High Flow Nasal Cannulae: poor man’s CPAP?

Posted on 1 May 2014 by Keith Barrington

The title is how I sometimes refer to HFNC, but one could ask whether that is all there is to high flow, is it just another way to deliver CPAP, but with no control, or knowledge, of the pressure delivered?

A new study examined the lung mechanics in infants receiving CPAP and HFNC, and they tried to match the actual distending pressure achieved between the groups. (Lavizzari A, Respiratory mechanics during NCPAP and HHHFNC at equal distending pressures. Archives of Disease in Childhood – Fetal and Neonatal Edition. 2014). In a randomized cross-over study of 20 preterm infants with mild RDS, babies received 2,4, or 6 cmH2O of CPAP or 2,4, or 6 L/min. They then measured the retropharyngeal pressure and compared lung mechanics between periods of CPAP and periods of HFNC which achieved matching pressures.

Not too surprisingly  pressures achieved during HFNC were very variable. 5 of the babies did not achieve a pressure of more than 2 cmH2O even with 6 liters per minute. only 5 babies got up to 6 cmH2O, so the comparisons were done at 2 and 4 cmH2O. There were basically no differences found. Although all the inspiratory work of breathing estimates were a little higher with HFNC than with CPAP.

The babies had very low oxygen requirements, and fairly good lung compliance, I guess it is possible that the results might have been different with subjects that had stiffer lungs; but this study does suggest that HFNC is indeed a ‘poor man’s CPAP’, with CPAP actually delivered often being less than 2 cmH2O but, when CPAP is generated, the physiological effects are similar to traditional CPAP. Again suggesting that the only real benefit of HFNC is comfort.

Or is it? Another small cross-over trial evaluated comfort using the EDIN scale during 24 hours periods with either CPAP (at 4 to 5 cmH2O) or HFNC (at 5 or 6 L/min) in 20 preterm infants with mild respiratory distress. (Klingenberg C, et al. Patient comfort during treatment with heated humidified high flow nasal cannulae versus nasal continuous positive airway pressure: a randomised cross-over trial. Archives of Disease in Childhood – Fetal and Neonatal Edition. 2013). No difference in the discomfort scores was found. A nice aspect of this study was that the authors asked parents how they felt about the therapies, the parents clearly preferred the HFNC, they thought their child was more satisfied, they could do more in the care of the baby, and they had improved interaction with them.

Finally another small cross-over study compared pressures achieved with 2 different HFNC systems (Collins CL, et al . Comparison of the pharyngeal pressure provided by two heated, humidified high-flow nasal cannulae devices in premature infants. Journal of Paediatrics and Child Health. 2013). Basically, at the same flow the pressures were the same. And again, very variable, at the highest flows they tested, 7 and 8 L/minute, the pressures were a bit lower with the Fisher-Paykell device, probably because of the pressure limiting valve. At 8 liters per minute the average pressure was between 4 and 5 with each device, but the standard deviation was 2.2, meaning that 95% of the time the pressures were between 0 and about 9 (if they were truly normally distributed, which is unlikely to be exactly true). So poor man’s CPAP, with unreliable pressures, no apparent physiologic advantage, a possibility of having very high or very low distending pressures, but parents prefer it, and there is less nasal trauma. Clinical outcomes are not any worse, and babies who are failing on HFNC (which is likely to be sometimes due to them not actually getting any pressure) can often be rescued with CPAP.

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Executive Function?

Posted on 29 April 2014 by Keith Barrington

Raju TNK, Mercer BM, Burchfield DJ, Joseph GF. Periviable birth: executive summary of a Joint Workshop by the Eunice Kennedy Shriver National Institute of Child Health and Human Development, Society for Maternal-Fetal Medicine, American Academy of Pediatrics, and American College of Obstetricians and Gynecologists. J Perinatol. 2014.

I have previously mentioned the participation of Annie and me in the Workshop at the beginning of last year. We were very appreciative of being invited as the only non-Americans (I think) who presented, and I think it was a valuable process. On the other hand Annie and I were both a bit perturbed that there were no parents of preterms involved (except us, and maybe that was one reason we were invited). Many of us now feel that the time should be past when doctors get together in a room and decide on policy for the populus. We need to find ways to get input from families and from a wide variety of what I hate to call ‘consumers’ of health care.

Also there was a lot of debate and some areas of disagreement, so I did not envy the task of Tonse Raju and his co-authors in trying to summarize what went on. The Executive Summary that has now been published is, overall, a reasonable reflection of our discussions, but there are still some things that I am in disagreement with.

As one example there is a table of what obstetricians should do to mothers who present at high risk of extremely preterm delivery in the peri-viable period. I think we should be past this also: a list of what is and what is not recommended at varying gestational ages.

The table (3) includes, for example, that cesarean delivery is not recommended for fetal indications up to and including 22 weeks and 6 days, but then suddenly becomes recommended at 23 weeks and 0 days.

I will go over my litany of why I think this is mistaken, yet again. Firstly as we never know exactly the gestational age (except in cases of IVF) to make exact recommendations is irrational.

Secondly I think this recommendation must be nuanced and take into account the particular clinical circumstances of the mother, and her values and desires. I think there are many situations in which a cesarean delivery might be quite inappropriate for a mother who has passed the 23 week threshold, and that should be a decision for the woman and her doctor, (in concert with others, such as a partner). Surely the recommendation should be that the risks of extremely preterm cesarean are clearly explained to the mother, and an outline of what those risks are, without suggesting that as the clock ticks past midnight the OR should be called. The main additional risk of an extremely preterm cesarean, compared to one at term, is the risk to future pregnancies; so that is what needs to be discussed with the mother in addition to the overall risks of abdominal surgery (unfortunately it is hard to find good published data on this specific issue).

I could make similar comments about most items in the table, antenatal steroids for example. Even though the text introduces  many of the other considerations, the table ends up over-simplifying the issues.

In contrast table 5 is a table of ‘Considerations regarding family counseling for anticipated or inevitable periviable birth’ and is to my mind a good reflection of our discussions, and an appropriately nuanced list of issues that need to be discussed with families.

Item Suggested steps
General Providers should be aware of local standards (for example, hospital) and regulations (for example, state laws).
Counseling should be personalized and in the best interest of the family and their child, considering aspects beyond the gestational age.
Written guidelines should be developed by obstetric and neonatal teams with input from other stakeholders (for example, ethicists, nursing, administration, risk management and former NICU families).
Use protocols and checklists as adjuncts to proper counseling, and not as ‘stand-alone’ tools.
The institution should develop structured checklists and documentation processes to standardize use of counseling and obstetric and neonatal interventions, including newborn resuscitation.
The institution should provide for regular multidisciplinary conferences and teaching sessions.
Before and after counseling sessions Obstetric and neonatal care providers should confer to avoid conflicting information. Obstetric and neonatal care providers should meet the parent(s) together if feasible. Post-counseling debriefing should occur to share and confirm the decisions (if any). Repeated counseling should occur as clinical circumstances change.
During counseling Provide counseling in the families’ preferred language using trained professional interpreters as needed, and use family interpreter only if the family makes such a request.
Foster informed, collaborative decision making in an open, transparent and supportive atmosphere.
Seek out the family’s concerns and how they can be helped.
Content of counseling Individualize the information to be provided, based on family preferences, wants and needs.
Some will want to receive detailed statistics, whereas others prefer hearing only the ‘big picture.’
Investigate how much the family wants to be directed in their decision-making process.
Consider the use of decision aids or other materials.
Recognize that the family’s wishes may be influenced by their cultural background, religious beliefs or both.
Specific information Provide institutional data regarding survival and disability, if available. Otherwise, share regional, national or other population-based outcome information.
Provide information regarding available obstetric interventions, including their potential benefits and risks.
Provide information regarding the possibility of survival and disabilities separately.
Offer information regarding anticipated NICU care; provide more information about potential NICU stay according to family’s wishes: appearance of baby at birth, NICU complications, family-centered care in the NICU, provision of breast milk and so on.
Discuss options for comfort care and circumstances that might result in reconsideration of life-sustaining interventions.
Inform the family that the baby’s appearance at birth and Apgar scores are of limited prognostic value for survival and long-term morbidities.
State that infants born at extremely low gestational ages have a reduced survival and increased risks of adverse long-term outcomes.
Information given to families should include what some children cannot do because of disabilities and what many can do.
Mention adaptation and coping difficulties; the meaning of disability and the effect on families should be included.
Follow-up Offer the family time to think about the information provided and needed decisions if circumstances permit. Encourage input by prospective parents’ important supports (for example, friends, family members and faith leaders) according to family preferences.

I think if we can incorporate most of this into our counselling we will respond better to the needs of families.

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Necrotising Enterocolitis: is abdominal ultrasound helpful?

Posted on 29 April 2014 by Keith Barrington

I am still not convinced. (Maybe I could ask, and answer, the same thing about abdominal radiography!)

In recent years in my practice we have had examples of echographic diagnosis of intramural gas in stable infants who had an abdominal ultrasound for other reasons (follow up of antenatal diagnosis of pylectasis for example). In follow up exams of babies with a clinical diagnosis of NEC we have seen ultrasound giving a diagnosis of necrotic bowel loops which were well perfused at laparotomy. One problem is the lack of a gold-standard non-invasive diagnosis, so determining sensitivity and specificity is not possible.

A new article suggests in contrast that ultrasound is useful for prognosis (Garbi-Goutel A, Brevaut-Malaty V, Panuel M, Michel F, Merrot T, Gire C. Prognostic value of abdominal sonography in necrotizing enterocolitis of premature infants born before 33weeks gestational age. J Pediatr Surg. 2014;49(4):508-13).

This article only includes infants who had a diagnosis of NEC and had both ultrasound and x-rays, so it would exclude our first group of problematic babies, and it does suggest some findings that might be useful for prognostication.

Free intra-peritoneal air was more frequently seen on ultrasound than on x-ray, so for diagnosis of perforation it may be more sensitive. It has already been shown that portal venous gas is much more commonly seen on ultrasound, this study confirms that, and I think gives you a definite diagnosis of NEC if you are not sure; at least if it happens to be present.

Peritoneal fluid was often seen on ultrasound in the new study, and had a positive correlation with a poorer outcome. One of the problems with this study though, is that a poorer outcome includes having surgery, and, as a retrospective study, it is not clear how many babies had surgery because the ultrasound showed peritoneal fluid.

One thing that the authors do not discuss is evaluation of bowel perfusion, which has been described previously, but I am very unsure how reliable it is, even with fancy colour doppler and the latest machines and software. I think we need more investigation of these techniques, with prospective studies evaluating reliability of diagnoses and prognoses.

On the other hand, abdominal radiography is subject to a lot of inter-observer variability, (see for example here) except in the most severe cases with extensive pneumatosis, where the agreement is higher (see here), and probably a third of perforations do not have visible free air on abdominal radiography, so we need more reliable, more objective ways of diagnosing NEC and determining need for surgery.

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Better research, for better care

Posted on 28 April 2014 by Keith Barrington

I hope this commentary in JAMA receives a lot of ‘likes’!

Eapen ZJ, Lauer MS, Temple RJ. The imperative of overcoming barriers to the conduct of large, simple trials. JAMA. 2014;311(14):1397-8.

The commentary includes a report of a conference about the issues outlined in the title, a conference which reached 3 conclusions with which it is hard to disagree.

First, trials determining the risk-benefit balance of therapies must be larger. Improvements in existing standards of care are likely to be incremental (10%-25% relative reduction in events), and large studies with numerous events are needed to identify moderate treatment effects. It is important that these trials use clinical, not surrogate, end points.

Second, trials must be simpler. The cost of large, complex trials—often hundreds of millions of dollars—is a significant hurdle, in both initially bringing a treatment to market and subsequently conducting comparative studies. Moreover, restrictive inclusion criteria and excessive exclusion criteria often limit clinicians’ abilities to extrapolate findings to a broader, heterogeneous population. Data collection during the trial may also be excessive, and this too adds to the cost. According to the Tufts Center for the Study of Drug Development, the typical clinical trial in 2012 involved 13 end points, 169 case report form pages, and 175 days of on-site monitoring.1

Third, for most therapies, studies must be randomized. Estimates of effect size in large observational studies may be precise but remain fundamentally hampered by bias and confounding that can be controlled only through random allocation.

Simplifying approval processes, reducing the burden of data collection, using existing registries for data collection, and at the same time maintaining protection of subjects are top priorities for the future.

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Retraction of a systematic review

Posted on 28 April 2014 by Keith Barrington

Exactly when should an article be retracted? That is not so easy a question to answer, fraud and significant data or image manipulation are one fairly obvious group of reasons. Making errors and/or poor research design are more tricky. When the errors are such that the major results are unreliable, then retraction should be considered.

Retractions have been very few in neonatology, but one recent example, is an article that I blogged about previously, a systematic review of NIDCAP from a French group. The retraction notice states that the authors had included some data twice, which I hadn’t realized. Some of (or at least 2 of ) the articles that they included in fact were reporting data from the same infants.

The retraction notice also notes that there were errors in the description of the outcome variable. As far as I can see this is because some of the scores that were included were actually from the 1st version of the Bayley scales, but in the systematic review it was stated that they were from the 2nd edition. I already noted that it really isn’t appropriate to mix Bayley scores at different ages, especially very early scores at 9 months of age, mixing version 1 and version 2 scores makes that error worse. In fact the second edition of the Bayley became available in 1993, so all the babies in the first NIDCAP trial were examined with the first edition. These babies were also re-reported in the paper in 2009 by McAnulty, at which time some of them were 25 years old. So I think it is the duplicated publication of data in McAnulty 2009 which is the culprit.

I think the right decision has been made here, once those data points are subtracted, and once the Bayley 1 are evaluated separately to Bayley 2, then it seems unlikely that there will be any difference between NIDCAP and control. So the results were unreliable and the literature is better with a retraction.

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Neonatal Updates

Posted on 27 April 2014 by Keith Barrington

Corvaglia L, Martini S, Battistini B, Rucci P, Aceti A, Faldella G. Bolus versus continuous feeding: effects on splanchnic and cerebral tissue oxygenation in healthy preterm infants. Pediatr Res. 2014. During a 6 hour period, preterm infants had either a bolus feed an a 3 hour infusion of milk. Bolus feeding led to an increase in the intestinal NIRS signal.  A 3 hour infusion led to a decrease. I’m not sure what this means, Randomized comparisons of clinical outcomes generally show now substantial difference between bolus and continuous feeding. So if the oxygenation is lower but the clinical function is OK, do we need to worry?

Fox LM, Choo P, Rogerson SR, Spittle AJ, Anderson PJ, Doyle L, et al. The relationship between ventricular size at 1 month and outcome at 2 years in infants less than 30 weeks’ gestation. Archives of Disease in Childhood – Fetal and Neonatal Edition. 2014;99(3):F209-F14. If you have bigger ventricles, and therefore, on average, less brain, your outcome is worse. That is a facetious comment on an interesting paper, which confirms that one of the better predictors of outcome is ventricular enlargement.

Wang D, Aubertin C, Barrowman N, Moreau K, Dunn S, Harrold J. Examining the effects of a targeted noise reduction program in a neonatal intensive care unit. Archives of Disease in Childhood – Fetal and Neonatal Edition. 2014;99(3):F203-F8. The NICU is a noisy place, especially if you have fragile preterm baby ears. Reducing noise intensity is not very easy, and may even have contrary effects to those that you desire.

Emond A, Ingram J, Johnson D, Blair P, Whitelaw A, Copeland M, et al. Randomised controlled trial of early frenotomy in breastfed infants with mild–moderate tongue-tie. Archives of Disease in Childhood – Fetal and Neonatal Edition. 2014;99(3):F189-F95. Tongue-tie has always been rather controversial, but I think overall the evidence shows that cutting a severe tongue-tie has short term benefits in breast feeding success. This new RCT investigated immediate frenotomy in moderate cases compared to breast feeding support. The primary outcome was the LATCH score of breast-feeding efficacy at 5 days of age, and it was not different between groups: but the proportions of mothers who gave up breast-feeding (a secondary outcome) was substantially lower in the frenotomy group than in the controls. There were no adverse effects noted. So with the usual proviso about secondary outcomes, this appears modestly successful.

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Pulse Oximetry Screening : It’s About Time

Posted on 27 April 2014 by Keith Barrington

It is about time! Timely diagnosis, and timely intervention for children with potentially lethal cardiac defects make an enormous individual difference to their survival and other outcomes.

A new enormous study in the lancet from China (over 120,000 babies screened) has similar findings to the previous studies, showing good sensitivity, low false positives and overall acceptability of pulse oximetry screening of apparently healthy newborns.

The study is accompanied by one of the best editorials that I have read, measured, reasonable, evidence based, and clearly written (Ewer AK. Pulse oximetry screening: do we have enough evidence now? The Lancet). As he notes, the added value of pulse oximetry screening will depend upon the background rate of detection of critical heart disease in your health care system: but all of the studies show some added value. False positives are much less frequent with pulse oximetry screening than with physical exam, so the added burden to your health care system is likely to be quite small, and in developed economies, minimal.

I certainly think it is time that Canada had a national policy, and that we introduced routine universal pulse oximetry screening for our babies.

 

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Treating pneumothoraces? Either a tube or leave them alone.

Posted on 21 April 2014 by Keith Barrington

I never understood why it was recommended to give 100% oxygen to treat a pneumothorax. I think the idea was that the gas in the pneumothorax could be replaced by oxygen which would then be reabsorbed more quickly if we gave oxygen rather than air or another mixture with lower oxygen content and more nitrogen. But that would only work if the pneumothorax was being ventilated, and there was an open bronchopleural fistula, which is not usually the case. so we needed someone to examine the data.

This retrospective study shows absolutely no sign of an effect of giving 100% oxygen. Clark SD, Saker F, Schneeberger MT, Park E, Sutton DW, Littner Y. Administration of 100% oxygen does not hasten resolution of symptomatic spontaneous pneumothorax in neonates. J Perinatol. 2014.

Another therapy to consign to the garbage can of history.

Oxygen is toxic. Oxygen is life saving. Give only as much as you need to maintain ‘adequate saturations’ : whatever they are.

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Something else that doesn’t work in sepsis; albumin

Posted on 21 April 2014 by Keith Barrington

Another multi-center RCT in adults with severe sepsis or septic shock with a negative result. This time 1800 adults in 100 ICUs in Italy were randomized. Fluid boluses were either crystalloid or 20% albumin and crystalloid. Blood pressure was somewhat higher in the albumin group (by a massive 2 mmHg in the mean BP on day 1 and 1 mmHg on day 2), and they had a better short term fluid balance. There were no differences in any clinically important outcome, including the primary outcome of mortality.

The study confirms once more that severe sepsis is bad for you, mortality in both groups was around 40%.

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Bloody Placentas

Posted on 21 April 2014 by Keith Barrington

No, literally.

There is now quite good evidence of the advantages of delayed cord clamping in the term infant, with most particularly an improvement in iron stores in the baby that has lasting effects during the first year of life. The current recommendation is to hold the baby at the level of the vaginal introitus. But it is also recommended to place the baby directly on the mother’s abdomen, and then to encourage immediate skin to skin contact.

So you can’t do both. Keeping the baby at the level of the vagina is recommended in order to encourage the transfusion of placental blood, but it may not be necessary. Gravity may not be that important, as the forces of uterine contraction can probably easily overcome the weight of a few centimeters of a column of blood.

Nestor Vain and colleagues from Argentina have just published a trial in term delivered mother infant pairs where they randomized to either keeping the baby down low, or lifting the baby onto the mother’s abdomen. They weighed the baby as quickly after birth as possible (usually within 15 seconds), and the again after 2 minutes, which is when the cord was clamped and cut.

In both groups the weight  of the baby increased by about 50g, there were no differences by group assignment, and no apparent effect of the position of the mother’s body. There were about 270 babies in each group, with about 80 exclusions in each group, for quite appropriate reasons (c-section, need for resuscitation, cord around the neck etc).

I congratulate Nestor and his colleagues for this study, I would never have thought of doing this, but it is very useful information for obstetricians everywhere, you can deliver the baby onto the mother’s abdomen and delay clamping the cord for 2 minutes; getting the benefits of both early skin to skin contact and placental transfusion.

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