It gives me great pleasure to write this piece as it is about research that two of my colleagues Dr. Yasser Elsayed and Dr. Shyamala Dakshinamurti authored along with colleagues in Saudi Arabia. Both colleagues have worked in the fields of hemodynamics and pulmonary hypertension for some time. For those of you who know Yasser you would know that he has had an interest in what one can glean from careful attention to a patient monitor for some time. In fact we created some short Youtube videos on these topics a few years ago that are available on the accompanying Youtube channel to this site.
What if you don’t have ready access to an ECHO?
If you are like me, you are blessed to work in a centre that has easy access to evaluation of hemodynamics. What if you are in a centre that doesn’t have such access? Alternatively, in the spirit of using resources wisely what if you don’t want to exhaust your hemodynamics team by asking them to assess every murmur that comes along in a preterm infant. In other words, is there a way to tell whether a ductus is hemodynamically significant or not? There is a lot of preceding research that would tell us that our stethescope and fingertips are not as accurate as we would like to think in determining which ducts are likely significant, if open at all.
In comes the pulsatility index. The pulsatility index is derived from the formula;
(peak systolic velocity – end diastolic velocity) /mean velocity
Moreover, this value can be obtained using an oxygen saturation probe based on the absorption of light by pulsatile and non-pulsatile tissues. Patient monitors can express this number with > 2 being higher than the upper limit of normal in preterm infants, 1–2 being normal, 0.4–1 being low normal, and < 0.4 low PI. The patient monitor moreover is capable of providing histograms for this data providing the user with a bar graph indicating the percentage of time over twenty four hours that the infant has been in each of these ranges. Osman AA et al used this information to study the relationship between PI in the periods of time before an infant develops a HS PDA, during treatment and afterwards in their paper The perfusion index histograms predict patent ductus arteriosus requiring treatment in preterm infants. They studied 34 preterm infants in four time periods, namely 24 h before starting treatment of PDA, during PDA treatment, and 24 h after completion of the course of treatment, and confirmed PDA closure by echo. The data was obtained from a oxygen saturation probe placed on the right wrist in a preductal location. They also compared PI during matched time periods in infants without a HS PDA in order to determine what the PI ranges would be for patients of a matched gestational age without a ductal concern.
For the ECHO diagnosis of a HS PDA they used the following criteria:
A ductal diameter at the pulmonary side ≥ 1.5 mm and at least one of the following:
Before the PDA was treated but was identified as being significant the figure below shows that the incidence of low flows were statistically more likely to be present ini HS PDA. This remained true during treatment with a stabilization follwoing treatment.
The authors examined the best predictive findings from the histogram analysis and discovered that “presence of a PI <0.4 for > 10% of the recorded time, together with the presence of a PI > 2 for > 8% of the time recorded, is predictive of a PDA requiring treatment, with a sensitivity and specificity of 77 and 96%; positive and negative predictive values of 94 and 81%, respectively;and an area under the curve of 0.88 (95% confidence interval 0.78–0.95, p = 0.004)”
How do we explain this in terms of physiology? The low flow state I think is the easier one to think about. If you have a HS PDA blood is “stolen” from the aorta and is directed to the lungs. This stolen flow may lead to lower perfusion than normal to the distal extremities as aortic flow is less than what it normally would be. Therefore with less flow in a vessel the pulsatility index declines. How then could you find a high PI in the same patient? The situation may arise if there is intermittent hypoxia that increases pulmonary vascular resistance thereby lessening the flow and restoring good flow in the aorta. The combination therefore was found to be predictive of a HS PDA with a reasonable specificity in particular. If you don’t have a low PI it is unlikely you have a HS PDA.
How could we use this?
Don’t worry I am not going to suggest that we can do away with the hemodynamics assessment. I do wonder though if this information could be very useful in helping to triage resources when they may be quite limited. In other words, if you hear on morning report that a 27 week infant has become tachypneic and has a murmur, instead of jumping to call the Hemodynamics service why not check the 24 hour PI histogram? If you don’t see low flows it is unlikely as I read this that a HS PDA is present. To be clear I am not saying that I am totally sold on this! I think it needs to be recognized this was a small study and will need further larger samples to confirm as there would be more babies with varying levels of PDAs in terms of hemodynamics to study. In the meantime though I think it would be very interesting to take a look at the 24 hour PI histograms for the next number of babies I see and look at how it does correlate with the ECHO I ask for. No doubt as two of the authors in the paper work with me I won’t have to remember this post to check the values as I am sure this is not the last I will hear of this!
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.
Cool title for a post I think. If you have children or even if you are an adult who likes to play video games you would be aware of virtual reality headsets. These headsets take games to a new level by immersing you in the experience so all you see is the game in your field of vision. It is easy to get lost in this world and lose your sense of the outside world. It seems reasonable then that someone might think to adapt some of the principals of this type of gaming to use in medicine.
I am no stranger to posts on video laryngoscopy having written about it several times already. A search of this site should easily find posts on the topic if you are so inclined. In these posts I think I have made a compelling argument for the use of videolaryngoscopy over direct laryngoscopy to improve inubation success.
A New Way of Doing Things
In each of those posts there has been a comparison of two groups in with one uses IVL in which the video image is generally off to the side of where the intubation is taking place and DL or direct layngoscopy with video aid. A new study entitled Augmented Reality–Assisted Video Laryngoscopy and Simulated Neonatal Intubations: A Pilot Study by Patricia L. Dias, et al compares a third method to the other two. The third method is to use a disposbale laryngoscope as shown below with a video camera attached that connects to a tablet. The video captured on the laptop is then sent to glasses the person intubating is wearing that is projected into the line of site as per the image below. In essence its like a car with heads up display. No need to take your eyes off the airway as you are seeing it directly in front of you. Where the tech becomes even more interesting is that the person on the tablet can make notations on the video that appear in the view of the person wearing the glasses. For example one could put an arrow showing where to put the ETT or label the esophagus as such.
In the study there were 45 nursing participants who were assigned to one of three different intubation strategies being DL, IVL and Augmented Reality VL (ARVL). As such there 15 participants in each arm. Each participant was read a script on how to intubate and then had 5 consecutive intubation attempts on a maniken using a miller 1 blade.
How Did They Do
Interestingly there was no difference in success with the ARVL vs the IVL in terms of success on being able to get the ETT into the manequin successfully as shown below but both were better than the DL.
Looking at the details of the success and failure there was also no difference in the two types of videolaryngoscopy.
So Where Does That Leave Us
At the very least what we have seen is once again the ability to intubate is enhanced with VL. There was no difference seen in this group of nurses learning to intubate whether they used a indirect or augmented reality VL. This however is a small study and really to me is a proof of concept study. The authors created a novel method of doing VL although one could argue it is not that differrent that use of the CMAC with the small screen attached to the top of the laryngoscope
The difference though is in the ability of the instructor to write feedback on the tablet and have that show up in the line of sight of the intubator. I see this novel ability as a wonderful educational tool. There is not a learner out there who hasn’t had the experience of looking down at an airway and thinking “what am I looking at?” Sometimes with secretions it can be awfully hard to determine which structure is what. Having someone on a tablet seeing the image you are seeing and rather than having to describe to you what you seeing, they could draw it for you I think is a huge advance. Like many pilots I would suggest this is not the last we have heard of this technology. With this in the literature now I suspect there will be trials to come with more developed devices rather than those put together piecemeal. If these larger trials with less and more advanced intubators demonstrate increased rates of success I could see this becoming the new standard for video laryngoscopy.
This post is a written as a tribute to John Minski RRT who taught me much about ventilation over the years and has been a champion for innovation in our unit. As he prepares to move on to the next phase of his life I thought it would be a nice send off to talk about something that he has been passionate about for some time. That passion is inhaled nitric oxide for more than just pulmonary hypertension.
Prior Evidence
This is actually nothing really new. For a review on the background behind the theory you can read The potential of nitric oxide releasing therapies as antimicrobial agents. While we think of iNO as being a drug for pulmonary hypertension it has other capabilities. It can diffuse across cell membranes and damage pathogens by causing nitrosative and oxidative damage. The amount of iNO needed though to accomplish this bactericidal action is much higher than the typical levels of 20 – 40 ppm that we use. Last year in August Bogdanovski et al published Antibacterial activity of high-dose nitric oxide against pulmonary Mycobacterium abscessus disease. They describe a protocol of providing 30 minute doses of 160 ppm for 21 days in a 24 year old patient with cystic fibrosis who was infected with mycobacterium abscessus. While they were not able to eradicate the organism, they were able to demonstrate functional improvement in the patient. Also notable was the absence of adverse effects in terms of methemoglobin levels. Other prior research in-vitro has shown iNO at high levels to be truly bacteriocidal as per the review above.
In this paper they describe the use of iNO at 160 ppm in 5 spontaneously breathing patients with confirmed COVID19 infection. This was provided as a rescue therapy in the absence of any high quality therapies for this disease. The protocol was to give them the same dose of 160 ppm for 30 minutes at a time until resolution of their symptoms with those that received multiple treatments getting anywhere from 5-9 courses. In each case after each 30 minute period the treating physicians measured levels of methemoglobin and nitrogen dioxide and found in each patient acceptable levels after these brief exposures.
Results
Of the 5 patients treated 2 died from COVID19 and three survived. The two patients who died interestingly were the ones who each only received one treatment each. The other three received 5, 8 and 9 treatments respectively. The authors recorded mean arterial pressure, heart rate, respiratory rate, SpO2/FiO2 and finally measurements of inflammatory markers in the two patients who died (E) and the 3 who survived in (F) in the figure below.
What is interesting from the figure above is the reduction in respiratory rate during treatment (certainly could be placebo from believing they will get better) but the oxygenation during the treatment improved as well. Could this be from a reduction in associated pulmonary hypertension? Certainly could be. Looking at the patients who died in (E) vs the ones in (F) who survived (patient 3 not shown) demonstrate that use of iNO stopped the rise in CRP and in the case of those who died reduced it significantly. There could be an argument made then that the changes in respiratory pattern observed during treatment are associated with a concomitant attenuation of inflammation. This treatment just might work but of course needs far more studies to be certain of that. On that note a review of iNO for this type of indication reveals there are currently 16 studies enrolling in this area of research so I imagine there will be more info to come with this story.
What about the neonate with pneumonia?
I sent this paper around to my colleagues and it generated some great discussion. I am no Ethicist but the question raised was could this be considered a “last ditch” treatment for the neonate succumbing to a pneumonia? I have no doubt if you are reading this that you will have seen in neonatal units around the world that there are infants who develop pneumonia unresponsive to traditional treatments such as iNO at regular doses, antibiotics, higher PEEP, surfactant etc. If we have this knowledge with respect to the potential use of iNO at high dose and a positive impact on pulmonary infective disease is this something that should be offered to parents?
We have no date to my knowledge in babies on the use of this type of dosing but it comes down to a question of what is the alternative? If a patient is dying on the ventilator are we at the point of knowledge here that it is worth offering the family this treatment? One could do so with full disclosure about the lack of neonatal data both for effectiveness and safety. Or do you fall on the side of it could be harmful and expedite death so should not be used. If you use it though and wait till the patient is in extremus on 100% oxygen might it be too late? Do parents have the right to know when they ask the question “is there anything else you can do?” For me I think the answer is that there should be a discussion with this evolving research out there. I am comfortable with it as long as the parents understand the potential for it to make things worse and shorten their time with their child. Alternatively if they choose not to that is their prerogative but should they have the choice when the competing outcome is death?
I can’t tell you whether you should or shouldn’t offer this in your institution but my suspicion is that you will be discussing this among colleagues before long. Who knows you might just one day say you saw it here first!
Thanks John M for the inspiration and keep sending those articles!
I am not saying we go back to a paternalistic time in medicine but I am saying that one size does not fit all.
