has been able to keep piglets alive for progressively longer durations. My understanding is that despite the best efforts infectious complications over arise limiting how long one can sustain such animals.

This leads me to my final thoughts on where we might be able to go. I see a future where we apply such technology to humans but not in the way that people might have thought. Keeping a fetus after delivery at 21 or 20 weeks on an artificial placenta for many weeks is not likely a realistic goal. What if we could get 1 or 2 weeks though and allow the fetus to be oxygenated without using positive pressure on their developing lungs and transition them at 23 or 24 weeks gestation? We may in this way be able to allow for postnatal maturation in a artificial uterine environment and give babies a chance who would otherwise never had the opportunity for a shared decision with medical staff.

Sound like science fiction? Well the beauty of the internet as my friend told me today is that once it’s out there it out there for good. Let’s see how this post stands the test of time and to all the babies out there in NICUs and to their families I wish you all a good and uneventful World Prematurity Day wherever you may be!

Families in NICU deserve more than just a say

Families in NICU deserve more than just a say

The journey from conception to the labour floor and then for some to the NICU is not a straight one.  There are times of joy, interspersed with sadness, denial, anger and eventually acceptance, as initial news of being pregnant leads to complications in pregnancy and then eventual admission of an infant to the NICU.

Much has been said in recent years about the building of partnerships with parents and in fact there is a new catchphrase attached to the concept “shared decision making” (SDM).  There is no question that in the perfect world this is exactly the relationship that we should be striving for with all of our patients.  The world however is not perfect and although this may not be the most popular opinion I have given, I question how applicable this really is in many situations.

A Reality Check

Take for instance the parents who present to the labour floor of their local hospital in advanced labour at 24 weeks.  Proponents of this SDM model would suggest that a meeting take place and pertinent information be given to a family and together with the assistance of literature applicable to their situation (possibly a pamphlet) the health care providers and families come to a mutually agreeable decision as to what the best course of action is for them and their unborn infant.  This all sounds wonderful but examining the real life situation a little more closely is it actually reasonable to assume we can obtain this?  I have not been, nor will I ever be pregnant and certainly have never experienced contractions and felt the veil clouding my vision as the first dose of analgesia enters my veins to deal with the discomfort a woman experiences during labour.  Not to mention there are people admitting this couple, taking histories, establishing IV access, scanning bellies and a whole host of other pokes and prods along the way.

My Role Better Defined

Then I come in.  Among all this chaos I deliver the information, pass along a pamphlet and do the best job I can to inform said couple of the upcoming decision.  The trouble of course is how do we come to this mutual decision in the 15 – 30 minutes I spend with them during this crisis?  The answer sadly is we do our best but don’t for a minute think that SDM has occurred.  I don’t believe this is possible unless the family has prior experience with a preterm birth or perhaps is a HCP working with newborns or children with disabilities themselves.  In fact Boss RD et al in their own research on the subject identified that in hindsight religion, spirituality and hope are what motivated parents rather than what was said at the time.  In essence their minds are already made up.  It doesn’t mean we shouldn’t strive for the SDM but at least in my opinion, unless their contractions settle, a calmness ensues, they have time to digest the information being given and then meet again under less stressful circumstances, the SDM is a nice idea but for many not a reality.

Shifting To The NICU

I recall a significant moment in my training when I saw how the SDM model can actually cause more grief than help.  Dr. Keith Barrington a fellow blogger (if you haven’t discovered him, his work is fascinating over at Neonatal Research) published one of the most impactful pieces of research of the decade during my fellowship.  The adverse neuro-developmental effects of postnatal steroids in the preterm infant: a systematic review of RCTs. Following this analysis there was a near moratorium on the use of post natal steroids.  The issue this created was that to now receive them you had to be close to the end of the limits of care.  At this point you either died (thereby concluding they are of no help) or you survived with disability that was due in part no doubt to how sick you had become (thereby concluding they are dangerous).

The moment I am referring to was a conversation with a family in which the attending managing the unit presented the risks and benefits of postnatal steroids to the family when the FiO2 was at 40% one day.  The language used was non directive and the parents asked for another day to decide. The next day and each of the following two days they were unable to choose between giving the steroids and the perceived risk of brain damage versus not and watching the FiO2 climb by about 10% per day.  By the time the FiO2 several days later was at 80-90% they were distraught, teary and feeling helpless.  What they needed was direction; someone to give them some advice or more simply an educated opinion.

We can strive to share in the decision making but I continue to believe there is a time and place to help our families by taking a stance or side.  We can equip them with as much information as we want but is there really any replacement for actually taking care of these infants, experiencing the ups and downs and hearing how they have done in follow-up? We simply can’t expect the average parent to understand the true long term consequences of their decisions.  one-size-does-not-fit-allI am not saying we go back to a paternalistic time in medicine but I am saying that one size does not fit all.

We owe it to our families to pursue SDM when we can but we have an equal obligation to recognize when this ideal state is simply not possible.  At this point we have to use the experiences and knowledge we have to provide them with the best advice we can.  We have gone through medical training, and gone down these paths so many times.  We can avoid biased opinion and rely on the facts as they are in our institutions but to not take a stand when it is needed at least for me is doing a disservice to those we are so eager to help.

At 22-24 weeks does practice make perfect?

At 22-24 weeks does practice make perfect?

In the book Outliers by Malcolm Gladwell he talked about 10000 hours being the threshold at which if you practiced or gained that much experience with something you could become an expert. In Sweden the approach to 22 week pregnancies and above is to resuscitate all as a strategy. I wrote about this before in At 22 weeks of gestation does your faith matter most to outcome? The information gleaned from that paper was that if you have a policy of resuscitation at these gestational ages and you compare outcomes to a centre that is selective in who they resuscitate the outcomes are better when you believe all should be resuscitated.

New Study Expands Data

The same group has published this time around the results of the same cohort from 2006-2015 but this time with developmental outcome data. The paper is entitled Outcomes of a uniformly active approach to infants born at 22-24 weeks of gestation In this paper they discuss outcomes at 234 and 24 weeks respectively in addition to the findings for 22 weeks which they covered in the paper mentioned above. The reason for sharing this study is that if I asked you to imagine going into a room right now and talking to a family at 22 – 24 weeks and predicting the outcome of their infant, my hunch is that you would not provide as rosy a picture as the group in Uppsala, Sweden.

The authors looked at a group of infants with the following breakdown by gestational age.

As you can see, there were 222 infants in total and reasonable samples at each gestational age. What differs from other larger reports such as the work by Rysavy et al in Between-Hospital Variation in Treatment and Outcomes in Extremely Preterm Infants is that in this study ALL infants were resuscitated with intention.

Not surprisingly as gestational age declines the incidence of complications rise but looking at Table 3 even at 22 weeks there was no difference in rate of NEC or need for PDA surgery. Nor was there a difference in rates of severe IVH/PVL. Rates of BPD were higher and likely attributable to the longer durations of positive pressure ventilation. Are these rates for these complications terrible though when the other option is non-intervention which for certain means death?

What about outcome?

Looking at the outcome at 2.5 years, the rate of cerebral palsy is about 1:10 to 1:20 for all GA. Hearing impairment is almost non-existent and while developmental delay is detected in 50 percent of survivors at 22 weeks only about a quarter of the infants have severe impairment.

Deciding what to do

There is no question that many of you seeing what this post was about would simply say “NO WAY” but in the end isn’t it really about a shared decision with the family? It wasn’t that long ago that we had to have a real paradigm shift in thinking about resuscitating 23 week infants. The amount of mental energy spent for teams worldwide coming to this decision was tremendous and now if you were to suggest compassionate care at 24 weeks you get a look back like you are crazy! It wasn’t that long ago that 24 weeks was considered viability in many places and now that 23 is the new 24 this is the struggle some people have now. Should we go to 22 weeks everywhere as the Swedes have? Clearly this is a decision that institutions need to look at critically and determine if they have the space to accomodate. Each infant should they survive will occupy a bed for at least 6 months. This needs to be looked at before one can just say sure this is a good idea.

In the end what the study demonstrates I believe is that the outcome at 22 and 23 weeks for that matter need not be universally dismal. There certainly is a good chance that a surviving infant will have one or more deficits but in the end I would advocate this is a conversation all units need to be having and critically look at whether each institution has the capactity to consider.

My bet is that five years from now this discussion will be moot as we will be mostly in that direction but at this time I think we are still in evolution.

This Vitamin Could Save A Babies Life

This Vitamin Could Save A Babies Life

It has been a few months now that I have been serving as Chair of the Fetus and Newborn Committee for the Canadian Pediatric Society. Certain statements that we release resonate strongly with me and the one just released this week is certainly one of them. Guidelines for vitamin K prophylaxis in newborns is an important statement about a condition that thankfully so few people ever experience.  To read the statement on the CPS website click here.

Similar story to vaccinations

Prior to the American Academy of Pediatrics in 1961 proclaiming that all newborns should receive IM Vitamin K at birth the incidence of Vitamin K deficient bleeding was 0.25 – 1.7%. Think about that for a moment. A new parent could expect that 1/100 babies roughly might have intestinal bleeding or worse an intracranial hemorrhage due to an insufficient amount of vitamin K levels in the newborn. The types of bleeding could be categorized into three different time epochs. Early onset (occurring in the first 24 hours post-birth), classic (occurring at days 2 to 7) and late onset (at 2 to 12 weeks and up to 6 months of age).

With a rate that high detractors of providing Vitamin K at birth would say “why should we give it; I haven’t heard of any baby getting such bleeding?” Looking at it another way though, why don’t you see congenital rubella or kids with measles much these days? It’s due to vaccination. Thankfully as a Neonatologist, I don’t see Vitamin K deficient bleeding since most parents provide Vitamin K to their babies at birth.  If you went back to the era prior to 1961 when widespread supplementation of Vitamin K began in the US, I imagine it would not have been too uncommon to hear about a baby who had bleeding issues after birth.  Just because we don’t hear about German Measles much anymore doesn’t mean the virus causing it doesn’t still exist!

How Effective is Vitamin K?

How effective is Vitamin K administration at birth in preventing hemorrhagic disease of the newborn (HDNB)? Studies estimate an incidence of 0.25 per 100000 live births or 1 in 400000 babies vs the 1/100 risk without any vitamin K. That is one effective intervention! At this point I would ask those families that are still concerned about giving Vitamin K to their infants if this is a risk they can accept? If they refuse Vitamin K and there is a significant bleed how will they react?

The Change in this CPS Statement From the Past

In the last statement on Vitamin K, the authors suggested that the oral route was a reasonable option. Instead of giving 1 mg of Vitamin K IM one would dose it as 2 mg orally and then repeat at 2-4 weeks and then 6-8 weeks. In looking at the effectiveness though it is worth noting that while we can assure that families will get the first dose, as with any medication that needs repeat dosing there is the risk of forgetfulness leading to missed dosing down the road. In fact when the authors looked at the risk of late HDNB they found the following “The relative risk for VKDB, when comparing PO versus IM vitamin K administration in these two studies, was 28.75 (95% CI 1.64 to 503.45) and 5.97 (95% CI 0.54 to 65.82), respectively [19][20].”

The outcome of course remains rare but the risk based on two studies was almost 30 times higher than if IM dosing was given.

On this basis IM is recommended.

Having said all this I recognize that despite all this information, some families will choose for a number of reasons to still opt for the oral dose. As the statement suggests we need to encourage such use when a family refuses IM vitamin K. The 30 fold risk compared to IM administration is magnitudes lower than the approximate 1/100 risk of giving nothing at all!

In the end I believe that one case of intracranial hemorrhage from inadequate vitamin K is too much. This one vitamin indeed could save a life.

Is paralysis for intubation really needed?

Is paralysis for intubation really needed?

A few weeks back I wrote about the topic of intubations and whether premedication is really needed (Still performing awake intubations in newborns? Maybe this will change your mind.) I was clear in my belief that it is and offered reasons why. There is another group of practitioners though that generally agree that premedication is beneficial but have a different question. Many believe that analgesia or sedation is needed but question the need for paralysis. The usual argument is that if the intubation doesn’t go well and the patient can’t spontaneously ventilate could we be worse off if the patient loses their muscle tone.

Neonatal Intubation Registry

At the CPS meeting last month in Quebec City. I had the pleasure of listening to a talk by Dr. Elizabeth Foglia on the findings from a Neonatal intubation registry that many centres have been contributing to. The National Emergency Airway Registry for Neonates (NEAR4NEOs), records all intubations from a number of centres using an online database and allows for analysis of many different aspects of intubations in neonates.

This year, J. Krick et al published Premedication with paralysis improves intubation success and decreases adverse events in very low birth weight infants: a prospective cohort study. This study compared results from the registry of two centres, the University of Washington Medical Center (UWMC) and Seattle Children’s Hospital where the former rarely uses paralysis and the latter in almost all instances of non-emergent intubation. In all, 237 encounters were analyzed in the NICU for babies < 1500g with the majority of encounters (181) being from UWMC. The median PMA at intubation was 28 completed weeks (IQR: 27, 30), chronological age was 9 days (IQR: 2, 26) and weight was 953 g (IQR: 742,1200). The babies were compared based on the following groups. Premedication with a paralytic 21%, without a paralytic 46% and no premedication 31%.

This was an observational study that examined the rates of adverse events and subdivided into severe (cardiac arrest, esophageal intubation with delayed recognition, emesis with witnessed aspiration, hypotension requiring intervention (fluid and/or vasopressors), laryngospasm, malignant hyperthermia, pneumothorax/pneumomediastinum, or direct airway injury) vs non-severe (mainstem bronchial intuba- tion, esophageal intubation with immediate recognition, emesis without aspiration, hypertension requiring therapy, epistaxis, lip trauma, gum or oral trauma, dysrhythmia, and pain and/or agitation requiring additional medication and causing a delay in intubation.).

How did the groups compare?

It turns out paralysis seems to be a big deal (at least in this group of infants). Use of paralysis resulted in less attempts to intubate (median 1 attempt; IQR: 1, 2.25 vs. 2; IQR: 1, 3, p < 0.05)). In fact success was no different between the groups with no paralysis or no premedication at all! When it comes to  tracheal intubation adverse events the impact of using paralysis becomes more evident.   Paralysis does make a difference in reducing the incidence of such events and moreover when only looking at the rate of severe adverse events as defined above the finding was that none occurred when paralysis was used vs 9 when no paralysis was employed and 5 when no premedication was used at all.  The rate of bradycardic events was less in the paralytic group but rates of oxygen desaturation between the three arms were no different.

How do we interpret the results?

Based on the results from the registry it looks like paralysis is a good thing here when electively intubating infants.   If we try to determine the reason for it I suspect it may have much to do with the higher likelihood of success on the first attempt at placing an ETT. The longer it takes to place the ETT or the more number of attempts requiring intermittent PPV in a patient who truly needs a tube the greater the likelihood that you will see adverse events including bradycardia.  It may simply be that a calm and still patient is an easier intubation and getting the tube in faster yields a more stable patient.

I am biased though and I think it is worth pointing out another possible reason for the differing results.  One hospital in this study routinely used premedication and the other did not.  Almost 3/4 of the patients came from one hospital which raises the possibility that skill set could be playing a role.  If the skill of providers at the two hospitals differed, the results could reflect the variable skill in the practitioners versus the difference in the medications used themselves.  What I don’t know though is whether the two share the same training program or not.  Are the trainees the same at both sites (google maps says the two sites are 11 minutes away by car)?  The difference still might be in local respiratory therapists or Neonatologists intubating as well.  Regardless, the study provides evidence that paralysis makes a difference.  To convince those out there though who remain skeptical I think we are going to need the registry to take part in a prospective trial using many centres.  A format in which several centres that don’t use paralysis are compared to several who do routinely would help to sort out the concern in skill when looking only at two centres.  This wouldn’t be randomized of course but I think it would be very difficult at this point to get a centre that strongly believes in using paralysis to randomize so a prospective study using groups chosen by the individual centre might be the next best thing.  If anyone using the registry is reading this let me know what you think?

Still performing awake intubations in newborns? Maybe this will change your mind.

Still performing awake intubations in newborns? Maybe this will change your mind.

If I look back on my career there have been many things I have been passionate about but the one that sticks out as the most longstanding is premedicating newborns prior to non-emergent intubation.  The bolded words in the last sentence are meant to reinforce that in the setting of a newborn who is deteriorating rapidly it would be inappropriate to wait for medications to be drawn up if the infant is already experiencing severe oxygen desaturation and/or bradycardia.  The CPS Fetus and Newborn committee of which I am a member has a statement on the use of premedication which seems as relevant today as when it was first developed.  In this statement the suggested cocktail of atropine, fentanyl and succinylcholine is recommended and having used it in our centre I can confirm that it is effective.  In spite of this recommendation by our national organization there remain those who are skeptical of the need for this altogether and then there are others who continue to search for a better cocktail.  Since I am at the annual conference for the CPS in Quebec city I thought it would be appropriate to provide a few comments on this topic.

Three concerns with rapid sequence induction (RSI) for premedication before intubation

1. “I don’t need it.  I don’t have any trouble intubating a newborn” – This is perhaps the most common reason I hear naysayers raise.  There is no question that an 60-90 kg practitioner can overpower a < 5kg infant and in particular an ELBW infant weighing < 1 kg.  This misses the point though.  Premedicating has been shown to increase success on the first attempt and shorten times to intubation. Dempsey 2006, Roberts 2006, Carbajal 2007, Lemyre 2009

2.  “I usually get in on the first attempt and am very slick so risk of injury is less.” Not really true overall.  No doubt there are those individuals who are highly successful but overall the risk of adverse events is reduced with premedication. (Marshall 1984, Lemyre 2009). I would also proudly add another Canadian study from Edmonton by Dr. Byrne and Dr. Barrington who performed 249 consecutive intubations with predication and noted minimal side effects but high success rates at first pass.

3. “Intubation is not a painful procedure”.  This one is somewhat tough to obtain a true answer for as the neonate of course cannot speak to this.  There is evidence available again from Canadian colleagues in 1984 and 1989 that would suggest that infants at the very least experience discomfort or show physiologic signs of stress when intubated using an “awake” approach.  In 1984 Kelly and Finer in Edmonton published Nasotracheal intubation in the neonate: physiologic responses and effects of atropine and pancuronium. This randomized study of atropine with or without pancuronium vs control demonstrated intracranial hypertension only in those infants in the control arm with premedication ameliorating this finding.  Similarly, in 1989 Barrington, Finer and the late Phil Etches also in Edmonton published Succinylcholine and atropine for premedication of the newborn infant before nasotracheal intubation: a randomized, controlled trial. This small study of 20 infants demonstrated the same finding of elimination of intracranial hypertension with premedication.  At the very least I would suggest that having a laryngoscope blade put in your oral cavity while awake must be uncomfortable.  If you still doubt that statement ask yourself whether you would want sedation if you needed to be intubated?  Still feel the same way about babies not needing any?

4.  What if I sedate and paralyze and there is a critical airway?  Well this one may be something to consider.  If one knows there is a large mass such as a cystic hygroma it may be best to leave the sedation or at least the paralysis out.  The concern though that there might be an internal mass or obstruction that we just don’t know about seems a little unfounded as a justification for avoiding medications though.

Do we have the right cocktail?

The short answer is “I don’t know”.  What I do know is that the use of atropine, an opioid and a muscle relaxant seems to provide good conditions for intubating newborns.  We are in the era of refinement though and as a recent paper suggests, there could be alternatives to consider;Effect of Atropine With Propofol vs Atropine With Atracurium and Sufentanil on Oxygen Desaturation in Neonates Requiring Nonemergency IntubationA Randomized Clinical Trial.  I personally like the idea of a two drug combination for intubating vs.. three as it leaves one less drug to worry about a medication error with.  There are many papers out there looking at different drug combinations.  This one though didn’t find a difference between the two combinations in terms of prolonged desaturations between the two groups which was the primary outcome. Interestingly though the process of intubating was longer with atropine and propofol.  Given some peoples reluctance to use RSI at all, any drug combination which adds time to the the procedure is unlikely to go over well.  Stay tuned though as I am sure there will be many other combinations over the next few years to try out!