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

  1. 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.
  2. 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!
  3. 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?
  4. 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.
  5. 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
  6. 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!
  7. 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?”
  8. 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.
  9. 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.
  10. 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.
  11. 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.
  12. 2 points
    The medical term for this is placentophagy and it is a real thing. If you follow the lay press you may have seen that originally this was promoted by Kourtney Kardashian who did this herself and then by Kim who planned on doing the same after delivery. See Did Kourtney Kardashian Eat Her Placenta? This is not completely without basis as many readers will be thinking already that they have heard about the health benefits of doing the same. Reports of improved mood and reductions in the baby blues following ingestion of placenta as well as improvements in breast milk production have led to this growing practice. The evidence for this up until recently though was quite old and fraught with poorly design of such studies. The bigger driver however has been word of mouth as many women having heard about the promises of better mood at the very least have thought “why not? Can’t hurt.” What I will do in this post is run through a little background and a few recent studies that have shed some light on how likely this is to actually work. Where did the idea come from? Animals eat their placentas after delivery. It turns out that unprocessed placenta is quite high in the hormone prolactin which is instrumental for breastfeeding. Given the large amount of this hormone as well as the number of other hormones present in such tissue it was thought that the same benefits would be found in humans. Eating unprocessed human tissue whether it is put in a capsule or not is unwise as unwanted bacteria can be consumed. In fact, a case of GBS sepsis has been linked to such a practice in which the source of the GBS was thought to be due to contaminated unprocessed maternal placenta that had been ingested. Buser GL, Mat´o S, Zhang AY, Metcalf BJ, Beall B, Thomas AR. Notes from the field: Late-onset infant group B streptococcus infection associated with maternal consumption of capsules containing dehydrated placenta. What happens when you process placenta by steaming and drying? This would be the most common way of getting it into capsules. This process which renders it safe to consume may have significant effects on reducing hormonal levels.This was found in a recent study that measured oxytocin and human placental lactogen (both involved positively in lactation) and found reductions in both of 99.5% and 89.2%, respectively compared versus raw placenta. I would assume that other hormones would be similarly affected so how much prolactin might actually wind up in these capsules after all? Clinical Randomized Double Blind Controlled Trial Twenty seven women from Las Vegas were recruited into a pilot trial (12 beef placebo vs 15 steamed and dried placenta) with the authors examining three different outcomes across three studies. The first study Effects of placentophagy on maternal salivary hormones: A pilot trial, part 1 looked at a large number of salivary hormones at four time points. Plasma samples were taken as well to determine the volume of distribution of the same. First samples were at week 36 of gestation then within 4 days (96 h) of birth followed by days 5–7 (120–168 h) postpartum and finally Days 21–27 (504–648 h) postpartum. All consumption of capsules was done in the home as was collection of samples. As per the authors in terms of consumption it was as follows “two 550 mg capsules three times daily for the first 4 days; two 550 mg capsules twice daily on days 5 through 12, and then to decrease the dose to two 550 mg capsules once daily for the remainder of the study (days 13 through approximately day 20 of supplementation). Outcomes No difference was found between salivary concentrations of hormones at any time point other than that with time they declined following birth. Curiously the volume of distribution of the hormones in serum was slightly higher in the placenta capsule groups but not enough to influence the salivary concentrations. It was felt moreover that the amount of incremental hormone level found in the serum was unlikely to lead to any clinical response. The second study was on mood Placentophagy’s effects on mood, bonding, and fatigue: A pilot trial, part 2. Overall there were no differences for the groups but they did find “some evidence of a decrease in depressive symptoms within the placenta group but not the placebo group, and reduced fatigue in placenta group participants at the end of the study compared to the placebo group.” The last paper published from the same cohort is Ingestion of Steamed and Dehydrated Placenta Capsules Does Not Affect Postpartum Plasma Prolactin Levels or Neonatal Weight Gain: Results from a Randomized, Double-Bind, Placebo-Controlled Pilot Study. This study specifically addressed the issue of prolactin levels and found no difference between the groups. Neonatal weight gain was used as a proxy for breastmilk production as it was thought that if there was an effect on breastmilk you would see better weight gain. About 80% in both groups exclusively breastfed so the influence of formula one can’t take out of the equation. In the end weight gain was no different between groups although a trend to better weight gain was seen in the placebo group. To eat or not to eat that is the question? What is clear to me is that the answer to this question remains unclear! What is clear is that I don’t think it is wise to consume raw placenta due to the risks of bacterial contamination. Secondly, the levels of hormones left in the placental preparation and the most common preparation of steaming and drying leave hormone levels that are unlikely to influence much at all from a biochemical standpoint. It also seems that breastmilk production and neonatal weight gain aren’t influenced much by consumption of these pills. The issue though in all of this is that while the previous research was of low quality, the current research while of better quality is at a low volume. These were pilot trials and not powered to find a difference likely. The finding in the subgroup of some effect on mood at the end of the study does leave some hope to those that believe in the power of the placenta to help. Would a larger study find benefit to this practice? My suspicion from a biochemical standpoint is not but that one may feel a benefit from a placebo response. Should you go out and have your placenta prepared for consumption? If you have Kardashian like wealth then go for it if you think it will help. If you don’t then I would suggest waiting for something more definitive before spending your money on placentophagy.
  13. 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!
  14. 2 points
    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?
  15. 2 points
    I know how to bag a baby. At least I think I do. Providing PPV with a bag-valve mask is something that you are taught in NRP and is likely one of the first skills you learned in the NICU. We are told to squeeze the bag at a rate of 40-60 breaths a minute. According to the Laerdal website, the volume of the preterm silicone bag that we typically use is 240 mL. Imagine then that you are wanting to ventilate a baby who is 1 kg. How much should you compress the bag if you wish to delivery 5 mL/kg. Five ml out of a 240 mL bag is not a lot of squeeze is it? Think about that the next time you find yourself squeezing one. You might then say but what about a t-piece resuscitator? A good choice option as well but how much volume are you delivering if you set the initial pressures at 20/5 for example? That would depend on the compliance of the lung of course. The greater the compliance the more volume would go in. Would it be 5 mL, 10 ml or even 2.5 mL based on the initial setting? Hard to say as it really depends on your seal and the compliance of the lung at the pressure you have chosen. If only we had a device that could deliver a preset volume just like on a ventilator with a volume guarantee setting! Why is this holy grail so important? It has been over 30 years since the importance of volutrauma was demonstrated in a rabbit model. Hernandez LA et al published Chest wall restriction limits high airway pressure-induced lung injury in young rabbits. The study used three models to demonstrate the impact of volume as opposed to pressure on injuring the lung of preterm rabbits. Group 1 were rabbit ventilated at pressures of 15/30/45 cm H2O for one hour, group 2 rabbits with a cast around their thorax to limit volume expansion and group 3 sets of excised lungs with no restriction to distension based on the applied pressures. As you might expect, limitation of over distension by the plaster cast led the greatest reduction in injury (measured as microvascular permeability) with the excised lungs being the worst. In doing this study the authors demonstrated the importance of over distension and made the case for controlling volume more than pressure when delivering breaths to avoid excessive tidal volume and resultant lung injury. The “Next Step” Volume Ventilator BVM Perhaps I am becoming a fan of the Edmonton group. In 2015 they published A Novel Prototype Neonatal Resuscitator That Controls Tidal Volume and Ventilation Rate: A Comparative Study of Mask Ventilation in a Newborn Manikin. The device is tablet based and as described, rather than setting a PIP to deliver a Vt, a rate is set along with a volume to be delivered with a peep in this case set at +5. This study compared 5 different methods of delivering PPV to a 1 kg preterm manikin. The first was a standard self inflating bag, the next three different t-piece resuscitators and then the Next Step. For the first four the goal was to deliver a pressure of 20/5 at a rate of 40-60 breaths per minute. A test lung was connected to the manikin such that each device was used for a one minute period at three different levels of compliance (0.5 ml/cmH2O, 1.0 ml/cmH2O and then 2.0 ml/cm H2O representing increasing compliance. The goal of the study was to compare the methods in terms of delivering a volume of 5 mL to this 1 kg model lung. The order in which the devices were used was randomized for the 25 participants in the study who were all certified in NRP and included some Neonatologists. Some Concerning Findings As I said at the beginning, we all like to think we know how to ventilate a newborn with BVM. The results though suggest that as compliance increases our ability to control how much volume we deliver to a lung based on a best guess for pressures needed is lacking. One caveat here is that the pressures set on the t-piece resucitators were unchanged during the 1 minute trials but then again how often during one minute would we change settings from a starting point of 20/5? Vt (mL) 0.5 mL/cmH20 1.0 mL/cmH20 2.0mL/cmH20 Self inflating 11.4 17.6 23.5 Neo-Tee 5.6 11.2 19.3 Neopuff 6.1 10 21.3 Giraffe 5.7 10.9 19.8 Next Step 3.7 4.9 4.5 Without putting in all the confidence intervals I can tell you that the Next Step was the tightest. What you notice immediately (or at least I did) was that no matter what the compliance, the self inflating bag delivers quite an excessive volume even in experienced hands regardless of compliance. At low compliance the t-piece resuscitators do an admirable job as 5-6 ml/kg of delivered Vt is reasonable but as compliance improves the volumes increase substantially. It is worth pointing out that at low compliance the Next Step was unable to deliver the prescribed Vt but knowing that if you had a baby who wasn’t responding to ventilation I would imagine you would then try a setting of 6 ml/kg to compensate much like you would increase the pressure on a typical device. How might these devices do in a 29 week infant for example with better compliance than say a 24 week infant? You can’t help but wonder how many babies are given minutes of excessive Vt after birth during PPV with the traditional pressure limited BVM setup and then down the road how many have BPD in part because of that exposure. I wanted to share this piece as I think volume resuscitation will be the future. This is just a prototype or at least back then it was. Interestingly in terms of satisfaction of use, the Next Step was rated by the participants in the study as being the easiest and most comfortable to use of all the devices studied. Adding this finding to the accuracy of the delivered volume and I think we could have a winner.
  16. 2 points
    When I think back to my early days as a medical student, one of the first lessons on the physical exam involves checking central and peripheral perfusion as part of the cardiac exam. In the newborn to assess the hemodynamic status I have often taught that while the blood pressure is a nice number to have it is important to remember that it is a number that is the product of two important factors; resistance and flow. It is possible then that a newborn with a low blood pressure could have good flow but poor vascular tone (warm shock) or poor flow and increased vascular tone (cardiogenic shock or hypovolemia). Similarly, the baby with good perfusion could be in septic shock and be vasodilated with good flow. In other words the use of capillary and blood pressure may not tell you what you really want to know. Is there a better way? As I have written about previously, point of care ultrasound is on the rise in Neonatology. As more trainees are being taught the skill and equipment more readily available opportunities abound for testing various hypotheses about the benefit of such technology. In addition to my role as a clinical Neonatologist I am also the Medical Director of the Child Health Transport Team and have pondered about a future where ultrasound is taken on retrievals to enhance patient assessment. I was delighted therefore to see a small but interesting study published on this very topic this past month. Browning Carmo KB and colleagues shared their experience in retrieving 44 infants in their paper Feasibility and utility of portable ultrasound during retrieval of sick preterm infants. The study amounted to a proof of concept and took 7 years to complete in large part due to the rare availability of staff who were trained in ultrasound to retrieve patients. These were mostly small higher risk patients (median birthweight, 1130 g (680–1960 g) and median gestation, 27 weeks (23–30)). Availability of a laptop based ultrasound device made this study possible now that there are nearly palm sized and tablet based ultrasound units this study would be even more feasible now (sometimes they were unable to send a three person team due to weight reasons when factoring in the ultrasound equipment). Without going into great detail the measurements included cardiac (structural and hemodynamic) & head ultrasounds. Bringing things full circle it is the hemodynamic assessment that I found the most interesting. Can we rely on capillary refill? From previous work normal values for SVC flow are >50 ml/kg/min and for Right ventricular output > 150 ml/kg/min. These thresholds if not met have been correlated with adverse long term outcomes and in the short term need for inotropic support. In the absence of these ultrasound measurements one would use capillary refill and blood pressure to determine the clinical status but how accurate is it? First of all out of the 44 patients retrieved, assessment in the field demonstrated 27 (61%) had evidence using these parameters of low systemic blood flow. After admission to the NICU 8 had persistent low systemic blood flow with the patients shown below in the table. The striking finding (at least to me) is that 6 out of 8 had capillary refill times < 2 seconds. With respect to blood pressure 5/8 had mean blood pressures that would be considered normal or even elevated despite clearly compromised systemic blood flow. To answer the question I have posed in this section I think the answer is that capillary refill and I would also add blood pressure are not telling you the whole story. I suspect in these patients the numbers were masking the true status of the patient. How safe is transport? One other aspect of the study which I hope would provide some relief to those of us who transport patients long distance is that the head ultrasound findings before and after transport were unchanged. Transport with all of it’s movement to and fro and vibrations would not seem to put babies at risk of intracranial bleeding. Where do we go from here? Before we all jump on the bandwagon and spend a great deal of money buying such equipment it needs to be said “larger studies are needed” looking at such things as IVH. Although it is reassuring that patients with IVH did not have extension of such bleeding after transport, it needs to be recognized that with such a small study I am not comfortable saying that the case is closed. What I am concerned about though is the lack of correlation between SVC and RVO measurements and the findings we have used for ages to estimate hemodynamic status in patients. There will be those who resist such change as it does require effort to acquire a new set of skills. I do see this happening though as we move forward if we want to have the most accurate assessment of clinical status in our patients. As equipment with high resolution becomes increasingly available at lower price points, how long can we afford not to adapt?
  17. 2 points
    As a Neonatologist I doubt there are many topics discussed over coffee more than BPD. It is our metric by which we tend to judge our performance as a team and centre possibly more than any other. This shouldn't be that surprising. The dawn of Neonatology was exemplified by the development of ventilators capable of allowing those with RDS to have a chance at survival. As John F Kennedy discovered when his son Patrick was born at 34 weeks, without such technology available there just wasn't much that one could do. As premature survival became more and more common and the gestational age at which this was possible younger and younger survivors began to emerge. These survivors had a condition with Northway described in 1967 as classical BPD. This fibrocystic disease which would cripple infants gave way with modern ventilation to the "new bpd". The New BPD The disease has changed to one where many factors such as oxygen and chorioamnionitis combine to cause arrest of alveolar development along with abnormal branching and thickening of the pulmonary vasculature to create insufficient air/blood interfaces +/- pulmonary hypertension. This new form is prevalent in units across the world and generally appears as hazy lungs minus the cystic change for the most part seen previously. Defining when to diagnose BPD has been a challenge. Is it oxygen at 28 days, 36 weeks PMA, x-ray compatible change or something else? The 2000 NIH workshop on this topic created a new approach to defining BPD which underwent validation towards predicting downstream pulmonary morbidity in follow-up in 2005. That was over a decade ago and the question is whether this remains relevant today. Benchmarking I don't wish to make light of the need to track our rates of BPD but at times I have found myself asking "is this really important?" There are a number of reasons for saying this. A baby who comes off oxygen at 36 weeks and 1 day is classified as having BPD while the baby who comes off at 35 6/7 does not. Are they really that different? Is it BPD that is keeping our smallest babies in hospital these days? For the most part no. Even after they come off oxygen and other supports it is often the need to establish feeding or adequate weight prior to discharge that delays things these days. Given that many of our smallest infants also have apnea long past 36 weeks PMA we have all seen babies who are free of oxygen at 38 weeks who continue to have events that keep them in hospital. In short while we need to be careful to minimize lung injury and the consequences that may follow the same, does it matter if a baby comes off O2 at 36, 37 or 38 weeks if they aren't being discharged due to apnea or feeding issues? It does matter for benchmarking purposes as one unit will use this marker to compare themselves against another in terms of performance. Is there something more though that we can hope to obtain? When does BPD matter? The real goal in preventing BPD or at least minimizing respiratory morbidity of any kind is to ensure that after discharge from the NICU we are sending out the healthiest babies we can into the community. Does a baby at 36 weeks and one day free of O2 and other support have a high risk of coming back to the hospital after discharge or might it be that those that are even older when they free of such treatments may be worse off after discharge. The longer it takes to come off support one would think, the more fragile you might be. This was the goal of an important study just published entitled Revisiting the Definition of Bronchopulmonary Dysplasia: Effect of Changing Panoply of Respiratory Support for Preterm Neonates. This work is yet another contribution to the pool of knowledge from the Canadian Neonatal Network. In short this was a retrospective cohort study of 1503 babies born at <29 weeks GA who were assessed at 18-21 months of age. The outcomes were serious respiratory morbidity defined as one of: (1) 3 or more rehospitalizations after NICU discharge owing to respiratory problems (infectious or noninfectious); (2) having a tracheostomy (3) using respiratory monitoring or support devices at home such as an apnea monitor or pulse oximeter (4) being on home oxygen or continuous positive airway pressure at the time of assessment While neurosensory impairment being one of: (1) moderate to severe cerebral palsy (Gross Motor Function Classification System ≥3) (2) severe developmental delay (Bayley Scales of Infant and Toddler Development Third Edition [Bayley III] composite score <70 in either cognitive, language, or motor domains) 3) hearing aid or cochlear implant use (4) bilateral severe visual impairment What did they find? The authors looked at 6 definitions of BPD and applied examined how predictive they were of these two outcomes. The combination of oxygen and/or respiratory support at 36 weeks PMA had the greatest capacity to predict this composite outcome. It was the secondary analysis though that peaked my interest. Once the authors identified the best predictor of adverse outcome they sought to examine the same combination of respiratory support and/oxygen at gestational ages from 34 -44 weeks PMA. The question here was whether the use of an arbitrary time point of 36 weeks is actually the best number to use when looking at these longer term outcomes. Great for benchmarking but is it great for predicting outcome? It turns out the point in time with the greatest likelihood of predicting occurrence of serious respiratory morbidity is 40 weeks and not 36 weeks. Curiously, beyond 40 weeks it becomes less predictive. With respect to neurosensory impairment there is no real difference at any gestational age from 34-44 weeks PMA. From the perspective of what we tell parents these results have some significance. If they are to be believed (and this is a very large sample) then the infant who remains on O2 at 37 weeks but is off by 38 or 39 weeks will likely fair better than the baby who remains on O2 or support at 40 weeks. It also means that the risk of neurosensory impairment is largely set in place if the infant born at < 29 weeks remains on O2 or support beyond 33 weeks. Should this surprise us? Maybe not. A baby who is on such support for over 5 weeks is sick and as a result the damage to the developing brain from O2 free radical damage and/or exposure to chorioamnionitis or sepsis is done. It will be interesting to see how this study shapes the way we think about BPD. From a neurosensory standpoint striving to remove the need for support by 34 weeks may be a goal worth striving for. Failure to do so though may mean that we at least have some time to reduce the risk of serious respiratory morbidity after discharge. Thank you to the CNN for putting out what I am sure will be a much discussed paper in the months to come.
  18. 2 points
    In the UK an "intensive care" day for a newborn is defined as a day where the baby is intubated and ventilated, or is on non-invasive respiratory support (CPAP of non-invasive ventilation) AND parenteral nutrition, or on the day of surgery, or on the day of death, or a day when they have any of the following: Presence of an umbilical arterial line Presence of an umbilical venous line Presence of a peripheral arterial line Insulin infusion Presence of a chest drain Exchange transfusion Therapeutic hypothermia Prostaglandin infusion Presence of replogle tube Presence of epidural catheter Presence of silo for gastroschisis Presence of external ventricular drain Dialysis (any type) The next level of care is referred to as "high-dependency" and includes for example CPAP with full enteral feeds, or parenteral nutrition without positive pressure respiratory support. The British Association of Perinatal Medicine standards state that on an intensive care day a baby should have a 1:1 nurse ratio, on a high-dependency day they should have 1 nurse per 2 babies. A new publication from a group in the UK has found that in 2008 only 9% of intensive care days had 1:1 staffing, and in 2012 that had fallen to 6%, when examining data from 30 to 40 NICUs around the country. As you are all aware, the severity of illness of babies who would be classified as "intensive care" using the BAPM criteria varies hugely. In order to determine whether there is an impact of nursing ratios on outcomes, it is necessary to try to adjust for this severity. But just crudely, if the reduction of days of 1:1 ratio is because the babies are less sick (and someone thought they didn't really need 1:1) then mortality should have fallen. In fact it increased. Over the years where the proportion of days with less 1:1 nursing was falling mortality increased from 4 out of every 100 babies receiving intensive care to 4.5, passing a peak of 5.3 in 2010 and 2011. Of course the authors have much more sophisticated analysis than that, and after doing all the adjustments that they could, they calculate that, from a median mortality rate of 4.5, every time you decrease the proportion of 1:1 days by 10% you increase mortality by 0.6, that is, to 5.1, then to 5.7... An accompanying editorial says it all: The data may not be directly applicable to other health care systems, where some of the roles of NICU nurses in the UK are covered by other professionals, in the UK, for example they do not have respiratory therapists, and it is the nurses who do the tasks that RTs do in our NICU. Nevertheless I am convinced that the same principle applies in North American NICUs, when the workload is higher, and we can provide fewer 1:1 nurse assignments, then infection rates are higher, and probably, mortality also. I also think that maybe the BAPM should rethink their criteria. Does every child with an Umbilical Venous Line really need 1:1 nursing? A full term baby with hypoglycemia who has a UVC placed for glucose administrator would be classified as "intensive care" and would be supposed to have 1:1. A nurse could probably safely look after 2 babies whose only criteria for "intensive care" was the presence of a chest tube. If you could rationalize the criteria you would probably be able to put more pressure on the system to provide 1:1 for those babies that really need it. On the other hand a baby who no longer needs parenteral nutrition, but who has just been extubated to CPAP would not be "intensive care" but really needs expert dedicated nursing at a high ratio to prevent re-intubation, and should maybe be considered "intensive care" if they are under 28 weeks for the first 48 hours at least. I have said many times that I think the most important factor in mortality and morbidity of the extremely immature babies is the quality of the nursing care they receive. In order to give care of good quality, as this study shows, you need adequate quantity.
  19. 2 points
    It has been some time since I wrote on the topic of point of care ultrasound (POC). The first post spoke to the benefits of reducing radiation exposure in the NICU but was truly theoretical and also was really at the start of our experience in the evolving area. Here we are a year later and much has transpired. We purchased an ultrasound for the NICU in one of our level III units and now have two more on the way; one for our other level III and one for our level II unit. The thrust of these acquisitions have been to reduce radiation exposure for one but also to shorten the time to diagnosis for a number of conditions. No matter how efficient x-ray technologists are, from the time a requisition is placed to the arrival of the tech, placement of the baby and then processing of the film, it is much longer than using a POC at the bedside. Having said that though is it accurate? There are many examples to choose from but when thinking about times when one would like an answer quickly I can’t think of anything much better than a pneumothorax. Chest X-ray vs POC for Diagnosis of Pneumothorax The diagnosis of a pneumothorax is easily diagnosed by ultrasound when there is an absence of lung sliding as seen in this video. In the majority of cases employing POC we are looking at ultrasound artifacts. In the case of pleural sliding which is best described as ants marching, it’s absence indicates the presence of a pneumothorax. The “lung point” sign as shown in thisvideo marks the transition from pleural sliding to none and in a mode called “M” appears as a bar code when the pneumothorax is present. Using such signs Raimondi F et al as part of the LUCI (Lung Ultrasound in the Crashing Infant) group compared traditional x-ray diagnosis as the gold standard to POC for diagnosis of pneumothorax. This study is important as it demonstrated two very important things in the 42 infants who were enrolled in the study. The first was the accuracy of POC. In this study each patient had both an ultrasound and an x-ray and the results compared to determine how accurate the POC was. Additionally in cases where there was no time for an x-ray to confirm the clinical suspicion the accuracy of the study was determined based on the finding of air with decompression along with abrupt clinical improvement. In case people are wondering infants as small as 24 weeks were included in the study with an average weight of 1531 +/-832 g for included infants. The accuracy was stunning with a sensitivity and specificity of 100% each. Comparing this with clinical evaluation (transillumination, assessment of breath sounds) was far less accurate with a sensitivity of 84% (65-96) and specificity 56% (30-80). Adding to the accuracy of the test is the efficiency of the procedure. “After clinical decompensation, lung ultrasound scans were completed in a mean time of 5.3 +/- 5.6 minutes vs a mean time of 19 +/- 11.7 minutes required for a chest radiograph (P < .001).” In short, it is very accurate and can be done quickly. In an emergency, can you think of a better test? If efficiency weren’t enough what about the reduction in radiation exposure? This was the focus of a recent paper by Escourrou G & Deluca D entitled Lung ultrasound decreased radiation exposure in preterm infants in a neonatal intensive care unit. The authors in this study chose to examine retrospecitively the period from 2012 – 2014 as in 2013 they rolled out a program of teaching POC ultrasound to clinicians. The purpose of this paper was to see if practitioners educated in interpretation of ultrasound would actually change their practice and use less ionizing radiation. Their main findings are indicated in the table Test 2012 2014 p Min 1 x-ray during admission 81% 70% <0.001 Total x-rays 1976 1476 Mean x-rays per patient 4.9+/-1.5 2.6+/-1.0 <0.001 Mean radiation dose (microGy) 183+/-78 68+/-30 <0.001 As they predicted use of ionizing radiation dropped dramatically. I should also mention that they tracked outcomes such as IVH, mortality and BPD to name a few and found no change over time. In conclusion the use of ultrasound did not affect major outcomes but did spare each neonate ionizing radiation. Now before anyone hits the panic button I still think the amounts of radiation here are safe for the most part. In Canada the maximum allowed dose for the public per year is 1 mSv which is the equivalent of 1000 microGy. This was obtained from the Nuclear Safety agency in Canada in case you are interested in finding out more about radiation safety limits. Back in 2012 at least in this study, 2 standard deviations from the mean would have put the level received at a little over a third of what the annual limit is but it is the outliers we need to think of. What about kids getting near daily x-rays while on high frequency ventilation or for monitoring pleural fluid collections? There certainly are many who could receive much higher dosages and it is for those kids that I believe this technology is so imperative to embrace. It will take time to adopt and much patience. With any new roll out there is a learning curve. Yes there will be learners who will need to handle patients and yes there will be studies done at times to obtain the skills necessary to perform studies in an efficient and correct manner but I assure you it will be worth it. If we have a way of obtaining faster and accurate diagnoses and avoiding ionizing radiation don’t we owe it to our patients and families to obtain such skill? I look forward to achieving a centre of excellence utilizing such strategies and much like this last study it will be interesting to look back in a year an see how things have changed.
  20. 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.
  21. 2 points
    I will admit it. I resist change at times just like many others. This may come as a surprise to some of you who have worked with me and accused me of bringing too much change at times to the units. The truth though is that when one understands something and is enthusiastic about implementation the change does not seem so difficult. When it isn't your idea though we may find ourselves a little uneasy about adopting this unfamiliar practice. Such has been my experience with nasal HFOV. It is a strategy that has been around for over five years but has seen slow adoption among centres in Canada and has trickled into practice in Winnipeg on a few occasions. In each occasion when I have been asked about either continuing or perhaps starting this therapy I have shrugged my shoulders and confessed my inexperience with the modality. Sure I have used HFOV through an ETT but through prongs or a mask?! How would it work? Could it cause harm? What would the actual indications be? How would our in house physicians and NNPs respond to abnormal gases overnight even if I felt comfortable with using it? These sorts of questions have led to virtual inertia in my acceptance of the strategy. Before I go on it would be good to see an example of how it is set up. The MedinCNO device is capable of delivering such non-invasive HFOV and can be seen in this short video. One could use the strategy either prophylactically to extubate an infant or as rescue to prevent reintubation if trials of either CPAP or NIPPV were unsuccessful. HFOV is known to be very effective at clearing CO2 when used through an ETT so perhaps nasal application could also lower pCO2 and achieve a similar effect. This was tested using a neonatal lung simulator by Mukeji A et al Nasal high-frequency oscillation for lung carbon dioxide clearance in the newborn. In this study CO2 was introduced into the manequin and the amount of exhaled CO2 determined while on CPAP, NIPPV and nasal HFOV. Interestingly during CPAP no exhaled CO2 could be detected while CO2 clearance occurred during NIPPV and nasal HFOV although it was three-fold greater with HFOV. In theory then CO2 clearance would appear to be better so in the case of ventilatory failure as evidenced by CO2 retention this modality would seem to win out. Clinical Evidence for Use There is one RCT in term infants with TTN to support the practice while the rest are unblinded case series with no controls. Four Canadian NICUs recently described their experience however using a retrospective analysis. Included were 79 instances of HFOV distributed as follows; 73% utilized as rescue from another mode and in 27% used as the primary mode for extubation. The outcomes are shown in the table: In 45% of cases the patients needed intubation after first trialing CPAP or NIPPV while in 33% of cases following extubation the infants needed replacement of the endotracheal tube. The numbers here are small so it is difficult to truly compare them to other studies with confidence but reintubation rates of 40-44% have been noted recently when using NIPPV or CPAP so the numbers are at least consistent. One aspect though that caught my eye was the duration of use for HFOV across these 79 patients. The median use was 57 hours with the longest duration being just over 400 hours. It would seem that the use of this modality for the most part is as a bridge to something else. The median duration of 2.5 days is much shorter than the weeks that some of our smallest infants remain on CPAP/NIPPV for. Whether for rescue or prophylaxis this is not a long term option. Another point worth noting though is the question of whether it is the pressure or oscillatory wave that is leading to success. As the authors note, there were a wide range in applications of MAP, delta P and frequency. MAP ranges from 8 - 24 cm H2O while frequency from 6 - 14 hz and amplitude varied widely depending on the device used but was as high as 100%. While high MAP has been used invasively though an ETT I can't help but wonder if in some cases the real benefit was the high MAP. What would happen for example if the centres had simply raised the CPAP to 10, 12 or even higher? In the end it would seem that in principal it is an effective therapy that may be able to remove CO2 more efficiently than the other modes. What we don't have are RCTs in the smallest babies comparing HFOV to NIPPV or CPAP with adequate power to detect differences. I suspect these will come soon enough but what do we do in the meantime? The main reservation I have has to do with safety. We truly have little if any data on this without proper trials to ease such worry. When a patient is in front of us though and is failing CPAP or NIPPV what are we to do? Should we intubate or trial this modality based on the evidence thus far? I might be tempted to trial HFOV in this circumstance but as with any new therapy we need education for all staff. Everyone caring for our infants need to understand what they are using and how to respond based on clinical findings. This is the real issue with safety that I see and until such time that we have widespread education across RRT, nursing and medicine I would suggest we use this with trepidation. This is not a rejection of the modality in the least but rather a call to come together as a team and see how implement this in such a way that will provide direction to caregivers, provide a consistent approach with respect to length of use, indications and when to change direction entirely. Time to call a meeting of the minds I think.
  22. 2 points
    Originally posted at: https://winnipegneonatal.wordpress.com/ Facebook Page: https://www.facebook.com/allthingsneonatal/ The journey from conception to the labour floor and then for some to the NICU is not a straight one. There are times of joy, interspersed with sadness, denial, anger and eventually acceptance, as initial news of being pregnant leads to complications in pregnancy and then eventual admission of an infant to the NICU. Much has been said in recent years about the building of partnerships with parents and in fact there is a new catchphrase attached to the concept "shared decision making" (SDM). There is no question that in the perfect world this is exactly the relationship that we should be striving for with all of our patients. The world however is not perfect and although this may not be the most popular opinion I have given, I question how applicable this really is in many situations. A Reality Check Take for instance the parents who present to the labour floor of their local hospital in advanced labour at 24 weeks. Proponents of this SDM model would suggest that a meeting take place and pertinent information be given to a family and together with the assistance of literature applicable to their situation (possibly a pamphlet) the health care providers and families come to a mutually agreeable decision as to what the best course of action is for them and their unborn infant. This all sounds wonderful but examining the real life situation a little more closely is it actually reasonable to assume we can obtain this? I have not been, nor will I ever be pregnant and certainly have never experienced contractions and felt the veil clouding my vision as the first dose of analgesia enters my veins to deal with the discomfort a woman experiences during labour. Not to mention there are people admitting this couple, taking histories, establishing IV access, scanning bellies and a whole host of other pokes and prods along the way. My Role Better Defined Then I come in. Among all this chaos I deliver the information, pass along a pamphlet and do the best job I can to inform said couple of the upcoming decision. The trouble of course is how do we come to this mutual decision in the 15 - 30 minutes I spend with them during this crisis? The answer sadly is we do our best but don't for a minute think that SDM has occurred. I don't believe this is possible unless the family has prior experience with a preterm birth or perhaps is a HCP working with newborns or children with disabilities themselves. In fact Boss RD et al in their own research on the subject identified that in hindsight religion, spirituality and hope are what motivated parents rather than what was said at the time. In essence their minds are already made up. It doesn't mean we shouldn't strive for the SDM but at least in my opinion, unless their contractions settle, a calmness ensues, they have time to digest the information being given and then meet again under less stressful circumstances, the SDM is a nice idea but for many not a reality. Shifting To The NICU I recall a significant moment in my training when I saw how the SDM model can actually cause more grief than help. Dr. Keith Barrington a fellow blogger (if you haven't discovered him, his work is fascinating over at Neonatal Research) published one of the most impactful pieces of research of the decade during my fellowship. The adverse neuro-developmental effects of postnatal steroids in the preterm infant: a systematic review of RCTs. Following this analysis there was a near moratorium on the use of post natal steroids. The issue this created was that to now receive them you had to be close to the end of the limits of care. At this point you either died (thereby concluding they are of no help) or you survived with disability that was due in part no doubt to how sick you had become (thereby concluding they are dangerous). The moment I am referring to was a conversation with a family in which the attending managing the unit presented the risks and benefits of postnatal steroids to the family when the FiO2 was at 40% one day. The language used was non directive and the parents asked for another day to decide. The next day and each of the following two days they were unable to choose between giving the steroids and the perceived risk of brain damage versus not and watching the FiO2 climb by about 10% per day. By the time the FiO2 several days later was at 80-90% they were distraught, teary and feeling helpless. What they needed was direction; someone to give them some advice or more simply an educated opinion. We can strive to share in the decision making but I continue to believe there is a time and place to help our families by taking a stance or side. We can equip them with as much information as we want but is there really any replacement for actually taking care of these infants, experiencing the ups and downs and hearing how they have done in follow-up? We simply can't expect the average parent to understand the true long term consequences of their decisions. I am not saying we go back to a paternalistic time in medicine but I am saying that one size does not fit all. We owe it to our families to pursue SDM when we can but we have an equal obligation to recognize when this ideal state is simply not possible. At this point we have to use the experiences and knowledge we have to provide them with the best advice we can. We have gone through medical training, and gone down these paths so many times. We can avoid biased opinion and rely on the facts as they are in our institutions but to not take a stand when it is needed at least for me is doing a disservice to those we are so eager to help.
  23. 2 points
    Does being rude stimulate people to do better, or does it have adverse effects on performance, and team functioning? And how to prove it on way or another? This really interesting, innovative paper from a team in Israel has performed an RCT to address the problem. Riskin A, et al. The Impact of Rudeness on Medical Team Performance: A Randomized Trial. Pediatrics. 2015. The authors created 24 NICU teams and arranged for them to receive some comments from a supposed visiting expert from the USA. Half of them included some mildly rude comments, which the team received either just before or midway through a simulated resuscitation of a newborn manikin. Just before the simulation, to the rudeness exposed group, the "expert" stated that he was "not impressed with the quality of medicine in Israel". Ten minutes later the simulation was stopped and the participants heard that "medical staff like those observed wouldn’t last a week in his department". He added that he "hoped that he would not get sick while in Israel". The study found substantial negative effects of what they refer to as "mild incivility" on both diagnosis of problems during the simulation and on procedural performance. For example the subjects were much less likely to correctly verify the position of a tube when they had been the target of the rudeness. They also showed that the rude comments affected information sharing within the team, and on whether the team members sought help from each other. I must say I have been exposed to rudeness, sometimes much more direct and biting than the comments in this research, at many times during my career, and have, to be honest, also occasionally been rude to others myself. Sometimes a transient irritation or annoyance can lead to comments or attitudes that are negative and to "incivility". In a very high stress environment like the NICU, making snarky comments when things don't go well is a common reaction. I think that we should all try even harder to avoid such responses, not just because they may hurt feelings and harm morale, but because it actually looks like they can have adverse effects on the medical care that our patients receive.
  24. 2 points
    As Internet is everywhere (sort of), 99nicu.org has become a truly global network! From Google analytics we could see that people browsing 99nicu the past month (May 9 - June 8) comes from all over the world. The final goal for our outreach is Greenland and countries in Central Africa.
  25. 2 points
    Three recent articles have investigated whether we should wait until a week or so after birth to perform brain imaging in infants with encephalopathy, or whether earlier imaging might be just as predictive. The three articles have consistent findings, which is remarkable in itself! All three note that infants at high risk, most of whom have undergone hypothermia treatment, when they have MRI at 2 to 4 days of age, the results are very similar to the findings if you wait until a week or so to do the study. Agut T, et al. Early identification of brain injury in infants with hypoxic ischemic encephalopathy at high risk for severe impairments: accuracy of MRI performed in the first days of life. BMC Pediatrics. 2014;14(1):177. Boudes E, et al. MRI obtained during versus after hypothermia in asphyxiated newborns. Archives of Disease in Childhood - Fetal and Neonatal Edition. 2015;100(3):F238-F42. Skranes JH, et al. Brain imaging in cooled encephalopatic neonates does not differ between four and 11 days after birth. Acta Paediatrica. 2015. Now I think you could say the same about many of these type of studies as about the studies of brain imaging in very preterm babies. Which is, that if the reason that you want to do the study is to aid in medical decision making (which is explicitly stated in the first of the 3 articles) we need much better data of the positive predictive value of the findings for profoundly adverse outcomes. The best data I think come from the analysis of the TOBY trial, Rutherford M, et al. Assessment of brain tissue injury after moderate hypothermia in neonates with hypoxic-ischaemic encephalopathy: a nested substudy of a randomised controlled trial. The Lancet Neurology. 2010;9(1):39-45. That study used a scoring system, created by the same group, and showed that the positive predictive value of moderate or severe lesions in the basal ganglia and thalami, severe white matter lesions, or an abnormal posterior limb of the internal capsule for death or severe disability at 18 months of age was 0·76 (95% CI 0·65–0·87). Severe disability was defined as at least one of: mental development index (MDI) less than 70 (2 or more SD below the mean) on the Bayley infant scales (BSID II) at 2 years; cerebral palsy with a GMFCS of 3–5 (unlikely to be ambulant) or bilateral cortical visual impairment with no useful vision. There is some evidence that a 2 year Bayley is more predictive of limited longer term functioning after HIE than it is for former extreme preterm infants, for example this article from the follow up of the NRN trial, Pappas A, et al. Cognitive outcomes after neonatal encephalopathy. Pediatrics. 2015;135(3):e624-34. Of 30 babies with a Bayley 2 MDI less than 70, 27 of them had a full scale IQ less than 70 at 6 to 7 years of age. (Most of the infants with an MDI less than 70 were below 55, 24 of the 30; also 23 of the 31 babies with an IQ below 70 were below 55). If we put all this together it seems that it might be possible to have a reasonably accurate prediction of severely abnormal outcome using MRI shortly after, or even during the final day of, therapeutic hypothermia. I think before we rush to performing early MRI, and use them for decision making, we should have more, and more direct, evidence that a certain severity of abnormality on the early MRI, accurately predicts profound impairment, and that this is better than clinical examination, or other predictive indices.
  26. 2 points
    It sounds simple, but actually it turns out to be very complicated and controversial. The question is are we improving our NICU ? Has our NICU performance remained the same for the past few years? What about the performance of our NICU staff members (Medical and Nursing ) ? Are they improving themselves? That was the easy part. Now the difficult part. We can only improve a thing which can be measured. So to improve our NICU, we have to monitor some parameters of our NICU and then trend it and then find what we want to improve in that measure and then plan an intervention and then implement that intervention and then monitor the performance after the implementation of the interventions. (phew that was difficult to type right !) So lets see....if we heard that NICU in XYZ hospital had mortality of ELBW babies 5 years back of 50 % and that now they are reporting ELBW mortality of 20%...we definitely know they have improved themselves. How about nosocomial infection rate in a NICU in XYZ hospital was 5 per 1000 patient-days 5 years back and now was 1.5 per 1000 patient-days...we definitely know they have improved. One very nice example to illustrate this improvement is here: http://www.lafayettegeneral.com/pavilion/Level-III-Neonatal-Intensive-Care-Unit-1/Key-Performance-Indicators-3 There are so many parameters to be monitored in a NICU..I think we just have to select what is suitable in our setup balancing our resources. We have to be cautious not to overdo it...as then it will only be on paper and have no actual benefit for the NICU. the other (more difficult part) is to monitor the performance of NICU staff. Here also there are many options. One beloved one is compliance with infection control practices (especially ...hand hygiene). Success rate of intubations could be used for residents. How about IV infiltration (IV burns) rate for nurses? Morbidity/Mortality outcomes for consultants/attending ? Once staff know that they are being monitored...performance automatically improves. Once you start rewarding good performance......then people start having a healthy competition to improve themselves....the ultimate winner is the patient...NICU performance measures improve.....And thats the ultimate aim...to improve patient outcomes... The floor is open.
  27. 1 point
    Glucose metabolism in the newborn can be a tricky thing to manage. Neonates can have significant fluctuation in their serum glucose in the first few days of life which can lead heels to look like pin cushions. How many times have you been asked as a physician if there is anything we can do to reduce the number of pokes? That something may have arrived at least in a feasibility study that could pave the way for this becoming the standard approach to hypo/hyperglycemia in the newborn. This is an important area to improve tightness of control as hyperglycemia has been associated in VLBW infants with such adverse outcomes as IVH, ROP and NEC. Continuous glucose monitoring (CGM) with closed loop insulin delivery The principle here is that a meter is inserted subcutaneously that detects blood glucose fluctuations and responds by either increasing infusion of dextrose for low glucose or delivery of insulin. The technology has been around for some time and used in the adult population but is relatively new in this population. I have written about it before in Continuous glucose monitoring in NICU may be around the corner. What follows is the latest pilot study to test this out coupled with glucose or insulin delivery in a closed loop system. The study in this case is out of Cambridge in the UK and entitled Feasibility of automated insulin delivery guided by continuous glucose monitoring in preterm infants . What did they do? The study was a pilot of 20 patients randomized to have an automated system to regulate glucose based on CGM data from 48-72 hours of age vs a paper based algorithm to manage dextrose or insulin infusion rates during the same period. The sample size was one of convenience to test the concept and the period was chosen to allow for time to recruit patients. The sensor used was an Enlite attached to a laptop with software capable of delivering infusion rates to two alaris pumps (one with 20% dextrose and the other with insulin). Target serum glucose levels were set to be between 4-8 mmol/L. The babies included were all under 1200g and had mean weights of 962g in the closed loop and 823g in the control arm. The Results were fairly dramatic in my mind at least. A remarkable 91% of the infants in the closed loop system had glucose levels in the target range vs 26% in the control arm. Nutritional intakes and mean insulin dosing were not any different between groups. No harm in addition was noted from use of the CGMs. You don’t escape pokes all together though as the device does require q6h checks to calibrate and ensure it is reading properly. Every 6 hours is better though than every three for those with brittle control! The Benefit Tightly regulating blood glucose and avoiding both lows and highs has benefits on the low end to neurological preservation. On the high end some complications such as IVH, NEC and ROP may be avoided by better control. The challenge with the system as is at the moment is that it is not widely available. I am eager for a company out there to create software for mass distribution that would enable us to try this out. While the calibration is still required I can’t help but think this is an improvement over what we have at the moment. Stay tuned as I think this one is for real and will appear in NICUs sooner than you think!
  28. 1 point
    We have all been there. After an uneventful pregnancy a mother presents to the labour floor in active labour. The families world is turned upside down and she goes on to deliver an infant at 27 weeks. If the infant is well and receives minimal resuscitation and is on CPAP we provide reassurance and have an optimistic tone. If however their infant is born apneic and bradycardic and goes on to receive chest compressions +/- epinephrine what do we tell them? This infant obviously is much sicker after delivery and when the family asks you “will my baby be ok?” what do you tell them? It is a human tendency to want to reassure and support but if they ask you what the chances are of a good outcome it has always been hard to estimate. What many of us would default to is making an assumption that the need for CPR at a time when the brain is so fragile may lead to bleeding or ischemia would lead to worse outcomes. You would mostly be right. One study by Finer et al entitled Intact survival in extremely low birth weight infants after delivery room resuscitation.demonstrated that survival for infants under 750g was better if they had a history of CPR after delivery. The thought here is that more aggressive resusctiation might be responsible for the better outcome by I would presume establishing adequate circulation sooner even if the neonates did not appear to need it immediately. The Canadian Neonatal Network In Canada we are fortunate to have a wonderful network called the Canadian Neonatal Network. So many questions have been answered by examining this rich database of NICUs across the county. Using this database the following paper was just published by Dr. A. Lodha and others; Extensive cardiopulmonary resuscitation of preterm neonates at birth and mortality and developmental outcomes. The paper asked a very specific and answerable question from the database. For infants born at <29 weeks gestational age who require extensive resuscitation (chest compressions, epinephrine or both) what is the likelihood of survival and/or neurodevelopmental impairment (NDI) at 18-24 months of age vs those that did not undergo such resuscitation? For NDI, the authors used a fairly standard definition as “any cerebral palsy (GMFCS1), Bayley-III score <85 on one or more of the cognitive, motor or language composite scores, sensorineural or mixed hearing impairment or unilateral or bilateral visual impairment.” Their secondary outcomes were significant neurodevelopmental impairment (sNDI), mortality, a Bayley-III score of <85 on any one of the components (cognitive, language, motor), sensorineural or mixed hearing loss,or visual impairment.sNDI was defined as the presence of one or more of the following: cerebral palsy with GMFCS 3, Bayley-III cognitive, language or motor composite score <70, hearing impairment requiring hearing aids or cochlear implant, or bilateral visual impairment” What did they discover? It is a fortunate thing that the database is so large as when you are looking at something like this the number of infants requiring extensive resuscitation is expected to be small. The authors collected data from January 1, 2010 and September 30, 2011 and had a total number of infants born at less than 29 weeks of 2760. After excluding those with congenital anomalies and those who were born moribund they were left with 2587. From these 80% had follow-up data and when applying the final filter of extensive resuscitation they were left with 190 (9.2%) who received delivery room CPR (DR-CPR) vs 1545 who did not receive this. Before delving into the actual outcomes it is important to note that neonates who did not receive DR-CPR were more likely to be born to mothers with hypertension and to have received antenatal steroids (89 vs 75%). With these caveats it is pretty clear that as opposed to the earlier study showing better outcomes after DR-CPR this was not the case here. The results are interesting in that it is pretty clear that receiving DR-CPR is not without consequence (higher rate of seizures, severe neurological injury, BPD). Looking at the longer term outcomes though is where things get a little more interesting. Mortality and mortality or neurodevelopmental impairment are statistically significant with respect to increased risk. When you take out NDI alone however the CI crosses one and is no longer significant. Neither is CP for that matter with the only statistically significant difference being the Bayley-III Motor composite score <85. The fact that only this one finding came out as significant at least to me raises the possibility that this could have been brought about by chance. It would seem that while these infants are at risk of some serious issues their brains in the long run may be benefiting for the neurological plasticity that we know these infants have. The study is remarkable to me in that an infant can have such a difficult start to life yet hope may remain even after dealing with some of the trials and tribulations of the NICU. Parents may need to wade through the troubling times of seizures, long term ventilation and CPAP and then onto a diagosis of BPD but their brains may be ok after all. This is one of the reasons I love what I do!
  29. 1 point
    Last month I got a chance to day pass at ems2019 to get an update on hospital tranfer#picu by la paz and update on ilcor peadiatric resus by Dr Maconochiel who gave us an insight into how guidelines are elaborated -quite complex.I also the tech lover and intetact resus decives. The Mechanical for compression in for fevices look impressive , and fumctional .I was suprised to see many there are available to date x adult use only. My NLS Top medical devices -tried and tested Monivent(wireless &app). @99NICU so easy to use and it does show the volume needed and how softly you have to press the mask for proper Ventilation. Glad to Paul extensive high skill training , impressised complete with video screens -vocal cords. Brayden @ems2019 new baby manikin (coming soon) great sim as the illumination lines show you when you are putting in depth and the correct rhythm. The adult and pediatric manikins works, glad I could try all three. Adults @ems2019 Lifeband #zoll 👌 visual and descriptive demostration of cardiac arrest scenaritrauma e the mechanical compression can continue as the patient is move to a a safer place. While it was stationary it was also also allow clinicians to administer drug or can use the defibililator. In all was was most engaging challenge to teach about ALS/PLS . Instead if just getting a freebee you had to participate in rheir scenarios. Respirator portable :no o2 short journey .as it has a compressor. 02 Optional port for longer journey Charges:epocc from siemmes health seems a like alternative to istat cartiges if need a change. This thing cartiges Allow for testing of 11 items , as well as a capillary option too. The best feature in terms of transport is the don't require refrigeration. Add Perks - incubator for transfer MRI.allow less handling of the neonate, certainly smaller and more elegant. Clotting granules .These are ganulea that you our onto a bleeding site. look good for trauma Pic of a good transport monitor and compact with optoon to print by corpus credit: corpus minutor z--/DISCLAIMER: I have no ties or Funding from the companies reviews---.z
  30. 1 point
    We are on important missions in the NICU. From time to time, we all sense the strong rewarding feeling that our work mattered a lot. I love the hands-on work in the NICU, but I also believe strongly in pursuing work at the meta-level of things. That we can change care and improve outcomes through research, quality improvement, and taking our professionalism outside the box. And to the web! Naturally, the 99nicu “global village” is one of those meta-level journeys for me. I have shared small bits of information previously about a new project with a really big scope, Neobiomics, an academic startup company founded in 2016, that will provide a super-high quality bifidobacterial product, “from the community, to the community”. Launch is planned in Europe mid-2019. Although the product itself is much requested, I personally think that this project has a much wider potential. With access to a highly advanced machinery (literally!) at the production facility, it should be possible to make other compositions (other sets of bacteria, other bacterial numbers, +/- other compounds etc) for some really cool comparative trials. We are still working mainly behind the scenes in the Neobiomics HQs, but relatively soon, we will step on stage and start creating buzz Stay tuned PS. The project above has nothing and everything to do with the talk below. Creativity is the Power to Act.
  31. 1 point
    My colleague Ewa Henckel defended her thesis at Karolinska Institutet on "Cellular consequences of preterm birth : telomere biology, immune development and oxidative stress" last week, including four projects on telomere length, inflammation and lung function viral respiratory infections and cellular aging immune system development and environmental exposures hyperoxia-induced lung damage and the capacity to counter-act surfactant inactivation with a novel antioxidant A great thesis, available for download here: https://openarchive.ki.se/xmlui/handle/10616/46531 For the table seating at the dissertation party, her husband had made clever and funny personal drawings for all guests. I translate mine for you below, it is on the spot Best regards from Mr Conference Organiser PS. BTW, hope to meet up with you at the next "Future of Neonatal Care" conference in Copenhagen. Click here to find out more.
  32. 1 point
    Much has been written about methylxanthines over the years with the main questions initially being, “should we use them?”, “how big a dose should we use” and of course “theophylline vs caffeine”. At least in our units and in most others I know of caffeine seems to reign supreme and while there remains some discussion about whether dosing for maintenance of 2.5 -5 mg/kg/d of caffeine base or 5 – 10 mg/kg/d is the right way to go I think most favour the lower dose. We also know from the CAP study that not only does caffeine work to treat apnea of prematurity but it also appears to reduce the risk of BPD, PDA and duration of oxygen therapy to name a few benefits. Although initially promising as providing a benefit by improving neurodevelopmental outcomes in those who received it, by 5 and 11 years these benefits seem to disappear with only mild motor differences being seen. Turning to a new question The new query though is how long to treat? Many units will typically stop caffeine somewhere between 33-35 weeks PMA on the grounds that most babies by then should have outgrown their irregular respiration patterns and have enough pulmonary reserve to withstand a little periodic breathing. Certainly there are those who prove that they truly still need their caffeine and on occasion I have sent some babies home with caffeine when they are fully fed and otherwise able to go home but just can’t seem to stabilize their breathing enough to be off a monitor without caffeine. Then there is also more recent data suggesting that due to intermittent hypoxic episodes in the smallest of infants at term equivalent age, a longer duration of therapy might be advisable for these ELBWs. What really hasn’t been looked at well though is what duration of caffeine might be associated with the best neurodevelopmental outcomes. While I would love to see a prospective study to tackle this question for now we will have to do with one that while retrospective does an admirable job of searching for an answer. The Calgary Neonatal Group May Have The Answer Lodha A et al recently published the paper Does duration of caffeine therapy in preterm infants born ≤1250 g at birth influence neurodevelopmental (ND) outcomes at 3 years of age? This retrospective study looked at infants under 1250g at birth who were treated within one week of age with caffeine and divided them into three categories based on duration of caffeine therapy. The groups were as follows, early cessation of caffeine ≤ 14 days (ECC), intermediate cessation of caffeine 15–30 days (ICC), and late cessation of caffeine >30 days (LCC). In total there were 508 eligible infants with 448 (88%) seen at 3 years CA at follow-up. ECC (n = 139), ICC (n = 122) and LCC (n = 187). The primary outcome here was ND at 3 years of age while a host of secondary outcomes were also examined such as RDS, PDA, BPD, ROP as typical morbidities. It made sense to look at these since provision of caffeine had previously been shown to modify such outcomes. Did they find a benefit? Sadly there did not appear to be any benefit regardless of which group infants fell in with respect to duration of caffeine when it came to ND. When looking at secondary outcomes there were a few key differences found which favoured the ICC group. These infants had the lowest days of supplemental oxygen, hospital stay ROP and total days of ventilation. This middle group also had a median GA 1 week older at 27 weeks than the other two groups. The authors however did a logistic regression and ruled out the improvement based on the advanced GA. The group with the lowest use of caffeine had higher number of days on supplemental oxygen and higher days of ventilation on average than the middle but not the high caffeine group. It is tempting to blame the result for the longer caffeine group on these being babies that were just sicker and therefore needed caffeine longer. On the other hand the babies that were treated with caffeine for less than two weeks appear to have likely needed it longer as they needed longer durations of oxygen and were ventilated longer so perhaps were under treated. What is fair to say though is that the short and long groups having longer median days of ventilation were more likey to have morbidities associated with that being worse ROP and need for O2. In short they likely had more lung damage. What is really puzzling to me is that with a median GA of 27-28 weeks some of these kids were off caffeine before 30 weeks PMA and in the middle group for the most part before 32 weeks! If they were in need of O2 and ventilation for at least two weeks maybe they needed more caffeine or perhaps the babies in these groups were just less sick? What is missing? There is another potential answer to why the middle group did the best. In the methods section the authors acknowledge that for each infant caffeine was loaded at 10 mg/kg/d. What we don’t know though is what the cumulative dose was for the different groups. The range of dosing was from 2.5-5 mg/kg/d for maintenance. Lets say there was an over representation of babies on 2.5 mg/kg/d in the short and long duration groups compared to the middle group. Could this actually be the reason behind the difference in outcomes? If for example the dosing on average was lower in these two groups might it be that with less respiratory drive the babies in those groups needed faster ventilator rates with longer durations of support leading to more lung damage and with it the rest of the morbidities that followed? It would be interesting to see such data to determine if the two groups were indeed dosed on average lower by looking at median doses and total cumulative doses including miniloads along the way. We know that duration may need to be prolonged in some patients but we also know that dose matters and without knowing this piece of information it is tough to come to a conclusion about how long exactly to treat. What this study does though is beg for a prospective study to determine when one should stop caffeine as that answer eludes us!
  33. 1 point
    When it comes to inserting tubes, NICU staff is probably the most experienced in the world. Intubation is one of the first procedures we learn as young doctors in NICU. Some of us perform it through nose, some through mouth. But who performs it on mother’s or father’s chest? Well, I’ve seen it only once or twice, but that is a practice in Uppsala University Hospital. What do you need to perform it? An intubation set. A baby, that actually needs that intubation. It can be a planned or an acute one. And then you need that special thing- a parent (or a caregiver), that is willing to help you with the procedure. When I came back from Sweden, I shared this crazy idea with one neonatal nurse. She told me, that it must be extremely stressful for the parent and that she considers it inhumane to push parents to do that. Well, I can say that I partly agree with her, giving the specification of the unit she worked in at that time. It was a medium size NICU of the highest reference, where parents were welcome to visit the baby, but there were no beds for them, and the chairs for the kangaroo care were each time brought in for that short „session” of skin-to-skin care. LET’S TALK ABOUT SPONTANEITY THERE! But in Uppsala University Hospital this procedure is possible, because you have parents there all the time. They basically never leave the unit. If they are not doing skin-to-skin with their baby (watching a movie on a little player approved by the unit or reading a book), they are cooking or eating in the parent’s area or taking shower in their bathroom. They are not patients there, but they are staying there overnight, so in the morning you can see some of them sneaking out to the bathroom in their pyjamas. So in that situation, you don’t just have a scared parent, who is there from time to time, smiling nervously to his or her child through the plastic incubator. You have a semi-professional companion, who knows his or her baby’s needs best and who is there to care for their own infant. So back to the main topic. Intubation on parent’s chest. Ok, you may say- that sounds okay, but what are the benefits? Why should we risk intubating on an unstable ground? I asked Erik Normann, the Head of the Department of Neonatology in Akademiska Hospital in Uppsala the same question. His opinion is, that in that way child stays in it’s preferred care site during this stressful moment. And in case of spontaneous extubation during skin-to-skin care, you don’t have to move the child back to the incubator to place the tube, so this is quicker. And that skin-to-skin care just continues after the procedure. There’s no special technique or limitations for that procedure, but he admits, that it creates some logistic problems with the staff position around the bed. Also, bending over parent’s chest is not the most optimal working position (especially for taller doctors 😉). But what you get in return for that effort is a happier baby, supported and stabilized by their parents hands. I’m not sure if all of us are „there yet”. What is the more important, is that we are heading in that direction- to this mental NICUland, where parents are there for the baby all the time, to offer warmth of their skin and delicacy of their touch, and where medical staff is ready to accept their help and presence. Together we can do more! So hands up guys- who does that too in their unit? Who would like to try?✋✋✋
  34. 1 point
    The APTS (Australian placental transfusion study) trial has just appeared on line. This was a high-quality multicenter, international RCT of immediate cord clamping (less than 10 seconds) compared to delayed clamping (60 seconds) for babies born less than 32 weeks gestation. (Tarnow-Mordi W, et al. Delayed versus Immediate Cord Clamping in Preterm Infants. the FPNEJM 2017.) Another trial arriving almost simultaneously is a smaller trial from the UK, which compared cord clamping at less than 20 seconds to clamping at at least 2 minutes, with reuscitation staring with the cord intact in the intervention group. (Duley L, et al. Randomised trial of cord clamping and initial stabilisation at very preterm birth. Archives of disease in childhood Fetal and neonatal edition. 2017.) I will come back to that trial in part 2. The benefits of delayed cord clamping for term babies are quite obvious from the RCTs, and basically show a significantly improved Hemoglobin/Iron status for the first year of life, which seems to lead to some improvement in fine motor function, in the long term, with no important down-side. The higher bilirubin levels among late-clamped babies do not lead to more phototherapy, if modern restrictive phototherapy guideline are followed. The only real disadvantage is that it is much harder to give blood to a public cord blood bank after delayed clamping. Public banks have been the source of stem cells for bone marrow transplants for hundreds of children (and as far as I know adults as well) so this should not be dismissed... For the preterm baby I thought that much of the evidence had been over-hyped, with claims of reduced IVH, and reduced NEC, based on tiny numbers from tiny trials, with no robust evidence of benefit, apart from higher hemoglobins, probably leading to fewer transfusions. What we really needed was a large RCT with enough power to answer questions about efficacy and safety. The APTS trial gives that power, with over 1500 babies randomized, and, although much smaller, the trial from England is the second largest trial, with over 260 babies. The remaining trials that have been quoted as the justification for the worldwide movement for delayed clamping in the preterm, have mostly been tiny, with sample sizes between 32 and 200. What did the APTS trial show? Speaking in the strictest sense it showed no difference between groups in the primary outcome. The primary outcome was a composite outcome of death, serious brain injury, late-onset sepsis, necrotising enterocolitis or severe retinopathy. When the study was planned bronchopulmonary dysplasia was also part of the primary outcome, but with changes in practice the authors found that the incidence of "BPD" was much higher than expected (many babies were on respiratory support with positive pressure and 21% oxygen at 36 weeks post-menstrual age), so during the trial, before the final data were analysed, BPD was deleted from the composite outcome. When you look at the individual components of the composite outcome, there is no sign of a benefit for any of the components of that composite, except one, that is mortality. When only one part of a composite outcome is positive, but it is much less frequent than the remaining parts, the overall composite may well be negative. This is one of the problems with composite outcomes, you can actually lose power for the most important part of the composite, whereas these composites are usually being used to try to increase power! The outcome of death should therefore strictly be considered to be a secondary outcome, and therefore treated with some scepticism. I'll come back to this point. Also important is the fact that 26% of the delayed clamping group did not get 60 seconds of delay, which was most often due to concerns about the neonatal status (70% of the time). This was unavoidable given the design, as most centers were not resuscitating babies with the cord intact. 20% of the delayed clamping group got the cord clamped before 30 seconds, the other 6% who did not follow protocol it was between 30 and 60 seconds. It would be interesting to have a "per-protocol" analysis of mortality results, which I would guess would show a greater difference between groups, as babies who had the delayed clamping interrupted because of concerns about neonatal status might well have a higher mortality. There is an analysis of the per-protocol effects on the primary outcome (in the supplementary appendix) which shows a difference (which may just be due to chance, p=0.2) : 37% with immediate clamping, and 33% with delayed clamping, but no mention of the components of that outcome. There is also a report of the causes of death in the supplementary appendix, causes which cover the entire range of causes of death among very preterm babies. The biggest single cause was septicemia, which was also the cause that showed the biggest difference between groups, 2.2% immediate clamping, and 0.5% delayed clamping. There is also an analysis in detail of head ultrasound findings which show no tendency to be different in any aspect between groups. Finally there were many fewer babies who needed blood transfusions with the delayed clamping (61% with immediate clamping, 52% with delayed clamping) but more babies with polycythemia (2% had hematocrit >65% with immediate clamping, 6% with delayed clamping, 1% over 70% immediate, 2% with delayed). There was no clinically important difference in bilirubin concentrations (mean was 3 micromoles higher with delayed). Overall then, a potential decrease in mortality, a decrease in the number of babies receiving transfusion, with a very small increase in polycythemia, which was probably not due to chance (p<0.001). What to do with these results? Well, as yet there is no signal for a clinically important harm of delayed cord clamping; with the proviso that babies who are intended to have delayed cord clamping may often have the cord clamped early. I think that a clinical approach planning for delayed clamping at, or perhaps after 60 seconds, is consistent with the best evidence, it will decrease the number of babies receiving transfusions, and might decrease mortality. We also need an updated systematic review and meta-analysis. But for that you will have to wait for part 3!
  35. 1 point
    I don’t envy our nurses who care for babies withdrawing from various opiates and other substances. These assignments are definitely a challenge and require a great deal of patience and depending on the shrillness of an infant’s cry a good set of earplugs. Nonetheless we do our best with these infants to keep them calm and avoid as much stimulation as we can as we attempt to minimize the excitability of their nervous system. Over 40 years ago the Finnegan Neonatal Abstinence scoring system was developed to assist medical teams by providing as objective a system as possible to compare one infant to another and determine when and if a patient should be treated pharmacologically. Unfortunately there is a problem inherent with this scoring system. It is the same problem that exists when you don’t have a blinded research trial. Imagine you are caring for an infant and you were given no history about drug exposure. How might you score a patient like that compared to one in which you are told has been exposed to illicit substances? Your senses are heightened and moreover if you were told this baby is “withdrawing terribly” or “is awful at night” you are biased. How are you likely to score such a patient when they are “on the edge” of being counted as a 1 or a 0 in a category? I bet in many cases, especially if you haven’t taken care of many such patients you err on the side of caution and score them on the high side. It is human nature. When the possible outcome of failing to recognize a withdrawing patient is a seizure, no one wants to be on when it happens having their scoring questioned. Have a look at the scoring tool though. There is a lot of stuff in there to check off! What if it could be simpler? The ESC Tool In early May, news began to break of an abstract being presented at the Pediatric Academic Society meeting. The news story from the AAP can be found here. The ESC tool is a three question tool used to assess whether an infant requires treatment for withdrawal. E – Eat (is an infant is able to eat 1 or more ounce per feeding) S – Sleeping (sleep for an hour or longer undisturbed) C – Console (Be consoled in 10 minutes or less.) If all three criteria are met, the patient does not need treatment. If one or more criteria are not met the housestaff are notified and first non-pharmacologic and then pharmacologic means are employed if necessary to control symptoms. The authors did something quite interesting. They looked at 50 patients with 201 hospital days with prenatal exposures to opiates and applied the ESC criteria to guide treatment. Concurrently they captured the Finnegan scores but did not use them to guide treatment. The findings I hope you will agree are quite interesting! “FNASS scores indicated starting morphine in 30 infants (60%). Morphine was actually started on only 6 patients (12%) (p< 0.0001) based on the ESC approach. The FNASS led protocol directed initiating or increasing meds on 24.6% of days compared to 2.7% of days using the ESC approach (p< 0.0001). The FNASS approach directed that morphine was either not started or decreased on 65.8% of days compared with 94.4% of days using the ESC approach (p< 0.0001). There were no readmissions or reported adverse events. Pretty amazing but… The ESC approach greatly reduced the need for treatment and as the authors state there were no readmissions or reported adverse events. What we don’t know and will be needed I suspect before anyone will adopt this strategy (which I have to say again is so much simpler that current approaches) is how these children do in the long run. If the system is undertreating withdrawal, could we see downstream impacts of a “kinder and gentler” approach? One outcome that will be reported soon in the next month is length of stay. I am eagerly awaiting further results as I for one think that a simpler approach to these patients may be just what the doctor ordered. I think the nurses might thank us as well but we will see just how appropriate it is! The Abstract reporting these findings can be found below Novel Approach to Evaluating and Treating Infants with Neonatal Abstinence Syndrome
  36. 1 point
    The infant car seat challenge(ICSC) is a test which most definitely fits the definition of a battleground issue in Neonatology. After publishing the Canadian Pediatric Practice point on the same topic I received interesting feedback through the various social media forums that I frequent. While some were celebrating the consensus of the statement as verification that a centres’ non practice of the test was acceptable, others seriously questioned the validity of the position. The naysayers would point out that extremely infrequent events unless intentionally tracked may be difficult to pick up. In the case of the ICSC, if a few patients were to suffer a hypoxic event leading to an ALTE or worse after discharge, could the ICSC have picked out these babies and prevented the outcome? The evidence for adverse events associated with the use of car seats as discussed in the position statement is poor when using autopsy records over decades but when many clinicians can point to a failed ICSC picking up events, the thought goes that they “caught one”. Does catching one make a difference though? The Well Appearing Infant Shah et al in their recent paper Clinical Outcomes Associated with a Failed Infant Car Seat Challenge attempt to address this very point. They performed a retrospective study of 148 patients who were either <37 weeks GA or < 2500g at birth. The study was made possible by the fact that all such infants in their hospital admitted to a well newborn area meeting these criteria by policy must have an ICSC prior to discharge. Keep in mind that these were all infants who were on the well newborn service since they were asymptomatic. The definition of an event in this group was one or more of pulse oximeter saturation ≤ 85% for > 10 seconds, apnea > 20 seconds, bradycardia < 80 bpm for > 10 seconds, or an apnea or bradycardia event requiring stimulation. The failure rate was 4.5% which is very similar to other reported studies. Why did they “fail”? Failure of the ICSC was owing to desaturation 59% Bradycardia 37% Tachypnea 4% Combination of 2 in 11% What is interesting about these results is what happened to these infants after admission to the NICU in that 39% were identified with apnea (48% in preterm vs 17% in term infants). These events were in the supine position which is a curious finding since the ICSC was designed to find risk of cardiorespiratory stability in a semi-recumbent position. This has been shown previously though. What does it all mean? The infants in this study ultimately had more NG feeding, prolonged length of stay and septic workups after failing the ICSC that comparable infants who passed. At first blush one would read this article and immediately question the validity of the CPS position but then the real question is what has this added to the “pool of knowledge”. That infants may fail an ICSC at a rate of 4.5% is already known. That such infants may demonstrate apneic events has also been shown before and a study like this may help to support those clinicians who feel it is still imperative to find these infants in order to achieve a safe discharge. I think it is important to put these findings in the context of what would have happened if such a unit did not routinely test these types of babies. As all were seemingly well and I presume feeding with their families, they would have been discharged after 24-48 hours to home. We have no evidence (since they have not compared this sample to a group who did not have such testing) that if these babies were discharged they would have faired poorly. The supporters of the ICSC would point to all the support these babies received by admitting them for 6-8 days, providing NG feeding and ruling out sepsis that they were unsafe for discharge. The other possible way to look at it was that the infants were subjected to interventions that we have no evidence helped them. Whether any of these infants had a positive blood culture justifying antibiotics or needed methylxanthine support is not mentioned. Judging however by the short length of stay I suspect that none or few of these infants needed such medication as I would expect they would have stayed much longer had they needed medical treatment for apnea. Conclusion I do commend the authors for completing the study and while it does raise some eyebrows, I don’t see it changing at least my position on the ICSC. While they have described a cohort of patients who failed the ICSC nicely, the fundamental question has been left unanswered. Does any of this matter? If you look well, are feeding well and free of any clinically recognizable events but are late preterm or IUGR can the ICSC prevent harm? This has not been answered here and perhaps the next step would be for a centre that has abandoned the ICSC to follow their patients after discharge prospectively and see whether any adverse outcomes do indeed occur. Any takers?
  37. 1 point
    Positive pressure ventilation puts infants at risk of developing chronic lung disease (CLD). Chronic lung disease in turn has been linked many times over, as a risk for long term impacts on development. So if one could reduce the amount of positive pressure breaths administered to a neonate over the course of their hospital stay, that should reduce the risk of CLD and by extension developmental impairment. At least that is the theory. Around the start of my career in Neonatology one publication that carried a lot of weight in academic circles was the Randomized Trial of Permissive Hypercapnia in Preterm Infants which randomized 49 surfactant treated infants to either a low (35-45) or high (45-55) PCO2 target with the thought being that allowing for a higher pCO2 should mean that lower settings can be used. Lower settings on a ventilator would lead to less lung damage and therefore less CLD and in turn better outcomes. The study in question did show that the primary outcome was indeed different with almost a 75% reduction in days of ventilation and with that the era of permissive hypercapnia was born. The Cochrane Weigh in In 2001 a systematic review including this and another study concluded that there was insufficient evidence to support the strategy in terms of a benefit to death or chronic lung disease. Despite this lack of evidence and a recommendation from the Cochrane group that permissive hypercapnia be used only in the context of well designed trials the practice persisted and does so to this day in many places. A little lost in this discussion is that while the end point above was not different there may still be a benefit of shorter term ventilation. A modern cohort It would be unwise to ignore at this point that the babies of the late 90s are different that the ones in the current era. Surfactant and antenatal steroid use are much more prevalent now. Ventilation strategies have shifted to volume as opposed to pressure modes in many centres with a shift to early use of modalities such as high frequency ventilation to spare infants the potential harm of either baro or volutrauma. Back in 2015 the results of the PHELBI trial were reported Permissive hypercapnia in extremely low birthweight infants (PHELBI): a randomised controlled multicentre trial. This large trial of 359 patients randomized to a high or low target pCO2 again failed to show any difference in outcomes in terms of the big ones “death or BPD, mortality alone, ROP, or severe IVH”. What was interesting about this study was that they did not pick one unified target for pCO2 but rather set different targets as time went on reflecting that with time HCO3 rises so what matters more is maintaining a minimum pH rather than targeting a pCO2 alone which als0 reflects at least our own centre’s practice. There is a fly in the ointment here though and that is that the control group has a fault (at least in my eyes) Day of life Low Target High Target 1-3 40-50 55-65 4-6 45-55 60-70 7-14 50-60 65-75 In the original studies of permissive hypercapnia the comparison was of a persistent attempt to keep normal pCO2 vs allowing the pCO2 to drift higher. Although I may get some argument on this point, what was done in this study was to compare two permissive hypercapnia ranges to each other. If it is generally accepted that a normal pCO2 is 35-45 mmHg then none of these ranges in the low target were that at all. How did these babies do in the long run? The two year follow-up for this study was published in the last month; Neurodevelopmental outcomes of extremely low birthweight infants randomised to different PCO2 targets: the PHELBI follow-up study. At the risk of sounding repetitive the results of Bayley III developmental testing found no benefit to developmental outcome. So what can we say? There is no difference between two strategies of permissive hypercapnia with one using a higher and the other a lower threshold for pCO2. It doesn’t however address the issue well of whether targeting a normal pCO2 is better or worse although the authors conclude that it is the short term outcomes of shorter number of days on ventilation that may matter the most. The Truth is Out There I want to believe that permissive hypercapnia makes a difference. I have been using the strategy for 15 or so years already and I would like to think it wasn’t poor strategy. I continue to think it makes sense but have to admit that the impact for the average baby is likely not what it once was. Except for the smallest of infants many babies these days born at 27 or more weeks of gestation due to the benefits of antenatal steroids, surfactant and modern ventilation techniques spend few hours to days on the ventilator. Meanwhile the number of factors such chorioamniotitis, early and late onset sepsis and genetic predisposition affect the risks for CLD to a great degree in the modern era. Not that they weren’t at play before but their influence in a period of more gentle ventilation may have a greater impact now. That so many factors contribute to the development of CLD the actual effect of permissive hypercapnia may in fact not be what it once was. What is not disputed though is that the amount of time on a ventilator when needed is less when the strategy is used. Let us not discount the impact of that benefit as ask any parent if that outcome is of importance to them and you will have your answer. So has permissive hypercapnia failed to deliver? The answer in terms of the long term outcomes that hospitals use to benchmark against one and other may be yes. The answer from the perspective of the baby and family and at least this Neonatologist is no.
  38. 1 point
    This is becoming “all the rage” as they say. I first heard about the strategy of feeding while on CPAP from colleagues in Calgary. They had created the SINC (Safe Individualized Feeding Competence) program to provide an approach to safely introducing feeding to those who were still requiring CPAP. As news of this approach spread a great deal of excitement ensued as one can only imagine that in these days when attainment of oral feeding is a common reason for delaying discharge, could getting an early start shorten hospital stay? I could describe what they found with the implementation of this strategy but I couldn’t do it the same justice as the presenter of the data did at a recent conference in Winnipeg. For the slide set you can find them here. As you can imagine, in this experience out of Calgary though they did indeed find that wonderful accomplishment of shorter hospital stays in the SINC group. We have been so impressed with the results and the sensibility of it all that we in fact have embraced the concept and introduced it here in both of our units. The protocol for providing this approach is the following. I have to admit, while I have only experienced this approach for a short time the results do seem to be impressive. Although anecdotal a parent even commented the other day that she felt that SINC was instrumental in getting her baby’s feeding going! With all this excitement around this technique I was thrown a little off kilter when a paper came out suggesting we should put a full stop to feeding on CPAP! Effect of nasal continuous positive airway pressure on the pharyngeal swallow in neonates What caused my spirits to dampen? This study enrolled preterm infants who were still on CPAP at ≥ 34 weeks PMA and were taking over 50% of required feeding volumes by NG feeding. The goal was to look at 15 patients who were being fed on CPAP +5 and with a mean FiO2 of 25% (21-37%) using video fluoroscopic swallowing studies to determine whether such patients aspirate when being fed. The researchers became concerned when each of the first seven patients demonstrated abnormalities of swallowing function indicating varying degrees of aspiration. As such they took each patient off CPAP in the radiology suite and replaced it with 1 l/min NP to achieve acceptable oxygen saturations and repeated the study again. The results of the two swallow studies showed remarkable differences in risk to the patient and as such the recruitment of further patients was stopped due to concerns of safety and a firm recommendation of avoiding feeding while on CPAP was made. Table 2. Percentage of all swallows identified with swallowing dysfunction on-nCPAP off-nCPAP Variable Mean ± s.d. Mean ± s.d. Median (q1–q3) Mean ± s.d. Median (q1–q3) P-value Mild pen. % 20.1±16 20 (4.5–35) 15.4± 7.6 20 (9–20) 0.656 Deep pen. % 43.7±15.4 38.5 (30–59) 25.3± 8.8 25 (18.2–32) 0.031 Aspiration % 33.5±9.4 30 (27.3–44.4) 14.6± 7 15 (9.1–20) 0.016 Nasopharyngeal reflux % 42.8±48.5 18.2 (0–100) 44.2± 45.4 18.2 (5–92) 0.875 Taking these results at face value it would seem that we should put an abrupt halt to feeding while on CPAP but as the saying goes the devil is in the details… CPAP Using Ram Cannulae Let me start off by saying that I don’t have any particular fight to pick with the RAM cannulae. They serve a purpose and that is they allow CPAP to be delivered with a very simple set of prongs and avoid the hats, straps and such of more traditional CPAP devices. We have used them as temporary CPAP delivery when moving a patient from one area to another. As the authors state the prongs are sized in order to ensure the presence of a leak. This has to do with the need to provide a way for the patient to exhale when nasal breathing. Prongs that are too tight have a large leak and may not deliver adequate pressure while those that are too tight may inadvertently deliver high pressure and therefore impose significant work of breathing on the patient. Even with appropriate sizing these prongs do not allow one to exhale against a low pressure or flow as is seen with the “fluidic flip” employed with the infant flow interface. With the fluidic flip, exhalation occurs against very little resistance thereby reducing work of breathing which is not present with the use of the RAM cannula. A comparison of the often used “bubble CPAP” to a variable flow device also showed lower work of breathing when variable flow is used. The Bottom Line Trying to feed an infant who is working against a constant flow as delivered by the RAM cannulae is bound to cause problems. I don’t think it should be a surprise to find that trying to feed while struggling to breathe increases the risk of aspiration. Similarly, under treating a patient by placing them on nasal prongs would lead to increased work of breathing as while you may provide the needed O2 it is at lower lung volumes. Increasing work of breathing places infants at increased risk of aspiration. That is what I would take from this study. Interestingly, looking at the slide set from Calgary they did in fact use CPAP with the fluidic flip. Smart people they are. It would be too easy to embrace the results of this study and turn your nose to the SINC approach to feeding on CPAP. Perhaps somewhere out there someone will read this and think twice about abandoning the SINC approach and a baby will be better for it.
  39. 1 point
    As you may have noticed, we have opened the registration for the 99nicu Meetup 12-15 June. I hope many of you will be able to come! Click here for more infor! We got some feedback from a member in an African country about the fee for the meeting, which is 5600 SEK (excl VAT) corresponding to ~630 USD, and whether we had plans to add a differentiated lower fee for members coming from middle- and low-income countries. I really wished we could offer a reduced fee but to with a limited number of seats and to cover the costs for the venue, lunches, speakers' travels etc-etc, we need to charge this fee as the general cost level is this high in Sweden. Further, 99nicu is still a project based on volontary work and without funds (and viable business model, but that's another story...). In other words, we have none backing our budget in case of a deficit, and are pressed to go break-even financially. The better news are though that we plan to video-record all lectures and will make those available through 99nicu.org. Given funding, of course!
  40. 1 point
    If you work in the NICU then you have seen your fair share of septic workups for late onset sepsis. Sepsis is such a common diagnosis that if I had to guess I would say that at least 50% of all discharge summaries would include this in a list of final diagnoses for any VLBW infant. If you were to look through the chart though you would find that while workups are common, the recovery of a pathogenic bacterium is not as much. This is in part due to the low threshold that many people have for doing such workups. A little bit of temperature instability, a few more apneic events than normal or a rise in O2 requirements may all trigger such investigations. When they come back negative we all feel good that we looked but we also are then quick to blame the etiology on something else. Mild fluctuations in temperature are written off as overbundling, apnea due to outgrowth of caffeine and a rise in FiO2 to evolving CLD. Maybe though the explanation at least in some cases is that there was a pathogen but we didn’t test for it. Viruses are everywhere Tis the season so to speak so everyone is on high alert for viruses in our homes, schools, malls etc but many of us consider the NICU to be mostly free of such pathogens. The truth is we mostly are provided that we all wash our hands well, keep sick contacts from visiting and put on a mask when our coughing starts. Alas, if you have done a handwashing audit as we have you would know that when looking at technique and duration of handwashing, we don’t always hit 100%. These audits are for health care practitioners but I have often wondered what sort of results we would see were we to do the same for parents and visitors. When we know the viruses are out there such as during outbreaks of RSV and influenza we can’t help but send off our samples for respiratory viruses more frequently but what if we did this with intention for every late onset septic workup? Lucky For Us Someone Did Just That! Back in 2014 the following study was published. Viral respiratory tract infections in the neonatal intensive care unit: the VIRIoN-I study. This was a simple prospective and elegant study in which any infant in the NICU who had never been home and was greater than 72 hours had respiratory samples sent for viral panels within 72 hours of starting antibiotics for presumed late onset sepsis. The findings were certainly interesting in that 6% of 135 sepsis evaluations tested positive for a virus. In the analysis, the infants had the following characteristics: tended to be older (41 vs 11 days; P = .007) exposed to individuals with respiratory tract viral symptoms (37% vs 2%; P = .003) lower total neutrophil counts (P = .02) best predictor of viral infection was the caregivers’ clinical suspicion of viral infection (P = .006) What interests me about these results are a couple things. The first is that as I was once told, the sensitivity of asking if someone has been around sick people is low during peaks in viral outbreaks as who hasn’t? Perhaps what this study tells us is that within the NICU environment we actually do a reasonable job of keeping such contacts away but when they slip through infections happen. The second point worth mentioning is that a low neutrophil count is associated which is interesting given how often neutropenia is pointed to as a reason to start antibiotics. These viruses are troublesome creatures indeed! Further Evidence Arrives At the end of last year a similar study was published by the same group Viral Respiratory Infections in Preterm Infants during and after Hospitalization. They took a different approach this time out and took nasopharyngeal samples from 189 infants in the NICU (96 term and 93 preterm) within 7 days of birth and then sent samples weekly while in hospital followed by monthly for four months after discharge. In this collection of infants a mere 4 patients tested positive in NICU and all of them under 28 weeks of age at birth! How do we account for the remarkable reduction in risk while in hospital? To answer that you can read through the NICU environment in the full article if you have access. In short, they had a very rigorous infection control set of precautions set up. Interestingly only one of the infections was with RSV and the unit did not provide prophylaxis for infants in hospital. Perhaps with precautions like theirs they felt it was unnecessary. Once discharged a little over a third of patients acquired a viral infection in the first four months at home. Given the potential risk for readmission and with that to a PICU this rate of viral infection is concerning. Vision for the future! Taken together we can state that viruses do make their way into the NICU but fortunately not as commonly as one might think. What the last study in particular does remind us though is that we need to ensure that as part of discharge teaching parents take home many of the practices that we have used in the hospital with respect to hand hygiene, limiting visitors and not being afraid to holster some hand sanitizer for those times when soap and water are not so easy to come by. To be sure viruses are out there but at least for the first few months after discharge for our most vulnerable babies a little paranoia about viruses could go a long way.
  41. 1 point
    This is something that I continue to hear from time to time even in 2016 and I imagine I will continue to hear rumblings about this in 2017. Certainly, there are physical limitations when a baby is born at less than 500g. Have you tried fitting a mask to deliver NIPPV or CPAP to a baby this small? I have and it didn’t work. The mask was simply too big to provide a seal and while I am all for INSURE and emerging minimally invasive surfactant techniques they still require transitioning to a form of non invasive positive pressure ventilation to allow extubation success. Certainly though above the 500g barrier it may be that the greatest impediment to extubation is our own bias. If this sounds a little familiar it is because I have written about this topic before Extubation failure is not a failure itself. The reason for bringing the topic up again though is that aside from needing to address our own fears there is a new systematic review that acts somewhat of a how to guide to optimizing your chance at a successful extubation. The review encompasses findings from 50 studies with successful extubation as defined as no need for reintubation within 7 days. Before getting into the details of the optimal approach it is worth reminding people that failure of extubation in even our smallest babies is not a failure itself. Such babies who “fail” up to 5 times do not suffer any long term consequences and may wind up with less risk of BPD than those who are kept intubated due to fear of failure. So After Reviewing The Evidence What Are the Recipes To Success? Continuous positive airway pressure Reduced extubation failure in comparison with head-box oxygen (risk ratio [RR], 0.59;95%CI, 0.48-0.72; number needed to treat [NNT], 6; 95%CI, 3-9). If you aren’t extubating to nCPAP then chances are I would bet your success rates are quite low. Head boxes certainly can tell you how much O2 a patient requires but do nothing to help inflate alveolar spaces. Nasal intermittent positive pressure ventilation (NIPPV) vs. CPAP Higher prevention of extubation failure (RR, 0.70; 95%CI, 0.60-0.81; NNT, 8; 95%CI, 5-13). This one is of particular interest to me. The evidence has suggested this for some time and with a number needed to treat of 8 it would seem illogical to use anything else at the outset, especially in the smallest of infants. The issue here though is that at least here in Canada the options for delivering such NIPPV are currently quite limited. At the moment we are limited to use of ventilator NIPPV and the stability of the CPAP offered from such devices and the imposed work of breathing are most likely inferior to that found in variable flow devices which at this point have been pulled from the market. See Comparison of nasal continuous positive airway pressure delivered by seven ventilators using simulated neonatal breathing. What I hope 2017 brings is a comparison of the effectiveness of extubation success using new variable flow devices capable of generating previously unreachable CPAP pressures above 9 or 10 cm H2O. Will these attain similar effectiveness to the NIPPV devices? Methylxanthines reduced extubation failure (RR, 0.48; 95%CI, 0.32-0.71; NNT, 4; 95%CI, 2-7) compared with placebo or no treatment. Ok, pretty much anyone working in Neonatology would assume this but what really is at the crux of the discussion in 2016 and beyond is “what dose?” It has been pretty clear during my career thus far that there are some preterm infants that just don’t respond to conventional doses of caffeine base from 2.5 – 5 mg/kg/d. In our own units we have increased doses to 6, 7 or 8 mg/kg/d to achieve some degree of respiratory stimulation and usually been limited by tachycardia in determining how high we can go. Given the sparse literature regarding safety on this topic we are relegated to ask ourselves what is worse, leaving a baby on a ventilator or using higher doses of caffeine? I have given some thoughts on this before as well Are we overdosing preemies on caffeine? Doxapram did not aid successful extubation (RR, 0.80; 95% CI, 0.22-2.97). For selfish reasons I have to admit I was happy to see this. We can’t access this medication very easily here in Canada so hearing that it doesn’t seem to work to enhance the likelihood of a successful extubation is somewhat of a relief. A Cautionary Note While I applaud the authors of the systematic review for performing such a thorough job I do feel the need to raise one concern with the analysis. It is not a major concern but one that I just feel the need to mention. Success if the studies was defined as not requiring reintubation within 7 days of extubation. My concern is that having such a lengthy time frame leaves the possibility that the decision to reintubate had nothing to do with the patient in fact not being ready. Seven days is a long time and much can happen in the life of a preterm infant in an NICU that triggers a reintubation. What if a patient needed to be transferred to a different NICU and for safe air transport it was deemed safest to replace the ETT? How many patients could have developed NEC or sepsis in the seven days? What if a PDA was being semi-electively ligated after a failed NSAID course? In the end the impact of such conditions could be minimal but I am less convinced that a patient failed extubation when up to 7 days have passed. I would be very interested to see a similar study looking at a period of 24 or 48 hours after extubation and seeing how many stay that way. Would the predictors of success stay the same? Probably but I suspect the number safely extubated would rise as well. featured image from the March of Dimes
  42. 1 point
    A strange title perhaps but not when you consider that both are in much need of increasing muscle mass. Muscle takes protein to build and a global market exists in the adult world to achieve this goal. For the preterm infant human milk fortifiers provide added protein and when the amounts remain suboptimal there are either powdered or liquid protein fortifiers that can be added to the strategy to achieve growth. When it comes to the preterm infant we rely on nutritional science to guide us. How much is enough? The European Society For Pediatric Gastroenterology, Hepatology and Nutrition published recommendations in 2010 based on consensus and concluded: “We therefore recommend aiming at 4.0 to 4.5 g/kg/day protein intake for infants up to 1000 g, and 3.5 to 4.0 g/kg/day for infants from 1000 to 1800 g that will meet the needs of most preterm infants. Protein intake can be reduced towards discharge if the infant’s growth pattern allows for this. The recommended range of protein intake is therefore 3.5 to 4.5 g/kg/day.” These recommendations are from six years ago though and are based on evidence that preceded their working group so one would hope that the evidence still supports such practice. It may not be as concrete though as one would hope. Let’s Jump To 2012 Miller et al published an RCT on the subject entitled Effect of increasing protein content of human milk fortifier on growth in preterm infants born at <31 wk gestation: a randomized controlled trial. This trial is quite relevant in that it involved 92 infants (mean GA 27-28 weeks and about 1000g on average at the start), 43 of whom received a standard amount of protein 3.6 g/kg/day vs 4.2 g/kg/d in the high protein group. This was commenced once fortification was started and carried through till discharge with energy intakes and volume of feeds being the same in both groups. The authors used a milk analyzer to ensure consistency in the total content of nutrition given the known variability in human milk nutritional content. The results didn’t show much to write home about. There were no differences in weight gain or any measurements but the weight at discharge was a little higher in the high protein group. The length of stay trended towards a higher number of days in the high protein group so that may account for some of the difference. All in all though 3.6 or 4.2 g/kg/d of protein didn’t seem to do much to enhance growth. Now let’s jump to 2016 This past month Maas C et al published an interesting trial on protein supplementation entitled Effect of Increased Enteral Protein Intake on Growth in Human Milk-Fed Preterm Infants: A Randomized Clinical Trial. This modern day study had an interesting question to answer. How would growth compare if infants who were fed human milk were supplemented with one of three protein contents based on current recommendations. The first group of 30 infants all < 32 weeks received standard protein intake of 3.5 g/kg/d while the second group of 30 were given an average intake of 4.1 g/kg/d. The second group of 30 were divided though into an empiric group in which the protein content of maternal or donor milk was assumed to be a standard amount while the second 15 had their protein additive customized based on an analysis of the human milk being provided. Whether the higher intake group was estimated or customized resulted in no difference in protein intake on average although variability between infants in actual intake was reduced. Importantly, energy intake was no different between the high and low groups so if any difference in growth was found it would presumably be related to the added protein. Does it make a difference? The results of this study failed to show any benefit to head circumference, length or weight between the two groups. The authors in their discussion postulate that there is a ceiling effect when it comes to protein and I would tend to agree. There is no question that if one removes protein from the diet an infant cannot grow as they would begin to break down muscle to survive. At some point the minimum threshold is met and as one increases protein and energy intake desired growth rates ensue. What this study suggests though is that there comes a point where more protein does not equal more growth. It is possible to increase energy intakes further as well but then we run the risk of increasing adiposity in these patients. I suppose it would be a good time to express what I am not saying! Protein is needed for the growing preterm infant so I am not jumping on the bandwagon of suggesting that we should question the use of protein fortification. I believe though that the “ceiling” for protein use lies somewhere between 3.5 – 4 g/kg/d of protein intake. We don’t really know if it is at 3.5, 3.7, 3.8 or 3.9 but it likely is sitting somewhere in those numbers. It seems reasonable to me to aim for this range but follow urea (something outside of renal failure I have personally not paid much attention to). If the urea begins rising at a higher protein intake approaching 4 g/kg/d perhaps that is the bodies way of saying enough! Lastly this study also raises a question in my mind about the utility of milk analyzers. At least for protein content knowing precisely how much is in breastmilk may not be that important in the end. Then again that raises the whole question of the accuracy of such devices but I imagine that could be the source of a post for another day.
  43. 1 point
    I had a chance recently to drive a Tesla Model S with autopilot. Taking the car out on a fairly deserted road near my home I flicked the lever twice to activate the autopilot feature and put my hands behind my head while the vehicle took me where I wanted to go. As I cruised down the road with the wheel automatically turning with the curves in the road and the car speeding up or slowing down based on traffic and speed limit notices I couldn’t help but think of how such technology could be applied to medicine. How far away could the self driving ventilator or CPAP device be from development? I have written about automatic saturation adjustments in a previous post but this referred to those patients on mechanical ventilation. Automatic adjustments of FiO2. Ready for prime time? Why is this goal so important to attain? The reasoning lies in the current design trends in modern NICUs. We are in the middle of a large movement towards single patient room NICUs which have many benefits such as privacy which may lead to enhanced breastfeeding rates and increased parental visitation. The downside, having spoken to people in centres where such designs are already in place is the challenge nursing faces when given multiple assignments of babies on O2. If you have to go from room to room and a baby is known to be labile in their O2 saturations it is human nature to turn the O2 up a little more than you otherwise would to give yourself a “cushion” while you are out of the room. I really don’t fault people in this circumstance but it does pose the question as to whether in a few years we will see a rise in oxygen related tissue injury such as CLD or ROP from such practice. In the previous post I wrote about babies who are ventilated but these infants will often be one to one nursed so the tendency to overshoot the O2 requirements may be less than the baby on non- invasive ventilation. A System For Controlling O2 Automatically For Infants on Non-Invasive Ventilation This month in Archives Dr. Dargaville and colleagues in Australia provide two papers, the first demonstrating the validation of the mathematical algorithm that they developed to control O2 and the second a clinical report outlining how well the system actually performed on patients. The theoretical paper Development and preclinical testing of an adaptive algorithm for automated control of inspired oxygen in the preterm infant. is a challenge to comprehend although validates the approach in the end while the clinical paper at least for me was easier to digest Clinical evaluation of a novel adaptive algorithm for automated control of oxygen therapy in preterm infants on non-invasive respiratory support. The study was really a proof of concept with 20 preterm infants (mean GA 27.5 weeks, 8 days of age on average) included who each underwent two hours of manual control by nursing to keep saturations between 90-94% and then 4 hours of automated control (sats 91 – 95%) then back to manual for two hours. The slightly shifted ranges were required due to the way in which midpoint saturations are calculated. The essential setup was a computer equipped with an algorithm to make adjustments in FiO2 using an output to a motor that would adjust the O2 blender and then feedback from an O2 saturation monitor back to the computer. The system was equipped with an override to allow nursing to adjust in the event of poor signal or lack of response to the automatic adjustment. The results though demonstrate that the system works and moreover does a very good job! The average percentage of time that the saturations were in the target range were significantly better with automated control (81% automated, 56% manual). As well as depicted in the following figure the amount of time spent in both hypoxic and hyperoxic ranges was considerable with manual control but non-existent on either tail with automated control (defined as < 85% or > 98% where black bars are manual control and white automatic). From the figure you can see that the amount of time the patients are in target range are much higher with automatic control but is this simply because in addition to automatic control, nurses are “grabbing the wheel” and augmenting the system here? Not at all. “During manual control epochs, FiO2 adjustments of at least 1% were made 2.3 (1.3–3.4) times/hour by bedside staff. During automated control, the minimum alteration to FiO2 of 0.5% was being actuated by the servomotor frequently (9.9 alterations/min overall), and changes to measured FiO2 of at least 1% occurred at a frequency of 64 (49–98) /hour. When in automated control, a total of 18 manual adjustments were made in all 20 recordings (0.24 adjustments/hour), a reduction by 90% from the rate of manual adjustments observed during manual control (2.3/hour).” From the above quote from the paper it is clear that automated control works to keep the saturation goal through roughly 7 X the number of adjustments than nursing makes per hour. It is hard to keep up with that pace when you have multiple assignments but that is what you need I suppose! The use of the auto setting here reduced the amount of nursing interventions to adjust FiO2 by 90% and yields tighter control of O2 saturations. Dare to Dream Self driving oxygen administration is coming and this proof of concept needs to be developed and soon into a commercial solution. The risk of O2 damage to developing tissues is too great not to bring this technology forward to the masses. As we prepare to move into a new institution I sincerely hope that this solution arrives in time but regardless I know our nurses and RRTs will do their best as they always do until such a device comes along. When it does imagine all of the time that could be devoted to other areas of care once you were able to move away from the non-invasive device!
  44. 1 point
    Acupuncture is nonsense. There I have said it. I'll probably get at least a few comments for this post, but I'm not backing down. Acupuncture is based on pre-scientific ideas about how the body works, believing that some sort of vital energy flows along meridians in the body, and that sticking a needle into the skin at certain specific points can have distant effects, by letting out the Xi. Xi is non-existent, meridians are non-existent and there are no acupuncture points, they just don't exist. This is all ridiculous, and people with a medical education should know better. Trials of acupuncture in adults have shown that it doesn't matter where you put the needles, or even if you puncture the skin or not. The better controlled the trials are the less effect there is, and trials with really good sham procedures don't show a difference between the sham procedure controls and the actually needled groups. Any effect is simply a placebo effect, and the whole procedure with its insertion of needles and fake explanations has been characterized as a "theatrical placebo". For a sampling of deconstructions of acupuncture studies just search acupuncture on the blog "respectful insolence" which you can do by following this link . Unfortunately there are many who have been taken in by the pseudoscience of this quackery, even in neonatology. A few trials have even been published, including those using electrical stimulators of non-existent acupuncture points, and a few where lights have been shone onto those same points. The two most recent studies I glimpsed are examples of those 2 methods, Abbasoglu A, et al. Laser acupuncture before heel lancing for pain management in healthy term newborns: a randomised controlled trial. Acupuncture in medicine. 2015;33(6):445-50. 42 term babies having a heelstick were randomized to laser acupuncture or sucrose. The study found that sucrose was better than shining a light on the Yintang point (the non-existent acupuncture points, scattered along the non-existent meridians, all have names, this one is between the eyebrows and is also called EX2). Mitchell AJ, et al. Does Noninvasive Electrical Stimulation of Acupuncture Points (NESAP) reduce heelstick pain in neonates? Acta Paediatrica. 2016. This study used different fake acupuncture points (ZuSanLi (ST36), SanYinJiao (SP6), KunLun(Bl60), and TaiXi (KI3) which are on the legs) and randomized babies undergoing heelstick to 4 groups, sucrose with "Sham NESAP", NESAP plus water, NESAP with sucrose, and sham NESAP with water. They randomized 142 term infants who were undergoing a heelstick procedure and analyzed the videos of their faces for PIPP scoring. In the Sham NESAP groups the electrodes were placed adjacent to these fantasy acupuncture points but the stimulator was not turned on, All babies at least had facilitated tucking and a soother, which are both effective at reducing pain from heelstick, which was shown by the relatively small mean increases in PIPP scores in all the groups. Sucrose limited the increases in PIPP compared to the groups which didn't get sucrose, and electrical stimulation of ZuSanLi etc didn't do anything. This study did at least have the potential for a measurable effect, because, unlike shining a light on the skin, there is at least a potential that the transcutaneous electrical stimulation could have an analgesic effect. As it appears to for, in particular, chronic pain. Although the NESAP groups without sucrose didn't have a large mean increase in PIPP scores, the mean peak scores were up to 4.9 and 5 (compared to 4 or less for the sucrose groups), but the standard deviations of those scores were much larger than the sucrose groups, (4 compared to less than 2) which means that there were probably substantially larger numbers of babies who had pain scores of over 6, and had appreciable pain. Which means that yet again I can say that we shouldn't be performing heelsticks without using all the proven evidence-based methods for reducing pain prior to such procedures, of which sucrose is top of the list. Lets stop investigating this nonsense in neonatology, we should be using our time and efforts and resources to examine therapies that have some basis in reality and science. Whatever next, ear candling, or craniosacral therapy for newborns? OH NO!
  45. 1 point
    We have been seemingly under siege over the last year or so by a relentless flow of preterm infants through our units in the city. Peaks and valleys for patient census come and go for the most part but this almost unwavering tendency to be filled to the rafters so to speak is unusual. Much has been said and will continue to be acknowledged that we are all doing incredible work, that we are dedicated and putting patients first but where is the breaking point? When does fatigue lead to errors no matter how well intentioned and selfless we are. In those cases when it is not a matter of being selfless but we are mandated to come in fatigue is no less an issue. Like many units in North America and in other parts of the world, rates of neonatal sepsis have been on the decline but during a recent peak in both acuity and volume in the region we saw a spike in the rate of culture proven sepsis. At a time when we were at our busiest our sepsis rate worsened which raised many eyebrows as to what could be contributing. It is tempting to blame it on patient volumes but what is the actual evidence to support such a claim. This is the thrust of this piece and I hope you find the topic of some relevance to you as we continue on this journey of a higher state of patient volumes in the city. Nurse to Patient Ratio is Likely Important This has to be important right?! NICUs come in many shapes and sizes but if you can staff appropriately with 1:1, 1:2 and 1:3 ratios based on patient acuity if you had enough nurses would your sepsis rates be ok? To answer this a useful study is by Jeannie P. Cimiott et al entitled Impact of staffing on bloodstream infections in the neonatal intensive care unit. The study group was actually from an RCT on hand hygiene and this study was a reanalysis of the data to determine for infants with confirmed sepsis what impact nursing hours had in the context of a patient with their first positive blood culture. In her study there were 2675 infants in two New York level III NICUs that had 224 positive blood cultures. The impact of nursing hours on risk of infection was dramatic. The NICU with greater nursing coverage had a significantly decreased risk (HR, 0.21; 95% CI, 0.06-0.79) of bloodstream infection. Moreover, the more RN hours per nursing intensity weight was associated with a 79% reduction in the risk of bloodstream infection in the unit with greater nursing work hours. Looking also at the impact of greater nursing hours on time to infection demonstrated the following curve. From the graph one can see that two patients both of which develop an infection at 100 days of life have markedly different chances of survival based on the staffing level. The Neonatologist, RRT, dietician could all be the same but if the nursing hours are lacking the patient is more likely to die. A very significant concern indeed! What Effect Does The Percentage of Preterm Babies In The Unit Have On The Rate of Infections? The next question may be answered by looking at a study from this year by Goldstein et al entitled Characteristics of late-onset sepsis in the NICU: does occupancy impact risk of infection? This study looked retrospectively at a 17 year period between 1997 and 2014 to determine the risk of systemic infection from two standpoints; occupancy and percentage of infants < 32 weeks. In other words they were looking at whether the presence of many smaller babies in the units increases such risk of infection specifically. This was a rather large study population of 19810 infants of which 446 had confirmed late onset sepsis. Not surprisingly 70% of the cases of sepsis were with CONS. The authors examined hazard ratios to determine whether occupancy or proportion of infants < 32 weeks had an effect on risk and determined that the average occupancy did not correlate with risk of infection but did for the category of infants < 32 weeks. Interestingly the HR for this was 1.03 with a CI that touches 1 so I am not sure how they make this claim but in the end they conclude: "For each additional percentage of infants <32 weeks gestation in the unit, neonates had an increased late-onset sepsis hazard of 2% (HR 1.02, 95% CI: 1.00, 1.03) over their NICU hospitalization." For arguments sake let's say this is a real effect. I do have to call into question the diagnosis of sepsis. I could not find mention of the definition of sepsis in this cohort and with so many CONS infections I do worry that some of these were in fact contaminants. Did they draw one or two blood cultures in each instance? How many of these if they had would have had one positive and the other negative? Having just a few of these labelled as contaminants may have negated any effect seen. What About The Nurses? You also can't ignore the fact that while they looked at occupancy they made no attempt to control for the amount of staff. To not do so I think misses a very important point. Whether your unit is functioning at 60, 70, 80 or more occupancy while giving a measure of patient volumes tells you nothing about the coverage for such patients. In a well staffed unit with adequate nurse to patient ratios there might be minimal risk of error. If assignments though that are ideally 2:1 are stretched to 3 or 4: 1 that is likely where the errors start to come in. Coming back to our situation that likely mirrors many other centres across the globe I believe all of this comes down to ensuring a safe environment to care for our patients. A safe environment means having enough staff to cover the number of patients and that includes medical, RRTs, dieticians and others. The message from all of this is that to do our best we need the right amount of staff to do it. We can handle the volume, just provide us with the resources to handle it. If it is money that we are hoping to save consider the amount of dollars that could be saved by avoiding prolonged stays from infection and all the associated morbidities that follow. Then there is the increase in mortality to consider and I for one will not even begin to put a price on that.
  46. 1 point
    Azzopardi D, et al. Moderate hypothermia within 6 h of birth plus inhaled xenon versus moderate hypothermia alone after birth asphyxia (TOBY-Xe): a proof-of-concept, open-label, randomised controlled trial. The Lancet Neurology. 2016;15(2):145-53. Babies who undergo therapeutic hypothermia for perinatal encephalopathy are still at high risk of significant long term impairments. Other therapies to add to hypothermia are being sought and tested, one of them being Xenon. Inhaled xenon gas has neuroprotective effects in many models; but it is expensive and difficult to use, in order to make it affordable for use over several hours you need to recirculate the exhaled xenon, so you need a special ventilator, which has been developed for this trial. In this "pilot' RCT, eligible babies were typical of infants who are cooled, and had to have started on hypothermia within 6 hours after birth. As is usual, most of the 92 enrolled babies (2/3) were born in peripheral hospitals and transported in, many babies were cooled quite quickly, 93% before 4 hours of age. Xenon or standard care was started after randomization which was after arrival in the study centre, so the assigned treatment didn't start until an average of 10 hours of age. Xenon (or no xenon) was then continued for exactly 24 hours of age. The primary outcomes of the study were MR findings; using spectroscopy they calculated the ration of lactate to N-acetyl aspartate in the thalamus, and using diffusion tensor imaging they calculated the fractional inosotropy of the posterior limb of the internal capsule. Scans were performed after the end of cooling at about 6 days of age. Because of deaths and a small number of scans not done in survivors, they ended up with around 75 babies with data for each of the two primary outcomes, data from the MRI were analyzed by a masked individual (images of the lone ranger... radiologist) . Basically the study showed no effect of Xenon. Which is a bummer. (that is colloquial English for "a real shame") Why didn't it work? I think first off we have to be careful in saying it didn't work, there was no effect on the primary outcomes, but the primary outcomes are surrogates. Surrogates should always be mistrusted, even when they are called "biomarkers". Is the surrogate an accurate enough predictor of good or adverse clinically important outcomes? I think that is questionable here, mostly because I don't know the data well enough to answer the question, but is it possible that a clinically significant benefit of xenon will be shown if (hopefully when) these babies are followed up? My guess is that such an outcome is quite unlikely, but possible. In fact I think this study is a good opportunity to prove the value of the MR surrogates. If the authors are right (and usually Dennis Azzopardi, Dave Edwards and the many associated luminaries who wrote this article are indeed right) then using similar surrogates in future trials will help to screen for effective adjunctive therapies in cooled babies, and more quickly than waiting 2 years or so for follow up. Maybe starting xenon at 10 hours of age is just too late? As the authors point out, they performed a trial in a real world environment, it would be possible, if you had the ventilator always ready and available, to start Xenon the moment a baby enters the referral NICU, but that would still lead to significant delays of evaluation and transport. Maybe 24 hours is too short? It was based on the best previously available literature, and again technically feasible, before doing another study with longer Xenon administration I think we would need some very good rationale. In the end, this real-life application of xenon in cooled babies didn't show any sign of being effective. We should look elsewhere I guess, something that could be given very quickly when a baby is cooled, such as melatonin, or erythropoietin look like they are the most worthy of further investigation. A review of the literature from 3 to 4 years ago concluded that, and I haven't seen much to change the situation since then. Robertson NJ, et al. Which Neuroprotective Agents are Ready for Bench to Bedside Translation in the Newborn Infant? The Journal of pediatrics. 2012;160(4):544-52.e4.
  47. 1 point
    The oxygen saturation targeting trials showed more retinopathy with higher oxygen saturation targets. Will this translate into more retinopathy in actual practice? Many units have increased their saturation targets as a result of those studies. This may indeed lead to more RoP, and the expected result seems to have happened, in Melbourne at least. A before and after study showed that there was an increase in retinopathy, both overall and of stage 2 or more. They evaluated the outcomes in babies under 30 weeks or under 1250 g who survived to get retinal screening, about 150 before they changed and nearly 200 afterward. They saw more total RoP. There were very few babies who needed laser, 1 before and 3 after, which may have been due to chance, with such small numbers, but it certainly didn't go down. Among infants of less than 28 weeks, the stage 2 disease incidence went from 16% to 34%. What can we do to counter this? Which is likely to be repeated in many different units who have raised their saturation limits. What interventions are there that can reduce retinopathy? Well, we know that poor early neonatal growth is associated with an increased risk of retinopathy. So optimizing neonatal nutrition in at-risk infants should help, although that hasn't been proven in randomized trials, as far as I am aware. An RCT from Poland (with the collaboration of Michael Sherman) suggests that a mixed lipid source, including some fish oil/omega-3 fatty acids may reduce RoP in very preterm infants. They randomized infants <1250g and less than 32 weeks. The 70 control infants received a mixture of soy and olive oil lipids (Clinoleic, which is used in Europe, but I don't think is licensed in North America). The 60 babies in the intervention group received half Clinoleic, and half Omegaven (the fish oil emulsion with lots of omega-3 goodies) by volume, but the Clinoleic is a 20% emulsion, the Omegaven is a 10% emulsion. So they had about 1/3 omegaven, 2/3 the other stuff. It was an unblinded study, apart from the ophthalmologist who was apparently… uuh…blinded. (Sorry about that). The primary study outcome was "an assessment of ROP severity and whether laser photocoagulation was required to save vision" which isn't a primary study outcome, of course, you can't have a study outcome which is an "assessment of" something. The sample size was calculated based on an extremely high frequency of retinal ablation in the controls, of 27%, and a massive reduction to 7.5% in the fish oil group. so we will call that the primary outcome variable. The babies in the study were on average just under 1000g birth weight, and were 28 weeks gestational age. Those in the new-lipid group got much more DHA (docosahexaenoic acid, an omega-3 FA) which they incorporated into red cell membranes. They defined cholestasis as more than 20% of the bilirubin being conjugated; which was very frequent in the controls, 20/70 vs 3/60 in the group with the fish oil. Treated retinopathy was extremely frequent in the controls, 22/70 and decreased to become very frequent in the fish oil group, 9/60. The proportions of fish oil are not the same with their mixture as with SMOFLipid, a mixture of Soy, Medium chain triglycerides, Olive oil, and Fish Lipids, which is commercially available. In SMOF about 15% of the lipids are fish oil derived. This looks hopeful, but we will need to be sure that the results are the same with an approved lipid in Canada (SMOFLipid is approved, but not specifically for newborns in Canada), or wherever you are in the world. Also that it is effective in NICUs with a much lower rate of retinopathy needing treatment, then providing enough omega-3 FAs from early life in the very preterm infant might help to counter the effects of keeping the saturations a little higher.
  48. 1 point
    A large multi-center trial (n=511) led by Roberta Ballard has just been published. (Ballard RA, et al. Randomized Trial of Late Surfactant Treatment in Ventilated Preterm Infants Receiving Inhaled Nitric Oxide. J Pediatr 2015.) In this trial infants had similar enrollment characteristics to the NOCLD trial; babies were between 500 and 125o grams birthweight and less than 32 weeks gestation. They had to be receiving assisted ventilation. There were the following differences to the previous study I alluded to: in NOCLD infants were 7 to 21 days, in this trial 7 to 14 days; in NOCLD the smallest infants could be enrolled if they were on CPAP; not in this trial, everyone had to be intubated and ventilated. The idea was, that infants with persistent respiratory distress after a week of age have evidence of surfactant dysfunction, so perhaps if we gave them more functional surfactant they would be able to overcome this, and then have reduced lung function abnormalities, would be able to breathe more efficiently and would end up with less lung injury. There are a couple of pilot studies showing short term improvements in pulmonary function and gas exchange in very preterm infants who were still getting respiratory support at a week of age, and who received surfactant. So the investigators thought that a big RCT to examine clinically relevant outcomes was warranted. Which I think is fine. This was a reasonable question to ask, and a reasonable, clinically important, outcome to investigate (especially with a local treatment very unlikely to have systemic adverse effects). Given the previous data on inhaled NO in a very similar group of babies (in whom a secondary analysis suggested that the earlier part of the postnatal age group, i,e, 7 to 14 days, was more effective) you can't fault the investigators for using iNO in all the babies. Even if the, as yet still unpublished, NewNO trial did not show a benefit. All the babies were getting inhaled NO, according to the NOCLD protocol. The surfactant was randomly given to half of the babies. But I can't tell you how much surfactant was given, or with what frequency. A major problem with this report of the study is that I can't figure out exactly what was the intervention. Which is a big problem. The investigators went to great (and probably unnecessary) lengths to mask the procedure, with a separate team, not otherwise involved in clinical care, who gave the surfactant (or didn't) into the ETT behind screens. But they don't actually say what dose was given. Babies in the study got a dose of surfactant (or a sham procedure), as I said, the study report doesn't even say how much they got (it was "standard clinical doses") or how often they got it (it was every 24 to 72 hours if they remained intubated, starting at 48 hours after the first dose with a maximum of 5 doses; but 24 to 72 is a huge range...), they don't say what were the criteria for retreatment, or for not retreating and extubating etc. There are several guidelines presented for steroids, for re-intubation etc, but not for surfactant/sham administration. Table 3 of the results does show that about 80% in each group got 5 doses (of either surfactant or standing behind a curtain). There was no benefit shown. Nothing, not even a whisper of a hint of a benefit. Which is disappointing, but at least seems at first look rather definitive. Or at least it would be definitive if we knew what the intervention group had received. Even though surfactant dysfunction is a real problem in these babies, giving them additional Infasurf, according to this uncertain schedule, isn't sufficiently effective to improve their outcomes. This does, I think, help to improve care, (as there is no longer any stimulus to give surfactant to babies at this age) but it would have been much more useful, after what is probably several million dollars of investment, to know exactly what was done. All we know is that, giving some dose of surfactant (Infasurf) and giving, mostly, 5 of those doses, didn't reduce BPD or death with a certain degree of confidence (see below). To return to a comment I made above, why did I say that the sham procedure was unnecessary? Masking the intervention has become an essential feature of neonatal (and much clinical) research in order to get good funding; however, there is actually little empirical evidence that blinding/masking the intervention makes much difference to the size or direction of the effect of an intervention, particularly if objective outcomes are being studied. Diagnosis of BPD, if the 'physiologic" definition is being used, is relatively objective, and is unlikely to be influenced by knowledge of an intervention performed several weeks earlier. I think, if it is relatively easy, and relatively inexpensive, to mask an intervention (such as an orally administered drug, for example) then go for it, there is often no good reason to not do so. But having an on-call surfactant or sham administration team, who will go through the ritual of masking used in this study, will have enormously increased the cost. They could have studied twice as many babies (I guess) for the same cost, and have a much better estimate of the size of the effect, or of the confidence with which we can eliminate a benefit or risk. Many of the original surfactant trials for treatment of HMD were masked, in a similar fashion, but not all. There is no clear difference in the estimates of efficacy between those that were masked and those that were not. Which brings me neatly to the final comment, the study was stopped by the DSMB, because "based on a determination that the study treatment is very unlikely to demonstrate efficacy" they didn't think they should continue. They actually made this determination when they had the outcome data of 301 infants. There is a lot of debate about stopping trials early for futility, one paper in Critical Care (freely available on-line) is actually a real debate. But I am a bit mystified in this case, when the decision to stop the trial was taken they had actually randomized 511, of the planned 524 babies. One of the justifications for early stopping for futility is that it saves wasting money. That clearly isn't an issue in this case. But even with all the data from 511 babies available there is still major uncertainty about whether this intervention is actually futile; the 95% CI for death or BPD include a 25% increase or decrease in that outcome. Which is huge, and clinically important. A 25% reduction (or increase) in death or BPD is something I would be interested in. When the DSMB recommended stopping the trial they only had data from 300 babies, which means the confidence for saying there is no benefit (or harm) was extremely lacking in, er, confidence. Depending on how you calculate it, (assuming that the groups both had a 40% incidence of death or BPD at that point) when they stopped the trial showed that the likely real difference in that outcome was between about a 35% increase or decrease in risk of death or BPD. The sample size for the study was based on a hypothesized 13% change in the incidence of "death or BPD", so why would the trial be stopped early when the confidence intervals included the hypothesized difference.
  49. 1 point
    Presenting the 2nd Presentation of Neonatal CME @ Jamnagar on 25th October. Its : " NEONATAL JAUNDICE- Current Concepts by Dr.Maulik Shah MD. Video link on You Tube: https://www.youtube.com/watch?v=hLMP4FHOdIk. Comments and feedback most welcome.
  50. 1 point
    Geloneck MM, Cet al: Refractive outcomes following bevacizumab monotherapy compared with conventional laser treatment: a randomized clinical trial. JAMA Ophthalmol 2014, 132(11):1327-1333. In this follow-up of the BEAT-RoP trial, eyes randomized to have laser were more likely to have severe myopia on follow-up at about 2.5 years than those randomized to bevacizumab. The difference is very large, 51% with laser, and 4% with bevacizumab. The severe (very high) myopia was defined as worse than 8 diopters, which is bad. The advantage of bevacizumab was for eyes treated both for zone 1 disease and for zone 2 disease. The results are very similar to a small case-control study (Harder BC, et al: Early refractive outcome after intravitreous bevacizumab for retinopathy of prematurity. Arch Ophthalmol 2012, 130(6):800-801), which showed a mean refractive error after laser of between 5 and 8 diopters. Another observational study showed much the same thing: (Chen YH, et al: Refractive errors after the use of bevacizumab for the treatment of retinopathy of prematurity: 2-year outcomes. Eye (Lond) 2014, 28(9):1080-1086; quiz 1087.). As yet there is no evidence of systemic toxicity from bevacizumab, although I can't find a formal publication of other clinical or developmental outcomes. Such severe myopia, in infants with a destroyed peripheral retina, can't be a good thing. Bevacizumab does get into the circulation, and, like other antibodies has a long half-life (21 days in this study : Kong L, et al: Pharmacokinetics of bevacizumab and its effects on serum VEGF and IGF-1 in infants with retinopathy of prematurity. Invest Ophthalmol Vis Sci 2015, 56(2):956-961). Those authors also showed that serum VEGF levels were lower after beva.... (Im getting tired of typing that over and over, Ill call it BVZ) than after laser, and that seemed to persist for 60 days, although I can't tell from the way the data are reported whether the differences between the laser and BVZ groups were statistically important, (they say that the decrease in the BVZ groups was 'more significant' than the laser group, which is not clear to me). There also didn't seem much difference in this paper between the 2 different doses of BVZ, 0.625 mg, which the BEAT-RoP trial used, or a lower dose of 0.25 mg. Which is a shame, as a lower dose seems to be effective, (Harder BC et al: Intravitreal low-dosage bevacizumab for retinopathy of prematurity. Acta Ophthalmol 2014, 92(6):577-581.) These authors trialed a dose of 0.375 mg and found good effects, with regression of disease in all babies, one very sick baby needed a second treatment. We should add into the mix the need for anaesthesia, and usually intubation, for laser therapy, whereas intravitreal injections cause very little pain. (Castellanos MA et al: Pain assessment in premature infants treated with intravitreal antiangiogenic therapy for retinopathy of prematurity under topical anesthesia. Graefes Arch Clin Exp Ophthalmol 2013, 251(2):491-494). What to do now? We have a treatment which appears highly effective, with only 4% recurrence, which leaves the peripheral retina intact and dramatically reduces the incidence of very severe myopia. But for which there remain uncertainties about extra-ocular safety. I think the answer is that we should ask parents. We should ask parent representatives about their opinions about standards for this potential off-label use, and we should ensure that individual parents are fully informed about the options prior to a decision about what treatment should be used for babies who qualify for treatment. If a parent might reasonably opt for BVZ rather than laser, do we have enough reason to deny them that option?
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