It has been over two years since I have written on this subject and it continues to be something that I get excited about whenever a publication comes my way on the topic. The last time I looked at this topic it was after the publication of a randomized trial comparing in which one arm was provided automated FiO2 adjustments while on ventilatory support and the other by manual change. Automated adjustments of FiO2. Ready for prime time? In this post I concluded that the technology was promising but like many new strategies needed to be proven in the real world. The study that the post was based on examined a 24 hour period and while the results were indeed impressive it left one wondering whether longer periods of use would demonstrate the same results. Moreover, one also has to be wary of the Hawthorne Effect whereby the results during a study may be improved simply by being part of a study.
The Real World Demonstration
So the same group decided to look at this again but in this case did a before and after comparison. The study looked at a group of preterm infants under 30 weeks gestational age born from May – August 2015 and compared them to August to January 2016. The change in practice with the implementation of the CLiO2 system with the Avea ventilator occurred in August which allowed two groups to be looked at over a relatively short period of time with staff that would have seen little change before and after. The study in question is by Van Zanten HA The effect of implementing an automated oxygen control on oxygen saturation in preterm infants. For the study the target range of FiO2 for both time periods was 90 – 95% and the primary outcome was the percentage of time spent in this range. Secondary outcomes included time with FiO2 at > 95% (Hyperoxemia) and < 90, <85 and < 80% (hypoxemia). Data were collected when infants received respiratory support by the AVEA and onlyincluded for analysis when supplemental oxygen was given, until the infants reached a GA of 32 weeks
As you might expect since a computer was controlling the FiO2 using a feedback loop from the saturation monitor it would be a little more accurate and immediate in manipulating FiO2 than a bedside nurse who has many other tasks to manage during the care of an infant. As such the median saturation was right in the middle of the range at 93% when automated and 94% when manual control was used. Not much difference there but as was seen in the shorter 24 hour study, the distribution around the median was tighter with automation. Specifically with respect to ranges, hyperoxemia and hypoxemia the following was noted (first number is manual and second comparison automated in each case).
Time spent in target range: 48.4 (41.5–56.4)% vs 61.9 (48.5–72.3)%; p<0.01
Hyperoxemia >95%: 41.9 (30.6–49.4)% vs 19.3 (11.5–24.5)%; p<0.001
< 90%: 8.6 (7.2–11.7)% vs 15.1 (14.0–21.1)%;p<0.0001
< 85%: 2.7 (1.4–4.0)% vs 3.2 (1.8–5.1)%; ns
Hypoxemia < 80%: 1.1 (0.4–1.7)% vs 0.9 (0.5–2.1)%; ns
What does it all mean?
I find it quite interesting that while hyperoxemia is reduced, the incidence of saturations under 90% is increased with automation. I suspect the answer to this lies in the algorithmic control of the FiO2. With manual control the person at the bedside may turn up a patient (and leave them there a little while) who in particular has quite labile saturations which might explain the tendency towards higher oxygen saturations. This would have the effect of shifting the curve upwards and likely explains in part why the oxygen saturation median is slightly higher with manual control. With the algorithm in the CLiO2 there is likely a tendency to respond more gradually to changes in oxygen saturation so as not to overshoot and hyperoxygenate the patient. For a patient with labile oxygen saturations this would have a similar effect on the bottom end of the range such that patients might be expected to drift a little lower then the target of 90% as the automation corrects for the downward trend. This is supported by the fact that when you look at what is causing the increase in percentage of time below 90% it really is the category of 85-89%.
Is this safe? There will no doubt be people reading this that see the last line and immediately have flashbacks to the SUPPORT trial which created a great deal of stress in the scientific community when the patients in the 85-89% arm of the trial experienced higher than expected mortality. It remains unclear what the cause of this increased mortality was and in truth in our own unit we accept 88 – 92% as an acceptable range. I have no doubt there are units that in an attempt to lessen the rate of ROP may allow saturations to drop as low as 85% so I continue to think this strategy of using automation is a viable one.
For now the issue is one of a ventilator that is capable of doing this. If not for the ventilated patient at least for patients on CPAP. In our centre we don’t use the Avea model so that system is out. With the system we use for ventilation there is also no option. We are anxiously awaiting the availability of an automated system for our CPAP device. I hope to be able to share our own experience positively when that comes to the market. From my standpoint there is enough to do at the bedside. Having a reliable system to control the FiO2 and minimize oxidative stress is something that may make a real difference for the babies we care for and is something I am eager to see.
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?
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!
The 1960s saw the emergence of newborn screening for phenylketonuria. This was an important milestone in the field of newborn care as it allowed us to screen children for something that we could do something about. Dietary manipulation could for the first time prevent the repercussions of this condition and allow these children to avoid the severe neurological impairment that would follow the natural course of the condition. Since that time, our ability to screen for and offer treatment to modify other disease courses has expanded many fold which no doubt in terms of population health is a wonderful thing.
Here in Manitoba we are now screening for over 40 conditions with a useful site for information being provided by Manitoba Health.
The expansion of these programs has been possible due to the use of Tandem Mass Spectrometry. This technique provides the ability to screen for many conditions without increasing the amount of blood required.
The downside to more screening is that as the number of tests being sampled increases the risk of false positive results due to the presence of dietary additives. An example of this is carnitine supplementation. In our centre we were providing this to low birth weight infants based on demonstrated low levels of carnitine facilitated lipid metabolism. After failing to find a clinical benefit after the metabolic derangements were noted we identified a larger issue in that many of our premature infants receiving carnitine supplementation had elevated acylcarnitine profiles on their Newborn Metabolic Screening (NMS) samples. These false positive results led to repeated sampling via bloodspot analysis leading to unnecessary blood sampling and pain from heel lances.
Another set of conditions that we are now able to screen for are the aminoacidopathies. This group of disorders involve abnormalities of amino acid metabolism leading to toxic elevations of one or more amino acids that can have significant neurodevelopmental impairment as a consequence. Clearly in all of these tests the purpose is to avoid long-term deleterious consequences but as with carnitine, false positive results are very concerning as they lead to repeated sampling, and potentially larger blood draws if confirmation of the screening results are needed. Add to this, that this further analysis requires consultation with metabolics consultants, nursing time for repeated sampling, and laboratory costs and you can see why minimizing false positives is needed. Lastly the greatest impact is on the family who in many cases experience unneeded anxiety as they await confirmatory testing which may take a week or more to come back if the sample needs to be sent offsite.
A few years back I attended the PAS meeting in Boston and heard about a study on this subject from California that they were presenting in abstract form. Withholding TPN and using D10W for a three hour period prior to collection of the NMS could reduce false positive aminoacidopathy screens by about 70%. The reaction of our local laboratory was one of disbelief as the consensus was that such a short time frame could not clear the TPN sufficiently from the circulation. Since the reference ranges for normal amino acid profiles in infants are from patients who are not receiving TPN this could create false positive elevations, which would require either repeat blood spot sampling or as above, trigger a formal consult to metabolics if the subsequent test is also positive.
In following up on the original abstract presentation I noted that the findings were in fact published as Reduction in Newborn Screening Metabolic False- Positive Results Following a New Collection Protocol.
In this 2 year retrospective cohort study, in 2010 NMS was done for all infants between 24-48 hours with no withholding of TPN and in 2011 the protocol was changed to hold TPN for 3 hours and use D10W before collection of the NMS. The main results of the study are shown below and of note all the False Positive results post intervention were statistically different to a significant degree after the change in practice. Examining the entire group there was a 74% reduction in false positive results post practice change.
||Post Intervention (N=265)
||False Positive (%)
||False Positive (%)
Furthermore an 81% savings in health care costs per patient were realized in the change as well. This is outlined below:
|Supplies for testing
|Supplies for new protocol
The results speak for themselves yet the practice I don’t believe has been widely adopted and certainly not in our centre. This past week however the following study was released in abstract form and inspired me to write this post as I believe the evidence is overwhelmingly in support of this practice change Stopping Parenteral Nutrition for Three Hours Reduces False Positives In Newborn Screening.
12 567 consecutive births in 1 hospital between May 2010 and June 2013 were analyzed to determine the FP for AA levels in the NMS. The FP rate in infants > 1500g was much lower overall than for those under 1500g which may have been explained by less TPN use in that cohort. Similar to the first study TPN was changed to D10W for three hours prior to collection of the NMS and resulted in a FP rate of 3.1% in the D10W group vs 11.8% in the TPN group. This represents again an overall 74% reduction.
So there you have it. Two studies showing the same results. The concept is simple, saves hospitals money and more importantly avoids unnecessary parental anxiety, needless blood sampling and consumption of time by nursing staff and other consultants. This is not a high tech strategy that takes a great deal of education to implement. Rather this can be started tomorrow wherever you are and it is my hope that by reading this at least one hospital out there aside from our own may adopt this small change to make a big impact on our patients.
This post is meant to supplement an earlier post on the same topic.
Since introducing POC U/S in our unit there has been great enthusiasm and we will begin shortly introducing our nursing group to it’s use in order to enhance usage. Now that we have had some exposure we took the time to capture some our thoughts on this technology in this accompanying video graciously supported by the Children’s Hospital Foundation in Winnipeg. To watch this wonderful video by Dr. Ganesh Srinivasan a Neonatologist and technology aficionado in our institution click on the link below.
What follows is a local news story that I had the pleasure of being involved in. I am posting on the blog not to show off in the least but rather highlight how true collaboration between professionals (who on the surface might not seem to be related) can accomplish incredible things. The strategy employed in this case had not been described before in the literature and thus it is my hope that this post may be shared at your local institutions and in the event a child with a cleft lip and palate is born and needs CPAP this appliance could be utilized.
If you would like further information on this approach please email me at [email protected] and I would be happy to provide you with assistance. The link to obtain the abstract and from there if you have personal or facility access to the full article can be found here: http://www.ncbi.nlm.nih.gov/pubmed/25794910
Within the last year a team of professionals from Dentistry, Neonatology and Respiratory Therapy came together to solve an unusual problem. A baby had been born prematurely at 26 weeks gestational age and less than 2 lbs and relied on a ventilator to help her breathe. As many of these children age, their reliance on a ventilator becomes less and they are changed to a non-invasive level of support called CPAP (continuous positive airway pressure). This consists of a mask put over the nose, which passes air into the lung thereby keeping a babies lungs inflated while we wait for continued development of their lungs. In this case however this premature infant had been born with a complete unilateral cleft lip and palate. Having this cleft created a leak, which makes the use of CPAP very challenging. The flow of air leaks out through the cleft instead of getting to the lungs to keep them inflated. One day, one of our respiratory therapists John Minski asked the Neonatologist on service (Dr. Michael Narvey) whether we could use a 3D scanning and printing technology to create an appliance that would seal the palate and allow pressure to be maintained in the lungs through the flow of air in the nose. Dr. Narvey had not heard of such a strategy being employed before but consulted Dr. Igor Pesun from the Faculty of Dentistry for an opinion and what came out of this discussion was a novel concept that we believe is the first of its kind.
A dental obturator was created to seal the palatal defect. A child who is as small as Michaela, made the use of current intra oral scanning technology not possible. An impression using conventional dental materials was used to record the anatomy of the palate. A model was made and used to fabricate the obturator that was connected to the CPAP tubing.
Over a period of 4 days the obturator was used to maintain a palatal seal and allowed for sufficient pressure to be maintained to manage the child off the ventilator. After this point she was deemed ready to transition to being off CPAP.
The collaboration between these services was instrumental in taking an idea from concept to reality. We were able to demonstrate that a premature infant, who previously would have been forced to remain on a ventilator until they were ready to come off breathing support completely, could be managed with a novel airway appliance. This type of approach has never been tried before in the literature and exemplifies some of the creative and innovative collaborative work happening at the Health Sciences Centre. Finally it serves as a shining example of how different seemingly unrelated specialties can come together within the Faculty of Health Sciences at the University of Manitoba.