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Found 9 results

  1. As time goes by, I find myself gravitating to reviews of Canadian research more and more. We have a lot of great research happening in this country of ours and especially when I see an author or two I know personally I find it compelling to review such papers. Today is one of those days as the lead author for a paper is my colleague Dr. Louis here in Winnipeg. Let me put his mind at ease in case he reads this by saying that what follows is not a skewering of the paper he just published using Canadian Neonatal Network data (CNN). Over the last twenty years that I have had the privilege of working in the field of Neonatology we continue to discuss the same things when it comes to the PDA. Does it really cause problems or is it an association for many outcomes? Does treatment make a difference? If you treat then what should you use (ibuprofen, indomethacin, paracetamol)? When should you treat and if you treat early should it be in the first few days or right after birth using a prophylactic approach (provided within 12 hours of delivery)? It is the prophylactic approach which is the subject of this post! Why treat prophylactically? The TIPP trial reported the results in 2001 of the study whose goal was to determine if prophylactic indomethacin use could improve neurosensory impairment at 18 months by reducing rates of severe IVH. The results of the study are well known and showed that while the rates of severe IVH and PDA ligations were reduced through this approach, there was no actual effect on long term outcome. The use of this approach fell off after that for many years but recently resurfaced as some units in Canada opted to start the practice again as the two benefits seen above appeared to be worth using the approach. The thought from a family centred approach, was that eliminating the stress for families of informing them their tiny preterm infant had a serious intracranial bleed and potentially avoiding a surgical ligation with probably vocal cord impairment afterwards were good enough outcomes to warrant this practice. Having used this approach myself I have to admit one consequence is that indomethacin was so effective at closing the PDA most of the time that over time one begins to assume the PDA is in fact closed and is less likely to go hunting for one when the baby is misbehaving later on in their course. What if it didn’t close though? Are there any predictors that can increase our index of suspicion? Answering the question The CNN provides a large database to look retrospectively to answer such a question. In this article, the authors looked at a period from 2010 to 2015 including all infants < 28 weeks gestational age at birth yielding a very large sample of 7397 infants. Of these 843 or 12% received prophylactic indomethacin and from there a little over half (465) still had a PDA. From there, 367 received treatment with eventually 283 needing only medical, 11 having a PDA ligation and 73 having both medical and surgical closure. From this analysis so far I can tell you that providing prophylactic indomethacin certainly does not guarantee closure! When a myriad of risk factors were put into logistic regression a number of interesting risk factors arose accounting for more of less risk of a PDA that needed surgical ligation despite prophylactic treatment. Much like all infants in the NICU, the risk for a persistent PDA was highest with declining GA. The combination of outborn status and short interval of ruptured membranes predicted higher risk. No doubt this is reflective of less frequent antenatal steroid use and even if provided time for it to work. Looking at medical or surgical treatment, surfactant therapy increased risk which may be explained by an improvement in oxygenation contributing to increased left to right shunting as PVR drops. Maternal hypertension and longer duration of rupture of membranes again play a role in reducing risk likely through the mechanism of the former increasing endogenous steroid production and the latter again allowing for steroids to be provided. What can we learn from this paper? I suppose the biggest benefit here is the realization that even with prophylactic indomethacin we are not assured of closure. In particular if there is a lack of antenatal steroid use or a stressed fetus one should be vigilant for the PDA. Interestingly, all of the risks seem to point towards antenatal steroid use. The bottom line then is that this reinforces what is already known and should be the focus of improvement strategies for centres. Increase the rate of antenatal steroid use and you will reduce the risk of a PDA even in the baby receives prophylactic indomethacin. I am happy to report that our centre has taken one step towards this goal by reinforcing to our Obstetrical colleagues that when they receive a call from a referring centre and have a woman who might be in labour it is better to err on the side of caution and just give the steroid course. If they are wrong on arrival then one can always repeat a course later on as we do although repeated courses of steroids are in and of themselves a contentious issue. What can your centre do to improve your results when it comes to antenatal steroid coverage?
  2. There may be nothing that is harder in medicine. We are trained to respond to changes in patients condition with a response that more often than not suggests a new treatment or change in management. Sometimes the best thing for the patient is in fact to do nothing or at least resist a dramatic response to the issue in front of you. This may be the most common issue facing the new trainee who is undoubtedly biased towards doing something. Take for instance the situation in which the trainee who is new to the service finding out that their 26 week infant has a PDA. Their mind races as they digest this information from morning signover. There is less than 2 hours until they come face to face with their attending who no doubt will ask them the dreaded question. “What are you going to do about it?”. When having to choose a path, if they state “I want to sit tight and watch” they fear the thought of the attending thinking they don’t know what to do. Conversely they could stick their neck out and choose to treat with a variety of approaches but then might they be seen as too aggressive?! The likely path is suggesting treatment but in fact the more I think about it the option of benign neglect may be the best approach or at least one in which if you treat and it doesn’t work the first time you just shrug your shoulders and say “I’ll deal with it till it closes on it’s own”. This post really is a follow-up to a previous one entitled The Pesky PDA. A Puzzle After All These Years. What triggered this writing was another before and after comparison of two periods in which the management of PDAs for a unit took a 180 degree turn. Know When to Hold Em And No When to Fold Em This is the essence of the issue for one unit. Sung SI et al published a paper this month entitled Mandatory Closure Versus Nonintervention for Patent Ductus Arteriosus in Very Preterm Infants. They describe a before and after comparison of 81 infants from 2009-11 and 97 infants from 2012-14. All babies were born between 23-26 weeks gestational age. In the first time period their unit had a mandatory PDA closure policy. That is they gave one course of indomethacin and if possible a second course followed by surgical ligation. A significant PDA was defined as one that had a left to right shunt and was at least 2 mm in diameter and the patient had to be ventilated. Any patient who had been extubated regardless of need for CPAP did not have to have their PDA closed. In the second time period the group attempted to avoid indomethacin and ligation at all costs and in fact in this cohort none received either. So What Happened? In the first time period 52 (64%) received indomethacin but only 29% responded and a full 37/52 (71%) went on to receive surgical ligation. Of the 29 that did not receive indomethacin due to contraindications they underwent primary ligation for a total of 82% receiving surgical ligation. The average day of closure for period 1 was 12.9 days. In period 2 a number of interesting findings occurred. The average day of closure was at 44.2 days. Five infants were discharged with a PDA with 3 experiencing spontaneous closure after discharge and the remaining infants undergoing transcatheter occlusion. In period 2 there were more diuretics and fluid restriction employed. Comparing the two periods for a number of other outcomes reveals some other intriguing findings. Even with such differing approaches there is no difference in mortality, severe IVH, ROP, PVL, NEC or sepsis. What is different though is the diagnosis of BPD yet there is no difference in total ventilation. In period 2 there is a shift towards more of this ventilation being HFOV less CPAP use at the same time. What Might It All Mean? It is retrospective and therefore we cannot be certain that there are not other variables that are not affecting the results that would have had a better chance of being evened out in an RCT. Having said that it is intriguing that having a PDA has been associated with BPD in the past but in this study having a PDA for a longer time is associated with a reduction in BPD. We know that longer periods of invasive mechanical ventilation increase the risk of developing BPD so it is intriguing that that there is no difference in mechanical ventilation yet there is more BPD when you are aggressive with the PDA. You might postulate that the need for surgery leads to greater need for ventilatory support and therefore damages the lungs but the needs for HFOV was higher in the second phase which at least hints that in terms of aggressiveness, Period 2 infants had a tougher go. The culprit may be the heart. In period 1 there was a significantly increased rate of myocardial dysfunction and need for inotropes following ligation. It could well be that left ventricular dysfunction led to pulmonary edema such that in the 24-28 hours after the surgery ventilator requirements were increased and damaged the lung. The lack of a difference in overall ventilation days supports this possibility. Looking at the other common risk factors for BPD such as chorioamnionitis and lack of antenatal steroids these are no different between groups. Although not statistically significant there are more male infants in period 2 which would usually tip the scales towards worse outcome as well. It does need to be stressed as well that the rate of surgical ligation is higher than any study I have come across so the contribution of the surgery itself to the disparate outcome needs to be seriously considered. What would I do? Despite this study and some others that have preceded it I am not at the point of saying we shouldn’t treat at all. Our own approach is to give prophylactic indomethacin to such babies and then for the most part if a PDA remains treat one more time but at all costs try and avoid ligation. An RCT sounds like it is in the works though comparing the two approaches so that will certainly be interesting to see. It is tough to say what the future holds but to any young trainees who are reading this, the next time you are asked what to do about a PDA you are well within your rights to suggest “Maybe we should do nothing”!
  3. Several people contacted us after the webcast on Echocardiographic assessment of PDA (broadcasted Thursday 26th), and asked if it was possible to view it afterwards. The answer was first no... but Orphan-Europe, the company organizing the webcast, generously emailed a copy and allowed sharing here through the Vimeo-service. The webcast was presented by Dr Nim Subhedar, Consultant Neonatal Paediatrician NICU Liverpool Women’s Hospital. Enjoy!
  4. until
    Participate in an interactive webcast on the Echocardiographic Assessment of PDA Thursday 26th of November at 3pm CET The webcast is presented by Dr Nim Subhedar, Consultant Neonatal Paediatrician NICU Liverpool Women’s Hospital, and is organized by Orphan-Europe. Connection details Link: meet.republic-m.comGuest code: 57876FLYERA5.pdf
  5. Finally, the first 99nicu Journal Club is scheduled, on Tuesday the 24th of November, 5 PM (GMT). The JC will be held in the Chat room on 99nicu.org. To attend, you need to log in with your membership credentials (username/password), and then you find the "Chat" in the navigation menu above. Our current software license enables up to 20 people to attend, so there is a risk that some may not get in. If the discussions will be attracting lots of people, we could upgrade the license to allow more people in the Chat room (although that means a higher license cost). the Topic of the first JC is ductal shunting, and the natural evolution of the PDA and the great chance of spontaneous closure. The paper was published in ADC some time ago. A complementing paper is the findings from Epipage2, published in JAMA this summer, about the benefits of early echocardiography. Find the papers here: http://fn.bmj.com/content/100/1/F55.abstract http://jama.jamanetwork.com/article.aspx?articleid=2338255 the JC Discussion will be semi-structured. The aim is to dissect the paper and get a feeling whether the paper is good (research-wise) and relevant (clinical-wise). Please have a look at this poster from Elsevier about how to read a paper
  6. We would like to high-light an interactive webcast on the Echocardiographic Assessment of PDA Thursday 26th of November at 3pm CET The webcast is presented by Dr Nim Subhedar, Consultant Neonatal Paediatrician NICU Liverpool Women’s Hospital, and is organized by Orphan-Europe. Connection details Link: meet.republic-m.comGuest code: 57876Find more details in our Calender: And here is a PDF to share within your networks: FLYERA5.pdf
  7. Just learned from the EvidenceUpdates- service that the Cochrane review on Ibuprofen for the treatment of patent ductus arteriosus has been updated. No sensational news really... Here the URL to EvidenceUpdates: http://plus.mcmaster.ca/EvidenceUpdates/NewArticles.aspx?Page=1&ArticleID=62564 And here the URL to Cochrane: http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD003481.pub6/abstract
  8. There is a very good lecture available as a web cast: professor Nick Evans and "Diagnosis and treatment of PDA - important clinical implications" The company Orphan-europe provides the web cast: you may need to register at http://www.pda-solutions.eu/ (but... I could also connect directly using the link: http://www.orphan-webcast.com/viewer/?presentation=64 )
  9. I guess you may already have read about the paper in Nature Medicine showing that trombocytes contribute to duct closure. A "Research News" note is posted here! Nice paper, not often neonatal research finds its way into a Nature journal! Biologically plausible. Would be interesting to think about how this could be studied in clinical settings? Interventions?
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