Neonatal Updates : Therapeutic hypothermia

Posted on 21 March 2014 by Keith Barrington

Three recent articles dealing with the effects of therapeutic hypothermia:

Drury PP, Gunn ER, Bennet L, Gunn AJ. Mechanisms of Hypothermic Neuroprotection. Clin Perinatol. 2014;41(1):161-75. the first is an excellent review article describing how hypothermia works, SPOILER ALERT, its mostly about apoptosis.

Hochwald O, Jabr M, Osiovich H, Miller SP, McNamara PJ, Lavoie PM. Preferential Cephalic Redistribution of Left Ventricular Cardiac Output during Therapeutic Hypothermia for Perinatal Hypoxic-Ischemic Encephalopathy. The Journal of pediatrics. 2014. Left ventricular outputs during cooling were much lower than health controls, and increased with re-warming. SVC flows in contrast were similar to health infants, and didn’t change during re-warming. Suggesting that there is a redistribution of blood flow to the upper body, probably the brain. Maybe the lack of a decrease in SVC flow during cooling shows that the cerebral vessels are reacting abnormally to hypothermia, and maybe that is a good thing.

Nestaas E, Skranes JH, Støylen A, Brunvand L, Fugelseth D. The myocardial function during and after whole-body therapeutic hypothermia for hypoxic–ischemic encephalopathy, a cohort study. Early Human Development. 2014. A comparison of features of myocardial function by echocardiography between hypothermic babies, and a historical control group treated before hypothermia became standard, and a group of healthy controls. Most of the data presented are derived from tissue doppler studies. The indices of function were similar between the 2 asphyxiated groups, even though the hypothermia treated seemed to probably have a more severe insult. All the indices recovered to be near normal after re-warming.

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Hypotension after PDA ligation

Posted on 19 March 2014 by Keith Barrington

A new prospective multi-center evaluation, of cardiac function and the causes of hypotension after PDA ligation, has just published data about adrenal function.

Clyman RI, et al: Hypotension following patent ductus arteriosus ligation: The role of adrenal hormones. The Journal of pediatrics.

The babies all had a serum cortisol measured before the surgery, and had a 1 microg/kg ACTH stimulation test. They had cortisol measured post-op also, at between 10 and 12 hours postop, which is the average time of peak use of inotropes, and the time when El-Khuffash, Jain, and McNamara have demonstrated the worst left ventricular dysfunction. (that link is to a very nice, fairly brief, review article about the important issues).  The new study found no difference in the cortisol levels or the ACTH response between normotensive and hypotensive infants (about half were in each group). They did, however, show that the worst infants, who needed at least 15 mics of dopamine or dobutamine total dose per kg per min, had substantially lower post-operative cortisol concentrations. Although there was some overlap with the less sick infants.

This is somewhat different to a previous study (El-Khuffash A, McNamara PJ, Lapointe A, Jain A. Adrenal function in preterm infants undergoing patent ductus arteriosus ligation. Neonatology. 2013;104(1):28-33) published last year from the Sick Kids group, (including Anie Lapointe who is now my colleague at Sainte Justine). That previous study also did ACTH stimulation tests before PDA ligation, and showed that infants who had lower responses (<750 nmol 1 h after 35 microg/kg ACTH) were more likely to have postoperative hypotension, and more likely to have post-operative deterioration of their respiratory function as well. Interestingly in that study, the left ventricular output (LVO) was not associated with the pre-op cortisol responses. So perhaps less cortisol reserve s associated with an inability to maintain SVR, leading to hypotension rather than low cardiac output. Patrick McNamara’s group at Sick Kids uses a lot of milrinone in the babies with lower LVO, which might also be implicated in these responses.

I am not sure why the differences between these 2 studies, they are of course both observational, the differences may just be random variations. The much lower dose for the ACTH test in the new study might be one reason. (By the way to convert from the ‘american’ units of ng/ml to nmol/ml multiply by 2.8 (or to be precise by 2.759) I just had to look that up). But what test is preferable, and how to define relative adrenal insufficiency is still a mystery to me.

One other interesting aspect of the new study is that they measured other cortisol precursors and metabolites, and they were all low in the severe hypotension babies. Which implies that the problem is not with the adrenal gland but with the responsiveness of the entire hypothalamo-pituitary-adrenal axis.

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S’il suffisait d’aimer

Posted on 18 March 2014 by Keith Barrington

Sainte Justine is a unique hospital, we are a ‘full-service’ children’s hospital with an integrated maternity service. The obstetricians, of course, think that we are a maternity hospital with a children’s hospital tacked on!

We have a fund-raiser at the present.

The foundation has asked various choral groups to submit entries, the winning group will get to sing with Céline Dion. Many of the entries are spectacular, and show how creative we are  in Quebec. Two or three of the groups have sung the Jean-Jacques Goldman song which is called ‘S’il suffisait d’aimer’ (if it was enough to love). It is a very moving song; one of the best versions is currently in the lead for overall votes. Another version of the song is performed by a school where a child of 12 years of age died of leukemia. If you are like me, you will need a least one box of kleenex to get through that one. The chorales have to choose one of 4 songs that Céline has recorded, one of them is in English ‘because you loved me’, the other 3 are french.

J-J Goldman is not known all that well outside of the ‘francophonie’ which I think is a shame, and I don’t remember having heard of him before becoming a francophone…(or at least someone who lives and works in french). Some of his songs are great, such as the one in the title of this post, as well as ‘on ira‘ which I think is one of the best contemporary love songs of all. ‘Pour que tu m’aimes encore’ is another of his songs, of which there is a video of him singing with the very same Céline Dion. Some  of these songs I think are better than any English songs of the same period, they are not as well known, simply because they are in French…As a critic of uncontrolled IVF I also like ‘elle a fait un bébé toute seule‘.

So in case anyone thinks I am a music snob, because I was very rude about ABBA in a recent post, you can see from these links that I have no problem with pop.

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Please, please, not ABBA!

Posted on 18 March 2014 by Keith Barrington

I think whoever designed this study should be subjected to prolonged and unrelenting auditory torture. the only thing worse than ABBA that I can think of would have been Rolf Harris’s 2 little boys; so that is the sentence I pronounce on Dr Roehr and his colleagues, being subjected to that tune for a few hours every day might make them rethink this intervention.

The authors took experienced neonatal resuscitators and played different songs during resuscitation simulations. They found that the rates of chest compressions and respiratory inflations were higher when they played ABBA’s song SOS over an iphone at maximum volume.

They interpret this as meaning that the ‘music’ (and I use the term loosely) improved the compliance with recommended rates of chest compressions and ventilation, and maybe this should be more widely investigated.

I interpret as meaning that the participants, on hearing the ABBA song, wanted to get out of there as fast as possible, and did everything more quickly to try and get it to go away.

Seriously, if this becomes standard I will have to reconsider my career.

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Sticking needles into babies doesn’t reduce colic. Who’d have thought…

Posted on 17 March 2014 by Keith Barrington

More nonsense, this time acupuncture for babies!

Ninety babies were randomized in a multicenter trial of sticking needles into non-existent meridians to channel imaginary Qi energy. Unfortunately the condition they were investigating, infantile colic, causes a lot of real distress to parents.

Reasonably blinded study, found nothing.

Go figure.

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Waving your hands around is not analgesic! Who’d have thought…

Posted on 17 March 2014 by Keith Barrington

Really, who’d have thought it was worth testing.

I have a lot of respect for several of the authors of this trial, but I can’t for the life of me understand why they did this study. Celeste Johnston, Marsha Campbell-Yeo, Francoise Filion and I have been co-authors on a couple of studies together, and they have all done good things improving pain control in the NICU.

But this study should never have been done, and should never have received a penny of grant money. They were testing the idea that ‘therapeutic touch’  (which they start to describe as follows:

Therapeutic Touch does not involve direct tactile stimulation, but is based on a trained therapist working with energy fields)

might be analgesic in preterm babies. At that point, they should have been laughed out of town, and the grant application thrown in the waste basket. In order to be ethically valid there has to be a valid scientific rationale for doing a study. There has to be some prior plausibility to the intervention. Manipulating non-existent ‘energy fields’ is not plausibly effective at anything, no matter what kind of training the therapist has!

The intervention is described in more detail as follows:

For the Therapeutic Touch intervention, the therapist used her hands to assess and rebalance the energy field of the patient using the following steps: (1) centering her state of awareness; (2) assessing the energy field of the patient; and (3) modulating the energy field. The average time for this was 5 minutes. Both therapists were nurses and had several years of experience in Therapeutic Touch.

How on earth could the authors write that paragraph without laughing themselves silly, like I did when I read it!

Why on earth would a good journal publish such drivel? How on earth could you convince an ethics committee to allow this nonsense, and why would anyone give grant money to a team who proposed wasting it on this inanity?

The only reason I can think of for doing this, (as I said I know several of the authors, and I know they have the best interests of their patients, and of promoting good research and good patient care at heart: I hope they will still consider me a friend and colleague after my critical remarks) is that some misguided individuals are already doing such stuff, and they wanted to prove that it was ineffective, and that you should use real pain control when doing painful things to babies.

My response to that would be that anyone who is prepared to modulate a babies energy field is unlikely to be convinced with an actual scientific study. They should just be told to stop it, or go work in another environment, perhaps in a homeopathic Emergency Room.

(BTW not surprisingly, modulating the energy field, even after centering the state of awareness, didn’t do squat).

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Article now listed on PubMed

Posted on 17 March 2014 by Keith Barrington

The commentary that a large group of us wrote in reply to the CPS statement on extreme prematurity is now listed on PubMed.

(Janvier A, Barrington KJ,  et al: CPS position statement for prenatal counselling before a premature birth: Simple rules for complicated decisions. Paediatrics & child health 2014, 19(1):22-24.)

I am not sure, but I think it may be freely available, you can go to the link if you wish and try. If you want a pdf and it doesn’t work, a judicious inquiry might be able to get you a copy.

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Premature babies, should the school know?

Posted on 17 March 2014 by Keith Barrington

I saw a link to this article, a paediatrician from Glasgow thinks that because premature babies have more problems as they grow up than children who are born at term, the schools should have the gestational age on their entry forms.

I disagree.

We actually lied about Violette’s birth history when she was enrolled in school. Our reasoning was that a) we did not want her to be labelled, as many other premature babies are, we did not want teachers and the school to have lower expectations for her because she was extremely preterm. b) premature babies have more difficulties it is true, but many children born at term have difficulties at school also, they should all be able to get the assistance they need. The school should be able (and appears to be able) to identify any problems she has, and develop interventions if needed to address them. How does knowing she was born at 24 weeks help the school to help her?

On the other hand if she had a specific learning problem identified, that the school needed to know about in order to intervene, then yes, they need to be informed and we would have told them. Premature babies have a range of abilities and difficulties when they grow up, just like babies born at term, being born prematurely is not an impairment!

If she now had difficulties organizing her work, and staying on task (the kind of executive functions that many ex-preterms have) then they are not such unusual problems! Lots of children who were born at term also have those problems, and they all need strategies to help them out. Preterm babies problems in such fields tend to improve over time, so when would you stop telling people that she was an ex-premie?

If she had cerebral palsy, and needed help to climb the stairs in the school, then the school needs to know about that specific issue. They still wouldn’t need to know that she was born too early.

I am very proud of my little girl, and not at all shy about telling people that she was born extremely prematurely, but, on balance, I think the school are better to teach her, and evaluate her, without any preconceptions based on her birth history.

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Neonatal Intensive Care Units work!

Posted on 17 March 2014 by Keith Barrington

The first Epicure study had relatively poor survival rates, especially for the more immature babies. Of course the data were regional data, including all babies born in the UK and Ireland, so they included babies born in places with very low levels of care, many of whom were never transferred to intensive care units. Although I think EpiCure1 was an amazing effort, the results were often used as a way of suggesting that neonatology was very ineffective. Every position statement of learned societies referred to the data, often with no description of the context . In the UK though the data were used to try and improve their regionalization, with what are called managed clinical networks. There were at the time of Epicure1 many very small units treating tiny numbers of extremely preterm babies per year, the data were never presented by level of care of the birth hospital.

The new Epicure study has rectified that (Marlow N, Bennett C, Draper ES, Hennessy EM, Morgan AS, Costeloe KL. Perinatal outcomes for extremely preterm babies in relation to place of birth in England: the EPICure 2 study. Archives of Disease in Childhood – Fetal and Neonatal Edition. 2014.. Open Access)

The data show quite convincingly that being born in a hospital with level 2 services, and then transferred later leads to much poorer survival.

They show that being born in a level 3 hospital leads to better survival, and without more morbidities, so survival free of morbidity is much better (morbidity being defined as one or more of retinopathy of prematurity requiring retinal surgery, moderate or severe bronchopulmonary dysplasia, a severe brain injury (haemorrhagic parenchymal infarct, cystic changes or hydrocephalus on cerebral ultrasound) or surgical necrotising enterocolitis. They also showed that among level 3 hospitals, those which have higher patient volume have substantially better survival.

They also show, depressingly, that

Despite national policy, only 56% of births between 22 and 26 weeks of gestation occurred in maternity services with a level 3 neonatal facility

The proportion can never be 100% of course, but adequate regionalization can make that figure much more than 56%. The exact proportion will depend upon many factors of health care organization, and geography, but aiming for 90% is reasonable, and would save many lives.

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Letter in Early Human Development

Posted on 17 March 2014 by Keith Barrington

Some of you might recall a report in Early Human Development that I strongly criticized on this blog. The title was ‘The effect of in-hospital developmental care on neonatal morbidity, growth and development of preterm Taiwanese infants: A randomized controlled trial.’

When I wrote the blog post I also sent a letter to the editor suggesting in quite strong terms that the article was fatally flawed and should be retracted. I never received any reply from the editor, but the publishers sent me an automated message asking me to submit the letter on their website. There was actually no way to submit a letter on the website, it had to be submitted as a regular article submission. Which I did, almost a year ago. I recently received an automated email congratulating me that my article had been accepted!

Anyhow, the letter has now been published, as I originally wrote it, along with a reply from the authors.

My letter is actually very rude, and I would not have written it quite like that if I had thought it would just go to publication, I intended it to be read by the editors, the tone is much more the kind of thing I write in this blog, but I will have to live with that.

The authors’ reply is, I think, entirely inadequate. you can read it yourselves, but the authors now state that some of the exclusion criteria were actually ‘early dropout’ criteria. In other words they planned the trial from the start to not be an ‘intention to treat’ analysis but to exclude certain babies after they had been enrolled. These early dropout criteria include, for example, severe intraventricular hemorrhage, and they state that there were 7 babies with intracranial hemorrhage or calcification who were enrolled and then dropped out because of those findings. Again, this makes no sense, IVH occurs in the first couple of days of life, there would be no reason for enrolling such babies and the dropping them out again.

The authors state that the publication did indeed follow the CONSORT statement, but there are many ways in which that statement is not accurate. One major example is the following, item 6a from the CONSORT statement of things which must be included in the report:

Completely defined pre-specified primary and secondary outcome measures, including how and when they were assessed

As I mentioned before there is no primary outcome mentioned in their report, the authors state in their reply to my letter :

the primary purpose of our study was to investigate the effect of early intervention (consisting of in-hospital and after-discharge developmental care) on child, parent and mother–child interaction outcomes in VLBW  infants

Which is so vague as to be meaningless. they go on to state

Previous in-hospital intervention studies and have commonly used child medical, growth and developmental variables as the short-term outcome measures. Our paper has therefore considered all these variables as the primary outcomes.

Which just shows that they don’t understand what a primary outcome variable is. Rather than continue to beat down on these authors, I really want to ask the question, how on earth did all this get through peer review? Someone clearly did not do their job.

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