A real change is coming and with this post you will get a glimpse into where the next big thing in Neonatology is likely to be. 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
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.
Hi, my name is Diane Schultz and Michael has asked me to write a series of posts on his blog about Kangaroo Care (KC). Seeing as I am one of the Champions (they call you that, but sometimes the word begins with a B) for KC in my unit, I was thrilled. I thought I would begin with an introduction as to why I want to write about this.
I have been a Neonatal Nurse for 29 years working in the NICU at St. Boniface Hospital in Winnipeg. I felt that I had always given good care to the families but did not really make connections with them.
I was fortunate enough to meet Dr. Susie Ludington about 10 years ago at an Academy of Neonatal Nursing conference. She was a general session presenter and was speaking about Kangaroo Care. The first thing she said was “My goal is Kangaroo Care 24/7”. All I could think of was WTF!? I would have to listen to this Nutbar for an hour? Our unit had been doing KC for years but only occasionally and usually the parent would ask for it, we certainly did not promote it or do it with our more fragile infants.
After listening to Dr. Ludington present, my world changed. What she said hit a cord; she presented benefit after benefit with rationale and evidence that made complete sense to me. I felt guilty I had not been doing this at work and guilty that I had not held my own daughters this way. I am now lucky to be able to call Dr. Ludington a friend, and know she has changed my life.
Now, there is a lot of evidence out there touting the benefits of KC, but the real way to understand and believe in it is to do it. KC creates its own evidence. Every time I bring out a medically fragile infant to be held in KC, I know that this is the right place for that infant to be: with their parent being held. You can see the relaxation on all of their faces (decreasing cortisol), the infant is able to go into a deep sleep (promotes brain maturation), and the family is able to connect in the best way possible. I feel KC is as important as anything else we do at the bedside and is an extremely necessary therapy.
Promoting KC in my unit has benefited me at so many levels; I believe it has actually saved my career and given me a focus that I didn’t have before. You can’t help but make connections with your families, and these families are able to make connections with their little ones. KC is also a very important part of Family Integrated Care, as this is something that the family can contribute to their child’s care.
I also couldn’t be more proud of my unit; the staff I have the pleasure to work with are some of the best health care professionals around. They make every effort to bring our fragile infants out for KC and it has become part of our culture in our NICU. KC happens in our unit with almost all of our infants, the only exceptions being actively cooling babies and infants with chest tubes. We have also created a Standard Work Protocol so all medically fragile infants come out the safest way possible without creating extra stress on the infant or family.
In my series of posts I will present the many benefits of KC for infants and their families and share some of my experiences. I hope you will be able to take something away from this, begin to try KC in your own unit, and create your own evidence.
Welcome to the home page for our Integrated Evaluation of Hemodynamics program at the University of Manitoba. This program began in Winnipeg, Manitoba, Canada in 2014 and has been growing ever since.
What is considered normal hemodynamics?
1. Intact or normal hemodynamics implies blood flow that provides adequate oxygen and nutrient delivery to the tissues.
2. Blood flow varies with vascular resistance and cardiac function; both may be reflected in blood pressure(2). Normal cardiovascular dynamics should be considered within the context of global hemodynamic function, with the aim of achieving normal oxygen delivery and end organ performance
3. The current routine assessment of hemodynamics in sick preterm and term infants is based on incomplete information. We have addressed this by adopting an approach utilizing objective techniques, namely integrating targeted neonatal echocardiography (TNE) with near-infrared spectroscopy (NIRS). Implementation of these techniques requires an individual with the requisite TNE training, preferably in an accredited program, who also has a good understanding of perinatal and neonatal cardiovascular, respiratory, and other specific end organ physiology.
Why are premature infants more susceptible to cardiovascular compromise?
Hemodynamic compromise in the early neonatal period is common and may lead to unfavorable neurodevelopmental outcome4. A thorough understanding of the physiology of the cardiovascular system in the preterm infants, influence of antenatal factors, and postnatal adaptation is essential for the management of these infants during the early critical phase5. The impact of the various ventilator modes, the presence of a patent ductus arteriosus (PDA), and systemic inflammation all may affect the hemodynamics6. The poor clinical indicators of systemic perfusion and the relative insensitivity of conventional echocardiographic techniques in assessing myocardial contractility mean that monitoring of the hemodynamics of the preterm infant remains a challenge7.
What is integrated hemodynamics in neonatal care?
Integrated hemodynamics focuses on how to interpret multiple tools of hemodynamics evaluation in sick infants (TNE, clinical details, NIRS, organ specific ultrasound) and the art of formulating a pathophysiologic relevant medical recommendation.
Main objectives of applying Targeted Neonatal Echocardiography and Evaluation of Neonatal hemodynamics
Optimise care of infants with hemodynamic compromise to prevent progression into late irreversible stages of shock (Hypoxia)
Decrease overall PDA related complications (Hypoxemia and hypoxia)
Optimize care of infants with hypoxemic respiratory failure (HRF)
Decrease the incidence of progression of infants with hypoxemic respiratory failure and shock to end organ dysfunction
Objective of the program
Orientation to the hemodynamics concepts and basics
Orientation to the 3 level of the pathophysiologic approach to hemodynamics:
Level one: Relying on blood pressure trends (systole, diastole, and pulse pressure) and waveforms with other clinical parameters (all NICU practitioners)
Level one plus (advanced monitoring): Relying on blood pressure trend and near infrared spectroscopy (NIRS) for assessment of hemodynamics and oxygen extraction (optional to NICU practitioners)
Level two (TNE approach): Relying on both clinical parameters and TNE for objective assessment of cardiac output, extra and intra cardiac shunts, systemic and pulmonary vascular resistance. (Neonatologist trained on TNE)
Level three (integrated evaluation of hemodynamics): integrating blood pressure trends, TNE and NIRS for assessment of oxygen delivery, specific end organ oxygen consumption and the degree of compensation (comprehensive hemodynamic approach)
Understanding the rationale for the measurements and the specific values for each disease, and recognize limitations of the 3 models
To see research that we have done in the area of Integrated Hemodynamics please see our publication list that can be found here.
To access our video series providing examples of TNE and presentations on the use of hemodynamics in clinical application please see our Youtube channel playlist “Integrated Neonatal Hemodynamics”
Wolff CB. Normal cardiac output, oxygen delivery and oxygen extraction. Adv Exp Med Biol. 2008;599:169-182. doi:10.1007/978-0-387-71764-7-23.
Azhan A, Wong FY. Challenges in understanding the impact of blood pressure management on cerebral oxygenation in the preterm brain. Front Physiol. 2012;3 DEC(December):1-8. doi:10.3389/fphys.2012.00471.
de Boode WP. Clinical monitoring of systemic hemodynamics in critically ill newborns. Early Hum Dev. 2010;86(3):137-141. doi:10.1016/j.earlhumdev.2010.01.031.
Sehgal A. Haemodynamically unstable preterm infant: an unresolved management conundrum. Eur J Pediatr. 2011;170(10):1237-1245. doi:10.1007/s00431-011-1435-4.
Vutskits L. Cerebral blood flow in the neonate. Paediatr Anaesth. 2014;24(2):22-29. doi:10.1111/pan.12307.
Noori S, Stavroudis T a, Seri I. Systemic and cerebral hemodynamics during the transitional period after premature birth. Clin Perinatol. 2009;36(4):723-36, v. doi:10.1016/j.clp.2009.07.015.
Elsayed YN, Amer R, Seshia MM. The impact of integrated evaluation of hemodynamics using targeted neonatal echocardiography with indices of tissue oxygenation: a new approach. J Perinatol. 2017. doi:10.1038/jp.2016.257.
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?