Sniffing out lung injury

Apparently exhaled breath analysis can be used to detect a number of pulmonary and systemic diseases. As a medical student I was taught  about some of the classical clinical signs of certain diseases (such as diabetic ketoacidosis) which make the patient’s breath have a characteristic smell. I never thought I was very good at detecting those smells. So if you could use a machine to smell things for you, and be objective about their analysis, maybe that would be a good idea? You could detect volatile organic compounds from the patient’s breath and make non-invasive diagnoses.

There are now several electronic noses available which can reportedly provide a ‘breath print’ of exhaled compounds. Their usefulness in clinical practice is still being debated, but this new study (Rogosch T, Herrmann N, Maier RF, Domann E, Hattesohl A, Koczulla AR, et al. Detection of Bloodstream Infections and Prediction of Bronchopulmonary Dysplasia in Preterm Neonates with an Electronic Nose. The Journal of pediatrics. 2014) is probably the first in newborn infants. Because of the difficulty of obtaining breath samples the authors took endotracheal secretions from intubated preterm babies, and then held the ‘snout’ of the ‘e-nose’ over the secretions to get a breath print.

I will have to get quite sniffy about this article however; the authors report the results of 38 samples from 28 babies of whom 8 had a blood stream infection. They never report the timing of the infection, or how it related to the timing of the sampling, so we get no idea of whether the aspirates were taken from babies already being treated for infection, or during a sepsis evaluation, or even afterwards, or days before. The authors show different breath prints from babies with infection and those without. They also analyze the first aspirate from the same babies, at least the 23 of them who were under 32 weeks gestation, and show some differences in breath prints from babies who went on to develop BPD and those who did not. They don’t say which of these babies had infections and which did not.

An interesting idea, but the way the data are presented makes it impossible to tell whether this might be clinically useful, or not.

 

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Non-invasive HiFi? Much more info needed.

This is an interesting idea, I believe that initially it was thought that bubble CPAP might deliver some high frequency pressure oscillations to the lungs, as the bubbling in the circuit causes some small amplitude variations in the pressure in the circuit.  I think that has probably been debunked, there is likely no significant CO2 removal as a result of these small oscillations in pressure.

On the other hand if you hitch up your CPAP prongs to a real high frequency ventilator then you might be able to deliver some non-invasive high-frequency ventilation, at least while the airways are open.

This group of researchers (Mukerji A, Singh B, Helou SE, Fusch C, Dunn M, Belik J, et al. Use of Noninvasive High-Frequency Ventilation in the Neonatal Intensive Care Unit: A Retrospective Review. American journal of perinatology. 2014) report a retrospective group of babies who were treated with this kind of intervention. During high frequency non-invasive ventilation there was  a reduction in apneas, in oxygen requirements and in CO2. Of course the question is what would happen to a similar group  of babies treated with standard non-invasive techniques.

The only way to know is by doing an RCT, which I hope is being done.

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Probiotics work in Germany also

A new study from the German Neonatal Network Database compares the incidence of NEC between centers that used probiotics, centers that did not use probiotics, and centers that changed their practice part way through the data collection period from being non-users to users. They all seem to have chosen the same probiotic combination (Infloran), and they only report the cases of surgical NEC (and separately surgery for other neonatal acute intestinal complications), the data base includes babies under 1500 grams who are between 23 and 32 weeks gestation.

I think its safe to assume that the diagnostic variability in stage 3, surgical, NEC is less than in stage 2 disease, although it probably isn’t perfect, and the precise indications for surgery may differ from one center to the next, also it isn’t clear if an infant who perforated, but was not considered a candidate for surgery, would be included as a case or not (but that would likely be a very small proportion).

The authors of the paper (Hartel C, Pagel J, Rupp J, Bendiks M, Guthmann F, Rieger-Fackeldey E, et al. Prophylactic Use of Lactobacillus acidophilus/Bifidobacterium infantis Probiotics and Outcome in Very Low Birth Weight Infants. The Journal of pediatrics. 2014) found that centers using probiotics had a percentage of surgical NEC in their babies of 2.6% compared to 4.2% in those with no probiotics. Centers that changed during the course of the study showed a reduction after the introduction of probiotics from 6.2 to 4.0%.

In the logistic regression analysis, the use of probiotics gave an Odds Ratio for surgical NEC of 0.58, and for death or surgical NEC of 0.43.

Not surprisingly, probiotics reduce the incidence of NEC in Germany, just as they do elsewhere. Infloran seems to be an effective mixture, even though its formulation has changed slightly it was one of the mixtures used in randomized controlled trials, it is widely available in many countries.

Rather than another polemic about the moral necessity to routinely use probiotics in at-risk preterm infants, I will simply refer you to my several previous posts, which you can find using the search function if you wish,

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The voice of parents

Kudos to Acta Paediatrica, for an article by a group of parents who were all faced with antenatal counseling in a situation of high risk for extremely preterm delivery. (Staub K, Baardsnes J, Hébert N, Hébert M, Newell S, Pearce R. Our child is not just a gestational age. A first-hand account of what parents want and need to know before premature birth. Acta Paediatrica. 2014)

The families (who I believe were all treated in Canadian perinatal centers : UPDATE: one of the families was actually seen in an Australian center) recount their experiences, the first is very distressing, an infant about to be born at 23 weeks gestation, with an estimated weight which is in the expected range for 23 weeks, who was not even given an option of attempted stabilization. Rather than giving Marcus a 20% chance of survival (a chance which is even higher than that in some parts of the world with a more positive attitude), he was given a 100% chance of dying. I would say that if fully informed parents shared in a decision that this decision was consistent with their values, and that they wished for comfort care only at birth, then it should be considered reasonable to provide that approach, but the family writing in this article was not given that as an option, they were given a ‘fait accompli’ : they were just told : we don’t do that here.

One of the babies, Domenica, should be dead according to the CPS guidelines; she was born some days before she reached 23 weeks gestation, and, according to our Professional Society, stabilization should not be offered. As you will see from the article she is doing really well.

The list of recommendations from the parents at the end of the article should be required reading for neonatologists everywhere. They should not be hugely surprising to ‘us’. but unfortunately as some of these stories show, they will surprise some health care professionals. I will reproduce them below for those who do not have full text access to the article, but if you are a health care provider and have access, please read the vignettes and the discussion that go before.

Recommendations for healthcare providers

1. Tell women that there is nothing they could have done to prevent the premature birth from happening.
2. Our unborn children have a story and are part of our hopes and dreams. Do not use gestational age to categorise our child. Ask us if our unborn baby has a name.
3. Each baby is different. Have a personalised approach. You can tell us what generally happens to children about to be born at the same stage of gestation as our child, but please also describe to us the particularities of our child that will influence his or her outcome.
4. Each family is different. We disagree that every family needs to receive extensive information about everything negative that may happen. Some parents want statistics, others want the general picture. Some parents want to make important decisions on their own, while others want recommendations. Please listen to us individually.
5. We need to trust you. Do not tell us that babies at 22 or 23 weeks do not survive. Do not tell us that most preterm infants are disabled. We rely on you to know your data. Reflect on the difference between medical numbers and medical values. Do not tell parents that their child will have a negative impact on their family. You do not have data to support these claims. Many clinicians decide that giving babies a chance is not worth it for a 10%-20% survival rate. Our discussions should be about values and not so much about percentages.
6. Give us balanced information. Tell us about what our children may, or may not, be able to do. Also tell us about the quality of life of other preterm infants have when they get older
7. Words are important. Before our child’s birth, do not ask us if we want to do “everything” or “nothing”. Have you ever met parents who wanted “nothing” for their child? Do not use the word resuscitation, as premature infants are not usually defibrillated. That is what we think resuscitation means when you use that language. Use the word stabilisation instead.
8. Do not take away the hope we have. There is always hope that we will deliver tomorrow. There is hope that we will be able to spend some time with our child. There is hope that we can survive the death of our child with positive memories. Do not abandon us. Instead, tell us that you will be there whatever happens.
9. Empower parents. When other family members are present, emphasise that strong families are important.
10. Be proud of the work you do. It is so important to us. You make it possible for us to share precious time with our babies. You are the heroes for so many families. You help babies survive and we are thankful for that.

One thing I want to re-iterate is the need to give balanced information. Most position statements and decision aids for extreme preterm delivery are designed to ensure that families know all of the bad things that can happen to extremely preterm infants.

It is analogous to a decision aid for prostate cancer therapy only listing death, infection, incontinence and impotence as potential outcomes of a prostatectomy, without mentioning that it might also save your life! How could anyone make a balanced, informed, decision if they only hear of the downside?

Surely our pride in our work (and I am proud of what I do, thank you Mme Staub et al) should lead us to acknowledge that most extreme preterm survivors so well, that, among survivors, disabilities are variable and often quite manageable, and that quality of life is acceptable to excellent for the large majority of those who survive, both those with and those without disability.

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A philosopher and a theologian debate neonatology; confusion results

I came across this article from a philosopher who apparently does bioethics, the title is, ‘what should we do about severely impaired newborns?’ The article is a report (by the philosopher) of a debate at the American Association of Thoracic Surgery.

The problem, simply put, is this: Every year a small number of fetuses are carried to term who have no reasonable chance of living a life worth living. They are so severely impaired that they will live a miserable, short life until they eventually expire. The good news is that, courtesy of prenatal screening, only few such births take place and the numbers are decreasing. We have some data from the Netherlands, where a few hundred out of about 200,000 newborns annually tend to fall into this category.

We can immediately here see the problem. He is ignorant. He has no idea what he is talking about: what antenatal diagnosis gives a fetus ‘no reasonable chance of a life worth living’? One could perhaps include anencephaly, and complete hydranencephaly where there is no ability to perceive the world at a conscious level, but apart from those 2 rare diagnoses, I am not sure there is anything else that would fit that definition, in my opinion. There are many diagnoses that are life-limiting, many that lead to serious impairment, but to automatically assume that a short life with impairments is not worth living is to ignore the experience of families who have been there. Furthermore a life with impairments is not necessarily miserable, at all. In Saroj Saigal’s study, if I remember right, the only person who rated their quality  of life as being below zero, i.e. worse than being dead, was one of the non-impaired full term controls (probably someone suffering from depression).

The ‘good news’ as he puts it, also has nothing to do with predictions of being miserable. The majority of terminations for fetal anomaly are of fetuses who could easily survive and have long happy lives, such as trisomy 21, or surgically treatable lesions. Termination for an ‘impairment’ that is severely life limiting and predicts a miserable life, if we could even do that, is rare. In addition the title of the debate was ‘Can a Physician Ever Justifiably Euthanize a Severely Disabled Newborn’. Confusing impairments and disability is something a philosopher should certainly not do, I thought the meaning and implications of words were quite important to them.

In addition, where on earth does he get the figure ‘a few hundred’ from? It seems he made it up. In a recent publication covering 5 years in the Netherlands there were 2 cases of neonatal euthanasia, both of them for epidermolysis bullosa letalis, which is certainly not what most people would consider an impairment (even though it is a very serious and unpleasant disease, where the skin forms blisters at the slightest contact, and then separates, leading to pain and infections, and eventually, as the name implies, death).

Well, the topic of our debate was a dicey one. We were given a scenario whereby the child’s prospect were sufficiently miserable that the attending doctors suggested to parents – among other options – the withdrawal of nutrition and hydration while providing palliative care to ensure the newborn does not suffer unnecessarily, as well as active euthanasia. The outcome of both scenarios: the death of the child. The jurisdiction where our case played out permitted the active ending of the newborn’s life.

There are only 2 scenarios where withdrawal of fluids and nutrition are considered in neonatology, one is in severely brain injured (almost always full-term) newborns, who are so profoundly injured that they show no signs that they experience hunger or thirst, or alternatively, cases of lethal intestinal failure, where there is no way to provide fluids and nutrition by the GI tract. Both of these are ethically challenging; in the first group the infants tend to have a brain which is so severely damaged that they don’t appear to be conscious, make no eye contact and don’t usually show signs of ‘suffering’, although certainly everyone around them is suffering. These are infants for who, the only prospect is a life without human interaction and supported by medically administered nutrition, i.e. tube-feeding. There may be a debate to be had for such children, what kinds of interventions around the end of life are appropriate? But that certainly is not the kind of infant that is implied in the title of the debate, nor in the other comments he makes in this article

…… Would it make much sense to undertake significant surgery with the – unlikely but possible – result that the newborn might live a miserable life for another year or two before his impairment eventually catches up with him and kills him?

This is incomprehensible drivel, I don’t know how Udo Schuklenk (the philosopher’s name) thinks we can predict misery, although there are certainly some situations where children experience pain, these usually have nothing to do with impairment, and pain can almost always be controlled. What kind of impairment catches up with children and kills them? I know he is trying ot use colorful, metaphorical language, but it conjours up images of cerebral palsy chasing after children trying to suffocate them!

…On the one hand we have – typically – religiously motivated opponents of euthanasia for severely impaired newborns.

I am certainly not religiously motivated, far from it, and the fact that I value the lives of all babies, regardless of impairment, is based on our common humanity, on the belief that being smart doesn’t make you more worthwhile as a person than someone who is less smart, that the value of a life is not correlated with the number or severity of impairments

The distinguished theologian panel member who I debated argued that we should let nature takes its course, that we should provide clinical care not aimed at shortening the newborn’s life and that we should eventually let nature takes its course. The problem with the nature-takings-its-course argument is that we invented medicine to stop or delay nature from taking its brutal course. So, the letting nature take its course argument was a non-starter.

I agree that this argument is a non-starter, if we let nature take its course, then the average life expectancy would still be about 25 years!

….If we merely go by the newborn’s quality of life and life prospects it seems indeed best to end the unfolding tragedy sooner rather than later, but probably a decision should be arrived at with parental consent as opposed to against the unfortunate parents. It turns out that one can reasonably answer the rhetorical question of whether one would want to live in a society that terminated the lives of certain severely impaired newborns if one held the view – as I do – that the newborn’s current and future quality of life is all that matters here. I could live in such a society where empathy for human suffering trumps religious conviction.

And so could I, but you need to have some understanding of what you are dealing with, some experience of dealing with families who are going through these terrible ordeals, and some basic medical understanding of the conditions that they face. Knowledge of the quality of life as experienced by families, and whether children with impairments are often ‘suffering’ or not would be a good start. The idea that we can predict misery is profoundly misled. The lives of children with impairments may sometimes be considered to be an ‘unfolding tragedy’ but that is more commonly the case when you ask the opinions of caregivers, rather than parents or families. Finding ways to support and assist these families, to provide respite care and counseling, to improve rather than shorten their lives; those are goals that I think we should be aiming for as a society.

I won’t say much more about the debate, but I think it is very strange that a society of thoracic surgeons would ask a theologian and a philosopher to debate things that neonatologists actually have to deal with. I actually think that people with those backgrounds might sometimes have important things to add to such a debate, but first of all we need to educate them, and make sure they have some basic understanding of the issues. A medically trained participant in that debate could have, primarily, clarified the question and made the case description appropriate to the question, then could have explained the real dilemmas that are faced, and could have described the medical options that most philosophers and theologians have no training to consider.

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Doing research using Youtube

When my kids went to have their immunizations we took some sucrose solution with us to the hospital (don’t ask me how we came to have sucrose solution, its a secret) and were ready to either have the immunizations done during a breast feed, or if that didn’t work due to timing then to give the sucrose.

These simple analgesic interventions have been tested in older infants having their immunizations, and they work, they are cheap and they are simple.

The staff in the clinic looked at us as if we were either severely over-protective nuts, or perhaps just nuts. Maybe that’s a form of self-protection, if you have given hundreds of immunizations to young infants and have never used any sort of analgesic intervention, its better to believe that it doesn’t hurt that much, pain is not such a big deal, and it is too much fuss to worry about getting something sweet in the babies mouth.

In this newly published study from the children’s hospital of Eastern Ontario in Ottawa (CHEO) the authors looked at all the youtube videos they could find which showed an infant being immunized. They found 142. I think that’s a bit weird, why would you do that? Not the research, I mean, why would you take a video of your kids having a jab and then crying? Hopefully there was a least one parent cuddling and comforting the baby.

None of the infants got sweet solutions, and none were breast fed during the jab, few of them were held front to front by a parent. Its perhaps not too surprising, but a bit depressing, that our experience is the usual experience of families getting their vaccines.

The methodology probably also needs some development, what are appropriate search terms for a scientific review of youtube? What do we call the biases involved in whether you are open to having public videos of intimate medical moments displayed (TMI bias? over-sharing bias?) Should journals require searching other video sites? I think there are many other research studies we could do once the methodology is sorted. Episiotomy techniques, are the standardised? Neonatal resuscitation adequacy when being video-ed, I wonder which ethics committee I should apply to, do Google have one?

 

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Position statements and overtreatment

A few years ago when I was chair of the Canadian Paediatric Society Fetus and Newborn Committee, we produced a statement about what to do with full term babies with risk factors for sepsis. Our recommendation was, to put it simply, for risk factors screen and observe, for clinical signs culture and treat. One risk factor that we had a lot of debate about was chorioamnionitis. The overall frequency of early onset sepsis is high after confirmed chorioamnionitis (as high as 8% in some studies), but placental pathology or cultures to get a confirmed diagnosis take too long to make a treatment decision. There are also data that infants who appear well at birth, despite definite, chorioamnionitis are at much lower risk, so we recommended screening and close observation, as long as the baby remained well.

Clinical diagnosis of chorioamnionitis is very unreliable, fever during labour may be due to multiple other causes, and when the obstetrician suspects chorioaminonitis many patients don’t have pathologically confirmed disease (only a third of them are histologically positive if the main sign is fever).

Shortly thereafter the CDC published some standards which counseled that all babies with a history of ‘Chorioamnionitis’ get cultures and antibiotics.

I think that is not unreasonable if you look at the scary 8% figure: if you can treat empirically a group of patients with an 8% chance of having a positive blood culture then that would be a good thing. In practice however, with the poor ability to clinically diagnose chorioamnionitis and the low incidence of disease in babies who look well at birth, there is a good chance that to follow such advice will end up treating hundreds of babies for every positive culture.

The most recent version of the AAP position statement, or clinical report or whatever they call them, recommends antibiotic therapy for all babies born after chorioamnionitis, and even if the cultures are negative to continue antibiotics for 7 days if the screening lab tests (a CBC and differential adn a CRP) are abnormal.

What actually happens if you do that?   Kiser C, Nawab U, McKenna K, Aghai ZH: Role of Guidelines on Length of Therapy in Chorioamnionitis and Neonatal Sepsis. Pediatrics 2014. This study shows that following the AAP strategy leads to large numbers of healthy-appearing babies with negative cultures receiving prolonged antibiotic therapy. Of 554 term and late preterm babies exposed to chorioamnionitis, 134 of them had 7 days of antibiotics, in 112 of those cases it was solely because the lab tests were abnormal.

This story highlights the difficulty of writing guidelines, you may have unintended consequences, even with the best of intentions. Interestingly the Swiss neonatal association guidelines are very similar to the CPS, with treatment only for those who develop clinical signs.

As a result of concerns about over-long treatment in healthy babies, the AAP have now revised their guideline, although they still recommend starting the antibiotics, even in healthy appearing infants, they no longer recommend prolonging therapy beyond 48 to 72 hours if the infant remains well. A step in the right direction.

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