Weekly Updates #5

Posted on 8 September 2012 by Keith Barrington

Ing C, DiMaggio C, Whitehouse A, Hegarty MK, Brady J, von Ungern-Sternberg BS, Davidson A, Wood AJJ, Li G, Sun LS: Long-term Differences in Language and Cognitive Function After Childhood Exposure to Anesthesia. Pediatrics 2012. Further data, again from Australia about the potential long term effects of anesthesia (or surgery or both), this time examining specific intellectual domains and showing associations of reduced language and abstract reasoning with having had anesthesia before the age of 3.

Morley CJ, Keszler M: Ventilators do not breathe. Archives of Disease in Childhood – Fetal and Neonatal Edition 2012. A well reasoned plea from Colin Morley and Marty Keszler to use different terminology when talking about assisted ventilation. Babies inspire, ventilators inflate, etc. I agree!

Thomson T, Habeeb O, DeChristopher PJ, Glynn L, Yong S, Muraskas J: Decreased survival in necrotizing enterocolitis is significantly associated with neonatal and maternal blood group: the AB isoagglutinin hypothesis. J Perinatol 2012, 32(8):626-630. I was a bit surprised by this, but, if confirmed, it shows that mortality is different depending on infants blood group, specifically, worse if the infant is AB. The authors suggest that this may be due to increased concentrations of isoagglutinins in these babies.

Legrand C, Michaud L, Salleron J, Neut D, Sfeir R, Thumerelle C, Bonnevalle M, Turck D, Gottrand F: Long-term outcome of children with oesophageal atresia type III. Archives of Disease in Childhood 2012, 97(9):808-811. The long term complications of children who had a repair of the commonest type of oesphageal atresia are much more frequent than I realized. With reflux, dysphagia, and respiratory symptoms being very common.

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CPAP or PAF?

Posted on 7 September 2012 by Keith Barrington

Several devices marketed as CPAP devices are not in fact devices designed to deliver constant pressure. For example the Infant Flow device, widely used in NICUs, delivers a constant flow into its circuit, but there is no mechanism to respond to changes in resistance, and the pressure in the circuit is therefore very variable depending on down-stream resistance, and should therefore I think be called a positive airway flow device. It is often referred to as variable flow CPAP, as the flow into the baby varies depending on the phase of respiration of the infant, so this can get very confusing. However, as I said, the pressure is not constant, so CPAP is not the right terminology; and the flow into the circuit is actually constant, it is supposedly the flow into the baby that varies, based on the so-called ‘fluidic flip’.

Now the flow across the prongs changes according to this ‘fluidic flip’ principle, which is supposed to reduce expiratory work of breathing; but as others have pointed out, in normal use the baby does not breathe out through the prongs, most of the expiratory gas leaves the airway through the mouth, or around the prongs, wherever the resistance is lowest. So although under very specific experimental conditions there may be a reduction in respiratory work, I am unsure if this translates into any real advantage in clinical use. If the infants changes head or mouth position, or the prongs are slightly displaced, anything which changes the resistance, the delivered pressure may change dramatically, very often falling well below the desired pressure. I find this most problematic during non-invasive intermittent positive pressure ventilation, we might set up the device to give a peak pressure of 10 and an expiratory pressure of 5, but when I go round to review the baby a few minutes later the pressures being delivered may be 5 over 4, or even less.

In contrast using a ventilator to deliver CPAP uses a very expensive machine to deliver a constant pressure, the pressures can be maintained over a much wider range of infant conditions. A simple constant pressure circuit which is very much cheaper, and probably as good as ventilator derived CPAP, is the so-called bubble CPAP which delivers a constant pressure as a result of the height of the water column, and may deliver some pressure oscillations as a result of the bubbling, more of which below.

Does the difference between CPAP and PAF matter? A new multicenter RCT from Poland randomized 276 babies between 750 and 1500 g birth weight to either the Infant Flow, or CPAP using a Draeger Babylog within the first 6 hours of life. The primary outcome was never needing to be intubated, and there were no substantial differences in outcomes between the groups. (Bober K, Swietlinski J, Zejda J, Kornacka K, Pawlik D, Behrendt J, et al. A multicenter randomized controlled trial comparing effectiveness of two nasal continuous positive airway pressure devices in very-low-birth-weight infants. Pediatr Crit Care Med. 2012;13(2):191-6. Epub 2011/06/15.)

Another RCT from 3 years ago compared the Infant flow device to bubble CPAP. (Gupta S, Sinha SK, Tin W, Donn SM. A Randomized Controlled Trial of Post-extubation Bubble Continuous Positive Airway Pressure Versus Infant Flow Driver Continuous Positive Airway Pressure in Preterm Infants with Respiratory Distress Syndrome. The Journal of Pediatrics. 2009;154(5):645-50.e2.) Samir Gupta and colleagues from the NICU in Middlesborough randomized 140 babies of 24 to 29 weeks gestation when they were extubated. The primary outcome of extubation failure was not different between the groups, however, the failure rate was lower than expected, so the study was underpowered, the non-significant differences in outcomes favored the bubble CPAP group, and subgroup analyses also showed some benefits for bubble CPAP.

A recent review by Thomas Shaffer and his colleagues reviews many of the physiologic effects of non-invasive respiratory support.  (Shaffer TH, Alapati D, Greenspan JS, Wolfson MR: Neonatal non-invasive respiratory support: Physiological implications. Pediatric Pulmonology 2012 http://onlinelibrary.wiley.com/doi/10.1002/ppul.22610/abstract) this very complete and clearly written review covers all forms of non-invasive support, including oxygen, CPAP, nIMV and high flow cannulae. They point out that the pressure oscillations which occur during the bubbling of bubble CPAP are far less than those which are produced by a high frequency ventilator, and that under usual circumstances it seems unlikely that there is measurable ventilation from the oscillations caused by the bubbles.

So overall, I think that a true constant pressure system is probably preferable, and that bubble CPAP is as good, and may be preferable, to a ventilator, and is very much cheaper. The main limitation being that bubble CPAP can’t do non-invasive ventilation.

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Not neonatology: Hermit Crab Migration

Posted on 5 September 2012 by Keith Barrington

I saw this link on one of my favorite websites (the owner doesn’t want it called a blog!) which is Why Evolution is True.

The annual hermit crab migration in St John in the U.S. Virgin Islands. St John is an island without an airport, which protects it from too many visitors, and allows natural phenomena like this to continue. the photographer is Steve Simonsen and you can see the original web submission at the link above.

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Predicting Long Term Outcomes: MRI at term for very preterm babies

Posted on 4 September 2012 by Keith Barrington

The most recent Acta Paediatrica includes 2 articles. One from parents of a very preterm infant that we looked after at Sainte Justine. They recount their experiences of having a baby at 25 weeks, and what happened to them when they had a brain MRI when their daughter reached term.

This story is accompanied by an article by Annie and me, discussing how that situation affected us, and what the evidence is regarding whether or not the information that we gain from a term MRI actually helps parents or not. If you read the article you will see photos of neonatology’s very attractive power couple (Annie and me), and also our skepticism about routine MRI just before discharge of very preterm babies. An investigation that is now being used as a screening test in many centers, but which does not fit any criteria for a screening test, as there are many false positives and many false negatives (if long term impairment is the problem that we are screening for) and nothing treatable (or very rarely anything treatable) to be discovered.

I have been reviewing the articles regarding this issue for a while, and the best large cohort studies have very low positive predictive value for developmental delay (almost always less than 50%) and very low positive predictive value for movement disorders. In contrast the negative predictive value for cerebral palsy is high, but as most cerebral palsy among preterm infants is relatively mild, and does not lead to serious disability, I am not sure how useful it is to do a test which reduces the probability of having that diagnosis. Especially when the PPV for other abnormalities is so low. There is also no standardized way of doing the test (with many sequences available) and no standardized way of interpreting them.

One thing that many want to screen for is cerebellar injury as it is said to have a much higher PPV for long term problems, indeed that is what Maren Baardsnes had. But as you can see from the article, and appreciate from the great photo of Maren, that hasn’t actually happened. She is great. (In fact another article from earlier this year Hou D, Shetty U, Phillips M, Gray PH: Cerebellar haemorrhage in the extremely preterm infant. J Paediatr Child Health 2012, 48(4):350-355. showed that infants with cerebellar hemorrhage may actually do quite well, even though it was very rare in their cohort, and therefore few affected babies to evaluate).

We would be much better off using the resources currently used for doing the MRI to provide services to the families, including early intervention programs for families who have limited means.

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‘Do everything’

Posted on 3 September 2012 by Keith Barrington

A wonderful article just published by Chris Feudtner, who dissects a phrase that we hear all too often. ‘I want you to do everything’. He examines what families mean when they say this, and how we might respond as medical professionals. As he explains we can’t ‘do everything’ as everything includes therapies that may be themselves in conflict, or harmful or ineffective. Families will often mean that they aren’t ready to give up, they don’t want to withdraw or limit active care, and if there remains a flicker of hope for survival they want us to follow it. He particularly states that we should refrain ourselves from using the term as it is ‘dangerous nonsense. If we really don’t mean it, then we really must not say it. A moratorium is warranted, halting all medical personnel from further casual utterances of “do everything” ‘.

Chris writes very well; clear, thoughtful and stimulating. I would also recommend his article from 3 years ago in the New England Journal, ‘the Breadth of Hopes‘, which addresses some of the same issues, of examining what families hope for, and finding common, realistic hopes that we can share.

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Neonatal Heart Surgery and Surgical volumes

Posted on 3 September 2012 by Keith Barrington

I wanted to write about this issue for a while, but it is a very complex problem. There are many studies which show varying outcomes of pediatric, and in particular neonatal, heart surgery. By which I mean that some programs have fewer survivors than others. This discrepancy has been most closely examined in the UK, where the centrally controlled nature of the health service, and what is widely known as the ‘Bristol heart scandal’, led to a revolution in transparency. Survival figures for various pediatric heart surgeries are now publicly available. (you can see them easily, follow this link for overall survival figures for each condition then click on the name of the individual procedure or condition for a comparison between hospitals). Unfortunately these data are not risk adjusted, but they do show how far transparency has progressed, from the days when everything was secret, and no-one new anyone else’s success rates, (unless they published them in a journal, which was usually when the results were considered extra good!)

I want to mention one amazing publication from several years ago, from a very well respected children’s heart surgeon, Marc de Leval from GOSH in London (that’s Great Ormond Street Hospital as anyone who watched the olympic opening ceremony will know).  He published his own series of arterial switch procedures for transposition of the great vessels, noting that he started doing the procedure with good success, then had a series of deaths, so, instead of doing what many have done in the past (either ignoring the situation, blaming sicker than usual patients, or blaming the intensive care staff of anyone else that they can think of) analyzed the data very carefully (using a statistical technique that I later used for a publication), realized there was a real problem, stopped doing the surgery, went away and got retrained and closely examined every aspect of peri-operative care, and then started operating again with better results. He also then published his series of surgical failures, which may well have been a first! Most importantly he described how he had reacted to situation and demonstrated how a competent, compassionate, and thoughtful physician should respond when things aren’t going how they should. (He subsequently published another important paper examining how ‘human factors’ affect survival rates for the same procedure.)

I think Dr de Leval’s example and influence made a big difference in how subsequent events in the UK have played out.

One thing that became clear was that bigger programs had lower mortality than smaller programs, and that risk adjustment did not change this. A systematic review was carried out (entitled The Relation Between Volume and Outcome in Paediatric Cardiac Surgery. A Literature Review for the National Specialised Commissioning Group) which has confirmed that this is a reproducible effect.

As a result, many pediatric heart surgery programs in England have been closed, and the patients are cared for in one of a very small number of hospitals, and the latest round of re-organization will reduce this to only 7 centers for England and Wales.

Now a recent publication notes that center volume is not the only issue in the variation in survival between centers (using the Norwood procedure as an example: Pasquali SK, Jacobs JP, He X, Hornik CP, Jaquiss RD, Jacobs ML, O’Brien SM, Peterson ED, Li JS: The complex relationship between center volume and outcome in patients undergoing the norwood operation. Ann Thorac Surg 2012, 93(5):1556-1562.) which is sort of self-evident, but this new publication does show that there is still a statistically significant relationship between center volume and survival.

What should this mean for a health care system? The overall recommendations for pediatric heart surgery in England and Wales are presented in a very pretty pdf document. These evidence based recommendations are: that a surgeon should have at least 125 cases a year, that each center should have at least 4 surgeons , and that this means only 7 centers, for a population of about 50 million. If we translate this to Quebec, where we have multiple small programs at present, there should be 1 pediatric heart surgery center. That is what a previous health minister (Couillard) tried to do some years ago, but the vested interests in the different universities all colluded to prevent it happening. We do not know what the survival rates are in the various centers in Quebec, I do not even know what they are in my own hospital, but unless we are different to everywhere else in the world it could only help the babies to amalgamate the programs and put them in one center. Personally I don’t care where that would be, we need to do it for the babies with heart disease.

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Not neonatology- Nature Photography

Posted on 29 August 2012 by Keith Barrington

I have only once before posted a non-neonatology post on this blog. But occasionally if there is something I find especially striking I will provide a simple link. Here is a link to the BBC nature website, which by itself is an amazing resource, this is a 5 minute slideshow of some of the best photos from the nature photographer of the year competition. Amazing.

Anyone with an interest in the natural world could do much worse than spend a few hours doodling around the BBC nature website. There are videos, photos, news items, etc. See for example ‘Female crickets eat virgin males‘!

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Weekly updates #4

Posted on 29 August 2012 by Keith Barrington

Ok not even nearly weekly, but I am now back from vacation, and after clearing though my inbox pressing the delete button several hundred times, I am ready to start posting again.

van der Ham DP, Vijgen SM, Nijhuis JG, van Beek JJ, Opmeer BC, Mulder AL, Moonen R, Groenewout M, van Pampus MG, Mantel GD et al: Induction of labor versus expectant management in women with preterm prelabor rupture of membranes between 34 and 37 weeks: A randomized controlled trial. PLoS Med 2012, 9(4):e1001208.
536 women with ruptured membranes at 34 to 37 weeks were randomized. In many hospitals currently labour is induced in these circumstances. This study found no advantage of induction compared to expectant management.

Weisman LE, Leeming AH, Kong L: Approriate antibiotic therapy improves ureaplasma sepsis outcome in the neonatal mouse. Pediatr Res 2012.
As study in a neonatal mouse model of ureaplasma sepsis. Azithromycin was much more successful than erythromycin for eliminating ureaplasma, and this improved survival. I rarely treat ETT ureaplasma infections, and when I do it seems to be very difficult to eliminate them, maybe I have been using the wrong antibiotic!

Choi WW, McBride CA, Bourke C, Borzi P, Choo K, Walker R, Nguyen T, Davies M, Donovan T, Cartwright D et al: Long-term review of sutureless ward reduction in neonates with gastroschisis in the neonatal unit. Journal of Pediatric Surgery 2012, 47(8):1516-1520. This technique I think has been a major advance, what we call here umbilical flap closure, and this article calls sutureless ward reduction. This article shows that about 50% can be reduced using this method, and that the babies do very well. They do it mostly on non-intubated patients, and 3/4 remain extubated after the procedure. We are more ‘aggressive’ I think, with many of our babies requiring ventilation after the procedure, but we are able to reduce a larger proportion of the cases without going to the OR. Recovery times appear to be shorter, but maybe they are the less severe lesions…

Petraglia AL, Moravan MJ, Dimopoulos VG, Silberstein HJ: Ventriculosubgaleal shunting – a strategy to reduce the incidence of shunt revisions and slit ventricles: An institutional experience and review of the literature. Pediatric Neurosurgery 2011, 47(2):99-107. There is enormous variation between institutions in the frequency and indications for shunts for post hemorrhagic hydrocephalus. Part of this may be because of varying frequencies of complications, and how the individual surgeon weighs the balance between complications and benefits.  A new-ish technique which shunts to the subgaleal space appears to be a good temporizing measure, and has low complication and infection rates.

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Predicting Successful Extubation

Posted on 21 August 2012 by Keith Barrington

A couple of years ago I wrote an editorial for the Jornal de Pediatria, a Brazilian journal, about extubation failure. (full text available free here). At that time the most promising test fo predicting extubation failure appeared to be some variant of the Spontaneous Breathing Test.

Tests of pulmonary mecahnics or lung volumes have been disappointing as a rule, and test of maximal inspiratory force have also not worked out. A variant of a test where the infant is switched to CPAP for a certain limited duration of time, and the infant then observed seems most useful. But what exactly to observe?

Lorna Gillespie and her colleagues measured minute ventilation during assisted ventilation, then repeated the measure during ETT CPAP for 10 minute, the minute ventilation test, MVT. If the CPAP minute ventilation was less than 50% of that during assisted ventilation then the baby is considered ready for extubation. This is one of the few (or perhaps the only) randomized controlled trials in this area. Infants randomized to have the MVT were extubated earlier than those randomized to be extubated when the clinical team thought they were ready.

The Melbourne group  (those guys again!) compared the measuring minute ventilation approach to observing the baby for hypoxia and bradycardia. Most of the babies who were reintubated had a VE ratio more than 0.5, so they would have passed the MVT. The test they devised, the spontaneous breathing test, SBT, requires switching to ETT CPAP for 3 minutes, and observing the baby. “A failed SBT was recorded if the infant had either a bradycardia for more than 15 seconds and/or a fall in SpO2 below 85% despite a 15% increase in FIO2″.

A new study by Sanjay Chawla and coworkers evaluating the SBT has just been published. (Chawla S, Natarajan G, Gelmini M, Kazzi SNJ: Role of spontaneous breathing trial in predicting successful extubation in premature infants. Pediatric Pulmonology 2012:n/a-n/a.) They used an almost identical SBT, except that it lasted 5 minutes, and they do not mention the FiO2 in their definition of hypoxia. Nevertheless they found that an SBT pass was strongly predictive of successful extubation, and failing the SBT was modestly predictive of extubation failure (8 failed the test and of these 5 babies were later extubation failures).

I think this test deserves a modestly sized RCT to see if duration of intubation and lung injury can be improved by using the test, and the number of extubation/intubation episodes can also be decreased. I think the test seems sufficiently predictive that it could be used to encourage earlier extubation if the test is passed, and a serious consideration of delaying extubation if failed, although there are some extubation successes among infants who fail the test, so if everything else is optimal then a trial of extubation might still be worth it. Failing extubation isn’t such a bad thing if you can re-intubate the baby with minimal trauma, using pre-medication.

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Weekly Updates #3

Posted on 8 August 2012 by Keith Barrington

A few new publications (I know it’s not quite weekly, but I am on vacation!):

Nguyen TP, Amon E, Al-Hosni M, Gavard JA, Gross G, Myles TD: “Early” versus “late” 23-week infant outcomes. Am J Obstet Gynecol 2012(0). Not too surprisingly, being born just after you reach 23 weeks gives you a lower chance of survival (25%) than being born just before 24 weeks (56%) in a single center retrospective cohort, n=126. Another good reason for throwing away guidelines that have intervention thresholds based on completed weeks of gestation!

Holsti L, Oberlander TF, Brant R: Does breastfeeding reduce acute procedural pain in preterm infants in the neonatal intensive care unit? A randomized clinical trial. Pain 2011, 152(11):2575-2581. For preterm infants in the NICU breastfeeding was no better than a soother during heel-lance (RCT n=57), the babies were not fully established on breast feeds, and those that were better at suckling may have had an effect. The controls did not receive sucrose: is this ethical?

Beeram MR, Loughran C, Cipriani C, Govande V: Utilization of Umbilical Cord Blood for the Evaluation of Group B Streptococcal Sepsis Screening. Clinical Pediatrics 2012, 51(5):447-453. You can use cord blood for the initial CBC and for the blood culture without worrying about contamination, prospective comparative study, n=200.

Bellieni CV, Tei M, Coccina F, Buonocore G: Sensorial saturation for infants’ pain. Journal of Maternal-Fetal and Neonatal Medicine 2012, 25(S1):79-81. A systematic review of multi-modal sensory stimulation as a pain control technique. This approach has been championed by Carlo Bellieni, See here for example, this SR shows that it is effective, and more effective than sweet solutions by themselves. It consists of giving the sucrose, and then talking gently to the baby, and massaging them (often a gentle stroking of the face). I don’t think this is much done in North America, but is part of some European guidelines, and probably should be more widely used, it is very simple to add to giving sugar.

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