Extubation is a regular occurrence in the NICU. We do our best to predict who will succeed and who will fail but it isn’t always easy to figure out who they are in advance. We use techniques such as looking at oxygenation histograms and using thresholds for PIP, PEEP or MAP but in the end sometimes it works and other times it doesn’t. In an effort to improve on intubation success, some creative researchers in Switzerland employed a technique called end-expiratory lung impedance or EELI to measure lung volume before, during and after the extubation process. The use of EELI is based on the impendance of the lung changing with the distribution of tissue and air and by placing electrodes one can generate a cross sectional volume that has been shown in neonates to be representative of total lung volume. The EELI technique creates an image like this which is use to generate the estimate of lung volume.
The researchers in this study were seeking to do a quality improvement project and use EELI to estimate lung volume at different time points in an extubation. The time points were all 30 seconds including, immediately before first handling of the infant (baseline), tracheal suctioning (suction), start and end of adhesive tape removal (adhesive tape begin and adhesive tape end), pulling the endotracheal tube (extubation), initiation of non-invasive ventilation (NIV), immediately before and after turning the infant to prone position (supine and prone, respectively), and 10 min after turning to prone position (prone10). As per unit policy all babies were ventilated with Draeger VN500 ventilators and if <28 weeks went on to NIPPV when extubated or if 28 weeks or more straight CPAP. The purpose of this quality initiative was to determine using EELI at what point in the extubation process infants might be losing lung volume and then based on the information see if they could ultimately use this to improve the chances of successful extubation in the future.
What makes this study interesting is that the infants were found to lose volume but at a time when I would not have expected it.
Below is a graphical depiction of EELI and estimates of FRC during the different time points. The changes in electrical impedance by EELI were converted on the right Y axis to an FRC in mL/kg.
What is surprising at least to me here is the loss of volume occurs not with extubation but rather when the tape removal process happens. With the placement of the prongs on the infant at extubation the FRC gradually rises and recovery occurs. Moreover as shown in the 12 patients included in this study, the recovery once non-invasive ventilation is provided is quite rapid and evident within 1-2 breaths.
A couple other things to note. The loss of FRC during tape removal was about 10 mL/kg and if typical FRC in a preterm infant is 20-25 mL/kg you can see the impact this would have on lung volume and reserve. As this was a small study it could not detect a threshold at which extubation would fail but one infant who developed a pneumothorax and required reintubation did not get back to their baseline FRC.
What is this signaling?
Yes this is a small study but it did look at about 3000 breaths so there is a fair amount of data to look at. What the paper demonstrates I think is that there is a vulnerable time during tape removal where likely due to the fact that we use uncuffed ETTs in neonatology it is possible for these infants to lose lung volume. It may be that as they strain and bear down the ventilator may not be as effective at delivering volume to them. Measures that might help during this time could be skin to skin care, breastmilk drops or scent, sucrose or a variety of other non-pharmacologic measures to keep them calm. This might help to minimize such volume loss. Secondly, knowing the significant risk of volume loss it underlines the importance of placing nasal prongs on as quickly as possible during the transition from invasive to non-invasive ventilation as recovery of lung volume is possible. It think it also suggests that if we are “peepaphobic” and use an insufficient amount of support at extubation these infants may be vulnerable to experience significant volume loss as well.
While EELI may not be perfect, this study is the first of its kind and may shed some light into why some infants fail after extubation. While usually I say less is more, I do wonder if in the case of extubation, this study gives some evidence to support starting with a higher PEEP than you think you need non-invasively and then backing off after one has successfully extubated. This may be the first study I have seen on this but I am certain it won’t be the last.
If you work in Neonatology or in Pediatrics for that matter there is no doubt that at some point you took the neonatal resuscitation program (NRP). Ideally you should be recertified every year or two years depending on your profession. In the course you are taught that the depth of chest compressions required to achieve the best chances of ROSC is 1/3 the diameter of the chest. The evidence to support this comes from a CT evaluation of neonatal thoraces in the paper Evaluation of the neonatal resuscitation program’s recommended chest compression depth using computerized tomography imaging. In this study the authors found that using a mathematic model the 1/3 chest compression recommendation should in theory yield the best hemodynamic outcome.
What about ROSC?
Hemodynamics is one thing in a model but what about real life? I don’t think you could reasonably do an RCT these days with the outcome of interest being ROSC in humans. What research ethics board would allow you to randomize to the outcome of death in babies and deviate from an international organizations recommendations for best practice? My former colleagues in Edmonton had an answer to this issue though by using a piglet model to test the hypothesis that 33% is indeed better than either 12.5%, 24% or 40% chest compression depth. Their paper Assessment of optimal chest compression depth during neonatal cardiopulmonary resuscitation: a randomised controlled animal trial tackles just that question.
How did they do it? In an animal lab that is equipped with a mechanical device to simulate chest compressions they were able to instrument piglets and after asphyxiating them with an occluded ETT they began the process of trying to revive them. After being asphyxiated they initiated a combination of PPV with a neopuff and gave epinephrine (0.02 mg/kg/dose) intravenously2 min after the start of positive pressure ventilation and every 3 min until ROSC with a maximum of three doses, with a maximum resuscitation time of 10 min. The groups were divided in the following manner.
What did they find?
Two very interesting things came out of the study. The first was that they abandoned the 12.5% group early in the study when it became apparent that no piglet would survive using this depth. The other thing they found in support of greater depths of 33 and 40% compression depth is shown in the following graph.
The authors found that in terms of systolic and diastolic blood pressure the best chances in particular for systolic blood pressure were the 33 and 40% compression depths. Looking at the bottom right figure it is also evident that cerebral blood flow increases with increasing depth of compression.
With respect to the primary outcome they found this:
“The median (IQR) time to ROSC was 600 (600–600) s, 135 (90–589) s, 85 (71–158)* s and 116 (63–173)* s for the 12.5%, 25%, 33% and 40% AP depth groups, respectively (p<0.001 vs 12.5% AP depth group). The number of piglets that achieved ROSC was 0 (0%), 6 (75%), 7 (88%)** and 7 (88%)** in the 12.5%, 25%, 33% and 40% AP depth groups, respectively (*p<0.05 and **p<0.005 vs 12.5% AP depth group).
Of note, one of the piglets randomized to 40% depth of compression had pulmonary contusions at autopsy.
Putting it all together
The article supports the use of 33-40% chest compression but it raises an important point in my mind. The study used a mechanical device to ensure the percentage compression and it is clear that if you fall below these numbers the ROSC and hemodynamics is impaired while if you go to high you run the risk of damaging the lungs (I know it was just one but a previous study demonstrated harm at 50% compression depth as well).
This raises the question about failed resuscitations. Do we know how deep we are actually compressing during these situations? Sure, everyone can recite that we should be compressing to 1/3 of the chest diameter but what are we actually doing? In some cases are we not doing enough and in other cases doing way to much? I would imagine the answer to this question is yes. I do wonder as we continue to automate so much in our world through advances in technology if doing the same in neonatal resuscitation is not that far off. When our hands are sweaty and tremulous with adrenaline coursing through our veins how good are we really at controlling the precise depth of compression. Time will tell what happens but what is clear to me is that precision matters and really how precise can we be?
When I began my career in Neonatology we initially ventilated primarily with pressure limited time cycled modes of ventilation and only supported some of the breaths as in SIMV modes. With time and emerging research a movement to using set volumes came about and in many centres supporting every breath using an assist control mode or similar version. Although I don’t have access to it in my centre, ventilators such as the Avea also allow for automated FiO2 control in addition to having a choice of two different volume targeting modes. The difference between the modes is the subject of a study entitled Comparison of volume guarantee and volume-controlled ventilation both using closed loop inspired oxygen in preterm infants: a randomised crossover study (CLIO-VG study). I suppose it shouldn’t be a big surprise that as technology advances and we fine tune practice, different modes for volume targeting would arise.
What’s the difference?
Volume Controlled Ventilation (VCV) – flow based on a set volume and measurement of the PIP every 2 ms. Next breath is given the greater of PEEP+2 cm H2O or PIP-2 cmH2O. The ventilator at the end of each breath is able to determine if the baby is still demanding flow and continues providing flow but stops when inspiratory flow is <25% of peak set flow. There is constant inspiratory flow and peak volumes.
Volume Guarantee (VG)- inspiratory pressure is adjusted breath to breath. These breaths have a decelerating flow instead of a fixed flow as in VCV.
Using automated FiO2 control for both groups the study design was a crossover one. The concept was that better ventilation would help to keep O2 saturations more reliably in a target range of 90-95% and that one of these modes might be superior than the other in doing so. Infants in the study were born at 23+0 – 36+6 weeks and had to be intubated and on >21% FiO2 to be part of the study. Each group spent 12 hours in each arm with the starting mode randomly chosen before switching over to the other mode.
Based on a power calculation in which the authors selected looking for a 5% difference they determined they needed 19 patients in the study overall. The median GA of the infants was 25 weeks (IQR 24-28) with a BW of 685g.
On a personal note, I use only VG in my centre so I am pleased to see there is really no difference in the primary outcome but the trend in the secondary outcomes at least puts a slight smile on my face as well!
I have written a lot over the years on the topic of BPD. It isn’t by chance as it is a condition that Neonatologists have put a lot of weight on. In many ways it is a benchmark that is often the go to condition when comparing one unit to another. When two Neonatologists get together their first question isn’t what’s your rate of ROP or severe developmental delay but more often comparing rates of BPD. We like to compare this as a metric as it’s something we can see as compared to say rates of late onset sepsis. You can see a patient on a ventilator or on CPAP at 36 weeks but you can’t see bacteria coursing through veins.
Not all BPD is the same though. in 2000 the NIH produced a new consensus definition of BPD as shown below.
What stands out for the babies <32 weeks is how severe BPD is defined. Babies who are ventilated are classified in the same severity group as those who are on CPAP. Somehow that doesn’t seem quite right intuitively but alas that is what they decided at the time.
Type 1 sBPD: patients on nasal cannula or noninvasive positive pressure support (i.e., high flow nasal cannula (HFNC), nasal continuous positive airway pressure (nCPAP), noninvasive intermittent positive pressure ventilation (nIPPV)) Type 2 sBPD: infants receiving iMV
The authors then looked at a sample of 564 patients from 2015-2019 in the BPD collaborative registry and subdivided them into 429 (76%) Type 1 vs 135 (24%) Type 2 sBPD and compared outcomes between the two. The differences between the two types of BPD are quite significant and shown in Table I. Babies who went on to develop sBPD as Type 2 were younger and smaller than those with Type 1. Medication use within the NICU and after discharge was markedly different as were the total ventilator days which is likely not surprising since by definition they were still intubated at 36 weeks. Importantly if you were still intubated at 36 weeks PMA almost one quarter of the patients went on to receive a tracheostomy.
Looking at it another way using relative risks the signifance of having Type 2 sBPD is impactful.
Taking Meaning From This
You might be quick to say, Michael this is absolutely no surprise. On the other hand if you have read this blog for some time you may remember this piece The New BPD That Matters. This study looked at what gestational age really mattered when looking at long term pulmonary outcomes in a Canadian cohort. When you take all comers it was 40 weeks and not 36 weeks that really mattered. The likely differernce here though is that by selecting out only the severe patients in this current study it is indeed the 36 week mark that still has relevance. I actually think the two papers together are not contradictory but rather additive.
What I think one takes away from the current study is that failure to extubate by 36 weeks does in fact carry with it significant long term risk to the patient. It would be easy enough to say that these babies should be extubated but as you see from table I it isn’t that they didn’t try. From a medication standpoint it would appear that they ” threw the kitchen sink” at these babies. The only thing I find a little surprising is that only 47% of babies in the collaborative with type 2 sBPD received systemic steroids. If they were that sick I would have expected it to be higher although that also may just be a reflection of my own practice.
One thing that I think will be a hot topic moving forward is the use of higher levels of CPAP than what many units are accustomed to. This has also been recently discussed in High CPAP vs NIPPV. Is there a winner? There may be a reluctance by some units to use CPAP levels in the +9-12 cm H2O range but when looking at these downstream complications for patients who remain ventilated at 36 weeks I think people need to seriously consider their biases and whether they are based on science or what they were taught. I can’t help but think of the oft used expression absence of evidence is not evidence of absence and think that if we can all be a little humble who knows what we may discover that can help this population.
For as long as I can remember I was taught that there is a desperate need to intubate babies with congenital diaphragmatic hernia right after birth and place an NG to suction. The goal of this manouver was to minimize the amount of swallowed air into the GI tract and thereby give our best chance at ventilation. If there was a dogma in Neonatology this had to be one right near the top. In fact, attending the delivery of a baby with a known CDH has been ike watching a well trained SWAT team in action with everyone committed to their roles and importantly getting that ETT in as fast as possible being the first goal. Once the tube is in though we often have the problem of having a vigorous term infant who needs a fair bit of sedation to keep the tube in. Moreover, they don’t want to be intubated so keeping them settled may require significant doses of opiates and or benzodiazepines which in turn may wreak havoc with their hemodynamics and require pressor support. Not a great start to life.
There is a subset of patients with CDH who are said to have “mild CDH” Their characteristics are that they have an isolated leftsided CDH with an observed-to-expected lung to-head ratio (O/E LHR) greater than or equal to 50%, and intraabdominal liver position. The survival for this group exceeds 95%.
Researchers from the Netherlands published last year Routine Intubation in Newborns With Congenital Diaphragmatic Hernia. In the paper they make the argument that there could be another way to handle such babies whcih they call the spontaneous breathing approach or SBA. Basically, a team approach with perinatology is used to identify these lower risk fetuses with CDH and then at birth the following approach is used as per the paper.
“The newborn is positioned on the resuscitation table and a Replogle tube (10F catheter) is inserted for continuous stomach decompression. In the case of planned SBA, the infant is supported with oxygen if necessary (Neopuff infant T-piece resuscitator; Fisher & Paykel Healthcare, Ltd, Auckland, New Zealand), aiming for preductal saturations .85%.4 Continuous positive airway pressure isallowed. The infant is intubated if insufflation breaths or ventilation are needed because positive pressure ventilation via mask increases the air in the digestive tract, subsequently compressing the lungs, resulting in hypoxia and PH.”
They Tried it Out
Armed with this approach the authors performed a retrospective study to determine whether the approach above is a reasonable one to take based on their own experience. Looking at the figure below over about a 5 year period they had 71 patients with CDH. Eighteen met their criteria for low risk and 15 of those had a planned SBA. Of the 15, SBA was successful (meaning they did not require intubation prior to surgery) in 6 or 40% while the other 60% did not tolerate the approach.
Looking at characteristics of those who were successful vs not was presented in table 1 below. There were no baseline characteristics that stood out to indicate higher or lower likelihood of success but it is clear that not having success has an impact. Those who did not tolerate the SBA had longer durations of ventilation and length of stay. This is an association but I would imagine the increased durations have more to do with the fact that the infants were sicker than expected rather than anything else.
What Can We Say About It?
I think there are a number of interesting aspects to this approach. The first is that the old dogma of saying that all these infants need to be intubated to prevent intestinal distension is incorrect. Secondly, the use of CPAP as long as there was gastric suction did not impact these infants to any signicant degree. The survival of this group regardless of tolerance or failure of the SBA was 100% and only one patient needed iNO therapy with an LHR of 57%. Of course the numbers here are small so I am not suggesting for a moment that this clearly is the way to go. It does provide strong support though for a prospective trial that I understand is in the works. In the meantime what do we do with the babies that are to come? For the most part I think units need to decide as a group what approach they are willing to take with these low risk patients. It will cause great confusion for staff if one week a baby is put on CPAP and the next with a similar risk profile a baby is urgently intubated. Lastly let me say that I love that something I was taught 25 years ago to ALWAYS do is now being questioned. What’s next?