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Showing content with the highest reputation since 10/21/2013 in Blog Entries

  1. 7 points
    It has to be one of the most common questions you will hear uttered in the NICU. What were the cord gases? You have a sick infant in front of you and because we are human and like everything to fit into a nicely packaged box we feel a sense of relief when we are told the cord gases are indeed poor. The congruence fits with our expectation and that makes us feel as if we understand how this baby in front of us looks the way they do. Take the following case though and think about how you feel after reading it. A term infant is born after fetal distress (late deceleration to as low as 50 BPM) is noted on the fetal monitor. The infant is born flat with no heart rate and after five minutes one is detected. By this point the infant has received chest compressions and epinephrine twice via the endotracheal tube. The cord gases are run as the baby is heading off to the NICU for admission and low and behold you get the following results back; pH 7.21, pCO2 61, HCO3 23, lactate 3.5. You find yourself looking at the infant and scratching your head wondering how the baby in front of you that has left you moist with perspiration looks as bad as they do when the tried and true cord gas seems to be betraying you. To make matters worse at one hour of age you get the following result back; pH 6.99, pCO2 55, HCO3 5, lactate 15. Which do you believe? Is there something wrong with the blood gas analyzer? How Common Is This Situation You seem to have an asphyxiated infant but the cord gas isn’t following what you expect as shouldn’t it be low due to the fetal distress that was clearly present? It turns out, a normal or mildly abnormal cord gas may be found in asphyxiated infants just as commonly as what you might expect. In 2012 Yeh P et al looked at this issue in their paper The relationship between umbilical cord arterial pH and serious adverse neonatal outcome: analysis of 51,519 consecutive validated samples. The authors sampled a very large number of babies over a near 20 year period to come up with a sample of 51519 babies and sought to pair the results with what they knew of the outcome for each baby. This is where things get interesting. When looking at the outcome of encephalopathy with seizures and/or death you will note that only 21.71% of the babies with this outcome had a gas under 7.00. If you include those under 7.10 as still being significantly distressed then this percentage rises to 34.21%. In other words almost 66% of babies who have HIE with seizures and/or death have a arterial cord pH above 7.1! The authors did not look at encephalopathy without seizures but these are the worst infants and almost 2/3 have a cord gas that you wouldn’t much as glance at and say “looks fine” How do we reconcile this? The answer lies in the fetal circulation. When an fetus is severely stressed, anaerobic metabolism takes over and produces lactic acid and the metabolic acidosis that we come to expect. For the metabolites to get to the umbilcal artery they must leave the fetal tissues and enter the circulation. If the flow of blood through these tissues is quite poor in the setting of compromised myocardial contractility the acids sit in the tissues. The blood that is therefore sitting in the cord at the time of sampling actually represents blood that was sent to the placenta “when times were good”. When the baby is delivered and we do our job of resuscitating the circulation that is restored then drives the lactic acid into the blood stream and consumes the buffering HCO3 leading to the more typical gases we are accustomed to seeing and reestablishing the congruence our brains so desire. This in fact forms the basis for most HIE protocols which includes a requirement of a cord gas OR arterial blood gas in the first hour of life with a pH < 7.00. Acidosis May Be Good For the Fetus To bend your mind just a little further, animal evidence suggests that those fetuses who develop acidosis may benefit from the same and be at an advantage over those infants who don’t get acidemia. Laptook AR et al published Effects of lactic acid infusions and pH on cerebral blood flow and metabolism. In this study of piglets, infusion of lactic acid improved cerebral blood flow. I would suggest improvement in cerebral blood flow of the stressed fetus would be a good thing. Additionally we know that lactate may be used by the fetus as additional metabolic fuel for the brain which under stress would be another benefit. Finally the acidemic fetus is able to offload O2 to the tissues via the Bohr effect. In case you have forgotten this phenomenon, it is the tendency for oxygen to more readily sever its tie to hemoglobin and move into the tissues. I hope you have found this as interesting as I have in writing it. The next time you see a good cord gas in a depressed infant, pause for a few seconds and ask yourself is this really a good or a bad thing?
  2. 6 points
    It’s been some time since I last posted here. Many things have changed in my life since then- the most important transition being my decision to move to Finland to work as a research fellow with the Baby-friendly Ventilation Study Group in Turku. The life of a beginning clinical researcher deserves a separate post here (it may even come at some point). To celebrate my first anniversary in Finland I would like to share 3 things I wish somebody had told me before I moved here. Enjoy! 1.Get nylon pants. The weather in Finland is truly whimsical. We have had a kind spring, warm summer, and lovely, colorful autumn. I was able to enjoy each of these seasons, biking in the Archipelago, watching sun that never sets, traveling north to see ruska, and finally seeing Northern Lights for the first time in my life. My only concern here is rain. It doesn’t follow laws of gravity AT ALL. How is that possible, that those raindrops are not falling DOWN from the sky, but they are literally attacking you from every direction? It took me some time to overcome my frustration and find a solution. I have closely observed (relatively) happy Finns and discovered that the most important clothing item here is… nylon waterproof pants. The trick is they have to be big enough that you can pull them over your regular pants to keep you dry and warm when it rains. This small thing has definitely improved my comfort here. It has also created that precious feeling of belongingness- I could finally proudly join the rustling and swishing sisterhood of waterproof pants. 2. Drop in the fertility rate is a real thing. Ok, I am a doctor and I KNOW it is a real thing. I know that statistics don’t lie. I know. But I kind of didn’t want to acknowledge that it may actually impact my study. We have had a fairly good start of the patient recruitment, which had kept me busy in spring. But then summer had arrived, and the recruitment slowed down. I kept thinking that maybe it’s just because of the summertime in general (like preemies would be able to pick a season when they want to arrive early, right?). But then autumn has come, and it was time to face the music- I have a problem. In order to recruit the desired number of infants, I may either stay here forever OR I need to come up with a clever solution very soon. Thankfully, I have amazingly supportive supervisors here and we decided- we are expanding! That means more traveling for me (and possibly more blog posts for you)! 3. Compulsive talking about 99nicu may help you to dance more salsa. That statement may seem rather weird, but there is a logical explanation. Very recently I’ve had a chance to attend a regional neonatal meeting in Finland. I was asked to present highlights from the 99nicu Meetup in Copenhagen. Since I like the whole concept of 99nicu.org and loved two conferences I had attended, I took that task very seriously- meticulously prepared my PowerPoint presentation and practiced my performance out loud at home. I decided to tell participants about lectures I remembered the best- neonatal transports, simulations in the NICU and infants surviving at the limit of viability. You may argue that there were more important lectures there, but those were the ones that still “spark joy” after all these months. Do you remember that sim scenario of postpartum seizures in a birthing pool that Ruth Gottstein talked about? I’ve discussed it with so many people in so many places already, that it might have become my favorite topic of random conversations with strangers. Anyways, I think the presentation went well- participants awarded me the prize for the best presentation of the evening! I received a gift card that I can use for cultural or fitness activities in Turku- including more salsa classes in my favorite dance school. Voila! Thank you 99nicu!
  3. 6 points
    Our tiny babies have very tiny tracheas. So far you are probably all with me. Putting that tube in the right position is therefore tricky. In particular avoiding the right mainstem bronchus, which is the wrong position, is important. So first of all; where should the tip be? That seems obvious, it should be in the trachea, high enough above the carina that the tube never slips into the carina, but low enough that it doesn't slip out. On a plain AP radiograph, however, it isn't always clear exactly where the tube tip should be. In general ,studies have suggested that on the radiograph the tip of the tube should be T1-T2. That is based on studies where the position was directly observed, such as in post-mortem studies, and compared with an X-ray. A study from 7 years ago (Thayyil S, et al: Optimal endotracheal tube tip position in extremely premature infants. American journal of perinatology 2008, 25(1):13-16.) noted that babies who had a tube tip lower than T1-T2 were more likely to have right upper lobe collapse, localized PIE and pneumothorax. I think that confirms that T1-T2 is the appropriate location. Now how do we ensure that the tube tip is in that, optimal, position? The NRP (which clearly is not focussed on very preterm babies) suggests to add 6 cm to the infants weight in kg, which leads to tube insertion depths which are too low for most babies under 1 kg (see for example : Peterson J, et al: Accuracy of the 7-8-9 Rule for endotracheal tube placement in the neonate. J Perinatol 2006, 26(6):333-336.) I think it is clear we should not use that rule for babies under 1 kg. Various methods of calculation have been suggested, some are based on calculations using the babies weight, some on gestation, one on foot length (which actually seems to be a good idea, and relatively easy to get to during resuscitation, but I don't know if anyone does that. Embleton ND, et al: Foot length, an accurate predictor of nasotracheal tube length in neonates. Archives of Disease in Childhood - Fetal and Neonatal Edition 2001, 85(1):F60-F64) maybe Nick Embleton will let me know if anyone uses it. A newly published trial from Colm O'Donnel in Dublin (Flinn AM, et al: Estimating the Endotracheal Tube Insertion Depth in Newborns Using Weight or Gestation: A Randomised Trial. Neonatology 2015, 107(3):167-172.) randomly compared weight and gestational age based standards, unfortunately the weight based standard they used was depth= weight + 6, and they compared this to a table based on gestational age. The number of ET tubes in the right place was higher with the weight calculation, but it was not statistically significant, and there were very many that were malpositioned in both groups, 50% with the weight based calculation, and 60% with the GA table. Another study, which also trashed the 7-8-9 rule promoted by NRP, (Kempley ST, et al: Endotracheal tube length for neonatal intubation. Resuscitation 2008, 77(3):369-373) was a report of a quality improvement initiative in London. It is interesting in part because they showed that intubating the baby and then doing a clinical exam to see if it was in the right place was associated with more than half of the ETTs being mal-positioned. While using a table of distances (either GA based or weight based) was much better, with less than 20% needing repositioning. Colm O'Donnell has also published a letter with photos of endotracheal tubes (Gill I, O'Donnell CP: Vocal cord guides on neonatal endotracheal tubes. Archives of disease in childhood Fetal and neonatal edition 2014, 99(4):F344.) which clearly shows that you can't rely on the ETT marks to decide where to put the tube. Non-one ever evaluated this previously, as far as I can tell in the literature, but using those marks will lead to many being in the wrong place. I think it should be obvious that all babies who are intubated with a 2.5 tube do not have the same length of trachea! So using the same ETT tube marking wll often be wrong. So how best to do this? I think that the first step should be to use a table of insertion depth against body weight. (we are a center which attracts a lot of extremely growth restricted babies, so I would be wary of using a GA standard). I think the table below looks to be the best (the table below is from the study which I refer to above by Stephen Kempley) , I have added a column for nasal intubation based on the demonstration (autopsy study,with body weights down to 500 g) that the distance from nostril to carina is almost exactly 1.2 cm on average longer than the distance from lip to carina (Rotschild A, Chitayat D: Optimal Positioning of Endotracheal Tubes for Ventilation of Preterm Infants. AJDC 1991, 145:1007.) During the intubation procedure, prior to fixing the tube, palpation in the supra-sternal notch can confirm good tube position with very good accuracy, once you have been trained to do it. A randomized trial from Neil Finer's group (Jain A, et al: A randomized trial of suprasternal palpation to determine endotracheal tube position in neonates. Resuscitation 2004, 60(3):297-302.) who showed me the technique when I was his fellow) found a much higher proportion of tubes in the right position after adequate training, and another RCT (Saboo AR, et al: Digital palpation of endotracheal tube tip as a method of confirming endotracheal tube position in neonates: an open-label, three-armed randomized controlled trial. Pediatric Anesthesia 2013, 23(10):934-939) had a high proportion of tubes in good position, 83%, following a process such as I have just described, a table of insertion depths, accompanied by palpation to validate position. Here is that table: (sorry but I can't figure out how to make this table a good size, so click on it to view.). ((This is the initial length to which the tube should be inserted, followed by palpation of the tube to ensure good position, and then a chest radiograph to check its position. The tube length should then be adjusted to align its tip with the thoracic vertebrae T1–T2.)) Another important point, flexion of the neck advances the end of the ETT, but, in fact, the sze of the effect is fairly minor. A severe flexion of 55 degrees only advances the tube tip by about 3 mm (Rost JR, Frush DP, Auten RL: Effect of neck position on endotracheal tube location in low birth weight infants. Pediatric Pulmonology 1999, 27(3):199-202). So if the tube is on the carina when you do the x-ray and the head is flexed, you still need to reposition the tube, you can't rely on good head position to move the tube tip up much. Finally there are some data to support using ultrasound to confirm tube position, (Chowdhry R, Dangman B, Pinheiro JM: The concordance of ultrasound technique versus X-ray to confirm endotracheal tube position in neonates. J Perinatol 2015. Dennington D, Vali P, Finer NN, Kim JH: Ultrasound confirmation of endotracheal tube position in neonates. Neonatology 2012, 102(3):185-189.) It looks like this could be a reliable way of identifying malposition of the tube, and we should consider maybe training everyone to do this, including me!
  4. 5 points
    The professional communication during the Covid-19 pandemic really shows the potential to share expertise and experience through web-based channels. Journals, societies, regular news media, social media platforms etc-etc play an important role for us to keep updated, and many web sites have also opened up their content free of charge. We will learn many things from facing and tackling this pandemic, but one major change will certainly be our communication channels. Many are discovering the web-based possibilities to learn and discuss. We will do our best to facilitate professional communication within the neonatal community. And, finally it seems that the company providing our software (IPB) will finally roll out a smartphone app. Which means that 99nicu will literally become available in your pocket through a "99nicu App". The screen shots below comes from the beta-version of the app now used by the company providing our software. And yes, there will be light-mode and dark-mode Stay tuned!
  5. 5 points
    I must admit that it is a bit exciting to think about that 99nicu.org went live 12 years ago, at a time when Facebook and other “social media” web sites was yet to be invented. (@Zuckerberg, no offense here. Obviously, you created something far greater than 99nicu, still a grass rot project. BTW – could we apply for funding from you Foundation?) When starting 99nicu.org in 2006, we nourished an idea that experiences and expertise should not be hindered by geographical boundaries. In some sense, this was a statement, that we as medical professionals could help each other through other channels than journals and conferences, with inclusive and open mindsets, and new technologies. Back then we knew little about the powerful potential of the Internet. Neither could we foresee how the Internet would change our private and professional lives. We were just a group of young staff in Sweden, wanting to create a web based platform for discussions within a global group of neonatal pro’s. When I read this blog post by @AllThingsNeonatal (on his web site allthingsneonatal.com) where he reflects on how sharing and caring in social media has created a global village, I am struck by the thought - a global village was what we envisioned back in 2006. Coming from a small village myself, I think that also 99nicu.org parallells the village symbolism: a setting with small communication gaps (everyone knows everything about everyone, so we don't need formalities to get in touch and speak out), and where giving and taking advice is a bilateral process that may ultimately lead to “the best solution”. Or simply, that we find out that there are several good solutions for a given problem. Has 99nicu become as global village for neonatal staff on the Internet? Although biased, I’d say YES . Data also supports that. During January through April, the web site had 18.000 visitors from all over the globe, making 45.200 pageviews. From the Google Analytics dashboard we can all see that 99nicu reaches almost every corner of the world! Our principal idea has always been that the virtual space is where we operate. It is the Internet that creates the possibility to connect and exchange experience as expertise from where we are. However, meeting up IRL is also a powerful way to maintain sustainable networks and that idea is the driving force behind the “99nicu Meetups”. For the 1st and 2nd Meetup conferences in Stockholm and Vienna (in June 2017 and in April 2018), delegates came from 17 and 33 countries, respectively. Let’s hope we can have even a larger geographical representation at our IRL Meetup next year. Stay tuned for dates and location
  6. 5 points
    I just want to share some brief news about our next Meetup, 7-10 April 2019 at Rigshospitalet in Copenhagen/Denmark. We (i.e myself, @Francesco Cardona @RasmusR @Christian Heiring , Gorm Greisen and Morten Breindahl) are currently working on the program lectures and workshops. I just want to share the first five confirmed speakers and their topics: Morten Breindahl: Neonatal transports – how to do them safe and easy Ola Andersson: Cord Clamping, 1.0 and 2.0 Ravi Patel: How to explain when NEC rates persist – even when a NICU does everything “Right” Ulrika Ådén: Infants surviving at the limit of viability, what are the outcomes? What shall we do? Gorm Greisen: Ethical decision making around the limit of viability- lessons from Scandinavia I'll update you all with more names and topics as they are confirmed Looking forward to meet up in Copenhagen!
  7. 5 points
    The lungs of a preterm infant are so fragile that over time pressure limited time cycled ventilation has given way to volume guaranteed (VG) or at least measured breaths. It really hasn’t been that long that this has been in vogue. As a fellow I moved from one program that only used VG modes to another program where VG may as well have been a four letter word. With time and some good research it has become evident that minimizing excessive tidal volumes by controlling the volume provided with each breath is the way to go in the NICU and was the subject of a Cochrane review entitled Volume-targeted versus pressure-limited ventilation in neonates. In case you missed it, the highlights are that neonates ventilated with volume instead of pressure limits had reduced rates of: death or BPD pneumothoraces hypocarbia severe cranial ultrasound pathologies duration of ventilation These are all outcomes that matter greatly but the question is would starting this approach earlier make an even bigger difference? Volume Ventilation In The Delivery Room I was taught a long time ago that overdistending the lungs of an ELBW in the first few breaths can make the difference between a baby who extubates quickly and one who goes onto have terribly scarred lungs and a reliance on ventilation for a protracted period of time. How do we ventilate the newborn though? Some use a self inflating bag, others an anaesthesia bag and still others a t-piece resuscitator. In each case one either attempts to deliver a PIP using the sensitivity of their hand or sets a pressure as with a t-piece resuscitator and hopes that the delivered volume gets into the lungs. The question though is how much are we giving when we do that? High or Low – Does it make a difference to rates of IVH? One of my favourite groups in Edmonton recently published the following paper; Impact of delivered tidal volume on the occurrence of intraventricular haemorrhage in preterm infants during positive pressure ventilation in the delivery room. This prospective study used a t-piece resuscitator with a flow sensor attached that was able to calculate the volume of each breath delivered over 120 seconds to babies born at < 29 weeks who required support for that duration. In each case the pressure was set at 24 for PIP and +6 for PEEP. The question on the authors’ minds was that all other things being equal (baseline characteristics of the two groups were the same) would 41 infants given a mean volume < 6 ml/kg have less IVH compared to the larger group of 124 with a mean Vt of > 6 ml/kg. Before getting into the results, the median numbers for each group were 5.3 and 8.7 mL/kg respectively for the low and high groups. The higher group having a median quite different than the mean suggests the distribution of values was skewed to the left meaning a greater number of babies were ventilated with lower values but that some ones with higher values dragged the median up. Results IVH < 6 mL/kg > 6 ml/kg p 1 5% 48% 2 2% 13% 3 0 5% 4 5% 35% Grade 3 or 4 6% 27% 0.01 All grades 12% 51% 0.008 Let’s be fair though and acknowledge that much can happen from the time a patient leaves the delivery room until the time of their head ultrasounds. The authors did a reasonable job though of accounting for these things by looking at such variables as NIRS cerebral oxygenation readings, blood pressures, rates of prophylactic indomethacin use all of which might be expected to influence rates of IVH and none were different. The message regardless from this study is that excessive tidal volume delivered after delivery is likely harmful. The problem now is what to do about it? The Quandry Unless I am mistaken there isn’t a volume regulated bag-mask device that we can turn to to control delivered tidal volume. Given that all the babies were treated the same with the same pressures I have to believe that the babies with stiffer lungs responded less in terms of lung expansion so in essence the worse the baby, the better they did in the long run at least from the IVH standpoint. The babies with the more compliant lungs may have suffered from being “too good”. Getting a good seal and providing good breaths with a BVM takes a lot of skill and practice. This is why the t-piece resuscitator grew in popularity so quickly. If you can turn a couple dials and place it over the mouth and nose of a baby you can ventilate a newborn. The challenge though is that there is no feedback. How much volume are you giving when you start with the same settings for everyone? What may seem easy is actually quite complicated in terms of knowing what we are truly delivering to the patient. I would put to you that someone far smarter than I needs to develop a commercially available BVM device with real time feedback on delivered volume rather than pressure. Being able to adjust our pressure settings whether they be manual or set on a device is needed and fast! Perhaps someone reading this might whisper in the ear of an engineer somewhere and figure out how to do this in a device that is low enough cost for everyday use.
  8. 5 points
    I know - many of us want less emails... But the emails from Evidence Updates are great! Evidence Updates (a collaboration project by the BMJ Group and McMaster University) assists your reading of new research by grading articles by "Relevance" and "News-worthiness". For example, this trial on D-vitamin supplementation of preterm infants showed up in an email alert, an article I had missed otherwise. 1. You need to Register (here!) 2. Choose your clinical interest ("Pediatric Neonatology", I guess) 3. Set a minimum score for new articles you want to read about (set a higher minimum score to get fewer emails ) 4. Watch your inbox! Link to like: Evidence Updates.
  9. 5 points
    Originally posted at: https://winnipegneonatal.wordpress.com/ Facebook Page: https://www.facebook.com/allthingsneonatal/ As I read through the new NRP recommendations and began posting interesting points on my Facebook Page I came across a section which has left me a little uneasy. With respect to a newborn 36 weeks and above who is born asystolic and by ten minutes of age continues to remain so and has an apgar score of zero the recommendation that has been put forward is this: An Apgar score of 0 at 10 minutes is a strong predictor of mortality and morbidity in late-preterm and term infants. We suggest that, in babies with an Apgar score of 0 after 10 minutes of resuscitation, if the heart rate remains undetectable, it may be reasonable to stop resuscitation; however, the decision to continue or discontinue resuscitative efforts should be individualized. Variables to be considered may include whether the resuscitation was considered to be optimal, availability of advanced neonatal care, such as therapeutic hypothermia, specific circumstances before delivery (eg, known timing of the insult), and wishes expressed by the family (weak recommendation, very-low-quality evidence). There are some significant problems with this part of the statement. They claim that the apgar score at ten minutes is a strong predictor but when you look at the analysis of the evidence presented in the body of the paper it is weak at best. I am not clear how one declares the prediction is strong in the face of poor evidence but I will acknowledge intuitively that this makes some sense but do challenge them on the use of the word "strong". 2. They are correct in acknowledging that the introduction of hypothermia in such settings has changed the landscape in as much as I find it quite difficult to prognosticate unless a child is truly moribund after resuscitation. Given such uncertainty it is concerning to me that this recommendation may be committed to memory incorrectly in some places that do have access to cooling and may be used more rigidly as though shalt stop at 10 minutes. 3. In the middle of a resuscitation it is quite difficult to process all of the facts pertaining to a particular newborn while orders for chest compressions, emergency UVCs and epinephrine are being given. Can we really individualize within ten minutes accurately and take the families wishes truly into account? This just does not seem practical. 4. The families wishes are taken into account but inserted as a "weak recommendation". How can the wishes of the family in any family centred model of care be minimized in such a way even if we believe the situation to be dire? 5. Since the introduction of hypothermia there appears to be a near 50% survival rate in such newborns and as the authors state 27% of survivors who received cooling had no moderate or severe disability. Here in lies my greatest issue with this guideline and that is the hypocrisy this position takes when you compare populations at 23 and 24 weeks gestational age. Survival at these GA in the recent NEJM study of almost 5000 preterm infants under 27 weeks were 33 and 57 % respectively at 23 & 24 weeks with rates of survival without moderate or severe disability being 16 and 31% in the two groups. The fallout from this and other studies at the extremes of gestational age have been that we should be more aggressive as the outcomes are not as bad as one would predict. How can we argue this for the 23-24 week infants and for term infant with the same likelihood of outcomes we would unilaterally stop in many centres?! So Now What Do We Do? We are supposed to be practising family centred care and much like the argument at the edge of viability the same should apply here. The wishes of the family should never be minimized. Arguably it may be very difficult in such an unexpected scenario to appraise a family of the situation and have clarity around the issue but if a heart rate can be restored after a few more minutes do we not owe it to the family and the child to bring the infant back to the NICU and see what transpires especially if cooling is available? The million dollar question of course is where do we draw the line? No heart rate at 15, 20 minutes? Based on the evidence thus far it seems to me that a little longer than 10 minutes is reasonable especially in well equipped centres with access to cooling and modern ventilation and treatments for pulmonary hypertension. How long though must be individualized and should be determined in partnership with the team caring for the patient which must include the family.
  10. 4 points
    First off I should let you know that we do not do transpyloric feeding for our infants with BPD. Having said that I am aware of some units that do. I suspect the approach is a bit polarizing. A recent survey I posted to twitter revealed the following findings: I think the data from this small poll reveal that while there is a bias towards NG feeds, there is no universal approach (as with many things in NICU). Conceptually, units that are using transpyloric feeds would do so based on a belief that bypassing the stomach would lead to less reflux and risk of aspiration. The question though is whether this really works or not. New N of 1 Trial I don’t think I have talked about N of 1 trials before on this site. The trials in essence allow one patient to serve as a study unto themselves by randomizing treatments over time for the single patient. By exposing the patient to alternating treatments such as nasogastric or nasoduodenal feedings one can look at an outcome and get a sense of causality if a negative or positive outcome occurs during one of the periods consistently. That is what was done in the study Individualising care in severe bronchopulmonary dysplasia: a series of N-of-1 trials comparing transpyloric and gastric feeding by Jensen E et al from the Children’s Hospital of Philadelphia. The authors in this study determined that using a primary outcome of frequency of daily intermittent hypoxaemic events (SpO2 ≤80% lasting 10–180 s) they would need 15 patients undergoing N of 1 trials between nasogastric and nasoduodenal feeding. Included infants were born at <32 weeks and were getting positive airway pressure and full enteral nutrition at 36 0/7 to 55 6/7 weeks PMA. Infants who were felt to be demonstrating signs of reflux or frank regurgitation were enrolled. The findings Thirteen of 15 enrolled patients completed the study. The two who did not complete did so as their oxygen requirements increased shortly after starting the trial and the clinical team removed them and chose their preferred route of feeding. Randomization looked like this: Of the 13 though that completed and using an intention to treat analysis of the other two the findings were somewhat surprising. Contrary to what one might have thought that transpyloric would be a lung protective strategy, the findings were opposite. Overall the combined results from these 15 patients demonstrated that nasogastric feedings were protective from having intermittent hypoxic events. How can this be explained? To be honest I don’t really know but it is always fun to speculate. I can’t help but wonder if the lack of milk in the stomach led to an inability to neutralize the stomach pH. Perhaps distension has nothing to do with reflux and those with BPD who have respiratory distress with some degree of hyperinflation simply are prone to refluxing acid contents due to a change in the relationship of the diaphragmatic cura? It could simply be that while the volume in the stomach is less, what is being refluxed is of a higher acidity and leads to more bronchospasm and hypoxemic events. What seems to be clear even with this small study is that there really is no evidence from this prospective trial that transpyloric feeding is better than nasogastric. Given the size of the study it is always worth having some degree of caution before embracing wholeheartedly these findings. No doubt someone will argue that a larger study is needed to confirm these findings. In the meantime for those who are routinely using the transpyloric route I believe what this study does at the very least is give reason to pause and consider what evidence you have to really support the practice of using that route.
  11. 4 points
    If you are to read one paper on neonatal ethics this year, I'd argue that this is the one. Late last year, John Lantos, pediatrician and a leading medical ethicist, published a review in NEJM on the ethics around decision-making in the NICU. The paper is not open-access... but you can surely get it from within your hospital intranet or your university/hospital library. We have a fantastic toolbox in the NICU. We can provide live-saving treatments and support. Most newborns in the NICU survive to good long-term health. However, we also operate in a high-risk environment where some infant may suffer, some infants will die, and some infants will survive with difficult sequele. Which raises the question, by staff and by parents, what is the "right" thing to do in complex situations. When withholding and withdrawing life-sustaining therapies becomes a option to decide upon. How could we navigate in this landscape? IMHO, the review by Lantos is a good starting point on how to form a local practise. Lantos shares his reasoning about we cannot "solve" these discussion with "information" as such. Despite how hard we try, data alone does not lead the whole way. Outcomes is hard to measure, they change over time and we all percieve risks differently. Therefore, information is difficult to standardize. Furthermore, those of us sharing the information will filter our presentation through our subjective selves, coping with opinions, experiences and our expertise in different ways. The better alternative around ethical questions is shared decision-making. Two central quotes of the review is that and that Certainly, the future of neonatal care will bring more ethical questions to us. Refined prenatal diagnostics, the down-shifting boundary of viability and new treatment technologies in the future (like the artificial placenta) will impact how we think about fetal life and postnatal life, what is the "periviable grey zone" and what our fantastic toolbox can do. While improving our skills, from a medical/technical viewpoint, we also need to improve how we cope with the ethics around decision-making processes. Besides reading the review by John Lantos, I can recommend you to see this lecture from theh #99nicuMeetup in Copenhagen 2019, by Eduard Verhagen. (Feature Photo : Cropped photo by Liane Metzler on Unsplash)
  12. 4 points
    This has been a question that has befuddled Neonatologists for years. Get ten of us in a room and you will get a variety of responses ranging from (talking about caffeine base) 2.5 mg/kg/day to 10 mg/kg/day. We will espouse all of our reasons and question the issue of safety at higher doses but in the end do we really know? As I was speaking to a colleague in Calgary yesterday we talked about how convinced we are of our current management strategies but how we both recognize that half of what we think we know today we will be questioning in 10 years. So how convinced should we really be about caffeine? Even the Cochrane Review Suggests There Is Something Amiss Back in 2010 the Cochrane Collaboration examining 6 trials on caffeine for treating apnea of prematurity concluded “Methylxanthine is effective in reducing the number of apnoeic attacks and the use of mechanical ventilation in the two to seven days after starting treatment.” Notice the bolded section. Two to seven days. Interesting that we don’t see the effect last in perpetuity. Why might that be? Do babies become resistant with time or is there a change in the way these infants metabolize the drug such that levels in the bloodstream drop after that time point. It is almost certainly the latter and in the last 7 years have we really seen any response to this finding? I would say no for the most part although I don’t work in your unit so hard to say for sure. At least where I practice we pick a dose somewhere between 2.5-5 mg/kg/day and give a load of 10 mg/kg when we start the drug. From time to time we give a miniload of 5 mg/kg and may or may not increase the dose of maintenance based on the number of apneic events the babies are having. What if we could be proactive instead of reactive though. Do the babies need to have multiple events before we act or could we prevent the events from happening at all? Proactive Treatment With Caffeine We have known that caffeine clearance increases with postnatal age. The half-life of the drug shortens from about a week at the earliest gestational ages to 2-2.5 days by term equivalent age. For those infants who are older such as 32 weeks and above we expect them to be off caffeine (if they need it) within 2-3 weeks so I am not really talking about them but what about the babies born earlier than that or certainly MUCH earlier at 23 and 24 weeks who will be on caffeine possibly till term. Should one size (dose) fit all? No it really shouldn’t and some crafty researchers led by Koch G have published a paper that demonstrates why entitled Caffeine Citrate Dosing Adjustments to Assure Stable Caffeine Concentrations in Preterm Neonates. In this paper the authors armed with knowledge of the half life of caffeine at different gestational ages were able to calculate the clearance of the drug at different postnatal ages to demonstrate in a model of a 28 week male infant weighing 1150g. The authors further took into account predicted weight changes and were able to calculate what the expected caffeine levels would be in the fictional infant at various time points. The target caffeine levels for this patient were a trough level of 15 -20 mg/L which are the currently acceptable ranges in the literature. The testing was first done using a standard load of 10 mg/kg (base) followed by 5 mg/kg/d and demonstrated levels which yielded the following graph over time. What this demonstrates is that if the dose is unchanged over the first 7 weeks, this hypothetical infant will only achieve effective concentrations for the first week. Interesting isn’t it that the Cochrane review found clinical effect over the first 2-7 days? What if you were to double the dose to really “hit” the infant with a good dose of caffeine from the start and maintain at that level based on their weight gain as shown next. Well, you will get what you are hoping for and keep the trough level above 15 mg/L but you will hit 30 mg/L that some have said is too high and can lead to adverse effects (ever seen SVT with these high doses? I have). Like Goldilocks and the Three Bears could there be a dosing strategy that might be just right? The authors put in another model based on the knowledge of caffeine clearance over time and suggested a strategy in which after the first week the adjusted maintenance doses would be 3 mg/kg/day and 3.5 mg/kg/day in the third to fourth weeks and lastly 4 mg/kg/d in the 5th to 8th week. Using that dosing schedule the model produced this curve. As you can see, the infant would have a therapeutic target without reaching levels above 30 mg/L and potential for side effects. As many of you read this however you may ask the obvious question. Each of us have seen infants who require higher doses than this to rid themselves of significant apnea and escape reintubation. Given that this is a mathematical model it assumes that this fictional infant will respond beautifully to a trough level of 15 to 20 mg/L but some will not. Even in the curve shown it is clear that there is some room to go higher in the dosing as the curve is just touching 20 mg/L. A Suggestion For The Future What grabbed my attention here is the possibility that we could take a proactive rather than reactive approach to these infants. Once a small baby is controlled on their dose of caffeine whether it is 2.5, 3, 5 or even 6 mg/kg/d of caffeine should we wait for more events to occur and then react by increasing caffeine? What if we are too late to respond and the patient is intubated. What effect does this have on the developing lung, what about the brain that is subjected to bradycardic events with resultant drops in cardiac output and cerebral perfusion. Perhaps the solution is to work with our pharmacists and plan to increase dosing at several time points in the infants journey through the NICU even if they aren’t showing symptoms yet. No doubt this is a change in approach at least for the unit I work in but one that should start with a conversation!
  13. 4 points
    I have never been convinced that fluid restriction is a good thing for kids with BPD. I think the common practice came about because of the short-term improvements in lung function that sometimes follow if you start diuretics. The idea being that if diuretics improve lung function, then giving less fluid will also. But this is a false equivalency, diuretics cause sodium depletion, and therefore decrease total body water, and probably lung water content also. Fluid restriction in contrast leads to a reduction in urine output, and, within clinically reasonable limits, will not have an impact on total body water, and there is no reason to believe that they will reduce lung water content either. Diuretics may have other direct effects on pulmonary function, that will not occur with fluid restriction. Inhaled furosemide, for example, improves pulmonary mechanics in BPD, presumably by acting on the same sort of ion pump that loop diuretics block in the kidney. Even in adults with fluid overload (those with oedematous congestive heart failure) RCTs of fluid restricion show no effect, unless sodium intake is also severely restricted. Sodium restriction alone works as well, so the fluid restriction adds nothing. Despite this, there are recommendations from usually reliable people that babies with BPD should have their fluid intake restricted, such recommendations are often accompanied by a reference, usually a reference to another recommendation or to a narrative-type review article. I have been planning for years to do a systematic review for the Cochrane library, of fluid restriction as treatment for early or established BPD. We have finally finished the review and it has just appeared. (Barrington KJ, Fortin-Pellerin E, Pennaforte T. Fluid restriction for treatment of preterm infants with chronic lung disease. Cochrane Database of Systematic Reviews. 2017(2).) Using the usual search procedures we could only find one relevant trial. In fact the initial search didn't find the article (Fewtrell MS, et al. Randomized trial of high nutrient density formula versus standard formula in chronic lung disease. Acta Paediatrica. 1997;86(6):577-82.) even though I knew it existed; the Pubmed key words did not mention fluid volumes or restriction, so we tweaked the search to ensure that we found the article, and to make sure that we would find any others that exist. So the only RCT evidence addressing fluid restriction is a study of 60 preterm babies with early chronic lung disease (needing oxygen at 28 days of age) who were randomized to either get 180 mL/kg/day of a regular formula, or 145 mL/kg/d of a concentrated formula. Unfortunately they didn't report on one of our outcomes, oxygen requirement at 36 weeks, as it wasn't the standard outcome that it has since become. That study showed no benefit of fluid restriction on any outcome. The fluid restricted group had more apneas, a finding unlikely to be due to chance, and also had more babies who needed more than 30% oxygen during the trial, a difference which may have been due to chance. Fluid restriction risks nutritional restriction also; even though the idea may be to reduce the free water intake, babies often get fewer calories and less protein when fluid restricted, while babies with BPD actually need more calories. They will also produce more concentrated urine, which might increase the risk of nephroclacinosis as well. The final message is that there is no evidence to support the practice of fluid restriction of babies with early or established BPD. There is no physiologic rationale either. There are potential risks to the practice. We should stop doing it.
  14. 4 points
    It is one of the first things that a medical student pledges to do; that is to do no harm. We are a fearful lot, wanting to do what is best for our patients while minimizing any pain and suffering along the way. This is an admirable goal and one which I would hope all practitioners would strive to excel at. There are times however when we can inadvertently cause more harm than good when we try to avoid what we perceive is the greater harm. This is the case when it comes to collecting a sample of urine for culture as part of a full septic workup. If you ask most healthcare providers they will freely acknowledge that the gold standard for determining whether an infant has a UTI is a supra pubic aspirate (SPA). We so rarely do them these days however due to a whole host of reasons. Problems with collection include the timing and accuracy of needle placement both of which may often lead to an empty tap. Secondly after a number of missed attempts and a crying infant who appears to be in pain it is understandable why bedside nurses may become frustrated with the entire experience and urge the person performing such procedures to settle on a bladder catheterization (BC) to obtain the specimen. The Study That Compares BC and SPA Head to Head A recent Turkish study by Eliacik K et al published A Comparison of Bladder Catheterization and Suprapubic Aspiration Methods for Urine Sample Collection From Infants With a Suspected Urinary Tract Infection and should give us all cause for concern. The authors performed SPA on 83 infants under 12 months with a positive urine culture by BC but who had not yet started antibiotics. The outcome of interest was both the comparison with the culture result and to see if urinalysis from the BC could increase the strength of the information gleaned from a BC. All in all the BC performed quite poorly when compared to the gold standard. The false positive rate compared to SPA was 71.1%! That is to say that only 28.9% of SPA samples were positive compared to BC. Similarly urinalysis sensitivity and specificity from BC were 66.7% (95% CI, 44.68% to 84.33%) and 93.22% (95% CI, 83.53% to 98.08%), respectively. This means that only 2/3 of the time was the urinalysis abnormal on a BC in the presence of a true UTI. Somewhat reassuring is that when there really was no UTI the urinalysis was mostly negative but in almost 1/10 patients it would not by itself rule out a UTI. What Is The Harm in Continuing BC Instead of SPA? When we try to avoid the perceived painful experience of a SPA we are going to wind up treating a large number of patients for a presumed UTI who don't have one. The harm in this is the exposure of such infants to prolonged courses of antibiotics which has been a subject discussed many times over on this site. We put our patients at risk of antibiotic resistance and shifts in the gut microbiome which in the case of the preterm infant puts them at risk of necrotizing enterocolitis. There are many other concerns with prolonging antibiotics but these few should be reason enough to strive for accuracy in obtaining the right specimen in the right way. Putting it in a slightly different perspective, would you settle for an alternative test to a lumbar puncture which claimed to miss 1 in 10 cases and also found meningitis where there was none 71.1% of the time?! A Way Forward - A Recipe For Success As the saying goes, measure twice and cut once. With the use of bedside ultrasound there should be no need to guess as to whether the bladder is full or not. Secondly the placement of the needle should no longer need to rely on landmarking but actually seeing where the best place for needle placement is. Assessing the bladder by ultrasound is easy and is already employed at the bedside by nurses in many areas of the hospital. There should no longer be a reason for the empty tap as the practitioner can be called when the baby is ready as evidenced by a good amount of urine in the bladder. Given that we have some time to do the blood culture and LP, while we wait for the SPA to be done either sucrose in the premature infant or IV analgesic may be given for the SPA while in the term or older infant there is an opportunity to put a topical analgesic cream over the site. There really is little need for pain to factor into this any longer. Ask any health care provider and they will tell you they want to do the best they can for their patient. This study shows us that performing a BC is failing to meet that goal. We need to change our ways and return to the practice of the SPA but this time we have to get it right.
  15. 4 points
    Three recent-(ish) articles examining how we should ventilate babies and monitor what we are doing. Milner A, Murthy V, Bhat P, Fox G, Campbell ME, Milner AD, et al. Evaluation of respiratory function monitoring at the resuscitation of prematurely born infants. Eur J Pediatr. 2014:1-4. In this study, respiratory function monitoring with tidal volume, airway pressure and exhaled CO2 was routinely introduced in 2 London hospitals. The authors then asked trainees whether they found it useful, and what they thought the right tidal volume should be. As you might imagine the answers were quite variable, and integrating more than one sign, such as a lack of exhaled CO2 despite measured tidal volumes, was quite variable. van Vonderen JJ, Hooper SB, Hummler HD, Lopriore E, Te Pas AB. Effects of a Sustained Inflation in Preterm Infants at Birth. The Journal of pediatrics. 2014. Tony Milner was one of the authors of that previous article; many years ago he demonstrated that standard ventilation techniques led to an apparent 'opening pressure', where a substantial positive pressure was required to get air into the lungs, and that the end-expiratory volume of the lungs in the first few breaths remained very low. In contrast a long slow inflation (3 to 5 seconds) eliminated the opening pressure, in intubated babies, and led to establishment of an FRC. This new article used a pressure of 25 cmH2O and duration of 10 seconds, delivered by face mask, but was unable to show the establishment of an FRC, unless the babies were breathing. Murthy V, Creagh N, Peacock J, Fox G, Campbell M, Milner A, et al. Inflation times during resuscitation of preterm infants. Eur J Pediatr. 2012;171(5):843-6. This observational study during resuscitation, using the same respiratory function set up as in the first article, could not show that the variation in inflation times which occurred by chance during resuscitation (from 0.3 to 3 seconds) did not affect inspiratory flow duration. Neil Finer reviews the current state of the art of prolonged inflations, his conclusion: 'not ready for prime time'. Schilleman K, Witlox RS, van Vonderen JJ, Roegholt E, Walther FJ, te Pas AB. Auditing documentation on delivery room management using video and physiological recordings. Archives of Disease in Childhood - Fetal and Neonatal Edition. 2014. If you video record resuscitations, and then compare the tapes to what is actually written in the patients chart, this is what you get: Hmmm.. maybe we need cameras everywhere and make the recordings part of the patients chart... or maybe not!
  16. 3 points
    I recently had the honour of being asked to present grand rounds at the University of Manitoba. My former Department Head during the question period stumped me when he asked me what role angiotensin converting enzyme 2 receptor (ACE2) has in pediatric COVID19. Like all great teachers, after I floundered and had to confess that while I was aware there is a role in COVID19 I wasn’t sure of the answer, he sent me a paper on the subject. The reality is that a very small percentage of COVID19 illness is found in children. Some estimates have it at 2%. Why might that be? It’s what’s in the nose that matters What has been known for some time know is that the point of entry for SARS-CoV-2 is the nasal epithelium. What is also known is that the receptor that the virus binds to in order to gain access to the host. Such binding and what happens after the virus gains entry to the body is shown in this figure depicting the life cycle of SARS-CoV-2. In a research letter by Bunyavanich et al Nasal Gene Expression of Angiotensin-Converting Enzyme 2 in Children and Adults looked at 305 patients from ages 4-60 years to examine biomarkers of asthma. In the course of looking at the nasal epithelium of these patients, they found age related differences in the expression of ACE2 receptors as shown in the following figure. I think the results somewhat speak for themselves. The younger you are the less receptors you have. If you have less receptors maybe you are less likely to contract the virus! What we don’t know This research leads to some interesting questions. Drugs such as losartan and valsartan already exist and function by blocking he ACE2 receptor. Could blockade help to limit the spread of infection? I am not aware of any such trials going on at the moment but something worth looking at. The other point that needs to be raised is that the most vulnerable group of ages >60 were not looked at in this study. The trend would certainly indicate that with age we would expect the receptor numbers to increase but since we don’t actually have the data in the older groups we don’t know if receptor numbers start to fall again with age. Similarly we don’t know below the age of 4 what receptor numbers are like. In examining risk of vertical transmission it is worth noting that the recent placental positive RT-PCRs as in Detection of SARS-COV-2 in Placental and Fetal Membrane Samples. In that study while 3 of 11 placental membranes tested positive, none of the newborns were infected. Could it be the fetus and newborn is protected by having very little density of ACE2 receptors? Something to look at and will be no doubt. Regardless, in the fight against COVID19 maybe one direction for therapeutic targeting should be addressing this receptor and seeing if there is something we can’t do to make it less susceptible to binding.
  17. 3 points
    Dear fellow Ph.D. students, full-time researchers, and other fellow scientists, please #staythefuckhome. In many grant proposals, we write "this research has the potential to save lives, because... ". Let's face it- most of our research won't save lives (or at least not at once)*. No matter how fantastic our research projects are, science takes time. But what can actually save lives immediately is US STAYING HOME. This way we - the (relatively) young people in big academic campuses- won't be spreading the virus that might be deadly for others: for an old lady in the shop (who takes care of her ill husband at home), our senior supervisor (who is also an attending in the unit, so in case he gets sick, they would be running understaffed), a young mother (who will have only moderate symptoms, but will have to arrange some care for her children- possibly transferring them to her own parents, exposing them to an infection). Let's think outside of our own bubble. I don't know if there's much more we can do, but if we are lucky, it might be just enough. Work from home, write from home, think from home, read from home. We always complain that there's not enough time to read and learn- here's your chance! And if your main area of interest is neonatology, there's a fantastic treat for you- if you stay home. Karolinska NIDCAP Training and Research Center organizes a *fabulous* online conference. Go to their pages, write an email (stina.klemming@sll.se) and get your link to access this amazing event. Kind regards, Katarzyna #staythefuckhome Piatek *unless you're actually working on the vaccine or new drug for coronavirus- then just keep working ❤️
  18. 3 points
    After watching a documentary in ARTE about bacteriophages it made me think about how else is antibiotic resistance in NICU.? It available french / German Here the story phages was told. First discovered use by Felix Derrel to combat infections in the pre-antibiotics era and was later discredited and forget about in the western world Historically they worked rather well, so there is an attempt to bring them back in the light of increasing antibiotics resistance. This rediscovery started with lab study that showed that the phages were effective at clearing infection in rats population sample. Phagoburn Recently, a French team took it to human and show it feasible despite the many challenges. This study was a RCT which a specific process approval and protocols were established. The aim in *Phagoburn*was to see if phages could be useful using to fight infection in burn victims. It was lead by Dr. Patrick Jault and large team .Jerôme Gabbard head Start up tells Pherecydes provided the synthesis of phages. control got standard treatment {silver salts +antiobiotics} and othe got phages.This got published in nature. The was a reduction in the infection rate in phage group, a loading dosing issue among other practical things. Researchers in france say that there a scaling issue to produce larger amounts, as well a regulatory framework. From bioethical point of view it is possible, a more detail informed consent will be necessary.These days research still going a la Croix de Lion Hospital, France. University Hospital ~CHU Lyon~. ( initial used - discovered @pasteur Institute) https://www.arte.tv/fr/videos/078693-000-A/l-incroyable-histoire-des-tueurs-de-bacteries/ Thus what do think any future of phage in NICU?
  19. 3 points
    Oral immune therapy (OIT) has really taken off at least in our units. The notion here is that provision of small amounts (0.2 mL intrabucally q2or 24 hours) can prime the immune system. Lymphoid tissue present in the oropharynx and intestine exposed to this liquid gold in theory will give the immune system a boost and increase levels of IgA. Such rises in IgA could help improve the mucosal defence barrier and therefore lessen the incidence of late onset sepsis. Rodriguez et al described this in their paper Oropharyngeal administration of colostrum to extremely low birth weight infants: theoretical perspectives in 2009. They followed it up the next year with a pilot study demonstrating how to actually administer such therapy. The fact that this approach has been adopted so quickly I think speaks to the principle that this kind of therapy falls into the category of “can’t hurt and might help”. The real question though is does it actually make a difference? Recently, authors from Brazil presented their findings from a single centre double blind RCT entitled Randomized Controlled Trial of Oropharyngeal Colostrum Administration in Very-low-birth-weight Preterm Infants. This authors are commended for studying this practice in such a fashion and included infants <34 weeks who were <1500g at birth to receive the above mentioned intervention. These infants were compared to placebo who received the same intervention except instead of mother’s own colostrum they were given sterile water. In total there were 149 infants randomized with 81 receiving OIT vs 68 who received a placebo. The primary outcome of interest on which a power calculation was performed was the incidence of late onset sepsis. Other typical outcomes including NEC, ROP, BPD, IVH and death were also followed. Did they find a difference? Sadly to many of you I am sure they did not as is shown in the table below. Surprisingly the authors also looked at levels of IgA in infants in both arms and also found no difference. There is a big problem with this study however that no doubt will lead to a repeat version at some point. While the authors enrolled the numbers above, the numbers that were analyzed in the table are 34 lower in the OIT arm and only 2 lower in the placebo group. In essence, a large number of mothers after enrollment were not able to provide the colostrum that was needed for the study. The study called for 48 applications over a 48 hour period and a little more than half of the mothers were able to do it. Do not be dismayed then that no difference was found here. There is no need to “throw the baby out with the bathwater” and abandon OIT based on this one study. I think what is needed in the future though is a study that enrolls far more than needed to account for attrition due to loss of mothers who can complete the study. Without another study I think the practice will continue but does it really make a difference to rates of sepsis? Who knows but there is no doubt it helps parents who are feeling that they have lost control of a pregnancy that has gone wrong, a positive experience and the feeling that they are doing something for their child.
  20. 3 points
    To be sure there are fans of both HFNC and CPAP out there. I have often heard from other Neonatologists that they use HFNC and find positive results while other centres refuse to use it in favour of the tried and true CPAP. Turning to the literature you will find some conflicting results with some studies suggesting equity and others more recently favouring CPAP. There has been speculation as to why one would be superior to the other and now we appear to have some answers as to where the differences lie. A Physiologic Study Liew et al published Physiological effects of high-flow nasal cannula therapy in preterm infants this month in an elegant study of 40 infants. The study was fairly simple in design either randomizing infants <37 weeks to starting with nCPAP +6 and then transitioning to 8 l/min HFNC followed by stepwise reductions of 1 l/min until 2 l/min was reached or the reverse, starting with 2 l/min and working their way up and then transitioning to nCPAP+6. All infants were on one or the other modality at the start and were all at least 3 days old, they were randomized to one or the other arm regardless of where they started off. Physiologic measurements were taken at each step including the following: Mv -Minute ventilation pEEP – nasopharyngeal end-expiratory pressure pEECO2 -nasopharyngeal end-expiratory CO2 RR – respiratory rate; SpO2 – oxygen saturation TCCO2 – transcutaneous CO2 Vt – tidal volume A Fabian device was used to deliver either HFNC or CPAP at the different flows for all patients. The Results The authors certainly found some interesting results that I think shed some light on why comparisons of HFNC and CPAP have been so inconsistent. Table 2 contains the results of the study and I will point out the main findings below. 1. Flow matters – Compared to nCPAP+6 which is fairly consistent flows below 6 l/min deliver pEEP that is below 6 cm H2O. 2. Keep the mouth shut – With CPAP whether the mouth is open or closed the Fabian device delivers +6 cm H2O. As you can see from the table, when the mouth is open transmitted pressures drop off substantially. The infant put on a flow of even 6-8 l/min of HFNC sees pressures less than +6 consistently. 3. As flows increase end expiratory CO2 decreases. HFNC seems to help wash out CO2 4. Low flow rates on HFNC do not seem to help with ventilation as much as higher flow rates. In order to maintain Mv these infants at 2 l/min flow become tachypneic. The low pressures produced likely cause some atelectasis and hence tachypnea. Size matters! Beware of excessive pressures. An additional finding of this study was that on “multiple linear regression, flow rate, mouth position, current weight and gestation but not prong-to-nares ratio significantly predicted pEEP and account for a significant amount of its variance (F(4431)=143.768, p<0.0001), R2=0.572, R2=adjusted 0.568).” Essentially, infants under 1000g in particular could see pEEP levels as high as 13 cm H2O with flows of 8 l/min. The variability in transmitted pressures with HFNC is shown nicely in this figure from the study. As flows increase above 6 l/min the actual pressures delivered become less reliable. Conclusions Looking at this data, it becomes evident why HFNC may be failing in its attempt to dethrone nCPAP. In order to achieve higher pressures and provide comparable distending pressure to nCPAP you need higher flows. With higher flows though come the problem of greater variability in delivered pressure. While the average pressure delivered may be equivalent or even higher than a CPAP of +6, in some infants (especially those below 1000g) one may be delivering significantly higher pressures than intended which may help with oxygenation and preventing intubation but others may be seeing far less than needed. What it comes down to is that nCPAP is better at delivering a consistent amount of pressure. Studies using lower flows of HFNC likely failed to show superiority to CPAP as they just didn’t deliver enough pressure. An example of this was the study by Roberts CT et al Nasal High-Flow Therapy for Primary Respiratory Support in Preterm Infants, in which flows of 6-8 l/min were used. Other studies using higher pressures could have been problematic due to open mouths, or larger babies not receiving as much benefit. I am not saying that we should throw out HFNC entirely however. Depending on the unit you practice in you might not be able to use CPAP but HFNC may be allowed. If you had to choose between no support or HFNC I would likely go with the HFNC. For me at least, if I want to delivery reliable pressures in my tertiary care NICU I will be calling for the CPAP.
  21. 3 points
    Just about all of our preterm infants born at <29 weeks start life out the same in terms of neurological injury. There are of course some infants who may have suffered ischemic injury in utero or an IVH but most are born with their story yet to be told. I think intuitively we have known for some time that the way we resuscitate matters. Establishing an FRC by inflating the lungs of these infants after delivery is a must but as the saying goes the devil is in the details. The Edmonton group led by Dr. Schmolzer has had several papers examined in these blogs and on this occasion I am reviewing an important paper that really is a follow-up study to a previous one looking at the impact of high tidal volume delivery after birth. I have written on this previous paper before in It's possibile! Resuscitation with volume ventilation after delivery. On this occasion the authors have published the following paper; Impact of delivered tidal volume on the occurrence of intraventricular haemorrhage in preterm infants during positive pressure ventilation in the delivery room.This observational study had a simple enough premise. Will the use of Vt > 6 mL/kg in infants given PPV for at least two minutes lead to worse rates of IVH? All infants were < 29 weeks and if they had chest compressions or epinephrine were excluded. All infants were treated equally in terms of delayed cord clamping and antenatal steroid provision. Ventilation was done with a t-piece resuscitator and Vt measured with an NM3 monitor connected to the face mask. First ultrasounds were done for all at 3 days of age. What did the authors find? One hundred and sixty five infants comprised this cohort. Overall, 124 (75%) infants were in the high volume group compared to 41 (25%) with a mean VT<6 mL/kg. Median Vt were 5.3 (4.6-5.7) ml/kg for the low group and 8.7(7.3-10.6) mL/kg which were significantly different. When looking at the rates of IVH and the severity of those affected the results are striking as shown in the table. Hydrocephalus, following IVH developed in 7/49 (14%) and 2/16 (13%) in the >6 mL/kg and <6 mL/kg VT groups. Looking at other factors that could affect the outcome of interest the authors noted the following physiologic findings. Oxygen saturations were lower in the low volume group at 6, 13 and 14 min after birth while tissue oxygenation as measured by NIRS was similarly lower at 7,8 and 25 min after birth (P<0.001). Conversely, heart rate was significantly lower in the VT>6 mL/kg group at 5, 20 and 25 min after birth (P<0.001). Fraction of inspired oxygen was similar in both groups within the first 30 min. Systolic, diastolic and mean blood pressure was similar between the groups. What these results say to me is that despite having lower oxygen saturations and cerebral oxygen saturation at various time points in the first 25 minutes of life the infants seem to be better off given that HR was lower in those given higher volumes despite similar FiO2. Rates of volume support after admission were slightly higher in the high volume group but inotrope usage appears to be not significantly different. Prophylactic indomethacin was used equally in the two cohorts. Thoughts for the future Once a preterm infant is admitted to the NICU we start volume targeted ventilation from the start. In the delivery room we may think that we do the same by putting such infants on a volume guarantee mode after intubation but the period prior to that is generally done with a bag and mask. Whether you use a t-piece resuscitator or an anesthesia bag or even a self inflating bag, you are using a pressure and hoping not to overdistend the alveoli. What I think this study demonstrates similar to the previous work by this group is that there is another way. If we are so concerned about volutrauma in the NICU then why should we feel any differently about the first few minutes of life. Impairment of venous return from the head is likely to account for a higher risk of IVH and while a larger study may be wished for, the results here are fairly dramatic. Turning the question around, one could ask if there is harm in using a volume targeted strategy in the delivery room? I think we would be hard pressed to say that keeping the volumes under 6 mL/kg is a bad idea. The challenge as I see it now is whether we rig up devices to accomplish this or do the large medical equipment providers develop an all in one system to accomplish this? I think the time has come to do so and will be first in line to try it out if there is a possibility to do a trial.
  22. 3 points
    While at the #99nicuMeetup, I and @Francesco Cardona were filmed by Miris (one of our exhibiting partners). It was a one-time shot without rehearsal, so we spoke from the heart
  23. 3 points
    Recent statements by the American Academy of Pediatric’s, NICHD, the American College of Obstetricians and Gynecologists (ACOG), the Society for Maternal-Fetal Medicine (SMFM), and recommend selective approaches to mothers presenting between 22 0/7 to 22 6/7 weeks. The decision to provide antenatal steroids is only recommended if delivery is expected after 23 weeks. Furthermore the decision to resuscitate is based on an examination of a number of factors including a shared decision with the family. In practice this leads to those centres believing this is mostly futile generally not resuscitating or offering steroids while other more optimistic hospitals having higher rates of proactive (steroids and resuscitation) rates. Then there are other centres where the standard approach is proactive such as one in Uppsala, Sweden where this approach is used almost exclusively. What would happen then if one compared the outcome for infants born at 22 weeks between this hospital and another where a selective approach is generally offered. In this case you would have a lot of experience with resuscitating infants at 22 weeks and the other a fraction of all presenting as a few to many would receive compassionate care. This is exactly what has now happened. A Tale of Two Cities The University Children’s Hospital, Uppsala, Sweden has been compared retrospectively to Nationwide Children’s Hospital, Columbus, Ohio, USA (NCH) with respect to survival and outcomes for their infants born at 22 weeks. The paper by Backes CH et al entitled Outcomes following a comprehensive versus a selective approach for infants born at 22 weeks of gestation tells a very interesting story about the power of belief or faith that one can accomplish something if they set their mind to it. The authors examined a period from 2006-2015, dividing this time into two epochs with the first being 2006-2010 to account for differing practices and resources over time. Given that Uppsala took a proactive approach to all of their 40 live born infants during this time, it provided an opportunity to look at the 72 infants who were live born in the Ohio and examine their differences. In Ohio the approach was as follows; 16 (22%) received proactive care, 18 (25%) received inconsistent care (steroids but no resuscitation), and 38 (53%) received comfort care. In other words, although the total number of infants live born in Ohio was almost double that of Uppsala, only 16 were proactively treated in Ohio compared to all 40 in Uppsala. The differences in outcome are striking Survival in delivery room: (38/40, 95% vs 12/16, 75%; P = 0.049) Provision of delivery room surfactant: (40/40, 100% vs 9/16, 56%; P<0.01) Survival at 24 h (37/40, 93% vs. 9/16, 56%; P < 0.01). Survival to 1 year (21/40, 53% vs. 3/16, 19%; P < 0.05). Among the infants treated proactively, median age of death (17 postnatal days at range 0 h–226 days vs. 3 postnatal hours at NCH, range 0 h–10 days; P < 0.01). All surviving infants had BPD All infants surviving to initial hospital discharge were alive at 18 months’ postnatal age. With respect to long term outcome the authors note: “Outpatient follow-up (qualitative or non-qualitative neurodevelopmental testing) was available in 26 out of 27 infants (96%) Eleven of the 26 (42%) were unimpaired, and all unimpaired infants were in the UUCH cohort. Among the 15 infants with impairment at UUCH, 3 had mild impairment and 12 had moderate or severe impairment. All surviving infants at NCH had moderate or severe impairment.” A word about antenatal steroids as well. In Uppsala 85% of mothers received 2 doses of antenatal steroids vs 25% in Ohio. People sometimes question whether ANS at this age are effective. It is interesting to note that 44% of babies in the Ohio group vs 3% p<0.01 received chest compressions +/- epinephrine in the delivery room. Might this explain the better state of some of these infants at birth? The Power of Belief When I do rounds I often remark that try as we might we can’t will babies to do better. I also commonly say however that we need to be optimistic and although I am accused of seeing the world through rose coloured glasses I think there is an important lesson to be learned from this study. This comparison is really a contrast between a system that believes they can do a good thing for these families by actively promoting a proactive approach vs a system in which I imagine a reluctant approach exists even for those infants where a proactive plan is enacted. One sign of this might be that in Sweden 100% of these deliveries had a Neonatologist present vs 75% in the US. It could be due to other factors such as ability of the Neo to get in within time of the delivery however rather than a sign they didn’t feel they were needed due to futility. There is evidence as well that the aggressiveness of the proactive approach also differs between the two sites based on a couple observations. The first is the rate of surfactant provision in the delivery room which was 100% in Sweden but only 56% in the US. The other thing of note is the time of death for those who did not survive. The median time of death in the US was 3 hours vs 17 days in Uppsala. What does this tell us about the approaches? I would imagine (although the numbers are small) that the teams in the US were much more likely to lose hope (or faith) and withdraw early while the other centre possibility motivated by their past successes pushed forward. Remarkably, although one might think that the teams in Uppsala were simply creating significantly impaired survivors, 42% of the survivors were unimpaired from a developmental standpoint in follow-up. All surviving infants though from Ohio had moderate to severe impairment. What this story may also really be about is practice. The reality is that the team in Sweden had over twice the exposure to such infants over time. Although the number presenting at this GA was higher, the ones that actually were resuscitated and given steroids was less than half. One cannot take away though that Uppsala in the end demonstrated that a proactive approach is definitely not futile. Not only can these children survive but almost half will be developmentally intact. We must acknowledge as well though that since this is a retrospective study there may be factors that may have affected the results. As the saying goes “Individual results may vary”. Are the teams the same in both centres in terms of number of Neonatologists? Are there more residents caring for these infants vs fellows? Are the resources the same? What about proximity of the Neonatologist to the hospital? There are other factors such as cohesiveness of the team and communication between team members that may be influencing the results. In the end though, this is a story of a team that believed it could and did. Perhaps seeing the world through rose coloured glasses is not such a bad thing in the end.
  24. 3 points
    One of the first things a student of any discipline caring for newborns is how to calculate the apgar score at birth. Over 60 years ago Virginia Apgar created this score as a means of giving care providers a consistent snapshot of what an infant was like in the first minute then fifth and if needed 10, 15 and so on if resuscitation was ongoing. For sure it has served a useful purpose as an apgar score of 0 and 0 gives one cause for real worry. What about a baby with an apgar of 3 and 7 or 4 and 8? There are certainly infants who have done very well who initially had low apgar scores and conversely those who had higher apgar scores who have had very significant deleterious outcomes including death. I don’t mean to suggest that the apgar scores don’t provide any useful predictive value as they are used as part of the criteria to determine if a baby merits whole body cooling or not. The question is though after 60+ years, has another score been created to provide similar information but enhance the predictive value derived from a score? The Neonatal Resuscitation and Adaptation Score (NRAS) Back in 2015 Jurdi et al published Evaluation of a Comprehensive Delivery Room Neonatal Resuscitation and Adaptation Score (NRAS) Compared to the Apgar Score. This new score added into a ten point score resuscitative actions taken at the 1 and 5 minute time points to create a more functional score that included interventions. The other thing this new score addressed was more recent data that indicated a blue baby at birth is normal (which is why we have eliminated asking the question “is the baby pink?” in NRP. Knowing that, the colour of the baby in the apgar score may not really be that relevant. Take for example a baby with an apgar score of 3 at one minute who could have a HR over 100 and be limp, blue and with shallow breathing. Such a baby might get a few positive pressure breaths and then within 10 seconds be breathing quite well and crying. Conversely, they might be getting ongoing PPV for several minutes and need oxygen. Were they also getting chest compressions? If I only told you the apgar score you wouldn’t have much to go on. Now look at the NRAS and compare the information gathered using two cardiovascular (C1&2), one neurological test (N1) and two respiratory assessments (R1&2). The authors in this study performed a pilot study on only on 17 patients really as a proof of concept that the score could be taught and implemented. Providers reported both scores and found “superior interrater reliability (P < .001) and respiratory component reliability (P < .001) for all gestational ages compared to the Apgar score.” A Bigger Study Was Needed The same group in 2018 this time led by Witcher published Neonatal Resuscitation and Adaptation Score vs Apgar: newborn assessment and predictive ability. The primary outcome was the ability of a low score to predict mortality with a study design that was a non-inferiority trial. All attended deliveries were meant to have both scores done but due to limited numbers of trained personnel who could appropriately administer both scores just under 90% of the total deliveries were assigned scores for comparison. The authors sought to recruit 450 infants to show that a low NRAS score (0–3) would not be inferior to a similar Apgar at predicting death. Interestingly an interim analysis found the NRAS to be superior to Apgar when 75.5% of the 450 were enrolled, so the study was stopped. What led the apgar score to perform poorly in predicting mortality (there were only 12 deaths though in the cohort) was the fact that 49 patients with a 1 minute apgar score of 0-3 survived compared to only 7 infants with a low NRAS score. The other interesting finding was the ability of the NRAS to predict the need for respiratory support at 48 hours with a one minute apgar score of 0-3 being found in 39% of those on support compared to 100% of those with a low NRAS. Also at 5 minutes a score of 4-6 for the apgar was found in 48% of those with respiratory support at 48 hours vs 87% of those with a similar range NRAS. These findings were statistically significant while a host of other conditions such as sepsis, hypoglycemia, hypothermia and others were no different in terms of predictive ability of the scores. An Even Bigger Study is Needed To be sure, this study is still small and missed just over 90% of all deliveries so it is possible there is some bias that is not being detected here. I do think there is something here though which a bigger study that has an army of people equipped to provide the scoring will add to this ongoing story. Every practitioner who resuscitates an infant is asked at some point in those first minutes to hour “will my baby be ok?”. The truth is that the apgar score has never lived up to the hope that it would help us provide an accurate clairvoyant picture of what lies ahead for an infant. Where this score gives me hope is that a score which would at the very least help me predict whether an infant would likely still be needing respiratory support in 48 hours provides the basic answer to the most common question we get in the unit once admitted; “when can I take my baby home”. Using this score I could respond with some greater confidence in saying “I think your infant will be on support for at least 48 hours”. The bigger question though which thankfully we don’t have to address too often for the sickest babies at birth is “will my baby survive?”. If a larger study demonstrates this score to provide a greater degree of accuracy then the “Tipping Point” might just be that to switching over to the NRAS and leaving the apgar score behind. That will never happen overnight but medicine is always evolving and with time you the reader may find yourself becoming very familiar with this score!
  25. 3 points
    July was very eventful for me and that had caused my on-line silence. I had a chance to visit again my beloved Finland and now I'm back with fresh thoughts and ideas (and also hundreds of photos). Enjoy! Kotiloma is a word in Finnish that means „vacation at home”. But in some NICUs around Finland it has grown into a bit different meaning. Kotiloma is a practice of arranging a little vacation at home for NICU patients before their final discharge. The routine is quite simple. On the kotiloma day parents come to the unit with a car seat and a set of clothes. When the seat is warm and the baby is ready, they just simply take their baby home for a day. Before they leave, they inform the staff about the time of their return. If they would feel insecure, they can always return to the unit sooner and their room will be waiting for them. The duration of the stay away from the unit can last from a couple of hours up to a whole weekend. Sounds interesting? There are two basic conditions: parents' willingness and staff's trust in parents' abilities. Parents need to be confident when it comes to securing baby’s needs. Since kotiloma applies mostly to preemies, parents are generally well prepared (hello Family Centered Care!) and very eager to take the baby home for this vacation. It’s like a free trial of full-time parenthood and you can still bring the baby back But seriously speaking, after spending several weeks in the unit with the baby, they really just want to change the surroundings and go out for a while. If the home is too far away, or if the thing is just logistically too difficult, they can take their child for a long walk in a baby stroller instead. Since parents are in the unit every day, taking care of their little one, it is quite simple for the medical staff (especially for the fantastic nurses!) to assess their preparedness, encourage them and prepare them also technically for kotiloma. Basically there are two types of kids who go for a vacation to home. The first one is when the baby is being fed by a feeding tube and getting close to the discharge date. Parents generally feel quite comfortable with using the tube and since they are practically living in the unit, it’s not a big hassle for them to take the baby home with this tube. The second group of babies are the ones on an "apnea countdown" . Those are sent home with saturation monitors and parents are specifically educated by nurses to interpret heart rate and SatO2. They are additionally trained in infant resuscitation. This whole „crash course” takes no more than 1 hour. If the parents are eager for the kotiloma and the staff is ready to train them, they can take the baby home for the daytime (so they can observe the monitors, but those babies have to return to the Unit for the nighttime.) If you are even a bit like me, and I know many of you are, you will ask „BUT WHO IS LEGALLY RESPONSIBLE FOR THAT BABY? WHO IS IN CHARGE IF ANYTHING HAPPENS?”. Well, since the kid is not really discharged from the hospital, that would be you. I know it sounds tricky, but my (not-so-)confidential informant Samuli Rautava from the TYKS NICU says, that since they’ve been doing that (already 5 years!), nothing has ever happened. If the family has any questions or concerns during the kotiloma, they are encouraged to call the nursing station. They are never left alone with their worries. When it comes to financial issues, I would say (naively) that nobody pays anything extra for that vacation. Since the kid hasn’t been discharged, the healthcare fund pays for the day in the unit. Parents provide their own car, clothes and the car seat. No more costs are involved. Easy as that Is it safe? Generally life is known to be a dangerous adventure But it’s easy to notice, that this practice is based on a mutual trust agreement. "You- The Parents- trust us- The Medical Staff- every day, that we perform medical procedures based on our best knowledge and best available evidence. So WE trust YOU, that you will not idle away our efforts and do your best to provide the best possible care to your baby". This cooperation is working well. Parents are properly educated in their baby’s needs (thanks to Close Collaboration with Parents Training Program). They learn how to perform CPR and call 112 in case of emergency. The nursing staff always gets the information about the condition of other siblings and cohabitants (to avoid infections etc). Okay, but what are the benefits? Besides empowerment of the parents (which is a huge thing, especially since they are on-their-way to the discharge date), it actually makes the whole discharge process easier. After the kotiloma parents' confidence grows. It is like a short trial of full stay-at-home parenthood. When you take your precious, fragile baby home, some questions may arise in your head. It feels good to know, that you will be able to ask them to your own pediatrician and nurses when you return to the unit. This practice enables parents to observe their child in a home setting. They notice how the baby looks around and curiously contemplates the new environment. It is also a good chance for other cohabitants (those furry ones too!) to get to know their future housemate. Kotiloma is simply a joy for parents, baby and whole family. A sign saying „our baby is doing fine”. Some happy moment to cherish. We all need those sometimes!
  26. 3 points
    I had an amazing opportunity to visit NICU in the Turku University Hospital in 2016. They admit around 550 problematic newborns per year. About 10% of them are born below 30 weeks of gestation. The whole unit is practically based on 11 family rooms (single family rooms when possible) and additionally one larger room for 4 patients. The larger room is usually used for babies who are admitted due to transient issues (tachypnea, hypoglycemia, hyperbilirubinemia etc). Single family rooms are equipped with an incubator/open warmer bed/cot, one adult bed, one reclining armchair and a nappy changing station. There is also a breast pump and a refrigerator for breast milk in the room. Parents are constantly involved in the care of their preterm baby and are welcome to stay and care for their child all day and night. That’s the theory. So what is the reality? Entering the unit for the first time, the word that came to my mind was „serenity”. The unit welcomes you with knitted octopuses and tiny socks everywhere. The whole design of the unit is somehow soft, warm and calming. Each family room is „protected” by a closed door with a window in them - and the window is also covered with a pastel-color quilt. If you want to enter the room, or you’re just looking for your co-worker, you can just „peek in” and check without disturbing the family much. Then you can knock on the door and enter the room. This way you are giving the family the maximum privacy we can offer in those special circumstances. Well, you have those tiny, „problematic” children in those private family rooms, with their parents being their primary caretakers, guardians and gate-keepers. Yet, nobody feels that their access to the patient is limited. How is that even possible? Maybe this is what we call „the change of the caring culture”? When you’re „letting go” of some of your duties and delegating them to the parents, you also learn to trust them with your little patient. After all, we all have the same goal- and the parents are personally and emotionally interested in their own child’s well-being, so they have even stronger motivation to perform well. Visiting you patient in the single family room feels like visiting your friends, who had just brought their newborn back from the hospital. Imagine the situation, that you’re paying them that first visit, with a little gift wrapped in a pink paper and a big pink balloon. What will you expect? I think it’s quite normal that their room will be a bit messy and everybody will be whispering around the sleeping baby. It’s normal that the mother will be breastfeeding (or pumping milk) in your presence. And again- it’s normal that parents will be touching and cuddling the baby. I’ve visited several neonatal intensive care units around the Europe. They all announce proudly, that they are „family centered units”. They all know that skin-to-skin care is a recommended, good and beneficial procedure. Yet in the same time, they actually treat it like a medical procedure - which is time-limited and full of exclusion criteria. That procedure also seems to be quite stressful for the medical staff, because they feel like they can’t access their patient anymore. What if something happens, what if we need to react, how to save that baby when the baby is outside the cot? How can we be medical professionals, when the patient is out of reach? It comes straight to the question: what exactly is skin-to-skin care for you? Is it a medical procedure, which is performed once or twice a week, for one hour, when the baby (and the parent!) is fully dressed? Or do you consider mother’s and father’s bare chest as a new space of care for your patient? A safe surrounding, stabilizing baby’s body temperature, breathing and heart rate? And what do you consider a contraindication for skin-to-skin care? Recently I’ve heard from my friend that in their NICU (highest reference centre) kangaroo care is performed only after the baby reaches 1600g. In other place, I’ve seen a healthy 31-weeker in his second week of life, on full enteral feeds, happily kicking in a closed incubator, who couldn’t be kangarooed or even touched by his parents, just because there was a PICC-line placed in his arm. I still remember those sad parents, wearing plastic gowns, standing by that closed incubator, not being able to even touch their own baby, just because it was a preemie. Prematurity is a diagnosis, but it’s not a sentence! If we are treating similar babies with similar equipment and similarly trained staff - why does our practice differ so much? Leave your comment and join the discussion!
  27. 3 points
    I met the author of this article at a CPS meeting a few years ago, she immediately impressed me with her unique perspective. Paige is a developmental pediatrician who does long-term follow-up of preterms, and is involved in developmental evaluation and intervention of children with other challenges, including Spina Bifida. Church P. A personal perspective on disability: Between the words. JAMA Pediatrics. 2017. As you will see if you read the article, Paige has a form of Spina Bifida herself, a Lipomyelomeningocele, with a neurogenic bladder and neurogenic bowel, requiring life-long interventions. She discusses the poor tolerance many medical people have of disability, and such how things are often discussed as black or white, whereas having a profound personal experience of disability has made her much more nuanced. She recounts being involved in a discussion regarding a "selective reduction" of a twin pregnancy where the twin being considered for "reduction", i.e. abortion, had a similar lesion to her own. That is an experience that I can barely understand: how would I react if a family was considering terminating a pregnancy because of a condition that I had? Paige recounts the episode with tact and humanity. I can imagine, as I have heard them many times, the words of the other physicians involved in such a decision, I am sure they talked about handicaps and limitations, poor quality of life, pain, and restrictions on family life. Most of which is said with good intentions but with no real knowledge of the literature, or of the range of experiences of families living with the challenges. Just as with similar discussions regarding extreme preterm infants, a list of complications, interventions, disabilities, and long-term problems is often presented, but with no similar list of benefits, achievements, abilities, long-term adaptation, and happiness. Near the end of her moving piece Paige writes: Like most things in life, and medicine, disability is sharp, painful, humbling, as well as tremendous, giving, awe-inspiring. It is human. It is not easily distilled to an all or none discussion. Medicine sets the tone for this discussion and, to date, has done a miserable job. More is needed to appreciate the incredible opportunities that disability poses. More education is needed to provide the counselling families deserve: balanced, sensitive, thoughtful, and individualized rather than “objective.” I sincerely hope that this piece by Paige will be part of a new discussion about these issues. (Of note, even though the article is behind a paywall, JAMA lets you see the first page of the article before buying, in this case there is only one page, so you can read the whole thing for free!)
  28. 3 points
    The human body truly is a wondrous thing. Molecules made from one organ, tissue or cell can have far reaching effects as the products take their journey throughout the body. As a medical student I remember well the many lectures on the kidney. How one organ could control elimination of waste, regulate salt and water metabolism, blood pressure and RBC counts was truly thought provoking. At the turn of the century (last one and not 1999 – 2000) Medical school was about a year in length and as the pool of knowledge grew was expanded into the three or four year program that now exists. Where will we be in another 100 years as new findings add to the ever growing volume of data that we need to process? A good example of the hidden duties of a molecule is erythropoetin (Epo) the same one responsible from stimulating red blood cell production. Double Duty Molecule In saying that I am simplifying it as there are likely many processes this one hormone influences in the body but I would like to focus on its potential role in neuroprotection. In 1999 Bernaudin Et al performed an animal study in mice to test this hypothesis. In this elegant study, strokes were induced in mice and the amount of Epo and Epo receptors measured in injured tissues. Levels of both increased in the following way “endothelial cells (1 day), microglia/macrophage-like cells (3 days), and reactive astrocytes (7 days after occlusion)”. To test the hypothesis that the tissues were trying to protect themselves the authors then administered recombinant human Epo (rhEpo) to mice prior to inducing stroke and the injury was clearly reduced. This established Epo as a potential neuroprotectant. Other animal studies then followed demonstrating similar findings. A Human Trial When you think about hypoxic ischemic encephalopathy (HIE) you can’t help but think of whole body cooling. The evidence is pretty clear at this point that cooling in this setting reduces the combined outcome of death or neurodevelopmental disability at 18 months with a number needed to treat of 7. The risk reduction is about 25% compared to not those not cooled so in other words there is room to improve. Roughly 30-40% of infants who are cooled with moderate to severe HIE will still have this outome which leaves room for improvement. This was the motivation behind a trial called High-Dose Erythropoietin and Hypothermia for Hypoxic-Ischemic Encephalopathy: A Phase II Trial. This was a small trial comparing 50 patients (24 treated with rhEpo and cooling to 26 given placebo) who were treated with 1000 U of rEpo on days 1,2,3,5 and 7. Primary outcome was neurodevelopment at 12 months assessed by the Alberta Infant Motor Scale (AIMS)and Warner Initial Developmental Evaluation. A significant improvement in a subset of mobility on the latter was found and a significant difference in the AIMS overall. An additional finding giving support for a difference was that blinded reviews of MRI scans demonstrated a singificant improvement in brain tissue in those who received rhEPO. One curious finding in this study was that the mean timing of administration of rhEPO was 16.5 hours of life. Knowing that the benefit of cooling is best when done before 6 hours of age one can only wonder what impact earlier administration of a neuroprotective agent might have. This suggests that the addition of rEPO to cooling has additional impact but of course being a small study further research is needed to corroborate these findings. The Next Step This past week Malla et al published an interesting paper to add to the pool of knowledge in this area; Erythropoietin monotherapy in perinatal asphyxia with moderate to severe encephalopathy: a randomized placebo-controlled trial. This study was done from the perspective of asking if rhEPO by itself in resource poor settings without access to cooling in and of itself could make a difference in outcome for patients with HIE. This was a larger study with 100 Hundred term neonates (37 weeks or greater) with moderate or severe HIE. Fifty were randomized by random permuted block algorithm to receive either rhEPO 500 U kg− 1 per dose IV on alternate days for a total of five doses with the first dose given by 6 h of age (treatment group) or 2 ml of normal saline (50 neonates) similarly for a total of five doses (placebo group) in a double-blind study. The primary outcome was combined end point of death or moderate or severe disability at mean age of 19 months and the results of this and other important outcomes are shown below. Outcome Treatment Placebo p Death/disability (mod/severe HIE) 40% 70% 0.003 Death/disability (mod HIE only) 21% 61% 0.004 Cerebral Palsy 23% 45% 0.04 MRI abnormalities 40% 60% 0.04 Seizures treatment at 19 months 19% 43% 0.03 To say that these results are impressive is an understatement. The results are on par with those of cooling’s effect on reduction of injury and improvement in outcome. When looking at the primary outcome alone the result in dramatic when put in perspective of looking at number needed to treat which is 4! This is significant and I can’t help but wonder if the impact of this medication is at least in part related to starting the dosing within the same window of effectiveness of therapeutic hypothermia. Importantly there were no adverse effects noted in the study and given that rhEpo has been used to treat anemia of prematurity in many studies and not found to be associated with any significant side effects I would say this is a fairly safe therapy to use in this setting. Next Steps I find this puts us in a challenging position. The academic purists out there will call for larger and well designed studies to test the combination of rhEPO and cooling both initiated within 6 hours of age. While it takes years to get these results might we be missing an opportunity to enhance our outcomes with this combination that is right in front of us. The medication in question other than raising your RBC count has little if any side effects especially when given for such a short duration and by itself and possibly with cooling increases the rate of neuroprotection already. I don’t know about you but I at least will be bringing this forward as a question for my team. The fundamental question is “can we afford to wait?”
  29. 3 points
    This may sound familiar as I wrote about this topic in the last year but the previous post was restricted to infants who were under 1000g. High Flow Nasal Cannula be careful out there had a main message that suggested the combined outcome of BPD or death was more prevalent when HFNC is used alone or with CPAP than when CPAP is used alone. The question remains though whether this applies to larger infants. Without looking at the evidence for that combined outcome most people would say there is unlikely to be a difference. Larger more mature babies have a much lower risk of BPD or death so proponents of HFNC would say it is simpler to use and helps prevent nasal breakdown as well. The question remains as to whether all outcomes are the same in larger infants and that is the point of this post. A Non-Inferiority Trial First off it is important to understand what this type of trial is. The first requirement is that the two treatments have both been compared to a placebo and found to be both effective. Once you establish that you have a choice between two treatment options then you eliminate the placebo and compare them head to head. What you are looking for in this type of trial is to determine not whether one is better than the other but that there is no difference in a clinical outcome of interest. If you find no difference then the next step is to look at other outcomes that might be of interest and see if there are any benefits to picking one versus the other. In the case of CPAP vs HNFC, if a non-inferiority trial showed no difference in an important outcome such as length of stay but nasal breakdown was less with HFNC it might lead a unit to use HFNC for their infants. Okay, now that we have that cleared up we can move on to an actual study examining this very subject. Nasal High-Flow Therapy for Primary Respiratory Support in Preterm Infants. This was an interesting study with a great name (The HIPSTER trial) that enrolled infants > 28 weeks and 0 days with none of the infants receiving surfactant but either being randomized to HFNC or CPAP after delivery. These infants were your typical modern day cohort of babies who may avoid intubation and surfactant by establishing FRC early with positive pressure applied to the nose through one of these devices. The end point for the study was treatment failure within 72 hours. If an infant failed in the HFNC they could have a trial of CPAP whereas in the CPAP group they were intubated. For each infant in the HFNC group flow was set from 6-8 l/min and for CPAP 6-8 cmH2O. Treatment was considered to have failed if an infant receiving maximal support (high-flow therapy at a gas flow of 8 liters per minute or CPAP at a pressure of 8 cm of water) met one or more of the following criteria: FiO2 of 0.4 or higher Arterial or free flowing cap gas with a pH of 7.2 or less plus a pCO2 > 60 mm Hg obtained at least 1 hour after starting treatment Two or more episodes of apnea requiring positive-pressure ventilation within a 24-hour period or six or more episodes requiring any intervention within a 6-hour period. Infants with an urgent need for intubation and mechanical ventilation. So what happened? The trial randomized 583 infants (278 HFNC, 286 CPAP) but was halted by the data and safety monitoring committee after an analysis of the first 515 revealed that the outcome was worse in the HFNC group (25.5% failure rate vs 13.3 for CPAP). Interestingly treatment failures were more common in babies below and above 32 weeks so it was not just the smallest infants who failed. Another interesting finding was that the most common reason for treatment failure was criteria 1 (FiO2 > 40%) while intubation was higher for all infants but did not reach statistical significance. Curiously what did reach a significant difference was criteria #4 (18.4% urgent intubations in the CPAP group vs 5.6% in the HFNC group). You might be tempted to therefore ponder which is worse, a little O2 or being intubated but you need to recall the trial design which was set up to provide this kind of result. If you failed HFNC you were placed on CPAP whereas if you failed CPAP you were intubated. In the HFNC group, 78 infants were deemed to have failed but 28 of them were in fact “rescued by CPAP”. It therefore isn’t a fair comparison when it comes to urgent intubation since if you failed CPAP there wasn’t another option. Not a total loss Nasal trauma was indeed much lower in the HFNC group, occurring only 8.3% vs 18.5% of the time with CPAP. Pneumothorax was also found to be significantly different with none of the patients in the HFNC group having that complication vs 2.1% in the CPAP group. What this study tells us is that as a primary modality to treat newborns with RDS who have not received surfactant it is preferable to use CPAP in the first 72 hours. Some of you may say it might not say that at all but consider the impact of having more babies exposed to high FiO2. We know from other studies that high FiO2 can be quite damaging to preterm infants and this study was certainly not powered to look at all those important outcomes such as ROP, PVL and BPD. The authors report them and found no difference but without adequate power to show a difference I wouldn’t take much comfort in those findings. I think were things may settle out though is what to do in more mature infants. There is no question that for those on chronic respiratory support there is some risk of nasal breakdown. Although I don’t have much experience with HFNC I would think that for the older patient who either already has BPD at 36 weeks or is close to that point but reliant on +4 or +5 CPAP that HFNC might help “give them a break”. As such I don’t see this as a total loss but rather an option to try when CPAP for whatever reason is not tolerated. As a primary therapy for non-invasive management RDS I will keep my CPAP for all babies thank you.
  30. 3 points
    This publication appeared on-line a couple of months ago, and still isn't in print. Prentice T, et al. Moral distress within neonatal and paediatric intensive care units: a systematic review. Arch Dis Child. 2016. It is a systematic review from Melbourne, with the help of Annie Janvier, of the literature surrounding moral distress in health care workers in the NICU and the PICU. All of the studies included nurses, and some of them also studied other health care workers. Moral Distress refers to subjective feelings of distress in response to the ethical challenges of health care work. It is a term which first appeared in the nursing literature, and, although other terms have been suggested, I think it fits. Moral residue is another term these authors refer to, which is the lingering feelings which persist after the "morally distressing" case has ended. As we deal with children and babies who are fragile, dependent, and may have life-long complications, the NICU and PICU are places where moral distress is likely to be frequent. How frequent it is, and what causes the situations most likely to lead to distress, where the questions that lay behind this systematic review. They found 13 articles, of varying size and quality, (including one of ours); from the results of the systematic review article: One of their findings is the different ways in which moral distress is discussed in the articles, publications in the nursing literature frequently emphasize the subjective experience of the nurses, and the fact that they lack power and are having to provide interventions that they do not always agree with; they are sometimes portrayed as the victims of the aggressive care being perpetrated by the physicians. Whereas in the medical literature moral distress is described in terms of the objective situations that create confrontations or dilemmas. The reality is though, that physicians also experience moral distress (with about the same frequency as nurses), they also find themselves sometimes performing tasks and providing care which is against their own conception of what the best interest is for their patients. What has been shown previously is that moral distress may lead to burnout, and decrease retention of staff. It is also probably unavoidable in intensive care, but we should, and could, work harder to minimize it, and minimize its impact.
  31. 3 points
    As I was preparing to settle in tonight I received a question from a reader on my Linkedin page in regards to the use of sustained inflation (SI) in our units. We don't use it and I think the reasons behind it might be of interest to others. The concept of SI is that by providing a high opening pressure of 20 - 30 cm H2O for anywhere from 5 to 15 seconds one may be able to open the "stiff" lung of a preterm infant with RDS and establish an adequate functional residual capacity. Once the lung is open, it may be possible in theory to keep it open with ongoing peep at a more traditional level of 5 - 8 cm of H20. The concept was tested 25 years ago by Vyas et al in their article Physiologic responses to prolonged and slow-rise inflation in the resuscitation of the asphyxiated newborn infant. In this study, 9 newborn infants were given a relatively short 5 second sustained inflation and led to earlier and larger lung volumes with good establishment of FRC. Like many trials in Neonatology though sceptics abound and here we are 25 years later still discussing the merits of this approach. As I have a warm place in my heart for the place that started my professional career whenever I come across a paper published by former colleagues I take a closer look. Such is the case with a systematic review on sustained inflation by Schmolzer et al. The inclusion criteria were studies of infants born at <33 weeks. Their article provides a wonderful assessment of the state of the literature on the topic and I would encourage you to have a look at it if you would like a good reference to keep around on the topic. What it comes down to though is that there are really only four randomized human studies using the technique and in truth they are fairly heterogeneous in their design. They vary in the length of time an SI was performed (5 - 20 seconds), the pressures used (20 - 30 cm H2O), single or multiple SIs and lastly amount of oxygen utilized being 21 - 100%. In fact three of the four studies used either 100% or in one case 50% FiO2 when providing such treatments. What Did They Show? This is where things get interesting. SI works in the short term by reducing the likelihood that an infant will need mechanical ventilation at 72 hours with a number needed to treat of only 10! In medicine we normally would embrace such results but sadly the results do not translate into long term benefits as the rate of BPD, mortality and the combined outcome do not remain significant. Interestingly, the incidence of a symptomatic PDA needing treatment with either a medical or surgical approach had a number needed to harm of 11; an equally impressive number but one that gives reason for concern. As the authors speculate, the increased rate of PDA may be in fact related to the good job that the SI does in this early phase. By establishing an open lung and at an earlier time point it may well be that there is an accentuation in the relaxation of the pulmonary vasculature and this leads to a left to right shunt that by being hemodynamically significant helps to stent the ductus open at a time when it might otherwise be tending to close. This outcome in and of itself raises concern in my mind and is the first reason to give me reason to pause before adopting this practice. Any other concerns? Although non-significant there was a trend towards increased rates of IVH in the groups randomized to SI. There is real biologic plausibility here. During an SI the increased positive pressure in the chest could well simulate a similar effect to a pneumothorax and impede the passive drainage of blood from the head into the thorax. In particular, longer durations and/or frequent SIs could increase such risk. Given the heterogeneous nature of these studies it is difficult to know if they all had been similar in providing multiple SIs could we have seen this cross over to significant? I believe the biggest concern in all of this though is that I would have a very hard time applying the results of these studies to our patient population. The systematic review addresses the question about whether SI is better than IPPV as a lung recruitment strategy in the preterm infant with respiratory distress. I have to say though we have moved beyond IPPV as an initial strategy in favour of placement of CPAP on the infant directly after birth. The real question in my mind is whether providing brief periods of SI followed by CPAP of +6 to +8 is better than placement on CPAP alone as a first strategy to establish good lung volumes. If I am to be swayed by the use of SI someone needs to do this study first. The possibility of increasing the number of hemodynamically significant PDAs and potentially worsening IVH without any clear reduction in BPD is definitely placing me firmly in the camp of favouring the CPAP approach. Having said all that, the work by the Edmonton group is important and gives everyone a glimpse into what the current landscape is for research in this field and opens the door for their group or another to answer my questions and any others that may emerge as this strategy will no doubt be discussed for years to come.
  32. 3 points
    I don't know about you but I have deeply rooted memories from the 1990s of donning a yellow gown and gloves before examining each and every patient on my list before rounds. This was done as we firmly believed such precautions were needed to prevent the spread of infections in the NICU. As time went on though the gowns were removed and not long after so went the gloves as priority was placed on performance of good hand hygiene to reduce rates of infection in our units. You can imagine that after having it entrenched in my mind that hand hygiene was the key to success that I would find it surprising to see a paper published a few months ago suggesting that the use of gloves after hand hygiene may offer a benefit after all. Kaufman DA et al published Nonsterile glove use in addition to hand hygiene to prevent late-onset infection in preterm infants: randomized clinical trial and given it's challenge to a practice that is at least two decades old I thought it may be worth sharing with you the reader. Essentially the authors hypothesized that the use of non-sterile gloves after performing hand hygiene (compared to hand hygiene alone) would reduce late-onset invasive infection (>72 hours after birth), defined as 1 or more episodes per patient of a BSI, urinary tract infection,meningitis, and/orNEC associated with clinical signs and symptoms of infection and treated with antimicrobials. When determining the size of study needed, they used a baseline incidence of 60% and looked to find a 25% reduction in their outcome. Unfortunately for them (although very fortunate for their patients, the incidence of LOS in the experimental arm was 32% with a 45% incidence in the control group (hand hygiene alone). What does this mean when your expected rate is higher than your observed? In short you need more patients to show a difference and indeed they failed to show a significant difference between the two groups. They did however find a difference in gram positive infections being 15 vs 32% p=0.03 and seem to take some comfort in this finding. If you were to give the paper a quick read you might be impressed with the finding and might even shrug your shoulders and say the common expression "Can't hurt but might help" Maybe we should adopt this? Not so Fast There is a significant potential source of error here that needs to be addressed. The definition of a proven blood stream infection as per the CDC is two positive cultures for the same organism. In this study only one culture was required to be positive so the potential for diagnostic error is high. In our own centre although unpublished we have noted since adopting a mandatory two culture collection approach for LOS that there have been a significant number of occasions where one culture was noted to be positive and the other negative. Antibiotics in these cases have been stopped (for gram positive organisms) after 48 hours without consequence. In this study however the findings of increased rates of positive cultures in the hand hygiene only group is heavily influenced by the presence of only one positive culture as is seen in this table. When looking at the numbers of times there were greater than or equal to 2 positive cultures in the CoNS group one sees the vast majority were only based on one culture. Furthermore, of the 20 infections in the hand hygiene only group, 19 were gram positve CoNS of which only 4 had more than one culture. Based on this finding and the lack of any other significant difference in infectious outcomes the proof that gloves add anything to reducing infection rates is tough to argue. Could Gloves Actually Make Things Worse? Several studies have actually indicated that wearing gloves reduces hand hygiene compliance. One such study although in adults "The dirty hand in the latex glove": a study of hand hygiene compliance when gloves are worn. suggests that this is indeed the case with a 9% decrease in proper hand hygiene when gloves were worn. Others such as Flores in 2006 found similar poor perfomance when gloves were used Healthcare workers' compliance with glove use and the effect of glove use on hand hygiene. I would speculate that although we all want to do what is best for our patients there may be a psychological trick being played here. Perhaps knowing we will cover up with gloves leads people to take shortcuts on hand hygiene as they subconciously think they will be covered anyway. Never mind that the "dirty" hand touches the gloves they will put on making proper hand hygiene a must. Conclusion It certainly was a shock to see such a paper as I saw flashes of my past yellow gowned self coming back to haunt me. Based on my take of this paper however I would say that at least for the time being I will take my time, wash my hands before and after every patient encounter and keep the gloves around for handling those yet unbathed newborns. Spend your energy where it counts and that is ensuring your hands are properly cleaned before touching your patient or lines.
  33. 3 points
    I have often wondered why my obstetrical colleagues would often induce labour once a woman with ruptured membranes reached 34 weeks. I wasn't aware of any data to support doing this, or, on the other hand, any good data to say that you shouldn't. It turns out that I was well-informed, there just wasn't any good data, until now. Morris JM, et al. Immediate delivery compared with expectant management after preterm pre-labour rupture of the membranes close to term (PPROMT trial): a randomised controlled trial. Lancet. 2015;387(10017):444-52. In this study over 1800 women with singleton pregnancies and ruptured membranes without labour, who were between 34 and 37 weeks gestation, were randomized to either immediate delivery (induction or cesarean) or expectant management, in which case the woman and her obstetrician waited for spontaneous labour or another indication to deliver. Women whose membranes ruptured before 34 weeks became eligible when they hit that mark. This remarkable study took 10 years to recruit their subjects. It was run out of Sydney, and funded by the NHMRC of Australia and enrolled mothers from 11 different countries. What did they find? Well, neonatal sepsis occurred in 23 (2%) of the babies in the immediate delivery group, 29 (3%) of the expectant group, a difference which could easily be due to chance. There were 3 neonatal deaths in each group. On the other hand, expectantly managed pregnancies ended up with a significantly higher gestational age and birthweight, not surprisingly, and as a result less NICU admission, less respiratory distress, less assisted ventilation, and fewer days in hospital, all of which were highly statistically significant. For the mothers there were some downsides, there was a slight increase in antepartum or intrapartum haemorrhage from 3% to 5% and they had one day more of hospital stay with expectant management, but they had many fewer cesarean deliveries. 19% in the expectant group compared to 26%. This is very high quality evidence that we should not be doing what ACOG currently states, which is to deliver immediately because of the risk of neonatal sepsis. If things are going well, and there is no sign of infection, pre-labour preterm rupture of membranes can be followed closely, with delivery for other obstetric indications.
  34. 3 points
    Many of you will have heard of the "Choosing wisely" campaign, an attempt to improve decision making, by clarifying efficacy and risks of common procedures or therapies. Many specialty societies have come up with lists of the Top-5 questionable practices that should be reconsidered. The AAP has just published a list of 5 neonatal practices that they say should be avoided. It is interesting that some of the other societies have made very clear recommendations to not do certain things (“Don’t do….” a particular test, for example). The AAP list instead states to “Avoid Routine…” for each one of the 5 practices. I think for a couple of their practices they could have been more forthright. 1. Avoid routine use of antireflux medications for treatment of symptomatic GERD or for treatment of apnea and desaturation in preterm infants. This is one where that prior comment applies. I think this should have been stated “Do not use antireflux medications in the newborn”. The reason being that there is no such animal. There is no medication that has been shown to reduce reflux. There is no way clinically to diagnose abnormal reflux. There is no effect of antireflux medication on apnea or desaturation. All the medications in use are toxic. Now if by antireflux medications, they include anti-gastric acidity medications (and when you look at the supplemental materials it seems that they do) then I guess you could temper those comments a little. It is possible that sometimes acid-caused reflux disease is an issue, and the agents are effective at reducing gastric acid production, even in the newborn. Whether they improve any acid-related disease findings is less certain, most of the rare small RCTs have shown no clinical benefit. They are also associated with more infections, more NEC and increased mortality in the preterm. So maybe in a baby after diaphragmatic hernia repair, or after Oesphageal Atresia repair they could be indicated, but it would be great to have some actual data. 2. Avoid routine continuation of antibiotic therapy beyond 48 hours for initially asymptomatic infants without evidence of bacterial infection. Again I think this could be a stronger statement, given the 2 provisos that the babies are initially asymptomatic and that they have no evidence of bacterial infection. In other words it is for babies with risk factors for infection, but who develop no clinical signs. In those babies you could appropriately say “Stop antibiotics at 36 hours”. 3. Avoid routine use of pneumograms for predischarge assessment of ongoing and/or prolonged apnea of prematurity. I think this is appropriately stated, there may be indications for selective predischarge pneumograms, for diagnostic rather than screening purposes, so “Avoid routine” is about right. 4. Avoid routine daily chest radiographs without an indication for intubated infants. I agree with this, I didn’t know it was a common practice in the NICU. Some babies are intubated for months, that would be an awful lot of radiation. 5. Avoid routine screening term-equivalent or discharge brain MRIs in preterm infants. Again I agree with this, as many of you will already know! The justification given however, is that there is no evidence that they improve long term outcome. While that is true, I don’t think that is why they are being done, not many people think a few minutes in a magnet will make the babies better. The data show a poor positive predictive value of abnormal findings for long term outcomes, which make them of questionable value.
  35. 3 points
    All food is brain food when your brain is making 250,000 new neurones every minute. In a small two-center trial first published in 2013 50 very preterm babies were randomized to different parenteral nutritional intakes. The main differences between the groups were that the controls started at 2 g/kg/d of protein, compared to 3.5 in the intervention group. The controls started at 0.5 g/kg/d of lipid given as ClinOleic, the intervention group started at 2 of SMOFLipid; both gradually increased to a max of 3.4. One they were receiving 110 mL/kg/d of milk the fortification was different between the groups, with the enhanced group getting an extra 0.8 g/kg/d of protein, to achieve 4.4 g/kg/d, and getting extra omega 3 fatty acids to arrive at a total of 166 kcal/kg/d, compared to 146. (which is a whole lot of calories!) Unfortunately the planned sample size was not achieved, the study was stopped early because there was more sepsis in the enhanced nutrition group (p<0.04). Stopping a trial for a barely significant difference between groups is really not a good idea, but it is often a difficult decision, especially when the difference is an important adverse outcome. The primary outcome was post-natal growth restriction. The authors were following a number of secondary outcomes as were the data monitoring committee. The risk that one of those outcomes will be 'statistically significant' at some point during the data accumulation is enormous. That is why stopping rules should be much more stringent than that. Of course if you continue the study and it turns out that there really is more sepsis at the end of the study, you may then be criticized, and you might feel bad. You might indeed face totally ridiculous criticisms similar to those that were directed at the SUPPORT trial by Public Citizen, who don't understand how interim analyses work. Having said that the authors published a second paper with the growth data; because of the small sample size there was a difference in the birth growth variables between groups, which actually favoured the controls, more SGA babies in the enhanced nutrition group. Despite this there were significant advantages of the enhanced protocol. None of the non-growth restricted babies in the intervention group became growth restricted, compared to 1/3 of the babies in the control group. The z-scores for weight dropped by about 0.3 for the intervention group, between birth and 30 days of age, and by about 0.7 in the controls. Head growth was also better. A subset of the infants had MRI performed at term, which has just been published, and which is why I am writing this post. Strømmen K, Blakstad EW, Moltu SJ, Almaas AN, Westerberg AC, Amlien IK, et al. Enhanced Nutrient Supply to Very Low Birth Weight Infants is Associated with Improved White Matter Maturation and Head Growth. Neonatology. 2015;107(1):68-75. (yes its the first article of 2015 on the blog). There were differences between the groups. Which is about as much as I can say about head MRI, the mean diffusivity was lower in the intervention group. Which is good, apparently. In just about every region of the brain there were significant differences in what I shall from now on refer to as MD, as if I knew what I was talking about. So give more food. It makes the babies grow better, including their head, and it improves their MD, which is a good thing to do.
  36. 3 points
    Necrotizing Enterocolitis remains a devastating disease. One of the major causes of mortality in Very Low Birth Weight Infants, it often strikes when babies are starting to do well. Because it is relatively unpredictable, observational studies are potentially useful, but can easily be misleading. In particular, observational studies which are performed as a result of a perceived change in incidence might easily be biased. One recent study that was published has received some publicity, I myself received some links on Linked-In pointing to this study, which at first sight seems to show that advancing feeds slowly might decrease NEC. Lets examine the data a bit more carefully. In 2009 a hospital changed their feeding policies. A paper published in 2014 reported their data from 2009 to 2012. According to the published article the paper was received on July 24th 2014, and accepted on August the 5th. Which immediately makes me wonder two things, why the authors decided to perform this study, and how do they get a paper accepted so quickly? If the authors performed the study because they saw a decrease in NEC, and then decided to do the analysis, that immediately creates a bias, many other hospitals could possibly have made a similar change and not noted any change in NEC, and therefore not looked at their data. Studies such as this are more likely to be reliable if the decision to prospectively collect and try to publish their data is made at the time that the change in therapy is introduced. But then a similar study showing no effect on NEC would be very difficult to publish, and probably not be accepted in under 2 weeks! There are a couple of concerning things in their findings, one is that after the change in the protocol there was not actually statistically any less NEC overall than before the change in protocol. Only by a subgroup analysis, was the group of babies under 750g significant, and then they did not report the p-value of the interaction, which is really essential. They showed much less NEC in the babies under 750 g birth weight than those between 750 and 1000g. Which really strongly suggests to me that this is just the result of the random nature of NEC incidence, I don't know any large study that has ever found more NEC in the larger babies. More worryingly, the new protocol led to babies having later commencement of feeds, longer use of intravenous nutrition, longer use of picc lines, and really horrendous nutritional outcomes, with over half of the babies being under the 10th percentile at discharge (admittedly that was better than the 75% with their older protocol). The feeding protocol that they introduced is entirely non-evidence based, as I have noted before here, there is no evidence from controlled trials that varying the advancement of feeds has any effect at all on the incidence of NEC. A slightly older study (from 2009) provides interesting data from the German Neonatal Network, and is, I think, much more reliable. They compared the outcomes of babies from centers where it took on average less than 12.5 days to get their VLBW babies on full feeds, to centers where it took on average more than 12.5 days to get the babies to full feeds. You can see here the clinical outcomes from the study. The only things that were different between the groups were the late-onset sepsis, which was much higher in the babies with slower feeding. Surgical NEC was slightly (non-significantly) more frequent with slower feeding, and severe retinopathy was also higher, which is entirely consistent with the recent information linking retinopathy with poorer nutrition.
  37. 3 points
    One of Annie Janvier's first research projects was a case control study of the influence of prophylactic indomethacin on intestinal perforations. Under my supervision she analyzed cases of spontaneous intestinal perforation (SIP), and we analyzed the influence of prophylactic indomethacin, which was highly significantly related. As we knew at the time, there are numerous biases in this type of research. For one, we decided to do the study because we had just had a run of SIP; often such studies are stimulated by just this kind of phenomenon. Which immediately introduces bias: what you should probably do, if you have a cluster of adverse outcomes, is to take your suspicions and analyze data from a completely independent data set, of which you are not a part. But few of us have access to such data. We had recently introduced indomethacin prophylaxis, and had this run of SIP, so the analysis did show an associations between the 2, which made us worry, but we certainly weren't convinced that the association was causal, nor that our data were free of bias. As an aside, Annie, a fellow at the time, was really pissed off when a well known senior researcher, who shall remain nameless, walked past her poster and sniggered. Don't do that folks (most of my good friends and colleagues wouldn't dream of it): even if there are flaws in the research, we should encourage junior people to be thoughtful, to try and analyze their experiences and find ways to ask and answer questions. That is a long introduction to a new publication from the NICHD database. And another beef, is it really necessary, when someone does an analysis of the NICHD database, that there are 19 authors? Did all 19 have a substantial intellectual contribution to this work? Or is it more of a little present thrown to the waiting hordes, a sort of quid pro quo, you scratch my data, I'll scratch your CV? Just asking. Kelleher J, et al, et al, et al. Prophylactic Indomethacin and Intestinal Perforation in Extremely Low Birth Weight Infants. Pediatrics. 2014. This prospective cohort comparison used the generic database to examine the incidence of SIP in babies who received prophylactic indomethacin or not, and subdivided each group as to whether they had early feeding or not. Early feeding was defined as receiving any feeds in the first 3 days of life. My European readers might laugh at that as a definition of early feeding, but there were plenty of these babies, 400 to 1000 g birth weight, who were npo for at least 3 days, indeed there were 11,000 of the 15,000 who got no enteral feeding during the first 3 days (between 1999 and 2010). As for the results, there was no evidence that prophylactic indomethacin increased SIP, and early feeding is associated with a lower rate (there may be some confounding here, as babies who have abdominal signs and maybe early signs of SIP might have feeds held as a result). Babies who had early feeding had less developmental delay at 20 months, (or, as the NICHD persists in calling it, 'neurodevelopmental impairment': if I have to say it again, a low Bayley score is not an impairment!) and the association of early feeding with better Bayley scores, was seen whether or not the babies got prophylactic indomethacin. The prophylactic indomethacin babies also did not have more NEC, and they had fewer PDA ligations. They also had much less frequent treatment with indomethacin or ibuprofen later in their hospital course, but the RR is reported as being over 1, and significant, which I don't understand. The early enteral feeds groups also had much quicker advancement to full feeds, and many fewer days of parenteral nutrition. This confirms the RCT results, with a lot more babies but an observational study design, indomethacin doesn't seem to increase SIP (despite our case-control findings) decreases PDA ligations, and adds very positive data about early feeds, at least starting feeds before 3 days of age. I think you should have a very good reason for not feeding a very preterm baby, such as shock requiring inotropes perhaps.
  38. 3 points
    Call me prescient, OK, you won't, but I will. Two recent observational studies suggest that the recent NICE guidelines have had adverse effects on infants evaluated for potential early neonatal sepsis. 'NICE' of course is not an adjective for how good the guidelines are, but the acronym for the National Institute of Health and Care Excellence in the UK. Any long time neonatalresearch watchers will remember vividly my perceptive analysis and critique of those guidelines. Which included the good (to stop antibiotics at 36 hours if no signs of sepsis) and the questionable; universal measurement of CRP at the start, with a repeat at 18 to 24 hours, and stopping the antibiotics if the trend is 'reassuring'. My concern being that CRPs are relatively sensitive but with low specificity. Infants exposed to many different stressors, infectious and not, may have increased CRP. As early onset sepsis in term infants is relatively uncommon in most of the at-risk situations outlined, the proportion of babies who have unnecessary prolongation of antibiotic therapy solely for a CRP which is not 'reassuring' might be substantial. You have, of course, to balance that against the theoretical benefit of continuing antibiotics in an infant who is truly septic, in whom the antibiotics would have been stopped were it not for the non-reassuring CRP. A benefit which is likely to occur much less often. Two recent studies have sought to quantify these impacts. Mukherjee A, Davidson L, Anguvaa L, Duffy DA, Kennea N. NICE neonatal early onset sepsis guidance: greater consistency, but more investigations, and greater length of stay. Archives of Disease in Childhood - Fetal and Neonatal Edition. 2014. This is a before-after study which investigated the impacts on babies evaluated for possible sepsis. I think this is from a single hospital in London (it is a short report so some details are missing, also weirdly there is not a single reference, not even to the NICE guidelines), and it appears that about 8-9% of babies had sepsis work-ups, with around 70 babies affected in each of the 2 month cohorts, before and after the NICE guidelines. They looked at how many babies stayed in the hospital less than 72 hours, this decreased from 38.1% to 18.4%. More babies stayed over 5 days, from 20.9% up to 27.7%. They found that 58% of the repeat CRPs were used to change management, including leading to more LPs (14% up to 23%). In all of their babies there were no positive cultures. We envisaged shorter hospital stays with new NICE standards, particularly, with the aim of 36 h blood culture reporting. However, repeat CRP led to further investigations, increased LPs and longer durations of treatment and stay. This, in turn, impacted on workload and cost, and influenced parental experience in the first few days of life Naydeva-Grigorova T, Manzoor A, Ahmed M. Management of early-onset neonatal infections. Archives of Disease in Childhood - Fetal and Neonatal Edition. 2014. This experience, published as a letter in Archives, recounts what happened with about 40 babies, before and after the guidelines. 1 of 40 before the guidelines had an LP, compared to 8 afterward. Entirely because the CRP was raised. Hospital stay increased after the guidelines, and duration of antibiotic use increased. None of the babies had positive cultures. Our results indicate that babies in group B had prolonged hospital stay requiring longer duration of intravenous antibiotics without much clinical benefit. I think there should be a rapid re-evaluation of these guidelines, which seem to be only having negative effects, at least from these 2 experiences. I think the reason that the NICE guidelines are not very nice is that the data being used to support the recommendation are based largely upon a single study from 1998, a good study from Bill Benitz in California, unfortunately (for the NICE guidelines) that study was not among asymptomatic babies, but only babies who had symptoms, the list of which includes shock, new apnea, lethargy, respiratory distress and so on, and also includes preterm infants down to 550 grams birth weight. It only included babies treated for sepsis in one of 3 NICUs. (See evidence table 10.3 in the guideline that you can find here). So it is of no relevance to the healthy full term baby with risk factors alone, in whom the false positives are clearly going to be much more frequent. In the more recent study by Thierry Lacaze and colleagues, which only included asymptomatic infants being evaluated because of signs of sepsis, a single CRP at 18 hours of age had a PPV of 14% for proven or probable sepsis. I discussed the article when it first came out, and I think the suggestion of those authors, that a low CRP at 18 hours of age, using a method which gave a result immediately to the medical team, could lead to earlier stopping of antibiotics and earlier discharge is reasonable. The implication being that a non-reassuring CRP would then mean waiting until 36 hours and making a decision independent of the CRP. For asymptomatic babies CRPs are too sensitive, being elevated for all sorts of reasons unrelated to sepsis requiring treatment.
  39. 3 points
    Neil Marlow has published a thoughtful, and thought provoking, article to address the issue outlined in the title. What are the appropriate outcomes when designing neonatal research studies? It has become almost a rule, that a multi-center trial of an intervention in neonatology, especially if it is planning to enroll very preterm infants, has to have 'survival without neurological or developmental disability' as the primary outcome, with the 'disability' part measured at about 2 years. There is some value to this outcome, very preterm infants have high mortality and high morbidity in those domains, infants who die cannot be developmentally delayed, so they are competing outcomes that need to be taken into account if we are trying to construct a dichotomous end-point. Like most things in trial design we have to make compromises, later follow up might be nice, but it will increase costs and increase drop-out rate; follow up to 2 years allows good retention rates, if you work hard at getting parents to return, but means you need to use developmental screening tools which are developed for very young infants. There are however, numerous problems with this approach, which are discussed in this piece. (Marlow N. Is survival and neurodevelopmental impairment at 2 years of age the gold standard outcome for neonatal studies? Archives of Disease in Childhood - Fetal and Neonatal Edition. 2014). I also think we do need to rethink this approach for some of the following reasons (which overlap with the reasoning of Neil Marlow) 1 Developmental delay is not a dichotomous outcome. It is convenient for research planning to think of children either having impairment or not, but of course, developmental delay is a continuum, arbitrarily deciding that a Bayley score of 69 is delayed, but a score of 71 is not, misses all sorts of nuances in outcomes. 2. Developmental delay is not stable over time: many children labelled as delayed at 2 years have intellectual abilities in the long term that are close to, or above, average (in fact according to the work of Maureen Hack, 2/3 of them do). The improvement in developmental scores is correlated more closely with social advantages than to anything which occurs in the neonatal period. 3. Developmental delay has little or no influence of quality of life. Children with developmental delay can, and usually do, have an excellent QoL. If the purpose of your research project is to decided which therapies we should use in the future, then whether or not the therapy affects quality of life should be our main consideration, but as far as I know, no therapy has been shown to affect quality of life, apart from effects on quantity of life. In other words, surfactant for RDS increases quality of life, because more children are alive to have a life of good quality! 4. Very few neonatal preterm studies have ever shown an effect on neurological impairment or developmental delay. Of all the studies in the very preterm baby, which have actually been confirmed to reduce developmental delay? Maybe someone should do a systematic review to answer that question, of the top of my head there is Caffeine (at least when defined by developmental screening at 2 years, but not when examined at 5 years), and then there is... well that's about it. So many of our decisions about which treatments are proven to be beneficial are really based on their impacts on survival, or on other morbidities, such as lung injury (another non-dichotomous outcome that we 'dichotomize' for facilitating compound outcomes). 5. Another important consideration is that the effect of an intervention on survival and on neurological or developmental outcomes may be in different directions. Which means that a trial might be 'negative' but still have important results that should change practice. I don't know if this has happened for the outcome of survival and 2 year developmental screening test scores, but it is analogous to what SUPPORT showed. SUPPORT was a negative trial. The composite primary outcome (survival without severe retinopathy) was not affected by different saturation target ranges, because the impacts on the two components of the outcome were in opposite directions. Neil Marlow includes a discussion of the TIPP trial, which showed a reduction in severe brain injury, a reduction in serious pulmonary hemorrhage, and a reduction in need for PDA ligation. But, the study did not show an overall improvement in developmental outcomes with indomethacin prophylaxis compared to control. I think it was an excellent trial with reliable results, but because of the lack of improvement in the primary outcome it has discouraged the use of prophylactic indomethacin. However, there was a reduction in severe hemorrhage from 13 to 9%: if the only effect of indomethacin on the brain or on development was the reduction in IVH, and if the patients who had a severe IVH had an increase in neurodevelopmental 'impairment'; then any benefit would only have been on those 4% who escaped IVH, and the impact on the scores of the groups as a whole would have been very small. This study was therefore grossly underpowered, in the sense that it would not be able to show that a reduction in severe IVH of that magnitude had an overall effect on the developmental scores of the entire group. In their answer to an article which questioned why prophylactic indomethacin was not more widely used, De Mauro et al stated " TIPP failed to demonstrate any long-term benefit of indomethacin prophylaxis, but the study also failed to prove the absence of long-term harm'' Which is true, but I would say it is not the whole story, because you could equally well say, ''TIPP failed to prove the absence of long term benefit, but the study also failed to demonstrate any long-term harm '' A study with no statistically significant overall effect on developmental outcome always means that there is some possibility that developmental outcomes are actually improved, or actually harmed, depending on the range of the confidence intervals of the result. TIPP gives some confidence that developmental outcomes are not dramatically harmed by indomethacin, but there will also be a possibility that in reality there is some impact on development: the confidence intervals of the study result gives us a range within which we can say, with 95% confidence, the true difference in the means of the Bayley scores lie. Uncertainty has been reduced by doing the trial, it means it is likely that the true impact on the Odds of an infant (similar to those eligible for the trial) having a Bayley score below 70 are between an Odds ratio of 0.8 and 1.4 if they receive prophylactic indomethacin rather than not. Or, to put it in terms that I find easier to conceptualize, the risk of having a Bayley score below 70 is probably (with 95% confidence) between a 17% reduction and 29% increase in risk, if you get prophylactic indomethacin. If most survivors of NICU do well (as they do) and almost all have a good quality of life (which they do) and the history of neonatal intensive care research has shown it is extremely difficult to demonstrate improved developmental outcomes at 2 years (as I discuss above); and developmental outcomes at later ages than that (when testing is more relevant for functional ability) have never been affected by a neonatal intervention, then maybe we should reconsider our outcomes. I think that trials should be designed and powered to examine effects on improving survival and other serious short term complications, such as severe cerebral hemorrhage, necrotizing enterocolitis and so forth, and that surveillance for other medium and long term outcomes, including developmental screening test scores, should be considered important for ensuring safety. I also think we should be asking parents about these things. Is a reduction in severe brain hemorrhage an outcome that they think is important, even if we can't prove an advantage in terms of Bayley scores? Which is all very similar to what Neil Marlow says in his article. So he must be right.
  40. 2 points
    This week on social media this seemed to be a hot topic. What should we do to protect ourselves as we start to see more mothers infected or at least suspected of having COVID-19 presenting in labour. Should we be assuming all of these infants are infected and if so should we all don personal protective equipment (PPE) including the N95 mask? Let’s see what we know so far. The Media The big concern with this began after a report of a 36 hour old newborn in China contracting the virus. This was published in Clinical Infectious Diseases in the paper A case report of neonatal COVID-19 infection in China. As the authors point out in this paper it is difficult to determine if the baby was born with the infection or was seeded with virus at birth and then tested positive at that point. This story made the news and sparked a lot of questions about whether newborns could be infected. The latest story to hit the news though is more worrisome as it leaves little to the question of when the infant was infected. Newborn baby tests positive for coronavirus in London from the Guardian as well as other sources publicized that a newborn who was swabbed within minutes of birth tested positive. This is enough to strike fear in just about everyone but there are questions that need to be answered before panic can set in. There really are little if any details about this patient. Were they symptomatic or was a nasopharyngeal swab positive for the virus alone? While it is tempting to link the infected newborn with transmission from amniotic fluid, there are other sources of virus such as blood and stool that can be present at delivery from the mother than could have yielded the positive result. What does the evidence say about amniotic fluid Bear in mind the data is sparse but here is what we know about amniotic fluid thus far. In a recent paper in the Lancet entitled Clinical characteristics and intrauterine vertical transmission potential of COVID-19 infection in nine pregnant women: a retrospective review of medical records. some good information was found. It is important to note that all of the infants were born via c-section so the issue of potential contamination by stool or blood was greatly reduced. All of these women had their amniotic fluid sampled and all nine tested negative for the virus. Yes I realize nine samples does not totally guarantee that virus cannot be transmitted into amniotic fluid but it is certainly reassuring as they were pure samples. Also notable was that none of the babies in the study presented with any symptoms of respiratory distress. Additionally another recent paper Infants Born to Mothers With a New Coronavirus (COVID-19) in Frontiers of Pediatrics demonstrated no neonatal infections in the three infants whose parents consented to testing for COVID-19. Presumably their amniotic fluid was free of virus as well. If you look at the total number of known cases to this point in the world summarized below we know there have been now 30 infants tested in total aside from the two cases above that have been negative. Things for the most part are looking good on the neonatal front (at least at delivery) Planning for deliveries In the twitter world this week there was much discussion about this issue. To use PPE including an N95 mask or not. I would love to tell you what you should do but that is up to your own institutions and their risk tolerance. While the media can certainly sensationalize things (and these two cases above haven’t helped stop that), the evidence would suggest at this time that these newborns are not born infected for the most part. One of the issues though is sample size for sure. How many pregnant women with COVID-19 have there been to this point? Hard to say especially since not every person can be tested. For the time being though my bet is that these babies are not born viremic but may be contaminated at birth. How long the virus takes to grab hold of the newborn and possibly cause disease is a different story altogether. Once a baby is in an NICU and develops symptoms our approach must be more cautious. We will have to see where this all goes but be careful out there.
  41. 2 points
    I have written about non-traditional methods of providing surfactant to newborns previously. The practice of intubating a preterm infant to administer surfactant and leaving the endotracheal tube in with a slow wean of ventilation is mostly a thing of the past (at least in my units). Strategies have evolved and have seen the development of the INSURE technique, LISA methods, use of an LMA to delivery surfactant and even simple deposition into the pharynx all with variable success. The Holy Grail To me at least, the Holy Grail of surfactant delivery has been aerosolization. A small non randomized study was done in by Finer et al in 2010 An open label, pilot study of Aerosurf® combined with nCPAP to prevent RDS in preterm neonates. This study noted a reduction in CPAP failure with nebulized surfactant but as a pilot was not large enough to move the needle. Since then the Cochrane group weighed in and declared that there was not enough evidence to support the practice. The CureNeb group anchored by Dr. Pillow though has now published a double blind RCT entitled Nebulised surfactant to reduce severity of respiratory distress: a blinded, parallel, randomized controlled trial. It certainly sounds interesting and might help determine if the needle has indeed moved. The Study Poractant alfa at 200 mg/kg was used in this study and delivered via aerosolization using a vibrating membrane called the eFlow. The authors chose to look at infants from 29 0/7 to 33 6/7 weeks at birth and stratified them into two groups of 29 0/7 to 31 6/7 and 32 0/7 to 33 6/7 weeks. They estimated a need for 70 babies based on an anticipated failure rate of 30% in the control group vs 5% in the treatment group. Unfortunately, due to several reasons the study was only able to recruit 64 babies for randomization before being stopped due to the recruitment issues. The design of the study included adequate blinding with a sham procedure and there were predefined “failure criteria” necessitating intubation at the outset of the study. These criteria are acceptable to me as they are similar enough to my own practice and were: 1. FiO2 >0.35 over more than 30 min OR FiO2 >0.45 at anytime. 2. More than four apnoeas/hour OR two apnoeas requiring bag and mask ventilation. 3. Two capillary blood gas samples with a pH <7.2 and partial pressure of carbon dioxide >65 mm Hg (or partial pressure of carbon dioxide in arterial blood (PaCO2) >60 mm Hg if arterial blood gas sample). 4. Intubation deemed necessary by the attending physician. What did they find? The primary outcome CPAP failure within 72 hours of birth was indeed different in the two groups. CPAP failure by 72 hours CPAP + surfactant 11/32 (34%) CPAP 22/32 (69%) (RR (95% CI)=0.526 (0.292 to 0.950)) Clearly the event rates were quite off from what they expected in the power calculation but given that they found a difference as opposed to no difference at all the fact that they didn’t recruit the numbers they planned is of less importance. However, what is interesting is when they looked at the planned analysis by stratification an interesting finding emerged. Group 1 (29 0/7 to 31 6/7) CPAP failure by 72 hours CPAP + surfactant 12/21 (57%) CPAP 12/19 (63%) (RR (95% CI)=0.860 (0.389 to 1.90)) Group 2 (32 0/7 to 33 6/7 CPAP failure by 72 hours CPAP + surfactant 1/11 (9%) CPAP 10/13 (77%) (RR (95% CI)=0.254 (0.089 to 0.727)) There were a number of secondary outcomes looked at as well which may be of interest to you but as the numbers here are quite small I will not comment other than to say there was no increased incidence of complications with surfactant administration in this fashion. Also for those who ultimately failed CPAP the time when they did so was quite delayed compared to CPAP alone. Age at intubation for nCPAP failure, hours 4.9 (2.7–10.6) 11.6 (9.0–31.1) 0.008* What can we take from this? I believe these results are encouraging even if the study is a small one. The message I take from this study is that aerosolization of surfactant delivers some amount of product to the lungs. Those with more significant RDS or smaller lungs (those in the 29 0/7 to 31 6/7 group) may not get enough surfactant to treat their RDS sufficiently to avoid intubation. Those with less significant RDS or a larger number of alveoli get “enough” of a dose delivered to the alveoli to make a difference and avoid intubation. It is worth stressing that there can be no specific comment about using this strategy in even more immature infants as they weren’t tested. If I had to guess though, I would expect no difference given the findings in the smaller group. As a physician responsible for transport though I am interested in the potential benefits to those born in non-tertiary centres. Many centres lack individuals with the confidence and skill to regularly place endotracheal tubes. For these centres it may be that providing nebulized surfactant could delay the time to treatment failure, allowing more time for a trained transport team to arrive. Training of course would be needed in these centres on how to administer surfactant in this way but it is an interesting concept to consider. With a near tripling of the average time to treatment failure the extra hours on CPAP would be much appreciated when weather delays or difficulty securing air assets means long delays in transport team arrivals. To be sure this isn’t the last study of this kind but it certainly is an interesting start and one that will no doubt produce questions that will help formulate the next study design.
  42. 2 points
    A catchy title for sure and also an exaggeration as I don’t see us abandoning the endotracheal tube just yet. There has been a lot of talk about less invasive means of giving surfactant and the last few years have seen several papers relating to giving surfactant via a catheter placed in the trachea (MIST or LISA techniques as examples). There may be a new kid on the block so to speak and that is aerosolized surfactant. This has been talked about for some time as well but the challenge had been figuring out how to aerosolize the fluid in such a way that a significant amount of the surfactant would actually enter the trachea. This was really a dream of many Neonatologists and based on a recently published paper the time may be now for this technique to take off. A Randomized Trial of Aerosolized Surfacant Minocchieri et al as part of the CureNeb study team published Nebulised surfactant to reduce severity of respiratory distress: a blinded, parallel, randomised controlled trial. This trial set out to obtain a sample size of 70 patients between 29 0/7 to 33 6/7 weeks to demonstrate a difference in need for intubation from 30% down to 5% in patients treated with CPAP (30% was based on the historical average). The authors recognizing that the babies in this GA bracket might behave differently, further stratified the randomization into two groups being 29 0/7 – 31 6/7 weeks and 32 0/7 to 33 6/7 weeks. Those babies who were on CPAP and met the following criteria for intubation were either intubated in the control group and given surfactant (curosurf) using the same protocol as those nebulized or had surfactant delivered via nebulisation (200 mg/kg: poractant alfa) using a customised vibrating membrane nebuliser (eFlow neonatal). Surfactant nebulisation(100 mg/kg) was repeated after 12 hours if oxygen was still required. The primary dichotomous outcome was the need for intubation within 72 hours of life, and the primary continuous outcome was the mean duration of mechanical ventilation at 72 hours of age. Criteria for intubation 1. FiO2 >0.35 over more than 30 min OR FiO2 >0.45 at anytime. 2. More than four apnea/hour OR two apnea requiring BVM 3. Two cap gases with pH <7.2 and PaCO2 >65 mm Hg (or) >60 mm Hg if arterial blood gas sample). 4. Intubation deemed necessary by the attending physician. Did It Work? Eureka! It seemed to work as 11 of 32 infants were intubated in the surfactant nebulisation group within 72 hours of birth vs.22 out of 32 infants receiving CPAP alone (RR (95% CI)=0.526 (0.292 to 0.950)). The reduction though was accounted for by the bigger babies in the 32 0/7 to 33 6/7 weeks group as only 1 of 11 was intubated when given nebulized surfactant compared to 10 of 13 managed with CPAP. The duration of ventilation in the first 72 hours was not different between the groups: the median (range) 0 (0–62) hour for the nebulization group and 9 (0–64) hours for the control group (p=0.220). It is important in seeing these results that the clinicians deciding whether infants should be intubated for surfactant administration were blind to the arm the infants were in. All administration of curosurf via nebulization or sham procedures were done behind a screen. The total number of infants randomized were 66 so they did fall shy of the necessary recruitment but since they did find a difference the results seem valid. Importantly, there were no differences in complications although I can’t be totally confident there really is no risk as this study was grossly underpowered to look at rarer outcomes. Breaking down the results This study has me excited as what it shows is that “it kind of works“. Why would larger babies be the ones to benefit the most? My guess is that some but not a lot of surfactant administered via nebulization reaches the alveoli. Infants with lesser degrees of surfactant deficiency (32 0/7 to 33 6/7) weeks might get just enough to manage without an endotracheal tube. Those infants (in particular less than 32 0/7 weeks) who have more significant surfactant deficiency don’t get enough and therefore are intubated. Supporting this notion is the overall delay in time to intubation in those who were intubated despite nebulization (11.6 hours in the nebulization group vs 4.9 hours in the control arm). They likely received some deposition in the distal alveoli but not enough to completely stave off an endotracheal tube. One concerning point from the study though had to do with the group of infants who were intubated despite nebulization of surfactant. When you look at total duration of ventilation (hours) it was 14.6 (9.0–24.8) in the control arm vs 25.4 (14.6–42.2) p= 0.029*. In other words infants who were intubated in the end spent about twice as long intubated as those who were intubated straight away. Not a huge concern if you are born at 32 weeks or more but those additional thousands of positive pressure breaths are more worrisome as a risk for CLD down the road. As it stands, if you had an infant who was 33 weeks and grunting with an FiO2 of 35% might you try this if you could get your hands on the nebulizer? It appears to work so the only question is whether you are confident enough that the risk of such things as pneumothorax or IVH isn’t higher if intubation is delayed. It will be interesting to see if this gets adopted at this point. The future no doubt will see a refinement of the nebulizer and an attempt to see how well this technique works in infants below 29 weeks. It is in this group though that prolonging time intubated would be more worrisome. I don’t want to dismiss this outright as I see this as a pilot study that will lead the way for future work that will refine this technique. If we get this right this would be really transformative to Neonatology and just might be the next big leap.
  43. 2 points
    If I look back on my career there have been many things I have been passionate about but the one that sticks out as the most longstanding is premedicating newborns prior to non-emergent intubation. The bolded words in the last sentence are meant to reinforce that in the setting of a newborn who is deteriorating rapidly it would be inappropriate to wait for medications to be drawn up if the infant is already experiencing severe oxygen desaturation and/or bradycardia. The CPS Fetus and Newborn committee of which I am a member has a statement on the use of premedication which seems as relevant today as when it was first developed. In this statement the suggested cocktail of atropine, fentanyl and succinylcholine is recommended and having used it in our centre I can confirm that it is effective. In spite of this recommendation by our national organization there remain those who are skeptical of the need for this altogether and then there are others who continue to search for a better cocktail. Since I am at the annual conference for the CPS in Quebec city I thought it would be appropriate to provide a few comments on this topic. Three concerns with rapid sequence induction (RSI) for premedication before intubation 1. "I don't need it. I don't have any trouble intubating a newborn" - This is perhaps the most common reason I hear naysayers raise. There is no question that an 60-90 kg practitioner can overpower a < 5kg infant and in particular an ELBW infant weighing < 1 kg. This misses the point though. Premedicating has been shown to increase success on the first attempt and shorten times to intubation. Dempsey 2006, Roberts 2006, Carbajal 2007, Lemyre 2009 2. "I usually get in on the first attempt and am very slick so risk of injury is less." Not really true overall. No doubt there are those individuals who are highly successful but overall the risk of adverse events is reduced with premedication. (Marshall 1984, Lemyre 2009). I would also proudly add another Canadian study from Edmonton by Dr. Byrne and Dr. Barrington who performed 249 consecutive intubations with predication and noted minimal side effects but high success rates at first pass. 3. "Intubation is not a painful procedure". This one is somewhat tough to obtain a true answer for as the neonate of course cannot speak to this. There is evidence available again from Canadian colleagues in 1984 and 1989 that would suggest that infants at the very least experience discomfort or show physiologic signs of stress when intubated using an "awake" approach. In 1984 Kelly and Finer in Edmonton published Nasotracheal intubation in the neonate: physiologic responses and effects of atropine and pancuronium. This randomized study of atropine with or without pancuronium vs control demonstrated intracranial hypertension only in those infants in the control arm with premedication ameliorating this finding. Similarly, in 1989 Barrington, Finer and the late Phil Etches also in Edmonton published Succinylcholine and atropine for premedication of the newborn infant before nasotracheal intubation: a randomized, controlled trial. This small study of 20 infants demonstrated the same finding of elimination of intracranial hypertension with premedication. At the very least I would suggest that having a laryngoscope blade put in your oral cavity while awake must be uncomfortable. If you still doubt that statement ask yourself whether you would want sedation if you needed to be intubated? Still feel the same way about babies not needing any? 4. What if I sedate and paralyze and there is a critical airway? Well this one may be something to consider. If one knows there is a large mass such as a cystic hygroma it may be best to leave the sedation or at least the paralysis out. The concern though that there might be an internal mass or obstruction that we just don't know about seems a little unfounded as a justification for avoiding medications though. Do we have the right cocktail? The short answer is "I don't know". What I do know is that the use of atropine, an opioid and a muscle relaxant seems to provide good conditions for intubating newborns. We are in the era of refinement though and as a recent paper suggests, there could be alternatives to consider;Effect of Atropine With Propofol vs Atropine With Atracurium and Sufentanil on Oxygen Desaturation in Neonates Requiring Nonemergency IntubationA Randomized Clinical Trial. I personally like the idea of a two drug combination for intubating vs.. three as it leaves one less drug to worry about a medication error with. There are many papers out there looking at different drug combinations. This one though didn't find a difference between the two combinations in terms of prolonged desaturations between the two groups which was the primary outcome. Interestingly though the process of intubating was longer with atropine and propofol. Given some peoples reluctance to use RSI at all, any drug combination which adds time to the the procedure is unlikely to go over well. Stay tuned though as I am sure there will be many other combinations over the next few years to try out!
  44. 2 points
    Given that today is world prematurity day it seems fitting to talk about prematurity at the absolute extreme of it. It has been some time since as a regional program we came to accept that we would offer resuscitation to preterm infants born as early as 23 weeks gestational age. This is perhaps a little later in the game that other centers but it took time to digest the idea that the rate of intact survival was high enough to warrant a trial of resuscitation. This of course is not a unilateral decision but rather a decision arrived at after consultation with the family and interprofessional team. To be sure it is not an easy one. Other centers have argued that resuscitation should be offered to those infants as young as 22 weeks gestational age and data now exists due to enough centres doing so to provide families with some guidance as to expected survival rates and importantly the likelihood of disability. This topic has been covered previously in /2015/09/25/winnipeg-hospital-about-to-start-resuscitating-infants-at-23-weeks/. Why cover this topic again? Well an article on CNN might have something to do with it. Resuscitating Below 22 weeks This week as I was perusing the news I came across a rather shocking article on CNN. Born before 22 weeks, ‘most premature’ baby is now thriving. The article tells the tale of a baby delivered at 21 weeks and 4 days that now as a three year old is reaching appropriate milestones without any significant impairments. It is a story that is filled with inspiration and so I am not mistaken I am delighted for this child and their family that this outcome has occurred. When the lay press latches onto stories like this there is no doubt a great deal of sensationalism to them and in turn that gathers a lot of attention. This in turn is a great thing for media. A Few Caveats Though With the exception of pregnancies conceived through IVF the best dating we have is only good to about +/- 5 days when an early first trimester ultrasound is performed or the date of the last menstrual period is fairly certain. A baby though who is born at 21 weeks + 4 days may in fact be 22 +3 days or even more depending on when the dating was done (second trimester worse). Let’s not take away though from the outcome being this good even at 22 weeks. That is a pretty perfect outcome for this family but the point is that this baby may in fact be older than 21 weeks. Secondly, there are millions of babies born each year in North America. Some of these infants are born at 22 weeks. How do they fare overall? From the paper by Rysavy et al from 2015 the results are as follows. If you look at the overall rate of survival it is on an average of 5.1%. If you take a look though at those infants in whom resuscitation is provided that number increases to a mean of 23%. Intact survival is 9% overall. The odds aren’t great but they are there and I suspect the infant in the article is one of those babies. Flipping the argument though to the glass is half empty, 91% of infants born at 22 weeks by best estimate who are offered resuscitation will have a moderate or severe disability if they survive. I am not saying what one should do in this situation but depending on how a family processes the data they will either see the 110 chance of intact survival as a good thing or a 9/10 chance of death or disability as a very bad thing. What a family chooses though is anyone’s best guess. Should we resuscitate below 22 weeks if the family wishes? I guess in the end this really depends on a couple things. First off, how certain are the dates? If there is any degree of uncertainty then perhaps the answer is yes. If the dates are firm then I at least believe there is a barrier at which futility is reached. Perhaps this isn’t at 21 weeks as some patients may indeed be older but think about what you would offer if a family presented at 20 weeks and wanted everything done. What if it were 19 weeks? I suspect the point of futility for all lies somewhere between 19-21 weeks. As I prepare to attend the annual meeting in Ottawa tomorrow for the Fetus and Newborn Committee I think it is prudent to point out just how difficult all of this is. The current statement on Counselling and management for anticipated extremely preterm birth I think hits on many of these issues. The statement is the product on not only the think tank that exists on this committee but was the product of a national consultation. I know I may be biased since I sit on the committee but I do believe it really hits the mark. Should we be thinking about resuscitating at 21 weeks? For me the answer is one clouded by a whole host of variables and not one that can be easily answered here. What I do think though is that the answer in the future may be a yes provided such infants can be put onto an artificial placenta. Even getting a few more weeks of growth before aerating those lungs is necessary may make all the difference. The NICUs of tomorrow certainly may look quite different than they do now.
  45. 2 points
    I have written about respectful communication before in Kill them with kindness. The importance of collaborating in a respectful manner cannot be overemphasized, as a calm and well prepared team can handle just about anything thrown their way. This past week I finally had the opportunity to take the 7th ed NRP instructor course. What struck me most about the new version of the course was not the approach to the actual resuscitation but the preparation that was emphasized before you even start! It only takes 30 seconds to establish who is doing what in a resuscitation and while it would seem logical to divide up the roles each will take on it is something that has not been consistently done (at least in our institution). When a baby is born and responds to PPV quickly, this may not seem that important but in a situation where a team is performing chest compressions, placing an emergency UVC and moving on to epinephrine administration it certainly is nice to know in advance who is doing what. The Golden Hour We and many other centres have adopted this approach to resuscitation and at least here developed a checklist to ensure that everyone is prepared for a high risk delivery. While teams may think they have all the bases covered, when heart rates are racing it may surprise you to see how many times crucial bits of information or planning is missed. As I told you in another post I will be releasing a series of videos that I hope others will find useful. The video in this case is of a team readying itself for the delivery of a preterm infant that they anticipate will have respiratory distress. Ask yourself as you watch the film whether your team is preparing to this degree or not. Preparing in such a fashion certainly reduces the risk of errors caused by assumptions about who is doing what or what risk factors are present. As you can tell I am a big fan of simulation in helping to create high functioning teams! More of these videos can be accessed on my Youtube channel at All Things Neonatal YouTube To receive regular updates as new videos are added feel free to subscribe! Lastly a big thank you to NS, RH and GS without whom none of this would have been possible!
  46. 2 points
    A 28 week preterm infant now two weeks of age develops bilious emesis and abdominal distension. An x-ray reveals an intestinal perforation and surgery is consulted. Arrangements are made to go to the operating room for a laparotomy and due to apnea and hypotension the baby is both intubated and placed on dopamine. The resident on service ensures that blood is available in the operating room and an hour after presentation the baby is found to have a HgB of 102 g/L with a HcT of 35%. I don’t know about you but if I am then asked whether we should give blood now or in the OR I might say at that level with the degree of illness to give blood or I might say wait till the baby gets to the OR if perhaps they were fairly stable on the support. You the reader might be more convinced of your actions but if I manipulate the numbers a little bit to say 105 g/l and HcT of 37% might you feel different? What about 110 g/L and 39%? You get the picture. Where is that magic cutoff where we say prior to an OR that a baby needs blood or can wait? In our heads of course we conjure up the equation for delivery of O2 to tissues Cardiac output X (1.39 X HgB X Sat +0.003*pO2) and realize that the delivery of oxygen is critically dependent on HgB level but how much is enough? The truth is I don’t think we really know but we do a good job of coming up with some markers such as lactate or more recently near infrared spectroscopy to give us an idea of how much O2 the tissues are seeing. How much HgB does a baby need before surgery? Although this may seem like something that is well known, the truth is we don’t really know. We may have an inkling though based on a recent paper entitled Association of Preoperative Anemia With Postoperative Mortality in Neonates by S. Goobie et al. They performed a retrospective review of a US surgical quality database to examine mortality after operations and identified 2764 neonates out of 114395 children who underwent surgery. Similar to previous studies the neonatal postoperative mortality rate was higher at 3.4% than the rest of childhood at 0.6%. When examining the effect of low hematocrit prior to surgery they further identified a cutoff of 40% below which the risk of mortality increased. Of the neonatal group that survived 31% had a preop hematocrit of 40% or more while of those who died 72% had a hematocrit < 40%. Hematocrit was not the only factor predicting mortality though as ASA class 3 – 5 (an anesthesiology risk score where these scores indicate severe systemic disease or emergencies), weight < 2 kg, preoperative ventilation and inotropic support. Put simply, sicker small patients have worse outcomes which I suppose should not surprise anyone. So how do we interpret this data? One important point that this article does not control for is the specific type of condition that the patient had. Clearly all conditions of the newborn are not the same as for example an umbilical flap closure of gastroschisis compared to fulminant necrotizing enterocolitis. The authors do try and control somewhat for this by demonstrating that the ASA categories demonstrate if you have severe systemic disease you are worse off but where does this leave the hematocrit? The other possible explanation is that the anemia is simply a reflection of the critical nature of the patient. Sicker patients are more likely to be anemic and also patients who present later are as well. A baby needing a colostomy for a bowel obstruction diagnosed after birth is likely to have low risk of mortality and also have a normal HgB. Contrast this with the baby who develops NEC at 3 weeks of age who is likely anemic or close to being so when they present and in the presence of shock and DIC becomes even more so. Is the low HcT just a proxy for severity of disease? I suspect for the otherwise well infant who is electively intubated for surgery, having a hematocrit alone below 40% is not dangerous. What do we do though with the baby who is on inotropes for example. To truly answer this question we need a randomized controlled trial comparing transfusing patients with a hematocrit below 40% vs choosing a higher threshold of say 50% to say whether it makes a difference. That doesn’t help us though in the here and now. This gold standard for studies won’t tell me what to do for a few years but right now I have to decide what to do for a patient in front of me. Not everyone may agree with me on this but I think in such circumstances I would transfuse based on this publications results. To the naysayers out there I would suggest that whether I choose to give the blood or not before the operation, they will be getting it after they enter the OR. Why not give them a boost before they undergo the knife? It is not a question of whether they will be transfused or not it is a difference in time. If I have the chance I will “top them up” but what will you do?
  47. 2 points
    As the practice seems to be winning the world over you can imagine that a headline entitled, 'Skin-to-skin' fad blamed for deaths of babies would get some attention. This article was sent to me by a colleague after being published last month on Yahoo news service. The claim is based on the experience of a hospital in Perth that has seen some cases of neonatal suffocation after mothers who were performing skin to skin care fell asleep and rolled onto their newborn. This "fad" they say is attributable as the cause of death. Before looking into whether there is any basis for such a claim it may be worth exploring whether Kangaroo Care (KC) otherwise known as Skin to Skin (STS) care is effective. Is KC Effective in the NICU? KC or is an ideal method of involving parents in the care of their premature infant. It fosters bonding between parents and their hospitalized infant, encourages the family to be with their child and thereby exposes them to other elements of neonatal care that they can take part in. Before you reach the conclusion that KC only serves to enhance the parental experience it does so much more than that. The practice began in Bogota Columbia in 1979 in order to deal with a shortage of incubators and associated rampant hospital infections. The results of their intervention were dramatic and lead to the spread of this strategy worldwide. The person credited with helping to spread the word and establish KC as a standard of care in many NICUs is Nils Bergman and his story and commentary can be found here. The effects of KC are dramatic and effective to reduce many important morbidities and conclusively has led to a reduction in death arguably the most important outcome. An analysis of effect has been the subject of several Cochrane Collaboration reviews with the most recent one being found here. To summarize though, the use of KC or STS care has resulted in the following overall benefits to premature infants at discharge or 40 - 41 weeks' postmenstrual age: Reduction in mortality (typical RR 0.68, 95% CI 0.48 to 0.96) nosocomial infection/sepsis (typical RR 0.57, 95% CI 0.40 to 0.80) hypothermia (typical RR 0.23, 95% CI 0.10 to 0.55) Increase in KMC was found to increase some measures of infant growth, breastfeeding, and mother-infant attachment To put this in perspective, medicine is littered with great medications that never achieved such impact as simply putting your child against your chest. This is another shining example of doing more with less. This is not to say that modern medicine and technology does not have its place in the NICU but KC is simply too powerful a strategy not to use and promote routinely in the NICU. What About Term Infants? Much has been written on the subject. A Pilot study in 2007 by Walters et al found benefits in newborn temperature, glycemic control and initiation of breastfeeding. Perhaps the strongest evidence for benefit comes from a cochrane review of the subject last updated in 2012. Early skin-to-skin contact for mothers and their healthy newborn infants. This analysis included 34 RCTs with 2177 participants (mother-infant dyads). Breastfeeding at one to four months postbirth (13 trials; 702 participants) (risk ratio (RR) 1.27, 95% confidence interval (CI) 1.06 to 1.53, and SSC increased breastfeeding duration (seven trials; 324 participants) (mean difference (MD) 42.55 days, 95% CI -1.69 to 86.79) but the results did not quite reach statistical significance (P = 0.06). Late preterm infants had better cardio-respiratory stability with early SSC (one trial; 31 participants) (MD 2.88, 95% CI 0.53 to 5.23). Blood glucose 75 to 90 minutes following the birth was significantly higher in SSC infants (two trials, 94 infants) (MD 10.56 mg/dL, 95% CI 8.40 to 12.72). Taken together there are benefits although the impact on breastfeeding rates in term infants show a strong trend while not reaching statistical significance. Importantly though in this large sample we don't see any increase in mortality nor to my knowledge has there ever been a study to show an increase. How do we deal with this claim from Australia then? I think the problem with this claim is that KC is being blamed after a "root cause analysis" has come to the wrong conclusion. The problem is not KC but rather a lack of a "falls prevention" strategy on the postpartum units. Mothers after delivery are exhausted and may be on pain medication so as the saying goes "there is a time and a place". As our hospital prepares for accreditation again, safety to prevent falls (including babies falling out of mom's arms or in a similar vein mothers falling onto babies) is something that every hospital needs. Whether a mother is practicing KC, breastfeeding or simply holding her baby if a mother falls asleep while doing so there is a risk to the infant. If the hospital in this case has seen an increase in such cases of newborn deaths while performing KC then it is likely the hospitals lack of attention to minimizing risk in the postpartum period that is to blame and not KC itself. Certainly the evidence from rigorously done trials would not support this claim. This hospital would do well to have a comprehensive plan to educate parents about the risks of fatigue, ensure bassinets are next to every bed to provide mothers with an easy transfer if they are tired. Certainly during the immediate period after delivery mothers, partners of mothers who have just delivered should be encouraged to be with them or advise the mothers if they are tired to put the baby down and rest. A little education could go a long way! I think it is a cheap out to blame KC for such problems as it turns our attention away from the real issue and that is a lack of policy and education. So in the end I would like to state emphatically that... No I don't believe the "skin-to-skin fad" is to blame for an increase in deaths!
  48. 2 points
    The long-running epic of the oxygen saturation targeting trials is nearing completion. This publication of the joint results of the Australia and UK trials now includes the primary outcome for the trials, the combined rate of death or "disability". Australia Boost-II and United Kingdom Collaborative Group. Outcomes of Two Trials of Oxygen-Saturation Targets in Preterm Infants. The New England journal of medicine. 2016. Disability is defined as being a cognitive or language score on the Bayley-3 of less than 85, severe visual loss, or disabling CP (GNFCS of 2 or more). I will avoid (for a change) ranting about the inappropriateness of referring to a Bayley cognitive or language score of less than 85 as a "disability". Because of what happened during the trials the analysis can seem quite complex. But the overall message is that the adverse outcome was increased in the low saturation group when the two trials are combined, however you slice the data. In case there are any readers who don't know, a calibration artefact was discovered during the trials, which was corrected, leading to each of these trials, and the COT trial, to have babies with oximeters from a before-correction group and an after-correction group. In the two trials, the difference in mortality only occurred after the change in oximeter algorithm, whereas the smaller NZ trial used only the original algorithm and didn't find an effect on mortality (or on long term outcome) and SUPPORT, with somewhat different entry criteria, did show a difference in mortality despite using only the original oximeters. The Canadian Oxygen Trial also showed a higher mortality in the low saturation group after the oximeter adjustment, but it didn't reach statistical significance. The new publication shows no effect of the trial on "disability", but the analysis of the primary outcome "death or disability" was significant for the pooled data. What gets complicated is that the UK group changed their primary outcome during the trial to be the rate of death or disability with the revised oximeters, whereas the Australians kept this as the whole group. In the UK the oximeters were changed after roughly ¼ of the babes were enrolled, while in Australia 3/5 of the babies were studied with the original devices. So the primary outcome analysis of the original trials presented doesn't include some of the randomized babies (in the UK trial), which bothers me a bit, but their data are presented and analyzed. And then there is quite a lot of detail in one of the tables. The combined outcome of death or disability was significant for the pooled data which included all of the randomized babies (48% vs 43%) and not far from significant for the revised oximeters (49% vs 44%, RR 1.12, 95% CI 0.99-1.27). As I mentioned above, there isn't any sign of an effect on disability, the difference is all in mortality, now updated to mortality before 2 years of age, most dramatically when the analysis is restricted to the revised oximeters. For the revised oximeters alone the relative risk of death in the low saturation target group was 1.45, (95% CI 1.16 to 1.82). As everyone now who has Masimo oximeters, they use the new algorithm, and other oximeters were never affected, this is the part of the results which is now most relevant, and I think needs to be taken very seriously. One comment I would like to make is that the primary analysis for the trials is described as "pre-specified". But how can the analysis by oximeter algorithm be pre-specified if the problem was discovered during the trial? Pre-specified is supposed to mean, "determined before the trial started". I think the analysis is just fine, the dilemma about what to do when this was discovered part way through a trial is not easily resolved, and the different choices of the 2 trials can both be justified. It is the use of the word "pre-specified" that I think is incorrect. Also the definition of disability was changed after the study commenced as they (quite appropriately) changed from the Bayley version 2 to the Bayley version 3. The authors describe these events quite clearly in the text, but as they were changed after the trial started they shouldn't be referred to as pre-specified. the authors are using the term to mean specified before the analysis was started, which is of course essential and very important, to avoid picking data that look interesting after they have been collected. To end the saga that I mentioned at the beginning now only needs the NeoPROM collaborative to analyze the individual patient data. It's hard to think that this will give any result other than an increase in mortality with the lower oxygen target. One other outcome of interest is that in this trial, as in all the others, there was no increase in blindness. This despite an increase in retinopathy requiring treatment. This was also seen in the SUPPORT trial, but there was no increase in retinopathy in COT. I think this means we can be a bit re-assured that the use of carefully targeted saturations in the low 90's will not lead to a new epidemic in blindness; but should not be sanguine about the risks of targeting the higher saturation group, treatment of retinopathy is not, by any means, without consequences, even if we can usually prevent blindness, very severe myopia, loss of peripheral vision, and poor cosmetic results are common.
  49. 2 points
    Ask almost anyone who has worked in the field of Neonatology for some time and they will tell you that babies are not as sick as they once were. We can give a lot of credit to better antenatal steroid use, maternal nutrition and general management during pregnancy. Additionally, after birth we now rush to place infants on CPAP and achieve adequate expansion of the lungs which in many cases staves off intubation. The downside to our success though is that the opportunities to provide positive pressure ventilation (PPV) and moreover intubation are becoming less and less. How then do we perform when we are asked to do such procedures on an infrequent basis? The answer as you might expect is not that well. Dr. Schmolzer et al studied the ability of people to keep a good seal and found a 29% leak on average with as high as 63% in one patient. As this was a study in which people were being observed one might think the Hawthorne Effect might artificially decrease the percentage leak compared to real world scenarios when you know you aren't being watched. What is the cause of the leak? Leaks most commonly occur on either side of the nasolabial folds. Although at least in my experience we educate trainees about this issue it remains a problem. I would also speculate that at the times when we need to be at our best during an advanced resuscitation involving chest compressions we may well function at our worst. This is the effect of the adrenalin rushing through our system as our sympathetic system turns into overdrive. The question therefore is one of getting around human error in particular when we need to minimize such inefficiency the most. The Solution? If the masks are prone to leaking and with it the ability to properly ventilate compromised, how could we minimize such human error. The answer may lie in what I consider to be an ingenious way to apply a mask. The concept and it is just that at the moment is to use suction to apply the mask to the face without risk of leak. Lorenz L et al have just published a proof of concept study utilizing a mannequin with a "seal skin" layer applied to the face to simulate human skin. The article is entitled A new suction mask to reduce leak during neonatal resuscitation: a manikin study. In this study, the mask was applied to the face of the mannequin and 100 cm H2O pressure was applied through a side port on the mask. There is an inner and outer ring such that the internal 41 mm diameter mask is surrounded by a double wall in which the suction is applied to the space between the two walls leading to the mask seating itself firmly against the face. The authors then studied the amount of leak found when using a Neopuff set to deliver 40 - 60 breaths per minute at pressures of 25/5. For this study 60 courses were tested. How did it do compared to PPV through a traditional mask? As you might expect (since you can feel my excitement!) it did very well. The average leaks using a conventional approach were quite good at 12.1% but the suction mask was only 0.7% leak. Importantly the ranges were quite different. PPV through a conventional mask had a range of 0.6 - 39% leak while with the suction version it was 0.2 - 4.6%. These results were statistically different. What does the future hold? As mentioned this study is what one would consider a proof of concept study. We do not know how this would fare in the real world and that of course is the next step. In terms of harm, the authors did note that when applied to the forearm of an adult it caused some mild redness from the suction that vanished quickly on breaking of the seal but we do not know if there could be greater harm in a newborn in particular one who is quite small. Such testing will be needed as part of any further study. Having said that I think this rethink of the mask for PPV could be transformative to those who perform neonatal resuscitation infrequently. If this mask is found not only to be effective in a clinical trial but safe as well I would suggest a change to this type of mask could quite literally be life saving. Placed in the hands of those who are inexperienced in keeping a seal, PPV would become much more effective and in particular for rural sites the infants being transported in much more stable than some are at present. Keep your eyes peeled for future work using this mask. Something tells me if it proves to be efficacious outside of a seal skin covered mannequin, your toolkit for providing NRP may be in for a change.
  50. 2 points
    As anyone who has been reading this blog knows, I have an affinity for anything that is non-invasive and improves the care of newborns. Add to this my interest in Neonatal Abstinence (which has been the focus of other pieces such as Long term cognitive deficits in infants exposed to in-utero opioids and polysubstance use. In a rare finding, girls may have worse outcomes.) and a recent report of laser acupuncture for adjuvant treatment of neonatal abstinence syndrome would have to pique my interest. In 2014 a case report entitled Laser acupuncture as an adjuvant therapy for a neonate with neonatal abstinence syndrome (NAS) due to maternal substitution therapy: additional value of acupuncture. was published by Raith. I recall seeing this paper prior to starting this blog and Facebook page and made a mental note to check it out someday. That someday is upon me now that an RCT has been published on the subject which will be looked at below. What is laser acupuncture? Before we get into critiquing such a study it is worth explaining what laser acupuncture is. From the website acupuncture today I found the following background: "In 1991, a study was done in Novosibirsk, Russia that applied directly to the study of acupuncture. Researchers shined light on various parts of the body and found that light traveled under the skin to other acupuncture points, but it didn't travel to places that were not on acupuncture meridians. It appears that the body contains a sort of fiber optic network—where light enters an acupuncture point, travels through the meridian and can be detected at other places along the meridian with a sensitive photon detector. This is a fascinating study showing how light is actually received, used and transmitted throughout the body." The RCT in question above is another paper by Raith W et al Laser Acupuncture for Neonatal Abstinence Syndrome: A Randomized Controlled Trial. This study compared patients receiving treatment for NAS with morphine and phenobarbital and compared 14 in each group on a blinded fashion to laser acupuncture or nothing in addition to the standard regimen. They avoided the need for a placebo in that the intervention was done by the health care provider and then a separate person calculated a pain score who was blind to whether the laser had been provided or not. By blinding the people scoring they hoped to address the criticism that would be present had the study been unblinded. The acupuncture was performed daily at five ear and four body points bilaterally with the primary outcome being duration of oral opiate use. The authors found a reduction in days of opiate treatment but being a small study it would be considered a pilot at best. The results were 28 days (22 to 33) vs 39 days (32 to 48), respectively, P =.019 and the authors make a comment that phenobarb levels were similar between the groups as well but with overall shorter lengths of stay of 35 days (25 to 47) vs 50 days (36 to 56), respectively, P = .048. There are several issues with the study though and they are as follows. Yes, the light therapy was provided behind a closed door but how do we know that the providers truly kept it a secret during the whole stay of the patient? What medications were the mothers taking and at what doses and for what duration? Was the exposure between groups really the same? Also there was no standard means of weaning that I can see so how do we know by chance that the difference is simply who was on at the time with respect to physician deciding on aggressiveness of weaning. Another issue is that women on replacement medications such as methadone or suboxone were excluded as were women with polysubstance abuse. How close to our patient population really were these patients? Lastly, nearly significant was a preponderance of males in the conventional group and we all know how males generally do compared to females in most studies. Nonetheless it is a exciting study to imagine an effect from and that is what the authors I think were banking on. What about laser acupuncture for treatment of pain? One other study comparing sucrose to laser acupuncture for prevention of pain with heel lances. In this study of 42 infants randomized to the intervention or sucrose the authors concluded that sucrose was superior to acupuncture for managing pain from heel lancing. This study did not have a third arm in which no treatment was given (likely due to it being unethical) so what we can't say for sure is whether laser is better than nothing. Personally I find a bit of a leap to believe that shining a light through the skin would have an effect on pain perception by anyone. I can certainly understand the concept of putting a needle into tissue or applying pressure no different from the effect of rubbing ones temples when they have a headache (works for me at least). The Chemistry major in me though has trouble with the effect of photons passing through tissue even if directed at acupuncture points. Having said that the only positive thing I can say is that a quick search for such instruments shows them to be commercially available and as cheap as $50 or so. I have no doubt there are people who will read this RCT and be impressed with its additional purported impact on NAS and thankfully if they do decide to pursue this intervention they will not have spent a fortune on it. Money in health care should be directed to what works to help patients and the skeptic in me just isn't buying this even if it appeals to my curiosity with non-invasive strategies.
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