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… and how comfortable are you with your choice? So, we all know, that there has been and still is a wide variety of combinations for premedication for intubating a neonate - even more difficult when dealing with preterms. As far as I know, most current recommendations favour using an opioid, a muscle relaxants and mostly atropine. I “grew up” using thiopental and fentanyl +- Rocuronium and often times a second dose of fentanyl was needed until placing the tube (nasoteacheal) was tolerated. So for me, using Fentanyl and Rocuronium without an hypnoticum right away, makes me somewhat uncomfortable fearing too little medication effect and too much awareness. So, what is your combination and how do you feel using it? I’m curious ….

I have reviewed many articles on this site in the last few years. My favourite pieces are ones in which I know the authors and I have to say my ultimate favourite is when I know the authors as colleagues. Such is the case this time around and it pertains to a topic that is not without controversy. Nasal High Frequency Oscillatory Ventilation or NHFOV for short is a form of non-invasive ventilation that claims to be able to prevent reintubation whether used prophylactically (extubation directly to NHFOV) or as a rescue (failing CPAP so use NHFOV instead of intubation). I have written about the topic before in the piece Can Nasal High Frequency Ventilation Prevent Reintubations? but this time around the publication we are looking at is from my own centre! Retrospective Experience One of our former fellows who then worked with us for a period of time Dr. Yaser Ali decided to review our experience with NHFOV in the paper Noninvasive High-Frequency Oscillatory Ventilation: A Retrospective Chart Review. Not only is one of our fellows behind this paper but an additional former fellow and current employee Dr. Ebtihal Ali and two of my wonderful colleagues Dr. Molly Seshia and Dr. Ruben Alvaro who both taught be a few things about this chosen career of mine. The study involved our experience with using this technique (Draeger VN500 providing HFOV through first a RAM cannulae and then later with the FlexiTrunk Midline Interface (FlexiTrunk Midline Interface, Fisher & Paykel Healthcare) either using a prophylactic or rescue approach. The settings were standardized in both approaches as follows. Prophlyactic • Frequency of 6 to 8 Hz. • Mean airway pressure (MAP)2 cmH2Oabove the MAP of invasive ventilation (whether conventional or high-frequency ventilation). • Amplitude to achieve adequate chest oscillation while at rest. Rescue • Frequency of 6 to 8 Hz. • MAP 1 to 2 cm H2O higher than positive end expiratory pressure (PEEP) on CPAP or biphasic CPAP. • Amplitude to achieve adequate chest oscillation while at rest. All in all there were 32 occasions for 27 patients in which prophylaxis was used in 10 and rescue in 22. In the rescue group 77% of the time transfer onto NHFOV was done due to apneic events. The study was retrospective and lacked a control group as such so when it comes to the prophylactic approach it is impossible to know how many of these babies would have done fine with CPAP or Biphasic CPAP. Having said that, in that arm the intervention was successful in keeping babies extubated for at least 72 hours in 6/10. Since I really don’t know if those same babies would have done just as well with CPAP I will stop the discussion about them now. The Rescue Group These infants were on a fair bit of support though prior to going on to HFNOV with a mean SD CPAP of 7.9 cm H2O; while for the biphasic CPAP, the levels were 10.2 cm H2O and 7.7 cm H2O. In the rescue group 73% of the infants did not get intubated. Let’s Process This For A Minute I think most of you would agree that an infant on CPAP of +8 or NIPPV who is having repetitive apnea or significant desaturations would inevitably be intubated. In three quarters of these patients they were not but I can assure you they would have been if we had not implemented this treatment. When you look at the whole cohort including prophylactic and rescue you can see that the only real difference in the babies were that the ones who were on lower MAP before going onto NHFOV were more likely to fail. Interestingly, looking at the effect on apnea frequency there was a very significant reduction in events with NHFOV while FiO2 trended lower (possibly due to the higher MAP that is typically used by 1-2 cm H2O) and pCO2 remained the same. If pCO2 is no different how does this treatment work if the results are to be believed? Although high frequency ventilation is known for working well to clear CO2 I don’t think when given via this nasal interface it does much in that regard. It may be that the oscillations mostly die out in the nasopharynx. I have often wondered though if the agitation and higher mean airway pressures are responsible compared to straight CPAP or biphasic CPAP alone. There is something going on though as it is hard to argue with the results in our centre that in those who would have been otherwise intubated they avoided this outcome. You could argue I suppose since the study was not blinded that we were willing to ride it out if we believe that NHFOV is superior and will save the day but the information in Table 3 suggests that the babies on this modality truly had a reduction in apnea and I suspect had the sample size been larger we would have seen a reduction that was significant in FiO2. My thoughts on this therefore is that while I can’t profess that a prophylactic approach after extubation would be any better than going straight to CPAP, I do wonder if NHFOV is something that we should have in our toolkits to deal with the baby who seems to need reintubation due to rising FiO2 and/or apnea frequency. What may need to be looked at prospectively though is a comparison between higher pressures using CPAP and NHFOV. If you were to use CPAP pressures of +10, +11 or +12 and reach equivalent pressures to NHFOV would these advantages disappear?

I’m trying to identify a good fool proof method of securing ET tube and there doesn’t seem to be a consensus. I’d like to hear what methods do you all use on your units and if you could share any thoughts, experiences and ideas here please. Sent from my iPhone using Tapatalk

Continuing a topic started on twitter, I would like to ask the 99nicu community. What muscle relaxant do you use in preterms and neonates primarily? Tell us about your experiences? What dose do you use?

MultiProfessional Neonatal Education (MPROvE Academy) We have a number of toolkits for people who would like to do QI in neonatal care on www.mproveacademy.com and have a number of videos on a variety of neonatal procedures on the MPROvE video channel above. We have also added difficult neonatal airway and videolaryngoscopy videos. These can be used for training purposes. https://www.youtube.com/channel/UC22LMIG5Bwqhreic_DFHATw Best Wishes Dr Alok Sharma Consultant Neonatologist Princess Anne Hospital Southampton UK

A catchy title for sure and also an exaggeration as I don’t see us abandoning the endotracheal tube just yet. There has been a lot of talk about less invasive means of giving surfactant and the last few years have seen several papers relating to giving surfactant via a catheter placed in the trachea (MIST or LISA techniques as examples). There may be a new kid on the block so to speak and that is aerosolized surfactant. This has been talked about for some time as well but the challenge had been figuring out how to aerosolize the fluid in such a way that a significant amount of the surfactant would actually enter the trachea. This was really a dream of many Neonatologists and based on a recently published paper the time may be now for this technique to take off. A Randomized Trial of Aerosolized Surfacant Minocchieri et al as part of the CureNeb study team published Nebulised surfactant to reduce severity of respiratory distress: a blinded, parallel, randomised controlled trial. This trial set out to obtain a sample size of 70 patients between 29 0/7 to 33 6/7 weeks to demonstrate a difference in need for intubation from 30% down to 5% in patients treated with CPAP (30% was based on the historical average). The authors recognizing that the babies in this GA bracket might behave differently, further stratified the randomization into two groups being 29 0/7 – 31 6/7 weeks and 32 0/7 to 33 6/7 weeks. Those babies who were on CPAP and met the following criteria for intubation were either intubated in the control group and given surfactant (curosurf) using the same protocol as those nebulized or had surfactant delivered via nebulisation (200 mg/kg: poractant alfa) using a customised vibrating membrane nebuliser (eFlow neonatal). Surfactant nebulisation(100 mg/kg) was repeated after 12 hours if oxygen was still required. The primary dichotomous outcome was the need for intubation within 72 hours of life, and the primary continuous outcome was the mean duration of mechanical ventilation at 72 hours of age. Criteria for intubation 1. FiO2 >0.35 over more than 30 min OR FiO2 >0.45 at anytime. 2. More than four apnea/hour OR two apnea requiring BVM 3. Two cap gases with pH <7.2 and PaCO2 >65 mm Hg (or) >60 mm Hg if arterial blood gas sample). 4. Intubation deemed necessary by the attending physician. Did It Work? Eureka! It seemed to work as 11 of 32 infants were intubated in the surfactant nebulisation group within 72 hours of birth vs.22 out of 32 infants receiving CPAP alone (RR (95% CI)=0.526 (0.292 to 0.950)). The reduction though was accounted for by the bigger babies in the 32 0/7 to 33 6/7 weeks group as only 1 of 11 was intubated when given nebulized surfactant compared to 10 of 13 managed with CPAP. The duration of ventilation in the first 72 hours was not different between the groups: the median (range) 0 (0–62) hour for the nebulization group and 9 (0–64) hours for the control group (p=0.220). It is important in seeing these results that the clinicians deciding whether infants should be intubated for surfactant administration were blind to the arm the infants were in. All administration of curosurf via nebulization or sham procedures were done behind a screen. The total number of infants randomized were 66 so they did fall shy of the necessary recruitment but since they did find a difference the results seem valid. Importantly, there were no differences in complications although I can’t be totally confident there really is no risk as this study was grossly underpowered to look at rarer outcomes. Breaking down the results This study has me excited as what it shows is that “it kind of works“. Why would larger babies be the ones to benefit the most? My guess is that some but not a lot of surfactant administered via nebulization reaches the alveoli. Infants with lesser degrees of surfactant deficiency (32 0/7 to 33 6/7) weeks might get just enough to manage without an endotracheal tube. Those infants (in particular less than 32 0/7 weeks) who have more significant surfactant deficiency don’t get enough and therefore are intubated. Supporting this notion is the overall delay in time to intubation in those who were intubated despite nebulization (11.6 hours in the nebulization group vs 4.9 hours in the control arm). They likely received some deposition in the distal alveoli but not enough to completely stave off an endotracheal tube. One concerning point from the study though had to do with the group of infants who were intubated despite nebulization of surfactant. When you look at total duration of ventilation (hours) it was 14.6 (9.0–24.8) in the control arm vs 25.4 (14.6–42.2) p= 0.029*. In other words infants who were intubated in the end spent about twice as long intubated as those who were intubated straight away. Not a huge concern if you are born at 32 weeks or more but those additional thousands of positive pressure breaths are more worrisome as a risk for CLD down the road. As it stands, if you had an infant who was 33 weeks and grunting with an FiO2 of 35% might you try this if you could get your hands on the nebulizer? It appears to work so the only question is whether you are confident enough that the risk of such things as pneumothorax or IVH isn’t higher if intubation is delayed. It will be interesting to see if this gets adopted at this point. The future no doubt will see a refinement of the nebulizer and an attempt to see how well this technique works in infants below 29 weeks. It is in this group though that prolonging time intubated would be more worrisome. I don’t want to dismiss this outright as I see this as a pilot study that will lead the way for future work that will refine this technique. If we get this right this would be really transformative to Neonatology and just might be the next big leap.

The modern NICU is one that is full of patients on CPAP these days. As I have mentioned before, the opportunity to intubate is therefore becoming more and more rare is non-invasive pressure support becomes the mainstay of therapy. Even for those with established skills in placing an endotracheal tube, the number of times one gets to do this per year is certainly becoming fewer and fewer. Coming to the rescue is the promise of easier intubations by being able to visualize an airway on a screen using a video laryngoscope. The advantage to the user is that anyone who is watching can give you some great tips and armed with this knowledge you may be better able to determine how to adjust your approach. For those of you who have followed the blog for some time, you will recall this is not the first time video laryngoscopy has come up. I have spoken about this before in Can Video Laryngoscopy Improve Trainee Success in Intubation. In that piece, the case was made that training residents how to intubate using a video laryngoscope (VL) improves their success rate. An additional question that one might ask though has to do with the quality of the intubation. What if you can place a tube using a video laryngoscope but the patient suffers in some way from having that piece of equipment in the mouth? Lucky for us some researchers from the Children's Hospital of Philadelphia have completed a study that can help answer this additional question. Video Laryngoscopy may work but does it cause more harm than good? Using a video laryngoscope requires purchasing one first and they aren't necessarily cheap. If they were to provide a better patient experience though the added cost might well be worth it. Pouppirt NR et al published Association Between Video Laryngoscopy and Adverse Tracheal Intubation-Associated Events in the Neonatal Care Unit. This study was a retrospective comparison of two groups; one having an intubation performed with a VL (n=161 or 20% of the group) and the other with a standard laryngoscope (644 or 80% of the group). The study relied on the use of the National Emergency Airway Registry for Neonates (NEAR4NEOs), which records all intubations from a number of centres using an online database and allows for analysis of many different aspects of intubations in neonates. In this case the data utilized though was from their centre only to minimize variation in premedication and practitioner experience. Tracheal intubation adverse events (TIAEs) were subdivided into severe (cardiac arrest, esophageal intubation with delayed recognition, emesis with witnessed aspiration, hypotension requiring intervention (fluid and/or vasopressors), laryngospasm, malignant hyperthermia, pneumothorax/pneumomediastinum, or direct airway injury) vs non-severe (mainstem bronchial intubation, esophageal intubation with immediate recognition, emesis without aspiration, hypertension requiring therapy, epistaxis, lip trauma, gum or oral trauma, dysrhythmia, and pain and/or agitation requiring additional medication and causing a delay in intubation. Looking at the patient characteristics and outcomes, some interesting findings emerge. Patients who had the use of the VL were older and weighed more. They were more likely to have the VL used for airway obstruction than respiratory failure and importantly were also more likely to receive sedation/analgesia and paralysis. These researchers have also recently shown that the use of paralysis is associated with less TIAEs so one needs to bear this in mind when looking at the rates of TIAEs. There were a statistically significant difference in TIAEs of any type of 6% in the VL group to 19% in the traditional laryngoscopy arm but severe TIAEs showed not difference. Given that several of the baseline characteristics might play a role in explaining why VL seemed superior in terms of minimizing risk of TIAEs by two thirds, the authors performed a multivariable analysis in which they took all factors that were different into account and then looked to see if there was still an effect of the VL despite these seemingly important differences. Interestingly, us of VL showed an Odds ratio of 0.43 (0.21,0.87 95% CI) in spite of these differences. What does it mean? Video laryngoscopy appears to make a difference to reducing the risk on TIAEs as an independent factor. The most common TIAE was esophageal intubation at 10% and reducing that is a good thing as it leads to fewer intubation attempts. This was also sen as the first attempt success was 63% in the VL group vs 44% in the other. Now we need to acknowledge that this was not a randomized controlled trial so it could indeed be that there are other factors that the authors have not identified that led to improvements in TIAEs as well. What makes this study so robust though is the rigour with which the centre documents all of their intubations using such a detailed registry. By using one centre much of the variability in practice between units is eliminated so perhaps these results can be trusted. Would your centre achieve these same results? Maybe not but it would certainly be interesting to test drive one of these for a period of time see how it performs.

A few weeks back I wrote about the topic of intubations and whether premedication is really needed (Still performing awake intubations in newborns? Maybe this will change your mind.) I was clear in my belief that it is and offered reasons why. There is another group of practitioners though that generally agree that premedication is beneficial but have a different question. Many believe that analgesia or sedation is needed but question the need for paralysis. The usual argument is that if the intubation doesn’t go well and the patient can’t spontaneously ventilate could we be worse off if the patient loses their muscle tone. Neonatal Intubation Registry At the CPS meeting last month in Quebec City. I had the pleasure of listening to a talk by Dr. Elizabeth Foglia on the findings from a Neonatal intubation registry that many centres have been contributing to. The National Emergency Airway Registry for Neonates (NEAR4NEOs), records all intubations from a number of centres using an online database and allows for analysis of many different aspects of intubations in neonates. This year, J. Krick et al published Premedication with paralysis improves intubation success and decreases adverse events in very low birth weight infants: a prospective cohort study. This study compared results from the registry of two centres, the University of Washington Medical Center (UWMC) and Seattle Children’s Hospital where the former rarely uses paralysis and the latter in almost all instances of non-emergent intubation. In all, 237 encounters were analyzed in the NICU for babies < 1500g with the majority of encounters (181) being from UWMC. The median PMA at intubation was 28 completed weeks (IQR: 27, 30), chronological age was 9 days (IQR: 2, 26) and weight was 953 g (IQR: 742,1200). The babies were compared based on the following groups. Premedication with a paralytic 21%, without a paralytic 46% and no premedication 31%. This was an observational study that examined the rates of adverse events and subdivided into severe (cardiac arrest, esophageal intubation with delayed recognition, emesis with witnessed aspiration, hypotension requiring intervention (fluid and/or vasopressors), laryngospasm, malignant hyperthermia, pneumothorax/pneumomediastinum, or direct airway injury) vs non-severe (mainstem bronchial intuba- tion, esophageal intubation with immediate recognition, emesis without aspiration, hypertension requiring therapy, epistaxis, lip trauma, gum or oral trauma, dysrhythmia, and pain and/or agitation requiring additional medication and causing a delay in intubation.). How did the groups compare? It turns out paralysis seems to be a big deal (at least in this group of infants). Use of paralysis resulted in less attempts to intubate (median 1 attempt; IQR: 1, 2.25 vs. 2; IQR: 1, 3, p < 0.05)). In fact success was no different between the groups with no paralysis or no premedication at all! When it comes to tracheal intubation adverse events the impact of using paralysis becomes more evident. Paralysis does make a difference in reducing the incidence of such events and moreover when only looking at the rate of severe adverse events as defined above the finding was that none occurred when paralysis was used vs 9 when no paralysis was employed and 5 when no premedication was used at all. The rate of bradycardic events was less in the paralytic group but rates of oxygen desaturation between the three arms were no different. How do we interpret the results? Based on the results from the registry it looks like paralysis is a good thing here when electively intubating infants. If we try to determine the reason for it I suspect it may have much to do with the higher likelihood of success on the first attempt at placing an ETT. The longer it takes to place the ETT or the more number of attempts requiring intermittent PPV in a patient who truly needs a tube the greater the likelihood that you will see adverse events including bradycardia. It may simply be that a calm and still patient is an easier intubation and getting the tube in faster yields a more stable patient. I am biased though and I think it is worth pointing out another possible reason for the differing results. One hospital in this study routinely used premedication and the other did not. Almost 3/4 of the patients came from one hospital which raises the possibility that skill set could be playing a role. If the skill of providers at the two hospitals differed, the results could reflect the variable skill in the practitioners versus the difference in the medications used themselves. What I don’t know though is whether the two share the same training program or not. Are the trainees the same at both sites (google maps says the two sites are 11 minutes away by car)? The difference still might be in local respiratory therapists or Neonatologists intubating as well. Regardless, the study provides evidence that paralysis makes a difference. To convince those out there though who remain skeptical I think we are going to need the registry to take part in a prospective trial using many centres. A format in which several centres that don’t use paralysis are compared to several who do routinely would help to sort out the concern in skill when looking only at two centres. This wouldn’t be randomized of course but I think it would be very difficult at this point to get a centre that strongly believes in using paralysis to randomize so a prospective study using groups chosen by the individual centre might be the next best thing. If anyone using the registry is reading this let me know what you think?

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?✋✋✋

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!

A common concern in the NICU these days is the lack of opportunity to intubate. A combination of an increasing pool of learners combined with a move towards a greater reliance on non-invasive means of respiratory support is to blame in large part. With this trend comes a declining opportunity to practice this important skill and with it a challenge to get a tube into the trachea when it really counts. One such situation is a baby with escalating FiO2 requirements who one wishes to provide surfactant to. Work continues to be done in the area of aerosolized surfactant but as of yet this is not quite ready for prime time. What if there was another way to get surfactant to where it was needed without having to instill it directly into the trachea whether through a catheter (using minimally invasive techniques) or through an endotracheal tube? Installation of surfactant into the trachea Lamberska T et al have published an interesting pilot study looking at this exact strategy. Their paper entitled Oropharyngeal surfactant can improve initial stabilisation and reduce rescue intubation in infants born below 25 weeks of gestation takes a look at a strategy of instilling 1.5 mL of curosurf directly into the pharynx for infants 22-24 weeks through a catheter inserted 3-4 cm past the lips as a rapid bolus concurrent with a sustained inflation maneuver (SIM) of 25 cm of H2O for 15 seconds. Two more SIMs were allowed of the heart rate remained < 100 after 15 seconds of SIM. The theory here was that the SIM would trigger an aspiration reflex as the pressure in the pharynx increased leading to distribution of surfactant to the lung. The study compared three epochs from January 2011 - December 2012 when SIM was not generally practiced to July 2014 - December 2015 when SIM was obligatory. The actual study group was the period in between when prophylactic surfactant with SIM was practiced for 19 infants. A strength of the study was that resuscitation practices were fairly standard outside of these changes in practice immediately after delivery and the decision to intubate if the FiO2 was persistently above 30% for infants on CPAP. A weakness is the size of the study with only 19 patients receiving this technique being compared to 20 patients before and 20 after that period. Not very big and secondly no blinding was used so when looking at respiratory outcomes one has to be careful to ensure that no bias may have crept in. If the researchers were strongly hoping for an effect might they ignore some of the "rules around intubation" and allow FiO2 to creep a little higher on CPAP as an example? Hard to say but a risk with this type of study. What did they find? The patients in the three epochs were no different from one and other with one potentially important exception. There were higher rates of antenatal steroid use in the study group (95% vs 75 and 80% in the pre and post study epochs). Given the effect of antenatal steroids on reducing respiratory morbidity, this cannot be ignored and written off. Despite this difference it is hard to ignore the difference in endotracheal intubation in the delivery room with only 16% needing this in the study group vs 75 and 55% in the other two time periods. Interestingly, all of the babies intubated in the delivery area received surfactant at the same percentages as above. The need for surfactant in the NICU however was much higher in the study period with 79% receiving a dose in the study group vs 20 and 35% in the pre and post study groups. Other outcomes such as IVH, severe ROP and BPD were looked at with no differences but the sample again was small. What can we take from this? Even taking into account the effect of antenatal steroids, I would surmise that some surfactant did indeed get into the trachea of the infants in the study group. This likely explains the temporary benefit the babies had in the delivery suite. I suspect that there simply was not a big enough dose to fully treat their RDS leading to eventual failure on CPAP and a requirement for intubation. Is all lost though? Not really I think. Imagine you are in a centre where the Neonatologist is not in house and while he/she is called to the delivery they just don't make it in time. The trainee tries to intubate but can't get the tube in. Rather than trying several times and causing significant amounts of airway trauma (as well as trauma to their own self confidence) they could abandon further attempts and try instilling some surfactant into the pharynx and proving a SIM. If it works at all the baby might improve enough to buy some time for them to be stabilized on CPAP allowing time for another intubater to arrive. While I don't think there is enough here to recommend this as an everyday practice there just might be enough to use this when the going gets tough. No doubt a larger study will reveal whether there really is something here to incorporate into the tool chest that we use to save the lives of our smallest infants.

Intubation is not an easy skill to maintain with the declining opportunities that exist as we move more and more to supporting neonates with CPAP. In the tertiary centres this is true and even more so in rural centres or non academic sites where the number of deliveries are lower and the number of infants born before 37 weeks gestational age even smaller. If you are a practitioner working in such a centre you may relate to the following scenario. A woman comes in unexpectedly at 33 weeks gestational age and is in active labour. She is assessed and found to be 8 cm and is too far along to transport. The provider calls for support but there will be an estimated two hours for a team to arrive to retrieve the infant who is about to be born. The baby is born 30 minutes later and develops significant respiratory distress. There is a t-piece resuscitator available but despite application the baby needs 40% oxygen and continues to work hard to breathe. A call is made to the transport team who asks if you can intubate and give surfactant. Your reply is that you haven’t intubated in quite some time and aren’t sure if you can do it. It is in this scenario that the following strategy might be helpful. Surfactant Administration Through and Laryngeal Mask Airway (LMA) Use of an LMA has been taught for years in NRP now as a good choice to support ventilation when one can’t intubate. The device is easy enough to insert and given that it has a central lumen through which gases are exchanged it provides a means by which surfactant could be instilled through a catheter placed down the lumen of the device. Roberts KD et al published an interesting unmasked but randomized study on this topic Laryngeal Mask Airway for Surfactant Administration in Neonates: A Randomized, Controlled Trial. Due to size limitations (ELBWs are too small to use this in using LMA devices) the eligible infants included those from 28 0/7 to 35 6/7 weeks and ≥1250 g. The infants needed to all be on CPAP +6 first and then fell into one of two treatment groups based on the following inclusion criteria: age ≤36 hours, (FiO2) 0.30-0.40 for ≥30 minutes (target SpO2 88% and 92%), and chest radiograph and clinical presentation consistent with RDS. Exclusion criteria included prior mechanical ventilation or surfactant administration, major congenital anomalies, abnormality of the airway, respiratory distress because of an etiology other than RDS, or an Apgar score <5 at 5 minutes of age. Procedure & Primary Outcome After the LMA was placed a y-connector was attached to the proximal end. On one side a CO2 detector was placed and then a bag valve mask in order to provide manual breaths and confirm placement over the airway. The other port was used to advance a catheter and administer curosurf in 2 mL aliquots. Prior to and then at the conclusion of the procedure the stomach contents were aspirated and the amount of surfactant determined to provide an estimate of how much surfactant was delivered to the lungs. The primary outcome was treatment failure necessitating intubation and mechanical ventilation in the first 7 days of life. Treatment failure was defined upfront and required 2 of the following: (1) FiO2 >0.40 for >30 minutes (to maintain SpO2 between 88% and 92%), (2) PCO2 >65 mmHg on arterial or capillary blood gas or >70 on venous blood gas, or (3) pH <7.22 or 1 of the following: (1) recurrent or severe apnea, (2) hemodynamic instability requiring pressors, (3) repeat surfactant dose, or (4) deemed necessary by medical provider. Did it work? It actually did. Of the 103 patients enrolled (50 LMA and 53 control) 38% required intubation in the LMA group vs 64% in the control arm. The authors did not reach their desired enrollment based on their power calculation but that is ok given that they found a difference. What is really interesting is that they found a difference in the clinical end point despite many infants clearly not receiving a full dose of surfactant as measured by gastric aspirate. Roughly 25% of the infants were found to have not received any surfactant, 20% had >50% of the dose in the stomach and the other 50+% had < 10% of the dose in the stomach meaning that the majority was in fact deposited in the lungs. I suppose it shouldn’t come as a surprise that among the secondary outcomes the duration length of mechanical ventilation did not differ between two groups which I presume occurred due to the babies needing intubation being similar. If you needed it you needed it so to speak. Further evidence though of the effectiveness of the therapy was that the average FiO2 30 minutes after being treated was significantly lower in the group with the LMA treatment 27 vs 35%. What would have been interesting to see is if you excluded the patients who received little or no surfactant, how did the ones treated with intratracheal deposition of the dose fare? One nice thing to see though was the lack of harm as evidenced by no increased rate of pneumothorax, prolonged ventilation or higher oxygen. Should we do this routinely? There was a 26% reduction in intubations in te LMA group which if we take this as the absolute risk reduction means that for every 4 patients treated with an LMA surfactant approach, one patient will avoid intubation. That is pretty darn good! If we also take into account that in the real world, if we thought that little of the surfactant entered the lung we would reapply the mask and try the treatment again. Even if we didn’t do it right away we might do it hours later. In a tertiary care centre, this approach may not be needed as a primary method. If you fail to intubate though for surfactant this might well be a safe approach to try while waiting for a more definitive airway. Importantly this won’t help you below 28 weeks or 1250g as the LMA is too small but with smaller LMAs might this be possible. Stay tuned as I suspect this is not the last we will hear of this strategy!

Things aren’t the way they used to be. When I was training, opportunities abounded for opportunities to intubate infants. Then we did away with intubating vigourous infants born through meconium and now won’t be electively intubating them at all. Then you can add in the move towards use of non-invasive respiratory support instead of intubating and giving surfactant and voila…you have the perfect barrier for training residents and others how to intubate. On top of all of this the competition for learning has increased as the skill that was once the domain of the physician has now spread (quite rightly) to respiratory therapists, nurses in some places and with the growth of residency programs (ours is now 2.5X larger than when I trained) the scarce chances are divided among many. Enter the Video Laryngoscope To be clear this isn’t a post to promote a product but rather an examination of the effectiveness of a tool. I am putting this out there recognizing the possibility that someone out there might have heard of or have been contemplating purchasing one of these items. Those that are quite proficient at intubation (likely trained in the “good old days”) would likely question the need for such a device but I believe the device isn’t really aimed at that group except to use perhaps as a teaching tool. It really is targeted (at least I think) for those who don’t perform the skill often. Does use of the video laryngoscope improve success rates at intubation? This question has had an attempt now at being answered by Parmekar S et al in their paper Mind the gap: can videolaryngoscopy bridge the competency gap in neonatal endotracheal intubation among pediatric trainees? a randomized controlled study. The study involved taking 100 pediatric residents and randomizing them into two groups. The first would use the videolaryngoscope (VL group) and then intubate using the standard technique of direct laryngoscopy (DL group). The second group started with DL and then changed to VL. Both groups took part in a training session on intubation and then participated in three simulation scenarios from NRP. The findings demonstrated a couple interesting things. The first as shown in the graph was that the group that started with the laryngoscope had a near 90% success rate compared to about 60% for the traditional approach. When the groups swapped though they were both equal in effectiveness. This suggests that by visualizing the airway with the VL students were able to identify structures better after doing so such that success was improved simply by having used the device. The other finding worth mentioning was that when the times to intubation were looked at, there was no difference between the two groups at all. If the intubation success is no different, why might the times be the same? Having used the video laryngoscope myself it does take some getting used to. Rather than looking directly at the airway you find yourself looking off to the side and adjusting the approach that is in front of you to place the ETT. No doubt this does take some getting used to. What I would have liked to see is a repeat assessment a week later after using a few more trials with the VL as I suspect once you are used to it the speed of intubation would improve as well. I suppose though we will have to wait a little while until someone does such work but as a means of improving success in intubation I believe this tool has something to add.

We are the victims of our own success. Over the last decade, the approach to respiratory support of the newborn with respiratory distress has tiled heavily towards non-invasive support with CPAP. In our own units when we look at our year over year rates of ventilation hours they are decreasing and those for CPAP dramatically increasing. Make no mistake about it, this is a good thing. Seeming to overlap this trend is a large increase in demand by learners as we see the numbers of residents, subspecialty trainees, nurse practitioners on the rise. The combined effect is a reduction is the experience trainees can possibly hope to obtain when these rarer and rarer opportunities arise. The result of all of this is that at least by my eyes (although we haven’t documented it) the number of attempts for intubations seems to be much higher than it once was. It is not uncommon to see 3-4 attempts or sometimes more whereas in days gone by 1-2 attempts was the norm. We do our best to deal with these shortages using simulation as an example but nothing quite compares to dealing with the real thing even if it comes close. The Less Practice You Get The More Adverse Events You Can Expect This is just the way it is. Perfect practice makes perfect and it has been well documented that intubations can lead to many complications such as desaturation, bradycardia, bleeding, airway edema from multiple attempts and a host of other issues. Hatch and colleagues first described their experience with 162 intubations in which they found adverse events in 107 (39%) with 35% being classified as non-severe and severe events in 8.8%. Not surprisingly one of the factors associated with adverse events was the need for multiple intubation attempts. Based on this initial experience they determined that as a unit they could do better and soon after undertook a series of PDSA Quality Improvement cycles to see if they could reduce these events and that they did. What follows are the lessons learned from their QI project and it is my hope that some or all of these ideas may help others elsewhere who are experiencing similar frustrating rates. Steps To A Better Intubation The findings of their QI study were published last month in Pediatrics in their paper Interventions to Improve Patient Safety During Intubation in the Neonatal Intensive Care Unit. The strategies they used were threefold. Standardized checklist before intubation – This used a “do-confirm” approach in which the individuals on the team “do” what they need to prepare and then confirm with the group that they are done. An example might be an RRT who states “I have three sizes of ETT ready with a stylet already inserted, surfactant is thawed and the ventilator is set with settings of … if needed etc”. Another critical part of the checklist includes ensuring that everyone knows in advance their roles and who is responsible for what. Premedication algorithm – Prior to this project the use of premedication was inconsistent, drug selection was highly varied and muscle relaxation was almost non-existent. The team identified from the literature that a standard approach to premedication had been associated with reductions in adverse events in other centres so adopted the same here using fentanyl with atropine if preterm and muscle relaxation optional. Computerized order set for intubation – interestingly the order set included prompts to nursing to make sure intervention 1 and 2 were done as well. The results of there before and after comparison were numerous but I have summarized some of the more important findings in the table below. Outcome Period 1 (273 intubations) Period 2 (236 intubations) p Any AE 46.2% 36.0% 0.02 Severe events 8.8% 6.4% 0.04 Bradycardia 24.2% 9.3% <0.001 Hypoxemia 44.3% 33.1% 0.006 Esophageal intubation 21.3% 14.4% 0.05 # attempts 2 2 NS <10 intubations experience 15.1% 25.5% 0.001 The median number of attempts were no different but the level of experience in the second epoch was less. One would expect with less experienced intubators this would predict higher risk for adverse events. What was seen though was a statistically significant reduction in many important outcomes as listed in the table. I can only speculate what the results might have been if the experience of the intubators was similar in the first and second periods but I suspect the results would have been even more impressive. The results seem even more impressive in fact when you factor in that the checklist was used despite all of the education and order set 73% of the time and muscle relaxation was hardly used at all. I believe though what can be taken out of these results is that taking the time to plan each intubation and having a standard approach so that all staff practice in the same way reaps benefits. If you already do this in your unit then congratulations but if you don’t then perhaps this may be of use to you! What About Intubation For INSURE? We are in the process of looking in our own centre at the utility of providing premedication when planning to give surfactant via the INSURE technique. I couldn’t help but notice that this paper also looked at that very issue. Their findings in 17 patients all of whom were provided premedication were that only one could not be extubated right after surfactant. The one who was not extubated however was kept intubated for several hours without any reasoning provided in the records so it may well be that the infant could have been electively kept ventilated when they may have indeed been ready for extubation. The lesson here though is that we likely do not need to exclude such patients from premedication it will reduce the likelihood of complications without prolonging the time receiving positive pressure ventilation. Whatever your thoughts may be at this time one of the first questions you should ask is what is our local rate of complications? If you don’t know then do an audit and find out. Whatever the result, shouldn’t we all strive to lower that number if we can?

After the recent CPS meeting I had a chance to meet with an Obstetrical colleague and old friend in Nova Scotia. It is easy to get lost in the beauty of the surroundings which we did. Hard to think about Neonatology when visits to places like Peggy’s Cove are possible. Given out mutual interest though in newborns our our conversation eventually meandered along the subject of the new NRP. What impact would the new recommendations with respect to meconium have on the requirements for providers at a delivery. This question gave me reason to pause as I work in a level III centre and with that lens tend to have a very different perspective than those who work in level I and II centres (I know we don’t label them as such anymore but for many of you that has some meaning). Every delivery that is deemed high risk in our tertiary centre has ready access to those who can intubate so the changes in recommendations don’t really affect our staffing to any great degree. What if you are in a centre where the Pediatrician needs to be called in from home? Do you still have to call in people to prepare for a pending delivery of a baby through meconium stained fluid? What does the new recommendation actually say? These recommendations are from the American Heart Association and are being adopted by the NRP committees in the US and Canada. The roll-out for this change is coming this fall with all courses required to teach the new requirements as of September 2017. “However, if the infant born through meconium-stained amniotic fluid presents with poor muscle tone and inadequate breathing efforts, the initial steps of resuscitation should be completed under the radiant warmer. PPV should be initiated if the infant is not breathing or the heart rate is less than 100/min after the initial steps are completed. Routine intubation for tracheal suction in this setting is not suggested, because there is insufficient evidence to continue recommending this practice. (Class IIb, LOE C-LD)“ The rationale for the change is that is that there is a lack of evidence to demonstrate that routine suctioning will reduce the incidence of meconium aspiration syndrome and its consequences. Rather priority is placed on the establishment of adequate FRC and ventilation thereby placing a priority on teaching of proper bag-valve mask or t-piece resuscitator. Better to establish ventilation than delay while atempting to intubate and run the risk of further hypoxia and hypercarbia causing pulmonary hypertension. Does this mean you don’t need to have a person skilled in intubation at such deliveries? This question is the real reason for the post. At least from my standpoint the answer is that you do in fact still require such people. This may seem to be in conflict with the new position but if you move past that recommendation above you will see there is another line that follows afterwards that is the basis for my argument. “Appropriate intervention to support ventilation and oxygenation should be initiated as indicated for each individual infant. This may include intubation and suction if the airway is obstructed.” While we should not routinely perform such intubations there may be a time and a place. If one has intiated PPV with a mask and is not obtaining a rising heart rate, MRSOPA should be followed and attempts made to optimize ventilation. What if that is unsuccessful though and heart rate continues to be poor. You could have a plug of meconium distal to the vocal cords and this is the reason that intubation should be considered. In order to remove such a plug one would need to have an intubator present. Where do we go from here? As much as I would like to tell my colleague that he doesn’t need to have this skill set at a delivery for meconium I am afraid the skill still needs to be present. It will be interesting to see how instructors roll this out and answer such questions. It is a little concerning to me that in our world of wanting the “skinny” or “Coles’ Notes” version of things, the possibility of still needing the intubator on short notice may be lost. Having someone on call who is only “5 minutes away” may seem to be alright but at 3 AM I assure you the 5 minutes will become 15 as the person is woken, dresses, gets to the car and parks. Whether it is 5 or 15 minutes each centre needs to ask themselves if the baby is in need of urgent intubation are you willing to wait that amount of time for that to happen? I hope not.

In the spirit of full disclosure I have to admit I have never placed a laryngeal mask airway (LMA) in a newborn of any gestational age. I have played with them in simulated environments and on many occasion mentioned that they are a great alternative to an ETT especially in those situations where intubation may not be possible due to the skill of the provider or the difficulty of the airway in the setting of micrognathia for example. In recent years though we have heard of examples of surfactant delivery via these same devices although typically these were only case reports. More recently a small randomized study of 26 infants by Attridge et al demonstrated in the group randomized to surfactant administration through an LMA that oxygen requirements were reduced after dosing. This small pilot provides sufficient evidence to show that it is possible to provide surfactant and that at least some gets into the airway of the newborn. This proof of concept though while interesting, did not answer the question of whether such delivery of surfactant would be the same or better than through an ETT. As readers of my blog posts know, my usual stance on things is that the less invasive the better and as I look through the literature, I am drawn to concepts such as this to see if they can be added to our toolbox of non or less invasive strategies in the newborn. A Minimally Invasive Technique For The Masses? This past month, a small study by Pinheiro et al sought to answer this question by using 61 newborns between 29 0/7 - 36 6/7 weeks and greater than 1000g and randomizing them to either surfactant via the INSURE technique or LMA. I cannot stress enough so will get it out of the way at the start that this strategy is not for those <1000g as the LMA is not designed to fit them properly and the results (to be shown) should not be generalized to this population. Furthermore then study included only those infants who needed surfactant between 4 - 48 hours of age, were on CPAP of at least 5 cm H2O and were receiving FiO2 between 30 - 60%. All infants given surfactant via the insure technique were premedicated with atropine and morphine while those having an LMA received atropine only. The primary outcome of the study was need for subsequent intubation or naloxone within 1 hour of surfactant administration. The study was stopped early after an interim analysis (done as the fellow involved was finishing their fellowship - on a side note I find this an odd reason to stop) demonstrated better outcomes in the group randomized to the LMA. Before we get into the results let's address the possible shortcomings of the study as they might already be bouncing around your heads. This study could not be blinded and therefore there could be a significant bias to the results. The authors did have predetermined criteria for reintubation and although not presented, indicate that those participating stuck to these criteria so we may have to acknowledge they did the best they could here. Secondly the study did not reach their numbers for enrolment based on their power calculation. This may be ok though as they found a difference which is significant. If they had found no difference I don't think I would be even writing this entry! Lastly this study used a dose of surfactant at 3 mL/kg. How well would this work with the formulation that we use BLES that requires 5 mL/kg? What were the results? Intervention Failure LMA Group ETT group p Any failure 9 (30%) 23(77%) <0.001 Early failure 1 (3%) 20 (67%) <0.001 Late failure 8 (27%) 3 (10%) 0.181 What do these results tell us? The majority of failures occurred within an hour of delivery of surfactant in the ETT group? How does this make any sense? Gastric aspirates for those in the LMA group but not the INSURE group suggest some surfactant missed the lung in the former so one would think the intubation group should have received more surfactant overall however it would appear to be the premedication. The rate of needing surfactant afterwards is no different and in fact there is a trend to needing reintubation more often in the LMA group but the study was likely underpowered to detect this difference. Only two patients were given naloxone to reverse the respiratory depressive effects of morphine in those given the INSURE technique so I can't help but speculate that if this practice was more frequent many of the reintubations might have been avoided. This group was quite aggressive in sticking to the concept of INSURE as they aimed to extubate following surfactant after 5 - 15 minutes. I am a strong advocate of providing RSI to those being electively intubated but if the goal is to extubate quickly then I believe one must be ready to administer naloxone soon after extubation if signs of respiratory depression are present and this did not happen effectively in this study. Some may argue those getting the INSURE technique should not be given any premedication at all but that is a debate that will go on for years I am sure but they may have a valid point given this data. Importantly complications following either procedure were minimal and no different in either group. Where do we go from here? Despite some of the points above I think this study could prove to be important for several reasons. I think it demonstrates that in larger preterm infants it is possible to avoid any mechanical ventilation and still administer surfactant. Many studies using the minimally invasive surfactant treatment (MIST) approach have been done but these still require the skill of laryngoscopy which takes a fair bit of skill to master. The LMA on the other hand is quite easy to place and is a skill that can be taught widely. Secondly, we know that even a brief period of over distension from PPV can be harmful to the lung therefore a strategy which avoids intubation and direct pressure to the lung may offer some longer term benefit although again this was not the study to demonstrate that. Lastly, I see this as a strategy to look at in more rural locations where access to highly skilled level III care may not be readily available. We routinely field calls from rural sites with preterm infants born with RDS and the health care provider either is unable to intubate or is reluctant to try in favour of using high flow oxygen via mask. Many do not have CPAP either to support such infants so by the time our Neonatal Transport team arrives the RDS is quite significant. Why not try surfactant through the LMA? If it is poorly seated over the airway and the dose goes into the stomach I don't see them being in any worse shape than if they waited for the team to arrive. If some or all of the dose gets in though there could be real benefit. Might this be right for your centre? As we think about outreach education and NRP I think this may well become a strong reason to spend a little more time on LMA training. We may be on to something!