Nurses matter!

Posted on 4 February 2013 by Keith Barrington

There are a lot of qualitative studies that make huge generalizations from the very tiniest of samples; on the other hand, some studies of values and wishes of parents and patients can be valuable, and can be well studied only with qualitative techniques.  One example of the latter is a new study from 3 centers in France. (Guillaume S, Michelin N, Amrani E, Benier B, Durrmeyer X, Lescure S, Bony C, Danan C, Baud O, Jarreau P-H et al: Parents’ expectations of staff in the early bonding process with their premature babies in the intensive care setting: A qualitative multicenter study with 60 parents. BMC Pediatrics 2013, 13(1):18.) They interviewed 30 mothers and 30 fathers with very preterm babies in NICU. It is worth a read (freely available on BMC Pediatrics) and I will quote in its entirety the conclusion section of the abstract:

‘At birth and during the first weeks in the NICU, the creation of a bond between mothers and fathers and their premature baby is rooted in their relationship with the caregivers. Nurses’ caring attitude and regular communication adapted to specific needs are perceived by parents as necessary preconditions for parents’ interaction and development of a bond with their baby. These results might allow NICU staff to provide better support to parents and facilitate the emergence of a feeling of parenthood.’

Another study points out the importance of nurses attitudes to what happens in the NICU and to parental experiences. A US study, from an urban center, questioned nurses and mothers about things like whether parents should participate in care of the baby and whether they should be encouraged to be present and to do kangaroo care. (Hendricks-Munoz KD, Li Y, Kim YS, Prendergast CC, Mayers R, Louie M: Maternal and neonatal nurse perceived value of kangaroo mother care and maternal care partnership in the neonatal intensive care unit. American journal of perinatology 2013(EFirst).) I was very surprised by the results. Only 21% of nurses strongly agreed that parents should be encouraged to be present in the NICU, and only 67% of mothers! Knowledge and attitudes towards Kangaroo Care were also poor, and differed greatly between nurses and mothers. The authors identified many barriers to creation of maternal care partnerships that need to be overcome.

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Preventing Stillbirth

Posted on 4 February 2013 by Keith Barrington

A new observational study looking at the causes of Stillbirth in the UK (Gardosi J, Madurasinghe V, Williams M, Malik A, Francis A: Maternal and fetal risk factors for stillbirth: Population based study. BMJ 2013, 346:f108.) identifies potentially modifiable factors that were associated with stillbirth after 24 weeks; they were maternal obesity, smoking, and most importantly intra-uterine growth restriction. ‘195 of the 389 stillbirths in this cohort had fetal growth restriction, but in 160 (82%) it had not been detected antenatally.’

One of the reasons for the increase in prematurity in the developed world is an increase in medical indicated preterm deliveries, many of which are for concerns about fetal status. It looks like there is still much to do, to accurately screen and diagnose fetal growth restriction and develop strategies to avoid stillbirth, and do this without further increasing prematurity rates.

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Iron therapy for anemia of the preterm; now I’m confused!

Posted on 29 January 2013 by Keith Barrington

I thought I knew, sort of, what to do about iron supplementation in the preterm. Preterm babies outgrew their iron supply, there isn’t very much in breast milk, and you need to supplement to minimize the appearance of anemia of prematurity.

There was previously a trial which compared transfusions and iron status among 204 preterm infants (<1300g birth weight) who were randomized to start iron as soon as they were tolerating 100 mL/kg/d of milk, or to wait until they reached 61 days. The babies received 2 mg/kg/d at first and it was increased to 4 if the hematocrit was below 30. That trial showed fewer transfusions and less iron deficiency with early supplementation. They also published long term follow up, although not powered for that outcome, the 164 babies who were studied (most, 85%, of the survivors) tended to have better outcome in the early group.

There is also a Cochrane review showing improved hematocrits with routine enteral iron prophylaxis in the preterm.

Now a new trial has been published which compared giving 2 mg/kg/day of iron, started when the babies were tolerating 120 mL/kg/d of milk, to a multivitamin preparation without iron. The babies were 150 VLBW (<1500g) infants and the primary outcome was hematocrit at 36 weeks, transfusions were also noted. They note that the control group were receiving around 2 mg/kg/d already in the breast milk fortifier that they were adding to the breast milk. There were no differences in the results between the groups. The authors note that they have a ‘liberal’ transfusion policy, which they say is based on the previous evidence regarding ‘long-term benefits of maintaining higher hemoglobin levels in extremely low birth weight (<1000 g birth weight) infants’. What they don’t tell us is how many transfusions the infants received prior to entering the study. That info would have been helpful: a blood transfusion or two would have given substantial amounts of iron to the babies, and could be a reason for not finding a difference between the groups. that would make it less easy to extrapolate the findings to other NICUs, such as ours, where we have not liberalized our transfusion guidelines.

And just how good is that data about long term benefits of liberal transfusion? Although the authors reference the PINT trial and the Cochrane review, neither of those sources show an improved long term outcome! The PINT study showed slightly better 18 month Bayley scores, differences consistent with chance, p value about 0.09, and only when they looked at the proportion of babies less than 85 (not 70 which was pre-specified as the outcome of interest) did they show a difference that looked more convincing. The other trial that has reported some long term outcomes was the trial by Ed Bell and others, who followed only 56 of their 100 patients to early school age, and some measures of cognitive function were better in the liberal transfusion compared to the conservative group.

In summary I do think it seems possible that some outcomes are better with a higher transfusion threshold, but it certainly isn’t definite, and before using a lot more blood transfusions we should get better data. There are other trials in the works.

In the meantime, with a more restrictive transfusion policy, I think continuing to give iron supplementation early, in addition to what we have in the breast milk fortifier still makes sense.

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Not only Neonatology

Posted on 26 January 2013 by Keith Barrington

I really appreciate the writings of Atul Gawande, his articles and his books: ‘Complications’ ‘Better’ and ‘The checklist manifesto’.

I just saw a TED talk he gave in March last year, 19 minutes on how to fix medicine. Link here. I think a lot of his ideas can be used in the NICU, and the very complex care that we sometimes give there.

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Helping Babies Breathe is a Really Good Idea

Posted on 24 January 2013 by Keith Barrington

Two new articles showing that ‘Helping Babies Breathe‘ training really works.

Msemo G, Massawe A, Mmbando D, Rusibamayila N, Manji K, Kidanto HL, Mwizamuholya D, Ringia P, Ersdal HL, Perlman J: Newborn mortality and fresh stillbirth rates in tanzania after helping babies breathe training. Pediatrics 2013.

Goudar SS, Somannavar MS, Clark R, Lockyer JM, Revankar AP, Fidler HM, Sloan NL, Niermeyer S, Keenan WJ, Singhal N: Stillbirth and newborn mortality in india after helping babies breathe training. Pediatrics 2013.

Both used a before and after design, and both showed that stillbirth rates were lower after the HBB training. That may seem strange at first, how could stillbirths be reduced? Of course the answer is that after training, the health workers realize that some babies that were classified as stillbirths previously (either there wasn’t an attempt to resuscitate them or after a failed resuscitation they were called a stillbirth) are now being successfully resuscitated.

Wally Carlo has already shown that the infants who are resuscitated do well in the long run, in a study using a very similar resuscitation program, those babies who received assisted ventilation at birth had long term outcomes the same as the comparison group who had not resuscitation.

 

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Are babies and children so different?

Posted on 24 January 2013 by Keith Barrington

Matteo Fontana and his collaborators have just published an interesting paper evaluating modes of death in the PICU and NICU at my hospital, Annie Janvier is, of course, the senior author (Fontana MS, Farrell C, Gauvin F, Lacroix J, Janvier A: Modes of death in pediatrics: Differences in the ethical approach in neonatal and pediatric patients. The Journal of pediatrics 2013). They defined modes of death using the same schema that Annie has published previously (with Eduard Verhagen): as follows (1) children who died because admission to an ICU was withheld; (2) children who died despite active cardiopulmonary resuscitation (CPR); (3) children who died while receiving mechanical ventilation, without active CPR; (4) children who died after withdrawal or withholding of LSI who were extremely sick and expected to die and (5) children who died after withdrawal and withholding LSI of infants who were stable, because of prediction of a poor quality of life.

In both units the proportion of patients who died during CPR was low. There was in contrast a very large difference in the proportion of patients who died during on-going intensive care, but without CPR (51% of deaths in the PICU and 5% in the NICU), and in the proportion who died after withdrawing or withholding intensive care for quality of life reasons (16% of deaths in the PICU and 53% in the NICU).

Why is this? Why do we frequently redirect care in the NICU when usually all we have are indications of increased probability of impairments, with an enormous amount of uncertainty, while in the PICU, even when the children are known to already have the same sort of impairments, intensive care continues to the very end? Maybe we have something to learn from each other.

I note that there will be an editorial accompanying this article when it is published, I guess I will be re-blogging at that point!

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Weekly Updates #21

Posted on 23 January 2013 by Keith Barrington

Van Hus JW, Jeukens-Visser M, Koldewijn K, Geldof CJ, Kok JH, Nollet F, Van Wassenaer-Leemhuis AG: Sustained developmental effects of the infant behavioral assessment and intervention program in very low birth weight infants at 5.5 years corrected age. The Journal of pediatrics 2013(0). Long term follow up of an RCT of an early intervention program for preterm infants. about 180 infants were randomized to post-discharge intervention or control, which lasted for 6 months. At 5.5 years there appear to be significant benefits form the program among the 136 infants reviewed, fewer babies with an IQ below 85, as well as better motor skills. Most programs have not shown benefits persisting this long in the past.

Jiang P, Smith B, Qvist N, Nielsen C, Wan JM-F, Sit W-H, Jensen TK, Wang H, Sangild PT: Intestinal proteome changes during infant necrotizing enterocolitis. Pediatr Res 2013. This proteome analysis of parts of bowel from preterm infants with NEC which were necrotic and parts which were adjacent yet unaffected, showed expression of heat-shock proteins was enhanced, and several other proteins were also affected. This might be important, or it might not, I am not sure how the expression of such proteins in necrotic parts of bowel is affected just by them being necrotic… It would be nice to know how they were affected as the necrosis was progressing, but that of course is impossible.

Bharadwaj SK, Vishnu Bhat B: Therapeutic hypothermia using gel packs for term neonates with hypoxic ischaemic encephalopathy in resource-limited settings: A randomized controlled trial. Journal of Tropical Pediatrics 2012, 58(5):382-388. Therapeutic hypothermia for term infants with encephalopathy can be done cheaply and safely. This study shows that even using cheap simple methods it is still effective; in an RCT of 130 babies, survival without severe disability (at 6 months) was better when the babies where cooled with gel packs than the controls. Asphyxia is a major cause of death and disability in the developing world, this cheap intervention could make a big difference.

van den Broek MPH, Rademaker CMA, van Straaten HLM, Huitema ADR, Toet MC, de Vries LS, Egberts ACG, Groenendaal F: Anticonvulsant treatment of asphyxiated newborns under hypothermia with lidocaine: Efficacy, safety and dosing. Archives of Disease in Childhood – Fetal and Neonatal Edition 2013. Some centers use lidocaine frequently as an anticonvulsant in the newborn. This study documents the reduced clearance of lidocaine under hypothermia, and does suggest that it is effective. We really need better studies of comparative effectiveness of anticonvulsants and of long term outcomes.

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Slow Flow

Posted on 22 January 2013 by Keith Barrington

I have worked in a couple of NICUs in the past where infants were placed on low flow room air by nasal cannulae. The idea, I was told, was that a bit of flow would help the babies to inhale. Now this never seemed to have any possible physiologic basis to me, and now two recent studies, both from Dublin, confirm that there are no detectable clinical effects.

The first is by O’Donnell and collaborators at the Coombe hospital, with colleagues from a second hospital in Prague. They randomized 78 babies <1500g birth weight to either get 1 liter per minute of air by nasal cannulae or no flow when they were coming off CPAP. The babies were followed for 120 hours to see if they failed weaning from CPAP and had to go back on CPAP or not. There were no benefits of any kind detected.

The second is from Hensey and others at the National Maternity Hospital just down the road. Their study was a short term crossover study to look at whether breathing patterns and apnea were different between getting a little air in the cannulae, (at 0.1 l/min), getting nothing in the cannulae, (they were left in place but disconnected), or getting a little oxygen in the cannulae (100% oxygen at 0.1 l/min). 3 hour intervals were recorded to see the number of desaturations. They basically showed in 14 babies less than 33 weeks gestation that low flow air did nothing to desaturations, that low flow oxygen reduces desaturations but many of the infants spent time over 95% saturation. Even on very low flow oxygen you do need to have your high saturation alarms switched on.

Low flow air does nothing, which I think is what they expected to find!

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Supporting oxygen limits

Posted on 19 January 2013 by Keith Barrington

The initial results of the SUPPORT trial examining the effects of different oxygen limits stopped a lot of us in our tracks. We started these trials because most of us thought that aiming for lower oxygen saturation targets would reduce eye disease, would reduce chronic lung disease and would be safe. We were uncertain enough however to put together randomized trials to scientifically compare the effects of choosing 2 different oxygen targets, to make sure that what we thought we were seeing from observational studies was in fact true.

We confirmed that less oxygen meant less retinal disease, including more retinal disease severe enough to need surgery, there wasn’t really any effect on chronic lung disease (a probably chance reduction from 39.7 to 37%) but there was an increase in mortality. More babies died in the lower oxygen group than the higher group.

The newly published results (Vaucher YE, Peralta-Carcelen M, Finer NN, Carlo WA, Gantz MG, Walsh MC, Laptook AR, Yoder BA, Faix RG, Das A et al: Neurodevelopmental outcomes in the early cpap and pulse oximetry trial. The New England journal of medicine 2012, 367(26):2495-2504) from the 20 month follow up confirm that the difference in survival persists, and now shows that all the actual outcomes on visual function were not different, neither blindness, severe visual impairments nor squint. Even though there were twice as many infants who had eye surgery in the high saturation group as the low sat group.

In addition the neurological and developmental outcomes (at least as measured by the Bayley score) were not different. Significant cerebral palsy was 5% in each group, and a Bayley score less than 70 was about 7.5% in each group.

With the interim analysis that stopped the BOOST2 trials in the UK and Australia also showing an increased mortality, it certainly looks like we should avoid the lower saturation range of 85 to 89% that was targeted in each of the low groups of the oxygen trials. This evidence is also enough I think to encourage us to do further trials examining other targets, as well as looking for other ways of avoiding hyperoxia. If we are to target 90 to 95% saturation, then the risk of episodic hyperoxia will be increased, maybe automated FiO2 controllers, adaptive alarms and other interventions can help us make the higher limits safer to the eyes.

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Transplanting Poo

Posted on 18 January 2013 by Keith Barrington

That’s right, Poo not Pooh; this post is not an AA Milne tribute.

The smallest trial in a while at the PNEJM (van Nood E, Vrieze A, Nieuwdorp M, Fuentes S, Zoetendal EG, de Vos WM, Visser CE, Kuijper EJ, Bartelsman JFWM, Tijssen JGP et al: Duodenal infusion of donor feces for recurrent clostridium difficile. Prestigious New England Journal of Medicine 2013) only 42 patients were in the trial when it was stopped, they were planning 120. The patients were all adults with C difficile diarrhoea that had relapsed after treatment. They were randomized to either get Vancomycin, Vancomycin plus bowel washout with 4 litres of a special solution, or a short vancomycin treatment followed by the bowel washout followed by the infusion of donor feces into the duodenum. They created a pool of donors who had acceptable feces (they were healthy, had stool cultures screened for all sorts of bad stuff and were able to poo on demand (I added that last bit)) and on the day they had an eligible patient they provided a sample which was immediately transported to the hospital, diluted down and then infused into the patients duodenum through a tube.

This has actually been done many times, without controls but with good apparent success rates. So this study from the Netherlands was designed to answer an important question; recurrent C diff is really bad news; difficult to treat and with many complications. The study was stopped because almost all the poo recipients had a cure immediately, and 2 of the 3 failures responded to a second treatment (with another donors feces).

I think it is clear that this treatment is aimed at restoring a normal microbiome in patients in whom the microbiome was very disturbed. An accompanying editorial in the PNEJM does in fact refer to this as a microbiome transplant. And discusses why it has not become more widespread. He notes that it is aesthetically unappealing… what I would call an understatement!

Probiotics are of course attempting to do the same thing, with a less disturbing aesthetic! A recent editorial points this out, the wonderfully titled ‘The power of poop‘ (Floch MH: The power of poop: Probiotics and fecal microbial transplant. Journal of Clinical Gastroenterology 2012, 46(8):625-626.)

So normalizing the intestinal microbiome benefits not just preterm babies but clostridium difficile as well.

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